Functional Subdivisions of Magnocellular Cell Groups in Human Basal Forebrain: Test–Retest Resting-State Study at Ultra-high Field, and Meta-analysis

Abstract

The heterogeneous neuronal subgroups of the basal forebrain corticopetal system (BFcs) have been shown to modulate cortical functions through their cholinergic, gamma-aminobutyric acid-ergic, and glutamatergic projections to the entire cortex. Although previous studies suggested that the basalo-cortical projection system influences various cognitive functions, particularly via its cholinergic component, these studies only focused on certain parts of the BFcs or nearby structures, leaving aside a more systematic picture of the functional connectivity of BFcs subcompartments. Moreover, these studies lacked the high-spatial resolution and the probability maps needed to identify specific subcompartments. Recent advances in the ultra-high field 7T functional magnetic resonance imaging (fMRI) provided potentially unprecedented spatial resolution of functional MRI images to study the subdivision of the BFcs. In this study, the BF space containing corticopetal cells was divided into 3 functionally distinct subdivisions based on functional connection to cortical regions derived from fMRI. The overall functional connection of each BFcs subdivision was examined with a test-retest study. Finally, a meta-analysis was used to study the related functional topics of each BF subdivision. Our results demonstrate distinct functional connectivity patterns of these subdivisions along the rostrocaudal axis of the BF. All three compartments have shown consistent segregation and overlap at specific target regions including the hippocampus, insula, thalamus, and the cingulate gyrus, suggesting functional integration and separation in BFcs.

Phasic cholinergic signaling promotes emergence of local gamma rhythms in excitatory–inhibitory networks

“…Cholinergic neurons situated in the basal forebrain (BF) project to virtually all cortical layers and regions. In contrast to traditional descriptions of this projection system as “diffusely organized” and involved in the relatively slow regulation of cortical activity states, contemporary evidence indicates the presence of BF subpopulations of neurons with highly topographically organized afferent and efferent projections (Gielow & Zaborszky, 2017; Yuan, Biswal, & Zaborszky, 2018; Zaborszky, Buhl, Pobalashingham, Bjaalie, & Nadasdy, 2005; Zaborszky et al., 2015) and, in cortex, of spatially and temporally discrete, fast, phasic or “transient” cholinergic signaling (Parikh, Kozak, Martinez, & Sarter, 2007). Because cortical cholinergic activity is necessary for attentional performance in rodents and humans (Kim, Muller, Bohnen, Sarter, & Lustig, 2019; McGaughy, Kaiser, & Sarter, 1996), the role of cholinergic transients has been investigated specifically in the context of attentional performance.…”

Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors

“…Each functional group is linked to a subdomain of the basal forebrain and has specific target regions, including within the hippocampus, insula, thalamus, and cingulate gyrus. However there are also regions of functional overlap, such as the salience network which is associated with all three cBF functional clusters [56]. Thus there is mounting evidence that the wiring of cBF neurons, although extensive, is guided by unknown underlying mechanisms which may turn out to be a key component of functional modulation of cognitive processes by these neurons.…”

Rescuing the attentional performance of rats with cholinergic losses by the M1 positive allosteric modulator TAK-071

“…The basal forebrain cholinergic system broadly innervates telencephalic regions, including the cortex. Contemporary research has revealed the presence of highly topographic, afferent and efferent projections of basal forebrain neurons, dissociable clusters of basal forebrain cholinergic neurons, target region-specific integration of cholinergic synapses, and the presence of fast cholinergic signaling (scale of seconds) in performing rodents (e.g., Zaborszky, 2002;Parikh et al, 2007;Zaborszky et al, 2008;Howe et al, 2013;Sarter and Kim, 2015;Gritton et al, 2016;Gielow and Zaborszky, 2017;Howe et al, 2017;Yuan et al, 2018;Lean et al, 2019). Together, this evidence suggests that traditional views of this neuronal system as a "diffusely" organized ascending "arousal" system, that relatively slowly (on the scale of minutes) modulates target circuitry, require major revision (see also Hasselmo and Sarter, 2011;Dayan, 2012;Higley and Picciotto, 2014;Ballinger et al, 2016).…”