FMRI investigation of intertemporal discounting in schizophrenia

Schizophrenia is most recognizable by positive symptoms of hallucinations and delusions, but the cognitive deficits and negative symptoms contribute more to functional deficits. The delay discounting (DD) task, with choices between a small immediate reward and a larger delayed reward, tapping into both executive function and reward processing, may prove useful in identifying cognitive and reward processing abnormalities relevant to schizophrenia. In the present study, we used the discounting parameter, k, to assess whether patients with schizophrenia preferred more immediate rewards than healthy controls. We used a model fit statistic, R2, as a measure of choice consistency, quantified using a non-linear regression of participants' responses. Using functional magnetic resonance imaging (fMRI), we investigated group differences between patients with schizophrenia and controls in blood oxygen level-dependent (BOLD) responses to DD decisions in general. In addition, we investigated neural responses to delay discounting decisions varying in difficulty. Compared to controls, patients were more inconsistent in their pattern of responses and exhibited greater DD. However, the difference in DD disappeared when analysis was limited to patients who were consistent in their task performance. Controls, matched on performance and demographics to the consistent patients, displayed greater activation in executive function and reward areas in response to task trials compared to control trials. Compared to controls, consistent patients displayed greater activation to the task relative to the control trials in left insular and temporal cortices and in the precuneus. In response to hard DD trials, controls, when compared to patients, showed more activation in areas associated with executive function, such as the inferior frontal gyrus and the dorsal anterior cingulate cortex. In response to both hard and easy trials, controls showed more activation than consistent patients in the inferior parietal lobule and the ventral striatum. Patients unable to perform the task consistently, when compared to controls, showed greater activation to the DD task in the precuneus and posterior cingulate cortex. In general, patients with schizophrenia appear to have regions of hypoactivation contributing to executive function and reward processing deficits, in addition to hyperactivation in areas associated with resting state and conflict monitoring

Multimodal analysis of the hippocampus in schizophrenia using proton magnetic resonance spectroscopy and functional magnetic resonance imaging

BACKGROUND: Studies have shown that individuals with schizophrenia suffer from memory impairments. In this study, we combined proton magnetic resonance spectroscopy ((1)H-MRS) and functional magnetic resonance imaging (fMRI) to clarify the neurobiology of memory deficits in schizophrenia. METHODS: We used single-voxel MRS acquired in the left hippocampus and fMRI during performance of a memory task to obtain measures of neurochemistry and functional response in 28 stable, medicated participants with schizophrenia (SZ) and 28 matched healthy controls (HC). RESULTS: The SZ group had significantly decreased blood oxygen level-dependent (BOLD) signal in left inferior frontal gyrus (IFG) during encoding and in the anterior cingulate cortex (ACC) and superior temporal gyrus (STG) during retrieval. We did not find significant differences in N-acetylaspartate/creatine (NAA/Cr) or glutamate + glutamine (Glx/Cr) levels between the groups, but did find a significant positive correlation between NAA/Cr and Glx/Cr in the HC group that was absent in the SZ group. There were no significant correlations between BOLD and MRS measured in the hippocampus. Further analyses revealed a negative correlation between left IFG BOLD and task performance in the SZ group. Finally, in the HC group, the left IFG BOLD was positively correlated with Glx/Cr. CONCLUSIONS: We replicated findings of reduced BOLD signal in left IFG and of an altered relationship between IFG BOLD response and task performance in the SZ. The absence of correlation between NAA/Cr and Glx/Cr levels in patients might suggest underlying pathologies of the glutamate-glutamine cycle and/or mitochondria