Estimating changing contexts in schizophrenia

Abstract

SEE STEPHAN ET AL DOI101093/AWW120 FOR A SCIENTIFIC COMMENTARY ON THIS WORK: Real world information is often abstract, dynamic and imprecise. Deciding if changes represent random fluctuations, or alterations in underlying contexts involve challenging probability estimations. Dysfunction may contribute to erroneous beliefs, such as delusions. Here we examined brain function during inferences about context change from noisy information. We examined cortical-subcortical circuitry engaging anterior and dorsolateral prefrontal cortex, and midbrain. We hypothesized that schizophrenia-related deficits in prefrontal function might overestimate context change probabilities, and that this more chaotic worldview may subsequently gain familiarity and be over-reinforced, with implications for delusions. We then examined these opposing information processing biases against less expected versus familiar information patterns in relation to genetic risk for schizophrenia in unaffected siblings. In one experiment, 17 patients with schizophrenia and 24 normal control subjects were presented in 3 T magnetic resonance imaging with numerical information varying noisily about a context integer, which occasionally shifted up or down. Subjects were to indicate when the inferred numerical context had changed. We fitted Bayesian models to estimate probabilities associated with change inferences. Dynamic causal models examined cortical-subcortical circuitry interactions at context change inference, and at subsequent reduced uncertainty. In a second experiment, genetic risk for schizophrenia associated with similar cortical-subcortical findings were explored in an independent sample of 36 normal control subjects and 35 unaffected siblings during processing of intuitive number sequences along the number line, or during the inverse, less familiar, sequence. In the first experiment, reduced Bayesian models fitting subject behaviour suggest that patients with schizophrenia overestimated context change probabilities. Here, patients engaged anterior prefrontal cortex relatively less than healthy controls, in part driven by reduced effective connectivity from dorsolateral prefrontal cortex to anterior prefrontal cortex. In processing subsequent information indicating reduced uncertainty of their predictions, patients engaged relatively increased mid-brain activation, driven in part by increased dorsolateral prefrontal cortex to midbrain connectivity. These dissociable reduced and exaggerated prefrontal and subcortical circuit functions were accentuated in patients with delusions. In the second experiment, analogous dissociable reduced anterior prefrontal cortex and exaggerated midbrain engagement occurred in unaffected siblings when processing less expected versus more familiar number sequences. In conclusion, patients overestimated ambiguous context change probabilities with relatively reduced anterior frontal engagement. Subsequent reduced uncertainty about contextual state appeared over-reinforced, potentially contributing to confirmation bias a...

Motivational deficits in schizophrenia relate to abnormalities in cortical learning rate signals

“…The current results additionally provide preliminary support for the idea that a reduced ability to adaptively update expectations in PSZ could be related to decreased coupling between regions that signal and utilize the RPE to update behavior; the strength of learning rate modulation-dependent dmPFC-VS connectivity was decreased in PSZ, and especially so in PSZ with more severe motivational deficits. This finding echoes those of Kaplan et al (2016) who observed changes in ACC effective connectivity within a change-detection network. In that study, increased PFCmidbrain effective connectivity tracked with delusional severity, whereas we observed decreased dmPFC-VS connectivity as a function of motivational deficit severity.…”

“…In both studies, these impairments scaled with the severity of motivational deficits. Multiple other groups have reported abnormal prefrontal activity (or fronto-parietal connectivity) in association with belief updating in uncertain environments (Kaplan et al, 2016;Koch et al, 2010;Paulus, Frank, Brown, & Braff, 2003). While these findings suggest that abnormalities in learning rate modulation may contribute to RL deficits in PSZ, even when RPE signals are intact, no systematic investigation of dynamic learning rate modulation has been conducted in this population.…”

The dysconnection hypothesis (2016)

“…In recent years, DCM studies of schizophrenia have started to appear (Allen et al, 2010, Bastos-Leite et al, 2015, Benetti et al, 2009, Brodersen et al, 2014, Curcic-Blake et al, 2015, Dauvermann et al, 2013, Dima et al, 2012, Kaplan et al, 2016, Schmidt et al, 2014). Almost invariably, these studies disclose abnormal effective connectivity involving the prefrontal cortex.…”

“…Some DCM studies have looked explicitly for the synaptic correlates of precision. For example, “in processing subsequent information indicating reduced uncertainty of their predictions, patients engaged relatively increased mid-brain activation, driven in part by increased dorsolateral prefrontal cortex to midbrain connectivity” (Kaplan et al, 2016). …”

Dysfunctional and compensatory brain networks underlying math fluency

“…We used Dynamic Causal Modeling, DCM (Friston et al, 2003) as implemented in SPM12 (DCM10) to examine how cortical and subcortical brain regions interacted during TC-related tasks in Experiments 1 and 2. Time series during TC were extracted from each of 6 regions-of-interest (ROI) in the IPS, AG, FFG, IFG, DLPFC and Str for each individual at a peak within 10mm of the group-level activation peak (at p<0.05 whole brain FWE corrected) and with p<0.05 at the individual subject level, as before (Kaplan C.M. et al, 2016).…”