Processing Deficits Research Articles

Age-Related Deficits in Binaural Hearing: Contribution of Peripheral and Central Effects.

Pure-tone audiograms often poorly predict elderly humans' ability to communicate in everyday complex acoustic scenes. Binaural processing is crucial for discriminating sound sources in such complex acoustic scenes. The compromised perception of communication signals presented above hearing threshold has been linked to both peripheral and central age-related changes in the auditory system. Investigating young and old Mongolian gerbils of both sexes, an established model for human hearing, we demonstrate age-related supra-threshold deficits in binaural hearing using behavioral, electrophysiological, anatomical, and imaging methods. Binaural processing ability was measured as the binaural masking level difference (BMLD), an established measure in human psychophysics. We tested gerbils behaviorally with "virtual headphones," recorded single-unit responses in the auditory midbrain and evaluated gross midbrain and cortical responses using positron emission tomography (PET) imaging. Furthermore, we obtained additional measures of auditory function based on auditory brainstem responses, auditory-nerve synapse counts, and evidence for central inhibitory processing revealed by PET. BMLD deteriorates already in middle-aged animals having normal audiometric thresholds and is even worse in old animals with hearing loss. The magnitude of auditory brainstem response measures related to auditory-nerve function and binaural processing in the auditory brainstem also deteriorate. Furthermore, central GABAergic inhibition is affected by age. Because the number of synapses in the apical turn of the inner ear was not reduced in middle-aged animals, we conclude that peripheral synaptopathy contributes little to binaural processing deficits. Exploratory analyses suggest increased hearing thresholds, altered binaural processing in the brainstem and changed central GABAergic inhibition as potential contributors.

White matter network underlying semantic processing: evidence from stroke patients.

The hub-and-spoke theory of semantic representation fractionates the neural underpinning of semantic knowledge into two essential components: the sensorimotor modality-specific regions and a crucially important semantic hub region. Our previous study in patients with semantic dementia has found that the hub region is located in the left fusiform gyrus. However, because this region is located within the brain damage in patients with semantic dementia, it is not clear whether the semantic deficit is caused by structural damage to the hub region itself or by its disconnection from other brain regions. Stroke patients do not have any damage to the left fusiform gyrus, but exhibit amodal and modality-specific deficits in semantic processing. Therefore, in this study, we validated the semantic hub region from a brain network perspective in 79 stroke patients and explored the white matter connections associated with it. First, we collected data of diffusion-weighted imaging and behavioural performance on general semantic tasks and modality-specific semantic tasks (assessing object knowledge on form, colour, motion, sound, manipulation and function). We then used correlation and regression analyses to examine the association between the nodal degree values of brain regions in the whole-brain structural network and general semantic performance in the stroke patients. The results revealed that the connectivity of the left fusiform gyrus significantly predicted general semantic performance, indicating that this region is the semantic hub. To identify the semantic-relevant connections of the semantic hub, we then correlated the white matter integrity values of each tract connected to the left fusiform gyrus separately with performance on general and modality-specific semantic processing. We found that the hub region accomplished general semantic processing through white matter connections with the left superior temporal pole, middle temporal gyrus, inferior temporal gyrus and hippocampus. The connectivity between the hub region and the left hippocampus, superior temporal pole, middle temporal gyrus, inferior temporal gyrus and parahippocampal gyrus was differentially involved in object form, colour, motion, sound, manipulation and function processing. After statistically removing the effects of potential confounding variables (i.e. whole-brain lesion volume, lesion volume of regions of interest and performance on non-semantic control tasks), the observed effects remained significant. Together, our findings support the role of the left fusiform gyrus as a semantic hub region in stroke patients and reveal its crucial connectivity in the network. This study provides new insights and evidence for the neuroanatomical organization of semantic memory in the human brain.

