2018 American Neuropsychiatric Association Annual Meeting Abstracts

Background: Suicide is a common cause of death in the military. Traumatic brain injury is associated with suicidal ideation, but also with multiple sequelae including posttraumatic stress disorder (PTSD) and depression, both of which also predispose individuals to suicide. We wish to see if suicidal ideation (SI) occurs at different rates in populations with these conditions individually and comorbidly. Objective: Compare Veterans with mild TBI (mTBI) to those without mTBI on the basis of suicidal ideation (SI), PTSD, and depressive symptoms. Compare Veterans with mTBI and SI to Veterans with mTBI but without SI on the basis of PTSD and depressive symptoms. Determine if SI in mTBI correlates with depressive or PTSD symptoms. Methods: 28 Veterans were enrolled in the study. Classification of mTBI was based on a structured interview. The following self-report questionnaires were completed by all participants: Beck Depression Inventory-II (BDI-II) and the Clinician-Administered PTSD Scale-5 (CAPS-5). Results: Veterans with mTBI did not have different rates of PTSD than veterans without mTBI. Veterans with mTBI had significantly higher depression scores than those without mTBI (p=0.026). Veterans with mTBI were more likely to report SI, than those without mTBI [X² (1, N=22)=0.391, p=0.002]. Among Veterans with mTBI, there was no difference in depression or PTSD rates between Veterans who reported recent SI versus those who had not. Conclusion: Veterans with mTBI were more likely to report SI than those without. There was no difference in severity of PTSD, or depressive symptoms among Veterans with mTBI and SI and those without. This suggests that SI in the mTBI population may occur independent of PTSD and depression. This may help guide future therapies for suicidal ideation among Veterans with mTBI.

Background: Previously a subtype of schizophrenia, catatonia is now recognized as a syndrome associated with both psychiatric and medical conditions. Central and extrapontine myelinolysis (CPEM), is a disorder resulting from noninflammatory demyelination which is uncommonly associated. Case Report: 51-year-old incarcerated male with diabetes, hypertension and schizophrenia was admitted after left ear amputation after falling from bunkbed. He was having vomiting, dizziness, and disorientation during the preceding week. Labs revealed sodium of 99 and potassium of 2.2. After 3L of normal saline infusion, sodium increased by 10 within 12 hours. Psychiatry was consulted for odd behavior including verbigeration, repetitive movements and disinhibition. Home risperidone previously held due to concern for SIADH was resumed. Four days later patient demonstrated stupor, mutism, staring and negativism. After a positive lorazepam challenge, catatonia was diagnosed. Symptoms improved, and he was discharged on risperidone. Three days later he was readmitted with persistent catatonia. Initial MRI limited by motion artifact showed no significant abnormalities. Ativan was scheduled with mild improvement. Thiamine was<2, and replaced. MRI 5 days later showed focal area of restricted diffusion in central pons and abnormal T2/Flair signal in bilateral basal ganglia and left thalamus suggesting CPEM. Literature reports a biphasic course for CEPM¹ and behavioral features are rarely the main presentation. Proposed pathophysiology of behavioral manifestation includes damage of the RAS pathway to the thalamic nuclei affecting neurotransmitter pathways.² Conclusions: Catatonia occurring during treatment of hyponatremia should raise suspicion for CPEM particularly in cases with sodium<100, concurrent hypokalemia, and malnutrition.

1. Martin RJ: Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiatry 2004; 75(Suppl 3):iii22–iii28. Available at doi: 10.1136/jnnp.2004.045906

2. Gopal M, Parasram M, Patel H, et al: Acute Psychosis as Main Manifestation of Central Pontine Myelinolysis. Case Rep Neurol Med 2017; 2017:1471096. Available at doi: 10.1155/2017/1471096

3. Novac AA, Bota D, Witkowski J, et al: Special medical conditions associated with catatonia in the internal medicine setting: hyponatremia-inducing psychosis and subsequent catatonia. Perm J 2014; 18:78–81. Available at doi: 10.7812/TPP/13-143

Background: The treatment options for PTSD require an understanding of the nature of the trauma experienced by the person and a careful review of the risk factors exposing a person to development of disease and comorbid conditions. There are number of psychological and pharmacological approaches for the treatment of PTSD and comorbid conditions. The psychological component of treatment includes both generic therapies such as supportive therapy, psychodynamic therapy, hypnotherapy, and therapies particularly outlined for PTSD, such as CBT and EMDR. Aim of this Study: To assess the relative efficacies of Cognitive behavioral therapy (CBT) and Eye movement desensitization and reprocessing (EMDR) techniques for treatment of Posttraumatic stress disorder (PTSD) and also to determine which treatment modality is superior to other and is more effective in reducing the experience of symptoms. Design: Four major electronic databases were searched between 1999 and 2017 for trials demonstrating the relative efficacies of CBT and EMDR. After a systematic review of the data following the PRISMA guidelines, random effects meta-analysis and meta-regression were conducted to measure the efficacy of the two techniques and identify the impact of duration and number of sessions on effect size. The data were statistically analyzed using Comprehensive-Meta Analysis V3 Software (Biostat, Inc). Subjects: 10 relevant studies presented a total of 478 subjects, with 216 subjects allotted to CBT treatment, 200 to EMDR treatment and 62 patients were on the waitlist controls. 378 female and 80 male subjects were included in the studies, with a mean age of 27.07 years, and participants were on average exposed to 7.9 sessions, with an average duration of 75 minutes. Reported sources of trauma varied, including accidents, nonsexual assault, sexual assaults, war zone trauma, rape, attempted rape, molestation, physical abuse, emotional neglect, traumatic death or loss, kidnapping and disaster trauma. Outcome Measures: The primary outcome measure was the reduction in the symptoms of PTSD, as reported by the scores of valid scales of measurement. The different scales which were used to assess the primary outcomes included Posttraumatic Stress Disorder-Self Report (PTSD-SR), Child Report of Posttraumatic Symptoms (CROPS), Clinician-Administered PTSD Scale (CAPS), Children's Responses to Trauma Inventory (CRTI). Results: Comparison of the two techniques did not show any significant difference between CBT and EMDR in symptom reduction. The Forest Plot revealed that the overall standard difference in means was 0.21, p=0.11, at 95% interval. Furthermore, the heterogeneity plots revealed that no significant heterogeneity was present among the studies, confirmed by the I2 statistic value at 22.49%, p=0.25. Lastly, publication bias revealed symmetrical plots and insignificant value of Egger's rank test, 0.24, p=0.43. The meta-regression analysis revealed that duration and time of sessions had no impact on effect size, Q value=0.07 with df=2 and p=0.96. Conclusion: CBT and EMDR techniques are equally effective in improving symptoms of PTSD, with comparable efficiency and tolerance by the patients. However, the amount of homework associated with CBT could make it a bit undesirable for the patients.

Background: The prevalence of psychosis in patients with epilepsy is 2%−10%. Psychosis may be conceptualized as a manifestation of epileptic activity but often, epilepsy and psychosis are diagnosed as separate comorbid disorders. The occurrence of interictal psychosis in patients with epilepsy is not random and is sufficient to raise questions about shared neurobiological mechanisms. These are as yet not fully understood. In clinical practice there is often a dichotomous approach to treatment by neurologists and psychiatrists. Response to traditional use of neuroleptics is frequently poor and treatment can be quite challenging. Case History: A case of epilepsy in a patient with previous diagnosis of pervasive developmental disorder is presented. The patient eventually develops a psychosis with a very cyclical pattern, reminiscent of mania. As symptoms evolve, first rank symptoms appear. There is disagreement among treatment providers as to the etiology of the psychosis and its relationship to his underlying idiopathic generalized epilepsy. He fails several neuroleptic trials. The case is presented with some video samples. A literature review on the current evidence on convergent neurobiological mechanisms involved in epilepsy and psychosis follows. Conclusions: Several neuroanatomic regions have been implicated in the pathophysiology of epilepsy and psychosis and genetic studies suggest an overlap in these disorders. A summary of the available evidence support a network dysfunction however as the most logical framework to understanding this condition. It is hoped that with this understanding, a more evidence-based approach to management can ensue and a conceptualized preliminary template for treatment is discussed.

Background: Posttraumatic stress disorder (PTSD) has been associated with abnormalities in multiple neural circuits, including those involved in fear learning, threat detection and assessment, and emotion regulation. Current evidence suggests that psychotherapy is the optimal treatment modality. Patients are also typically treated with multiple psychotropics despite a lack of high-grade evidence to guide treatment selection. Biomarkers hold promise in filling this void. Objective: In the interest of developing a functional neuroimaging biomarker for PTSD, we sought to establish PTSD-relevant neural circuit abnormalities elicited by an emotional word paradigm. The task is simple, rooted in language and therefore relevant to psychotherapy, and has been shown to probe executive, self-referential, and fear-relevant neurocircuitry. Methods: Subjects included 29 patients with PTSD (childhood sexual abuse) and 23 controls. Symptom severity was assessed using the Clinician-Administered PTSD Scale (CAPS). BOLD imaging was performed using 3T scanners, z-shimmed to improve signal near the skull base. A multilevel mixed-effects model was used to establish within-group and between-group effects. Results: In the trauma-versus-neutral word contrast, PTSD subjects showed activations in the left amygdala, hippocampus, dmPFC, vmPFC, dACG, caudate heads, Broca and Wernicke areas, temporopolar cortices, and midbrain, and decreased activity in the DLPFC. Relative to healthy controls, there was increased activation in the dmPFC, vmPFC, dACG, caudate heads, and midbrain. Symptom severity positively correlated with limbic and caudate activity, and negatively with medial OFC. Conclusion: When reading trauma-relevant words, PTSD subjects demonstrate abnormal function in neurocircuitry pertaining to self-reference, threat detection and assessment, and emotion processing and regulation.

Background: The Neuropsychiatric Inventory (NPI) is the gold-standard assessment for neuropsychiatric symptom assessment. The NPI-Questionnaire (NPI-Q) was derived from the NPI to support clinical care, but has been primarily used for research applications. We report NPI-Q data obtained from routine clinical care to assess its utility and limitations in clinical settings. Methods: Among consecutive subjects evaluated at the UNC Memory Disorders Clinic, we examined NPI-Q symptom prevalence in mild cognitive impairment (MCI, N=78), Alzheimer’s disease (AD, N=75), Lewy body dementia (LBD, N=51), and Frontotemporal degeneration (FTD, 61) using a chi-squared test. Diagnostic classification was not blinded to NPI-Q data. Results: Apathy was present in more than 50% of all groups and was highest in FTD (75.4%). Nighttime behaviors were also highly prevalent in all groups, particularly in LBD (72.7%, p<0.05). Anxiety, hallucinations, and delusions were also more prevalent in LBD compared with other groups (p<0.05). Disinhibition, elation, motor behaviors and appetite/eating behaviors were more prevalent in FTD compared with other groups (p<0.05). Moderate-severe symptoms of apathy, anxiety, depression, and nighttime behaviors were present in more than 10% of MCI subjects. Conclusions: The NPI-Q provides clinical information that can inform differential diagnosis, identify psychiatric comorbidities, and guide therapeutic interventions based on the clinical significance of reported symptoms. Although informants do not always provide complete information regarding severity and distress rating (data forthcoming), and the NPI-Q does not provide specific symptom details, it is a useful tool for identifying and managing neuropsychiatric symptoms in clinical practice.

Background: Mild traumatic brain injury (mTBI) is associated with dynamic changes on magnetic resonance imaging (MRI). Modern auto-segmentation protocols facilitate volumetric MRI analysis after mTBI. Methods: We reviewed all available mTBI patients seen at the University of Colorado Hospital over a 5-year period whose MRI could be exported into NeuroQuant® for volumetric analysis. Patients with significant structural brain pathology were excluded. Standard scores for cerebral gray matter (GM) and white matter (WM), cerebellar GM and WM, ventricular system, and brainstem were compared. Results: We identified mTBI 10 patients who met criteria. The average age was 36.7 (SD=12.7) years, and 50% were men. The average time after injury was 84.1 (SD=64.8) days. Average mean percentile scores were 25.8 for cerebral GM, 95% CI [10.5, 41.1], 87.1 for cerebral WM, 95% CI [68.7, 105.4], 48.5 for cerebellar GM, 95% CI [28.7, 68.2], 93.5 for cerebellar WM, 95% CI [85.6, 101.441], 29.2 for ventricular system, 95% CI [15.0, 43.5], and 51.2 for brainstem, 95% CI [30.8, 71.6]. The patient with the longest time after injury (230 days) had no discrepancy between GM and WM volume. Conclusions: NeuroQuant® can be used to quantitate brain volumes after mTBI. While our results preclude a firm conclusion, we found that WM volumes were notably elevated in 8/10 patients, with a suggestion that this volume increase may be transient. Our data generate a testable hypothesis, which, if confirmed, could disclose that WM volume expansion may represent reversible edema or increased blood volume after mTBI.

Background: Brain injuries (BI) are common throughout the lifespan and associated with chronic neuropsychiatric symptoms. Frequently, for those with a history of BI, functional outcomes are poor and quality of life is decreased. Patients with BI exhibit extensive phenotypic heterogeneity and variable disease trajectories. There is a critical need to better understand contributing factors of phenotypic variance and clinical outcomes, as well as their modulation by underlying pathophysiology. Objective: Governed by a multidisciplinary team, including treating providers, the registry aims to characterize patients for ongoing and future research through aggregating biosamples and organizing clinical and outcomes data at the point-of-care. Methods: This project is conducted at Sheppard Pratt Health System's Neuropsychiatry Program. Processes for coordination and data management are facilitated by an IT and communication infrastructure using open architecture technology to allow point-of-care data capture and reporting. Retrospective data are curated using Common Data Elements through chart analysis and clinician report. The battery of measures includes cognitive and behavioral tests as well as patient, proxy and clinician reported outcomes. Measures are obtained retrospectively, cross-sectionally and longitudinally. Results: 393 patients with history of BI were identified. 341 are eligible for the registry. BI severity ranges from mild (50%) to moderate-severe cases (moderate, 5%; 45% severe). Recruitment and testing is currently in process. Conclusion: Patient registries improve the understanding and discovery of cohorts, naturally promote hypothesis development and support quality reporting of data. Longitudinal patient follow-ups will track symptom severity and should give insight into clinical utility of such point-of-care data collection.

Background: Tics are common in childhood. The received wisdom among clinicians has been that for most children the tics are temporary, disappearing within a few months. However, that opinion is based almost entirely on biased and incomplete data. Objective: To prospectively assess outcome of Provisional Tic Disorder. Methods: We identified 43 children with recent onset of tics (mean 3.3 months). Forty have reached the 12-month anniversary of their first tic, and we have re-examined 36 of these on that anniversary (mean 1 year+9 days after onset). Results: At 12 months, over 90% had no or minimal impairment from tics (YGTSS Impairment score≤10), and several had no tics on clinical examination. Remarkably, however, all but one child had tics when observed by video, and the remaining child had parent-reported tics within the past week and was observed to tic on a later encounter. All but 4 children met DSM-IV-TR criteria for Tourette’s Disorder. The mean Diagnostic Confidence Index score was 41, representing a fairly typical history for early Tourette syndrome. Conclusion: Although most children are no longer bothered by their tics one year after tic onset, 90%−100% meet DSM-5 criteria for a persistent tic disorder. Remission of Provisional Tic Disorder is the exception rather than the rule.

Background: Substantial numbers of military veterans returning from war display symptoms of poor sleep, poor concentration, irritability, and reckless behavior. These symptoms can be seen as a manifestation of either hypomania or posttraumatic stress disorder, but operational criteria for distinguishing between the two are lacking. Current research is scant on this issue. A search on PubMed for “Hypomania” and “PTSD” resulted in almost 600 hits, most of which discussed PTSD or bipolar disorder separately. Of this list, there were 18 hits that included a discussion on how these diagnoses exist as comorbidities, but there is little discussion about how the symptoms of hypomania can overlap or be confused with the symptoms of PTSD. How should a clinician differentiate between these two disorders? Case History: We present a case of a 24-year-old combat veteran with no formal psychiatric history. Upon returning home from the battlefield, he displayed increased irritability, emotional lability, difficulty concentrating and impaired sleep (less than 4 hours per night). Careful review of this patient’s history informs us that his symptoms are more consistent with bipolar disorder. We review the distinguishing clinical features between hypomania and PTSD. Conclusions: This case illustrates the importance of distinguishing between hypomanic and PTSD symptoms. Current and former military service members who are evaluated for posttraumatic stress disorder would benefit from being screened for hypomania. Research is needed to operationalize the distinction of these two conditions.

Background: Noninvasive neurostimulation is a promising new treatment for functional neurological disorders. However, potential therapeutic mechanism(s) are poorly understood and no studies have assessed longitudinal neurophysiological correlates of treatment. Objective: To investigate the cortical neurophysiology of a functional weakness patient before, immediately after and 6-months post peripheral neurostimulation treatment. Methods: A 26F with unilateral, right arm/hand functional weakness was prospectively enrolled. Transcranial Magnetic Stimulation (TMS) was used to collect motor evoked potential (MEP) amplitude, motor threshold and short-interval intracortical inhibition (SICI) at the three study time-points. Left and right motor cortex were evaluated, the latter acting as an internal control. Neurostimulation treatment consisted of 30 minutes of 30Hz nerve stimulation applied to the right arm. Results: Our subject had no immediate change in symptoms after treatment but improved gradually and reported full resolution by 6-months. Paralleling this clinical course, there was no significant difference in left MEP amplitude from pre- to immediately posttreatment. However, at 6-months, left MEP amplitude significantly increased from 0.98mV pretreatment to 2.81mV (two-way ANOVA, p<0.001). Consistent with this finding, left motor threshold decreased from 49% stimulator output pre- and immediately posttreatment to 42% at 6-months. Right MEP amplitude and right motor thresholds were stable across the three time-points. There were no significant differences in SICI. Conclusions: Longitudinal cortical excitability increased in parallel with clinical improvement in a functional weakness patient treated with peripheral neurostimulation. This hypothesis generating study provides a basis for further investigation of such changes as a potential neurophysiological outcome marker for functional weakness.

Background: Misidentification delusions in Alzheimer’s disease are common and contribute significantly to caregiver stress, but it is unclear what triggers these delusions. Case Histories: (1) 83-year-old man with Alzheimer’s disease and a history of stroke. He went with his grand-daughter to get a haircut, and no longer recognized her after she got her hair cut and colored. He also had a dog that got a haircut in the summer, and afterward the patient was unable to recognize the dog, asking “where is that other dog that used to be here?” (2) 80-year-old man with Alzheimer’s disease versus mixed Alzheimer’s and Lewy Body Disease. After his wife changed her hair color, and he failed to recognize her around the house, asking his daughter who was the “strange man” in their house. (3) 80-year-old woman with Alzheimer’s disease versus mixed Alzheimer’s and vascular dementia. After she returned home after a rehab stay, she experienced reduplicative paramnesia of her home, maintaining that she now lived in a replica house because of the presence of a new live-in health aide. Conclusions: Here we present three cases of misidentification delusions triggered by minor changes in appearance or environment in Alzheimer’s disease patients. Prior reports have identified that the Capgras delusion can be triggered by minor environmental changes after brain injury, and our case series suggest this may also be true in dementia. This may have important implications in counseling families to identify and minimize potential triggers for delusions.

