Limitations in human auditory spectral analysis at high frequencies.

Humans are adept at identifying spectral patterns, such as vowels, in different rooms, at different sound levels, or produced by different talkers. How this feat is achieved remains poorly understood. Two psychoacoustic analogs of spectral pattern recognition are spectral profile analysis and spectrotemporal ripple direction discrimination. This study tested whether pattern-recognition abilities observed previously at low frequencies are also observed at extended high frequencies. At low frequencies (center frequency ∼500 Hz), listeners were able to achieve accurate profile-analysis thresholds, consistent with prior literature. However, at extended high frequencies (center frequency ∼10 kHz), listeners' profile-analysis thresholds were either unmeasurable or could not be distinguished from performance based on overall loudness cues. A similar pattern of results was observed with spectral ripple discrimination, where performance was again considerably better at low than at high frequencies. Collectively, these results suggest a severe deficit in listeners' ability to analyze patterns of intensity across frequency in the extended high-frequency region that cannot be accounted for by cochlear frequency selectivity. One interpretation is that the auditory system is not optimized to analyze such fine-grained across-frequency profiles at extended high frequencies, as they are not typically informative for everyday sounds.

Effect of early versus late onset of partial visual loss on judgments of auditory distance.

SIGNIFICANCE: It is important to know whether early-onset vision loss and late-onset vision loss are associated with differences in the estimation of distances of sound sources within the environment. People with vision loss rely heavily on auditory cues for path planning, safe navigation, avoiding collisions, and activities of daily living. PURPOSE: Loss of vision can lead to substantial changes in auditory abilities. It is unclear whether differences in sound distance estimation exist in people with early-onset partial vision loss, late-onset partial vision loss, and normal vision. We investigated distance estimates for a range of sound sources and auditory environments in groups of participants with early- or late-onset partial visual loss and sighted controls. METHODS: Fifty-two participants heard static sounds with virtual distances ranging from 1.2 to 13.8 m within a simulated room. The room simulated either anechoic (no echoes) or reverberant environments. Stimuli were speech, music, or noise. Single sounds were presented, and participants reported the estimated distance of the sound source. Each participant took part in 480 trials. RESULTS: Analysis of variance showed significant main effects of visual status (p<0.05) environment (reverberant vs. anechoic, p<0.05) and also of the stimulus (p<0.05). Significant differences (p<0.05) were shown in the estimation of distances of sound sources between early-onset visually impaired participants and sighted controls for closer distances for all conditions except the anechoic speech condition and at middle distances for all conditions except the reverberant speech and music conditions. Late-onset visually impaired participants and sighted controls showed similar performance (p>0.05). CONCLUSIONS: The findings suggest that early-onset partial vision loss results in significant changes in judged auditory distance in different environments, especially for close and middle distances. Late-onset partial visual loss has less of an impact on the ability to estimate the distance of sound sources. The findings are consistent with a theoretical framework, the perceptual restructuring hypothesis, which was recently proposed to account for the effects of vision loss on audition.

Where was this thing again? Evaluating methods to indicate remembered object positions in virtual reality.

A current focus in sensorimotor research is the study of human perception and action in increasingly naturalistic tasks and visual environments. This is further enabled by the recent commercial success of virtual reality (VR) technology, which allows for highly realistic but well-controlled three-dimensional (3D) scenes. VR enables a multitude of different ways to interact with virtual objects, but only rarely are such interaction techniques evaluated and compared before being selected for a sensorimotor experiment. Here, we compare different response techniques for a memory-guided action task, in which participants indicated the position of a previously seen 3D object in a VR scene: pointing, using a virtual laser pointer of short or unlimited length, and placing, either the target object itself or a generic reference cube. Response techniques differed in availability of 3D object cues and requirement to physically move to the remembered object position by walking. Object placement was the most accurate but slowest due to repeated repositioning. When placing objects, participants tended to match the original object's orientation. In contrast, the laser pointer was fastest but least accurate, with the short pointer showing a good speed-accuracy compromise. Our findings can help researchers in selecting appropriate methods when studying naturalistic visuomotor behavior in virtual environments.

Estrogen receptor beta signaling enhances extinction memory recall for heroin-conditioned cues in a sex- and region-specific manner.

