All sectors of the human cerebral cortex receive dense cholinergic input. The origin of this projection is located in the Ch4 cell group of the nucleus basalis of Meynert. However, very little is known about the location of the pathways which link the cholinergic neurons of the nucleus basalis to the human cerebral cortex. This question was addressed in whole-hemisphere sections processed for the visualization of multiple cholinergic markers. Two highly organized and discrete bundles of cholinergic fibres extended from the nucleus basalis to the cerebral cortex and amygdala and were designated as the medial and lateral cholinergic pathways. These bundles contained acetylcholinesterase, choline acetyltransferase and nerve growth factor receptors, confirming their cholinergic nature and origin within the basal forebrain. The medial pathway joined the white matter of the gyrus rectus, curved around the rostrum of the corpus callosum to enter the cingulum and merged with fibres of the lateral pathway within the occipital lobe. It supplied the parolfactory, cingulate, pericingulate and retrosplenial cortices. The lateral pathway was subdivided into a capsular division travelling in the white matter of the external capsule and uncinate fasciculus and a perisylvian division travelling within the claustrum. Branches of the perisylvian division supplied the frontoparietal operculum, insula and superior temporal gyrus. Branches of the capsular division innervated the remaining parts of the frontal, parietal and temporal neocortex. Representation of these cholinergic pathways within a 3D MRI volume helped to identify white matter lesion sites that could interfere with the corticopetal flow of cholinergic pathways.
