Effects of Auditory and Visual White Noise on Oculomotor Inhibition in Children With Attention-Deficit/Hyperactivity Disorder: Protocol for a Crossover Study.

BACKGROUND: In attention-deficit/hyperactivity disorder (ADHD), poor inhibitory control is one of the main characteristics, with oculomotor inhibition impairments being considered a potential biomarker of the disorder. While auditory white noise has demonstrated the ability to enhance working memory in this group, visual white noise is still unexplored and so are the effects of both types of white noise stimulation on oculomotor inhibition. OBJECTIVE: This crossover study aims to explore the impact of auditory and visual white noise on oculomotor inhibition in children with ADHD and typically developing (TD) children. The study will investigate the impact of different noise levels (25% and 50% visual, 78 dB auditory), and performance will be evaluated both with and without noise stimulation. We hypothesize that exposure to white noise will improve performance in children with ADHD and impair the performance for TD children. METHODS: Memory-guided saccades and prolonged fixations, known for their sensitivity in detecting oculomotor disinhibition in ADHD, will be used to assess performance. Children diagnosed with ADHD, withdrawing from medication for 24 hours, and TD children without psychiatric disorders were recruited for the study. RESULTS: Data collection was initiated in October 2023 and ended in February 2024. A total of 97 participants were enrolled, and the first results are expected between September and November 2024. CONCLUSIONS: This study will examine whether cross-modal sensory stimulation can enhance executive function, specifically eye movement control, in children with ADHD. In addition, the study will explore potential differences between auditory and visual noise effects in both groups. Our goal is to identify implications for understanding how noise can be used to improve cognitive performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT06057441; https://clinicaltrials.gov/study/NCT06057441. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56388.

Active head movements contribute to spatial updating across gaze shifts.

Keeping visual space constant across movements of the eye and head is a not yet fully understood feature of perception. To understand the mechanisms that update the internal coordinates of space, research has mostly focused on eye movements. However, in natural vision, head movements are an integral part of gaze shifts that enlarge the field of vision. Here, we directly compared spatial updating for eye and head movements. In a virtual reality environment, participants had to localize the position of a stimulus across the execution of a gaze shift. We found that performing head movements increased the accuracy of spatial localization. By manipulating the speed of the visual scene displacement that a head movement produced, we found that spatial updating takes into account the sensorimotor contingencies of vision. When we presented gaze-contingent visual motion, subjects overestimated the position of stimuli presented across gaze shifts. The overestimation decreased if subjects were allowed to perform eye movements during the head movement. We conclude that head movements contribute to stabilizing visual space across gaze shifts and that contingencies of head movements, rather than being cancelled, facilitate the updating.

The activities of daily living partially mediate the relationship between rapid eye movement sleep behavior disorder and depressive symptoms in Parkinson's disease.

Objective: A longitudinal study was conducted to investigate whether rapid eye movement sleep behavior disorder affect depression in patients with Parkinson's disease through activities of daily living. Methods: A total of 387 Parkinson's disease patients' six-year follow-up data (one follow-up per year) were obtained from the Parkinson's Progression Markers Initiative. To allow causal effects to manifest, this study increased the lag period and divided the data from the six follow-ups into two groups: wave 1 (wave refers to time points), wave 3, and wave 5 as one group, and wave 2, wave 4, and wave6 as the other group. The time interval between two time points in each group was two years. To comprehensively and deeply analyze the dynamic relationships between variables, accurately infer causal relationships, control for individual differences, and detect the stability of these relationships, this study constructed the fixed effects cross-lagged panel model (CLPM), the random effects CLPM (RE-CLPM) model, and the Equating CLPM and Equating RE-CLPM models with applied restriction conditions. Additionally, a reverse path was added to verify the reverse prediction effect. The most suitable data analysis model was selected to explore the relationships between the study variables. Furthermore, the longitudinal mediating effect of daily living activities between rapid eye movement sleep behavior disorder and depression was investigated. Results: In the models, Equating cross-lagged panel model was the best. The lag effect was positive and significant. In wave 1, 3, 5, activities of daily living mediated 11.82% on the path from rapid eye movement sleep behavior disorder to depression; in wave 2, 4, 6, it mediated 13.13%. Therefore, attention should be paid to the treatment of activities of daily living. Conclusion: Longitudinal changes in activities of daily living have indirect effects on the relationship between rapid eye movement sleep behavior disorder and depression, which highlights the importance of changes in activities of daily living ability in Parkinson's disease patients with rapid eye movement sleep behavior disorder.

