Conditioned Hallucinations and Prior Overweighting Are State-Sensitive Markers of Hallucination Susceptibility.

BACKGROUND: Recent advances in computational psychiatry have identified latent cognitive and perceptual states that predispose to psychotic symptoms. Behavioral data fit to Bayesian models have demonstrated an overreliance on priors (i.e., prior overweighting) during perception in select samples of individuals with hallucinations, corresponding to increased precision of prior expectations over incoming sensory evidence. However, the clinical utility of this observation depends on the extent to which it reflects static symptom risk or current symptom state. METHODS: To determine whether task performance and estimated prior weighting relate to specific elements of symptom expression, a large, heterogeneous, and deeply phenotyped sample of hallucinators (n = 249) and nonhallucinators (n = 209) performed the conditioned hallucination (CH) task. RESULTS: We found that CH rates predicted stable measures of hallucination status (i.e., peak frequency). However, CH rates were more sensitive to hallucination state (i.e., recent frequency), significantly correlating with recent hallucination severity and driven by heightened reliance on past experiences (priors). To further test the sensitivity of CH rate and prior weighting to symptom severity, a subset of participants with hallucinations (n = 40) performed a repeated-measures version of the CH task. Changes in both CH frequency and prior weighting varied with changes in auditory hallucination frequency on follow-up. CONCLUSIONS: These results indicate that CH rate and prior overweighting are state markers of hallucination status, potentially useful in tracking disease development and treatment response.

Perceptual pathways to hallucinogenesis.

Recent advances in computational psychiatry have provided unique insights into the neural and cognitive underpinnings of psychotic symptoms. In particular, a host of new data has demonstrated the utility of computational frameworks for understanding how hallucinations might arise from alterations in typical perceptual processing. Of particular promise are models based in Bayesian inference that link hallucinatory perceptual experiences to latent states that may drive them. In this piece, we move beyond these findings to ask: how and why do these latent states arise, and how might we take advantage of heterogeneity in that process to develop precision approaches to the treatment of hallucinations? We leverage specific models of Bayesian inference to discuss components that might lead to the development of hallucinations. Using the unifying power of our model, we attempt to place disparate findings in the study of psychotic symptoms within a common framework. Finally, we suggest directions for future elaboration of these models in the service of a more refined psychiatric nosology based on predictable, testable, and ultimately treatable information processing derangements.

Measuring Voluntary Control Over Hallucinations: The Yale Control Over Perceptual Experiences (COPE) Scales.

Auditory verbal hallucinations (AVH) frequently cause significant distress and dysfunction, and may be unresponsive to conventional treatments. Some voice-hearers report an ability to fully control the onset and offset of their AVH, making them significantly less disruptive. Measuring and understanding these abilities may lead to novel interventions to enhance control over AVH. Fifty-two voice-hearers participated in the pilot study. 318 participants with frequent AVH participated in the validation study. A pool of 59 items was developed by a diverse team including voice-hearers and clinicians. After the pilot study, 35 items were retained. Factorial structure was assessed with exploratory (EFA, n = 148) and confirmatory (CFA, n = 170) factor analyses. Reliability and convergent validity were assessed using a comprehensive battery of validated phenomenological and clinical scales. CFA on the final 18 items supported two factors for a Methods of Control Scale (5 items each, average ω = .87), and one factor for a Degree of Control Scale (8 items, average ω = .95). Correlation with clinical measures supported convergent validity. Degree of control was associated with positive clinical outcomes in voice-hearers both with and without a psychosis-spectrum diagnosis. Degree of control also varied with quality of life independently of symptom severity and AVH content. The Yale control over perceptual experiences (COPE) Scales robustly measure voice-hearers' control over AVH and exhibit sound psychometric properties. Results demonstrate that the capacity to voluntarily control AVH is independently associated with positive clinical outcomes. Reliable measurement of control over AVH will enable future development of interventions meant to bolster that control.

Development of Voluntary Control Over Voice-Hearing Experiences: Evidence From Treatment-Seeking and Non-Treatment-Seeking Voice-Hearers.