Return to use, or relapse, is a major challenge in the treatment of opioid use disorder (OUD). Relapse can be precipitated by several factors, including exposure to drug-conditioned cues. Identifying successful treatments to mitigate cue-induced relapse has been challenging, perhaps due to extinction memory recall (EMR) deficits. Previously, inhibition of estradiol (E2) signaling in the basolateral amygdala (BLA) impaired heroin-cue EMR. This effect was recapitulated by antagonism of BLA estrogen receptors (ER) in a sex-specific manner such that blocking ERα in males, but ERß in females, impaired EMR. However, it is unclear whether increased E2 signaling, in the BLA or systemically, enhances heroin-cue EMR. We hypothesized that ERß agonism would enhance heroin-cue EMR in a sex- and region-specific manner. To determine the capacity of E2 signaling to improve EMR, we pharmacologically manipulated ERß across several translationally designed experiments. First, male and female rats acquired heroin or sucrose self-administration. Next, during a cued extinction session, we administered diarylpropionitrile (DPN, an ERß agonist) and tested anxiety-like behavior on an open field. Subsequently, we assessed EMR in a cue-induced reinstatement test and, finally, measured ERß expression in several brain regions. Across all experiments, females took more heroin and sucrose than males and had greater responses during heroin-cued extinction. Administration of DPN in the BLA enhanced EMR in females only, driven by ERß's impacts on memory consolidation. Interestingly, however, systemic DPN administration improved EMR for heroin cues in both sexes across several different tests, but did not impact sucrose-cue EMR. Immunohistochemical analysis of ERß expression across several different brain regions showed that females only had greater expression of ERß in the basal nucleus of the BLA. Here, in several preclinical experiments, we demonstrated that ERß agonism enhances heroin-cue EMR and has potential utility in combatting cue-induced relapse.

Threat-induced prosocial behavior: enhanced exogenous attention to protect others from harm.

As social animals, humans tend to voluntarily engage in pro-social behavior to prevent harm to others. However, to what extent prosocial behavior can be reflected at the level of less voluntary cognitive processes remains unclear. Here, we examined how threat to others modulates exogenous attention. Fifty-four participants performed an exogenous spatial cueing task where the participant's performance determined whether electric shocks would be delivered either to themselves or to their anonymous co-participant. Threat of shock to the co-participant elicited orienting and reorienting responses that were faster than in the safe condition and did not differ from performance when participants avoided shocks to themselves. This attentional improvement was not due to speed-accuracy trade off and was associated with arousal, i.e., increased pupil dilation in both threat conditions. Together, these findings suggest that pro-social behavior triggers automatic attentional processes which may be relevant for providing immediate help without relying on reflexive processes.

Attenuation and distortion components of age-related hearing loss: Contributions to recognizing temporal-envelope filtered speech in modulated noise.

Older adults with hearing loss may experience difficulty recognizing speech in noise due to factors related to attenuation (e.g., reduced audibility and sensation levels, SLs) and distortion (e.g., reduced temporal fine structure, TFS, processing). Furthermore, speech recognition may improve when the amplitude modulation spectrum of the speech and masker are non-overlapping. The current study investigated this by filtering the amplitude modulation spectrum into different modulation rates for speech and speech-modulated noise. The modulation depth of the noise was manipulated to vary the SL of speech glimpses. Younger adults with normal hearing and older adults with normal or impaired hearing listened to natural speech or speech vocoded to degrade TFS cues. Control groups of younger adults were tested on all conditions with spectrally shaped speech and threshold matching noise, which reduced audibility to match that of the older hearing-impaired group. All groups benefitted from increased masker modulation depth and preservation of syllabic-rate speech modulations. Older adults with hearing loss had reduced speech recognition across all conditions. This was explained by factors related to attenuation, due to reduced SLs, and distortion, due to reduced TFS processing, which resulted in poorer auditory processing of speech cues during the dips of the masker.

The Neural Representation of Binaural Sound Localization Cues Across Different Subregions of the Chicken's Inferior Colliculus.

