Multimodal gradients of basal forebrain connectivity across the neocortex

Area of Science:

• Neuroscience
• Neuroanatomy

Background:

• Cortical cholinergic projections originate from the basal forebrain (BF).
• Understanding the organization of BF projections is crucial for deciphering cognitive functions.
• Previous studies have hinted at BF subregion specialization but lacked detailed mapping.

Purpose of the Study:

• To investigate the organizational principles of human basal forebrain (BF) cholinergic projections.
• To map gradients of structural and functional connectivity within the BF and its cortical targets.
• To correlate BF connectivity with molecular markers and axonal arborization patterns.

Main Methods:

• Combined 7T diffusion MRI and resting-state functional MRI to compute multimodal BF connectivity gradients.
• Utilized [18F]fluoroethoxy-benzovesamicol (FEOBV) PET imaging to measure vesicular acetylcholine transporter (VAChT) concentration.
• Employed viral tracing in mice to study BF cholinergic projections and axonal arborization.

Main Results:

• Observed a gradient of decreasing structural-functional connectivity tethering from anteromedial to posterolateral BF, lowest in the nucleus basalis of Meynert.
• This BF gradient corresponds to a similar gradient in the neocortex, from unimodal to transmodal areas, notably the midcingulo-insular network.
• Cortical VAChT concentration, measured by FEOBV PET, spatially correlated with this connectivity gradient.
• Mouse models confirmed a gradient of BF cholinergic axonal arborization.

Conclusions:

• The basal forebrain exhibits a topographical organization of its cholinergic projections.
• Cholinergic neuron subpopulations differ in axonal complexity, influencing their functional integration with cortical targets.
• Findings provide insights into the neuroanatomical basis of cholinergic neuromodulation in the human brain.