The Gaze of Schizophrenia Patients Captured by Bottom-up Saliency

Schizophrenia (SCHZ) notably impacts various human perceptual modalities, including vision. Prior research has identified marked abnormalities in perceptual organization in SCHZ, predominantly attributed to deficits in bottom-up processing. Our study introduces a novel paradigm to differentiate the roles of top-down and bottom-up processes in visual perception in SCHZ. We analysed eye-tracking fixation ground truth maps from 28 SCHZ patients and 25 healthy controls (HC), comparing these with two mathematical models of visual saliency: one bottom-up, based on the physical attributes of images, and the other top-down, incorporating machine learning. While the bottom-up (GBVS) model revealed no significant overall differences between groups (beta = 0.01, p = 0.281, with a marginal increase in SCHZ patients), it did show enhanced performance by SCHZ patients with highly salient images. Conversely, the top-down (EML-Net) model indicated no general group difference (beta = −0.03, p = 0.206, lower in SCHZ patients) but highlighted significantly reduced performance in SCHZ patients for images depicting social interactions (beta = −0.06, p < 0.001). Over time, the disparity between the groups diminished for both models. The previously reported bottom-up bias in SCHZ patients was apparent only during the initial stages of visual exploration and corresponded with progressively shorter fixation durations in this group. Our research proposes an innovative approach to understanding early visual information processing in SCHZ patients, shedding light on the interplay between bottom-up perception and top-down cognition.

Asymmetry in Cortical Thickness of the Heschl's Gyrus in Unilateral Ear Canal Atresia.

Unilateral congenital conductive hearing impairment in ear canal atresia leads to atrophy of the gray matter of the contralateral primary auditory cortex or changes in asymmetry pattern if left untreated in childhood. Unilateral ear canal atresia with associated severe conductive hearing loss results in deteriorated sound localization and difficulties in understanding of speech in a noisy environment. Cortical atrophy in the Heschl's gyrus has been reported in acquired sensorineural hearing loss but has not been studied in unilateral conductive hearing loss. We obtained T1w and T2w FLAIR MRI data from 17 subjects with unilateral congenital ear canal atresia and 17 matched controls. Gray matter volume and thickness were measured in the Heschl's gyrus using Freesurfer. In unilateral congenital ear canal atresia, Heschl's gyrus exhibited cortical thickness asymmetry (right thicker than left, corrected p = 0.0012, mean difference 0.25 mm), while controls had symmetric findings. Gray matter volume and total thickness did not differ from controls with normal hearing. We observed cortical thickness asymmetry in congenital unilateral ear canal atresia but no evidence of contralateral cortex atrophy. Further research is needed to understand the implications of this asymmetry on central auditory processing deficits.

Profiles of mathematical deficits in children with dyslexia

Despite a high rate of concurrent mathematical difficulties among children with dyslexia, we still have limited information regarding the prevalence and severity of mathematical deficits in this population. To address this gap, we developed a comprehensive battery of cognitive tests, known as the UCSF Mathematical Cognition Battery (MCB), with the aim of identifying deficits in four distinct mathematical domains: number processing, arithmetical procedures, arithmetic facts retrieval, and geometrical abilities. The mathematical abilities of a cohort of 75 children referred to the UCSF Dyslexia Center with a diagnosis of dyslexia, along with 18 typically developing controls aged 7 to 16, were initially evaluated using a behavioral neurology approach. A team of professional clinicians classified the 75 children with dyslexia into five groups, based on parents’ and teachers’ reported symptoms and clinical history. These groups included children with no mathematical deficits and children with mathematical deficits in number processing, arithmetical procedures, arithmetic facts retrieval, or geometrical abilities. Subsequently, the children underwent evaluation using the MCB to determine concordance with the clinicians’ impressions. Additionally, neuropsychological and cognitive standardized tests were administered. Our study reveals that within a cohort of children with dyslexia, 66% exhibit mathematical deficits, and among those with mathematical deficits, there is heterogeneity in the nature of these deficits. If these findings are confirmed in larger samples, they can potentially pave the way for new diagnostic approaches, consistent subtype classification, and, ultimately personalized interventions.

Enabling brief assessments of alexithymia: psychometric properties of the Russian version of the Perth Alexithymia Questionnaire-Short Form (PAQ-S) and its correlates with ill-being and well-being

