The central theme of the "segregated circuits" hypothesis is that structural convergence and functional integration occurs within, rather than between, each of the identified circuits Admittedly, the anatomical evidence upon which this scheme is based remains incomplete The hypothesis continues to be predicated largely on comparisons of anterograde and retrograde labeling studies carried out in different sets of animals Only in the case of the "motor" circuit has evidence for the continuity of the loop been demonstrated directly in individual subjects; for the other circuits, such continuity is inferred from comparisons of data on different components of each circuit obtained in separate experiments Because of the marked compression of pathways leading from cortex through basal ganglia to thalamus, comparisons of projection topography across experimental subjects may be hazardous Definitive tests of the hypothesis of maintained segregation await additional double- and multiple-label tract-tracing experiments wherein the continuity of one circuit, or the segregation of adjacent circuits, can be examined directly in individual subjects It is worthy of note, however, that the few studies to date that have employed this methodology have generated results consistent with the segregated circuits hypothesis Moreover, single cell recordings in behaving animals have shown striking preservation of functional specificity at the level of individual neurons throughout the "motor" and "oculomotor" circuits It is difficult to imagine how such functional specificity could be maintained in the absence of strict topographic specificity within the sequential projections that comprise these two circuits This is not to say, however, that we expect the internal structure of functional channels (eg, the "arm" channel within the "motor" circuit) to have cable-like, point-to-point topography When the grain of analysis is sufficiently fine, anatomical studies have shown repeatedly that the terminal fields of internuclear projections (eg, to striatum, pallidum, nigra, thalamus, etc) often appear patchy and highly divergent, suggesting that neighboring groups of projection cells tend to influence interdigitating clusters of postsynaptic neurons While more intricate and complex than simple point-to-point topography, however, this type arrangement should also be capable of maintaining functional specificity As discussed briefly above, it is not yet clear to what extent the inputs to the "motor" circuit from the different precentral motor fields (eg, MC, SMA, APA) are integrated in their passage through the circuit It now appears that at the level of the putamen such inputs remain segregated(ABSTRACT TRUNCATED AT 400 WORDS)

Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions.

The Prefrontal Cortex, Fifth Edition, provides users with a thoroughly updated version of this comprehensive work that has historically served as the classic reference on this part of the brain. The book offers a unifying, interdisciplinary perspective that is lacking in other volumes written about the frontal lobes, and is, once again, written by the award-winning author who discovered "memory cells," the physiological substrate of working memory. The fifth edition constitutes a comprehensive update, including all the major advances made on the physiology and cognitive neuroscience of the region since publication in 2008. All chapters have been fully revised, and the overview of prefrontal functions now interprets experimental data within the theoretical framework of the new paradigm of cortical structure and dynamics (the Cognit Paradigm), addressing the accompanying social, economic, and cultural implications. * Provides a distinctly interdisciplinary view of the prefrontal cortex, covering all major methodologies, from comparative anatomy to modern imaging* Unique analysis and synthesis of a large body of basic and clinical data on the subject (more than 2000 references)* Written by an award-winning author who discovered "memory cells," the physiological substrate of working memory* Synthesizes evidence that the prefrontal cortex constitutes a complex pre-adaptive system* Incorporates emerging study of the role of the frontal lobes in social, economic, and cultural adaptation

The prefrontal cortex

Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia

The functional neuroanatomy of unipolar major depression was investigated using positron emission tomography to measure differences in regional cerebral blood flow (BF). A relatively homogeneous subject group was obtained using criteria for familial pure depressive disease (FPDD), which are based upon family history as well as upon symptoms and course. Because of the absence of certain knowledge about the pathophysiology of mood disorders and their underlying functional neuroanatomy, we used data obtained from the subtraction of composite images from one-half of depressed and control subjects to identify candidate regions of interest. The major cortical region defined in this manner was statistically tested on a second set of subjects. Using this strategy, we found increased BF in an area that extended from the left ventrolateral prefrontal cortex onto the medial prefrontal cortical surface. Based upon the connectivity between these portions of the prefrontal cortex and the amygdala and evidence that the amygdala is involved in emotional modulation, activity was measured in the left amygdala and found to be significantly increased in the depressed group. A separate group of subjects with FPDD who were currently asymptomatic were also imaged to determine whether these findings represented abnormalities associated with the depressed state, or with a trait difference that might underlie the tendency to become depressed. Only the depressed group had increased activity in the left prefrontal cortex, suggesting that this abnormality represents a state marker of FPDD. Both the depressed and the remitted groups demonstrated increased activity in the left amygdala, though this difference achieved significance only in the depressed group. This suggests that the abnormality involving the left amygdala may represent a trait marker of FPDD, though further assessment in a larger sample size is necessary to establish this. These data along with other evidence suggest that a circuit involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus is involved in the functional neuroanatomy of depression.

https://www.jneurosci.org/content/jneuro/12/9/3628.full.pdf

R Hasller

Papers

Effect of frontal cortex ablation on striatal glutamic acid level in rat.