Background: Alien hand syndrome is a disorder of involuntary, yet purposeful, hand movements that may be accompanied by agnosia, aphasia, weakness, or sensory loss. Anterior and posterior variants of the syndrome are identified, with the anterior variant being more commonly reported. Case: A 67-year-old female reported feeling her left arm was hot accompanied by a fluttering sensation in her chest and arm. She also complained that her arm was levitating outside of her voluntary control. Psychiatry was consulted due to patient’s atypical presentation and level of distress. Examination revealed grade 4/5 power on the left side with 5/5 power on the right. Touch, pain and temperature sensations were intact bilaterally and reflexes were preserved. She obeyed motor commands on the left side but could not copy kinesthetic positions of right extremity on the left. When she held her left hand with her right she asked the examiner if it was his hand. She had a past history of parieto-occipital stroke and current MRI showed an acute stroke affecting the same region. Management involved a multidisciplinary team including psychiatrists, neurologists, internists and social workers to help with disposition. Conclusion: Posterior variants of alien-hand syndrome are uncommon and often present with atypical findings which may often be confused with psychiatric presentations. A thorough neurological examination and a high index of suspicion often help clinch the diagnosis.

1. Sarva H, Deik A, Severt WL: Pathophysiology and treatment of alien hand syndrome. Tremor Other Hyperkinet Mov (N Y) 2014; 4:241. Available at doi: 10.7916/D8VX0F48

2. Gondim FA, Oliveira GR, Cruz-Flores S: Position-dependent levitation of the dominant arm after left parietal stroke: an unreported feature of posterior alien limb syndrome? Mov Disord 2005; 20:632–633. Available at doi: 10.1002/mds.20404

Background: Schizophrenia (SZ) is a devastating disorder associated with emotional and cognitive symptoms of disorganized language and communication [1]. Linguistic and emotional domains are intricately linked but few studies have examined their interactions in SZ. Objective: This study aimed to test the hypothesis that emotional word perception is impaired in subjects with SZ compared with healthy controls (HC). Methods: There were 31 subjects with SZ and 17 HC. SZ subjects were categorized into mild and severe subgroups based on positive, negative, and general PANSS (Positive and Negative Syndrome scale) scores. Participants were scanned with functional magnetic resonance imaging (fMRI) while silently reading schizophrenia-relevant negative and neutral words. Postscan, word valence ratings were tested. Results: SZ subjects with higher negative and general PANSS scores rated the neutral words more positively, and SZ subjects with higher general scores also rated the negative words more negatively. For the negative versus neutral words, there was greater fMRI activation in left angular (LAG), left middle occipital (LMOG) and left posterior middle temporal gyri (LpMTG) in SZ relative to HC. Less sustained activation in left inferior frontal gyrus (LIFG) and more sustained activation in right amygdala and LpMTG were seen in the SZ group. Conclusion: Processing of negative words was associated in SZ with greater activation in semantic (LAG, LpMTG) and emotion (right amygdala) areas, and weaker activation in a cognitive control area (LIFG). Together, the behavioral and fMRI results demonstrate enhanced reactivity and reduced cognitive control in the processing of negative words in SZ.

1. Brown M, Kuperberg GR: A hierarchical generative framework of language processing: Linking language perception, interpretation, and production abnormalities in schizophrenia. Front Hum Neurosci 2015; 9:643

Background: Focal brain lesions can disrupt free will perception, altering our desire to act (disordered volition; akinetic mutism) or our sense of responsibility for an action (disordered agency; alien limb syndrome). However, lesions in several different locations can cause each syndrome, making it difficult to determine the neuroanatomical basis for these processes. Objective: To determine if lesions impairing free will perception localize to a unique network of brain regions, rather than a single location. Methods: 28 cases of akinetic mutism and 53 cases of alien limb were identified. We used a new technique called lesion network mapping to determine brain regions functionally connected to each lesion location. We compared akinetic mutism patients to patients with weakness but normal volition (hemiparesis, N=25), and alien limb patients to patients with involuntary movements but intact agency (hemichorea, N=39). Finally, we compared this network localization to neuroimaging finding reported in psychiatric “disorders of free will” (functional movement disorders, PNES, catatonia). Results: 100% (28/28) lesions causing akinetic mutism were connected to the anterior cingulate cortex, which was specific versus hemiparesis. 93% (49/53) of lesions causing alien limb syndrome were connected to the precuneus cortex, which was specific versus hemichorea. While dissociable, there was significant overlap of the networks involved in disordered volition and agency. Finally, our lesion network localization of disordered free will perception matched reported neuroimaging abnormalities in psychiatric disorders of free will. Conclusion: Our results identify a causal substrate for disordered volition and agency, which together may underlie our perception of free will.

Echopraxia and echolalia are subsets of motor mimicry. These are essential developmental elements in social learning and may form a basis for mammalian empathy. Their persistence or reemergence after a certain developmental age may be a sign of underlying brain dysfunction. The list of disorders associated with echophenomena is growing and currently includes diverse diseases. We present the case of a 51-year-old female with a remote history of mild to moderate intellectual disability, who presented with cognitive dysfunction and impulsive behavior. Her symptoms have progressed and a diagnosis of frontotemporal dementia made after imaging and other diagnostic studies. She was subsequently noted to begin speaking synchronously with her mother, and later with caregivers and others despite being mute when directly questioned and having apparent lack of verbal comprehension. She displayed other motor copying behavior and visual agnosia. We discuss the different activities and neural mechanisms that have been attributed to echophenomena, mammalian empathy, and its importance as a form of communication. We also discuss and differentiate the various forms of echophenomena that have been discussed in literature.

Background: Soft Neurological Signs (SNS) are associated with first episode psychosis (FEP) and poor long-term psychosocial functioning. Recently, a meta-analysis localized SNS to the precentral cortex, inferior frontal, thalamus and cerebellum. However, the majority of the studies have not assessed these relationships in a neuroleptic-naïve population. Objective: To examine the relationship between SNS, global functioning and “cerebello-thalamo-prefrontal” MRI measures in a neuroleptic-naïve FEP population. Methods: SNS scores (Neurological Evaluation Scale), structural brain imaging (1.5T), and global assessment scale (GAS) were obtained in neuroleptic-naïve FEP (N=55) and HC (n=40) subjects. Images were processed using FreeSurfer 6.0. Group comparisons were assessed with ANCOVA controlling for age, sex and race. SNS relationships with structural and GAS were determined using Spearman correlations and corrected for multiple comparisons. Results: SNS cognitive perceptual (p=0.001) and total score (p<0.001) were significantly reduced in FEP compared with HC, but not repetitive motion. No group-wise differences were identified for the above specified brain regions. In FEP, SNS cognitive perceptual score was significantly associated with GAS (r=−0.31) and left cerebellum (r=−0.28), while repetitive motion subscale was significantly correlated with bilateral cerebellum (r=−0.28; r=−0.33), bilateral thalamus (r=−0.45; r=−0.29), and right inferior frontal thickness (r=0.34). HC did not show any relationships to SNS. Conclusion: Our findings suggest that cognitive perceptual SNS affect functioning and cerebellar atrophy, while repetitive motion SNS localize to cerebellar-thalamic brain networks and these changes occur before antipsychotic treatment in FEP subjects. Future directions include evaluating changes in ROIs with SNS scores and psychosocial functioning longitudinally.

Background: Catatonia is well documented in psychotic, mood, and underlying medical disorders. The prevalence of catatonia in Down Syndrome is unknown, though previous case reports suggest it may represent a treatable etiology of unexplained regression in this population. Case History: A 17-year-old male with Down Syndrome and mild intellectual disability had a 12-month history of gradual regressive symptoms, including decreased speech and social interactions, anorexia, weight loss, urinary incontinence, insomnia, and irritability. He developed slowed movements, hopping gait, and vocal and motor tics, and was ultimately diagnosed with depression and Tourette syndrome. No improvements occurred with SSRI, antipsychotic, or alpha−2 agonist trials, and minimal response to low dose lorazepam. With continued loss of function and significant weight loss, he was admitted to the inpatient psychiatric unit. Medical work-up was nondiagnostic, including serum, CSF, autoimmune studies, EEG, and brain MRI. Symptoms partially resolved with lorazepam 12 mg daily. ECT was initiated with significant improvement, and at discharge he was close to baseline after 11 treatments. Outpatient ECT every 1–2 weeks was maintained. Attempts at ECT reduction resulted in immediate recurrence of catatonia. Despite a return to baseline mood and cognition, hopping gait and tics showed limited response to benzodiazepines or ECT. Additional trials of SSRIs and antipsychotics worsened catatonia. Conclusions: This case illustrates the importance of recognizing symptoms of catatonia in adolescents and young adults with Down Syndrome. We hypothesize that catatonia may be more prevalent in the Down Syndrome population than previously recognized, representing a treatable cause of regression.

Background: Chemosensory hallucinations appearing after electroconvulsive therapy has not heretofore been described. Case History: After five years of medication unresponsiveness depression, a 43-year-old right handed male underwent eight sessions of ECT. Within one day he noted the onset an intermittent metallic phantom taste, persisting for five minutes, emanating from the entire tongue. Eating salami would eliminate the phantogeusia. He also noted frequent palinageusia, lasting for 5–20 minutes. Concurrent with this were epochs of déjà vu, and amnestic spells, without biting his tongue or urinary or fecal incontinence. Results: Abnormalities on Neurologic Examination: Mood sad and anxious with congruent affect. Motor: Drift testing: Right pronator drift. Cerebellar: Low amplitude high frequency tremors both upper extremities on extension. Reflexes: 1+bilateral upper extremities and absent in bilateral lower extremities. Neuropsychiatric Testing: Clock Drawing Test: 3 (abnormal). Olfactory Testing: Alcohol Sniff Test: 16 (normosmia). Conclusion: With concurrent symptomatology suggesting temporal lobe dysfunction, the possibility is raised that these represent temporal lobe seizures. Such discharging seizure foci might have been precipitated by ECT. This may represent not a direct effect of ECT but rather secondary effect, due to chemosensory effects of associated medication or anesthesia. Possibly a mechanical effect of ECT may have been the culprit. ECT induced biting of the mouth guard might have caused a rupture of abscesses or discharge of microabscesses in the gums, causing release of pyogenic particles, which are then perceived as a metallic taste. In those undergoing ECT, inquiries as to phantogeusia and palinageusia are warranted.

Introduction: Improvement of phantogeusia through ingestion of tomato juice has not heretofore been reported. Method: Case Study: A 71-year-old right-handed woman, presented with six years of smell loss of sudden onset. Three years prior to presentation she noted a gradual decrement in her ability to taste. Every three months, for two consecutive days, she notes a metallic taste, 8/10 intensity. This persists even when eating and causes food to taste metallic. Nothing reduces the phantogeusia except for drinking one half glass of Campbell’s Tomato Juice. This causes total elimination of the metallic taste for one hour, which gradually returns to the same level, 8/10 intensity. In response to recurrence, she will consume another half glass of Campbell’s Tomato Juice. This sequence will repeat itself multiple times throughout the day. The response to tomato juice has been replicate with recurrence of the phantogeusia on multiple occasions over several months. Her phantom taste is unresponsive to any other vegetable juice, fruit nectar or any vegetable or fruit. She denies palinageusia and cacogeusia. Results: Abnormalities in neurologic examination: Right cerebellar spooning with positive right Holmes phenomenon. Reflexes: decreased throughout. Orthonasal Olfaction: hyposmia. Retronasal olfaction: normosmia. Gustatory: normogeusia. MRI of brain: diffuse punctate hyperintensities. Conclusion: Through retronasal olfaction, tomato juice may act as a counter-stimulus, nullifying any impact of spontaneously discharging phantosmia. Given the cost and potential side effects of other treatment approaches for those who suffer from phantogeusia, a trial imbibing tomato juice is warranted.

Background: The habenula is a historically overlooked brain structure due to its small size. However, a growing body of research indicates that this evolutionarily preserved structure is pivotal in enabling adaptive behavior across species. The functional connections of the habenula provide important signals that are essential for survival. Furthermore, dysregulation may underlie many aspects of psychiatric disorders and conditions. Objective: Review and integrate translational research from other mammals with human studies. Determine functional similarities and differences and understand how the human habenula affects behavior and psychiatric conditions. Methods: Theory papers, meta-analyses, reviews, basic research studies, and clinical research studies were reviewed and synthesized. Results: Electrophysiological studies (rodent, nonhuman primate) indicate that modulation of neuronal activity in the habenula by positive and negative reward-related events is inverse to reward-related changes in brainstem. Human studies utilizing task activated fMRI also indicate that the habenula in specifically signaling negative/aversive behaviorally relevant events. In humans, the habenula is implicated in multiple disorders that share dysregulation of dopamine, serotonin, and acetylcholine including bipolar disorder, schizophrenia, substance-abuse, mood, pain, and sleep disorders. Conclusion: The habenula provides an important interface between limbic-related forebrain areas and brainstem nuclei that modulate multiple aspects of behavior, including reward, affect, and defense. It has been found to influence adaptive behaviors and bias choice in responding to both aversive/positive events. Habenular dysfunction is implicated in several symptom clusters across neuropsychiatric disorders. With connections to serotoninergic, cholinergic, and dopaminergic systems, this structure has immense potential as a future target for innovative treatment interventions.

Background: Research suggests posttraumatic stress disorder (PTSD) is associated with deficits in inhibitory control, verbal learning, and cognitive flexibility. It is unknown whether evidence-based treatments for PTSD can also improve these cognitive deficits. Objective: This study seeks to evaluate the impact of cognitive behavioral therapy (CBT) for PTSD on inhibitory control, verbal learning, and cognitive flexibility in post-9/11 veterans. Methods: Fourteen post-9/11 veterans presenting to Home Base (age M=35.1, SD=7.3, 21.4% female) underwent neuropsychological testing prior to beginning CBT for PTSD. Measures included the Rey Auditory Verbal Learning Test, a measure of verbal memory and learning, and the Delis-Kaplan Executive Function System Color-Word Interference Test, a two-part measure of inhibitory control and cognitive flexibility. Patients were reassessed within one month of treatment completion. Neurocognitive outcomes were assessed for improvement using paired Student’s t tests. Results: Patients showed significant improvement in inhibitory control from pre- to posttreatment assessment (10.4(2.4) vs. 11.5(2.1)), t(13)=–2.44, p=0.029, with a trend toward improvement in verbal learning (75.4(12.4) vs. 81.7(11.2)), t(13)=–1.91, p=0.078. Patients did not significantly improve in cognitive flexibility (9.8(3.0) vs. 10.6(3.1)), t(12)=–1.17, p=0.264. Conclusion: These findings suggest that CBT for PTSD is associated with cognitive improvement in the domains of inhibitory control and verbal learning pre- to posttreatment. If replicated in a larger sample, results would suggest cognitive performance improves after CBT for PTSD. Limitations include inadequate power due to small sample size; additionally, we cannot distinguish between improvement in cognitive scores due to treatment versus improvement due to retest learning effects.

Background: Temporal-occipital stroke is usually associated with visual field defects, anomia, reading disorders, and memory deficits. Previous case studies show right temporal-occipital infarction causes left hemimacropsia and left upper quadrantanopsia, topographical disorientation, posterior alexia, and prosopagnosia. Case History: In June 2011, a 43-year-old woman (Sarah) presented to a Boston-area emergency department complaining of bilateral acute visual changes, headaches, and vomiting. A brain CT scan showed no abnormalities. She was diagnosed with a migraine and sent home. A week later, Sarah presented to another emergency department with persisting symptoms. An MRI showed changes consistent with subacute right temporal-occipital infarction in the right posterior cerebral artery distribution. In subsequent months, Sarah worked with occupational therapy on visual-perceptual training with limited improvement. She experienced headaches; left-sided, homonymous, congruous, superior quadrantanopia; short-term memory loss; spatial and temporal disorientation; visual dissociation; and inability to drive or navigate crowds. Neurocognitive testing six months later found high intellectual function, impulsivity, and relative deficits in auditory attention, visual synthesis and integration, working and delayed memory, and contextual learning. Over five years, she participated in multimodality treatment. She trained for and completed the 2013 Boston Marathon, learned new musical and visual artistic skills, and began making musical instruments. In 2016, she reported noticeable improvements in cognition and daily functioning. Repeat neurocognitive testing six years postaccident documented sustained and substantial improvements. Conclusions: This case highlights the importance of recognizing unusual stroke presentations, neuropsychiatric symptoms associated with right temporal-occipital stroke, and long-term symptom improvement putatively related to brain plasticity.

Background: Inferences regarding age-related differences in behavioral and neural activity are most often based on results from single experimental testing sessions. However, there is limited information about whether such findings accurately reflect stable characteristics of the populations studied. Objective: To determine the six-week test-retest reliability of electrophysiological and behavioral responses to novel visual stimuli in healthy older adults. Methods: ERPs and behavioral data were collected on 70 healthy older adults (mean age 75.2) who participated in a visual novelty oddball task in which they controlled viewing duration. Alternate versions of the task were presented during two sessions approximately six weeks apart. P3 amplitude and viewing duration of novel stimuli served to index the allocation of attention to novelty. Between testing sessions, subjects participated in one of four randomly assigned, structured programs involving adaptive or nonadaptive computerized cognitive training, physical exercise, or mindfulness meditation. Results: Test-retest results were collapsed across the four structured programs because none of the findings were modulated by this variable. Viewing duration and P3 amplitude in response to novel stimuli did not differ between testing sessions (ps>0.3). Moreover, between-session correlation coefficients were very high for both P3 amplitude (r=0.77, p<0.0001) and viewing duration (r=0.68, p<0.0001). Conclusions: Older adults exhibit considerable stability in their electrophysiologic and behavioral responses to novel visual events over a six-week period. These results suggest that older individuals have a characteristic way of processing novelty that appears resistant to transient changes in their environment and can be indexed during a single testing session.

Background: Differentiating ictal panic from panic disorder is often challenging on the basis of symptoms alone highlighting an obscure boundary between epilepsy and psychiatric disorders. In patients for whom ictal panic are the sole manifestation of epilepsy, accurate diagnosis and effective management may elude providers for years with a consequential worsening of morbidity both medically and psychosocially. Case History: We describe two patients who presented with isolated intractable panic disorder, whose diagnosis of simple partial seizures was only confirmed after EMU monitoring. Patient 1 was a 45-year-old male with a five-year history of crippling medically refractory emotional lability and panic disorder who presented to neurology following the development of atypical starring episodes. EMU monitoring revealed a localized nondominant anterior temporal epilepsy and following stereotactic lobectomy has remained clinically free of panic attacks. Patient 2 was a 39-year-old woman with an extensive history of panic attacks, GAD, and unexplained gastrointestinal dysmotility who presented to neurology following an isolated provoked generalized convulsion. During EMU monitoring, witnessed panic attacks associated with bilateral occipital discharges that source localized to the nondominant insular cortex and subsequently improved on clozabam. Conclusions: In both cases, the patient initially presented to psychiatric services for management being referred to a neurologist only after a series of failed attempts to treat and developing salient seizure features. These cases both illustrate the value of prolonged electroencephalography in the differentiation of epileptic from nonepileptic attacks as well as reinforce the theory that these phenomena arise from a common neuroanatomical substrate.