Alexithymia is a trait involving deficits in emotion processing. As an important risk factor for a wide range of psychopathologies, its assessment is important in both research and clinical practice. Originally developed in English, the Perth Alexithymia Questionnaire-Short Form (PAQ-S) is a 6-item self-report measure of alexithymia, with its brevity designed to enable alexithymia assessments in a wide range of settings. In the present research, we aimed to introduce the first Russian version of the PAQ-S and examine its psychometric properties. Our sample consisted of 203 Russian-speaking adults aged 18–74 years, recruited from the general community in Russia. The PAQ-S’s factor structure was verified with confirmatory factor analysis. Convergent and divergent validity was assessed via relationships with psychopathology symptoms and well-being. Internal consistency reliability was evaluated. The Russian version of the PAQ-S demonstrated strong factorial validity, with support for the intended 1-factor structure as an overall marker of alexithymia. The PAQ-S total scale score showed good internal consistency reliability. As expected, its convergent and divergent validity was also supported. PAQ-S scores were significant predictors of higher ill-being (anxiety, depression, and stress) and lower well-being, thus demonstrating the high clinical relevance of the alexithymia construct as measured by the PAQ-S. There were no gender differences in PAQ-S scores, and alexithymia was higher in younger people and those with less education. Overall, the Russian PAQ-S therefore demonstrated strong psychometric properties as a brief and robust measure of overall alexithymia, performing similarly to other language versions.

Design and methodology for a proof of mechanism study of individualized neuronavigated continuous Theta burst stimulation for auditory processing in adolescents with autism spectrum disorder.

It has been suggested that aberrant excitation/inhibition (E/I) balance and dysfunctional structure and function of relevant brain networks may underlie the symptoms of autism spectrum disorder (ASD). However, the nomological network linking these constructs to quantifiable measures and mechanistically relating these constructs to behavioral symptoms of ASD is lacking. Herein we describe a within-subject, controlled, proof-of-mechanism study investigating the pathophysiology of auditory/language processing in adolescents with ASD. We utilize neurophysiological and neuroimaging techniques including magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) metrics of language network structure and function. Additionally, we apply a single, individually targeted session of continuous theta burst stimulation (cTBS) as an experimental probe of the impact of perturbation of the system on these neurophysiological and neuroimaging outcomes. MRS, fMRI, and MEG measures are evaluated at baseline and immediately prior to and following cTBS over the posterior superior temporal cortex (pSTC), a region involved in auditory and language processing deficits in ASD. Also, behavioral measures of ASD and language processing and DWI measures of auditory/language network structures are obtained at baseline to characterize the relationship between the neuroimaging and neurophysiological measures and baseline symptom presentation. We hypothesize that local gamma-aminobutyric acid (GABA) and glutamate concentrations (measured with MRS), and structural and functional activity and network connectivity (measured with DWI and fMRI), will significantly predict MEG indices of auditory/language processing and behavioral deficits in ASD. Furthermore, a single session of cTBS over left pSTC is hypothesized to lead to significant, acute changes in local glutamate and GABA concentration, functional activity and network connectivity, and MEG indices of auditory/language processing. We have completed the pilot phase of the study (n=20 Healthy Volunteer adults) and have begun enrollment for the main phase with adolescents with ASD (n=86; age 14-17). If successful, this study will establish a nomological network linking local E/I balance measures to functional and structural connectivity within relevant brain networks, ultimately connecting them to ASD symptoms. Furthermore, this study will inform future therapeutic trials using cTBS to treat the symptoms of ASD.

Language uncovers visuospatial dysfunction in posterior cortical atrophy: a natural language processing approach.

Posterior Cortical Atrophy (PCA) is a syndrome characterized by a progressive decline in higher-order visuospatial processing, leading to symptoms such as space perception deficit, simultanagnosia, and object perception impairment. While PCA is primarily known for its impact on visuospatial abilities, recent studies have documented language abnormalities in PCA patients. This study aims to delineate the nature and origin of language impairments in PCA, hypothesizing that language deficits reflect the visuospatial processing impairments of the disease. We compared the language samples of 25 patients with PCA with age-matched cognitively normal (CN) individuals across two distinct tasks: a visually-dependent picture description and a visually-independent job description task. We extracted word frequency, word utterance latency, and spatial relational words for this comparison. We then conducted an in-depth analysis of the language used in the picture description task to identify specific linguistic indicators that reflect the visuospatial processing deficits of PCA. Patients with PCA showed significant language deficits in the visually-dependent task, characterized by higher word frequency, prolonged utterance latency, and fewer spatial relational words, but not in the visually-independent task. An in-depth analysis of the picture description task further showed that PCA patients struggled to identify certain visual elements as well as the overall theme of the picture. A predictive model based on these language features distinguished PCA patients from CN individuals with high classification accuracy. The findings indicate that language is a sensitive behavioral construct to detect visuospatial processing abnormalities of PCA. These insights offer theoretical and clinical avenues for understanding and managing PCA, underscoring language as a crucial marker for the visuospatial deficits of this atypical variant of Alzheimer's disease.

