Structural and functional dichotomy of human midcingulate cortex

Abstract

Anterior cingulate cortex is comprised of perigenual and midcingulate regions based on cytology, imaging and connections. Its anterior (aMCC) and posterior (pMCC) parts and transition to posterior area 23 were evaluated in six human cingulate gyri with Nissl staining and immunoreactions for neuron-specific nuclear binding protein and intermediate neurofilament proteins (NFP), and their pain and emotion functions evaluated in standard coordinates. Morphological differences included a poorly differentiated layer III with few NFP-expressing neurons in aMCC and a very dense layer Va with small and large pyramids intermingled in pMCC. The density of NFP-positive, layer Vb neurons was higher in pMCC than in aMCC. The junction of pMCC with area 23 had a dysgranular area 23d with clumps of layer IV neurons and a very dense layer Va. Each case was co-registered to standard coordinates and the regional borders identified and measured. Although both regions had overall equivalent activations during noxious cutaneous thermal stimulation, the posterior two-thirds of pMCC was relatively inactive. About 60% of fear-induced activity was in aMCC, sadness and happiness activated perigenual cortex, and neither were activated with non-emotion tasks. Thus, pain activity is coupled to fear in aMCC, while other MCC processing is not related to affect. Beyond midcingulate duality, this is the first report of a very dense layer Va for areas p24' and 23 and the features of transitional area 23d. The MCC dichotomy suggests that two circuits differentially regulate the two cingulate motor areas, and involvement of aMCC in pain and fear make it selectively vulnerable to chronic pain and stress syndromes.