Background: Neuropsychiatric phenomena are a common complication of stroke ranging from mood disorders to personality changes. However cases of poststroke psychosis remain a rarity in the literature of which bilateral caudate infarctions constitute an even smaller subdivision. Case History: We report a 40-year-old male who presented with family reporting a three-day history of bizarre behavior. Per family, patient’s abnormal behavior began with insomnia, followed by excessive fatigue, disinhibition, headache, and then hallucinations. The night of admission patient had been found consuming uncooked fish and claiming that he was both in a restaurant and that the fish was cooked. On presentation patient was disorientated, confabulating, responding to internal stimuli, abulic with psychic akinesia demonstrating unusually slow motor responses and verbal cadence, without aphasia or focal neurological deficit. CT scan brain revealed hypoattenuation involving the bilateral caudate/anterior lentiform nuclei and the left medial frontal lobe. CT Angiography of the head and neck displayed a thrombus at the bifurcation of the left ICA with proximal stenosis of the left ACA with occlusion at the origin of the right ACA. MRI brain demonstrated high signal intensity consistent with bilateral infarction of the head of the caudate, anterior lentiform nuclei, anterior corpus callosum and the fornices. At discharge one week later, patient remained psychiatrically and cognitively incapacitated requiring long term skilled nursing care. Conclusions: This case further illustrates the critical role of the caudate nuclei in the frontal-subcortical circuit to control prefrontal behaviors, multimodal feedback, and the integration of memories.

Background: As ictal seminology is increasingly understood to arise from epileptogenic networks, high frequency oscillations (HFO) propagation patterns are helping elucidate networks relevant for surgical planning. Musical automatisms, a well-documented rare phenomenon of epilepsy, have yet to be examined as a manifestation of HFO propagation in the public literature. Case History: We report a 62-year-old left-handed female with a history of intractable complex partial seizures who presented as a candidate for surgical management of epilepsy. Patient’s typical episodes were preceded by an aura described as a generalized sensation of warmth with ringing in both ears subsequently followed by manual automatisms of mouth, hands and feet. Initially automatisms were restricted to palilalia however overtime evolved into a rhythmic melodic humming and concomitant singing. 3T MRI brain was significant for increased T2/FLAIR signal intensity in both mesial temporal lobes and right medial parieto-occipital area. EMU monitoring demonstrating rhythmic discharges at T3/T5 regions with rapid propagation to ipsilateral frontal lobe and slowing of contralateral frontal hemisphere. Intracranial video-EEG monitoring demonstrated spike and wave discharges in left inferior anterior temporal lobe followed by HFO in the same leads with evolving poly-spike and wave discharges. Functional mapping demonstrated source localization to left mesial anterior temporal lobes and lateral inferior temporal cortex. Following left anterior temporal lobectomy with hippocampectomy, patient remains seizure free one year postoperation. Conclusions: Our findings further support the theory that the rare phenomena of musical automatisms localize to a nondominant temporal network rather than a specific cortical territory.

Background: The neural circuitry mediating the influence of motivation on long-term episodic memory formation is delineated in young adults, but its status is unknown in healthy aging. Objective: To compare between younger and older adults the influences of motivation (reward and punishment) on long-term intentional memory formation and incidental motivational cue processing. Methods: We examined the effect of reward and punishment anticipation on intentional declarative memory formation for words using an event-related fMRI monetary incentive encoding task and a separate monetary incentive delay (MID) task that did not require learning in twenty-one younger and nineteen older adults. Results: At 24-hour memory retrieval testing, younger adults were significantly more likely to remember words associated with motivational cues than neutral cues. Motivational enhancement of memory in younger adults occurred only for recollection and not for familiarity. Older adults had overall diminished memory and did not show memory gains in association with motivational cues. Memory encoding associated with monetary rewards or punishments activated motivational (substantia nigra/ventral tegmental area) and memory-related (hippocampus) brain regions in younger, but not older, adults during target word periods. In contrast, older and younger adults showed similar activation of these brain regions during the anticipatory motivational cue interval. We found evidence for relatively preserved striatal reward anticipation in older adults on the MID task. Conclusion: Our results suggest a dissociation in healthy aging between tasks requiring intentional motivated learning with delayed feedback compared with tasks requiring incidental processing of motivational cues with low effort and immediate payoff.

Background: Childhood primary angiitis of the central nervous system (cPACNS) is a rare and a potentially fatal cause of childhood stroke. The disease itself poses a diagnostic dilemma for clinicians due to overlapping and varied manifestations including focal acute neurological deficits, cognitive impairment, or encephalopathy. Diagnosis continues to be challenging and little is known about the pathogenesis and long-term outcome of cPACNS. Case History: The authors report findings from serial neuropsychological evaluations, imaging studies, and genetic evaluation of a 14-year old right handed male with a diagnosis of cPACNS with posterior circulation vasculitis. From 2010, he experienced approximately 7 clinical strokes and >10 TIA and receives chronic anticoagulation and antiplatelet therapy. His most recent episode occurred in September 2017 when he was hospitalized due to left arm weakness and dizziness. His most severe presentation of vascular insufficiency occurred in January 2012, where he experienced diplopia, altered mentation, and respiratory arrest. Although the patient was described as an academically advanced student, parent endorsed concerns with his memory functioning. Serial neuropsychological evaluations revealed intact and stable intellectual/academic scores albeit somewhat lowered from baseline scores. Relative weaknesses were noted in processing speed and working memory skills (in the average range but declined from baseline evaluation). Conclusions: This case study emphasizes the need to identify vasculitis as a differential diagnosis in children and adolescents with multiple stroke and TIA events. Early identification followed by prompt and aggressive multidisciplinary treatment may offer a stable course.

Background: Maladaptive coping in the context of adverse life events is a predisposing factor for Functional Neurological Disorders (FND). Limited research to date has investigated neuropsychiatric factors associated with resilience in FND. Objective: This prospective cohort study investigated differences in self-reported resilience in patients with motor FND compared with healthy controls. Secondary within-group analyses characterized associations between resilience, affective symptoms, personality traits and adverse life events in patients with motor FND. Methods: 50 individuals with motor FND and 47 healthy controls participated. A Mann-Whitney U test evaluated group-level differences in Connor-Davidson Resilience Scale (CD-RISC) scores, followed by a logistic regression analysis adjusting for demographic factors. For within-group analyses, univariate screening tests followed by a multivariate linear regression analysis examined neuropsychiatric factors associated with self-reported resilience in the motor FND cohort. Results: Patients with FND reported significantly reduced CD-RISC scores (p<0.001; 63.2±16.5) compared with controls (78.7±12.1). This finding remained significant controlling for age, gender, education status, ethnicity and lifetime adverse event burden (p=0.032). In within-group analyses, mental health, NEO-extraversion, NEO-conscientiousness, and NEO-openness showed positive associations with CD-RISC scores; posttraumatic stress disorder symptom severity, depression, anxiety, alexithymia and NEO-neuroticism scores negatively correlated with CD-RISC scores. In a multivariate linear regression, extraversion independently predicted resilience scores in patients with FND (p=0.006). 66.7% of the variance was explained by the model. Conclusion: Patients with FND reported reduced resilience compared with controls, and CD-RISC scores covaried with personality and mood-anxiety factors. Future research should investigate if the CD-RISC is predictive of outcomes in FND.

Background: Explicit neural segregation of anticipatory anxiety (AA) versus fear of current aversive stimuli sufficient to be leveraged for developing syndrome-specific interventions for disorders marked by refractory anxiety remains elusive. Habituation to impending threat via experience represents a foundation for healthy adaptation, subserving resilience. Failure of habituation can be a component of disorders marked by threat-disconnected anxiety. Objective: We designed a neuropsychological paradigm, delivered within an fMRI protocol, to (1) independently induce AA and adverse stimulus fear to probe common/distinct neural substrates, and (2) elucidate neural mechanisms of healthy habituation. Methods: Eight right hand-dominant healthy subjects were presented with an AA-induction paradigm (via noxious but noninjurious electrodermal stimulation) while undergoing fMRI. Galvanic Skin Response (GSR) was synchronously recorded with fMRI acquisition. Results: A main effect of GSR amplitude change by condition type (“impending threat” versus “safe”; p≤0.001) was revealed: GSR amplitude in response to “impending threat” was greater relative to “safe” cue conditions (p≤0.001). A main effect in GSR amplitude between early and late runs was seen, attributable to amplitude reduction associated with cue signifying “impending threat” (p≤0.004) relative to cue signifying “safe”. fMRI contrasts of “impending threat” versus “safe” conditions demonstrated relative activations of insula, claustrum, thalamus, and visual areas. fMRI contrasts of late versus early impending threat revealed increased activity in medial-frontal regions, including cingulate. Conclusion: Recruitment of a visceral-sensory and visual-attentional neural network was associated with AA attendant to visually-signaled threat. Habituation was associated with activation of neural substrates implicated in top-down modulation of emotion.

Background: Distinct autoantibody profiles and blood-brain barrier (BBB) damage have been investigated as critical features of Alzheimer’s disease (AD) for pathogenic and diagnostic purposes. Objective: To demonstrate the mechanisms that occur in amyloid plaque formation following BBB breakdown in AD pathogenesis. Method: Immunohistochemistry (IHC) was used to assay BBB compromise and interactions of amyloid-β₄₂ with autoantibodies in AD brains. A cell culture model was used to test the neuronal internalization pathway of autoantibody-mediated amyloid deposition. Endocytosis inhibitors and antibody purification/treatment steps was used to detail the cellular and molecular events governing observed phenomena. Lastly, human protein microarrays were employed to identify specific autoantibodies as diagnostic biomarkers for AD detection and staging. Results: IHC experiments showed that neuron-binding autoantibodies selectively target pyramidal neurons and glia in regions of BBB damage. Cell culture experiments supported the pathological findings and helped to quantitatively elucidate the mechanistic details observed. The pathological sequence includes intraneuronal accumulation of amyloid-β₄₂ and lysosomal compartment expansion, that can be mitigated when antibody-depleted sera is used or appropriate inhibitors. Serum autoantibodies from controls and AD patients dramatically increased rate and extent of intraneuronal amyloid-β₄₂ deposition in the cell culture model. Conclusion: Results suggest neuron-binding autoantibodies have diagnostic utility and gain access to the brain parenchyma through dysfunctional BBB. This allows them to bind neuronal surfaces and enhance intraneuronal deposition of amyloid-β₄₂ in AD brains. We propose that in the context of BBB compromise, brain-reactive autoantibodies may be an important assayable risk factor for the initiation and progression of AD.

Background: Most patients with anti-NMDA receptor encephalitis (anti-NMDArE) are initially evaluated by a psychiatrist because of the complex behavioral or psychiatric symptoms that can be associated with it. Seizures are common, but hallucinations are also frequent, and are one reason that psychiatrists often misdiagnose the disorder as a primary psychiatric illness. A better appreciation of hallucinatory symptoms in anti-NMDArE is needed to improve diagnostic accuracy early in its course so long-term disability can be avoided. Objective: To characterize the frequency and prevalence of sensory abnormalities in anti-NMDArE. Methods: PubMed and EMBASE databases were systematically searched for reports of anti-NMDArE patients aged 19+years with behavioral or psychiatric symptoms. Results: The search yielded 75 reports describing 144 unique patients (17M, 127F). Seizures were present in 72.9%, whereas 41.7% experienced hallucinations. Sensory modalities affected were auditory (18.1%), visual (11.1%), tactile/somatic (2.1%), olfactory (1.4%), taste (0.7%), and unspecified (12.5%). Many patients experienced symptoms in more than one modality. Hallucinations on the whole were not associated with seizures (p=1.0), but visual hallucinations and seizures were positively associated (one-tailed p=0.036) whereas auditory hallucinations were not (one-tailed p=0.23). In addition, the quality of sensory symptoms in both modalities was often atypical for a primary psychotic disorder. Conclusion: It is likely that every psychiatrist will encounter a patient with anti-NMDArE in the course of his/her practice. The presence of seizures, especially when accompanied by visual hallucinations or atypical auditory hallucinations, should prompt active consideration of this diagnosis.

Background: Anti-NMDA receptor encephalitis (anti-NMDArE) is more common in women because the autoimmunity is usually triggered by a teratoma or pregnancy, but other neoplastic processes and viral infections can also produce these antibodies. Psychiatrists are usually the first clinicians to evaluate these patients because complex behavioral disturbances are common, but cognitive impairments are also prominent and can cause long-term residual disability if effective treatment is not given promptly. Objective: To estimate the prevalence of cognitive abnormalities in anti-NMDArE patients likely to be seen in psychiatric practice. Methods: An unrestricted systematic search of PubMed and EMBASE databases identified 75 reports of 144 unique anti-NMDArE patients aged 19+years (17M, 127F) with behavioral or psychiatric symptoms. Results: The most common cognitive abnormalities were disorientation/confusion (36.8%), memory impairment (usually anterograde) (25.0%), aphasia (18.1%), and executive dysfunction (17.4%); at least one of these was present in 58.8% of men and 57.5% of women. Memory deficits were equally prevalent in men and women (23.5% versus 25.2%), but executive dysfunction and disorientation/confusion were more frequent in women (11.8% versus 18.1%, 23.5% versus 38.5%) and aphasia was almost twice as likely in men (29.4% versus 16.5%). None of these differences was statistically significant (2-tailed p>0.19). There was considerable variability with respect to the sequencing and timing with which these abnormalities were observed. Conclusion: Significant cognitive dysfunction is common in anti-NMDArE and may provide important early diagnostic clues for psychiatrists who are vigilant for this disorder.

Background: Anti-NMDA receptor encephalitis (anti-NMDArE) and neuroleptic malignant syndrome (NMS) are rapidly evolving neuropsychiatric disorders with substantial mortality rates. Both can present with hyperthermia, mental status changes, motor signs and autonomic dysregulation, and anti-NMDArE is often misdiagnosed as NMS. The diagnostic confusion arises when anti-NMDArE presents with behavioral disturbances that appear to be psychiatric in nature, and antipsychotic medications are administered. However, the treatments for these disorders are distinct, and both require prompt intervention to avert long-term disability or death, so early and accurate diagnosis is essential. Objective: To identify clinical features of anti-NMDArE that distinguish it from NMS. Methods: An unrestricted computerized search of PubMed and Embase databases was performed in January 2017 using a highly inclusive strategy designed to identify all published reports of anti-NMDArE in which behavioral or psychiatric symptoms were present. Results: This procedure identified 17 men and 127 women with mean (S.D.) ages 37.6 (3.2) and 28.7 (9.3) years (p=0.044). Clinical features not usually observed in NMS included seizures (72.9%), orofacial dyskinesias (36.8%), aphasia (18.1%), stereotypies (18.1%), dysarthria (11.8%), and sensory abnormalities (8.3%). Among 39 patients who did not manifest seizures, 23 (59.0%) demonstrated at least one of the other abnormalities. Conclusion: In this sample of published reports, 88.9% of anti-NMDArE patients displayed one or more clinical signs that differentiate it from NMS. Despite the broad similarity of these disorders, detection of any of these features should facilitate accurate diagnosis in settings where both anti-NMDArE and NMS are in the differential diagnosis.

Background: Approach/avoidance behaviors have been shown to be impaired across a variety of psychiatric disorders. Approach involves overweighing reward relative to risk, while avoidance involves overweighting risk. To date, fMRI studies linking these behaviors to underlying neurocircuitry are riddled with inconsistent findings. Objective: To address this inconsistency, in this study healthy adults (n=34) completed both aversion-reward-conflict (ARC) and gambling (WAR) paradigms designed to evoke overlapping regions. Methods: In the ARC task, participants choose a risky (higher likelihood of shock) or safe option (no shock). In the WAR task, the subject and computer are dealt one card, and the participant places a bet with the assumption that the computer’s bet will be the opposite. Using the same logistic model to model behavior for both tasks, we computed the squared distance to the point of maximum conflict (50% probability to take reward). The behavioral model results were then used to parametrically modulate the fMRI signal. At the group level, a conjunction and dysjunction analysis was performed to determine overlapping and unique regions evoked in each task (maps included voxels that survived multiple comparison correction). Results: Interestingly, both tasks elicited overlapping circuitry including regions involved in reward processing (striatum (caudate and NaCC), STN) as well as cognitive control (dACC/dmPFC, dlPFC). Insula was also recruited for both tasks, further corroborating recent findings that suggest it is implicated in risk processing. The disjunction analysis revealed hippocampus as exclusive to ARC. On the contrary, no nodes were unique to WAR. Conclusion: These findings corroborate overlapping circuitry for conflict.

Background: Manganese poisoning is a rare but important cause of encephalopathy. Clinicians’ lack of recognition to its neuropsychiatric manifestations can lead to misdiagnosis and mismanagement. There is also limited literature on the association of manganese toxicity with autoimmune antibody response. Case History: We describe the case of a 55-year-old Chinese man who presented with recurrent episodes of confusion, psychosis, dystonic limb movement and cognitive impairment. He was initially diagnosed with antivoltage-gated potassium channel (VGKC) complex limbic encephalitis in view of previous positive anti-VGKC complex antibodies. Nevertheless, in this current admission his serology titer was equivocal and there was no clinical improvement despite immunotherapy. Testing of heavy metal poisoning came back positive, with spot urine manganese at 62.11ug/L (cut-off<50) and 24-hour urine manganese at 19.7mcg/24hr (cut off<4.0mcg/24hr). A diagnosis of chronic manganese toxicity from occupational exposure was subsequently made. His cognitive and behavioral symptoms improved with empirical rivastigmine. Functional near-infrared spectroscopy of his brain revealed reduced prefrontal activity compared with matched healthy control. Conclusions: This is the first report of a patient with relapsing neuropsychiatric illness from chronic manganese toxicity associated with VGKC-complex antibodies. Acetylcholinesease inhibitors and immunotherapy are proposed to have unique roles in alleviating symptoms of manganese toxicity. Anti-VGKC complex antibodies could be related to manganese via toxicity-related cell damage or could be a nonspecific epiphenomenon. There is a need to consider nonautoimmune trigger in patients presenting with encephalopathy associated with anti-VGKC complex antibodies in absence of Caspr2 or LgI1 antigenic specificity.

Background: Catatonia most often manifests from a known underlying psychiatric illness. However, multiple other etiologies exist that may cause catatonia including drug-induced states. Most often thought of and studied are antipsychotics. However, illicit substances too have been implicated but not as often described. Rarely is methamphetamine use suspected to produce catatonia. Case History: Two cases of possible methamphetamine-induced catatonia will be discussed. The first is a case of a 30-year-old man presenting after a suicide attempt by overdose of methamphetamine with rhabdomyolysis, transaminitis, and a BFCRS of 18 with negativism, stupor and mutism. The second case is a 39-year-old woman with hypothyroidism recovering from myxedema coma with known recent use of methamphetamines and heroin presenting with a BFCRS also of 18 with mutism, stereotypy, posturing, and stupor. Both patients had no previous psychiatric history, a history of polysubstance use, and both improved with Ativan. The second patient improved also with the addition of memantine. Conclusion: The possible causes producing catatonia are numerous, but among the differential, illicit drug use should be thoroughly explored including consideration of recent methamphetamine use which may tailor treatment, including the more ready use of an NMDA antagonist.

Background: In the early 20th century, new onset psychosis secondary to neurosyphilis was not uncommon. With antibiotics, cases of neurosyphilis-induced psychosis became rare, though a rise occurred in the latter half of the century with HIV coinfection. According to the CDC, the rates of primary and secondary syphilis increased from 2.1 (2000–2001) to 8.7 (2015–2016) cases per 100,000. Neurosyphilis could result from any stage of the infection. With the increased rate, there may be an increase in CNS presentations. Case Histories: Two cases will be discussed. Both were without a history of psychiatric illness or immune compromise. Both received partial treatment in 2016. Both rapidly declined into disorganization, bizarre behavior, and psychosis. The first patient is a 36-year-old man, presenting with severe catatonia, improving with penicillin and lorazepam, but now with multiple neurological exam findings: left sided weakness, hyperreflexia, decreased vibratory sense to the knees, flat affect, apathy, and psychosis. The second is a 59-year-old man with a prior CVA presenting with prefrontal and mesio-temporal deficits: perseveration, impaired concentration, dysexecutive function, amnesia, confabulation, hyperorality, right-sided Babinski’s, and lesions on MRI concerning for meningio-vascular syphilis. He too improved with a course of penicillin, though not to baseline. Conclusions: These cases emphasize the importance of testing for syphilis in new-onset psychosis as well as ensuring complete treatment to prevent further complications and disability. If discovered and treated sooner, these two patients may have had better outcomes.

