The Three-Dimensional Approach to Neuropsychiatric Assessment

The first step in the 3DA is reminding students of general neurology’s clinical dictum: localize the lesion. Neurology students learn that “Where is the lesion?” is the first question to answer in assessing new cases. Localizing the region of dysfunction is a crucial first step in clinical evaluation because it orients us to the fundamental organizing principle of clinical assessment of neurological disease: as a first approximation, the signs and symptoms of neurological disease are usually best accounted for by identifying the site and, thereby, the neural system affected. Localization is also valuable because the number and location of lesions has implications for diagnosis and treatment.

The 3DA is based on three dimensions; however, general neurology usually uses just two. Why three dimensions for the 3DA? In general neurology, laterality and verticality—left/right, up/down—suffice for most clinical questions, and certainly suffice to introduce the basics of clinical neurology. Refined questions may benefit from a three-dimensional approach. For introductory purposes though, a two-dimensional approach usually suffices. For example, it is helpful to know that the association of a left hemiparesis with right facial weakness suggests a right-sided pontine lesion.

In neuropsychiatry, a two-dimensional approach is helpful, too. For example, a dense, right hemiparesis associated with aphasia suggests dysfunction of the left hemisphere, and this relationship has psychiatric implications: left anterior hemisphere dysfunction is associated with depression and with executive cognitive dysfunction. Left hemiparesis associated with the same nonfluent aphasia calls for a different explanation. We may delve further into the history, perhaps to find a history of previous stroke,³ left-handedness, or a diagnosis of lung cancer with bilateral hemispheric metastases.

However, limiting ourselves to two dimensions creates problems in neuropsychiatry. Without distinguishing all three dimensions: left/right, front/back, up/down—students will have trouble making clinical sense of patients who show more complex symptom pictures. For example, it is not easy to make a functional-anatomical interpretation of supranuclear palsy’s symptom picture: memory complaints, executive cognitive loss, extrapyramidal motor dysfunction, oculomotor signs, personality change, and motivational loss (see Case #4 and Conclusions). The 3DA organizes such data into clinical patterns in ways that are helpful anatomically, diagnostically, and therapeutically.

Presenting brain–behavior relationships in three dimensions speeds up learning. Students may know that hemispheric behavioral organization is complex; what they don’t know is how to keep track of it all, how to see the coherence of brain–behavior relationships, and how to apply these relationships in clinical assessment.

Over the past 25 years, delineation of the frontal–subcortical reentrant circuits has become, with little question, the single most important functional-anatomic model for understanding neuropsychiatric dysfunction. Building on the groundbreaking work of Alexander, Delong, and Strick,⁶ and others,⁷ clinical neuropsychiatry acquired⁵ an anatomically-based model for understanding the functions and connectivity of the prefrontal regions of the cerebral cortex. The frontal–subcortical model elegantly parses prefrontal cortex into a small number of regions, each with a specific relationship to a major domain of adaptive capacity—personality change, executive cognition, motivation, oculomotor function, and somatic motor function. Like all models, it has its limits. It oversimplifies. It is incomplete. It is in flux. However, it remains a solid framework for introducing students to the clinical spectrum of hemispheric behavioral dysfunction. And it offers a simple, easily-digested, visual image (Figure 1) for understanding the paradox that patients with basal ganglia disease often have neurobehavioral symptoms that might otherwise be attributed to frontal cortex dysfunction. Therefore, the functional-anatomic connectivity of the frontal–subcortical circuits answers the DBQ we used to introduce the vertical dimension of the 3DA: How do you explain the fact that some patients with basal ganglia disease behave as if they have a frontal lobe syndrome? The reason patients with basal ganglia disease show signs of “frontal lobe” dysfunction is, simply, that the basal ganglia are integral parts of the frontal–striatal–pallidal–thalamic circuits that mediate these capacities. The problem here is not clinical; we do not have to decide whether the lesion is cortical or subcortical. Rather, the problem is that “where is the lesion?,” the first principle of clinical neurology, is not a principle of neurological function. As we learned many years ago: lesions are localized; functions are not. Functions reflect actions and interactions of systems and subsystems, circuits and subcircuits. Functions are anatomically-mediated, but they are not anatomically localized. We want students to understand this. The frontal–subcortical paradox gives us a good opportunity to make the point.

How does the 3DA resolve the frontal–subcortical paradox? The 3DA reminds students, or, perhaps more often, introduces them to the functional organization of the cortical–striatal–pallidal–thalamic reentrant circuits. My approach is to present a question: “What is the subcortical connectivity of the cerebral cortex? Choose a point on the cerebral cortex and describe its connections with the basal ganglia and thalamus? An occasional student, usually an M.D.-Ph.D. neuroscientist, will know the answer. The cerebral cortex, virtually every part of it, projects to striatum (i.e., caudate or putamen); striatum projects to globus pallidus; globus pallidus projects to thalamus; and thalamus projects back to the cerebral cortex, roughly the same region of the cerebral cortex from which we began.

This is complicated. So a diagram or two helps. The presentation of Mega and Cummings,⁵ (Figure 1), because it’s clear and color-coded, makes this particularly easy to visualize and, furthermore, lets us introduce the functional specificity of the prefrontal circuits, three with psychological features (executive cognitive function [A; dark shading], personality [B; light shading], and motivation [C; white]) and two with motor features (general motor and oculomotor). This description foreshadows the use, shortly, of progressive supranuclear palsy as a model disorder in Step 4.