The correlation between rapid eye movement sleep behavior disorder and the progress of Parkinson's disease: a systematic review and meta-analysis.

Background: This meta-analysis was conducted to evaluate potential differences in symptoms between PD patients with or without RBD. Methods: A systematic search was conducted in PubMed, Cochrane, Embase, and Web of Science databases (as of August 16, 2023), to identify relevant studies on PD and RBD. Statistical analysis was performed using Stata 15.0. Continuous variables were analyzed using the standardized mean difference (SMD) and 95% confidence interval (95% CI), while count data were assessed using the odds ratio (OR) and 95% CI as statistical effect sizes. Heterogeneity among all included studies was tested; for studies with low heterogeneity (I2 < 50%), a fixed-effects model was used to calculate statistical results. For studies with relatively high heterogeneity (I2 > 50%), a random-effects model was applied, followed by sensitivity and subgroup analyses to identify sources of heterogeneity. Results: A total of 5,672 subjects were involved in this study. Compared to the NRBD group, the UPDRS-III score in the RBD group was significantly higher (SMD = 0.20, 95% CI: [0.11, 0.29], P < 0.001), and the Hoehn-Yahr score in the RBD group was also significantly higher (SMD = 0.29, 95% CI: [0.03, 0.55], P < 0.001). Patients with PD in the RBD group had more severe cognitive impairments than those in the NRBD group (SMD = -0.30, 95% CI: [-0.48, -0.11], P < 0.001). The incidence of hallucination in PD patients in the RBD group was 3.0 times that of the NRBD group (OR = 3.0, 95% CI: [2.15, 4.20], P = 0.110). PD patients in the RBD group also experienced more severe anxiety symptoms (SMD = 0.13, 95% CI: [-0.26, 0.51], P < 0.001), had higher scores in depression scales (SMD = 0.22, 95% CI: [0.02, 0.43], P < 0.001), and higher scores in sleep disorder scales than those in NRBD group (SMD = 0.10, 95% CI: [-0.11, 0.31], P < 0.001). Conclusion: Results show PD patients with co-occurring RBD have more severe motor and non-motor symptoms likely due to overlapping affected regions in RBD and PD-related pathology, plus broader neurodegeneration seen in PD patients with RBD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42023476331.

Oculomotor Patterns in Children with Poor Reading Abilities Measured Using the Development Eye Movement Test.

Objectives: The main purpose of this work was to clinically assess the oculomotricity of one hundred Mexican children with poor reading skills but without any specific learning disorder. Methods: The D.E.M. psychometric test was used. Sex and age analyses of the ratio, type, horizontal and vertical performance, and errors were carried out. Results: Our data suggest that 84% of poor readers exhibit oculomotor difficulties. Sex did not significantly influence the results (p > 0.05), whereas age was associated with the horizontal (p = 0.04) and vertical (p = 0.29) performance, as well as the number of errors (p = 0.001). Omissions were the most prevalent error type. Conclusions: This research gives insights into the role of oculomotricity in children with poor reading skills. Our results suggest that oculomotor performance should be included in the evaluation protocol to assess poor readers to identify any influence of the visual system.

Gaze cueing improves pattern recognition of histology learners.