Background: Autoimmune encephalitis is increasingly recognized as a cause of neurological and psychiatric illness. Diagnosis is challenging due to nonspecific clinical symptoms, lack of pathognominic imaging findings, and limited availability of rapid testing to verify diagnosis. An additional challenge is demonstrated when patients with pre-existing psychiatric illness then develop worsening of psychiatric symptoms, which are in fact due to an automimmune etiology. Accurate diagnosis is vital due to dramatically differing treatments for each illness. Case Histories: We present three cases in which primary psychiatric diagnosis delayed recognition of autoimmune encephalitis. Case 1: 58-year-old woman with premorbid bipolar disorder, presenting with relapsing and remitting behavioral changes and catatonia, diagnosed with hashimoto encephalitis. Case 2: 31-year-old woman with a history of bipolar disorder and personality disorder, hospitalized multiple times two years prior to diagnosis of NMDAR encephalitis. Presentation with her typical psychiatric symptoms as well as tachycardia, difficulty swallowing, rigidity, and Parkinsonism led to diagnosis. Case 3 is a 66-year-old woman with known bipolar disorder, with two years of severe relapsing and remitting catatonia, found to have an ovarian teratoma in the context of workup for readmission to psychiatry. Conclusion: Diagnosis of autoimmune encephalitis may be delayed in patients with known psychiatric illness, or may be the underlying cause of behavioral impairment in all cases. Consideration of immunological cause of neurobehavioral and neuropsychiatic illness may lead to more rapid diagnosis and treatment, with decreases in morbidity and mortality associated with this often-treatable illness.

Background: Poisons are classically divided into five categories: heavy metals, gases, organophosphates/solvents, complex metal ions, and drugs of abuse. CNS effects differ with each class. Exposures should be viewed in terms of length/amount of exposure, pre-exposure risk, and postexposure healthcare. Heavy metal exposures can occur in occupational (included war-related), accidental, or abuse settings. Evaluations from previous ANPA presentations in this poison/toxin series (2015, 2017) were very positive, and indicated the need for more teaching products of this type. Incorporating feedback allows further refinement and adaption of materials for use in additional clinical conditions. Objective: Create new teaching materials in which color carries a significant portion of the information, allowing large volumes of data on functional neuroanatomy and clinical presentation to be combined without overwhelming learners. Methods: New scientific and clinical research relevant to physiology of heavy metals, particularly regarding comorbid war-related injuries and exposures, as well as farming and sheet metal work were reviewed, synthesized, and summarized into graphic rich original teaching materials (e.g. diagrams, charts, models). Results: Use of graphic-rich materials that connect functional neuroanatomy, physiology, and clinical practice deepens interest in the individual aspects of each patient, and enhances appreciation of co-occurring pathologies and prognosis. Conclusion: These newly revised tools support guiding learners’ through the intricacies of this complicated field. Use of guided experiences strongly promotes development of the active, integrated knowledge of functional anatomy required for practice of neuropsychiatry as it relates to assessment and treatment of heavy metal exposures, particularly with comorbid war-related exposures.

Background: The most common method of completed suicide in children under 12 years of age is by use of firearms, followed by self-hanging. Hanging attempts are increasing in minors, but there is scarce research on the sequelae of survivors. We report on a 12-year-old patient who sustained a near-hanging episode after which he experienced behavioral and neurocognitive sequelae. Case History: A 12-year-old male with a history of major depressive disorder, anxiety disorder and attention-deficit hyperactivity disorder (ADHD) presented with delirium and visual hallucinations soon after the hanging attempt, followed shortly after by speech and language dysfunction, retrograde and partial anterograde amnesia, abnormal gait and regression of motor abilities. In the rehabilitation setting, repeat neurocognitive testing (April 2017) documented cognitive sequelae, in comparison to his prehanging episode testing (May 2016). Changes in cognitive ability were global, affecting primarily working memory and speed of information processing. Wechsler Intelligence Scale for Children (WISC)-V working memory (pre SS=100, post SS=76); processing speed (pre SS=86 and post SS=60) were documented. Postinjury behavioral changes impacted the patient’s function and included lethargy, impulsivity, emotional lability, noncompliance and aggressive tendencies. Conclusion: Near-hanging attempts can incur in significant behavioral and cognitive sequelae, which suggest that long term follow-up is required to facilitate early intervention and management for improved prognosis.

Purpose: Mint increases attention by stimulating the trigeminal nerve, and small nerve fiber discharge. The purpose of this study is to determine if chewing mint flavored gum affects reaction time as compared with chewing unflavored gum. Methods: Case Study: Twenty high school students were recruited on a convenience basis. After risks were described and consent was obtained, subjects performed the Ruler Drop Test of reaction time, with their dominant hand, while sitting ten times, while chewing flavorless gum, and ten times while chewing mint flavored gum, or vice versa. Average reaction time was computed for each condition, with the unflavored gum serving as the control condition. Significance of difference was delineated using the sign test. Results: For the group as a whole, (N=20), nine subjects demonstrated quicker reaction time with the flavorless gum and eleven were quicker with the mint gum. Using the one-tailed t test, no significance was found (p=0.41). Using the two-tailed t test, no significance was found (p=0.82). For only those with positive hedonics toward the mint gum (N=14), six had faster reaction times with flavorless gum and eight were faster with mint flavored gum. Again, no significance was seen using the one-tailed t test (p=0.40) or using the two-tailed t test (p=0.79). Conclusion: There was no significance difference in reaction time (p>0.05) between the two conditions. The null hypothesis was not rejected. There was no difference between chewing mint-flavored gum and unflavored chewing gum and reaction time. In this paradigm when chewing gum, no effect of additional mint flavor was seen to impact upon reaction time.

Background: Behavioral treatments are a first line, under-utilized, well tolerated treatment for migraine. With headache expert and patient stakeholder involvement, we developed a smartphone application (RELAXaHEAD) with progressive muscle relaxation (PMR) therapy and an electronic headache diary. Objective: To assess preliminary data of the feasibility of use of RELAXaHEAD in the outpatient Headache Center setting. Methods: Over a 6-week period from July-August 2017, adults ages 18–85 with migraine with no prior behavioral treatments for migraine in the past year were approached to participate in a study for smartphone based PMR for 3 months. An initial baseline questionnaire was completed and patients were asked to do PMR 20 minutes/day and complete a daily headache diary. All patients also completed one PMR session during the study enrollment meeting. Results: Of the 78 consecutive Headache Center patients approached, 37 (47%) agreed and were eligible to participate. 89% were female. Mean age was 36.24 [SD 12.12, range: 19–63]. Mean baseline MIDAS score was 49.2. Within the first 30-day period, mean number of days of diary entry was 25.14 [SD: 6.44, range: 7–30] and mean number of days of PMR was 11.24 [SD 6.64, range: 3–28]. To date, 57% were reached for an initial 30-day follow-up survey. Conclusions: Patients were successfully introduced to a free migraine behavioral treatment which they could do independently. On average, they performed PMR about three times weekly. The majority completed the diary entries on a near daily basis. The initial feasibility testing will inform protocol refinements.

Background: Patients with neurocognitive disorders are frequently admitted to the general hospital after neglecting their medical needs. These cases are often complicated by diagnostic uncertainty, questions regarding appropriate treatment, and unclear dispositional capacity (Bourgeois et al. 2017, Naik et al. 2009). Our institution developed a collaborative consultation model to provide formal executive function testing in the general hospital setting. We present two cases of patients who benefited from formal executive function testing. Case 1: 70-year-old female with history of psychosis and multiple medical comorbidities who was probated to the hospital due to paranoia, failure to care for herself, and refusing to allow healthcare workers to enter her home. Neuropsychiatric testing revealed significant executive dysfunction. Guardianship was pursued to facilitate placement in a skilled nursing facility. Case 2: 70-year-old female with history of schizoaffective disorder who was probated to the hospital due to aggressive behavior and refusal of care at her nursing facility. The consultation-liaison psychiatry team suspected a progressive neurocognitive disorder rather than schizoaffective disorder as the underlying cause of her behavioral changes. Neuropsychiatric assessment revealed severe executive dysfunction and confirmed diagnosis of neurocognitive disorder. The patient’s family obtained guardianship and the patient was discharged to a nursing facility. Conclusion: There are increasing numbers of self-neglecting patients who present involuntarily with perceived complications of primary mental illness who are often admitted to general medical units. When the consultation-liaison psychiatry team suspects the underlying cause of self-neglect is a neurocognitive disorder, additional consultation by neuropsychiatry and formal executive testing improves diagnostic clarification and discharge planning.

Bourgeois J, Cohen M, Erickson J, Brendel R. Decisional and Dispositional Capacity Determinations: Neuropsychiatric Illness and an Integrated Clinical Paradigm. Psychosomatics 2017. 58:6. 565-573.

Naik AD, Dyer CB, Kunik ME, et al: Patient autonomy for the management of chronic conditions: a two-component re-conceptualization. Am J Bioeth 2009; 9:23–30

Background: The consequences of untreated catatonia with psychosis can be detrimental to the mother and potentially the fetus. There is a dearth of information on how to manage pregnant patients with a previous history of postpartum catatonia. In general, initiation of postpartum prophylaxis in women with a history of postpartum psychosis has shown to be highly effective for preventing postpartum relapse. Cases: A 34-year-old G2P1 Indian woman had been previously successfully treated with a short course of Ativan after she developed severe psychotic and catatonic symptoms a few days after her first pregnancy on an inpatient psychiatric unit. She then received Lithium which was discontinued 12 months later after her perceptual disturbances disappeared. The patient did not become catatonic again. She is now in her first trimester of second pregnancy and presents to the outpatient clinic for prophylactic management for catatonia and psychosis. Conclusion: Given the serious adverse consequences of untreated psychosis with catatonia, it is important to closely monitor patients and provide prophylactic management as needed to prevent a postpartum relapse. We will provide the most recent literature of prophylactic medication regimen for preventing postpartum psychosis that has helped guide our recommendations for helping monitor symptoms of catatonia.

Gonzales N, Quinn DK, Rayburn W: Perinatal catatonia: a case report and literature review. Psychosomatics 2014; 55:708–714

Espínola-Nadurille M, Ramírez-Bermúdez J, Fricchione GL: Pregnancy and malignant catatonia. Gen Hosp Psychiatry 2007; 29:69–71

Background: Acute disseminated encephalomyelitis (ADEM) is an acute autoimmune demyelination of the central nervous system most commonly following infection and is rarely seen in adults. We previously reported a case of an adult with ADEM who did not return to her neuropsychological baseline after medication management. Now we report on the use of ECT in resolving her depression with psychosis and catatonic features secondary to ADEM. Case History: A 34-year-old female with a past history of depression with suicidal attempts was diagnosed with ADEM in 2014 after she developed paranoid ideations, perceptual disturbances, worsening mood, disorganization and a grand mal seizure for the first time. Diagnosis was confirmed with CSF and MRI. Her neuropsychiatric symptoms did not fully respond to lorazepam, antidepressants and antipsychotics. Her treatment resistant depression has since been stabilized with electroconvulsive therapy with resolution of the hallucinations and paranoia secondary to her ADEM. Conclusions: ECT was shown to be beneficial to this patient for treatment of the depression with psychosis and catatonic features associated with ADEM. We propose ECT as a management option for psychosis and catatonic features secondary to ADEM. Additionally, development or worsening of a depressive disorder with or without psychotic features occurring in an adult after a sudden infectious illness warrants a thorough diagnostic evaluation to rule out ADEM.

Background: The re-emergence of neuropsychiatry in the twentieth century occurred in the context of a history of neuropsychiatric contributions to medical science. In parallel to the growth of neuropsychiatry as a medical specialty, psychiatry has benefitted from developments in neuroscience, many of these built upon foundations established by neuropsychiatrists. Objective: We sought to enumerate the contributions by psychiatrists with neurological training to advances in medical science. Methods: We searched PubMed using the terms neuropsychiatry history, psychiatry and neurology history and cross-referenced physicians, scientists, doctors and clinicians in psychiatry and neurology, including publications in all languages. The search was repeated in PsychINFO. We reviewed several textbooks that include neuropsychiatric history and interviewed neuropsychiatrists, behavioral neurologists, and combined neurologists/psychiatrists. From these sources, we created a database of neuropsychiatrists and their contributions. Results: Electronic searches yielded 165 articles for review. Using these, combined with textbooks and interviews, we identified over 50 neuropsychiatrists who made important contributions to medical science since the inception of the field of psychiatry. Conclusion: Physicians who have trained and/or practiced in both neurology (or neurological sciences) and psychiatry have made major contributions to medical science. Rather than solely looking to the creation of clinician scientists to push the field of psychiatry forward, there is a strong argument to be made that interdisciplinary training in neurology and psychiatry will continue to spawn advances in psychiatric understanding.

Background: Mild traumatic brain injury (mTBI) is the most common type of brain injury. Following mTBI, many patients develop a cluster of symptoms which can be physical, cognitive, emotional or behavioral. Among sequelae from mTBIs, working memory (WM) is a core and chronic cognitive deficit. Pathophysiological changes that occur after mTBI do not explain the precise deficits in WM. Electrophysiological evidence demonstrates that oscillation between gamma and theta frequencies provides the foundation for WM and ordering of information. Impaired theta-gamma coupling is demonstrated in other patient populations like schizophrenia. Objective: We conducted a scoping review on studies using neurophysiological techniques to investigate WM changes in patients with mTBI. Methods: A systematic search of Medline and EMBASE databases using the terms to include “electrophysiology” and sub terms, “mild TBI”, “memory” and sub terms. Human studies in English involving mTBI patients without other neurological, psychiatric or substance use comorbidity and using standardized WM and electrophysiological measurements were included. Results: Our search yielded 33 articles. A total of 13 articles met inclusion/exclusion criteria. No studies used theta-gamma coupling to study WM in mTBI. Majority of studies used evoked response potential (ERP) and demonstrated decreased amplitude in mTBI cohort during WM tasks. Conclusion: WM impairment is an important consequence of mTBI and its underlying mechanism remains elusive. Theta-gamma coupling has been studied in other cognitive populations but not in mTBI. There is an opportunity to study this paradigm in mTBI especially with the potential for therapeutic intervention with noninvasive brain stimulation.

Background: The roles of prefrontal cortical dysfunction in psychosis and right frontal lobe lesions in mania have previously been discussed. Here, we describe a presentation of manic psychosis with incidental discovery of remote cryptogenic right frontal and left parietal strokes in a patient with mood and cognitive symptoms but no other focal neurological deficits. Case History: Ms. B is a 49-year-old woman with no psychiatric history who was brought in by police after chasing lawn care professionals with a shovel and knife. Collateral information noted an acute to subacute change in personality and behavior six years ago, following hysterectomy and bilateral oophorectomies for endometriosis. Presentation included symptoms of mania and psychosis. Both CT/MRI revealed chronic ischemia and encephalomalacia in the left parietal and right frontal lobes. Neuropsychiatric examination revealed dys-executive function, disinhibition, poor concentration, and impaired problem solving/reality testing, consistent with her right frontal lobe lesion. Patient also had cognitive impairments, including visuospatial difficulties (clock construction, mild neglect on embedded figures, prosopagnosia), anosagnosia, and slight motor apraxia consistent with her left parietal lobe dysfunction. No abnormalities were found in a full-workup for stroke in the young. Antipsychotic treatment resulted in decreased levels of paranoia and withdrawal, although still present, and a slow resolution of manic symptoms. Conclusions: This case demonstrates poststroke mania and psychosis with mild cognitive impairments but no other focal deficits as potential manifestations of cryptogenic right frontal and parietal strokes.

Background: Electroconvulsive Therapy (ECT) is the most effective treatment in psychiatry, and among the most effective in medicine. In addition to its efficacy in depression, mania, psychosis and catatonia, it has primary antisuicidal properties independent from its effects on the primary disorders. Understanding the mechanisms of action of this life-saving treatment may be a strategy to identify novel and much needed targets for antisuicidal therapies. Methods: We studied 16 patients treated with ECT for depression. Before and after the acute course of treatment, we obtained resting-state functional MRI measures, quantified depression severity with the QUIDS-SR and suicide risk with the CHRT. After standard data preprocessing steps, whole-brain connectivity analyses were conducted using anterior cingulate cortex (ACC) seeds. The ACC has been previously linked to suicide risk and severity using multiple research methodologies (postmortem pathology, PET, MRI, etc.). To examine the relationship between functional connectivity and clinical outcomes, whole-brain regressions were conducted using changes in CHRT and QUIDS scores. Results: We identified changes in connectivity in two overlapping nodes in the right Inferior Parietal Lobule, encompassed in the fronto-parietal Central Executive Network, that both explained and predicted the improvement in suicide risk specifically (CHRT changes), but not the syndromal changes in depression severity captured with the QUIDS. Conclusions: These results suggest a putative mechanism for the antisuicidal properties of ECT. Changes occur across regions known to be relevant for affective regulation, self-processing and top-down executive control, dimensions relevant to the “suicidal syndrome”. The observed circuit dynamics represent a possible target for treatment, potentially using alternative and less invasive therapeutic modalities like transcranial magnetic stimulation (TMS). In addition, patterns predicting positive response may be used as biomarkers to support clinical decision-making and ECT treatment selection and planning.

Background: C9orf72-related bvFTD can be a challenging diagnosis for clinicians. We report a case of C9orf72 mutation presenting with behavioral changes and late-onset mania showing unusual bifrontal elevated metabolism on FDG-PET despite advanced symptoms. Case History: A 68-year-old man presented with a two-year history of progressive behavioral and personality changes. His past medical history and family history were noncontributory. There was a psychiatric history of one manic or psychotic episode in his twenties. Initial symptoms included time-consuming compulsive behaviors, a preoccupation with his saliva, choking, increased sugar intake, loss of empathy, social withdrawal, and disinhibition. Following an unremarkable CT head, a brain FDG-PET was ordered, which surprisingly showed bifrontal metabolism at the higher end of normal, without any areas of hypometabolism. Given the strongly suggestive clinical picture, a diagnosis of possible bvFTD was maintained despite normal imaging, and the patient was started on citalopram. However, he subsequently exhibited symptoms of mania: over-excitation, insomnia, and talkativeness – this was eventually stabilized on divalproic acid and risperidone. While there was no suggestive family history, genetic testing was obtained after the patient developed dysphagia suggestive of FTD-ALS. A C9orf72 repeat expansion was identified, confirming the diagnosis of definite bvFTD. A repeat brain MRI three years after the onset of symptoms showed no significant atrophy. Conclusions: While psychiatric prodromes and atypical imaging have been well-documented in C9orf72 cases, this is the first report of a patient displaying bifrontal elevated metabolism despite relatively advanced bvFTD symptoms in the context of overlap with mania.

