Frontal–subcortical neuronal circuits and clinical neuropsychiatry: An update

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Abstract

Frontal–subcortical circuits form the principal network, which mediate motor activity and behavior in humans. Five parallel frontal–subcortical circuits link the specific areas of the frontal cortex to the striatum, basal ganglia and thalamus. These frontal–subcortical circuits originate from the supplementary motor area, frontal eye field, dorsolateral prefrontal region, lateral orbitofrontal region and anterior cingulate portion of the frontal cortex. The open afferent and efferent connections to the frontal–subcortical circuits mediate coordination between functionally similar areas of the brain. Specific chemoarchitecture and multiple neurotransmitter interactions modulate the functional activity of each circuit. Dorsolateral prefrontal circuit lesions cause executive dysfunction, orbitofrontal circuit lesions lead to personality changes characterized by disinhibition and anterior cingulate circuit lesions present with apathy. The neurobiological correlates of neuropsychiatric disorders including depression, obsessive–compulsive disorder, schizophrenia and substance abuse, imply involvement of frontal–subcortical circuits.

Section snippets

Frontal–subcortical circuits and neuropsychiatric disorders

The frontal lobes have an important role in human behavior. Dysfunction of orbitofrontal, medial and dorsolateral prefrontal is associated with a variety of neuropsychiatric syndromes. However, similar neuropsychiatric symptoms may arise with lesions in subcortical brain structures. The pathophysiological basis for this shared phenomenology remained unexplained until anatomic investigations provided a framework for the cognitive architecture of the brain. A series of parallel

Anatomy of frontal–subcortical circuits

The five frontal subcortical circuits share some common features [1]. The main anatomical structures are the same for all circuits. They originate in prefrontal cortex, project to the striatum (caudate, putamen, ventral striatum), connect to the globus pallidus and substantia nigra and from there connect to the thalamus. There is a final link back to the frontal cortex each circuit forms a closed loop. There are as well projections to and from other cortical and subcortical structures related

Open connections of frontal–subcortical circuits

In addition to these closed frontal–subcortical loops, there are open connections of the circuits that integrate information from anatomically distant but functionally related brain areas. The open afferent and efferent connections mediate coordination between functionally similar areas of the brain and the frontal–subcortical circuits. The major open afferent and efferent connections of the three frontal–subcortical circuits are listed in Table 1.

Major cortical afferents to the dordolateral

Neurochemical structure

The fibers in each circuit, originating from the frontal lobe are mediated by excitatory glutaminergic neurotransmission. They project to striatum, which is formed of caudate, putamen and ventral striatum. The connections from striatum to globus pallidus interna–substantia nigra complex as the direct pathway, and to globus pallidus externa as the indirect pathway, are both inhibitory and are mediated by γ-aminobutyric acid (GABA). In the indirect pathway, globus pallidus externa projects

Modulatory neurotransmitters

In the frontal–subcortical circuits, the corticostriatal information processing is modulated by different neurotransmitter systems.

Dopaminergic neurons from the substantia nigra project to the striatum and effect all frontal–subcortical functions. The inhibitory and excitatory effects of DA are dependent on the type of receptors with which it interacts postsynaptically. Five different (D1–D5) DA receptors are defined. The substantia nigra has inhibitory connections with the indirect pathways of

Frontal–subcortical circuit syndromes

Frontal–subcortical circuit syndromes may be observed due to different etiologies. Some of the diseases that may lead to frontal–subcortical circuit dysfunction are summarized in Table 2.

Neuropsychiatric disorders and frontal–subcortical circuits

A variety of neuropsychiatric disorders have associations with frontal–subcortical circuit dysfunction [20].

Obsessive–compulsive disorder (OCD) is characterized by intrusive and unwanted ideas, thoughts, urges and images known as obsessions together with repetitive ritualistic cognitive and physical activities comprising compulsions. The clinicopathological, functional and structural imaging studies support the involvement of frontal–subcortical circuit structures in the pathogenesis of OCD.

Summary

There are five frontal–subcortical circuits providing the neuroanatomical basis for movement and behavior. Each of the circuits shares the same member structures including the frontal cortex, striatum, globus pallidus/substantia nigra and thalamus. Neurotransmitters like DA, acetylcholine, glutamate and serotonin mediate and modulate the neurotransmission through the circuits. Frontal–subcortical circuits are named according to their cortical site of origin. The dorsolateral circuit conveys

Acknowledgements

Support for this work was provided by an NIA Alzheimer's Disease Research Center grant (P50AG16570), an Alzheimer's Disease Research Center of California grant, the Sidell-Kagan Foundation and Turkish Education Foundation.

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