Visual search patterns during exploration of naturalistic scenes are driven by saliency cues in individuals with cerebral visual impairment

We investigated the relative influence of image salience and image semantics during the visual search of naturalistic scenes, comparing performance in individuals with cerebral visual impairment (CVI) and controls with neurotypical development. Participants searched for a prompted target presented as either an image or text cue. Success rate and reaction time were collected, and gaze behavior was recorded with an eye tracker. A receiver operating characteristic (ROC) analysis compared the distribution of individual gaze landings based on predictions of image salience (using Graph-Based Visual Saliency) and image semantics (using Global Vectors for Word Representations combined with Linguistic Analysis of Semantic Salience) models. CVI participants were less likely and were slower in finding the target. Their visual search behavior was also associated with a larger visual search area and greater number of fixations. ROC scores were also lower in CVI compared to controls for both model predictions. Furthermore, search strategies in the CVI group were not affected by cue type, although search times and accuracy showed a significant correlation with verbal IQ scores for text-cued searches. These results suggest that visual search patterns in CVI are driven mainly by image salience and provide further characterization of higher-order processing deficits observed in this population.

Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study

Autoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods. In this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls - enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme - was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics. Between February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores. These findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed. The Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.

Childhood emotion dysregulation mediates the relationship between preschool emotion labeling and adolescent depressive symptoms.

Deficits in emotion processing (e.g., emotion labeling and regulation) are widely implicated in depression risk. While prior literature documents these deficits in concurrence with depression, more research is needed to investigate emotion processing pathways of depression risk across development. The purpose of this study was to investigate if emotion processes (i.e., emotion labeling and emotion regulation/dysregulation) in early and middle childhood predict adolescent depressive symptom severity in a prospective sample. Data were analyzed from a longitudinal study of diverse preschoolers oversampled for depressive symptoms using measures of preschool emotion labeling of faces (i.e., Facial Affect Comprehension Evaluation), middle childhood emotion regulation and dysregulation (i.e., emotion regulation checklist), and adolescent depressive symptoms (i.e., PAPA, CAPA, and KSADS-PL diagnostic interviews). Multilevel models indicated that preschoolers with depression had similar development of emotion labeling in early childhood as peers. Mediation analyses revealed that deficits in preschool-aged anger and surprise labeling ability indirectly predicted higher adolescent depressive symptom severity through increased middle childhood emotion lability/negativity, not decreased emotion regulation. Adolescent depression may be predicted by an emotion processing pathway that spans from early childhood to adolescence, and findings may generalize to high risk for depression youth samples. Specifically, poor emotion labeling in early childhood may lead to increased childhood emotion lability/negativity, which increases the risk for adolescent depressive symptom severity. Findings may help identify specific emotion processing relations in childhood that increase the risk for depression and inform intervention aimed at improving preschoolers' anger and surprise labeling. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Facilitation of sensorimotor temporal recalibration mechanisms by cerebellar tDCS in patients with schizophrenia spectrum disorders and healthy individuals

Core symptoms in patients with schizophrenia spectrum disorders (SSD), like hallucinations or ego-disturbances, have been associated with a failure of internal forward models to predict the sensory outcomes of self-generated actions. Importantly, forward model predictions must also be able to flexibly recalibrate to changing environmental conditions, for example to account for additional delays between action and outcome. We investigated whether transcranial direct current stimulation (tDCS) can be used to improve these sensorimotor temporal recalibration mechanisms in patients and healthy individuals. While receiving tDCS on the cerebellum, temporo-parietal junction, supplementary motor area, or sham stimulation, patients with SSD and healthy control participants were repeatedly exposed to delays between actively or passively elicited button presses and auditory outcomes. Effects of this procedure on temporal perception were assessed with a delay detection task. Similar recalibration outcomes and faciliatory effects of cerebellar tDCS on recalibration were observed in SSD and healthy individuals. Our findings indicate that sensorimotor recalibration mechanisms may be preserved in SSD and highlight the importance of the cerebellum in both patients and healthy individuals for this process. They further suggest that cerebellar tDCS could be a promising tool for addressing deficits in action-outcome monitoring and related adaptive sensorimotor processes in SSD.