Background: Social cognitive ability is a strong determinant of functional outcome. Deficits in social cognition are a prominent feature of psychotic disorders (Mancuso et. al. 2011). The neurobiological underpinnings of social cognition are not well understood, hampering our ability to ameliorate these deficits. Objective: Using a data-driven approach, we sought to identify the brain network basis of social cognition using a combination of fMRI (functional magnetic resonance imaging) and a validated measure of social cognition. Methods: Subjects included 60 participants with a diagnosis of schizophrenia or schizoaffective disorder and 46 healthy comparison participants. All participants underwent a resting-state fMRI scan. Social cognition was measured using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) administered as part of the MATRICS battery of cognitive tests. A connectome-wide analysis of brain connectivity examined how each individual brain voxel’s connectivity correlated with MSCEIT performance using multivariate distance matrix regression (MDMR). Results: We identified a region in the left superior parietal lobule (SPL) where functional connectivity strongly predicted social cognition. The ‘network membership’ (i.e. the extent to which this region correlated with two large brain networks) strongly predicted cognitive ability. This observation was replicated at multiple sites and the correlation between network membership and social cognitive ability was observed in both schizophrenia and healthy comparison participants. Conclusion: The SPL is known to be highly heterogeneous at the cytoarchitectural level (Scheperjans et al. 2008). The cognitive relevance of this was previously unknown. Here we observe that that individual variation in SPL brain network topology predicts complex social cognition.

Mancuso F, Horan WP, Kern RS, et al: Social cognition in psychosis: multidimensional structure, clinical correlates, and relationship with functional outcome. Schizophr Res 2011; 125:143–151

Scheperjans F, Eickhoff SB, Hömke L, et al: Probabilistic maps, morphometry, and variability of cytoarchitectonic areas in the human superior parietal cortex. Cereb Cortex 2008; 18:2141–2157

Background: The choroid plexus (CP) not only produces CSF and related proteins, but is also involved in neurodevelopment, neuroplasticity, stem cell regeneration, and inflammation. Post mortem brain studies identified CP hypersecretion in mania and schizophrenia, while case reports in schizophrenia associated CP calcifications with worsening symptoms, cognition and cortical thickness. However, the CP has been ignored in clinical neuroscience. Objective: To characterize 1) CP structure across the psychosis spectrum and in biotypes, 2) relationship with cortical thickness and ventricular measures, 3) association with symptoms and cognition, and 4) identify genetic underpinnings via genome-wide association study (GWAS). Methods: Patients with psychosis (schizophrenia, N=223; schizoaffective, N=142; and bipolar, N=190), biotypes (BT1, N=124; BT2, N=156; BT3, N=197), and controls (N=337) were recruited in the multisite, cross-sectional B-SNIP1 study. Assessed CP volume (FreeSurfer), symptoms (PANSS), cognition (BACS), functioning (SFS), and performed GWAS on CP volume (PLINK 1.9). Results: CP enlargements were seen in probands, diagnostic groups, and biotypes when compared with controls (p<0.05). CP volume was positively correlated with ventricular volume (r=0.47, p<0.001) and negatively correlated with frontal, temporal, parietal, and occipital lobe thickness. The CP volume in the BT1 group more strongly correlated with worse symptoms, verbal fluency, and functioning (p<0.05), compared with the other groups. Top SNPs associated with CP volume include ch3 region LOC105374002 (p<1×10–7), DCBLD2 (p<2×10−7) and ST3GAL6 (p<3×10–7). Conclusion: Our findings suggest the involvement of CP structure in psychosis spectrum disorders. The CP may be an important target for future research.

Background: Case reports of Wernicke’s encephalopathy have been reported in non-alcoholics receiving chemotherapy and in cases of neoplasm. Here we present a case presenting with Capgras syndrome. Case: A 75-year-old woman with a history of breast cancer, B-cell lymphoma, mild cognitive impairment, depression, and epilepsy was admitted to the neurology service with acute anterograde amnesia, and a Capgras delusion that her husband had been replaced by a conman. She had no history of alcoholism, but had received R-CHOP chemotherapy for lymphoma several months prior to admission. She was confabulatory, refused to comply with cognitive testing, and believed the hospital was staged (reduplicative paramnesia). Neurological examination was otherwise unremarkable. HIV, Treponemal antibodies, B12, folate, and TSH, were unremarkable. CSF was bland, negative for oligoclonal bands, with normal viral and autoimmune encephalitis studies. Continuous EEG monitoring revealed diffuse cortical slowing. MRI of the brain with gadolinium showed mild age-related global atrophy, mild periventricular FLAIR hyperintensities, and no evidence of leptomeningeal disease. She was transferred to inpatient psychiatry and treated with olanzapine 5mg for agitation and 300mg TID of thiamine intramuscularly empirically for possible Wernicke’s. Olanzapine was discontinued and she showed some improvement in memory, with abatement of delusions and paranoia. She was discharged home with her husband. At one-month follow-up, her Mini Mental State Examination score was 21/30, down from 26/30 fourteen months prior. Conclusion: Capgras syndrome and reduplicative paramnesia are potential manifestations of Wernicke’s encephalopathy, which should be considered in patients who have recently received chemotherapy.

Background: Patients with functional neurological disorders (FND) commonly present to Neurology, including acutely in the ED. The philosophy of care for this population is prompt positive diagnosis and outpatient management; the inpatient management of functional symptoms is sometimes necessary but not yet operationalized. Objective: To develop and implement a unique, “proof-of- concept” patient-specific collaborative inpatient management plan for patients newly diagnosed with FND. Case History: Methods: Resident team leaders for the Neurology and Psychiatry Inpatient services codeveloped a personalized expectation-based functional symptom therapy protocol for the inpatient management of FND. This protocol was trialed as a proof of concept intervention with a consenting patient and included expectation management, conceptual model groundwork (Stone et al. 2005), demedicalization, pain control, physiotherapy (PT) and occupational therapy (OT). Psychiatric assessment was completed in a graded fashion. The protocol emphasized interprofessional collaboration and included daily team meetings attended by neurology, psychiatry, PT, OT and pharmacy to ensure consistency of approach. The patient returned at 2 weeks postdischarge for a debrief meeting with all team members. Results: Here we present a proof of concept case study of a 51-year-old patient with early-onset Parkinson disease and a 4-year history of recurrent dystonic attacks, who presented acutely to the ED in a generalized dystonic crisis. She was diagnosed promptly with Functional Dystonia by the Neurology service and underwent a 5-day inpatient admission to the Neurology service in a tertiary hospital with the prospective intent of stabilizing her functional symptoms through the personalized protocol described above. The frequency and intensity of her dystonic attacks decreased. She accepted her diagnosis and returned her supply of rescue medication (apomorphine). We established outpatient care for ongoing treatment of her FND. She has not returned to the ED in the 6 months since discharge. Conclusions: Patients with FND can accrue significant morbidity iatrogenically through the use of unnecessary medications, medical procedures, and repeated admissions to hospital. Repeated diagnostic interventions, emergency visits and siloed care have a high economic burden. We have demonstrated the feasibility and effectiveness of a personalized expectation-based functional symptom therapy protocol in a N of 1 case study. This protocol may be particularly effective as a crisis intervention and may reduce morbidity and unnecessary burden on the health care system. The patient and provider team identified establishment of expectations, interprofessional collaboration and consistency of approach as key factors contributing to the positive outcome.

Stone J, Carson A, Sharpe M: Functional symptoms in neurology: management. J Neurol Neurosurg Psychiatry 2005; 76(Suppl 1):i13–i21

Background: Depression is a syndrome characterized by disruption in mood, motivation, behavior, and cognition. Recent randomized sham-controlled clinical trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD) have had poor outcomes (Dougherty et al. 2015; Holtzheimer et al. 2017). Yet, multiple independent studies highlight potential for success using alternative methodology, including prospective connectomic targeting or novel trial designs (Puigdemont et al. 2012; Schlaepfer et al. 2013; Bergfeld et al. 2016). Objective: To analyze patient selection criteria, target sites, stimulation parameters, outcome measures, efficacy, and adverse effects to identify areas of focus for optimization of clinical outcomes. Methods: Searched PubMed using the MeSH terms “deep brain stimulation” AND “treatment-resistant depression.” Studies including open-label trials, randomized control trials, and case reports were identified. Studies that used duplicate patient panels were excluded. Results: Seventeen studies comprising a total of 254 patients met our inclusion criteria. Patient selection criteria and definition of TRD varied across studies. Multiple stimulation sites were targeted. Significant variability was found regarding targeting approaches, stimulation parameters, outcome measures, efficacy, and adverse effects. Conclusions: DBS is a promising treatment modality for TRD despite variable outcomes. Multiple stimulation sites can be targeted successfully. Variability in stimulation parameters, network activation, and time-points of analysis affect outcome measures of DBS efficacy. Adverse effects were uncommon and temporary. Clinical efficacy can be enhanced using individualized, patient-specific targeting approaches borne out of neurobiological models. There remains significant opportunity to integrate our understanding of the mechanisms of action of DBS for TRD to optimize clinical outcomes.

Bergfeld IO, Mantione M, Hoogendoorn ML, et al: Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry 2016; 73:456–464

Dougherty DD, Rezai AR, Carpenter LL, et al: A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression. Biol Psychiatry 2015; 78:240–248

Holtzheimer PE, Husain MM, Lisanby SH, et al: Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry 2017; 4:839–849

Puigdemont D, Pérez-Egea R, Portella MJ, et al: Deep brain stimulation of the subcallosal cingulate gyrus: further evidence in treatment-resistant major depression. Int J Neuropsychopharmacol 2012; 15:121–133

Schlaepfer TE, Bewernick BH, Kayser S, et al: Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry 2013; 73:1204–1212

Background: Non-convulsive status epilepticus (NCSE) is a potentially treatable neuropsychiatric condition that poses considerable diagnostic challenges. This condition is thought to be more common in the elderly than in the general population, however additional diagnostic challenges complicate its recognition in older patients, because of the wide differential diagnosis with common underlying causes of acute confusional state in this age group. Objective: We set out to review the existing evidence on the clinical correlates of NCSE in the elderly population. Methods: We conducted a systematic literature review according to the methodological standards outlined in the PRISMA statement to assess the clinical correlates of NCSE in patients aged 60 or older. Results: Our literature search identified 10 relevant studies, which confirmed that the incidence of NCSE increases with age, in particular with regard to focal forms with impairment of consciousness. A history of epilepsy (or a recently witnessed seizure with motor features), abnormal ocular movements, and female gender appeared to correlate with the diagnosis of NCSE in the elderly, prompting prioritization of electroencephalography tests for diagnostic confirmation. Conclusion: Epidemiological data in the elderly vary widely because of the heterogeneity of definitions and diagnostic criteria applied across different studies. Our findings suggest that it is recommended to keep a low threshold for requesting electroencephalography tests to confirm the diagnosis of NCSE in elderly patients with acute confusional state, even in the presence of a presumed symptomatic cause.

Background: Huntington’s disease (HD) is a progressive neurodegenerative condition caused by trinucleotide repeat expansion. While HD is not an autoimmune disease, some evidence links HD to activation of an adaptive immune response. We present a case of acute mental status change and dysautonomic symptoms, with discovery of nicotinic ganglionic receptor autoantibodies and with eventual final diagnosis of HD. Case History: 33yo patient with history of depression and past suicide attempts was admitted to community hospital for acute cognitive worsening, cachexia, catatonic-like symptoms, and abnormal movements. He had rapidly progressive dementia work-up with finding of alpha3-AChR antibody level of 0.06; he was given steroids, IVIG, and plasma exchange with initial limited benefit before being transferred to VA. When seen at VA, he was noted to have confusion, myoclonic jerks, cogwheeling, and choreatic movements; he reported dry mouth, increased urination, knee pain, fatigue, and poor appetite. Outside hospital endoscopy, colonoscopy, ultrasound of scrotum, and bowel biopsies did not reveal cancer; full body CT and PET at VA were negative. Repeat brain imaging demonstrated diffuse atrophy. His dysautonomia resolved, but he continued to have cognitive issues and movements. Further work-up at Hines and at Rush Movement Disorders Clinic revealed diagnosis of Huntington’s disease, with 54 trinucleotide repeats. Conclusions: While HD has been associated with dysfunction in adaptive immunity and antiglialin and angiotensin II type 1 receptor (AT1R) antibodies, there has been no previously reported case of nonparaneoplastic alpha3-AChR antibodies in HD. It is unclear if this patient had two separate pathologic processes or if the alpha3-AChR autoantibody was related to the diagnosis of HD.

Background: Although certain neuropsychiatric symptoms are prevalent in multiple sclerosis (MS), more marked personality/behavioral change is the hallmark of behavioral-variant frontotemporal dementia (bvFTD). These conditions are not thought to commonly co-occur. One published case reported FTD-like symptoms ostensibly due to MS. We describe a patient whose clinical picture was most consistent with bvFTD despite a 30-year history of relapsing-remitting MS. Case History: This 60-year-old woman was referred to our clinic by neurology due to family-reported cognitive decline, presumably related to MS. Detailed clinical interview revealed apathy, disinhibition, compulsive behaviors, dietary changes, and functional declines with anosognosia over a reported 1-year timeframe. Neuropsychological assessment revealed marked executive dysfunction with otherwise intact cognition. Neurological examination was grossly normal. Brain MRI showed stable periventricular and subcortical demyelinating lesions without active disease. Severe bifrontal and bitemporal cortical volume loss was evident, the extent of which suggested a neurodegenerative course beyond the reported 1-year. ApoE genotyping was 3/3. Consensus diagnosis was probable bvFTD in the setting of MS. Conclusions: This is the first published case describing comorbid MS and bvFTD. Although clinical experience suggests that MS and neurodegenerative conditions do not commonly co-occur, recent GWAS findings identified shared loci among MS, FTD, Alzheimer’s and Parkinson’s disease. Whereas MS may present with neuropsychiatric features, this patient’s personality/behavioral changes were well beyond more prevalent neuropsychiatric phenotypes in MS, especially given her cortical atrophy. Cases like this encourage clinicians to challenge diagnostic biases that may arise when confronted with patients whose symptoms are inconsistent with their previous history.

Background: Human’s multitasking ability as well as the difficulty to perform too many tasks simultaneously have been intensively studied. Neural circuits of complex tasks are generally associated with the frontal cortex. The basal ganglia also play a role in performance of concurrently tasks. Methods: In order to explore the neural basis of multitasking in the human Subthalamic nucleus (STN) we recorded microelectrode multiunit activity in STN while Parkinson’s patients (N=43) undergoing deep brain stimulation (DBS) surgery performed increasingly complex oddball paradigm. Results: We found significant changes in STN activity between three complexity level tasks: one process (auditory discrimination); two processes (adding motor planning and movement); and three processes (adding stop signal). As the complexity of tasks increases the responses to frequent tones decrease and the ratio between frequent and deviant tones is changed. Auditory discrimination was found both in dorsal (motor) and ventral (cognitive-limbic) STN regions. Conclusions: We conclude that human STN neurons are capable of both allocation of neuronal resources and response to a nonpreferred stimuli. STN capacity limitation revealed by complex tasks produces a selective integration and prioritization of neural data that enables the STN to forward a clarified signal to the output nuclei of the basal ganglia.

Background: The clock drawing test (CDT) is a simple neuropsychological tool commonly used to detect cognitive dysfunction. To our knowledge, no prior studies have analyzed the clock drawing abilities in patients with catatonia. Objective: To analyze if errors on the CDT are related to severity of catatonia. Methods: A total of 20 CDTs were obtained from 10 patients (50% male, Mean age=30.0, range 16–52) during their catatonic episodes. Each CDT was scored using the Clock Drawing Interpretation Scale (CDIS), with lower scores representing greater cognitive dysfunction. Catatonic severity was assessed at each encounter using the Bush Francis Catatonia Rating Scale (BFCRS). We conducted linear mixed effect regression models to examine the relationship between CDIS and BFCRS, using subject as a repeated factor to control for the correlated observations in the sample. Results: We found a strong association between CDT scores and BFCRS scores (b=−0.83, se=0.13, t₉ = –6.21, p<0.001), indicating that greater catatonic severity is associated with greater cognitive dysfunction. CDT scores were also lower if it was their first episode of catatonia. Conclusions: Our findings suggest that the greater symptom severity of catatonia, the poorer the score on the CDT. The CDT is a brief, simple and underutilized tool that is useful in evaluating symptom severity and therapeutic response in patients with catatonia.

Background: There are limited data on adherence to recommendations for evidence-based behavioral treatments among migraine patients. Objective: Evaluate the frequency with which migraine patients initiated behavioral migraine treatment following a headache specialist recommendation, and the predictors for initiating behavioral migraine treatment. Methods: We conducted a prospective cohort study of consecutive patients diagnosed with migraine to examine whether the patients initiated behavioral migraine treatment following a provider recommendation. The primary outcome was scheduling the initial visit for behavioral migraine treatment. Patients who initiated behavioral migraine treatment were compared with those who did not. Results: Of the 234 eligible patients, 69 (29.5%) were referred for behavioral treatment. Fifty-three (76.8%) patients referred for behavioral treatment were reached by phone. Mean duration from time of referral to follow-up was 76 days. Thirty (56.6%) of patients initiated behavioral migraine treatment. There was no difference in initiation of behavioral migraine treatment with regard to sex, age, age of diagnosis, years suffered with headaches, healthcare utilization visits, MIDAS, and locus of control (p>0.05). Patients who had previously seen a psychologist for migraine were more likely to initiate behavioral migraine treatment than patients who had not. Time constraints were the most common barrier cited for not initiating behavioral migraine treatment Conclusions: Less than one third of eligible patients were referred for behavioral treatment and only about half initiated behavioral migraine treatment. Future research should further assess patients’ decisions regarding behavioral treatment initiation, and methods for behavioral treatment delivery to overcome barriers to initiating behavioral migraine treatment.

We are presenting an ongoing multidisciplinary telemedicine-based intervention to provide education on best practices for management of advanced dementia, targeting individuals residing in dementia care facilities who have distressing behavioral symptoms, jeopardizing their ability to remain in their current level of care. A HIPAA compliant conduit (Apple “FaceTime” technology) was used to provide an intervention by a physician or midlevel practitioner, plus a medical social worker, all with extensive experience and skill in directing dementia care. Issues addressed included medical comorbidities, appropriateness of medications, as well as pharmacologic and nonpharmacologic management of problematic behaviors. Fifteen subjects have been recruited to date, and the intervention was successfully delivered in ten subjects. Five subjects dropped out due to transfer to another facility, hospitalization or withdrawal of consent prior to the intervention, four passed away prior to completing 6 month outcome assessment, consistent with the expected mortality in this population with advanced disease. Outcome measures assessed were family impression of quality of life (QoLAD), caregiver impression of time spent providing care (RUD-NH), and the neuropsychiatric inventory total score (derived from the NPI-NH). Despite small numbers, we did identify a statistically significant reduction in neuropsychiatric symptoms as measured by the NPI total score at 6 months (p<0.03). We are continuing to provide this intervention and increase our data. This pilot project demonstrates the feasibility of providing expert focused clinical educational interventions via telemedicine and shows promise to provide meaningful patient centered improvements in distressing symptoms.

