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Essential Behavioral Neuroanatomy
The interpretation of the mental status examination depends on an understanding of behavioral neuroanatomy. As in the rest of neurology, the examination leads to localization, followed by a differential diagnosis of disease processes. This chapter gives the essentials necessary for localization of mental status abnormalities in the brain. It includes the different cortical lobes and the limbic structures that line the medial aspect of the cerebral hemispheres and contribute to memory and emotions. It covers the essentials only, as it would require the entire book for a complete and exhaustive review of behavioral neuroanatomy.
This chapter has three parts. The first part discusses general brain-behavior principles. They involve hemispheric specialization and cerebral dominance, disconnection phenomena, and the “anomalous dominance pattern.” The second part discusses the regional localization of specific behaviors in the brain. This section assumes a “localizationist” view that testable neurocognitive domains are located in different brain regions or centers. The last part of this chapter challenges this localizationist view and introduces neural networks and circuits. It emphasizes that, although we use a modular centers approach for localization of neurocognitive disorders, the reality is that they arise from changes in complex and distributed, interconnected circuits.
General Brain-Behavior Principles
The brain is composed of two cerebral hemispheres (telencephalon) along with subcortical white matter and basal ganglia, corresponding thalamic and hypothalamic nuclei (diencephalon), the brain stem, and the cerebellum. The six-layered neocortex is a convoluted structure, organized into gyri and sulci, which spans four major lobes: frontal, temporal, parietal, and occipital. The brain contains approximately 86 billion neurons, with 100 trillion synapses, resulting in numerous and complex networks. Histological areas of the brain are composed of “Brodmann areas” (BA) ( Fig. 4.1 ), which aid in localizing brain-behavior functions.
A basic principle of brain organization of importance to the mental status examination is the presence of hemispheric specialization and the related concept of cerebral dominance. The strongest evidence of differences between the two brains comes from the occurrence of distinct disorders from focal lesions in the left and right hemispheres ( Table 4.1 ). Further evidence for hemispheric specialization comes from studies on “split-brain” patients. To prevent seizure generalization, some patients have undergone a surgical transection of the corpus callosum, the main interhemispheric fiber bundle, with resultant inability to transfer information between the two hemispheres. The split hemispheres may manifest different emotional states along with interhemispheric cognitive differences evident on specialized testing of each side separately ( Fig. 4.2 ). With the left hand they may not be able to name (tactile anomia), perform learned motor movements (ideomotor apraxia), or write without linguistic errors (agraphia), whereas with their right hand they may not be able to copy or perform visuospatial tasks (dyscopia, left hemineglect).
TABLE 4.1
Signature Left and Right Hemisphere Deficits
| Left Hemisphere Abnormalities |
| Aphasias |
| Alexia and agraphia |
| Ideomotor apraxia |
| Acalculia and Gerstmann syndrome |
| Loss of detail in drawings/constructions |
| Somatotopagnosia or autotopagnosia |
| Associative visual agnosia |
| Color anomia or color agnosia |
| Right Hemisphere Abnormalities |
| Visuospatial difficulties |
| Abnormal visuospatial constructions with decreased overall pattern |
| Environmental disorientation or topographagnosia |
| Dressing apraxia |
| Left hemispatial neglect |
| Anosognosia |
| Aprosodia and amusia |
| Face discrimination difficulties |
TABLE 4.2
Brain Localization of Cognitive and Behavioral Disturbances
| The following lists are not exhaustive, and localization is approximate for many items. B = bilateral; L = left; R = right. |
| Frontal Lobes |
| Abstraction impairment on idioms and proverbs (B, L>R) |
