Pavlovian conditioning-induced hallucinations result from overweighting of perceptual priors

Abstract

Some people hear voices that others do not, but only some of those people seek treatment. Using a Pavlovian learning task, we induced conditioned hallucinations in four groups of people who differed orthogonally in their voice-hearing and treatment-seeking statuses. People who hear voices were significantly more susceptible to the effect. Using functional neuroimaging and computational modeling of perception, we identified processes that differentiated voice-hearers from non-voice-hearers and treatment-seekers from non-treatment-seekers and characterized a brain circuit that mediated the conditioned hallucinations. These data demonstrate the profound and sometimes pathological impact of top-down cognitive processes on perception and may represent an objective means to discern people with a need for treatment from those without.

Conflict of interest statement

Conflicts of Interest: The authors declare no conflicts of interest. Model code and data stored at ModelDB (http://senselab.med.yale.edu/ModelDB/showModel.cshtml?model=229278) Imaging data stored at NeuroVault (/collections/OCFEJCQE/).

Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Figures

Fig 1. Methods and Behavioral Results

A. Trials consisted of simultaneous presentation of a 1000-Hz tone in white noise and a visual checkerboard. B. We estimated individual psychometric curves for tone detection (left) and then systematically varied stimulus intensity over twelve blocks of 30 conditioning trials. Threshold tones were more likely early and absent tones were more likely later (right). C. Groups varied along two dimensions: the presence (+) or absence (-) of daily AVH (blue) and the presence (+) or absence (−) of a diagnosable psychotic-spectrum illness (red). D. Detection thresholds. Error bars represent ±1 SD, boxes represent ± 1 SEM. E. Probability of conditioned hallucinations varied according to hallucination status. Main panel: error bars represent ±1 SD, boxes represent ±1 SEM. Inset: error bars represent ±1 SEM. F. Differences between hallucinating and non-hallucinating groups were found only in the target-absent and 25% Likelihood of Detection conditions. Error bars represent ±1 SEM. G. Hallucinators were more confident than non-hallucinators when reporting a tone that did not exist. H–I. Both the probability of reporting conditioned hallucinations (H) and the confidence with which they were reported (I) correlated with a measure of hallucination severity.

Fig 2. Imaging Results

A. Bilateral supplemental auditory cortex co-varied with tone intensity during thresholding (FWE-corrected, P < 0.05). B. Parameter estimates from this region showed increased activation during conditioned hallucinations. C. Whole-brain analysis during conditioned hallucinations (FDR-corrected, P < 0.05). D. Clusters derived from a meta-analysis (17) of AVH experiences during functional imaging. E–F. Hallucinators were much less likely to engage anterior cingulate cortex during correct rejections. Error bars represent ±1 SEM.

Fig 3. Hierarchical Gaussian Filter Analysis

A. Computational model, mapping from experimental stimuli to observed responses through perceptual and response models. The first level (X1) represents whether the subject believes a tone was present or not on trial t. The second level (X2) is their belief that visual cues are associated with tones. The third level (X3) is their belief about the volatility of the second level. The HGF allows for individual variability in weighting between sensory evidence and perceptual beliefs (parameter ν). B. At X3 there was a significant block-by-psychosis interaction. C–D. Significant block-by-hallucination status interactions were seen at layers X1 (D) and X2 (C). E. Nu (ν), was significantly higher in those with hallucinations when compared to their non-hallucinating counterparts. F. No main effects of group or interaction effects were seen for the decision noise parameter within the response model. Error bars and line shadings represent ±1 SEM. P+H+: purple; P-H+: blue; P+H−: red; P-H−: white.

Fig 4. Hierarchical Gaussian Filter Imaging Results

A. HGF trajectories for X1 (blue) and X3 (red) regressed onto BOLD time courses for the conditioned hallucinations task. Regions identified significantly active during conditioned hallucinations (from Fig. 3C) are highlighted in yellow for reference. All images cluster-extent thresholded at starting value 0.05; critical ke for X1 = 545; X3 = 406. B–C. Parameter estimates of X1 fit extracted from 5-mm sphere centered on STS (B) and anterior insula (C) activation differ based upon hallucination status. D. Parameter estimates of X3 fit extracted from 1-mm sphere centered on cerebellar vermis activation differ based upon psychosis status. Error bars represent 1 SEM.