Patients with Schizophrenia have a Reduced Neural Response to Both Unpredictable and Predictable Primary Reinforcers

被引:142
作者
Waltz, James A. [1 ]
Schweitzer, Julie B. [2 ]
Gold, James M.
Kurup, Pradeep K. [3 ]
Ross, Thomas J. [3 ]
Salmeron, Betty Jo [3 ]
Rose, Emma Jane [3 ]
McClure, Samuel M. [4 ]
Stein, Elliot A. [3 ]
机构
[1] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA
[2] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA
[3] Natl Inst Drug Abuse, Neuroimaging Res Branch, Baltimore, MD USA
[4] Stanford Univ, Dept Psychol, Palo Alto, CA 94304 USA
关键词
schizophrenia; dopamine; reinforcement; basal ganglia; temporal difference error; POSITRON-EMISSION-TOMOGRAPHY; STRIATAL REWARD PREDICTION; SYSTEM ACTIVATION; RATING-SCALE; DYSFUNCTION; DOPAMINE; ANHEDONIA; FMRI; ABNORMALITIES; NEUROLEPTICS;
D O I
10.1038/npp.2008.214
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
One prevalent theory of learning states that dopamine neurons signal mismatches between expected and actual outcomes, called temporal difference errors (TDEs). Evidence indicates that dopamine system dysfunction is involved in negative symptoms of schizophrenia (SZ), including avolition and anhedonia. As such, we predicted that brain responses to TDEs in dopamine midbrain nuclei and target areas would be abnormal in SZ. A total of 18 clinically stable patients with chronic SZ and 18 controls participated in an fMRI study, which used a passive conditioning task. In the task, the delivery of a small amount of juice followed a light stimulus by exactly 6 s on approximately 75% of 78 total trials, and was further delayed by 4-7 s on the remaining trials. The delayed juice delivery was designed to elicit the two types of TDE signals, associated with the recognition that a reward was omitted at the expected time, and delivered at an unexpected time. Main effects of TDE valence and group differences in the positive-negative TDE contrast (unexpected juice deliveries juice omissions) were assessed through whole-brain and regions of interest (ROI) analyses. Main effects of TDE valence were observed for the entire sample in the midbrain, left putamen, left cerebellum, and primary gustatory cortex, bilaterally. Whole-brain analyses revealed group differences in the positive-negative TDE contrast in the right putamen and left precentral gyrus, whereas ROI analyses revealed additional group differences in the midbrain, insula, and parietal operculum, on the right, the putamen and cerebellum, on the left, and the frontal operculum, bilaterally. Further, these group differences were generally driven by attenuated responses in patients to positive TDEs (unexpected juice deliveries), whereas responses to negative TDEs (unexpected juice omissions) were largely intact. Patients also showed reductions in responses to juice deliveries on standard trials, and more blunted reinforcer responses in the left putamen corresponded to higher ratings of avolition. These results provide evidence that SZ patients show abnormal brain responses associated with the processing of a primary reinforcer, which may be a source of motivational deficits.
引用
收藏
页码:1567 / 1577
页数:11
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