Experts perceive and evaluate domain-specific visual information with high accuracy. In doing so, they exhibit eye movements referred to as "expert gaze" to rapidly focus on task-relevant areas. Using eye tracking, it is possible to record these implicit gaze patterns and present them to histology novice learners during training. This article presents a comprehensive evaluation of such expert gaze cueing on pattern recognition of medical students in histology. For this purpose, 53 students were randomized into two groups over eight histology sessions. The control group was presented with an instructional histology video featuring voice commentary. The gaze cueing group was presented the same video, but with an additional overlay of a live recording of the expert's eye movements. Afterward, students' pattern recognition was assessed through 20 image-based tasks (5 retention, 15 transfer) and their cognitive load with the Paas scale. Results showed that gaze cueing significantly outperformed the control group (p = 0.007; d = 0.40). This effect was evident for both, retention (p = 0.003) and transfer tasks (p = 0.046), and generalized across different histological contexts. The cognitive load was similar in both groups. In conclusion, gaze cueing helps histology novice learners to develop their pattern recognition skills, offering a promising method for histology education. Histology educators could benefit from this instructional strategy to provide new forms of attentional guidance to learners in visually complex learning environments.

Rapid Eye Movements during REM Sleep Differentiate PSP from Parkinson's Disease.

BACKGROUND: Little is known about the characteristics and occurrence frequencies of rapid eye movements (REMs) during REM sleep in movement disorders. OBJECTIVES: The aim of this study was to detect and characterize REMs during polysomnographically defined REM sleep as recorded by electro-oculography (EOG) in 12 patients with progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD) and 12 healthy controls. METHODS: Using a modified EOG montage, we developed an algorithm that automatically detects and characterizes REMs during REM sleep based on their presumptive saccadic kinematics. RESULTS: Compared to PD and healthy controls, REM densities and REM peak velocities were significantly reduced in PSP. These effects were most pronounced in vertical REMs. CONCLUSION: Ocular motor dysfunction, one of the cardinal features of PSP, seems to be equally at play during REM sleep and wakefulness. For future studies, we provide a novel tool for the unbiased analysis of REMs during REM sleep in movement disorders.

Proprioceptive intervention improves reading performance in developmental dyslexia: An eye-tracking study.

Developmental dyslexia is characterized by difficulties in learning to read, affecting cognition and causing failure at school. Interventions for children with developmental dyslexia have focused on improving linguistic capabilities (phonics, orthographic and morphological instructions), but developmental dyslexia is accompanied by a wide variety of sensorimotor impairments. The goal of this study was to examine the effects of a proprioceptive intervention on reading performance and eye movement in children with developmental dyslexia. Nineteen children diagnosed with developmental dyslexia were randomly assigned to a regular Speech Therapy (ST) or to a Proprioceptive and Speech Intervention (PSI), in which they received both the usual speech therapy and a proprioceptive intervention aimed to correct their sensorimotor impairments (prism glasses, oral neurostimulation, insoles and breathing instructions). Silent reading performance and eye movements were measured pre- and post-intervention (after nine months). In the PSI group, reading performance improved and eye movements were smoother and faster, reaching values similar to those of children with typical reading performance. The recognition of written words also improved, indicating better lexical access. These results show that PSI might constitute a valuable tool for reading improvement children with developmental dyslexia.

Processing causal structure sentences in Mandarin Chinese: an eye movements study.

It remains uncertain whether causal structure prediction can improve comprehension in Chinese sentences and whether the position of the headword mediates the prediction effect. We conducted an experiment to explore the effect of causal prediction and headword position in Chinese sentence reading. Participants were asked to read sentences containing causal connectives with their eye movements recorded. In the experiment, we manipulated the causal structure of the sentence and the position of the headword. We found a promoting effect of causal structure on first-pass reading time and a hindering impact on total reading time. However, the effect was not mediated by the headword position. The results show that causal syntactic prediction facilitated early-stage processing and increased the integration cost in the late stage of Chinese sentence processing. These findings also support the constraint-based approach, which suggests an isolation between semantic and syntactic processing.