The sound localization behavior of the nocturnally hunting barn owl and its underlying neural computations is a textbook example of neuroethology. Differences in sound timing and level at the two ears are integrated in a series of well-characterized steps, from brainstem to inferior colliculus (IC), resulting in a topographical neural representation of auditory space. It remains an important question of brain evolution: How is this specialized case derived from a more plesiomorphic pattern? The present study is the first to match physiology and anatomical subregions in the non-owl avian IC. Single-unit responses in the chicken IC were tested for selectivity to different frequencies and to the binaural difference cues. Their anatomical origin was reconstructed with the help of electrolytic lesions and immunohistochemical identification of different subregions of the IC, based on previous characterizations in owl and chicken. In contrast to barn owl, there was no distinct differentiation of responses in the different subregions. We found neural topographies for both binaural cues but no evidence for a coherent representation of auditory space. The results are consistent with previous work in pigeon IC and chicken higher-order midbrain and suggest a plesiomorphic condition of multisensory integration in the midbrain that is dominated by lateral panoramic vision.

Acoustic cues of keyboard mechanics enable auditory localization of upright piano tones.

Piano tone localization at the performer's listening point is a multisensory process involving audition, vision, and upper limb proprioception. The consequent representation of the auditory scene, especially in experienced pianists, is likely also influenced by their memory about the instrument keyboard. Disambiguating such components is not obvious, and first requires an analysis of the acoustic tone localization process to assess the role of auditory feedback in forming this scene. This analysis is complicated by the acoustic behavior of the piano, which does not guarantee the activation of the auditory precedence effect during a tone attack, nor can it provide robust interaural differences during the subsequent free evolution of the sound. In a tone localization task using a Disklavier upright piano (which can be operated remotely and configured to have its hammers hit a damper instead of producing a tone), twenty-three expert musicians, including pianists, successfully recognized the angular position of seven evenly distributed notes across the keyboard. The experiment involved listening to either full piano tones or just the key mechanical noise, with no additional feedback from other senses. This result suggests that the key mechanical noise alone activated the localization process without support from vision and/or limb proprioception. Since the same noise is present in the onset of the full tones, the key mechanics of our piano created a touch precursor in such tones that may be responsible of their correct angular localization by means of the auditory precedence effect. However, the significance of pitch cues arriving at a listener after the touch precursor was not measured when full tones were presented. As these cues characterize a note and, hence, the corresponding key position comprehensively, an open question remains regarding the contribution of pianists' spatial memory of the instrument keyboard to tone localization.

Actual and imagined music-cued gait training for people with multiple sclerosis: a multicentre qualitative study.

OBJECTIVES: To explore the experiences and acceptability of music-cued motor imagery (MCMI), music-cued gait training (MCGT), and combined MCMI and MCGT (MCMI-MCGT) in people with multiple sclerosis (pwMS). We also aimed to explore participants' self-rated health status postintervention and gather recommendations for further programme development. DESIGN: Qualitative study alongside the double-blind randomised controlled real and imagined gait training with music-cueing (RIGMUC) multicentre trial of MCMI, MCGT and MCMI-MCGT. SETTING: PwMS recruited for the RIGMUC trial from Departments of Neurology at Medical Universities of Innsbruck and Graz and Clinic for Rehabilitation Muenster, Austria. PARTICIPANTS: All 132 pwMS with mild to moderate disability randomised into the trial were included in the analysis. METHODS: Participants practised home-based MCMI, MCGT or MCMI-MCGT for 30 min, 4×/week, for 4 weeks. Three trained researchers conducted weekly semistructured telephone interviews during the intervention period, supporting adherence, addressing problems, sharing experiences and assessing intervention acceptability. Follow-up interviews at 4-week postintervention aimed to understand participants' self-rated changes in walking, fatigue and overall health compared with their prestudy condition. Investigator triangulation was employed among the researchers to enhance trustworthiness and credibility. RESULTS: Using thematic analysis, we identified five themes: (1) empowerment, (2) remaining in sync, (3) interconnection between imagined and actual walking, (4) sustaining focus and (5) real-world transfer. Participants appreciated and found the imagined and actual MCGT innovative. Problems included concentration issues, early fatigue in advanced disability and difficulty synchronising with music cues. Positive changes in walking, fatigue and overall health postinterventions were reported offering valuable insights for programme development. CONCLUSIONS: A participatory study to codevelop a music-cued exercise programme for pwMS seems appropriate as participants appreciated the innovation and effectiveness of both imagined and actual MCGT. Future studies should also investigate pwMS' potential and limitations in enhancing their MCMI abilities with intensive therapist-supported practice. TRIAL REGISTRATION NUMBER: DRKS00023978.

