Estimating changing contexts in schizophrenia | JoVE Visualize

Area of Science:

Neuroscience
Cognitive Psychology
Psychiatry

Background:

Real-world information is often imprecise, requiring probability estimations to discern context changes from random fluctuations.
Erroneous beliefs, such as delusions, may arise from dysfunction in processing uncertain or noisy information.
Schizophrenia is associated with cognitive deficits, particularly in prefrontal cortex function, potentially impacting probabilistic inference.

Purpose of the Study:

To investigate brain function during context change inference from noisy information in patients with schizophrenia.
To examine the role of cortical-subcortical circuitry, including prefrontal cortex and midbrain, in processing uncertainty and context change.
To explore the relationship between these neural processing biases, genetic risk for schizophrenia, and delusions.

Main Methods:

Two experiments were conducted using functional magnetic resonance imaging (fMRI) and Bayesian modeling.
Experiment 1: 17 schizophrenia patients and 24 controls inferred context changes from noisy numerical data.
Experiment 2: 36 controls and 35 unaffected siblings processed familiar versus less familiar number sequences to assess genetic risk effects.

Main Results:

Schizophrenia patients overestimated context change probabilities, showing reduced anterior prefrontal cortex engagement and altered connectivity.
Patients exhibited exaggerated midbrain activation when reducing uncertainty, linked to increased dorsolateral prefrontal cortex to midbrain connectivity.
These neural patterns were accentuated in patients with delusions and mirrored in unaffected siblings processing less familiar information, suggesting a link to genetic risk.

Conclusions:

Patients with schizophrenia exhibit aberrant probabilistic inference, overestimating context change in ambiguous situations.
Reduced anterior frontal engagement and over-reinforced processing of reduced uncertainty may contribute to confirmation bias and delusions.
Observed cortical-subcortical dysfunctions are associated with genetic risk for schizophrenia, impacting the processing of expected versus unexpected information.