The affective factors of depression symptoms in hypertensive patients and the protective effect of physical activity.

OBJECTIVE: To investigate the potential affective factors of depressive symptoms in patients with hypertension and explore the protective effects of physical activity. METHODS: 211 hypertensive patients aged over 18 years were consecutively recruited. All patients completed a self-designed questionnaire and the Hospital Anxiety and Depression Scale (HADS) to assess the coexistence of depressive symptoms, and psychiatrists were invited to diagnose depression when necessary. Full-night polysomnography was performed to detect the sleep pattern. The association between sleep structure and depressive symptoms was tested by using logistic regression analysis, and contributing factors as well as the effect of physical activity were assessed among patients with and without depressive symptoms. RESULTS: Of the 211 subjects, 33.6% of cases were coexistent with depressive symptoms. Female gender [OR (95%CI): 2.83 (1.44-5.57), P = 0.003) and the greater percentage of REM stage [OR (95%CI): 1.09 (1.01-1.18), P = 0.024] were the risk factors of depressive symptoms, while doing physical activity showed as the protective factor. Patients with REM stage ≥ 20% showed a higher score on HADS-D than those with REM stage < 20% [(4.9 ± 3.8) vs. (3.7 ± 3.1), P = 0.018]. Compared to individuals who never did physical activity, those who did physical activity 1-2 times per week and ≥ 3 times per week had a 52% and 62% risk reduction in depressive symptoms respectively. Patients who did physical activity had lower levels of high-sensitivity C-reactive protein (hs-CRP) compared to those who never did physical activity. CONCLUSION: Female gender and a higher percentage of REM stage are risk factors for depressive symptoms in hypertension, while physical activity may benefit depressive symptoms by reducing serum levels of hs-CRP.

Targeted memory reactivation to augment treatment in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder with traumatic memories at its core. Post-treatment sleep may offer a unique time window to increase therapeutic efficacy through consolidation of therapeutically modified traumatic memories. Targeted memory reactivation (TMR) enhances memory consolidation by presenting reminder cues (e.g., sounds associated with a memory) during sleep. Here, we applied TMR in PTSD patients to strengthen therapeutic memories during sleep after one treatment session with eye movement desensitization and reprocessing (EMDR). PTSD patients received either slow oscillation (SO) phase-targeted TMR, using modeling-based closed-loop neurostimulation (M-CLNS) with EMDR clicks as a reactivation cue (n = 17), or sham stimulation (n = 16). Effects of TMR on sleep were assessed through high-density polysomnography. Effects on treatment outcome were assessed through subjective, autonomic, and fMRI responses to script-driven imagery (SDI) of the targeted traumatic memory and overall PTSD symptom level. Compared to sham stimulation, TMR led to stimulus-locked increases in SO and spindle dynamics, which correlated positively with PTSD symptom reduction in the TMR group. Given the role of SOs and spindles in memory consolidation, these findings suggest that TMR may have strengthened the consolidation of the EMDR-treatment memory. Clinically, TMR vs. sham stimulation resulted in a larger reduction of avoidance level during SDI. TMR did not disturb sleep or trigger nightmares. Together, these data provide first proof of principle that TMR may be a safe and viable future treatment augmentation strategy for PTSD. The required follow-up studies may implement multi-night TMR or TMR during REM sleep to further establish the clinical effect of TMR for traumatic memories.

Bolstering family therapy: Assimilating EMDR into ABFT in youth residential treatment.