| Amusia and aprosodia, expressive (R) |
| Apathy, abulia, and akinetic mutism (B) |
| Aphasia, non-fluent or Broca (L) |
| Aphemia or isolated verbal language expression difficulty (L) |
| Attentional disengagement (R) |
| Complex problem-solving difficulty (L>R) |
| Compulsive or repetitive behaviors (B?) |
| Delusions or impaired reality testing (especially with temporal limbic involvement) (R) |
| Depression (L) |
| Design fluency impairment (L) |
| Disconnection ideomotor apraxia (L) |
| Disinhibition (B) |
| Dysexecutive syndrome (B) |
| Emotional lability (R>L) |
| Empathy impairment (R>L) |
| Environmental dependency, echolalia, echopraxia, imitation/utilization behavior (B) |
| Feedback responsiveness impairment (B) |
| Frontal lobe personality change (R) |
| Insight impaired and loss of personal and social awareness (R>L) |
| Jocular affect, euphoria (B, R>L) |
| Judgment impairment (B) |
| Manic-like affect (R) |
| Motor programming difficulty (B, L>R?) |
| Perseveration, intrusions, stimulus-bound (B, R>L?) |
| Phonagnosia, or inability to identify voices (R) |
| Psychomotor slowed, poor initiation (B) |
| Response inhibition impairment (B) |
| Set changing difficulty (L>R) |
| Social dysregulation (R>L) |
| Social judgment, tact, and social responsibility impairments (R>L) |
| Theory of mind impairment (R>L) |
| Verbal fluency or word-list generation impairment (L) |
| Working memory impairment (B) |
| Temporal Lobes (Lateral Neocortical and Mesial Limbic) |
| Amnesia, particularly declarative, episodic memory loss (B) |
| Amusia, receptive difficulty in music appreciation (B, R>L) |
| Aphasia, fluent, Wernicke (L) |
| Aprosodia, receptive difficulty in the melody and intonation of language (R) |
| Auditory agnosia (B, R>L) |
| Auditory perception disturbances (B, R>L) |
| Biological motion, difficulty in detection (B, R>L) |
| Conduction aphasia (L) |
| Contralateral superior quadrantanopia (L or R) |
| Cortical deafness (B) |
| Emotional empathy impairment (R) |
| Emotional learning or conditioning impairment (B) |
| Emotional reaction impairment (B) |
| Expert visual system disturbance (B, R>L) |
| Kluver-Bucy (placid, hypermetamorphosis, hyperoral, hypersexual, visual agnosia) (B) |
| Landmark agnosia (R) |
| Prosopagnosia, or impaired recognition of familiar faces (B, R>L) |
| Pure word deafness (B or L) |
| Rhythm agnosia (L) |
| Semantic anomia (L) |
| Semantic knowledge difficulty (B) |
| Sense of perceptual familiarity altered (R) |
| Social concepts impaired (R) |
| Surface agraphia (L) |
| Temporal lobe personality changes (B, R or L) |
| Theory of mind impairment (R>L) |
| Topographagnosia, or environmental disorientation from landmark agnosia (B, R>L) |
| Visual hallucinations, formed (R) |
| Visual word form alexia (L) |
| Word-selection anomia (L) |
| Parietal Lobes |
| Acalculia, or abnormal calculation (L>R) |
| Agency attribution impairment (R) |
| Agraphia, or writing disturbance (L) |
| Akinetopsia, or abnormal movement detection (R) |
| Alexia, or reading disturbance (L) |
| Alexithymia, or inability to recognize one’s feelings (R) |
| Anarithmetia, or loss of basic mathematical processes (L) |
| Anosodiaphoria, or loss of concern for illness (R) |
| Anosognosia, or loss of awareness or denial of illness (R) |
| Aphasia, transcortical sensory (L) |
| Asomatognosia, or the loss of awareness of parts of one’s body (R) |
| Attentional disengagement and disorientation (B, R>L) |
| Balint syndrome, or simultanagnosia, optic ataxia, oculomotor apraxia (B) |
| Body identity disorders or distortions (R) |
| Constructions with impaired basic form (R) |
| Constructions with impaired detail (L) |
| Contralateral inferior quadrantanopia (L and R) |
| Depersonalization or derealization (R) |
| Depth perception impairment (global stereopsis, monocular depth cues) (R) |
| Digit agnosia or difficulty knowing fingers or toes, and right-left confusion (L) |
| Dressing apraxia (R) |
| Egocentric spatial disorientation (R) |
| Environmental disorientation from topographic memory impairment (R) |
| Facial discrimination impairment (R) |
| Gerstmann syndrome (acalculia, agraphia, right-left confusion, digit agnosia) (L) |
