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Multimodal Connectivity of the Human...

Chakraborty, Sudesna.

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Multimodal Connectivity of the Human Basal Forebrain.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Multimodal Connectivity of the Human Basal Forebrain./
Author:	Chakraborty, Sudesna.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
Description:	140 p.
Notes:	Source: Dissertations Abstracts International, Volume: 85-06, Section: B.
Contained By:	Dissertations Abstracts International85-06B.
Subject:	Neurodegeneration. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30737607
ISBN:	9798381025033

Multimodal Connectivity of the Human Basal Forebrain.
Chakraborty, Sudesna.

Multimodal Connectivity of the Human Basal Forebrain. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 140 p.

Source: Dissertations Abstracts International, Volume: 85-06, Section: B.

Thesis (Ph.D.)--The University of Western Ontario (Canada), 2023.

The cholinergic innervation of the cortex originates almost entirely from populations of neurons in the basal forebrain (BF). This cholinergic signaling plays a crucial role in cognitive processing and failure of the circuitry causes cognitive impairment. Structurally, the ascending BF cholinergic projections are highly branched, with individual cells targeting multiple different cortical regions. However, much of our knowledge about cholinergic projection is based on non-human animal studies, and it is unclear how the BF cholinergic neurons are organized in the human brain and how it is related to their functional and structural integration with the cortex.We used high-resolution 7 Tesla diffusion and resting state functional MRI in humans to examine multimodal forebrain cholinergic connectivity with the neocortex. First, discrete parcellation analysis was employed to examine if structural and functional data-driven approach can recapitulate the known nuclear subdivisions based on previous studies. Similar to the topography observed in mice, both structural and functional parcellation broadly differentiated the anteromedial from posterolateral nuclei of BF. Next, we used gradient estimation to capture a more fine-grained connectivity profile of the BF-cortical projectome. Similar topographical organization of BF cholinergic projection was observed, however, moving from anteromedial to posterolateral BF, structural and functional gradients became progressively detethered, with the most pronounced dissimilarity localized in the nucleus basalis of Meynert (NbM).Structure-function tethering was shaped in part by the distance of cortical parcels from the BF and their myelin content. Functional but not structural connectivity with the BF grew stronger at shorter geodesic distances, with weakly myelinated transmodal cortical areas most strongly expressing this divergence. Additionally, an in vivo cell type-specific marker of the presynaptic cholinergic nerve terminals, [ 18F] FEOBV PET imaging was used to demonstrate that these transmodal cortical areas are also among the most densely innervated by its cholinergic projections. Altogether, multimodal gradients of BF connectivity revealed inhomogeneity in structure-function tethering which becomes most pronounced in the transition from anteromedial to posterolateral BF. Cortical cholinergic projections emanating from the NbM in particular exhibiting a broad repertoire of connections with key transmodal cortical areas associated with the ventral attention network.Finally, the intrinsic BF cholinergic connectivity map of cortex created from these results was compared with meta-analytic connectivity map of cholinergic modulation on attention. The results demonstrate that patterns of brain activity evoked by directed attention are altered by pharmacological activation of acetylcholine (ACh) compared to placebo and these patterns spatially overlap with the intrinsic BF cholinergic connectivity map. This study is the first to examine human BF connectivity using both structural and functional MRI in combination with molecular imaging. Our findings imply that the BF provides cholinergic innervation to the cortex in a topography characterized by branch complexity. The most highly branched cholinergic neurons may originate from the nucleus basalis of Meynert and innervate hubs of the ventral attention network-consistent with the role of these areas in orienting attentional resources throughout the brain.

ISBN: 9798381025033Subjects--Topical Terms:

3685376
Neurodegeneration.

Multimodal Connectivity of the Human Basal Forebrain.
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520 $a The cholinergic innervation of the cortex originates almost entirely from populations of neurons in the basal forebrain (BF). This cholinergic signaling plays a crucial role in cognitive processing and failure of the circuitry causes cognitive impairment. Structurally, the ascending BF cholinergic projections are highly branched, with individual cells targeting multiple different cortical regions. However, much of our knowledge about cholinergic projection is based on non-human animal studies, and it is unclear how the BF cholinergic neurons are organized in the human brain and how it is related to their functional and structural integration with the cortex.We used high-resolution 7 Tesla diffusion and resting state functional MRI in humans to examine multimodal forebrain cholinergic connectivity with the neocortex. First, discrete parcellation analysis was employed to examine if structural and functional data-driven approach can recapitulate the known nuclear subdivisions based on previous studies. Similar to the topography observed in mice, both structural and functional parcellation broadly differentiated the anteromedial from posterolateral nuclei of BF. Next, we used gradient estimation to capture a more fine-grained connectivity profile of the BF-cortical projectome. Similar topographical organization of BF cholinergic projection was observed, however, moving from anteromedial to posterolateral BF, structural and functional gradients became progressively detethered, with the most pronounced dissimilarity localized in the nucleus basalis of Meynert (NbM).Structure-function tethering was shaped in part by the distance of cortical parcels from the BF and their myelin content. Functional but not structural connectivity with the BF grew stronger at shorter geodesic distances, with weakly myelinated transmodal cortical areas most strongly expressing this divergence. Additionally, an in vivo cell type-specific marker of the presynaptic cholinergic nerve terminals, [ 18F] FEOBV PET imaging was used to demonstrate that these transmodal cortical areas are also among the most densely innervated by its cholinergic projections. Altogether, multimodal gradients of BF connectivity revealed inhomogeneity in structure-function tethering which becomes most pronounced in the transition from anteromedial to posterolateral BF. Cortical cholinergic projections emanating from the NbM in particular exhibiting a broad repertoire of connections with key transmodal cortical areas associated with the ventral attention network.Finally, the intrinsic BF cholinergic connectivity map of cortex created from these results was compared with meta-analytic connectivity map of cholinergic modulation on attention. The results demonstrate that patterns of brain activity evoked by directed attention are altered by pharmacological activation of acetylcholine (ACh) compared to placebo and these patterns spatially overlap with the intrinsic BF cholinergic connectivity map. This study is the first to examine human BF connectivity using both structural and functional MRI in combination with molecular imaging. Our findings imply that the BF provides cholinergic innervation to the cortex in a topography characterized by branch complexity. The most highly branched cholinergic neurons may originate from the nucleus basalis of Meynert and innervate hubs of the ventral attention network-consistent with the role of these areas in orienting attentional resources throughout the brain.
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