The combination operation of grouping and ensemble coding for structured biological motion crowds in working memory.

Massive studies have explored biological motion (BM) crowds processing for their remarkable social significance, primarily focused on uniformly distributed ones. However, real-world BM crowds often exhibit hierarchical structures rather than uniform arrangements. How such structured BM crowds are processed remains a subject of inquiry. This study investigates the representation of structured BM crowds in working memory (WM), recognizing the pivotal role WM plays in our social interactions involving BM. We propose the group-based ensemble hypothesis and test it through a member identification task. Participants were required to discern whether a presented BM belonged to a prior memory display of eight BM, each with distinct walking directions. Drawing on prominent Gestalt principles as organizational cues, we constructed structured groups within BM crowds by applying proximity and similarity cues in Experiments 1 and 2, respectively. In Experiment 3, we deliberately weakened the visibility of stimuli structures by increasing the similarity between subsets, probing the robustness of results. Consistently, our findings indicate that BM aligned with the mean direction of the subsets was more likely to be recognized as part of the memory stimuli. This suggests that WM inherently organizes structured BM crowds into separate ensembles based on organizational cues. In essence, our results illuminate the simultaneous operation of grouping and ensemble encoding mechanisms for BM crowds within WM.

Statistical learning shapes pain perception and prediction independently of external cues.

The placebo and nocebo effects highlight the importance of expectations in modulating pain perception, but in everyday life we don't need an external source of information to form expectations about pain. The brain can learn to predict pain in a more fundamental way, simply by experiencing fluctuating, non-random streams of noxious inputs, and extracting their temporal regularities. This process is called statistical learning. Here, we address a key open question: does statistical learning modulate pain perception? We asked 27 participants to both rate and predict pain intensity levels in sequences of fluctuating heat pain. Using a computational approach, we show that probabilistic expectations and confidence were used to weigh pain perception and prediction. As such, this study goes beyond well-established conditioning paradigms associating non-pain cues with pain outcomes, and shows that statistical learning itself shapes pain experience. This finding opens a new path of research into the brain mechanisms of pain regulation, with relevance to chronic pain where it may be dysfunctional.

Human navigation strategies and their errors result from dynamic interactions of spatial uncertainties.

Goal-directed navigation requires continuously integrating uncertain self-motion and landmark cues into an internal sense of location and direction, concurrently planning future paths, and sequentially executing motor actions. Here, we provide a unified account of these processes with a computational model of probabilistic path planning in the framework of optimal feedback control under uncertainty. This model gives rise to diverse human navigational strategies previously believed to be distinct behaviors and predicts quantitatively both the errors and the variability of navigation across numerous experiments. This furthermore explains how sequential egocentric landmark observations form an uncertain allocentric cognitive map, how this internal map is used both in route planning and during execution of movements, and reconciles seemingly contradictory results about cue-integration behavior in navigation. Taken together, the present work provides a parsimonious explanation of how patterns of human goal-directed navigation behavior arise from the continuous and dynamic interactions of spatial uncertainties in perception, cognition, and action.

Keystrokes: A practical exploration of semantic drift in timed word association tasks.