| Gestalt grouping perceptual impairment (R) |
| Ideomotor apraxia (L) |
| Idiokinetic apraxia (L>R)) |
| Neglect, hemispatial, contralateral sensory or body, or conceptual (R) |
| Oculomotor apraxia (B, R>L) |
| Optic ataxia (B, R>LR) |
| Planotopokinesia, or impaired map reading (R) |
| Spatial acalculia (R) |
| Spatial agnosia including visual search difficulty (R) |
| Visual line orientation impairment (R) |
| Occipital Lobes |
| Alexia without agraphia (L) |
| Apperceptive visual agnosia (B) |
| Associative visual agnosia (L) |
| Body form and body action agnosia (B) |
| Color agnosia, color anomia, and color aphasia (L) |
| Cortical blindness (B) |
| Figure-ground disturbance (B, R>L) |
| Hemiachromatopsia (L or R) |
| Homonymous hemianopsia (L or R) |
| Stereopsis disturbances (B) |
| Visual hallucinations, unformed (B) |
| Visual illusions (R>L) |
| Visual synthesis disturbance (B, R>L) |
Hemispheric specialization implies that there is cerebral dominance for cognitive functions in one hemisphere versus the other. Most of this focuses on language dominance, although the most common overt phenotypic expression is hand preference. The early work of Paul Broca, Karl Wernicke, and others demonstrated language in the left hemisphere localized in two hubs: the Broca area (BA 44, 45) for language production in the left inferior frontal region, and the Wernicke area (BA 22) for language comprehension in the left superior temporal gyrus. Broca further suggested an association between the dominant hand and the dominant hemisphere for language, and the majority of right-handed persons are left-hemisphere dominant for language. In contrast to the left hemisphere, the right hemisphere has a dominant role for global visuospatial processing. It may also have a “dominant” role in emotion, for example, determining the emotional prosodic aspects of communication and the emotional state of a speaker from tone of voice ( Table 4.1 ); however, the valence theory of emotion suggests that negative emotional tendencies arise from the right hemisphere and more positive emotional tendencies from the left.
As seen from hemispheric specialization and split-brain studies, there can be disconnection between hemispheres and between different neurocognitive centers within each hemisphere ( Fig. 4.3 ). Norman Geschwind described how disconnection of cortical centers, such as the Broca area and Wernicke area, could produce language syndromes that were distinct from those due to lesions in the Broca area or Wernicke area. The phenomena of disconnection syndromes led to an entirely different understanding of the origin of mental status deficits or neurocognitive disorders, for example, alexia without agraphia (reading difficulty without writing impairment) from disconnection of visual input to the left hemisphere language areas. The concept of localized disorders from disease in neurocognitive centers or their disconnection has continued to be useful for mental status testing, despite our current understanding that the brain is composed of widely distributed, but interconnected, neural networks, discussed in the final section of this chapter.
One further general principle is that of the “anomalous dominance pattern.” As described by Geschwind and others, this term indicates an alternative brain organization among left-handers that challenges the neat description of hemispheric specialization. Most right-handed individuals show anatomic differences between hemispheres, such as a larger left planum temporale (located on the surface of superior temporal gyrus) for Wernicke area, consistent with hemispheric specialization. In contrast, most left-handed individuals, rather than an inverse hemispheric dominance, have an “anomalous” pattern characterized by less hemispheric specialization. This manifests as decreased exclusive or predominant localization of traditional left or right hemisphere functions and a greater likelihood of bilateral representation compared with the majority of right-handers. One of the first things that mental status examiners determine is the patient’s handedness, as this is pertinent to the localization value of many lesions.
