""""""""Negative"""""""" symptoms of schizophrenia, such as anhedonia and amotivation, signal an absence of typical hedonic and motivational outputs, and may reflect underlying alterations in the way the brain processes rewarding stimuli. Recent advances in basic neuroscience are providing novel insights into reward-related neural circuitry that, when perturbed, could contribute to negative symptom manifestation. In particular, impairments in prefrontal-striatal connections may confer higher-order reward processing deficits in schizophrenia, such as deficits in how rewards are represented and valued, as well as in the motivation and execution of goal-directed behaviors that optimize reward seeking. Several fMRI studies have reported that reduced striatal brain activations to rewarding stimuli relate to worse negative symptomatology in schizophrenia patients. In addition, recent findings show that in healthy individuals reward availability enhances functional activity in regions, such as the lateral prefrontal cortex, that drive cognitiv control. Ostensibly, normative control-related brain responses are amplified by incentivized contexts in order to increase behavioral output and thereby maximize reward attainment. Together, these literatures suggest that to better understand the extent to which dysfunctions of the brain's reward system contribute to the real world deficits in goal pursuit and attainment associated with schizophrenia, it will be necessary to consider not only initial brain responses evoked by rewarding stimuli, but also how these more basic reward signals interact with higher-order cognitive features that drive motivated behaviors. Accordingly, this CDA study will examine basic features of evoked brain responses to rewarding stimuli, as well as the interaction of reward incentives on cognitive control functioning in young adults with recent-onset schizophrenia. The training plan will further develop the PI's expertise in psychiatric neuroimaging through a tailored combination of formal coursework, methodological workshops, seminars, and collaboration with established investigators in schizophrenia, reward neurobiology, and the integration of functional neuroimaging methods. More specifically, the proposed work will combine neuroimaging modalities (fMRI and EEG) to characterize neurobiological mechanisms underlying putative reward processing deficits in schizophrenia, as they relate to clinical features of avolition and anhedonia. Major project objectives are to inform understanding of the neurobiology of reward through: i) assessing brain functioning during passive anticipation, receipt and loss of monetary rewards in schizophrenia and ii) determining whether reward-related modulation of brain functioning during cognitive control deviates in schizophrenia from healthy control patterns. By providing information about both spatial and temporal features of brain activity, combination fMRI and EEG will enable a more comprehensive assessment of the aspects of reward-related brain activity that are the focus of the proposed work. Negative symptoms are strong predictors of poorer social and occupational functional outcomes in schizophrenia, suggesting that effectively intervening on this symptom class could demonstrably improve clinical prognosis. Findings from this CDA project could provide valuable insight into the pathophysiology of reward processing anomalies in schizophrenia, which may in turn, inform intervention efforts relevant to treating motivational and hedonic deficits.

Public Health Relevance

The VA provides health care to about 200,000 Veterans with psychotic disorders, including schizophrenia. Negative symptoms of schizophrenia, such as anhedonia and amotivation, have been strongly associated with functional outcomes in patients, emphasizing the importance of targeting this symptom class in mental health care delivery. Yet, there is widespread consensus that adequate treatments for negative symptoms are not available. Improved understanding of the neurobiology of negative symptoms is needed to inform the development of better therapeutic options to target these symptoms. Research aims of the current project are to combine clinical neuroimaging tools to generate new knowledge concerning the relationship between negative symptoms and reward-related brain alterations in schizophrenia. Findings from neuroimaging studies may help lead to improved intervention options to treat Veterans with severe mental illnesses.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Mental Health and Behavioral Science B (MHBB)
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Veterans Affairs Medical Center San Francisco
San Francisco
United States
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Fryer, Susanna L; Roach, Brian J; Wiley, Katherine et al. (2016) Reduced Amplitude of Low-Frequency Brain Oscillations in the Psychosis Risk Syndrome and Early Illness Schizophrenia. Neuropsychopharmacology 41:2388-98
Fryer, Susanna L; Roach, Brian J; Ford, Judith M et al. (2015) Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in Schizophrenia. Neuropsychopharmacology 40:2705-14