The final step in the 3DA is to demonstrate its clinical use with model disorders. The model disorders offer clinical-pathological paradigms for each of the three dimensions. They also permit students to analyze a clinical case in 3DA terms. Instructors may choose cases according to their background and the experience of their students. The cases I use are: for laterality, a case of stroke; for anteriority, FTD and DAT, illustrating, respectively, anterior and posterior aspects of anteriority; for verticality, progressive supranuclear palsy, to illustrate the subcortical, basal ganglia aspect. Regardless of the conditions chosen, it is particularly important to choose separate cases to illustrate anterior and posterior because clinical features in the anteriority dimension are often intermixed and difficult to distinguish.

Teachers will have their own ideas for how to make use of these cases. Based on the presentation here, one may highlight some of the following. Case #1 illustrates the laterality dimension and permits review of the basic features of hemispheric dominance and asymmetry. More advanced discussion enters into the qualitative differences between the hemispheres (Table 1). Case #1 makes the point that the hemispheres share basic sensorimotor functions, which are organized contralaterally, and that important domains of neuropsychological function—language versus attention and visuospatial capacity—are dominant functions of the left and right hemisphere, respectively. Discussion of other higher cortical functions follows naturally from this. Definitions and classifications of apraxia, agnosia, aphasia, and aprosodia may be introduced as time permits. Less-familiar concepts, for example, Gerstmann’s syndrome and prosopagnosia, may be introduced, depending on the audience. In turning to the anteriority dimension, the model cases demonstrate the fundamental difference between syndromes of anterior and posterior hemispheric dysfunction. DAT and FTD are readily appreciated for this purpose. However, it is equally important to point out that we are demonstrating anatomic-functional relationships that extend to all classes of neurological disease, not just degenerative diseases. It is also helpful to acknowledge the overlap of symptoms between diseases that are preponderantly anterior and posterior, making it clear that clinical diagnosis has limited validity and, as Hickam’s dictum¹⁰ tells us, many patients have more than one disease. In either case, the 3DA is a powerful organizing device for characterizing the clinical presentation. This benefit is clearly illustrated as we make use of Cases #2 and #4 to illustrate the intriguing overlap between diseases affecting prefrontal cortex and those affecting subcortical white matter and basal ganglia. Both may produce “frontal syndromes” due to disruption of frontal–subcortical circuits. In this context, we emphasize that lesions may be localized to location, but functions are localized to circuits and subcircuits. The 3DA makes this point in explaining the frontal–subcortical paradox. Students find the frontal–subcortical paradox a tidy way of holding on to the simple and paradoxical fact that patients with subcortical disease, as in Case #4, present so-called “frontal” signs. In using Case #4, it is also helpful to indicate that it is the presence of basal ganglia motor features (rigidity, bradykinesia, movement disorder, etc.) that points more specifically to the presence of basal ganglia disease. Absent motor features, the frontal–subcortical paradox implies that features of prefrontal disease may reflect either cortical or subcortical dysfunction.

Brain–behavior relationships form the practice foundation for neuropsychiatry and behavioral neurology. They are an essential element of content curricula and training programs in neuropsychiatry and behavioral neurology.^8,9 The complexity of the brain and its clinical disorders makes it important to have a systematic and useful way to apply them. The three-dimensional approach to neuropsychiatric assessment provides a simple, systematic approach for integrating brain–behavior relationships into this process. It is based on readily-identified, important clinical features of brain dysfunction. With practice, instructors will find that the essence of the 3DA can be effectively communicated in a very short period of time: 10 to 20 minutes is ample for an initial introduction. At the bedside, returning to 3DA principles makes it possible to refine basic points and show students how easily they can bring knowledge into practice.

The 3DA is a process-based approach to teaching neuropsychiatry and behavioral neurology. It is easy to understand and implement. Novice students find that it identifies the basics of behavioral neurology and neuropsychiatry so that scattered bits of clinical and neuroanatomical information quickly funnel into a systematic, easily remembered, and useful approach to dealing with diverse clinical problems. Like general neurology, it is anatomy-based and therefore gives users a disciplined way to assess new cases, regardless of specific disease process.

The 3DA allows modifications according to the interests of the instructor and the sophistication of the student. Although developed as an introduction to the basics of neuropsychiatric assessment, it is refinable to accommodate subtleties of functional-anatomic organization. The basic vocabulary of signs and syndromes can be expanded, for example, to include Gerstmann’s syndrome, subtypes of aphasia, apraxia, aprosodias, etc. Discussion of hemispheric function and organization can be refined to review concepts of hemispheric specialization, for example, sequential and holistic, analytic/synthetic; and complex cases can be elucidated by pointing out anatomically-based symptom clusters, for example, the way symptoms of PSP (Case #4) can be attributed to the dorsolateral (executive cognitive symptoms), orbitofrontal (personality change), mesial (apathy), oculomotor (visual and reading complaints) and supplementary motor (extrapyramidal findings) subcircuits of the frontal–subcortical systems.

In summary (Table 1), the 3DA is a four-step process for teaching neuropsychiatric assessment. The steps are 1) understand localization of function; 2) organize brain–behavior relationships in three dimensions; 3) apply the frontal–subcortical paradox; 4) illustrate the three dimensions with cases that represent model disorders. It uses dimension-bridging questions (DBQs) to prompt knowledge-integration across dimensions. Although it is intended primarily for initial assessment—as a way to orient the practitioner to the salient features of clinical presentation—the initial 3D formulation can be applied to later stages of treatment planning and evaluating changes in clinical status.

Comprehensive curricula^1,2 and training programs^8,9 in neuropsychiatry and behavioral neurology may readily integrate the 3DA. Also, 3DA principles may be used as springboards to deepen students’ knowledge of the symptoms, syndromes, and diseases that comprise a full content curriculum. In these and other ways, the three-dimensional approach to neuropsychiatric assessment invigorates the content curriculum with practice principles that enhance students’ appreciation of neuropsychiatry’s rich and challenging opportunities.