Highlights
- •Using simulated lesions, vulnerability of the connectome to localised damage was assessed.
- •Cholinergic forebrain integrity correlates with global network efficiency in MCI.
- •Preserved cholinergic nuclei contribute to reduced global impact of limbic lesions.
- •Cholinergic nuclei influence the efficiency and vulnerability of the connectome.
Abstract
Neurodegeneration leads to redistribution of processing, which is reflected in a reorganisation
of the structural connectome. This might affect its vulnerability to structural damage.
Cortical acetylcholine allows favourable adaptation to pathology within the memory
circuit. However, it remains unclear if it acts on a broader scale, affecting reconfiguration
of whole-brain networks. To investigate the role of the cholinergic basal forebrain
(CBFB) in strategic lesions, twenty patients with mild cognitive impairment (MCI)
and twenty elderly controls underwent magnetic resonance imaging. Whole-brain tractograms
were represented as network graphs. Lesions of individual nodes were simulated by
removing a node and its connections from the graph. The impact of simulated lesions
was quantified as the proportional change in global efficiency. Relationships between
subregional CBFB volumes, global efficiency of intact connectomes and impacts of individual
simulated lesions of network nodes were assessed. In MCI but not controls, larger
CBFB volumes were associated with efficient network topology and reduced impact of
hippocampal, thalamic and entorhinal lesions, indicating a protective effect against
the global impact of simulated strategic lesions. This suggests that the cholinergic
system shapes the configuration of the connectome, thereby reducing the impact of
localised damage in MCI.
Keywords
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Article info
Publication history
Published online: April 08, 2021
Accepted:
April 5,
2021
Received in revised form:
February 24,
2021
Received:
September 29,
2020
Identification
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© 2021 Elsevier B.V. All rights reserved.
