Dopamine precursor depletion affects performance and confidence judgements when events are timed from an explicit, but not an implicit onset.

Dopamine affects processing of temporal information, but most previous work has tested its role in prospective tasks, where participants know in advance when the event to be timed starts. However, we are often exposed to events whose onset we do not know in advance. We can evaluate their duration after they have elapsed, but mechanisms underlying this ability are still elusive. Here we contrasted effects of acute phenylalanine and tyrosine depletion (APTD) on both forms of timing in healthy volunteers, in a within-subject, placebo-controlled design. Participants were presented with a disc moving around a circular path and asked to reproduce the duration of one full revolution and to judge their confidence in performance. The onset of the revolution was either known in advance (explicit onset) or revealed only at the end of the trial (implicit onset). We found that APTD shortened reproduced durations in the explicit onset task but had no effect on temporal performance in the implicit onset task. This dissociation is corroborated by effects of APTD on confidence judgements in the explicit task only. Our findings suggest that dopamine has a specific role in prospective encoding of temporal intervals, rather than the processing of temporal information in general.

Time processing in neurological and psychiatric conditions.

A central question in understanding cognition and pathology-related cognitive changes is how we process time. However, time processing difficulties across several neurological and psychiatric conditions remain seldom investigated. The aim of this review is to develop a unifying taxonomy of time processing, and a neuropsychological perspective on temporal difficulties. Four main temporal judgments are discussed: duration processing, simultaneity and synchrony, passage of time, and mental time travel. We present an integrated theoretical framework of timing difficulties across psychiatric and neurological conditions based on selected patient populations. This framework provides new mechanistic insights on both (a) the processes involved in each temporal judgement, and (b) temporal difficulties across pathologies. By identifying underlying transdiagnostic time-processing mechanisms, this framework opens fruitful avenues for future research.

The processing of subthreshold visual temporal order is transitory and motivation-dependent.

Processing a sequence of events is different from encoding the relative order of the elements composing the sequence. Whether order processing arises automatically from the sequential processing of events is yet unknown, however the literature suggests that order processing can occur at an automatic level when the order of stimuli is not detected consciously. In the present study, we aimed to investigate the question of automatic order processing in a difficult visual task where participants identified one among two possible target luminances. The luminance of the targets was contingent on the order of presentation of two visual cues separated by a subthreshold asynchrony. Participants' performance was compared to that in a control condition where the cues were presented synchronously. In a first experiment, participants' performance benefited from the use of subthreshold order information compared to the control condition, however this facilitation effect was transient and disappeared over the course of the experiment. In a second experiment, we investigated and confirmed the role of motivation, via a monetary incentive, on the previously observed effect. Taken together, our results suggest that the processing of temporal order of sub-threshold asynchronies is possible, although fragile and likely dependent on task requirements.

Investigating racing thoughts via ocular temporal windows: deficits in the control of automatic perceptual processes.

BACKGROUND: Racing thoughts have been found in several states of bipolar disorder (BD), but also in healthy populations with subclinical mood alterations. The evaluation of racing thoughts relies on subjective reports, and objective measures are sparse. The current study aims at finding an objective neuropsychological equivalent of racing thoughts in a mixed group of BD patients and healthy controls by using a bistable perception paradigm. METHOD: Eighty-three included participants formed three groups based on participants' levels of racing thoughts reported via the Racing and Crowded Thoughts Questionnaire. Participants reported reversals in their perception during viewing of the bistable Necker cube either spontaneously, while asked to focus on one interpretation of the cube, or while asked to accelerate perceptual reversals. The dynamics of perceptual alternations were studied both at a conscious level (with manual temporal windows reflecting perceptual reversals) and at a more automatic level (with ocular temporal windows derived from ocular fixations). RESULTS: The rate of windows was less modulated by attentional conditions in participants with racing thoughts, and most clearly so for ocular windows. The rate of ocular windows was especially high when participants with racing thoughts were asked to focus on one interpretation of the Necker cube and when they received these instructions for the first time. CONCLUSIONS: Our results indicate that in subjects with racing thoughts automatic perceptual processes escape cognitive control mechanisms. Racing thoughts may involve not only conscious thought mechanisms but also more automatic processes.

Leveraging Unique Chromosomal Microarray Probes to Accurately Detect Copy Number at the Highly Homologous 15q15.3 Deafness-Infertility Syndrome Locus.

