Barriers and solutions to the adoption of translational tools for computational psychiatry.

Computational psychiatry is a field aimed at developing formal models of information processing in the human brain, and how alterations in this processing can lead to clinical phenomena. There has been significant progress in the development of tasks and how to model them, presenting an opportunity to incorporate computational psychiatry methodologies into large- scale research projects or into clinical practice. In this viewpoint, we explore some of the barriers to incorporation of computational psychiatry tasks and models into wider mainstream research directions. These barriers include the time required for participants to complete tasks, test-retest reliability, limited ecological validity, as well as practical concerns, such as lack of computational expertise and the expense and large sample sizes traditionally required to validate tasks and models. We then discuss solutions, such as the redesigning of tasks with a view toward feasibility, and the integration of tasks into more ecologically valid and standardized game platforms that can be more easily disseminated. Finally, we provide an example of how one task, the conditioned hallucinations task, might be translated into such a game. It is our hope that interest in the creation of more accessible and feasible computational tasks will help computational methods make more positive impacts on research as well as, eventually, clinical practice.

Attention Biases Competition for Visual Representation via Dissociable Influences from Frontal and Parietal Cortex.

What mechanisms underlie the prioritization of neural representations of visually perceived information to guide behavior? We assessed the dynamics whereby attention biases competition for representation of visual stimuli by enhancing representations of relevant information and suppressing the irrelevant. Multivariate pattern analysis (MVPA) classifiers were trained to discriminate patterns of fMRI activity associated with each of three stimuli, within several predefined ROIs. Participants performed a change-detection task wherein two of three presented items flashed at 1 Hz, one to each side of central fixation. Both flashing stimuli would unpredictably change state, but participants covertly counted the number of changes only for the cued item. In the ventral occipito-temporal ROI, MVPA evidence (a proxy for representational fidelity) was dynamically enhanced for attended stimuli and suppressed for unattended stimuli, consistent with a mechanism of biased competition between stimulus representations. Frontal and parietal ROIs displayed a qualitatively distinct, more "source-like" profile, wherein MVPA evidence for only the attended stimulus could be observed above baseline levels. To assess how attentional modulation of ventral occipito-temporal representations might relate to signals originating in the frontal and/or parietal ROIs, we analyzed informational connectivity (IC), which indexes time-varying covariation between regional levels of MVPA evidence. Parietal-posterior IC was elevated during the task, but did not differ for cued versus uncued items. Frontal-posterior IC, in contrast, was sensitive to an item's priority status. Thus, although regions of frontal and parietal cortex act as sources of top-down attentional control, their precise functions likely differ.

The Neural Consequences of Attentional Prioritization of Internal Representations in Visual Working Memory.

Although humans can hold multiple items in mind simultaneously, the contents of working memory (WM) can be selectively prioritized to guide future behavior. We explored whether the "same-object" benefits in visual processing may also be observed in visual WM. fMRI data were collected while participants performed a multistep serial retrocuing task in which they first viewed two 2-D objects (coherently moving colored dots). During retention, an initial relevance cue then indicated whether only the first or only the second object ("object-relevant"), or only the color of both objects or only their direction of motion would be relevant for the remainder of the trial ("feature-relevant"). On "object-relevant" trials, the ensuing priority cues selected either one of the features ("color" or "direction") bound to the relevance-cued object, whereas on "feature-relevant" trials, the priority cues selected one of the two relevance-cued features. Using multivariate inverted encoding models, we found a same-object benefit on object-relevant trials in occipitotemporal regions: On feature-relevant trials, the first priority cue triggered a strengthening of the neural representation of the cued feature and a concomitant weakening to baseline of the uncued feature, whereas on object-relevant trials, the cued item remained active but did not increase in strength and the uncued item weakened but remained significantly elevated throughout the delay period. Although the stimulus-specific representation in frontoparietal regions was weak and uneven, these regions closely tracked the higher order information of which stimulus category was relevant for behavior throughout the trial, suggesting an important role in controlling the prioritization of information in visual WM.

Overlapping and distinct contributions of stimulus location and of spatial context to nonspatial visual short-term memory.

