CORTICOCORTICAL AND SUBCORTICOCORTICAL PROJECTION CIRCUITS
The cerebral white matter consists of myelinated axons that link cortical areas with both cortical and subcortical regions. There exist three main categories of efferent fibers from a cortical area: association fibers, striatal fibers, and commissural/subcortical fibers. Corticocortical projections allow both adjacent and distant cortical regions to communicate, whereas corticosubcortical projections allow reciprocal communication between cortical regions and subcortical structures. These subcorticocortical projections connect the cortex to the thalamus, the pontocerebellar system, brainstem, and spinal cord.
Corticocortical Circuits. Local short association fibers, or U fibers, connect adjacent cortical gyri and lie beneath the sixth cortical layer. Neighborhood association fibers traverse longer distances than U fibers, but still connect nearby cortical regions. Long association fibers travel within the same hemisphere and connect more distant cortical regions. These include the superior, middle, and inferior longitudinal fasciculi, arcuate fasciculus, extreme capsule, frontoccipital fasciculus, uncinate fasciculus, and cingulum bundle (see Plate 2-5, Major Cortical Association Bundles).
Subcorticocortical Circuits. Striatal fibers describe fiber groups that connect cortical regions to the striatum (the caudate and putamen). For instance, these fibers allow cortical motor control. The commissural bundle is a collection of fibers that travel from a cortical region to the opposite hemisphere via the corpus callosum or anterior commissure. Subcortical fibers travel via the internal capsule to diencephalic structures (e.g., thalamus) and brainstem (e.g., pons). The origins of the subcorticocortical cell bodies are laminae V and VI.
Cortical activity is modulated via excitatory and inhibitory projections in subcortical areas. For instance, diffuse cortical cholinergic projections to the cortex rise from the nucleus basalis of Meynert, and norepinephrine projections from the locus ceruleus.
In the case of Alzheimer disease, a loss of corticocortical projection neurons is associated with neurofibrillary tangle formation. This indicates a “disconnection” of adjacent cortex and cortical association areas. The disconnection of subcorticocortical circuits is evident in the reduction of cholinergic projections throughout the cortex, resulting in reduced acetylcholine levels in the cortex. This observation led to the development of the first effective therapies for Alzheimer disease, acetylcholinesterase inhibitors, which boost acetylcholine levels in the brain.