Biology subjects

Beker, S.

Publications and source records attributed to Beker, S..

6 recordsLinked to original sources

bioRxiv2026

Age-Related Increases in 40Hz Neural Synchrony Are Specific to Typical Development: A Cross-Sectional Study of Autism Spectrum Disorder

Background: The 40Hz auditory steady-state response (ASSR) is a measure of gamma-band neural synchrony sensitive to excitation-inhibition (E/I) balance. Disruptions to E/I balance have been implicated in autism spectrum disorder (ASD), making ASSR an efficient tool for investigating neural synchrony development in this population. Whether age-related differences in 40Hz ASSR are detectable across development in ASD remains understudied. Phelan-McDermid syndrome (PMS), a rare genetic disorder with a phenotype overlapping with autism, caused by SHANK3 disruption, provides a genetically defined model for further investigating E/I-related neural synchrony disruptions. Methods: We examined 40Hz inter-trial phase coherence (ITPC) as an index of neural synchrony across a wide age range (2-37 years) in 127 participants from four groups: TD (n=43), ASD without intellectual disability (w/o ID; n=37), ASD with intellectual disability (w/ID; n=24), and PMS (n=23). Given the distinct age and cognitive profiles of ASD subgroups in this sample, analyses were conducted in separate models: TD vs. ASD w/o ID across all ages, and TD vs. ASD w/ID vs. PMS restricted to participants under 18. Results: For the first time in a cross-sectional sample spanning a large age range, we show that 40Hz ITPC increases significantly with age in TD individuals, while this developmental trajectory is absent in ASD without intellectual disability. Among children and adolescents under 18, 40Hz ITPC did not differ across TD, ASD w/ID, and PMS, and IQ did not predict ITPC in clinical groups. A post-hoc analysis revealed higher ITPC in TD males than females, with no sex differences in ASD or PMS. Conclusions: We demonstrate that gamma-band ITPC trajectories diverge between TD and ASD, specifically in adulthood, with no such difference detectable in childhood. No significant group differences were found among TD, ASD w/ID, and PMS individuals under 18. These findings highlight the importance of age as a critical variable when measuring ASSR, and underscore the need for lifespan studies, particularly in genetically defined conditions such as PMS, to determine whether similar divergence emerges in adulthood.

neuroscience↗

bioRxiv2026

Identifying Phelan-McDermid-Like Electrophysiological Subtypes in Autism Using EEG and Machine Learning

BackgroundPhelan McDermid syndrome (PMS), caused by SHANK3 haploinsufficiency, is a genetic form of autism spectrum disorder (ASD) that provides a genetically defined model for studying ASD-related circuit dysfunction. SHANK3 mutations disrupt synaptic organization and cortical synchrony, leading to attenuated gamma-band auditory steady-state responses (ASSRs). We investigated whether PMS-related electrophysiological signatures could be identified using machine learning and whether similar patterns are present in a subset of individuals with idiopathic ASD (iASD). MethodsEEG recorded during a 40-Hz ASSR paradigm was collected from 123 participants (42 TD aged 2-30, 56 iASD aged 3-31, 25 PMS aged 2-26). We extracted time-series, ERSP, FOOOF-derived spectral, and intertrial phase coherence (ITPC) features. XGBoost models with leave-one-out cross-validation classified PMS versus TD; the best age/sex-adjusted ITPC model was then applied to iASD participants to derive a Synchrony Atypicality Index (SAI). Unsupervised clustering of high-dimensional ITPC features was also performed. ResultsITPC-based models showed the strongest discrimination between TD and PMS participants (AUROC = 0.83). When applied to iASD participants, 35.7% exhibited elevated SAI, indicating a PMS-like gamma-band phase-locking profile. Classification of iASD versus PMS performed poorly in the full sample but improved markedly after excluding high-SAI iASD individuals, consistent with substantial heterogeneity within iASD. Unsupervised clustering of ITPC features identified PMS-enriched clusters that also captured high-SAI iASD participants. Results were consistent after controlling for age in sensitivity analyses. ConclusionsReduced 40-Hz ITPC is a mechanistically interpretable electrophysiological signature of PMS and identifies a biologically meaningful PMS-like subgroup within iASD, supporting biomarker-guided stratification.

neuroscience↗

bioRxiv2025

Disrupted Top-Down Modulation as a Mechanism of Impaired Multisensory Processing in Children with an Autism Spectrum Diagnosis.

Atypical sensory processing is a core feature of autism, particularly when integration across sensory modalities is required. The neural mechanisms underlying these multisensory differences remain unclear. We recorded high-density EEG while autistic children aged 8-13 (AU; n=40), unaffected siblings of autistic children (SIB; n=26), and non-autistic controls (NA; n=36) performed a simple reaction-time task to auditory (A), visual (V), and audiovisual (AV) stimuli. Analyses targeted event-related potentials (ERPs; P1/N1/P2), alpha-band event-related desynchronization (-ERD), and long-range theta-band functional connectivity (weighted phase-lag index, wPLI). Across all unisensory measures (ERPs, -ERD, and connectivity), groups did not differ, indicating broadly comparable unisensory processing. By contrast, multisensory integration (MSI; operationalized for ERPs and -ERD as AV - (A+V)) differed across groups: NA children showed significant ERP MSI over parieto-central sites that was absent in AU and SIB; and -ERD MSI was present in all groups but significantly reduced in AU, with SIB showing an intermediate profile. Connectivity analyses revealed that AV theta-band fronto-parieto-occipital coupling was reduced in autistic relative to non-autistic children, consistent with weaker large-scale coordination during multisensory processing. Together, these results point to a multisensory-specific deficit in autism spanning early sensory encoding, posterior -ERD, and fronto-posterior coupling. The convergence of results supports a mechanistic account of disrupted multisensory influences on sensory processing due to reduced multisensory attentional orientation. Intermediate SIB profiles suggest inherited liability for these neural phenotypes. These results help explain well-documented behavioral MSI differences in autism by linking impaired early enhancement with attenuated top-down control of sensory cortex.