Stimulus location is not always informative during visual short-term memory (VSTM) for nonspatial features. Nevertheless, there is considerable evidence for the automatic encoding and retention of location information, regardless of its task relevance. To explore the functional and neural bases of the representation of spatial context in VSTM for nonspatial information, functional magnetic resonance imaging was performed while subjects performed delayed recall for the orientation of individual stimuli. Stimulus location varied across trials, and although this information was irrelevant for task performance, multivariate pattern analysis decoding of stimulus location sustained across trials, and also the decoding strength, predicted the precision of the recall of orientation. The influence of spatial context on the representation of orientation was operationalized by comparing the orientation reconstructions with multivariate inverted encoding models (IEM) trained in location context-dependent vs. -independent data. Although orientation reconstructions were robust for both location-dependent and location-independent IEMs, they were markedly stronger for the former. Furthermore, the functional relevance of location context was demonstrated by the fact that only the location-dependent neural representations of stimulus orientation predicted recall precision. NEW & NOTEWORTHY Neural representation strength of stimulus location predicts the precision of visual short-term memory (VSTM) recall of nonspatial stimulus, even when this information is task irrelevant. Neural representations of nonspatial stimuli that incorporate location context are stronger than those that do not, and only the former representations are strongly linked to behavior. The contributions to nonspatial VSTM performance of the representation of location context are at least partly distinct from those of the representation of stimulus content.

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.

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.

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.

The Role of Location-Context Binding in Nonspatial Visual Working Memory.

Successful retrieval of an item from visual working memory (VWM) often requires an associated representation of the trial-unique context in which that item was presented. In experiment 1, fMRI of 16 male and female humans replicated a previous dissociation of the effects of manipulating memory load in comparison to the effects of manipulating context binding, by comparing VWM for one oriented line versus for three lines individuated by their location versus for three "heterogeneous" items drawn from different categories (orientation, color, and luminance): delay-period fMRI signal in frontal cortex and intraparietal sulcus (IPS) was sensitive to stimulus homogeneity rather than to memory load per se. Additionally, inspection of behavioral performance revealed a broad range of individual differences in the probability of responses to nontargets (also known as "swap errors"), and a post hoc comparison of high swap-error versus low swap-error groups generated several intriguing results: at recall, high swap-error subjects were seen to represent both the orientation and the location of the probed item less strongly, and with less differentiation from nonprobed items, and delay-period signal in IPS predicted behavioral and neural correlates of context binding at recall. In experiment 2, which was a preregistered replication, the 27 male and female humans were grouped into low and high swap-error groups by median split, and the results were broadly consistent with experiment 1. These results present a neural correlate of swap errors, and suggest that delay-period activity of the IPS may be more important for the operation of context binding than for representation per se of stimulus identity.

Dissociating Perceptual Confidence from Discrimination Accuracy Reveals No Influence of Metacognitive Awareness on Working Memory.

Visual awareness is hypothesized to be intimately related to visual working memory (WM), such that information present in WM is thought to have necessarily been represented consciously. Recent work has challenged this longstanding view by demonstrating that visual stimuli rated by observers as unseen can nevertheless be maintained over a delay period. These experiments have been criticized, however, on the basis that subjective awareness ratings may contain response bias (e.g., an observer may report no awareness when in fact they had partial awareness). We mitigated this issue by investigating WM for visual stimuli that were matched for perceptual discrimination capacity (d'), yet which varied in subjective confidence ratings (so-called relative blindsight). If the degree of initial subjective awareness of a stimulus facilitates later maintenance of that information, WM performance should improve for stimuli encoded with higher confidence. In contrast, we found that WM performance did not benefit from higher visual discrimination confidence. This relationship was observed regardless of WM load (1 or 3). Insofar as metacognitive ratings (e.g., confidence, visibility) reflect visual awareness, these results challenge a strong relationship between conscious perception and WM using a paradigm that controls for discrimination accuracy and is less subject to response bias (since confidence is manipulated within subjects). Methodologically, we replicate prior efforts to induce relative blindsight using similar stimulus displays, providing a general framework for isolating metacognitive awareness in order to examine the function of consciousness.

Consciousness and cortical responsiveness: a within-state study during non-rapid eye movement sleep.

When subjects become unconscious, there is a characteristic change in the way the cerebral cortex responds to perturbations, as can be assessed using transcranial magnetic stimulation and electroencephalography (TMS-EEG). For instance, compared to wakefulness, during non-rapid eye movement (NREM) sleep TMS elicits a larger positive-negative wave, fewer phase-locked oscillations, and an overall simpler response. However, many physiological variables also change when subjects go from wake to sleep, anesthesia, or coma. To avoid these confounding factors, we focused on NREM sleep only and measured TMS-evoked EEG responses before awakening the subjects and asking them if they had been conscious (dreaming) or not. As shown here, when subjects reported no conscious experience upon awakening, TMS evoked a larger negative deflection and a shorter phase-locked response compared to when they reported a dream. Moreover, the amplitude of the negative deflection-a hallmark of neuronal bistability according to intracranial studies-was inversely correlated with the length of the dream report (i.e., total word count). These findings suggest that variations in the level of consciousness within the same physiological state are associated with changes in the underlying bistability in cortical circuits.