Basal forebrain structural covariance resembles nicotinic and muscarinic cholinergic topographies

Poster No:

1768 

Submission Type:

Abstract Submission 

Authors:

Alexander Weuthen1, Meng Li1, Bianca Besteher1, Martin Walter1

Institutions:

1Jena University Hospital/Friedrich-Schiller-University Jena, Jena, Germany

First Author:

Alexander Weuthen  
Jena University Hospital/Friedrich-Schiller-University Jena
Jena, Germany

Co-Author(s):

Meng Li  
Jena University Hospital/Friedrich-Schiller-University Jena
Jena, Germany
Bianca Besteher  
Jena University Hospital/Friedrich-Schiller-University Jena
Jena, Germany
Martin Walter  
Jena University Hospital/Friedrich-Schiller-University Jena
Jena, Germany

Introduction:

The basal forebrain contains cholinergic projections which are crucial for attention, memory and neuroplasticity. It is not well understood how brain-wide gray matter density is influenced by nicotinic and muscarinic cholinergic synapses.

Methods:

The current study used T1-weighted magnetic resonance imaging data from three cohorts containing healthy participants and neuropsychiatric patients, i.e., Information eXtraction from Images (n = 587), Post-Covid-Brain (n = 118), Transdiagnostic Connectome Project (n = 245) datasets. Data were preprocessed using the computational anatomy toolbox (CAT12.9), deriving 1.5 mm3 segmented gray matter density maps. Cytoarchitectonic masks for the basal nucleus auf Meynert and medial septum/diagonal band of Broca were thresholded at 50% probability and used to extract basal forebrain gray matter density. Structural covariance between the basal forebrain seed and brain-wide gray matter density patterns was analysed in a general linear model, while controlling for age, sex and total intracranial volume. Based on publicly available density maps, similarity to nicotinic (α4β2) and muscarinic (M1) receptors, as well as vesicular acetylcholine transporter (VAChT) binding was assessed.

Results:

Basal forebrain structural covariance was strongest in regions among the basal ganglia, hippocampus, amygdala and thalamus. More than 10% of variance in brain-wide gray matter density patterns was explained by VAChT binding. The associations of basal forebrain gray matter density represented key regions of cholinergic binding such as muscarinic receptor density in the basal ganglia and nicotinic receptor density in the thalamus. Resulting topographical associations were replicated across the three independent cohorts.

Conclusions:

The results validate basal forebrain structural covariance as marker for cortical cholinergic projections, resembling a combination of muscarinic and nicotinic synapses. Future studies may reveal a cholinergic involvement in neuropsychiatric symptoms based on cohort effects or longitudinal changes in basal forebrain gray matter density associations.

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural)
PET Modeling and Analysis 2

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Transmitter Receptors
Transmitter Systems 1

Physiology, Metabolism and Neurotransmission:

Pharmacology and Neurotransmission

Keywords:

Acetylcholine
Morphometrics
Neurotransmitter
Positron Emission Tomography (PET)
Other - Gray Matter Density

1|2Indicates the priority used for review

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PET
Structural MRI

For human MRI, what field strength scanner do you use?

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