Non-invasive Cerebellar Stimulation and Predictive Coding in Schizophrenia - PROJECT SUMMARY/ABSTRACT Psychotic disorders such as schizophrenia are severe, treatment-resistant illnesses that often result in chronic, debilitating impairment and reduced quality of life for affected individuals. Yet, we still do not understand the underlying neurobiological causes that give rise to one of the disorders’ core and most prominent symptoms, delusions (i.e., firmed, fixed beliefs despite disconfirming evidence). Converging evidence from computational psychiatry suggests that delusions result from errors in the brain’s fundamental ability to update an internal model that generates predictions about the external world (i.e., predictive coding deficits). Due to the cerebellum’s uniform cytoarchitecture and extensive reciprocal connections with cortical regions involved in a wide range of higher-order processes, researchers have posited that the cerebellum’s primary function is to carry out the computational processes involved in predictive coding. Considering consistent evidence for both predictive coding and cerebellar abnormalities in schizophrenia, altered cerebellar circuitry function is a candidate for the causal neurobiological circuits driving predictive coding deficits contributing to delusions in schizophrenia. However, to date, there has been no causal test of the role of cerebellum in predictive coding abnormalities in psychosis. This project will address this gap by using transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation, to modulate cerebellar circuitry to test the causal impact of cerebellar function on behavioral, computational, and neural measures of predictive coding associated with delusions in patients with schizophrenia (N=90). Participants with schizophrenia will be enrolled into a 3-session within-person (i.e., cross- over), active-sham study design. Session 1 will include a baseline assessment of clinical, behavioral, computational, and neural measures. Sessions 2 and 3 will include either active or sham tDCS stimulation of the cerebellar midline (session order will be randomized), immediately followed by re-assessment of the behavioral, computational, and neural measures of predictive coding. Results from this study will generate critical information regarding the role of the cerebellum in predictive coding deficits in psychosis. This knowledge will enhance the field’s understanding of the pathophysiology of delusions and will inform treatment approaches by elucidating the specific brain mechanisms that should be targeted by such programs. Through this project, I will complete interdisciplinary training in noninvasive brain stimulation of the cerebellum, computational modeling to quantify measures of predictive coding, conceptual and clinical aspects of conducting research in patients with schizophrenia, and time-frequency analysis of neural oscillatory activity to quantify neural measures of predictive coding. I will also obtain training in professional development, service, and scientific writing. This project will provide me with preliminary data to be competitive for an R01 to facilitate my transition to independence.