Voluntary control over voice-hearing experiences is one of the most consistent predictors of functioning among voice-hearers. However, control over voice-hearing experiences is likely to be more nuanced and variable than may be appreciated through coarse clinician-rated measures, which provide little information about how control is conceptualized and developed. We aimed to identify key factors in the evolution of control over voice-hearing experiences in treatment-seeking (N = 7) and non-treatment-seeking (N = 8) voice-hearers. Treatment-seeking voice-hearers were drawn from local chapters of the Connecticut Hearing Voices Network, and non-treatment-seeking voice-hearers were recruited from local spiritually oriented organizations. Both groups participated in a clinical assessment, and a semi-structured interview meant to explore the types of control exhibited and how it is fostered. Using Grounded Theory, we identified that participants from both groups exerted direct and indirect control over their voice-hearing experiences. Participants that developed a spiritual explanatory framework were more likely to exert direct control over the voice-hearing experiences than those that developed a pathologizing framework. Importantly, despite clear differences in explanatory framework and distress because of their experiences, both groups underwent similar trajectories to develop control and acceptance over their voice-hearing experiences. Understanding these factors will be critical in transforming control over voice-hearing experiences from a phenomenological observation to an actionable route for clinical intervention.

A Review of fMRI Affective Processing Paradigms Used in the Neurobiological Study of Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a chronic and debilitating psychiatric disorder with a complex clinical presentation. The last two decades have seen a proliferation of literature on the neurobiological mechanisms subserving affective processing in PTSD. The current review will summarize the neuroimaging results of the most common experimental designs used to elucidate the affective signature of PTSD. From this summary, we will provide a heuristic to organize the various paradigms discussed and report neural patterns of activations using this heuristic as a framework. Next, we will compare these results to the traditional functional neurocircuitry model of PTSD and discuss biological and analytic variables which may account for the heterogeneity within this literature. We hope that this approach may elucidate the role of experimental parameters in influencing neuroimaging findings.

The neural correlates of the dominance dimension of emotion.

Emotion has been conceptualized as a dimensional construct, while the number of dimensions - two or three - has been debated. Research has consistently identified two dimensions - valence and arousal - though ample evidence exists that three dimensions are necessary to describe emotion. One proposed third dimension, identified as dominance, is relevant in clinical syndromes, personality and consumer psychology. Dominance refers to an individual's sense of having an ability to affect the environment. Neuroimaging studies have generally focused on the two dimensions of valence and arousal, leaving the neural correlates of dominance unexplored. The current study used functional magnetic resonance imaging to explore the neural basis of dominance in 17 healthy male controls. Participants viewed images from the International Affective Picture System that were selected to represent high and low dominance conditions. Results indicated activation in paralimbic regions, including the bilateral anterior insula for high dominance and the right precuneus for low. The findings of this exploratory study support the consideration of dominance in dimensional models of emotion and suggest that further research is needed to understand the neural representation of dominance in emotional experience.

Atrophy in distinct corticolimbic networks in frontotemporal dementia relates to social impairments measured using the Social Impairment Rating Scale.

Patients with frontotemporal dementia (FTD) often exhibit prominent, early and progressive impairments in social behaviour. We developed the Social Impairment Rating Scale (SIRS), rated by a clinician after a structured interview, which grades the types and severity of social behavioural symptoms in seven domains. In 20 FTD patients, we used the SIRS to study the anatomic basis of social impairments. In support of hypotheses generated from a prior study of healthy adults, we found that the relative magnitude of brain atrophy in three partially dissociable corticolimbic networks anchored in the amygdala predicted the severity of distinct social impairments measured using the SIRS. Patients with the greatest atrophy in a mesolimbic, reward-related (affiliation) network exhibited the most severe socioemotional detachment, whereas patients with the greatest atrophy in an interoceptive, pain-related (aversion) network exhibited the most severe lack of social apprehension. Patients with the greatest atrophy in a perceptual network exhibited the most severe lack of awareness or understanding of others' social and emotional behaviour. Our findings underscore observations that FTD is associated with heterogeneous social symptoms that can be understood in a refined manner by measuring impairments in component processes subserved by dissociable neural networks. Furthermore, these findings support the validity of the SIRS as an instrument to measure the social symptoms of patients with FTD. Ultimately, we hope it will be useful as a longitudinal outcome measure in natural history studies and in clinical trials of putative interventions to improve social functioning.

