Stronger Top-Down and Weaker Bottom-Up Frontotemporal Connections During Sensory Learning Are Associated With Severity of Psychotic Phenomena.

Recent theories in computational psychiatry propose that unusual perceptual experiences and delusional beliefs may emerge as a consequence of aberrant inference and disruptions in sensory learning. The current study investigates these theories and examines the alterations that are specific to schizophrenia spectrum disorders vs those that occur as psychotic phenomena intensify, regardless of diagnosis. We recruited 66 participants: 22 schizophrenia spectrum inpatients, 22 nonpsychotic inpatients, and 22 nonclinical controls. Participants completed the reversal oddball task with volatility manipulated. We recorded neural responses with electroencephalography and measured behavioral errors to inferences on sound probabilities. Furthermore, we explored neural dynamics using dynamic causal modeling (DCM). Attenuated prediction errors (PEs) were specifically observed in the schizophrenia spectrum, with reductions in mismatch negativity in stable, and P300 in volatile, contexts. Conversely, aberrations in connectivity were observed across all participants as psychotic phenomena increased. DCM revealed that impaired sensory learning behavior was associated with decreased intrinsic connectivity in the left primary auditory cortex and right inferior frontal gyrus (IFG); connectivity in the latter was also reduced with greater severity of psychotic experiences. Moreover, people who experienced more hallucinations and psychotic-like symptoms had decreased bottom-up and increased top-down frontotemporal connectivity, respectively. The findings provide evidence that reduced PEs are specific to the schizophrenia spectrum, but deficits in brain connectivity are aligned on the psychosis continuum. Along the continuum, psychotic experiences were related to an aberrant interplay between top-down, bottom-up, and intrinsic connectivity in the IFG during sensory uncertainty. These findings provide novel insights into psychosis neurocomputational pathophysiology.

Aberrant connectivity in auditory precision encoding in schizophrenia spectrum disorder and across the continuum of psychotic-like experiences.

BACKGROUND: The ability to generate a precise internal model of statistical regularities is impaired in schizophrenia. Predictive coding accounts of schizophrenia suggest that psychotic symptoms may be explained by a failure to build precise beliefs or a model of the world. The precision of this model may vary with context. For example, in a noisy environment the model will be more imprecise compared to a model built in an environment with lower noise. However compelling, this idea has not yet been empirically studied in schizophrenia. METHODS: In this study, 62 participants engaged in a stochastic mismatch negativity paradigm with high and low precision. We included inpatients with a schizophrenia spectrum disorder (N = 20), inpatients with a psychiatric disorder but without psychosis (N = 20), and healthy controls (N = 22), with comparable sex ratio and age distribution. Bayesian mapping and dynamic causal modelling were employed to investigate the underlying microcircuitry of precision encoding of auditory stimuli. RESULTS: We found strong evidence (exceedance P > 0.99) for differences in the underlying connectivity associated with precision encoding between the three groups as well as on the continuum of psychotic-like experiences assessed across all participants. Critically, we show changes in interhemispheric connectivity between the two inpatient groups, with some connections further aligning on the continuum of psychotic-like experiences. CONCLUSIONS: While our results suggest continuity in backward connectivity alterations with psychotic-like experiences regardless of diagnosis, they also point to specificity for the schizophrenia spectrum disorder group in interhemispheric connectivity alterations.