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Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

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Segarra, Nuria 
Metastasio, Antonio  ORCID logo
Spencer, Jennifer 
Reinders, Niels R 


Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.



Adult, Anhedonia, Brain Mapping, Depressive Disorder, Female, Frontal Lobe, Games, Experimental, Humans, Magnetic Resonance Imaging, Male, Motivation, Neural Pathways, Reward, Schizophrenia, Schizophrenic Psychology, Ventral Striatum

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Springer Science and Business Media LLC
Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) (unknown)
Medical Research Council (G0001354)
Medical Research Council (G0701911)
Medical Research Council (G1000183)
Wellcome Trust (093875/Z/10/Z)
Wellcome Trust (095692/Z/11/Z)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_PC_12012)
Medical Research Council (G0701911/1)
Supported by a MRC Clinician Scientist award (G0701911), a Brain and Behaviour Research Foundation Young Investigator, and an Isaac Newton Trust award to Dr Murray; an award to Dr Segarra from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and Wellcome Trust (G1000183 and 093875/Z/10Z respectively); by awards from the Wellcome Trust (095692) and the Bernard Wolfe Health Neuroscience Fund to Professor Fletcher, and by awards from the Wellcome Trust Institutional Strategic Support Fund (097814/Z/11) and Cambridge NIHR Biomedical Research Centre. The authors are grateful for the help of clinical staff in CAMEO, in the Cambridge Rehabilitation and Recovery service and Pathways, and in the Cambridge IAPT service, for help with participant recruitment.