Brain-Behavior Localization (see Table 4.2)
FRONTAL LOBES
The frontal lobes are much of what defines being human. We have the largest frontal/total brain quotient of the animal kingdom, making up more than one-third of the entire cortex. Lying anterior to the central sulcus, the frontal lobes consist of motor cortex and prefrontal cortex. The motor cortex includes not only primary motor cortex but also the premotor area for initiation and planning movements, the supplementary motor area for complex movements involving sequencing and coordination, and the frontal eye fields for overseeing saccadic eye movements. The much larger, prefrontal cortex is the seat of the highest cognitive functions and the main target of this discussion. The prefrontal cortex consist of at least six major behavioral divisions divided into two major groups: the lateral “executive-cognitive” group for goal-oriented behavior, and the medial “frontolimbic” group for socioemotional behavior.
The executive-cognitive prefrontal group enables goal-orientation by allowing deliberation between stimulus and immediate response, thus permitting a weighing of options, choices, and the potential outcomes of responses. The largest executive-cognitive division, the dorsolateral prefrontal cortex, has the greatest role in the strategic planning of goals. It receives input from the mediodorsal thalamic nucleus and interconnects with parietal and temporal association areas. It facilitates goal-orienting behavior through executive operations, such as working memory and complex attention (mental control), task setting and shifting, and task maintenance. These executive operations are evident in alternate or motor programming tasks, and they influence reasoning, decision-making, and judgment abilities. The adjacent executive-cognitive division, the ventrolateral prefrontal cortex, further enables goal-oriented behavior by reconciling stimuli and responses with the stored representations of past similar experiences. This division contains the Broca area on the left, which participates in language production (fluency) and syntax (rules for combining words into clauses or phrases); the corresponding area on the right participates in intonation and prosody.
The “frontolimbic” group is engaged in integrating emotion and social behavior. Disease here can significantly impair social propriety and interactions. This region interconnects with emotionally important areas, such as the insulae, the amygdalae, and other limbic regions. Frontolimbic divisions include the ventromedial, orbitofrontal, and dorsomedial prefrontal cortices, and output occurs through the anterior cingulate cortex. The ventromedial cortex links emotional meaning to scenarios (“affective valuation”), facilitates emotion by reconstituting somatic states when exposed to certain experiences, and contributes to the experience of empathy. On the right side, the ventromedial cortex is particularly involved in valencing social scenarios and experiences, in understanding the feelings of others, in “theory of mind” (appreciating that others have thoughts, feelings, and beliefs), and, generally, as part of the social brain (dedicated social-interpersonal neural systems). The theory of mind circuit also includes the temporal pole, temporoparietal junction, posteromedial (precuneus, posterior cingulate) cortex, and posterior superior temporal sulcus; the related social brain includes the temporal pole, orbitofrontal cortex, subgenual anterior cingulate cortex, anterior insula, posterior superior temporal sulcus, and temporoparietal junction. The orbitofrontal cortex runs into the ventromedial region and contributes to learning from reward and punishment. The orbitofrontal cortex is additionally involved in controlling or inhibiting rapid, “in-the-moment” responses to stimuli. The dorsomedial prefrontal cortex, which often includes the frontal pole, considers more long-term outcomes and the potential feedback from different courses of action. It is crucial for reflecting on delayed or “what-if” scenarios and for considering the “self” or self-aware perspectives. Finally, it is worth considering the anterior cingulate cortex, a part of the limbic system, and its relationship to frontolimbic areas. The anterior cingulate is a “motor” limbic area that motivates action for choosing the best available response. The dorsal anterior cingulate cortex (more properly the anterior midcingulate cortex) is engaged in set change detection in influencing response choices, whereas the subgenual and pregenual portions are more involved in emotional assessment.
Although useful for brain-behavior localization, the functions of the different divisions of the prefrontal cortex are not entirely distinct or discrete. There is much overlap, and many clinical disturbances, such as environmental dependency (drawn to external stimuli) and abstracting ability, are products of more than one division. They are, nevertheless, a guide to localization in the prefrontal cortex.
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