BACKGROUND: Biallelic deletions at 15q15.3, including STRC and CATSPER2, cause autosomal recessive deafness-infertility syndrome (DIS), while biallelic deletions of STRC alone cause nonsyndromic hearing loss. These deletions are among the leading genetic causes of mild-moderate hearing loss, but their detection using chromosomal microarray (CMA) is impeded by a tandem duplication containing highly homologous pseudogenes. We sought to assess copy number variant (CNV) detection in this region by a commonly-employed CMA platform. METHODS: Twenty-two specimens with known 15q15.3 CNVs, determined by droplet digital PCR (ddPCR), were analyzed by CMA. To investigate the impact of pseudogene homology on CMA performance, a probe-level analysis of homology was performed, and log2 ratios of unique and pseudogene-homologous probes compared. RESULTS: Assessment of 15q15.3 CNVs by CMA compared to ddPCR revealed 40.9% concordance, with frequent mis-assignment of zygosity by the CMA automated calling software. Probe-level analysis of pseudogene homology suggested that probes with high homology contributed to this discordance, with significant differences in log2 ratios between unique and pseudogene-homologous CMA probes. Two clusters containing several unique probes could reliably detect CNVs involving STRC and CATSPER2, despite the noise of surrounding probes, discriminating between homozygous vs heterozygous losses and complex rearrangements. CNV detection by these probe clusters showed 100% concordance with ddPCR. CONCLUSIONS: Manual analysis of clusters containing unique CMA probes without significant pseudogene homology improves CNV detection and zygosity assignment in the highly homologous DIS region. Incorporation of this method into CMA analysis and reporting processes can improve DIS diagnosis and carrier detection.

Enhanced temporal resolution of vision in action video game players.

Video game play has been suggested to improve visual and attention processing. Nevertheless, while action video game play is highly dynamic, there is scarce research on how information is temporally discriminated at the millisecond level. This cross-sectional study investigates whether temporal discrimination at the millisecond level in vision varies across action video game players (VGPs; N = 23) and non-video game players (NVGPs; N = 23). Participants discriminated synchronous from asynchronous onsets of two visual targets in virtual reality, while their EEG and oculomotor movements were recorded. Results show an increased sensitivity to short asynchronies (11, 33 and 66 ms) in VGPs compared with NVGPs, which was especially marked at the start of the task, suggesting better temporal discrimination abilities. Pre-targets oculomotor freezing - the inhibition of small fixational saccades - was associated with correct temporal discrimination, probably revealing attentional preparation. However, this parameter did not differ between groups. EEG and reconstruction analyses suggest that the enhancement of temporal discrimination in VGPs during temporal discrimination is related to parieto-occipital processing, and a reduction of alpha-band (8-14 Hz) power and inter-trial phase coherence. Overall, the study reveals an enhanced ability in action video game players to discriminate in time visual events in close temporal proximity combined with reduced alpha-band oscillatory activities. Consequently, playing action video games is associated with an improved temporal resolution of vision.

Temporal order processing in rats depends on the training protocol.

The perception of temporal order can help infer the causal structure of the world. By investigating the perceptual signatures of audiovisual temporal order in rats, we demonstrate the importance of the protocol design for reliable order processing. Rats trained with both reinforced audiovisual trials and non-reinforced unisensory trials (two consecutive tones or flashes) learned the task surprisingly faster than rats trained with reinforced multisensory trials only. They also displayed signatures of temporal order perception, such as individual biases and sequential effects that are well described in humans, and impaired in clinical populations. We conclude that an experimental protocol requiring individuals to process all stimuli in a sequence is compulsory to ensure temporal order processing. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sensed Presence, Attenuated Psychosis, and Transliminality: At the Threshold of Consciousness.

