Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Abstract

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

Whole-brain modeling explains the context-dependent effects of cholinergic neuromodulation

“…To assess this possibility, we tested if the regional density of cholinergic-related receptors could explain the effects of nicotine on FC. We used regional receptor density maps, obtained with PET, of the α 4 β 2 nicotinic receptor, the M 1 muscarinic receptor, and the vesicular acetylcholine transporter (VAChT) [36, 37, 38, 39, 40, 41]. We calculated the difference in the empirical FC nodal strength between nicotine and placebo conditions (both in RS and task blocks) and correlated this vector with the density maps.…”

“…Average volumetric PET images were collected for three different cholinergic receptors and transporters across 5 studies with open-dataset [40], which include nicotinic α 4 β 2 [36], muscarinic M 1 [41], and the vesicular acetylcholine transporter (VAChT) [37, 39, 40].…”

“…We informed the model with acetylcholine-related receptors maps obtained by PET [36, 37, 38, 39, 40, 41]. Specifically, we used the nicotinic α 4 β 2 receptor density map into Schaefer 100 parcellation.…”

“…We found that segregation is a signature of in-task performance, showing a link between functional network topology and behavior. Finally, under the hypothesis that nicotine decreases global correlations, we verified if the regional density of cholinergic-related receptors obtained by positron emission tomography (PET) [36, 37, 38, 39, 40, 41] correlates with regional changes in FC. We observed that changes in nodal strength FC, during the task, correlate with the regional density of the α 4 β 2 nicotinic acetylcholine receptor.…”

Low-dimensional organization of global brain states of reduced consciousness

“…Where z is a complex-valued variable (z = x + iy), ω is the intrinsic frequency of the oscillator. The bifurcation parameter a changes qualitatively the nature of the solutions of the system: if a>0 the system engages in a limit cycle and thus presents self-sustained oscillations (oscillating or supercritical regime), and when a<0 the dynamics decay to a stable fixed point (noisy or subcritical regime) 46 .…”