The psychotherapy field has a long history of integration to improve treatment effectiveness. One type, assimilative integration, offers innovative opportunities to family therapy to incorporate the clinical and research contributions of different approaches. This paper contributes to the literature on integration by exploring how Eye Movement Desensitization and Reprocessing (EMDR) can be assimilated into Attachment-Based Family Therapy (ABFT) for youth in residential psychiatric treatment. ABFT seeks to improve attachment security to parental figures by asking adolescents and young adults to discuss attachment ruptures. This process, specially designed for patients with internalizing disorders, can provoke anxiety, particularly for a patient population that commonly has a history of trauma and adverse life experiences. EMDR is a first-line therapy for post-traumatic stress disorder and has the potential to be effective in treating various other mental health conditions. When patient emotional withdrawal or dysregulation due to breaches in trust between child and parent emerges in ABFT, EMDR may help desensitize associated memories and bolster the family therapy process. The authors provide an overview of both models, and a detailed case study as an example. The paper concludes with a discussion on implications, integration efforts, and limitations.

Advancements in eye movement measurement technologies for assessing neurodegenerative diseases.

Eye movements have long been recognized as a valuable indicator of neurological conditions, given the intricate involvement of multiple neurological pathways in vision-related processes, including motor and cognitive functions, manifesting in rapid response times. Eye movement abnormalities can indicate neurological condition severity and, in some cases, distinguish between disease phenotypes. With recent strides in imaging sensors and computational power, particularly in machine learning and artificial intelligence, there has been a notable surge in the development of technologies facilitating the extraction and analysis of eye movements to assess neurodegenerative diseases. This mini-review provides an overview of these advancements, emphasizing their potential in offering patient-friendly oculometric measures to aid in assessing patient conditions and progress. By summarizing recent technological innovations and their application in assessing neurodegenerative diseases over the past decades, this review also delves into current trends and future directions in this expanding field.

The timing of sleep spindles is modulated by the respiratory cycle in humans.

OBJECTIVE: Coupling of sleep spindles with cortical slow waves and hippocampus sharp-waves ripples is crucial for sleep-related memory consolidation. Recent literature evidenced that nasal respiration modulates neural activity in large-scale brain networks. In rodents, this respiratory drive strongly varies according to vigilance states. Whether sleep oscillations are also respiration-modulated in humans remains open. In this work, we investigated the influence of breathing on sleep spindles during non-rapid-eye-movement sleep in humans. METHODS: Full night polysomnography of twenty healthy participants were analysed. Spindles and slow waves were automatically detected during N2 and N3 stages. Spindle-related sigma power as well as spindle and slow wave events were analysed according to the respiratory phase. RESULTS: We found a significant coupling between both slow and fast spindles and the respiration cycle, with enhanced sigma activity and occurrence probability of spindles during the middle part of the expiration phase. A different coupling was observed for slow waves negative peaks which were rather distributed around the two respiration phase transitions. CONCLUSION: Our findings suggest that breathing cycle influences the dynamics of brain activity during non-rapid-eye-movement sleep. SIGNIFICANCE: This coupling may enable sleep spindles to synchronize with other sleep oscillations and facilitate information transfer between distributed brain networks.

Reading with Screen Magnification: Eye Movement Analysis Using Compensated Gaze Tracks.

Eye movements while reading with screen magnification (which requires manual scrolling to center the magnified portion of the screen within the viewport) pose interpretation challenges. Standard representations in terms of alternating fixations and saccades don't apply to this case. This is because, during scrolling, eyes often track a moving text element, generating a movement akin to smooth pursuit. We propose a new representation that uses information from the mouse (which the reader uses to move the center of magnification) to undo the effect of magnification and scrolling. After this "compensation" operation, gaze tracks can again be described as alternating fixations and saccades. We present an analysis of gaze tracks obtained by applying this transformation on an existing dataset, recorded from low vision readers using two modalities of screen magnification. This analysis highlights similarities and differences in terms of dynamic properties of compensated gaze tracks vis-à-vis gaze during regular reading.

Modulation of sleep/wake patterns by gephyrin phosphorylation status.

