Investigating the role of cerebellar abnormalities in dysfunctional predictive coding in individuals with schizophrenia

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Project Summary Failure in predictive coding is an influential hypothesis regarding the neural mechanisms of schizophrenia that may account for cardinal symptoms of the disorder. Specifically, it has been hypothesized that all self-generated actions produce an efference copy, or a copy of the motor command, which results in a sensory corollary discharge, or a neural representation of the expected sensory consequences of that action, and that through this neural mechanism of predictive coding actions are classified at the neural level as originating from the self. This has been proposed to occur for internal processes as well, such that thoughts would also generate an efference copy and a corollary discharge. If a thought or action lacked this neural signature of self-generation, then delusions of control or hallucinations could arise to account for these seemingly external experiences. However, the precise neural mechanisms of this parsimonious and theoretically compelling hypothesis have yet to be elucidated. It may be informative to consider an analogous mechanism in the domain of motor control, wherein an efference copy is similarly generated in response to an action, but is then hypothesized to travel to the cerebellum, where an internal model simulates the dynamics of movement and outputs a corollary discharge (still the predicted sensory consequences), but for the purpose of motor control rather than predictive coding. Given the accumulating evidence of cerebellar dysfunction in schizophrenia and the striking similarities between these two mechanisms, the proposed research will examine whether the cerebellum is involved in predictive coding and whether cerebellar abnormalities contribute to predictive coding dysfunction in schizophrenia. The relationship of cerebellar integrity to measures of predictive coding will be assessed in controls and individuals with schizophrenia. Behavioral measures (postural sway and subsecond paced finger tapping) and a structural measure (anatomical MRI) of cerebellar integrity will be administered to 30 individuals with schizophrenia and 30 non-psychiatric controls. Previously established electrophysiological measures of the efference copy and corollary discharge will be quantified in EEG data in response to self-paced button presses; the effect of cerebellar abnormalities on the relationship between the strength of the efference copy and the corollary discharge will be assessed. Next, controls will undergo simultaneous EEG and cerebellar transcranial direct current stimulation to modulate cerebellar neuronal excitability, and the effect on corollary discharge strength will be assessed. Results will reveal whether cerebellar abnormalities contribute to predictive coding dysfunction in schizophrenia, as well as whether modulation of cerebellar neuronal excitability impacts predictive coding in controls. Public health implications include better elucidating pathophysiological mechanisms of schizophrenia and gaining a more precise understanding of the role of the cerebellum in predictive coding.