Background and Purpose: Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsons plus syndrome that is a clinical diagnosis with heterogeneous presentation. This makes early diagnosis and initiation of treatment difficult. This case report aims to demonstrate a possible atypical presentation of PSP and the methods used to reach that hypothesis. The case will add to the growing body of data characterizing PSP and related syndromes. Case History: The patient was a 52-year-old female with a history of depression and parkinsonism who presented to our hospital with nonbizarre delusions, anxiety, impaired judgement, and depression versus apathy. She had a symmetrical tremor, festinating gait, recent history of falls, no upward gaze palsy, but had complaints about her vision, with recent normal optometry evaluation. She had a recent DAT scan that was abnormal. A PET scan revealed hypometabolism in the bilateral mesial frontal lobe area. Brain MRI revealed no acute processes but subtle midbrain changes. Her presentation was consistent with Daniel et al.’s findings that PSP may present with eye abnormalities even without gaze palsy. Conclusion: The patient demonstrated symmetrical parkinsonism, psychiatric and cognitive changes, which are common signs of PSP. Although she had difficulty with her vision, she did not have vertical gaze palsy. Due to atypical presentations of PSP and lack of research on the syndrome, it is difficult to identify resulting in delayed treatment. Further characterizations of atypical PSP syndromes will allow for appropriate early management.

Background: The biological basis of mood disorders (major depressive disorder and bipolar disorder) is framed in terms of biogenic amines (e.g. serotonin, dopamine, norepinephrine, glutamate) and even neurotrophic factors and inflammation. Intricately involved with all of the above is the less understood nitric oxide (NO) system. Objective: Through a literature review, we summarize the current understanding of the NO system in context of mood disorders in order to identify underlying mechanisms. Methods: We searched Pubmed through 2017 for animal models and limited human data on the following: mapping of the NO pathway; effects of inhibition of nitric oxide synthase (NOS) and soluble guanylyl cyclase (sGC) on depression, and indirectly in conjunction with traditional and untraditional antidepressants; and the effects of antidepressant and mood stabilizers on the NO system. The data are summarized in tables and graphs. Results: The inhibition of NO (upstream via NMDA receptor antagonists, downstream via sGC inhibition, inhibition of NOS to synthesize NO) exerts antidepressant effects and also augments effects of antidepressant medications. In contrast, increasing NO levels (via direct NO donors, supplying the precursor L-arginine, or blocking the breakdown) prevents the beneficial effects of antidepressants. Finally, antidepressants and mood stabilizer led to an overall decrease of NO levels, but there was more variability in these results. Variability in results may arise in differences in agent, dose, duration, species, method of measurement, and location of measurement. Conclusion: NO is strongly implicated in pathogenesis and treatment of mood disorders. A better understanding can lead to novel treatment options.

Background: Several studies highlight an overlap between symptoms of primary psychiatric symptoms and FTD, as well as primary psychiatric symptoms being in some cases a prodrome to FTD. Despite this mentioned overlap little is known about the relationship between lifetime history of mental illness and the risk of FTD. Objective: Our aim in this study was to examine the prevalence of lifetime psychiatric disorders, medical conditions and environmental factors in subjects with behavioral variant of FTD (bvFTD) compared with Alzheimer’s disease (AD). We hypothesized that patients with bvFTD would have a greater history of past psychiatric disorders. Methods: Longitudinal data from the National Alzheimer’s Coordinating Center Uniform Data Set (NACC-UDS) yielding sociodemographic and clinical data of subjects with bvFTD (N=351) and AD (N=11769) was obtained. The lifetime prevalence rate of psychiatric disorders, medical conditions and several environmental risk factors was compared across disease groups (bvFTD versus AD) through univariate analyses. Results: Compared with AD, bvFTD subjects exhibited a significantly higher lifetime prevalence of depressive episodes (p=0.024), substance use disorders (p=0.003), bipolar disorders (p<0.001) and obsessive compulsive disorders (p<0.001). Interestingly, they showed an overall higher prevalence for history of traumatic brain injury when compared with AD (p<0.001). Conclusion: This study suggests that several psychiatric disorders could represent a risk factor for FTD, which underscores the importance of further examining the role of psychiatric disorders to gain a better understanding of their role in the progression to dementia.

Background: Scalable behavioral treatment options are needed for chronic pain conditions. Migraine is an ideal condition to test smartphone-based behavioral interventions such as progressive muscle relaxation (PMR). We sought to examine the usability of the RELAXaHEAD application, which has a headache diary and PMR capability. Using the “Think Aloud” approach, we iteratively beta-tested RELAXaHEAD using a convenience sample of people with migraine. One on one interviews were conducted, audio-recorded and transcribed. Using Grounded Theory, we conducted thematic analysis. Participants were also asked Likert scale questions about satisfaction with the app and the PMR. Cases: Twelve subjects who had a self-reported diagnosis of migraine participated in the study. The mean duration of the interviews was 36 (SD=11, range 19–53) minutes. From the interviews, four main themes emerged. People with migraine were most interested in App Aesthetic/Appearance, App functionality, App Utility/Practicality, and the potential utility of the PMR. Furthermore, participants reported that the daily diary: was easy to use (75%), was relevant to track headaches (75%), maintained their interest and attention (75%), was easy to understand (83%). Ninety two percent of the participants would be happy to use the app again. Participants reported that PMR maintained their interest and attention (75%) and improved their stress and low mood (75%). Conclusion: The RELAXaHEAD app appears to be acceptable and useful to migraine participants. Future studies can examine the use of the RELAXaHEAD app to deliver smartphone based MBI in a low cost, scalable manner.

Background: Oculomotor and visual abnormalities are common sequelae of traumatic brain injury, and often under-appreciated by clinicians, especially when psychiatric symptoms are a prominent feature of the clinical presentation. Furthermore, psychotropic medications can cause or worsen oculomotor abnormalities in at-risk patients through further pharmacological modification of a damaged visual system. We present a case in which a person with multiple traumatic brain injuries experienced an adverse outcome due to pharmacotherapy with the D2 receptor partial-agonist aripiprazole. Case Report: A 42-year-old Caucasian female with a history of several mild concussions, one right frontal traumatic brain injury, and one right fronto-temporal traumatic brain injury presented nine months after her most recent TBI for management of manic and depressive episodes, impulsivity and disinhibited behavior, intense anger, psychomotor restlessness, anxiety, and insomnia. She was initiated on divalproex with significant improvement and subsequently supplemented with guanfacine for cognitive enhancement, and eventually aripiprazole for residual depressive symptoms. Despite notable symptomatic improvement she developed acute-on-gradual onset pseudo-myopia which resolved upon discontinuation of aripiprazole. Conclusion: A growing body of evidence substantiates the hypothesis that catecholaminergic neurons are intricately involved in the visual system, and due to long projections are vulnerable to axonal injury in traumatic brain injury. Pharmacological modification of these damaged systems may place individuals at further risk for oculomotor and visual abnormalities, and careful consideration of agents may be necessary to mitigate this risk.

Background: Visual rating scales may aid clinicians in the assessment of atrophy on structural brain MRIs in neurodegenerative disorders. There is a need for a generalized visual rating scale to assess atrophy across disorders, but it is not known how well visual ratings on a scale correlate with automated measurements from neuroimaging software. Cases: Brain scans from 20 subjects were selected, representing a range of atrophy severity and neurodegenerative diagnoses. We developed a visual rating scale and correlated visual ratings with automated cortical thickness measurements extracted from Freesurfer 5.3. The rating scale was comprised of the hippocampus, central sulcus, and 16 cortical regions across the brain, and incorporated aspects of existing validated rating scales. Scans were visually rated by two raters. For each structure, ratings from the two raters were averaged and correlated with the respective Freesurfer cortical thickness values using Spearman’s correlations. Preliminary analyses from the first 13 scans revealed that higher atrophy ratings on our visual rating scale correlated with lower cortical thickness measurements. The correlation was strongest for the left ventromedial cortex (Spearman’s rho=−0.75, p=0.003) and weakest for the left posterior cingulate cortex (Spearman’s rho=0.35, p=0.24), with an average correlation of rho=−0.431 across all regions. Conclusions: Visual ratings correlated with quantitative measurements from software, with considerable variability across regions. Further work is needed to refine this scale and determine whether it can be used to predict pathology among neurodegenerative conditions.

Background: Over half of patients with treatment-resistant depression (TRD) experience robust antidepressant effects following intravenous infusion of ketamine, generating interest in ketamine’s potential as a rapid-acting antidepressant. Unfortunately, the effects of ketamine are short-lived, and it is prone to abuse. In contrast, repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for TRD that is well-tolerated and safely administered in an outpatient setting, however a standard course takes 4–6 weeks to complete. Objective: In this case series assess how 2 subjects respond to subanesthetic doses of intravenous ketamine as compared with a novel TMS paradigm, high-dose patterned theta-burst stimulation (TBS). Methods: We present 2 subjects with major depressive disorder (MDD) in a current depressive episode. Subjects first received intravenous ketamine infusion (0.5mg/kg). Following response and relapse, subjects received open-label intermittent TBS (90,000 pulses). Results: Antidepressant response was assessed using the Hamilton Depression Rating Scale (HDRS17). Both subjects achieved antidepressant response following ketamine infusion; maximal response was seen day 1 postinfusion, scores increased by day 14 (preinfusion mean HDRS17=24±5, day 1 mean HDRS17=1±1, day 14 mean HDRS17=15±8). Prior to TBS all subjects had relapsed. Following TBS subjects achieved maximal response on day 3 poststimulation and maintained remission until day 42 poststimulation (prestimulation mean HDRS17=29±2, day 3 mean HDRS17=2±3, day 56 mean HDRS17=2±1). Conclusion: High-dose spaced theta-burst transcranial magnetic stimulation may achieve antidepressant response with similar rapidity to ketamine. In addition, TBS appears to provide a more sustained antidepressant effect, for as long as 8 weeks posttreatment.

Background: Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD). This leads to delayed or erroneous diagnosis given the limitations of neuroimaging and cognitive tests. Objective: Develop a bedside clinical tool to improve diagnostic accuracy of early bvFTD versus PPD. Methods: An 18-item checklist of clinical features differentiating bvFTD from PPD was developed based on literature and clinical experience. The checklist was initially filled prospectively for 29 consecutive patients (Montreal) with mixed late-onset behavioral changes. Patients were followed longitudinally to establish a final diagnosis. The checklist was subsequently retrospectively completed on the baseline visit (N=137) of the Late-Onset Frontal Lobe study (Amsterdam). Based on final diagnoses, patients were categorized into Probable FTD (N=46), Possible FTD (N=8), Other Cognitive Disorder (N=36), Other Neurological Disorder (OND-N=10), or No Diagnosis/PPD (N=66). Results: Mean total score was significantly different across all groups (Oneway ANOVA F(4,161) = 24.578, p<0.001). The PPD group had significantly lower scores than all other dementia categories. The largest difference was found between Probable FTD (X̄=12.04) and No Diagnosis/PPD (X̄=7.48). The item “duration more than 5 years” did not distinguish the two groups. Chronbach’s Alpha of the full scale was 0.604. Using ROC curves aiming to maximize specificity, two cutoff scores were established: ≥12 being indicative of bvFTD (specificity 93.9%, PPV 88.9%), and ≤8 being indicative of PPD (specificity 91.3%, PPV 92.0%). Conclusion: Although prospective validation is required, this clinical checklist could provide a simple bedside tool to improve diagnostic accuracy between bvFTD and PPDs.

Background: Family caregivers often feel ill equipped to handle bothersome behavioral symptoms of dementia, such as agitation and sleep disturbances, leading to increased caregiver distress and nursing home placement. Therapies for such symptoms are limited and nonpharmacological options are preferred. Neurologic music therapy could provide an additional treatment option for managing behavioral problems in dementia. Objective: Evaluate the feasibility, acceptability, and efficacy of home-based neurologic music therapy for behavioral symptoms of dementia. Methods: Participants included 19 patient-caregiver dyads who received one-hour weekly sessions of home-based neurologic music therapy for 6 weeks. Demographic, quality of life, neuropsychiatric symptom, and caregiver burden and self-efficacy information was collected at baseline, 6 weeks, and 12 weeks. Results: The mean age of dementia participants was 76 years and average MoCA score was 15.2. 80% of dyads reported music therapy was subjectively beneficial, 13% reported negative effects, mainly increased stress and anxiety for patients. 9 dyads withdrew from therapy before completing all sessions; these patients had lower caregiver-reported quality of life (p=0.031) and higher neuropsychiatric inventory scores (p=0.049) at baseline. For those who completed therapy, patient-reported quality of life improved at 6 weeks (p=0.004), but was not sustained at 12 weeks (p=0.53). No other measures changed significantly after therapy. Conclusion: Home-based neurologic music therapy improved patient-reported quality of life, but this effect was not sustained. Initiating music therapy too late in the course of dementia, when behavioral symptoms are already present, may be too stressful and impractical for patients and caregivers.

Background: Communication accommodation describes how individuals adjust their communicative style to that of their conversational partner. Prosodic accommodation may include changes in frequency (e.g. pitch), timing (e.g. rate), or quality (e.g. intensity). Accommodation establishes a paralinguistic conversational baseline, which may be broken to introduce new socio-emotional information into the conversation. Objective: We predicted that accommodation would be decreased in behavioral variant frontotemporal dementia (bvFTD) but increased in right temporal FTD (rtFTD) due to respective loss or retention of neural substrate for modulation of timing and pitch (e.g. the basal ganglia and dorsal information processing stream) despite decreased social semantic knowledge in both disorders. Methods: 74 patients with FTD (29 with bvFTD, 14 nonfluent variant primary progressive aphasia (nfvPPA), 14 with rtFTD, 19 with semantic variant PPA (svPPA)), and 15 patients with Alzheimer's disease (AD) were compared with 170 healthy controls in a recorded conversation lasting between 10 to 15 minutes with a companion. Manual labeling of speakers and removal of nonspeech vocalizations and noise was performed using Praat acoustic analysis freeware. Data transformations were applied when appropriate to achieve normative distributions. Regression between patient and partner speech with an interaction term for patient diagnosis was performed, adjusting for patient age and gender. Results: Speech rate (p=0.001) and pitch variation (p=0.022) correlated most between speakers in conversations including RtFTD. No other groups differed from healthy controls in accommodation of any measure. Conclusion: RtFTD results in greater accommodation of pitch variation and speech rate than healthy controls or other FTD variants.

Background: Children with specific learning disorders (SLD) have shown impairments in several areas of executive functioning (EF). However, the question remains as to whether these impairments persist in adulthood. Objective: The present study examined EF in adults diagnosed with SLD to address the hypothesis that differences would be observed between participants with a math disability (MD) and those with a reading disability (RD). Specifically, participants with a RD would perform worse in set shifting (H1), while those with a MD would perform worse on working memory tasks (H2). Methods: Participants included 58 adults who presented for psychological and neuropsychological testing to assess cognitive complaints. All were administered the Wechsler Adult Intelligence Scale (WAIS-III and IV) and Delis-Kaplan Executive Function System (D-KEFS) as part of a larger battery. Included participants received a SLD diagnosis in math (N=39) or reading (N=19). Results: An ANOVA was conducted to examine group differences in EF. A significant difference in working memory was observed between MD and RD (p=0.045), with the MD group exhibiting lower scores (M=89.21, SD=10.19) compared with RD (M=96.58, SD=17.17). No significant differences were observed in other areas of EF. Conclusion: Our results were partially consistent with research in younger populations. Observed differences may suggest that working memory is a cognitive mechanism integral to MD. These results add to the understanding of the divergent characteristics of different SLDs, and may inform diagnosis.

Background: With disparity in olfactory ability between the nostrils, the worse is neglected. A case demonstrating the opposite, neglect of the normosmic nostril and predominance of anosmia, is presented. Case History: A 67-year-old male developed a severe upper respiratory infection, associated with an inability to smell and taste, which persisted for 6 months. Nothing smells normal to him, additionally some odors are distorted. He affirms occasional chemical phantosmias. Taste is perceived as 10% of normal. He occasionally has taste on first bite, however fades rapidly. Chemosensory Testing: Olfaction: Dirhinous Testing: Brief Smelling Identification: 7 (Hyposmic). Alcohol Sniff: 1 (Anosmic). Monorhinous Testing: Olfactometer Butanol Threshold: left (L) 0.00 (anosmia) right (R) 6.00 (normosmic). Olfactometer Identification: L 6. R 8 (Abnormal). Retronasal Olfaction: Jelly Bean Difference: 1 (anosmic). Radiology: MRI Scan of Brain: right parietal lacunar infarction. Conclusion: The mechanism of subjective anosmia in the presence of right nostril normosmia is unknown. Possibly this represents an olfactory equivalent of left hemispatial agnosia. This may be due to the lacunar infarct in the right parietal lobe. Finelli (1990) noted dirhinal testing is equal to that of the better nostril in unilateral testing. In the normal state, olfactory ability in both nostrils is unequal 15% of the time and demonstrates clinically significant difference. Contrary to Bechen’s findings (Bechen and Doty, 1998) we found the better nostril was neglected. This case highlights the need for monorhinus testing.

Background: Posterior cortical atrophy (PCA) is a neurodegenerative clinical syndrome often arising from Alzheimer’s disease pathology, usually characterized by visuoperceptual deficits and parieto-occipital atrophy. Recent work suggests a role for lateral parietal cortical regions in supporting select executive functions (auditory working memory, category fluency), but little is known about how these deficits arise from cortical atrophy in PCA. Objective: To determine associations between performance on verbal executive functioning tasks and cortical atrophy in the posterior parietal nodes of large-scale brain networks in PCA. Methods: Nineteen individuals (mean age=63.1 years, 16F) were diagnosed with PCA based on neurological, neuropsychological, and neuroimaging exams. Correlation analyses were conducted on normalized test scores to determine the association between performances on Digit Span Backward (DSB) and Animal Fluency, and cortical thickness in the superior parietal lobule (SPL) and the inferior parietal lobule (IPL). Results: On average, PCA participants demonstrated impairment in auditory verbal working memory and category fluency relative to the normative population. Correlation analyses revealed that performance on DSB was related to cortical thickness in left-hemisphere IPL (r=0.49, p=0.03), but not right-hemisphere IPL (r=0.10, p>0.5). Performance on Animal Fluency was associated with cortical thickness in both left-hemisphere IPL (r=0.56, p=0.01) and right-hemisphere IPL (r=0.51, p=0.02). Conclusions: This characterization of verbal executive functioning deficits associated with inferior parietal cortical atrophy helps extend the cognitive profile of PCA to include verbal impairments not usually considered to be part of this syndrome, and supports the idea that parietal cortex contributes to verbal executive functions.

Background: Dreaming is a unique state of consciousness in which vivid experiences are intrinsically generated during sleep. Cognitive processing within the dream state differs in fundamental ways from that of wakefulness; dreamers are relatively detached from their surroundings and they may not critically evaluate implausible events. The neuroanatomical basis of dreaming is poorly understood, but its elucidation could have insights for understanding psychopathology, such as impaired reality monitoring that occurs with psychosis. Objective: In this study we sought to systematically analyze focal lesions that cause cessation of dreaming in terms of lesion location and lesion-associated networks. Methods: We identified 29 cases in which dreaming cessation followed a focal brain lesion, with lesion location demonstrated in a published figure or figures that could be represented on a common template brain. Next, we evaluated the lesion-associated networks by identifying regions with positive BOLD correlations with each lesion site using functional connectivity MRI data from 98 normal healthy adults. Results: Lesions that disrupt dreaming were widely dispersed across cortical and subcortical regions and most commonly involved the visual cortex. Lesion-associated networks tended to overlap at the lateral extrastriate visual cortices even when those lesions were in remote brain areas. Conversely, the medial and lateral prefrontal cortices were negatively correlated with lesion sites that disrupt dreaming. Conclusions: Taken together these findings support the role of the extrastriate visual cortex in dreaming, whether lesions directly affect this region or localize to a broader network with positive functional connectivity to this region.

