Frontotemporal Dementia: A Window to Alexithymia

Emotion is a process that involves the insulae and a number of frontotemporal structures. Emotional processing in the brain begins with the identification of salient or emotional stimuli mediated by the amygdala. This results in physiological arousal and interoception, the perception of internal body or somatic sensations. Interoceptive sensitivity is strongly correlated with the strength of the physiological arousal in the posterior insulae (9). The anterior insulae, particularly on the right, merge these internal sensations with cognitive evaluation, resulting in the awareness of feelings (10). This process involves reciprocal interactions between the anterior insulae and the anterior cingulate cortex (ACC), which mediate emotional responding and the expression of affective arousal. The anterior insulae and ACC are core regions of the salience network, which activates in response to emotionally salient cues in the environment (11). In addition to interoception, the cognitive appraisal of one’s internal and external environment also contributes to emotional experience (12). Cognitive appraisal involves frontal regions such as the orbitofrontal cortex for emotional control, the ventromedial prefrontal cortex for affective meaning, and the ventrolateral prefrontal cortex for emotional integration and regulation. Finally, other temporal lobe structures such as the inferior temporal and fusiform gyrus are important for affective signal detection and integration, and the anterior temporal poles specifically link interoceptive stimuli with their conceptual meaning (13).

The mechanism for alexithymia may be a disassociation between internal physiological arousal and externally-based cognitive appraisal (14). In alexithymia, investigators describe difficulty “elevating emotions from a sensorimotor level of experience” to a representational level, where they can be used as signaling interoception (15). On the cognitive appraisal side, others propose relative dysfunction of neocortical areas for symbolically and linguistically representing emotion (16). Indeed, reports of patients who underwent a commissurotomy, or surgical incision into the callosal commissure, indicate increased alexithymia, as preserved interoceptive feelings in the right hemisphere could no longer access left hemisphere language and symbolization (14).

Still other information links alexithymia to a failure of interoception (17, 18). Persons with higher levels of alexithymia appear to have poor knowledge of their internal states and decreased interoceptive accuracy (9); alexithymia can impair interoception of cardiac and respiratory output, muscular effort, and taste sensitivity (17). Poor cardiac sensitivity correlates with high levels of alexithymia (19), and higher self-reported interoceptive confusion occurs among alexithymic individuals (18, 20). In autism, alexithymia is associated with decreased interoceptive sensitivity even in the presence of an intact interoceptive signal (21, 22). Much research also associates damage to the anterior insulae with both interoceptive difficulties and alexithymia (23, 24). Finally, poor recognition of facial negative emotions is linked to both high levels of alexithymia and low levels of interoception (25).

An important degenerative disorder that alters emotion is behavioral variant frontotemporal dementia (bvFTD). This disorder is the second most common neurodegenerative dementia among patients <65 years, after early-onset Alzheimer’s disease (26). Patients with bvFTD have behavioral changes such as impaired emotionality and empathy, apathy or abulia, disinhibition or impulsivity, dietary changes, and dysexecutive cognition from disease affecting the frontal and anterior lobes (26). The early focus of neuropathology in this disorder is in the anterior insulae, ACC, and the salience network.

In addition to bvFTD, the frontotemporal dementias include semantic dementia, also known as semantic variant primary progressive aphasia in its early stages. Semantic dementia results in a loss of semantics, or the meaning of words and objects, from atrophy in the anterior temporal lobes (27). The earliest changes in semantic dementia affect the meaning of words, manifesting as a semantic anomia, but as the disease progresses, there is a multimodal impairment in knowledge for objects, faces, sounds, smells, and other perceptions, regardless of modality, including confusion over the nature of somatic or bodily sensations (27).

Alexithymia is an important but poorly understood symptom that is present among a wide range of psychiatric disorders. Early descriptions of the mechanism of alexithymia suggested a primary disorder from a dissociation of “limbic” or interoceptive physiological signals from cortical representations or interpretations (15, 16). Investigators suggested that psychological trauma with overactive defense mechanisms blocked this “limbic-cortical” association; however, more recent studies point to disturbed interoceptive processing itself as central to alexithymia. Similar difficulties among two frontotemporal dementia syndromes, bvFTD and semantic dementia, shed light on the neurobiological mechanism of this symptom. Alexithymia in bvFTD results from a weak emotional and physiological signal with impaired interoceptive accuracy and a consequent overreliance on external context and rules for explaining the experience. Alexisomia in semantic dementia results from inability to correctly read intact interoception due to an impairment in the ability to derive the meaning of bodily sensations. These findings in brain syndromes known to affect the emotional centers of the brain, particularly insulae where interoception is centered, support a deficit in interoceptive accuracy as central to alexithymia from a blunted emotional physiological signal, from impaired cognitive appraisal, or from disturbance in interoceptive processing in the insulae. Clearly, more research can offer further insights into the neurobiological basis of alexithymia based on this model.