neuroscience↗

bioRxiv2025

Children with Autism Show Impaired Oculomotor Entrainment to Predictable Stimuli

Individuals with Autism Spectrum Disorder (ASD) show altered synchronization with external events, which may underlie the rigidity and reduced adaptability that characterize the condition. We previously demonstrated that electroencephalography (EEG) recorded from children with ASD reveals impaired neuronal entrainment to predictable visual sequences. Whether similar effects are reflected in other physiological signals remains unclear. Here, we investigated whether eye movement and pupil dilation responses exhibit comparable entrainment differences in ASD. Microsaccades (MS) and pupil diameter were recorded from 31 children with ASD (6-9 years) and 21 age- and IQ-matched typically developing (TD) controls during a task in which four equally spaced visual cues preceded an auditory target. We analyzed modulation of MS release time (MS RT) and pupil response time (pupil RT), along with trial-by-trial variability, as indices of ocular entrainment. Both groups exhibited periodic oculomotor responses to the cues, including phasic MS inhibition and repeated pupil constrictions. In TD children, MS RT and pupil RT increased across cues while their variability decreased, consistent with progressive temporal alignment. These effects were significantly reduced in the ASD group. Oculomotor entrainment measures correlated with EEG inter-trial phase coherence (ITPC) in TD but not ASD children. They also correlated with behavioral response times in both groups, and moderately correlated with autism severity scores. Children with ASD thus showed diminished oculomotor modulation and greater variability in response to predictable stimuli, paralleling earlier EEG findings. These results suggest convergence across physiological systems in indexing impaired processing of predictability in ASD and highlight the promise of multimodal approaches.

neuroscience↗

bioRxiv2025

Not Just Noise: Impaired Oscillatory Entrainment Reflects Reduced Temporal Flexibility in Autism

Rhythmic patterns in the environment enhance neural activity, perception, and action. However, natural rhythms are often imprecise, requiring flexible adaptation. In autism Spectrum Disorder (ASD), characterized by cognitive rigidity and atypical use of prior information - favoring immediate sensory input over predictive cues - entrainment to temporally variable input may be reduced at both neural and behavioral levels, though the neural mechanisms remain unclear. Here, we recorded high-density EEG and behavior in adults with ASD (n=20) and neurotypical (NT) controls (n=21) during a visual detection task with four rhythmic structures, parametrically varied from an isochronous fully regular rhythm, to a highly irregular one. Spectral analysis and temporal response function (TRF) models revealed significantly reduced modulation by temporal regularity in ASD, particularly in mildly jittered stimulation streams. Additionally, the coupling between phases of neural oscillations and behavior was diminished in ASD under the jittered conditions, suggesting reduced functional relevance of neural synchronization. Residual spectral power post-stimulation showed lower oscillatory entrainment in ASD, ruling out simple evoked-response explanations. Notably, the degree of neural modulation by temporal regularity was correlated with IQ within the ASD group, suggesting a link between temporal flexibility and individual cognitive profiles. These findings highlight impaired neural entrainment and reduced behavioral modulation by temporal structure in ASD, offering insight into inflexible responses to uncertain, volatile sensory environments. InnovationEntrainment to rhythmic events is reduced in autism, but it remains unclear whether this reflects a general, non-selective deficit in neuro-oscillatory alignment or a selective vulnerability to volatile temporal structures, such as those with embedded jitter. To address this, we recorded cortical activity and behavioral performance as participants with ASD engaged with visual sequences of varying rhythmic regularity, and examined how temporal predictability modulated oscillatory entrainment. By correlating neural entrainment with target detection and clinical profiles, we sought to uncover a key feature of the autistic phenotype: reduced temporal flexibility in adapting to unpredictable sensory environments.

neuroscience↗

bioRxiv2020

Oscillatory entrainment mechanisms and anticipatory predictive processes in Autism Spectrum Disorder (ASD)

Anticipating near-future events is fundamental to adaptive behavior, whereby neural processing of predictable stimuli is significantly facilitated relative to non-predictable inputs. Neural oscillations appear to be a key anticipatory mechanism by which processing of upcoming stimuli is modified, and they often entrain to rhythmic environmental sequences. Clinical and anecdotal observations have led to the hypothesis that people with Autism Spectrum Disorder (ASD) may have deficits in generating predictions in daily life, and as such, a candidate neural mechanism may be failure to adequately entrain neural activity to repetitive environmental patterns. Here, we tested this hypothesis by interrogating rhythmic entrainment both behaviorally and electrophysiologically. We recorded high-density electroencephalography in children with ASD (n=31) and Typically Developing (TD) age- and IQ-matched controls (n=20), while they reacted to an auditory target as quickly as possible. This auditory event was either preceded by predictive rhythmic visual cues, or not. Results showed that while both groups presented highly comparable evoked responses to the visual stimuli, children with ASD showed reduced neural entrainment to the rhythmic visual cues, and altered anticipation of the occurrence of these stimuli. Further, in both groups, neuro-oscillatory phase coherence correlated with behavior. These results describe neural processes that may underlie impaired event anticipation in children with ASD, and support the notion that their perception of events is driven more by instantaneous sensory inputs and less by their temporal predictability.

neuroscience↗