Background: Anti-N-methyl-D-aspartate Receptor Encephalitis (aNMDARE) is an increasingly recognized cause of autoimmune encephalitis. Presentations include a range of neuropsychiatric symptoms including catatonia, which has substantial morbidity and mortality risks. Immunotherapy is the standard treatment for aNMDARE. Electroconvulsive therapy (ECT) may be required to treat associated catatonia, mostly reported in adults. Cases: All three cases were refractory to immunotherapy and lorazepam prior to consideration of ECT. Case 1 was a 16-year-old female that made a full recovery with eight ECTs; her Bush Francis Catatonia Rating Scale (BFCRS) decreased from 27 to 2. Progressive improvement in the Clock Drawing Test pictorially documented her course. Case 2 was a six-year-old male who developed a minimally responsive state. He initially showed some improvement but failed to progress despite having 11 ECTs. His BFCRS reduced from 16 to 7, but there was no significant alteration in functional status. Case 3 was a three-year-old male that made a marked recovery with eight ECTs; his BFCRS decreased from 17 to 3. ECT in all cases was technically complicated. All had spontaneous seizures prior to ECT and were on anticonvulsant medications. Maximal device energies plus augmentation with flumazenil were required to elicit effective seizures. Conclusions: 27 ECTs were safely delivered to our three pediatric patients with aNMDARE. To our knowledge, case 3 represents the youngest reported recipient of ECT. The two cases with positive motoric features of catatonia had a robust response to ECT.

Background: There are currently no prognostic markers established for predicting the development of neuropsychiatric symptoms after traumatic brain injury (TBI). Objective: Based on previous studies identifying prognostic biomarkers implicated in brain injury (1–4), the current analyses focused on detected levels of Glial Fibrillary Acidic Protein (GFAP) shown to have utility in TBI diagnosis and outcome (3). Methods: The Head injury Serum Markers for Assessing Response to Trauma (HeadSMART) cohort, a prospective cohort of TBI patients presenting to two urban emergency departments, was examined in this study. GFAP was detected in replicate MSD-ELISA assays in serum obtained within the first 24 hours after injury. Subjects were assessed for neuropsychiatric symptoms at 1, 3 and 6 months postinjury. Results: TBI patients (N=503) were enrolled between April 2014, and August 2016. Male patients comprised 59.6% of the samples, 53.9% were Caucasian, 20.9% had abnormal head CT, and 14.9% had GCS scores less than 15. No statistically significant association was found between serum GFAP levels and raw scores on the Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale, Rivermead Post-Concussive Scale, or the Davidson Trauma Scale. There was a statistically significant association between GFAP and total Glasgow Outcome Scale Extended scores at 1 month (β=–0.06, p=0.025), but not at 3 or 6 months (β=–0.026, p=0.432; β=–0.033, p=0.326, respectively). Conclusion: This study provides preliminary evidence GFAP can serve as a prognostic marker for functional recovery at 1 month post-TBI. Analyses of other serum biomarkers are indicated for distinguishing between groups with varying neuropsychiatric symptoms following TBI.

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Background: The biological mechanisms underlying sadness and anhedonia after traumatic brain injury (TBI) are poorly understood. Objective: This study aims to identify neuroanatomical changes in patients with post-TBI sadness and anhedonia, by analyzing white matter integrity of specific brain regions using Magnetic Resonance Imaging, Diffusion Tensor Imaging (MRI DTI) in subjects with mild and moderate TBI. Methods: We analyzed data from The Head injury Serum Markers for Assessing Response to Trauma (HeadSMART) cohort, a prospective cohort of TBI patients presenting to two urban emergency departments. Atlas-based DTI data from a small neuroimaging pilot involving seven HeadSMART participants scanned within 72 hours of injury was analyzed. Based on prior studies identifying regions of interests (ROI)s implicated in TBI depression, fractional anisotropy (FA) was analyzed in the uncinate fasciculus and the cingulum. Linear regressions were constructed analyzing the relationship between regional FA and the sadness and anhedonia domains of the Patient Health Questionnaire-9 at three months postinjury. Results: Among TBI patients, 71.4% were male and 85.7% had mild TBI. For symptoms, 14.2% reported depressed mood, 42.9% reported anhedonia and 14.2% reported both. No statistically significant association was found between FA in the uncinate fasciculus and sadness or anhedonia (β=0.00, p=0.96; β=–0.03, p=0.19) or between FA in the cingulum and sadness or anhedonia (β=0.02, p=0.15, β=–0.03, p=0.21). Conclusion: Post-TBI sadness and anhedonia were not associated with reduced FA in the cingulum and uncinate fasciculus. Larger studies are required to show significant changes in these regions. This includes analyzing other regions implicated in depression (i.e. caudate and amygdala).

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Hollocks MJ, Lawrence AJ, Brookes RL, et al: Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes. Brain 2015; 138:3803–3815

Singh M, Jeong J, Hwang D, et al: Novel diffusion tensor imaging methodology to detect and quantify injured regions and affected brain pathways in traumatic brain injury. Magn Reson Imaging 2010; 28:22–40

Background: The latent variable “δ” (for “dementia”) appears to be uniquely responsible for the dementing aspects of cognitive impairment (Gavett et al., 2015). Age, depression, and the apolipoprotein E (APOE) e4 allele are independently associated with δ (Royall et al., 2013). On the other hand, education, especially in young age, plays a role in lowering the risk of dementia including Alzheimer’s Disease (AD) (Meng et al, 2012; Basu 2013). Objective: In this analysis, we combine SEM (Structural Equation Model) with longitudinal data from the Texas Alzheimer’s Research and Care Consortium (TARCC) to explore interleukins as a possible biomarkers of education’s specific effect on δ. Methods: We employed structural equation models (SEM) to examine the mediation effect of S100b on depression’s association with δ in a well characterized cohort, the Texas Alzheimer’s Research and Care Consortium (TARCC). Subjects included n=3385 TARCC participants [1240 cases of Alzheimer’s Disease, 688 “Mild Cognitive Impairment “(MCI) cases, and 1384 normal controls (NC)]. Serum biomarkers levels were determined at baseline by Luminex assay (Rules Based Medicine /Austin, TX). All observed measures were adjusted for depression, ethnicity, gender, Geriatric Depression Scale (GDS) scores, Hb1Ac, apoE4 and HCY. Biomarkers were additionally adjusted for batch effects. We used an ethnicity equivalent δ homolog (i.e., “dEQ”). Wave 2 dEQ scores were used. Thus, the model is longitudinal and arguable causal. Furthermore, we randomly divided the cohort into 2 groups. Group A (N=1691) was used to construct the model, while Group B (N=1694) was used to replicate and verify the parameters of interest. Analyses were conducted in Analysis of Moment Structures (AMOS). Results: Model fit was excellent [χ² = 506.361(49), p=0.0; CFI=0.895; RMSEA=0.053]. Serum IL-5 was found to mediate 20.0% of educations association with Wave 2 dEQ scores (p<0.001). IL3, Il-13 and IL-16 were significant mediators too [Table 1]. The effect generalized across random subsets of TARCC’s sample. Conclusion: Serum inflammatory proteins levels increase in patients with dementia and associated with increased risk of all-cause dementia (Koyama et al, 2013). Education is a protective factor for developing AD. This protective role is partially mediated by inflammatory biomarkers. IL-3, IL-5, IL-13 and IL-16 are significant mediators of education protective effect on dementia.

Royall DR, Palmer RF: Alzheimer’s disease pathology does not mediate the association between depressive symptoms and subsequent cognitive decline. Alzheimers Dement 2013; 9:318–325. Available at doi: 10.1016/j.jalz.2011.11.009

Basu R. Education and Dementia Risk: Results From the Aging Demographics and Memory Study. Research on Aging. Volume: 35 issue: 1, 7-31, 2013.

Gavett BE, Vudy V, Jeffrey M, et al: The δ latent dementia phenotype in the uniform data set: Cross-validation and extension. Neuropsychology 2015; 29:344–352

Meng X, et al: Education and Dementia in the Context of the Cognitive Reserve Hypothesis: A Mend Systematic Review with Meta-Analyses and Qualitative Analyses Plos, 2012

Koyama A, O’Brien J, Weuve J, et al: The role of peripheral inflammatory markers in dementia and Alzheimer’s disease: a meta-analysis. J Gerontol A Biol Sci Med Sci 2013; 68:433–440

Background: There are many neurological manifestations of chronic liver disease. One common but less recognized cause is non-Wilsonian hepatolenticular degeneration (NWHLD), also known as acquired hepatocerebral degeneration. Case History: A 35-year-old woman presented for neuropsychiatry outpatient follow-up seven months after a prolonged hospitalization for alcoholic withdrawal seizures and encephalopathy. Her medical history is notable for alcoholic cirrhosis without ascites and severe alcohol use disorder in remission for nine months. Neurological examination revealed retrieval-based memory problems and truncal ataxia. Magnetic resonance imaging (MRI) showed increased T1 signal in the globus pallidus bilaterally, as well as diffuse atrophy and mild small vessel ischemic disease (image will be displayed on poster). Conclusions: Common features of NWHLD include movement disorders (parkinsonism, chorea, dystonia, cranial dyskinesia), ataxia, and cognitive dysfunction. Diagnosis is based on clinical presentation, history of chronic liver disease, and bilateral T1 hyperintensities of the globus pallidus on MRI; T2-weighted sequences are generally normal. Manganese deposition in the brain (as a result of portohepatic shunting) has been implicated in the pathophysiology of NWHLD. Although NWHLD has traditionally been considered nonreversible, some case reports have described improvement following liver transplantation.

Background: Functional coma poses a unique diagnostic challenge. Patients in a functional coma are unresponsive to stimuli and appear comatose, yet their state is not caused by structural or metabolic damage to the brain. Treatment is supportive, in contrast to the necessary emergent management of other, usually life-threatening, causes of coma. This poster aims to increase recognition of this rare condition and encourage further research. Case History: The first patient is a forty-year-old female admitted for resection of a benign extracranial mass who developed functional weakness and photophobia postsurgically and then an episode of unresponsiveness lasting forty-five minutes five days postoperatively. The second patient is a twenty-three-year-old male with an amputated leg and complex regional pain syndrome who was admitted for targeted nerve surgery and experienced an episode of unresponsiveness lasting three hours eleven days postoperatively. In both cases, the neurological exam was normal apart from lack of response to painful stimuli; vital signs, laboratory tests, and computed tomography of the brain (which will be shown on the poster) were unremarkable. Conclusions: Comparison to prior literature indicates that although certain bedside clues may increase suspicion of functional coma, there are no sensitive or specific historical criteria and it remains a diagnosis of exclusion requiring additional work-up. Management is supportive, with episodes lasting on average a couple of hours; it is unclear if GABA-ergic medications accelerate recovery. The sparse literature on this topic remains vague and inconsistent. This paper argues that “psychogenic coma” or “pseudocoma” be renamed functional coma.

Background: Traumatic brain injury (TBI)-associated depression is often believed to be clinically distinct from other TBI-associated syndromes and from primary major depressive disorder (MDD). Clear physiologic distinctions remain elusive, possibly due to interindividual variability in the functional architecture of the injured brain. The recent advent of individualized resting-state network mapping (RSNM) allows fMRI-based mapping of such individual differences. Objective: To identify a neurophysiologic distinction between TBI-associated depression, TBI, and MDD by comparing connectivity between subject-specific brain network maps. Methods: fMRI scans were obtained for 15 subjects with TBI-depression, TBI, MDD, and healthy controls (HCs). Both groups of depressed subjects had failed at least one antidepressant trial. RSNM was used to identify individualized brain networks for each subject. Resting-state functional connectivity between these networks was compared between different groups using effect sizes with permutation testing for multiple comparisons correction. Results: The three disorders were associated with varying degrees of hyperconnectivity within ventral attention network (VAN). The effects of TBI-depression were not simply explained by the combination of TBI and depression. TBI-depression showed weaker VAN connectivity than TBI without depression, (effect size 1.35, p<0.001), but showed greater VAN connectivity than MDD (effect size 0.85, p<0.005). All four groups (including HCs) were significantly distinct from one another (p<0.005). Conclusions: Individualization of brain network maps reveals distinctions between TBI-depression, TBI, MDD, and healthy controls which were not apparent using prior brain mapping approaches. This not only serves as a promising diagnostic biomarker, but also provides a potential target for tailored and individualized neuromodulatory approaches.

Background: Investigators have shown an association between slower gait and lower executive function test scores. In a previous study, we concluded that measuring gait speed in the clinic with cognitive interference (reverse months) may detect the transition from MCI to dementia. Objectives: The primary objective of this study was to determine if a more challenging task (serial 3 subtractions) would also distinguish MCI and dementia subjects in dual-task gait speed. Methods: Seventeen subjects were recruited from the Mood and Memory Clinic at Acadia Hospital and classified as normal cognition (n=4), MCI (n=8) or dementia (n=5) on basis of standard assessment scales. Time to walk a 20-foot distance was recorded under 3 conditions: normal, with a simple cognitive task (counting by 2s) and a difficult task (serial 3 subtraction). Results: Mean times (±std.dev.) in seconds for normal subjects for standard gait speed, counting by 2’s and serial 3’s were 8.21 (±3.1), 8.79 (±3.9) and 10.96 (±5.5). MCI subject times were 9.53 (±2.6), 10.13 (±2.1) and 16.44 (±9.7). Dementia patients’ times were 10.13 (±2.9), 10.61 (±3.1) and 16.84 (±6.4). Conclusion: For the more challenging task (serial 3 subtractions) a trend is seen for gait speed slowing as much in the MCI group as for the dementia group. This contradicts our previous study using an easier task (reverse months). We conclude that the differential of MCI from early dementia based on executive function testing with dual-task gait speed measurement is highly dependent on the nature of the cognitive task employed.

Background: Mania and psychosis have been reported in cerebellar and brainstem lesions with tumors, stroke, and congenital anomalies. In posterior fossa tumors, psychiatric symptoms rarely arise years after resection in stable residual tumors. The few reports of postoperative psychosis with stable lesions occurred in individuals with family history of mental illness. Case History: A 15-year-old male with posterior fossa pilocytic astrocytoma resected at ages two and nine, VP shunt, epilepsy, and mild intellectual disability was admitted for aggression and psychosis. For 6–8 months, he developed decreased speech, hypophonia, staring, incontinence, anhedonia, and anorexia. Negative EEG raised concern for catatonia, though no improvement with lorazepam. At admission, parents report three weeks of uncharacteristic acute aggression, verbosity, hallucinations, grandiose delusions, and insomnia. Medical workup was unremarkable, including CSF, autoimmune studies, EEG, head CT, and brain MRI showing stable cystic mass with vermis involvement. He failed three antipsychotic and valproate trials, and ultimately responded rapidly to lithium, supporting bipolar I mania with psychosis diagnosis. He was discharged one week after starting lithium, near-baseline, remaining stable on lithium at follow-up months later. Conclusions: This is a rare case describing a child with stable postoperative posterior fossa tumor and negative psychiatric family history, presenting with mania with psychosis responsive to Lithium. We hypothesize that abnormalities in the posterior fossa in early development, related to tumor and postoperative changes, conferred increased risk of bipolar disorder. This is consistent with the growing understanding of the role of cerebellar and brainstem structures in mood disorders.

Background: Dyke Davidoff Masson syndrome (DDMS) is a rare entity due to abnormalities in brain development, either congenital or acquired, causes include: infections, tumors, trauma. It’s been associated with psychiatric manifestations: treatment resistant psychosis and schizophrenia. Case History: We present the case of a 20-year-old female patient with history of systemic lupus erythematosus (SLE) since was four, developing deep vein thrombosis and confirmed diagnosis of antiphospholipid syndrome (APS) at age nineteen; with treatment resistant left temporal lobe epilepsy with hippocampal atrophy five years ago to date. Developed an episode of severe depression one year ago, including two suicide attempts ingesting anticonvulsants developing status epilepticus. Presents to outpatient clinic of our department with behavioral symptomatology: impulsiveness, emotional dysregulation, insomnia and abulia, no established depressive or psychotic disorder. MRI revealed left cerebral hemisphere atrophy with compensatory skull thickening. Cognitive deficiencies during evaluation revealed total IQ of 65 indicating intellectual disability. The patient began treatment with antidepressant, continued with anticonvulsants, with partial treatment response. Our patient fulfilled clinicoradiological criteria for DDMS: cerebral hemiatrophy, ipsilateral sinuses hyperpneumatization, dilated ventricles/cisternal space, mental retardation and epilepsy. It’s been associated with vascular insults due to inflammatory diseases and this presentation alongside SLE supports a neuroinflammatory component for syndrome development. Conclusions: The association of DDMS/SLE in this case could be explained by early age of onset and complications, microvascular damage being the possible mechanism. Early identification of DDMS could provide appropriate treatment for epilepsy (including surgery), mental retardation and psychiatric comorbidities, improving quality of life.

Background: Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple motor and phonic tics. In addition to common behavioral comorbidities such as obsessive-compulsive disorder and attention-deficit and hyperactivity disorder, patients with TS can present with self-injurious behavior (SIB), defined as the ‘deliberate, nonaccidental, repetitive infliction of self-harm without suicidal intent’. Objective: This review aimed to determine the prevalence and clinical correlates of SIB in TS. Methods: We conducted a systematic literature review in accordance to the methodology described in the MOOSE Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies in Epidemiology. Results: Our literature search yielded 19 cohort studies that were suitable for quantitative synthesis. Combined results showed that SIB is present in 34% of patients with TS. The presence of comorbid OCD, obsessive-compulsive behaviors, and anxiety disorders were found to be associated with the presence of SIB. However this association was significant only for obsessive-compulsive behaviors (p=0.006). In addition to behavioral comorbidities (especially OCD), both tic severity and number of motor tics appeared to influence the presence of SIB. Conclusion: Obsessive-compulsive symptoms appear to be associated with SIB in patients with TS, and their presence should alert clinicians to the possible development of SIB, particularly if the patient has multiple behavioral comorbidities. Since the reviewed studies were methodologically heterogeneous and were conducted in specialist clinics, our findings cannot be generalized to patients with TS in the wider community.

Background: Traumatic brain injury (TBI) has become increasingly recognized and research is ongoing to better understand resilience and the factors that may contribute to it. Moderate to severe TBI has been associated with long-term impairments, including decreased social and occupational functioning after the injury. Factors that may impact resilience in moderate to severe TBI samples include education, preinjury substance abuse, postinjury anxiety, social support and coping skills. Case History: 42yo male graduate student presented for continued care for anxiety and on review of past history was noted to have a prior moderate TBI 6 years earlier in the context of heavy alcohol use. Afterward, he noted increased forgetfulness, difficulty with task initiation, low frustration tolerance, behavioral disinhibition, impaired balance, coordination and hearing. However, as he had been receiving prior psychotherapy and was enrolled in a doctoral program when presenting for treatment, he was diagnosed with generalized anxiety with no further workup. When further evaluation of the TBI was completed, imaging showed gliosis of the anterior inferior portion of his frontal lobes and neuropsychological testing showed notable impairment in manual dexterity, executive function, learning and memory out of proportion to his intellectual achievement. Conclusion: This case demonstrates the complexity of understanding resilience in moderate TBI. Though this patient did have high educational attainment, he was abusing substances, had significant anxiety, limited social support and limited coping skills. However, his recovery was substantial with preserved occupational functioning and some social difficulties. This highlights the complexities of resilience that transcend simplistic risk factors.

