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.

Serotonin (5-HT) is well known to affect the motivational properties of stimuli predictive of rewards as well as the inhibitory control of behavior. Here, central 5-HT depletion was induced by the acute tryptophan (TRP) depletion (ATD) procedure in young healthy volunteers to examine the role of 5-HT in motivated action and prepotent response inhibition. A novel reaction-time task, tailored to individual differences in general cognitive speed, was employed to measure the guidance of behavior by motivationally relevant signals predictive of reinforcement likelihood, while the stop-signal reaction-time task was used to measure response inhibition. Following the TRP-balancing control drink, cues predictive of high-reinforcement certainty induced faster, but less accurate responses compared with cues predictive of lower reinforcement certainty. Depletion of central 5-HT modulated this coupling between motivation and action by slowing responses and increasing accuracy as a function of incentive certainty. These effects of ATD on motivated action correlated highly with individual differences in the personality trait of Nonplanning Impulsiveness (Barratt Impulsivity Scale (BIS-11)), so that strongest effects on motivated action were observed in high-impulsive individuals. By contrast, ATD left unaltered the ability to inhibit prepotent responses. Our findings may have implications for a variety of neuropsychiatric disorders including impulsive aggressive disorders and depression.

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