Sleep/wake cycles intricately shape physiological activities including cognitive brain functions, yet the precise molecular orchestrators of sleep remain elusive. Notably, the clinical impact of benzodiazepine drugs underscores the pivotal role of GABAergic neurotransmission in sleep regulation. However, the specific contributions of distinct GABAA receptor subtypes and their principal scaffolding protein, gephyrin, in sleep dynamics remain unclear. The evolving role of synaptic phospho-proteome alterations at excitatory and inhibitory synapses suggests a potential avenue for modulating gephyrin and, consequently, GABAARs for sleep through on-demand kinase recruitment. Our study unveils the distinctive roles of two prevalent GABAA receptor subtypes, α1- and α2-GABAARs, in influencing sleep duration and electrical sleep activity. Notably, the absence of α1-GABAARs emerges as central in sleep regulation, manifesting significant alterations in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during dark or active phases, accompanied by altered electroencephalogram (EEG) patterns across various frequencies. Gephyrin proteomics analysis reveals sleep/wake-dependent interactions with a repertoire of known and novel kinases. Crucially, we identify the regulation of gephyrin interaction with ERK1/2, and phosphorylations at serines 268 and 270 are dictated by sleep/wake cycles. Employing AAV-eGFP-gephyrin or its phospho-null variant (S268A/S270A), we disrupt sleep either globally or locally to demonstrate gephyrin phosphorylation as a sleep regulator. In summary, our findings support the local cortical sleep hypothesis and we unveil a molecular mechanism operating at GABAergic synapses, providing critical insights into the intricate regulation of sleep.

Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.

PURPOSE: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs). METHODS: We coupled phenotyping with exome or genome sequencing of 467 probands (550 affected and 1108 total individuals) with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and de novo variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations. RESULTS: Analyses elucidated phenotypic subgroups, identified pathogenic/likely pathogenic variant(s) in 43/467 probands (9.2%), and prioritized variants of uncertain significance in 70/467 additional probands (15.0%). These included known and novel variants in established oCCDD genes, genes associated with syndromes that sometimes include oCCDDs (e.g., MYH10, KIF21B, TGFBR2, TUBB6), genes that fit the syndromic component of the phenotype but had no prior oCCDD association (e.g., CDK13, TGFB2), genes with no reported association with oCCDDs or the syndromic phenotypes (e.g., TUBA4A, KIF5C, CTNNA1, KLB, FGF21), and genes associated with oCCDD phenocopies that had resulted in misdiagnoses. CONCLUSION: This study suggests that unsolved oCCDDs are clinically and genetically heterogeneous disorders often overlapping other Mendelian conditions and nominates many candidates for future replication and functional studies.

Efferent pathways from the suprachiasmatic nucleus to the horizontal limbs of diagonal band promote NREM sleep during the dark phase in mice.

The regulation of circadian rhythms and the sleep-wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep-wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN-HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non-rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN-HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep-wake states regulation.

Habitual rapid eye movement sleep predicts changes in test-anxiety levels weeks in advance.

Previous research has linked rapid eye movement sleep to emotional processing, particularly stress. Lab studies indicate that rapid eye movement sleep deprivation and fragmentation heighten emotional reactivity and stress response. This relationship extends to natural settings, where poor-quality sleep among college students correlates with increased academic stress and lower academic performance. However, there is a lack of research into how specific sleep stages, like rapid eye movement, affect real-life stress development. This study investigated whether habitual rapid eye movement sleep in college students can predict the future development of real-life stress symptoms associated with final exams. Fifty-two participants (mean age = 19 years, 62% females) monitored their sleep for a week during the academic semester using a mobile electroencephalogram device, and then completed self-evaluations measuring test anxiety and other relevant factors. They completed the same evaluations again just prior to final exams. We found that rapid eye movement sleep was the most dominant factor predicting changes in participants' test anxiety. However, contrasting with our predictions, habitual rapid eye movement sleep was associated with an increase rather than decrease in anxiety. We discuss these results in terms of the rapid eye movement recalibration hypothesis, which suggests rapid eye movement sleep modulates activity in stress-encoding areas in the brain, leading to both decreased sensitivity and increased selectivity of stress responses.