Differential hemodynamic response in affective circuitry with aging: an FMRI study of novelty, valence, and arousal.

Emerging evidence indicates that stimulus novelty is affectively potent and reliably engages the amygdala and other portions of the affective workspace in the brain. Using fMRI, we examined whether novel stimuli remain affectively salient across the lifespan, and therefore, whether novelty processing--a potentially survival-relevant function--is preserved with aging. Nineteen young and 22 older healthy adults were scanned during observing novel and familiar affective pictures while estimating their own subjectively experienced aroused levels. We investigated age-related difference of magnitude of activation, hemodynamic time course, and functional connectivity of BOLD responses in the amygdala. Although there were no age-related differences in the peak response of the amygdala to novelty, older individuals showed a narrower, sharper (i.e., "peakier") hemodynamic time course in response to novel stimuli, as well as decreased connectivity between the left amygdala and the affective areas including orbito-frontal regions. These findings have relevance for understanding age-related differences in memory and affect regulation.

Intrinsic interhemispheric hippocampal functional connectivity predicts individual differences in memory performance ability.

When given challenging episodic memory tasks, young adults demonstrate notable individual differences in performance. Recent evidence suggests that individual differences in human behavior may be related to the strength of functional connectivity of large-scale functional networks as measured by spontaneous fluctuations in regional brain activity during quiet wakefulness (the "resting state"), in the absence of task performance. In this study, we sought to determine whether individual differences in memory performance could be predicted by the interhemispheric functional connectivity of the two hippocampi, hypothesized to reflect the intrinsic connectivity within the large-scale medial temporal lobe memory system. Results demonstrated that interhemispheric hippocampal functional connectivity during quiet wakefulness was predictive of the capacity to freely recall recently learned information (r = 0.47, P < 0.05). In contrast, functional connectivity of bilateral motor cortices had no relationship to free recall, supporting the specificity of the hippocampal data. Thus, individual differences in the capacity to perform episodic memory tasks, which may be persistent behavioral traits or transient states, may be at least partly subserved by individual differences in the functional connectivity of large-scale functional-anatomic memory networks.

Novelty as a dimension in the affective brain.

Many neuroscience studies have demonstrated that the human amygdala is a central element in the neural workspace that computes affective value. Emerging evidence suggests that novelty is an affective dimension that engages the amygdala independently of other affective properties. This current study is the first in which novelty, valence, and arousal were systematically examined for their relative contributions to amygdala activation during affective processing. Healthy young adults viewed International Affective Picture System (IAPS) images that varied along the dimensions of valence (positive, negative, neutral), arousal (high, mid, low), and novelty (novel, familiar). The results demonstrate that, in comparison to negative (vs. positive) and high (vs. low) arousal stimuli, the amygdala has higher peak responses and a selectively longer time course of activation to novel (vs. familiar) stimuli. In addition, novelty differentially engaged other affective brain areas including those involved in controlling and regulating amygdala responses (e.g., orbitofrontal cortex), as well as those transmitting sensory signals that the amygdala modulates (e.g., occipitotemporal visual cortex). Taken together with other findings, these results support the idea that an essential amygdala function is signaling stimulus importance or salience. The results also suggest that novelty is a critical stimulus dimension for amygdala engagement (in addition to valence and arousal).

Neural correlates of novelty and face-age effects in young and elderly adults.

The human amygdala preferentially responds to objects of potential value, such as hedonically valenced and novel stimuli. Many studies have documented age-related differences in amygdala responses to valenced stimuli, but relatively little is known about age-related changes in the amygdala's response to novelty. This study examines whether there are differences in amygdala novelty responses in two different age groups. Healthy young and elderly adults viewed both young and elderly faces that were seen many times (familiar faces) or only once (novel faces) in the context of an fMRI study. We observed that amygdala responses to novel (versus familiar) faces were preserved with aging, suggesting that novelty processing in the amygdala remains stable across the lifespan. In addition, participants demonstrated larger amygdala responses to target faces of the same age group than to age out-group target faces (i.e., an age in-group effect). Differences in anatomic localization and behavioral results suggest that novelty and age in-group effects were differentially processed in the amygdala.