INTRODUCTION: The experience of "sensed presence" or "felt presence" in the absence of "other" has been described as a complex multimodal experience to which meaning is given. Sensed presence (SenP) is a transdiagnostic experience that exists along a continuum that can appear during isolation, spirit quests, exposure to extreme elements, bereavement, anxiety, and psychosis. Given the prevalence and vast heterogeneity of SenP, in addition to a surprising lack of targeted research into this phenomenon, this research examined the interrelationship of SenP, attenuated psychosis symptoms (APS), and transliminality. Transliminality is composed of absorption, fantasy proneness, paranormal belief, mystical experiences, increased creativity, and hyperaesthesia. METHODS: A completely anonymous online survey of unusual experiences and mental health was distributed via social media (i.e., Twitter, Facebook, Reddit, and mass emailing lists) to recruit participants. Demographic data were analyzed using χ2 tests and one-way ANOVAs. A two-step cluster analysis was conducted to identify distinct sub-categories of transliminality followed by ANOVAs with bootstrapping at 1,000 iterations to compare SenP, increased APS, and transliminality. Pearson's bivariate correlations were conducted to determine the association between SenP, APS, and transliminality. RESULTS: Together with descriptive findings, we show distinct characteristics between clusters. T1 cluster consisted of individuals with few SenP experiences, low APS, and low transliminality. T2 consisted of individuals with a moderate prevalence of SenP, low APS, moderate transliminality, and increased overall feeling of closeness to G-d. There was no significant difference in APS between T1 and T2 or in the level of distress associated with APS. T3 individuals showed a significantly higher prevalence of SenP in all domains (frequency, distress, vividness, and total score), higher APS, and higher transliminality, compared to T1 and T2. The T3 cluster met criteria for high risk to develop psychosis. CONCLUSION: Thus, our findings demonstrate a strong association and entanglement of these experiences which suggests that the interrelatedness of transliminality/absorption and APS may serve as a potentially provocative underlying structure in the phenomenology of SenP.

Strong perceptual consequences of low-level visual predictions: A new illusion.

Predicting information is considered to be an efficient strategy to minimise processing costs by exploiting regularities in the environment, and to allow for adaptation in case of irregularities, i.e. prediction errors. How such errors impact conscious perception is unclear, especially when predictions concern elementary visual features. Here we present results from a novel experimental approach allowing us to investigate the perceptual consequences of violated low-level predictions about moving objects. Observers were presented with two squares moving towards each other with a constant speed, and reported whether they were in contact or not before they disappeared. A compelling illusion of a gap between the squares occurred when the leading edges of those squares contacted briefly. The apparent gap was larger than a physical and stable separation of 2.6 min of arc between the squares. The illusion disappeared only when the contact did not violate extrapolations of the contrast edge between the moving object and the background. The pattern of results is consistent with an early locus of the effect and cannot be explained by decisional biases, guesses, top-down, attentional or masking effects. We suggest that violations of the contrast edge extrapolation in the direction of motion have strong perceptual consequences.

Perceptual Functioning.

Perceptual disorders are not part of the diagnosis criteria for schizophrenia. Yet, a considerable amount of work has been conducted, especially on visual perception abnormalities, and there is little doubt that visual perception is altered in patients. There are several reasons why such perturbations are of interest in this pathology. They are observed during the prodromal phase of psychosis, they are related to the pathophysiology (clinical disorganization, disorders of the sense of self), and they are associated with neuronal connectivity disorders. Perturbations occur at different levels of processing and likely affect how patients interact and adapt to their surroundings. The literature has become very large, and here we try to summarize different models that have guided the exploration of perception in patients. We also illustrate several lines of research by showing how perception has been investigated and by discussing the interpretation of the results. In addition to discussing domains such as contrast sensitivity, masking, and visual grouping, we develop more recent fields like processing at the level of the retina, and the timing of perception.

Neurocognitive analyses reveal that video game players exhibit enhanced implicit temporal processing.

Winning in action video games requires to predict timed events in order to react fast enough. In these games, repeated waiting for enemies may help to develop implicit (incidental) preparation mechanisms. We compared action video game players and non-video game players in a reaction time task involving both implicit time preparations and explicit (conscious) temporal attention cues. Participants were immersed in virtual reality and instructed to respond to a visual target appearing at variable delays after a warning signal. In half of the trials, an explicit cue indicated when the target would occur after the warning signal. Behavioral, oculomotor and EEG data consistently indicate that, compared with non-video game players, video game players better prepare in time using implicit mechanisms. This sheds light on the neglected role of implicit timing and related electrophysiological mechanisms in gaming research. The results further suggest that game-based interventions may help remediate implicit timing disorders found in psychiatric populations.

The Blursday database as a resource to study subjective temporalities during COVID-19.

The COVID-19 pandemic and associated lockdowns triggered worldwide changes in the daily routines of human experience. The Blursday database provides repeated measures of subjective time and related processes from participants in nine countries tested on 14 questionnaires and 15 behavioural tasks during the COVID-19 pandemic. A total of 2,840 participants completed at least one task, and 439 participants completed all tasks in the first session. The database and all data collection tools are accessible to researchers for studying the effects of social isolation on temporal information processing, time perspective, decision-making, sleep, metacognition, attention, memory, self-perception and mindfulness. Blursday includes quantitative statistics such as sleep patterns, personality traits, psychological well-being and lockdown indices. The database provides quantitative insights on the effects of lockdown (stringency and mobility) and subjective confinement on time perception (duration, passage of time and temporal distances). Perceived isolation affects time perception, and we report an inter-individual central tendency effect in retrospective duration estimation.