Abstract TMP11: Cerebral Visual Impairment in Pediatric Stroke Patients Assessed by Virtual Reality Testing

Introduction: Pediatric stroke is one of the leading causes of disability in children, many of whom incur brain injury affecting critical visual anatomical networks. Dedicated ophthalmologic examinations that detect cerebral visual impairment (CVI) - the leading cause of congenital visual impairment in developed countries - are not standard of care and can delay diagnosis and interventions. There is limited CVI data in pediatric stroke patients, and in this work we present data defining visual processing deficits in pediatric stroke patients. Hypothesis: We hypothesize that pediatric stroke patients will (1) demonstrate greater visual-spatial processing impairments than controls and (2) demonstrate increasing performance impairment as a function of increasing visual task demands. Methods: Using a virtual reality (VR) based visual search task system, we characterized significant deficits in higher-order visual processing of pediatric stroke patients (n = 17) as compared to healthy controls (n = 13). Stroke patients suffered from a perinatal (n = 8) or pediatric (n = 9) stroke - confirmed with brain MRI - affecting various vascular territories of the anterior and posterior circulations. The task required searching for on-screen targets with increasing visual complexity. Metrics such as reaction time, gaze error, shifted ellipse area, success rate, and pursuit saccade ratio were analyzed using unpaired group-level t-tests and considered significant if p &lt; 0.05. Results: Stroke patients took longer to identify the target (p = 0.001), were less accurate in finding it (p = 0.007), and exhibited greater impairment in performance with an increasing number of distractors compared to healthy children. Groups had comparable task compliance, as indexed by an off-screen count metric. Conclusion: This original work demonstrates that pediatric stroke patients, particularly those with strokes affecting the middle cerebral artery and posterior circulation vascular territories, exhibit impaired higher-order visual processing. This highlights the urgent need for standardized clinical testing to provide quantitative performance measures of cortical visual processing. This will allow timely detection and implementation of interventional therapies.

Abstract WP223: Cerebral Visual Impairment in ACTA2 Patients Assessed by Virtual Reality Testing

Introduction: Heterozygous missense mutations disrupting arginine 179 (Arg179) in the ACTA2 gene which codes for the smooth muscle-specific isoform of α-actin, cause Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS). The clinical manifestations of this genetic condition include congenital mydriasis, patent ductus arteriosus, stroke, and/or aortic aneurysms or dissections among many others. White matter injury, impaired autoregulation, and neurovascular coupling (due to the cerebral vasculopathy affecting cerebral perfusion) are known factors that alter neural network performance and processing speed. The lack of a standardized ophthalmologic examination that detects cerebral visual impairment (CVI), precludes an early diagnosis and creates missed opportunities for intervention. There is a paucity of data regarding CVI in MSMDS patients, and through this novel work, we present data defining their visual processing deficits. Hypothesis: We hypothesize that: 1) individuals with MSMDS will exhibit more pronounced deficits in visual-spatial processing compared to the control group, and 2) their performance will deteriorate as the complexity of visual tasks increases. Methods: Using a virtual reality (VR) based visual search task system, we characterized the impairment of higher-order visual processing in MSMDS patients (n = 4) as compared to healthy controls (n = 13). The VR-based task required searching for targets on a screen among varying levels of visual complexity. Reaction time, gaze error, shifted ellipse area, success rate, and pursuit saccade ratio were statistically analyzed with unpaired group t-tests, with significance being defined as p &lt; 0.05. Results: Compared to controls, MSMDS patients took longer to identify the correct target, were less accurate in finding the target, and exhibited greater impairment in performance with an increasing number of distractors. Both groups showed similar task compliance, measured using an off-screen count metric. Conclusion: This novel work demonstrates that MSMDS patients exhibit impaired higher-order visual processing. This highlights the need for clinical tools that can assess these difficulties with quantitative methods to guide therapies and improve functional outcomes.

Dissociating the impact of alexithymia and impaired self-awareness on emotional distress and aggression after traumatic brain injury.

