The Human Brain:
The Structural Basis for Understanding Human Brain Function and Dysfunction


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Brent A. Vogt
SUNY Upstate Medical University, Syracuse, USA

2002-10-09, 11:30-12:15
Four Regions of Cingulate Cortex and Disease Vulnerability.

The cingulate gyrus forms a cingulum around the corpus callosum. Although cytoarchitectural studies identified many cingulate areas, limbic theories suggested it was one entity. Papez included the entire cingulate gyrus as a substrate for emotion and MacLean's visceral brain/thalamocingulate division viewed cingulate cortex a single entity. Although functional imaging refers to anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), it struggles with the notion that ACC is uniform. We present a four-region model of the cingulate gyrus and a modified Brodmann map. The key division between ACC area 24 and PCC area 23 is layer IV in the latter. Area 32 is dorsal ACC and area 31 is dorsal PCC. Histological analysis showed that areas 32, 24, and 23 are not uniform in their rostrocaudal or dorsoventral dimensions. Areas 24a/23a are relatively undifferentiated, areas 24b/23b have a prominent layer Va and inner layer III, and areas 24/23c in the cingulate sulcus with thick layers II-III. Area 32 differentiates adjacent to frontal areas as noted for areas 32 and 32˘. The former has a thin and continuous layer IV, while the latter has a variable thickness layer IV that forms islands. Braak identified a magnocellular region in perigenual cortex that was not the same as Brodmann's area 24 caudally and a primitive gigantopyramidal field in the cingulate sulcus that has spinal projections and contains the caudal cingulate motor area; 24d.

Anterior and posterior ACC differ cytologically and are termed perigenual ACC (pACC) and midcingulate cortex (MCC), respectively: 1. pACC receives massive amygdala input, while MCC receives significant posterior parietal afferents. 2. pACC regulates autonomic functions via the solitary nucleus and dorsal motor nucleus of the vagus, while sulcal MCC has two cingulate motor areas with spinal projections. 3. Internally generated emotions activate pACC, while MCC is engaged in motor and non-motor response selection including anticipation of movement or cognitive processing, working memory, motor imagery, mismatch detection, motor selection, and establishing changes in processing for new motor programs.

Opiate and serotonergic drugs influence affect and are active in pACC. Binding of the opiate diprenorphine distinguishes the 4 cingulate regions with highest binding in pACC and lowest in retrosplenial cortex (RSC). Opiate agonists reduce affective responses to noxious stimuli via high binding in pACC and the opiate placebo effect localizes to pACC. The pACC and MCC are differentially vulnerable to psychiatric diseases. The pACC has glucose hypometabolism in major depression, while obsessive-compulsive disorder tends to engage MCC. Although symptom provocation elevates blood flow in pACC, lesions in MCC relieve OCD symptoms. Midcingulotomies also relieve pain, acute noxious stimuli activate MCC in control and neuropathic pain patients, and irritable bowel syndrome can be associated with elevated visceral pain in this region that disappears upon symptom resolution as it does following lidocaine block of neuropathic pain. Since citalopram binding to the serotonin transporter is particularly high in pACC, this may explain the effectiveness of antidepressants in alleviating mood and pain disorders.

The posterior cingulate gyrus (PCG) includes gyral areas 23 and 31 and RSC. Small strokes and experimental animals show PCG is involved in visuospatial function and Minoshima reported an early feature of Alzheimer disease (AD) is reduced glucose metabolism in PCG. The highest level of brain basal glucose metabolism is in RSC and it colocalizes to the granular layer that receives most anterior thalamic input. Since the anterior thalamus is also metabolically active and releases glutamate, it is vulnerable to diseases associated with glutamate excitotoxicity such as AD.