The Burden and Benefits of Knowledge: Ethical Considerations Surrounding Population-Based Newborn Genome Screening for Hearing.

Recent advances in genomic sequencing technologies have expanded practitioners' utilization of genetic information in a timely and efficient manner for an accurate diagnosis. With an ever-increasing resource of genomic data from progress in the interpretation of genome sequences, clinicians face decisions about how and when genomic information should be presented to families, and at what potential expense. Presently, there is limited knowledge or experience in establishing the value of implementing genome sequencing into newborn screening. Herein we provide insight into the complexities and the burden and benefits of knowledge resulting from genome sequencing of newborns.

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss.

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.

Facing the pandemic and lockdown: an insight on mental health from a longitudinal study using diaries.

We conducted a longitudinal online study to examine attenuated psychotic symptoms (APS) over time in a sample of locked-down individuals. We used (i) questionnaires and (ii) the automatic analysis of the emotional content of narratives. Participants (N = 162) were recruited to complete an online survey 4 times between March and June 2020 (T1, T2, T3, T4). T1 completion coincided with the beginning of the lockdown, and T4 with the pandemic trough. Depression, anxiety, and stress were assessed with the DASS-42 and APS with the PQ-16. Psychosocial data such as the feeling of loneliness and social network size were also collected. The participants wrote daily narratives during the lockdown period. Anxiety and APS were the highest at T1 and decreased over time. APS and APS-associated distress were correlated with the DASS-42 at all times. APS arose acutely at the beginning of the pandemic, despite participants being socio-economically advantaged, and were related with negative emotions.

Eliciting false auditory perceptions using speech frequencies and semantic priming: a signal detection approach.

INTRODUCTION: Individuals experiencing auditory hallucinations (AH) tend to perceive voices when exposed to random noise. However, the factors driving this tendency remain unclear. The present study examined the interaction of a top-down (expectations) and bottom-up (type of noise) process to better understand the mechanisms that underlie AH. METHODS: Fifty-two healthy individuals (29 with high proneness and 23 with low proneness to AH) completed a signal detection task, in which they listened to pre-recorded sentences. The last word was either masked by noise or only noise was presented without the word. Two types of noise existed (speech-related versus speech-unrelated frequencies) and words were characterised by either high or low levels of semantic expectation. RESULTS: Participants with high proneness to AH showed a more liberal decision bias (i.e., they were more likely to report having heard a word) and poorer discrimination ability as compared to participants with low proneness to AH - but only when the word was masked by speech-related noises and the level of expectation was high. Further, the more liberal decision bias correlated negatively with the tendency to experience AH. CONCLUSION: This novel paradigm demonstrated an interaction between top-down (level of expectation) and bottom-up (type of noise) processes, supporting current theoretical models of AH.

Altered central vision and amacrine cells dysfunction as marker of hypodopaminergic activity in treated patients with schizophrenia.

BACKGROUND: Retinal dysfunction is widely documented in schizophrenia using flash (fERG) and pattern electroretinograms (PERG), but the role of dopamine transmission has seldom been explored. METHODS: We explored the role of dopamine transmission by evaluating the spatial location of retinal anomalies using multifocal ERG (mfERG) in photopic condition and the oscillatory potentials (OPs) extracted from fERG measured in scotopic condition in 29 patients with schizophrenia and 29 healthy controls. RESULTS: With the mfERG, our main results revealed reduced amplitudes in the center of the retina: P1 (p < .005) and N2 amplitudes (p < .01) in the <2° region, N1 (p < .0005) and P1 amplitudes (p < .001) in the 2-5° region and P1 amplitude (p < .05) in the 5-10° region. For OPs, our results showed a decrease in the O1 (p < .005), O2 (p < .005), O3 (p < .05) and overall O1, O2, O3 index amplitudes (p < .005) in patients with schizophrenia. CONCLUSIONS: Both the central location of retinal dysfunctions of the mfERG and OPs results could reflect a hypodopaminergic effect in patients with schizophrenia. In future studies, OPs should be considered as a measure to evaluate the hypodopaminergy in patients.