Alexithymia, a deficit in identifying and describing feelings, is prevalent in traumatic brain injury (TBI). Sometimes referred to as "emotional unawareness," we sought to investigate whether alexithymia after TBI was related to, or distinct from, impaired self-awareness (ISA) and whether the two predicted differentiable emotional and aggression profiles. Further, the mediating role of frontal system behaviors (disinhibition, dysexecutive function, apathy) was explored. Participants with TBI (N = 40) from diverse backgrounds completed self-report measures of alexithymia, emotional distress, aggression, and frontal system behaviors. For the assessment of ISA, significant other ratings were obtained to identify discrepancies from self-ratings. Data were analyzed quantitatively using independent samples t tests, correlations, partial correlations, and simple mediation. There was a negative correlation between alexithymia and ISA. Alexithymia, but not ISA, was associated with higher expressions of emotional distress and aggression even after controlling for the effects of ISA via partial correlations. Exploratory analyses found that frontal system behaviors mediated the relationships between alexithymia and aggression and alexithymia and emotional distress. Alexithymia is more accurately conceptualized as an emotional processing deficit than an awareness deficit. Indeed, self-awareness may be a prerequisite for the ability to identify alexithymic tendencies. Negative psychological effects of alexithymia are compounded by poorer executive function and disinhibition and call for the development of TBI-specific alexithymia screening tools and interventions. Alexithymia interventions are best delivered in conjunction with rehabilitation of emotion regulation and executive function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prenatal exposure to metal mixtures and childhood temporal processing in the PROGRESS Birth Cohort Study: Modification by childhood obesity

Children are frequently exposed to various biological trace metals, some essential for their development, while others can be potent neurotoxicants. Furthermore, the inflammatory and metabolic conditions associated with obesity may interact with and amplify the impact of metal exposure on neurodevelopment. However, few studies have assessed the potential modification effect of body mass index (BMI). As a result, we investigated the role of child BMI phenotype on the relationship between prenatal exposure to metal mixtures and temporal processing. Leveraging the PROGRESS birth cohort in Mexico City, children (N = 563) aged 6–9 years completed a Temporal Response Differentiation (TRD) task where they had to hold a lever down for 10–14 s. Blood and urinary metal (As, Pb, Cd, and Mn) measurements were collected from mothers in the 2nd and 3rd trimesters. Child BMI z-scores were dichotomized to normal (between −2 and +0.99) and high (≥1.00). Covariate-adjusted weighted quantile sum (WQS) regression models were used to estimate and examine the combined effect of metal biomarkers (i.e., blood and urine) on TRD measures. Effect modification by the child's BMI was evaluated using 2-way interaction terms. Children with a high BMI and greater exposure to the metal mixture during prenatal development exhibited significant temporal processing deficits compared to children with a normal BMI. Notably, children with increased exposure to the metal mixture and higher BMI had a decrease in the percent of tasks completed (β = −10.13; 95 % CI: −19.84, −0.42), number of average holds (β = −2.15; 95 % CI: −3.88, −0.41), longer latency (β = 0.78; 95 % CI: 0.13, 1.44), and greater variability in the standard deviation of the total hold time (β = 2.08; 95 % CI: 0.34, 3.82) compared to normal BMI children. These findings implicate that high BMI may amplify the effect of metals on children's temporal processing. Understanding the relationship between metal exposures, temporal processing, and childhood obesity can provide valuable insights for developing targeted environmental interventions.

Visuo-Cognitive Phenotypes in Early Multiple Sclerosis: A Multisystem Model of Visual Processing

Background: Cognitive impairment can emerge in the earliest stages of multiple sclerosis (MS), with heterogeneity in cognitive deficits often hindering symptom identification and management. Sensory–motor dysfunction, such as visual processing impairment, is also common in early disease and can impact neuropsychological task performance in MS. However, cognitive phenotype research in MS does not currently consider the relationship between early cognitive changes and visual processing impairment. Objectives: This study explored the relationship between cognition and visual processing in early MS by adopting a three-system model of afferent sensory, central cognitive and efferent ocular motor visual processing to identify distinct visuo-cognitive phenotypes. Methods: Patients with clinically isolated syndrome and relapsing–remitting MS underwent neuro-ophthalmic, ocular motor and neuropsychological evaluation to assess each visual processing system. The factor structure of ocular motor variables was examined using exploratory factor analysis, and phenotypes were identified using latent profile analysis. Results: Analyses revealed three ocular-motor constructs (cognitive control, cognitive processing speed and basic visual processing) and four visuo-cognitive phenotypes (early visual changes, efferent-cognitive, cognitive control and afferent-processing speed). While the efferent-cognitive phenotype was present in significantly older patients than was the early visual changes phenotype, there were no other demographic differences between phenotypes. The efferent-cognitive and cognitive control phenotypes had poorer performance on the Symbol Digit Modalities Test compared to that of other phenotypes; however, no other differences in performance were detected. Conclusion: Our findings suggest that distinct visual processing deficits in early MS may differentially impact cognition, which is not captured using standard neuropsychological evaluation. Further research may facilitate improved symptom identification and intervention in early disease.

