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The cerebral cortex contains ∼20% of the approximately 100 billion neurons in the central nervous system,1 arranged in multiple distinct areas characterized extensively with respect to their morphological and cellular specialization. The architecture of each of these cortical areas subserves functionally distinct domains of sensorimotor perception and action, complex reasoning, and emotional experience.

It is estimated that approximately 70% of the neurons in the central nervous system are located within the cerebellum, most of which are in the cerebellar granule cell layer. This underappreciated fact is consistent with the recognition that the cerebral cortex does not support nervous system function in isolation, and that all behaviors are subserved by distributed neural systems that comprise anatomic regions, or nodes, each displaying unique architectural properties, distributed geographically throughout cortical and subcortical areas, and linked anatomically and functionally in a precise and unique manner.2–16 Neuropsychiatric/neurobehavioral syndromes following lesions of cerebral white matter and subcortical regions, and demonstration of abnormalities in subcortical as well as cortical areas in imaging studies of psychiatric disorders provide clinical correlates of these distributed neural circuits.

Understanding the neuroanatomy of cognition is essential to the evaluation and care of patients with neurobehavioral and neuropsychiatric disorders. Anatomical textbooks, focused monographs, review papers, and the primary literature, many of which are included here in the reference section and which informed this work, contain extensive information regarding each of the nervous system structures and their functions described here. This chapter aims to provide both an overview of, and detailed information regarding, the neural substrates of behavior, synthesized in a manner that combines principles of organization, descriptions of evolutionary and hierarchical development, and elaboration of structural organization and complexity, guided by their relevance to the clinical neuroscience of behavioral neurology and neuropsychiatry. It presents an overview of cerebral cortical organization, the essentials of the limbic circuitry subserving emotion, the anatomical organization of the white matter tracts linking different cerebral cortical areas with each other, the connections between the cerebral cortex and subcortical areas, a consideration of the anatomical features of basal ganglia, thalamus, and cerebellum, and the clinical manifestations of lesions in each of these major brain areas. Building on Norman Geschwind’s (1926–1984) conceptualization of disconnection syndromes following lesions of cerebral cortical association areas and white matter structures4,5 we view the behavioral neurology/neuropsychiatry of lesions of focal subcortical areas also as disconnection syndromes: disruptions of the subcortical nodes of the circuits that subserve neurologic function.

Caution is necessary when extrapolating from rodent, cat, and monkey studies to the human because of the comparative evolutionary complexity of the human brain. Nevertheless, the organizing principles derived from physiological, tract tracing, and behavioral studies in animal models have largely been validated in healthy humans using contemporary imaging techniques, and in patients in whom behavioral deficits have been correlated with the anatomical locations of the lesions and the networks they disrupt.


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