This study investigates the phenomena of semantic drift through the lenses of language and situated simulation (LASS) and the word frequency effect (WFE) within a timed word association task. Our primary objectives were to determine whether semantic drift can be identified over the short time (25 seconds) of a free word association task (a predicted corollary of LASS), and whether more frequent terms are generated earlier in the process (as expected due to the WFE). Respondents were provided with five cue words (tree, dog, quality, plastic and love), and asked to write as many associations as they could. We hypothesized that terms generated later in the task (fourth time quartile, the last 19-25 seconds) would be semantically more distant (cosine similarity) from the cue word than those generated earlier (first quartile, the first 1-7 seconds), indicating semantic drift. Additionally, we explored the WFE by hypothesizing that earlier generated words would be more frequent and less diverse. Utilizing a dataset matched with GloVe 300B word embeddings, BERT and WordNet synsets, we analysed semantic distances among 1569 unique term pairs for all cue words across time. Our results supported the presence of semantic drift, with significant evidence of within-participant, semantic drift from the first to fourth time (LASS) and frequency (WFE) quartiles. In terms of the WFE, we observed a notable decrease in the diversity of terms generated earlier in the task, while more unique terms (greater diversity and relative uniqueness) were generated in the 4th time quartile, aligning with our hypothesis that more frequently used words dominate early stages of a word association task. We also found that the size of effects varied substantially across cues, suggesting that some cues might invoke stronger and more idiosyncratic situated simulations. Theoretically, our study contributes to the understanding of LASS and the WFE. It suggests that semantic drift might serve as a scalable indicator of the invocation of language versus simulation systems in LASS and might also be used to explore cognition within word association tasks more generally. The findings also add a temporal and relational dimension to the WFE. Practically, our research highlights the utility of word association tasks in understanding semantic drift and the diffusion of word usage over a sub-minute task, arguably the shortest practically feasible timeframe, offering a scalable method to explore group and individual changes in semantic relationships, whether via the targeted diffusion of influence in a marketing campaign, or seeking to understand differences in cognition more generally. Possible practical uses and opportunities for future research are discussed.

Perceptual error based on Bayesian cue combination drives implicit motor adaptation.

The sensorimotor system can recalibrate itself without our conscious awareness, a type of procedural learning whose computational mechanism remains undefined. Recent findings on implicit motor adaptation, such as over-learning from small perturbations and fast saturation for increasing perturbation size, challenge existing theories based on sensory errors. We argue that perceptual error, arising from the optimal combination of movement-related cues, is the primary driver of implicit adaptation. Central to our theory is the increasing sensory uncertainty of visual cues with increasing perturbations, which was validated through perceptual psychophysics (Experiment 1). Our theory predicts the learning dynamics of implicit adaptation across a spectrum of perturbation sizes on a trial-by-trial basis (Experiment 2). It explains proprioception changes and their relation to visual perturbation (Experiment 3). By modulating visual uncertainty in perturbation, we induced unique adaptation responses in line with our model predictions (Experiment 4). Overall, our perceptual error framework outperforms existing models based on sensory errors, suggesting that perceptual error in locating one's effector, supported by Bayesian cue integration, underpins the sensorimotor system's implicit adaptation.

Investigating the impact of schizophrenia traits on attention: the role of the theta band in a modified Posner cueing paradigm.

Joint attention is an indispensable tool for daily communication. Abnormalities in joint attention may be a key reason underlying social impairment in schizophrenia spectrum disorders. In this study, we aimed to explore the attentional orientation mechanism related to schizotypal traits in a social situation. Here, we employed a Posner cueing paradigm with social attentional cues. Subjects needed to detect the location of a target that is cued by gaze and head orientation. The power in the theta frequency band was used to examine the attentional process in the schizophrenia spectrum. There were four main findings. First, a significant association was found between schizotypal traits and attention orientation in response to invalid gaze cues. Second, individuals with schizotypal traits exhibited significant activation of neural oscillations and synchrony in the theta band, which correlated with their schizotypal tendencies. Third, neural oscillations and synchrony demonstrated a synergistic effect during social tasks, particularly when processing gaze cues. Finally, the relationship between schizotypal traits and attention orientation was mediated by neural oscillations and synchrony in the theta frequency band. These findings deepen our understanding of the impact of theta activity in schizotypal traits on joint attention and offer new insights for future intervention strategies.

Evaluating the Feasibility of Visual Imagery for an EEG-Based Brain-Computer Interface.

Visual imagery, or the mental simulation of visual information from memory, could serve as an effective control paradigm for a brain-computer interface (BCI) due to its ability to directly convey the user's intention with many natural ways of envisioning an intended action. However, multiple initial investigations into using visual imagery as a BCI control strategies have been unable to fully evaluate the capabilities of true spontaneous visual mental imagery. One major limitation in these prior works is that the target image is typically displayed immediately preceding the imagery period. This paradigm does not capture spontaneous mental imagery as would be necessary in an actual BCI application but something more akin to short-term retention in visual working memory. Results from the present study show that short-term visual imagery following the presentation of a specific target image provides a stronger, more easily classifiable neural signature in EEG than spontaneous visual imagery from long-term memory following an auditory cue for the image. We also show that short-term visual imagery and visual perception share commonalities in the most predictive electrodes and spectral features. However, visual imagery received greater influence from frontal electrodes whereas perception was mostly confined to occipital electrodes. This suggests that visual perception is primarily driven by sensory information whereas visual imagery has greater contributions from areas associated with memory and attention. This work provides the first direct comparison of short-term and long-term visual imagery tasks and provides greater insight into the feasibility of using visual imagery as a BCI control strategy.

