This pattern is consistent with the dense innervations (stronger than cortex) observed for both the hippocampus and amygdala, two regions with simplified cytoarchitecture (ie, pattern of laminar structure). Given its overall connectivity pattern, the magnocellular basal forebrain system is in a favorable position to influence cortical sites across the brain, including sensory cortex, and thus to influence the flow of information processing. These distributed effects result in increased vigilance, alertness, and attention, Inhibitors,research,lifescience,medical and more generally have the potential for widespread impact on cognitive function

both in health and mental illness.6,7 As with other neurotransmitter systems in the brain, the effects of the magnocellular system are at times described as relatively global, or at least unspecific. However, specific effects have also been documented.

Inhibitors,research,lifescience,medical For instance, visual responses that are conveyed to prefrontal cortex engage the basal forebrain in a polysynaptic way, which then further enhances visual responding.8 Direct stimulation of the basal forebrain also enhances the cortical coding of natural scenes in visual cortex Inhibitors,research,lifescience,medical by markedly improving the reliability of cell responses.9 Whereas the magnocellular system projects in a widespread, distributed fashion to cortical and subcortical regions, it is noteworthy that afferent fibers originate from a much more circumscribed set of regions. Cortically, inputs originate largely from nonisocortical areas.5,10

Given that these are exactly the regions that receive the densest inputs from the basal forebrain, potent basal forebrain-cortical Inhibitors,research,lifescience,medical circuits can be established. Amygdala A remarkable property of the primate amygdala is its massive interconnection with cortex. Based on the available data at Inhibitors,research,lifescience,medical the time, analysis of amygdala connectivity revealed that this structure was connected to all but eight of the cortical areas included in the study11 (see also refs 12,13). These connections involved multiple region clusters, suggesting that the amygdala14 is not only one of the most highly connected regions of the brain, but that its connectivity topology is consistent with that of a “connector” hub15 (where a hub is a region with a high degree of connectivity) PD184352 (CI-1040) that links multiple “provincial” hubs15 – where the latter refers to regions of dense connectivity more closely associated with a specific Cell Cycle inhibitor functional group, such as area V4 in visual cortex.16 In this manner, the amygdala has strong potential for integrating cognitive and emotional information.17 When whole-brain connectivity data are analyzed, prefrontal areas are among those most distant from the sensory periphery – based on the average number of connections.11 Thus, on average, the prefrontal cortex receives highly processed and integrated sensory information.