Background: Brain derived neurotrophic factor (BDNF) Val66Met polymorphism Met-positivity has been linked to increased rates of cognitive decline among those with higher beta-amyloid (Aβ) load and Apolipoprotein E (APOE) E4 carriage. It is not known how BDNF and its interaction with APOE4 carriage relate to cerebral metabolic rate for glucose (CMRgl) in preclinical Alzheimer’s disease (AD). Objective: To further examine the interaction of BDNF met and APOE4 carriage on glucose metabolism, amyloid burden, and cognitive decline among cognitively unimpaired (CU) adults. Methods: From our prospective cohort study of aging, we examined baseline CMRgl, Pittsburgh B (PiB) PET measured amyloid burden, both at p=0.001 uncorrected for voxel-wise multiple comparisons, and subsequent rate of change in cognition (at p=0.05) from 114 CU adults (59 with PiB PET) who had been both BDNF and APOE4 genotyped. Results: As expected, APOE4 carriers had significantly higher frontal amyloid, decreased CMRgl in a pattern similar to AD, and greater rate of decline in memory than APOE4 noncarriers. Among APOE4 carriers, BDNF Met carriers had significantly greater frontal amyloid, higher CMRgl, and a trend for increased rate of memory decline than Val carriers. These BDNF effects were not found among APOE4 noncarriers. Increased amyloid deposition was positively correlated with areas of greater cerebral metabolism. Conclusion: Our results confirm an interaction between BDNF met and APOE4 carriage suggesting that BDNF val/val carriage is protective for APOE4 carriers. The increased CMRgl in APOE4/BDNF met carriers may reflect a compensatory response leading to amyloid metabolism and Aβ deposition.

Background: Mania is a rare but potentially debilitating consequence of focal brain lesions. Lesions causing mania are frequently right-hemispheric but anatomically heterogeneous, with no single lesion location considered necessary for the emergence of mania. To date, no data are available to determine whether neuroanatomically distinct lesions causing mania share common underlying patterns of functional connectivity. Objective: To identify functional connectivity patterns common to anatomically heterogeneous brain lesions causing mania. Methods: Twenty cases of new-onset mania following a radiographically documented brain lesion were identified from the literature. Patients with prior history of bipolar or psychotic disorders were excluded. The radiographic lesions were mapped to a standardized brain atlas, and functional connectivity patterns for each lesion site were identified using high resolution human connectome data (N=1000). These individual lesion connectivity results were overlapped across all lesions to identify areas of common functional connectivity in lesion-induced mania. Results: Among the 20 patients included (14 male, 6 female), mean age was 50.7 (range 23–80). 16 lesions were right-sided, 3 bilateral, 1 left-sided. 11 lesions were cortical, 6 subcortical, 3 cortical/subcortical. Lesion sites were functionally connected to the right ventral-anterior insula in 19 of 20 patients (95%), the left ventral-anterior insula in 17 patients (85%), the right dorsal-anterior amygdala in 17 patients (85%), and the left dorsal-anterior amygdala in 17 patients (85%). Conclusion: Neuroanatomically diverse brain lesions causing mania are functionally connected to the ventral-anterior insular cortex and dorsal-anterior amygdala in humans, two reciprocally interconnected brain regions that are strongly implicated in human emotional states. Acknowledgments: Michael D. Fox has submitted a patent on using connectivity imaging to identify the ideal site for brain stimulation. This method is not discussed in this work.

Background: Electroconvulsive therapy (ECT) is an effective treatment for refractory depression. Subanesthetic ketamine infusions have rapidly acting antidepressant effects. Ketamine as anesthesia in ECT has not improved outcomes. Subanesthetic doses may have differing effects on neurocircuitry than anesthetic doses. We treated five patients with ECT-refractory or residual depressive symptoms with subanesthetic doses immediately before ECT to augment antidepressant response as measured by the Beck Depression Inventory (BDI). Case Histories: Four patients had major depressive disorder (one had comorbid obsessive compulsive disorder). One had bipolar depression. The first patient had reduction in BDI scores after two infusions and worsening postictal agitation that resolved prior to discharge. The second had transient subjective improvement in mood during two ketamine infusions which was not sustained. The third developed re-experiencing of trauma and suicidal ideation after one infusion that resolved quickly. The fourth patient felt “off” after one infusion and did not return for the next treatment. The fifth had reduction in BDI scores after two infusions however felt too “lethargic” to continue. Conclusions: Three out of five patients showed transient improvement with one showing a sustained response. We also observed worsening postictal agitation and intolerable psychiatric side effects that were all safely managed. Response rates in an ECT-refractory population would be expected to be low, however our series is insufficient to assess the risks and benefits of using subanesthetic ketamine as ECT augmentation. As evidence-based treatments for ECT-refractory depression are limited, further research into a role for ketamine in this population is warranted.

Background: Tourette syndrome (TS) is a neurodevelopmental condition characterized by the presence of multiple motor and phonic tics, often associated with comorbid behavioral problems. Tics can be modulated by environmental factors and are characteristically exacerbated by psychological stress, among other factors. This observation has led to the development of specific behavioral treatment strategies, including relaxation therapy. Objective: This review aimed to assess the efficacy of specific relaxation therapy to control or reduce tic symptoms in patients with TS in comparison to those undergoing no treatment or other treatment types. Outcomes measures included both tic severity and tic frequency. Methods: We conducted a systematic literature review of original studies on the major scientific databases, including Medline, EMBASE, and PsycINFO, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Our literature search identified three controlled trials, with a total number of 40 participants (range: 6–18 participants). In all three studies, relaxation therapy decreased the severity and/or the frequency of tic symptoms. However, only one trial compared relaxation therapy to two other behavioral techniques, and found it to be the least effective intervention, reducing number of tics by 32% compared with 44% by self-monitoring and 55% habit reversal. Conclusion: Provide some initial evidence for the use of relaxation therapy as a behavioral therapy for TS. The controlled trials appraised for this review had a small sample size and there was high heterogeneity across study protocols.

Background and Objective: Small Intestinal Bacterial Overgrowth (SIBO) was known to be associated with neurodegenerative disorder such as Parkinson’s disease. This study aims to correlate the presence of SIBO with Alzheimer’s disease (AD) and its neuropsychiatric symptoms. Methods: Patients who fulfill DSM-5 criteria for probable AD were recruited into the study. Hydrogen breathe test (HBT) was delivered for detection of SIBO. Neuropsychiatric symptoms were determined by Neuropsychiatric Inventory-Questionnaire (NPI-Q). Healthy control (HC) was also recruited for HBT for comparison. Statistical analysis used including Wilcoxon rank sum test with continuity correction for continuous variables and chi-square test for categorical variables. Results: A total of 17 AD and 32 HC were recruited into the study. There was no significant difference found between the presence of SIBO in AD and HC group (AD 13.3%, HC 13.8%, p=0.966). Among AD patients, presence of SIBO was only correlated with presence of aberrant motor behavior (p=0.047). Conclusion: Preliminary results suggest presence of SIBO in AD was not significantly different from HC. The only positive correlation of neuropsychiatric symptoms found in NPI-Q in this study still need to be interpreted with care due to the small sample size in this pilot study.

Phantom boarder symptom (PBS) is a type of misidentification in which the patient believes someone uninvited is residing in his or her home despite evidence to the contrary. Current literature suggests there is no link between the severity of cognitive impairment and PBS, meaning that the appearance of PBS can serve as a warning sign of early dementia. This was the case for a 72-year-old well educated Caucasian woman whose PBS was the first presenting symptom of Alzheimer disease. The patient was referred to our clinic by the police because of an intruder who had, for the past two years, broken into her home 590 times to sleep on her roof. The intruder was described as being Scottish with military clothes and is often accompanied by his girlfriend and son who poke her with needles, use cocaine, and steal her jewelry. Because the police refuse to respond, she began sleeping with a pistol for self-defense. Her functional brain MRI with FDG-PET was consistent with Alzheimer disease with extensive parieto-temporal hypometabolism extending to the frontal lobes bilaterally in disproportion to her clinical amnestic mild cognitive impairment profile. Her initial MoCA was 23/30, but after two months of Donepezil, she showed cognitive improvement with an MMSE of 29/30. Her PBS, however, has progressively worsened despite two months of Risperidone, and on her last visit, she stated that she was attacked by the intruder. This case illustrates the importance of screening for dementia when a previously healthy individual presents with PBS.

Background: Loneliness is a perception of social and emotional isolation that increases in prevalence among older adults during the eighth decade of life. Loneliness has been associated with higher neocortical amyloid-β (Aβ) deposition in cognitively-normal (CN) older adults, suggesting a link with preclinical Alzheimer’s disease (AD) pathophysiology, but its associations with sites of tau deposition are not yet defined. Objective: To assess whether tau deposition in entorhinal (EC) and inferior temporal (IT) cortices is associated with greater loneliness in CN older adults. The association of neocortical Aβ deposition with loneliness was also investigated. Methods: One-hundred and seventeen CN adults, ages 64–92, underwent clinical evaluations as well as Flortaucipir (FTP) and Pittsburgh Compound-B (PiB) Positron Emission Tomography to assess in-vivo tau and Aβ deposition. Loneliness was measured using the 3-item UCLA loneliness scale [(UCLA-loneliness); range 3–12]. In separate linear regression models, partial-volume corrected bilateral and unilateral EC and IT FTP and a partial-volume corrected aggregate measure of neocortical PiB were evaluated as predictors of UCLA-loneliness, controlling for age, sex, APOEε4 carrier status, socioeconomic status, depression, anxiety, and social network scores. Results: Higher FTP in right EC (β=1.20, p=0.02) and right IT (β=2.14, p=0.04) were associated with greater UCLA-loneliness. Higher PiB was also associated with greater UCLA-loneliness (β=1.09, p=0.02) and was stronger in APOEε4 carriers (Aβ×APOEε4: β=1.93, p=0.03). Associations of FTP in left/bilateral regions with UCLA-loneliness were nonsignificant. Conclusion: Loneliness may be a subjective socioemotional marker related to AD molecular pathologies in older adults prior to the onset of cognitive impairment.

Background: New-onset psychosis in mid to late life is an interesting and uncommon phenomenon. Typically, onset of psychosis is during adolescence. Earlier manifestations (childhood) and later manifestations (after 45 years old) are rare, as men tend to be diagnosed between 18–25 and women between 25–35 (albeit with a second peak noted near menopause). Clinicians should be wary when new psychotic symptoms develop in a patient outside of these peak times, as psychiatric diagnoses often follow a patient lifelong, prompting treatment with chronic medications that carry a risk of significant side effects. Below, I present a case of new-onset psychosis and pseudobulbar affect secondary to ciprofloxacin that without prudent investigation may have ended up receiving inpatient psychiatric treatment and chronic psychotropic medication for a chronic psychiatric condition she did not ultimately have. Case: My case involves a 52-year-old female who exhibited symptoms of psychosis (including delusions, paranoia, and visual hallucinations) as well as pseudobulbar affect following reception of ciprofloxacin. Her neuropsychiatric symptoms appeared to have been directly related to the administration of this drug, and resolved quickly after its removal. This is the first reported case to my knowledge of pseudobulbar affect deriving from ciprofloxacin. Conclusions: The fluoroquinolones (ciprofloxacin being a member) are a class of antibiotic medications used frequently in the treatment of infection. Psychiatrists and neurologists should be aware of the complex side effect profile of these medications, which can lead to concerning symptoms such as profound psychosis which could lead to lifelong treatments with all-but-benign side effect profiles, stigma, and major changes to care including unnecessary psychiatric hospitalizations. Thus, providers should be cautious when approaching a new-onset psychosis in an older patient, evaluating for reversible causes prior to making a primary psychiatric diagnosis.

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Background: Maladaptive coping and insecure attachment are predisposing factors for Functional Neurological Disorders (FND). No prior structural neuroimaging studies have investigated biomarkers associated with attachment or coping styles in FND. Objective: This MRI study investigated cortical thickness and subcortical volumes associated with self-reported coping, attachment style, and trait resilience in patients with FND. We hypothesized that maladaptive coping, insecure attachment, and low resilience would relate to limbic-paralimbic cortical thinning and volumetric reductions. Methods: FreeSurfer cortical thickness and subcortical volumetric analyses were performed in 26 patients with motor FND (21 women, 5 men) and 27 healthy controls. Patients with FND were stratified by Relationship Scales Questionnaire (attachment measure), Ways of Coping Scale-Revised, and Connor-Davidson Resilience Scale scores. Within-group analyses were also performed in patients with FND. All analyses were performed in mixed-gender, as well as women only, cohorts to consider gender effects. Cortical thickness analyses were whole-brain corrected at the cluster-wise level; subcortical analyses were Bonferroni corrected. Results: In women with FND, dismissive attachment inversely correlated with left parahippocampal cortical thickness (p_{whole-brain-corrected(wbc)}=0.0002). Accepting responsibility positively correlated with right ventral premotor cortical thickness (p_wbc=0.03), while confrontative coping was inversely associated with decreased right hippocampal volume (p_wbc=0.03). For all findings, regional structural profiles in women with FND were within the normal range when compared with healthy women. Conclusion: These findings link individual differences in limbic-paralimbic and premotor structures to attachment and coping styles in FND. The inverse relationship between parahippocampal thickness and dismissive attachment may indicate aberrant sensory-contextual processing in patients with FND.

Background: The FDA-approved rTMS approach requires 6 weeks to apply 90,000 magnetic pulses, and ∼30% of patients achieve remission. Objective: To examine a patterned theta-burst stimulation (pTBS) methodology as a method for producing rapid antidepressant action through patterned excitation of the established treatment-resistant depression (TRD) target, left dorsolateral prefrontal cortex (L DLPFC). We sought to recruit six patients with refractory TRD who meet inclusion criteria for deep brain stimulation (DBS) for TRD. Methods: Adults (N=6) who were 21–70 years old with TRD [≥20 on the Hamilton Rating Scale for Depression (HRSD17) and rating of 14/15 on the Maudsley Staging Method with failure to respond to 1) ≥7 antidepressant medications, 2) course of psychotherapy, 3) ≥1 course of traditional rTMS, and 4) failure/intolerance to electroconvulsive therapy (ECT)] were recruited. Participants were stimulated with pTBS over the L DLPFC for 5 days for a total of 90,000 pulses delivered at depth-adjusted 90% resting motor threshold (rMT). Results: The 6 participants with an average entry HRSD17 of 28.8 (SD 6.05). The mean improvements from prestimulation baseline on the HRSD17 were 21.83 (76% change from baseline) for these 6 TRD patients. Reductions in HRSD17 scores were statistically significant immediately post stimulation course (p=0.0033) as well as on the MADRS (p=0.0014) and the BDI II (p=0.0131). Conclusion: Patterned theta-burst stimulation (pTBS) over L DLFPFC is a new neuromodulation approach that in open-label usage resulted in remission of major depression in four of six individuals and response in one individual all with severe TRD.

Background: Impaired comportment and behavioral dysregulation are known sequelae of injury to the lateral orbitofrontal subcortical circuit (LOFC), and may include inappropriate sexual behaviors. The onset of behavioral disturbances typically occurs relatively soon after injury, as opposed to many years later. Here we present an atypical case involving extensive right OFC damage followed by over a decade of relative quiescence, with the subsequent emergence of problematic sexual behaviors resulting in criminal charges and court-ordered confinement. Case History: The patient, now in his late sixties, had been a high-functioning professional until undergoing resections of a right frontal arteriovenous malformation. The initial insult resulted in considerable neuropsychiatric impairment (executive dysfunction and reduced motivation), though significant behavioral issues did not emerge for over a decade, at which point highly inappropriate behaviors of a sexual nature started to occur. Behaviors soon resulted in criminal charges and incarceration. Subsequent MRI revealed extensive damage to the right OFC. Behaviors persisted, despite retained insight and awareness for serious consequences associated with reoffending. Subsequent behaviors resulted in additional charges, reincarceration, and court-mandated placement in a locked nursing home facility. Behaviors persisted until environment modifications and low dose risperidone seemingly afforded adequate behavioral control. Conclusions: The present case involves the atypical late emergence of sexually inappropriate behaviors over a decade after right OFC injury. Despite the lengthy delay between injury and the onset of behavioral problems, the nature of the behaviors, the magnitude and location of injury, and the otherwise out-of-character nature of the behaviors suggest a significant relationship.

Background: Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder that is thought to arise from a combination of aggregated genetic risk distributed across the genome and additional nongenetic risk factors. Adverse childhood experiences (ACE), such as child abuse and household dysfunction, have been shown to increase risk for multiple psychiatric disorders. However, no studies have examined the relationship between childhood adversity and TS. Objective: To examine whether ACE exposures and variation in TS polygenic risk are associated with increased worst-ever tic severity and/or impairment. Methods: 347 adult male TS subjects who had previously participated in a TS genetic study completed an online follow-up survey including a lifetime version of the Yale Global Tic Severity Scale (YGTSS) and the Adverse Childhood Experiences (ACE) questionnaire. Polygenic risk scores (PRS), measuring aggregated TS genetic risk, were derived from a TS genome-wide association study (GWAS) of 4232 European ancestry cases and 8282 ancestry-matched controls. The effects of psychiatric comorbidity (OCD and ADHD), ACE score, and TS PRS on worst-ever YGTSS Total Tic and Impairment scores were assessed using regression modeling. Results: In multivariable models, ACE score ≥2 was associated with a 3-point increase in worst-ever YGTSS Total Tic Score (p=0.03) and a 7-point increase in worst-ever YGTSS impairment (p<0.001). A significant gene-by-environment interaction was observed between TS PRS and ACE score for worst-ever tic severity (p=0.02), but not worst-ever impairment (p=0.13). Conclusion: Childhood adversity appears to increase worst-ever tic severity in individuals with higher underlying TS genetic risk, but does not influence impairment.

Background: Previously, we identified hippocampal volume reductions in bipolar I psychotic group (BPP) when compared with healthy controls (HC). Structural and functional neuroimaging studies comparing BPP with bipolar I nonpsychotic (BPNP) have not identified hippocampal differences. Whether there are cerebral blood flow (CBF) differences between BPP and BPNP subjects remains to determined. Objective: To characterize the CBF of the hippocampus, including its hippocampal subfields using a noninvasive measure of CBF. Methods: Subjects (BPP, N=48; BPNP, N=31; HC, N=60) underwent pseudo-Continuous Arterial Spin Labeling (pCASL) to measure CBF in the cross-sectional multisite PARDIP study. The hippocampus and its subfields were parcellated using FreeSurfer 6.0. Data were adjusted for site scanner. Group-wise CBF comparisons were assessed using MANCOVA, controlling for sex, age, and race, and adjusting for multiple comparisons. Results: There was a significant difference between groups for age (p=0.015) and site (p=0.046), but not gender or race. There was a significant CBF reduction in probands compared with controls for the left hippocampal–amygdaloid transition area (HATA) (p=0.043) and the left fimbria (p=0.018), but not for other hippocampal regions. The BPNP group demonstrated significantly reduced CBF values for the left hippocampus and several of its subfields compared with healthy control and BPP subjects, with the left HATA (BPNP<HC, p<0.001; BPNP<BPP, p<0.001) surviving both contrast and subfield correction. Conclusions: We identified CBF reductions across bipolar groups, driven by BPNP, which could be related to compensatory mechanisms. HATA CBF reductions suggest that amygdala and hippocampal integration may be affected in bipolar subtypes.