Aberrant social reward dynamics in individuals with melancholic major depressive disorder: An ERP study.

BACKGROUND: Compared to monetary rewards, depressive symptoms are specifically associated with abnormal social reward processing. In addition, individuals with melancholic depression may exhibit more significant reward-related impairments. However, there is still limited understanding of the specific alterations in social reward processing in individuals with melancholic depression. METHODS: Forty patients with melancholic major depressive disorder (MDD), forty patients with non-melancholic MDD, and fifty healthy controls participated in the social incentive delay (SID) tasks with event-related potential (ERP) recording. We measured one anticipatory ERP(cue-N2) and two consummatory ERPs (FRN, fb-P3). Furthermore, we examined correlation between FRN and consummatory anhedonia. RESULTS: Melancholic MDD patients showed less anticipation of social rewards (cue-N2). Concurrently, melancholic individuals demonstrated diminished reception of social rewards, as evidenced by reduced amplitudes of FRN. Notably, the group x condition interaction effect on FRN was significant (F (2, 127) = 4.15, p = 0.018, η2ρ = 0.061). Melancholic MDD patients had similar neural responses to both gain and neutral feedback (blunted reward positivity), whereas non-melancholic MDD patients (t (39) = 3.09, p = 0.004) and healthy participants (t (49) = 5.25, p < 0.001) had smaller FRN amplitudes when receiving gain feedback relative to neutral feedback. In addition, there was a significant correlation between FRN and consummatory anhedonia in MDD patients. CONCLUSIONS: Our findings indicated that individuals with melancholic MDD exhibit attenuated neural responses to both anticipated and consumed social rewards. This suggests that aberrant processing of social rewards could serve as a potential biomarker for melancholic MDD.

Study on the efficiency of virtual reality in the treatment of alcohol use disorder: study protocol for a randomized controlled trial : E-Reva.

CONTEXT: According to the World Health Organization, alcohol is a major global public health problem, leading to a significant increase in illness and death. To treat alcohol use disorders, new therapeutic tools are being promoted, among which virtual reality (VR) shows promise. Previous research has demonstrated the efficacy of VR in reducing alcohol cravings in patients, but there is a lack of data on its effectiveness in maintaining abstinence or reducing consumption in recently abstinent individuals. The E-Reva study aims to compare the efficacy of a treatment strategy combining virtual reality cue exposure therapy (VR-CET) and cognitive behavioral therapy (CBT) with conventional CBT in reducing alcohol consumption and craving in patients with alcohol use disorder (AUD). In addition to this primary objective, the study will compare the effects of VR-CET combined with CBT on anxiety, depression, rumination, and feelings of self-efficacy versus conventional CBT. METHODS: This prospective randomized controlled trial will be conducted over 8 months in four addiction departments in France. It includes two parallel groups: i) the VR-CET + CBT group, and ii) the CBT-only group, which serves as a control group. Participants will be recruited by the investigating doctor in the addiction centers. The sample will consist of 156 patients diagnosed with AUD and abstinent for at least 15 days. Both treatment groups will participate in four group CBT sessions followed by four individual sessions: i) the VR-CET group will be exposed to virtual environments associated with alcohol-related stimuli, ii) the CBT-only group will receive traditional CBT sessions. After completion of the 8 sessions, patients will be followed up for 6 months. The primary outcome is the cumulative number of standard drinks consumed at 8 months, assessed using the TLFB method. DISCUSSION: Despite the promise of VR-CET to reduce the desire to drink, the effect on alcohol consumption remains uncertain in the existing literature. Our protocol aims to address the limitations of previous research by increasing sample size, targeting consumption reduction, and incorporating neutral environments. E-Reva aims to enrich the literature on the use of VR in the treatment of AUD and open new perspectives for future interventions. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06104176, Registered 2023/11/13 ( https://clinicaltrials.gov/study/NCT06104176?id=NCT06104176&rank=1 ). N° IDRCB: 2022-A02797-36. Protocol version 1.0, 12/05/2023.

