Neural substrates of motivational dysfunction across neuropsychiatric conditions: Evidence from meta-analysis and lesion network mapping

Motivational dysfunction constitutes one of the fundamental dimensions of psychopathology cutting across traditional diagnostic boundaries. However, it is unclear whether there is a common neural circuit responsible for motivational dysfunction across neuropsychiatric conditions. To address this issue, the current study combined a meta-analysis on psychiatric neuroimaging studies of reward/loss anticipation and consumption (4308 foci, 438 contrasts, 129 publications) with a lesion network mapping approach (105 lesion cases). Our meta-analysis identified transdiagnostic hypoactivation in the ventral striatum (VS) for clinical/at-risk conditions compared to controls during the anticipation of both reward and loss. Moreover, the VS subserves a key node in a distributed brain network which encompasses heterogeneous lesion locations causing motivation-related symptoms. These findings do not only provide the first meta-analytic evidence of shared neural alternations linked to anticipatory motivation-related deficits, but also shed novel light on the role of VS dysfunction in motivational impairments in terms of both network integration and psychological functions. Particularly, the current findings suggest that motivational dysfunction across neuropsychiatric conditions is rooted in disruptions of a common brain network anchored in the VS, which contributes to motivational salience processing rather than encoding positive incentive values.