Variability in auditory processing performance is associated with reading difficulties rather than with history of otitis media.

The nature and cause of auditory processing deficits in dyslexic individuals have been debated for decades. Auditory processing deficits were argued to be the first step in a causal chain of difficulties, leading to difficulties in speech perception and thereby phonological processing and literacy difficulties. More recently, it has been argued that auditory processing difficulties may not be causally related to language and literacy difficulties. This study compares two groups who have phonological processing impairments for different reasons: dyslexia and a history of otitis media (OM). We compared their discrimination thresholds and response variability to chronological age- and reading age-matched controls, across three auditory processing tasks: frequency discrimination, rise-time discrimination and speech perception. Dyslexic children showed raised frequency discrimination thresholds in comparison with age-matched controls but did not differ from reading age-matched controls or individuals with a history of OM. There were no group differences on speech perception or rise-time tasks. For the dyslexic children, there was an association between phonological awareness and frequency discrimination response variability, but no association with thresholds. These findings are not consistent with a 'causal chain' explanation but could be accounted for within a multiple deficits view of literacy difficulties.

Amplitude Modulation Perception and Cortical Evoked Potentials in Children With Listening Difficulties and Their Typically Developing Peers.

Amplitude modulations (AMs) are important for speech intelligibility, and deficits in speech intelligibility are a leading source of impairment in childhood listening difficulties (LiD). The present study aimed to explore the relationships between AM perception and speech-in-noise (SiN) comprehension in children and to determine whether deficits in AM processing contribute to childhood LiD. Evoked responses were used to parse the neural origins of AM processing. Forty-one children with LiD and 44 typically developing children, ages 8-16 years, participated in the study. Behavioral AM depth thresholds were measured at 4 and 40 Hz. SiN tasks included the Listening in Spatialized Noise-Sentences Test (LiSN-S) and a coordinate response measure (CRM)-based task. Evoked responses were obtained during an AM change detection task using alternations between 4 and 40 Hz, including the N1 of the acoustic change complex, auditory steady-state response (ASSR), P300, and a late positive response (late potential [LP]). Maturational effects were explored via age correlations. Age correlated with 4-Hz AM thresholds, CRM separated talker scores, and N1 amplitude. Age-normed LiSN-S scores obtained without spatial or talker cues correlated with age-corrected 4-Hz AM thresholds and area under the LP curve. CRM separated talker scores correlated with AM thresholds and area under the LP curve. Most behavioral measures of AM perception correlated with the signal-to-noise ratio and phase coherence of the 40-Hz ASSR. AM change response time also correlated with area under the LP curve. Children with LiD exhibited deficits with respect to 4-Hz thresholds, AM change accuracy, and area under the LP curve. The observed relationships between AM perception and SiN performance extend the evidence that modulation perception is important for understanding SiN in childhood. In line with this finding, children with LiD demonstrated poorer performance on some measures of AM perception, but their evoked responses implicated a primarily cognitive deficit. https://doi.org/10.23641/asha.25009103.

Twice-exceptionality unmasked: A systematic narrative review of the literature on identifying dyslexia in the gifted child.

In this systematic narrative review, we synthesised the small existing body of research on children who are gifted and dyslexic (G-D) in order to investigate the claim that G-D students have a unique profile, characterised by well-masked word-level reading and spelling difficulties. Our focus was on both the cognitive and academic profiles of this subgroup of twice-exceptional (2e) children and the assessment protocols used to identify them. Findings suggest that despite having processing deficits associated with dyslexia, G-D students' gifted strengths, especially those relating to oral language, may enable them to compensate for their reading difficulties, at least to an extent that they fail to meet standard diagnostic criteria. However, G-D students also perform poorly on word-level reading, reading fluency and spelling tasks when compared with both control groups and their gifted, non-dyslexic peers, providing clear evidence of impaired achievement. Findings from this review highlight the need for (a) a more nuanced approach to the assessment of students presenting with highly discrepant profiles and (b) future research into both the cognitive and academic profiles and the instructional needs of this highly able yet poorly understood group of students, whose potential may be masked and thus underestimated in the school setting.