Circuitry of the frontal association cortex and its relevance to dementia

The prefrontal cortex reaches its peak size and complexity in the human brain where it occupies more than a quarter of the cerebral cortical surface. This paper reviews studies on that portion of the prefrontal cortex that is buried in and around the principal sulcus of macaque monkeys and corresponds to Brodmann's area 46 in man. Neuropsychological research as well as neurophysiology and 2-deoxyglucose metabolic mapping indicate that the principal sulcus is essential for regulation of motor behavior by internalized representations of visuo-spatial events. Conversely, the prefrontal cortex is unnecessary for behavior regulated by external stimuli, as is the case with many associative learning and recognition memory processes. Research over the past decade suggests that the principal sulcus accomplishes its regulatory functions by its interconnections with (1) the posterior parietal cortex which provides it with access to visuo-spatial data, (2) the parahippocampal gyrus and subiculum which allows information to be held 'on line' and deposited in long-term storage, and (3) motor centers such as the basal ganglia, deep layers of the superior colliculus and several premotor areas that control head, eye and hand movements. In addition, modulatory influences on prefrontal functions are exerted by (4) dopamine-, norepinephrine- and serotonin-containing fiber systems that originate in the brain stem and innervate the prefrontal cortex in a selective manner. Comparison between syndromes present in patients with a variety of diagnoses and human and nonhuman subjects with prefrontal injuries provides suggestive evidence that prefrontal dysfunction may underly the disordered thinking and abnormal social and affective responses found in many of these diseases. Accordingly, knowledge of the neural mechanisms underlying cognitive processing in nonhuman primates should be helpful in the analysis of the 'neurology' of many neurological and psychiatric illnesses.