Reward sensitivity predicts dopaminergic response in spatial neglect

Available online 18 September 2018.It has recently been revealed that spatial neglect can be modulated by motivational factors including anticipated monetary reward. A number of dopaminergic agents have been evaluated as treatments for neglect, but the results have been mixed, with no clear anatomical or cognitive predictors of dopaminergic responsiveness. Given that the effects of incentive motivation are mediated by dopaminergic pathways that are variably damaged in stroke, we tested the hypothesis that the modulatory influences of reward and dopaminergic drugs on neglect are themselves related. We employed a single-dose, double-blind, crossover design to compare the effects of Co-careldopa and placebo on a modified visual cancellation task in patients with neglect secondary to right hemisphere stroke. Whilst confirming that reward improved visual search in this group, we showed that dopaminergic stimulation only enhances visual search in the absence of reward. When patients were divided into REWARD-RESPONDERs and REWARD-NON-RESPONDERs, we found an interaction, such that only REWARD-NONRESPONDERs showed a positive response to reward after receiving Co-careldopa, whereas REWARD-RESPONDERs were not influenced by drug. At a neuroanatomical level, responsiveness to incentive motivation was most associated with intact dorsal striatum. These findings suggest that dopaminergic modulation of neglect follows an ‘inverted U’ function, is dependent on integrity of the reward system, and can be measured as a behavioural response to anticipated reward.This study was directly supported by the NIHR Biomedical Research Centre at Imperial College London and a HEFCE Clinical Senior Lectureship Award to PM. D.S. acknowledges support from the Spanish Ministry of Economy and Competitiveness (MINECO), through the 'Severo Ochoa' Programme for Centres/Units of Excellence in R&D (SEV-2015-490) and project grants PSI2016-76443-P from MINECO and PI-2017-25 from the Basque Government