Focal acetylcholinergic modulation of the human midcingulo‐insular network during attention: Meta‐analytic neuroimaging and behavioral evidence

Abstract

The basal forebrain cholinergic neurons provide acetylcholine to the cortex via large projections. Recent molecular imaging work in humans indicates that the cortical cholinergic innervation is not uniformly distributed, but rather may disproportionately innervate cortical areas relevant to supervisory attention. In this study, we therefore reexamined the spatial relationship between acetylcholinergic modulation and attention in the human cortex using meta‐analytic strategies targeting both pharmacological and non‐pharmacological neuroimaging studies. We found that pharmaco‐modulation of acetylcholine evoked both increased activity in the anterior cingulate and decreased activity in the opercular and insular cortex. In large independent meta‐analyses of non‐pharmacological neuroimaging research, we demonstrate that during attentional engagement these cortical areas exhibit (1) task‐related co‐activation with the basal forebrain, (2) task‐related co‐activation with one another, and (3) spatial overlap with dense cholinergic innervations originating from the basal forebrain, as estimated by multimodal positron emission tomography and magnetic resonance imaging. Finally, we provide meta‐analytic evidence that pharmaco‐modulation of acetylcholine also induces a speeding of responses to targets with no apparent tradeoff in accuracy. In sum, we demonstrate in humans that acetylcholinergic modulation of midcingulo‐insular hubs of the ventral attention/salience network via basal forebrain afferents may coordinate selection of task relevant information, thereby facilitating cognition and behavior.image

Multimodal gradients of basal forebrain connectivity across the neocortex

“…The midcingulo-insular areas are unique in that they exhibit positive temporal correlations with networks in both the exogenous and endogenous processing streams, implying a superordinate role in selecting between the two 36,[64][65][66] . We also recently provided meta-analytic evidence that task-related midcingulo-insular activations, as measured by fMRI, exhibit among the strongest patterns of pharmaco-modulation by cholinergic agonists and task-related co-activations with the BF 67 . The profile of BF cholinergic arborization and strength of its modulatory regulation on midcingulo-insular cortex provide further evidence of its privileged supervisory status.…”

Recent advances in cholinergic mechanisms: A preface for the ISCM2022 special issue

“…The authors' idea is that lipolytic activity of BChE may contribute to the release of low-level lipid mediators and may play a yet undetermined role in reducing these membrane lipids, which could lead to some sort of compensatory mechanism at high lipid concentrations (Gok et al, 2023). Furthermore, this special issue contains the first behavioral meta-analysis of ACh's pharmacological neuroimaging studies, aimed to determine whether cholinergic modulation impacts the response latency and accuracy measures of attentional performance (Chakraborty et al, 2023). The authors demonstrate that pharmacological activation of ACh alters the distributed patterns of midcingulo-insular brain activity during directed attention and may coordinate the selection of task relevant information, thereby facilitating cognition and behavior.…”

Abstract Book 6: OHBM 2024 Annual Meeting

“…However, the direct link between ACh signaling and attention has proven challenging to study experimentally in humans. Here, we used meta-analytic strategies targeting both pharmacological and non-pharmacological neuroimaging studies to examine the relationship between ACh and attention in humans (Chakraborty, Lee, et al 2023).…”