Virtual reality cue-exposure therapy in reducing cocaine craving: the Promoting Innovative COgnitive behavioral therapy for Cocaine use disorder (PICOC) study protocol for a randomized controlled trial.

BACKGROUND: Cocaine craving is a central symptom of cocaine use disorders (CUD). Virtual reality cue-exposure therapy for craving (VRCET) allows more immersive, realistic, and controllable exposure than traditional non-VR cue-exposure therapy (CET), whose efficacy is limited in treating substance use disorders. The purpose of this study is to evaluate the efficacy and acceptability of VRCET, as a stand-alone and add-on intervention (i.e., combined with cognitive therapy), compared to a picture-based CET (PCET), in reducing self-reported cocaine craving in inpatients hospitalized for CUD. METHODS: Fifty-four inpatients hospitalized for CUD will be randomized in one of two intensive 3-week treatment arms: 10 meetings/2-week treatment of VRCET plus 5 meetings/1-week treatment of memory-focused cognitive therapy (MFCT; experimental arm), or 15 meetings/3-week treatment of PCET (active control arm). The Craving Experience Questionnaire (CEQ - F & S) will be used to assess the primary outcome, i.e., the post-treatment decrease of self-reported cocaine craving frequency (within the past 2 weeks) and intensity scores (in VR exposure to cocaine cues). Secondary endpoints include urinary, physiological, and self-reported cocaine use-related measures. Assessments are scheduled at pretreatment, after 2 weeks of treatment (i.e., VRCET vs. PCET), post-treatment (3 weeks, i.e., VRCET + MFCT vs. PCET), and at 1-month follow-up. Acceptability will be evaluated via (i) the Spatial Presence for Immersive Environments - Cybersickness along VRCET and (ii) the Client Satisfaction Questionnaires after 2 weeks of treatment and post-treatment. DISCUSSION: This study will be the first to evaluate the acceptability and efficacy of VRCET for CUD, as a psychotherapeutic add-on, to reduce both cocaine craving frequency and intensity. Additionally, this study will provide evidence about the specific interest of VRCET, compared to a non-VR-based CET, as a cue reactivity and exposure paradigm for treating substance use disorders. TRIAL REGISTRATION: NCT05833529 [clinicaltrials.gov]. Prospectively registered on April 17, 2023.

Ocular working memory signals are flexible to behavioral priority and subjective imagery strength.

The pupillary light response was long considered a brainstem reflex, outside of cognitive influence. However, newer findings indicate that pupil dilation (and eye movements) can reflect content held "in mind" with working memory (WM). These findings may reshape understanding of ocular and WM mechanisms, but it is unclear whether the signals are artifactual or functional to WM. Here, we ask whether peripheral and oculomotor WM signals are sensitive to the task-relevance or "attentional state" of WM content. During eye-tracking, human participants saw both dark and bright WM stimuli, then were retroactively cued to the item that would most likely be tested. Critically, we manipulated the attentional priority among items by varying the cue reliability across blocks. We confirmed previous findings that remembering darker items is associated with larger pupils (vs. brighter), and that gaze is biased toward cued item locations. Moreover, we discovered that pupil and eye movement responses were influenced differently by WM item relevance. Feature-specific pupillary effects emerged only for highly prioritized WM items but were eliminated when cues were less reliable, and pupil effects also increased with self-reported visual imagery strength. Conversely, gaze position consistently veered toward the cued item location, regardless of cue reliability. However, biased microsaccades occurred at a higher frequency when cues were more reliable, though only during a limited post-cue time window. Therefore, peripheral sensorimotor processing is sensitive to the task-relevance or functional state of internal WM content, but pupillary and eye movement WM signals show distinct profiles. These results highlight a potential role for early visual processing in maintaining multiple WM content dimensions.NEW & NOTEWORTHY Here, we found that working memory (WM)-driven ocular inflections-feature-specific pupillary and saccadic biases-were muted for memory items that were less behaviorally relevant. This work illustrates that functionally informative goal signals may extend as early as the sensorimotor periphery, that pupil size may be under more fine-grained control than originally thought, and that ocular signals carry multiple dimensions of cognitively relevant information.