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Darrell, M.

Publications and source records attributed to Darrell, M..

6 recordsLinked to original sources

Asymmetric neural dynamics of visuospatial attention in autism spectrum disorder

BackgroundSelective attention enables the prioritization of behaviorally relevant information in complex sensory environments. Despite substantial evidence for altered attention in autism spectrum disorder (ASD), the neurophysiological mechanisms underlying these differences remain poorly understood. MethodsHere, we integrate high-density electroencephalography (EEG), pupillometry, and behavioral measures collected during a cued covert visuospatial selective attention task to characterize mechanisms of spatial attention in children and adolescents with ASD (n = 18; 13.4 {+/-} 3.0 YO), and how they differ from age- and IQ- matched individuals with typical-development (TD) (n = 21; 14.7 {+/-} 3.8 YO). ResultsBoth groups demonstrated high target detection accuracy and comparable response times, with no significant between-group differences in behavioral performance. Furthermore, neurophysiological measures demonstrated that during leftward attention, both TD and ASD participants exhibited canonical attentional processes, including lateralized anticipatory parieto-occipital alpha modulation and enhanced P1 sensory responses to attended stimuli. Additionally, across both groups, trial-level analyses revealed that decreased anticipatory alpha power and increased P1 amplitude contralateral to the attended hemifield were associated with faster reaction times. In contrast, there were notable group differences in the neural dynamics supporting rightward spatial attention. TD participants showed early sensory gain (P1 modulation) without alpha-band modulation, whereas ASD participants exhibited modulation of posterior alpha power without effective sensory gain. Interestingly, for rightward attention, only P1 amplitude predicted reaction time, and this was the case for both groups. Resting-state alpha dynamics did not differ between groups, indicating that the attended hemifield differences reflect task-dependent differences in attentional control rather than baseline oscillatory differences. LimitationsLimitations include modest sample size and restriction to autistic individuals with relatively low support needs, which may limit the generalizability of these findings to the broader autism spectrum. ConclusionsThe similarity of leftward attention mechanisms across groups, which includes intact recruitment of anticipatory alpha modulation, argues against a global disruption of basic visuo-spatial attentional function in autistic individuals with low support needs. However, group differences emerged specifically during rightward attention, where ASD participants showed a more uniform pattern of oscillatory modulation, warranting further investigation. Collectively, these findings provide novel insight into the neural architecture of visuospatial attention in ASD, revealing how preparatory oscillatory activity shapes early sensory responses and behavior during selective attention.

neuroscience↗

Instability of Alpha Oscillatory States in Autism and Familial Liability: Evidence from Burst-Resolved High-Density Electroencephalography (EEG)

Atypical sensory experiences are highly prevalent in autistic children and include both hyper- and hypo-responsivity, often accompanied by sensory overload. Alpha oscillations (7-13 Hz), which dynamically regulate cortical excitability, represent a plausible neural mechanism underlying these phenomena: reduced alpha activity is associated with enhanced sensory responsiveness, whereas increased alpha supports suppression of external input. Although decreased alpha power has been repeatedly reported in autism, it remains unclear whether this reduction reflects lower oscillatory amplitude or reduced temporal stability of alpha rhythms, two mechanisms with distinct neurophysiological implications. To better characterize alpha activity in autism, we examined resting-state alpha dynamics in non-autistic children (NA; n = 39), autistic children (AU; n = 52), and siblings of autistic children (SIB; n = 26), aged 8-14 years. We combined traditional broadband measures of relative alpha power, parametric separation of periodic and aperiodic activity, and single-event analyses that quantify the temporal structure of alpha oscillations. Both broadband relative alpha power and periodic alpha power were reduced in autism over parietal regions, replicating prior findings. Importantly, ordinal analyses revealed an intermediate profile in siblings, supporting a liability-related gradient of alpha alterations. However, single-event analyses demonstrated that the average amplitude of individual alpha bursts did not differ between groups. Instead, autistic children showed significantly shorter alpha burst duration and reduced alpha abundance (i.e., proportion of time occupied by rhythmic alpha episodes), with siblings again exhibiting intermediate values. Linear regression analyses confirmed that reductions in relative and periodic alpha power were primarily driven by decreased alpha abundance rather than diminished burst amplitude. These findings indicate that altered alpha activity in autism reflects reduced temporal stability and density of alpha events rather than weaker oscillatory amplitude per se. Reduced persistence of alpha rhythms may therefore represent a neural marker of altered cortical excitability and sensory regulation in autism. Lay summaryAutistic children often experience the world differently at the sensory level, including being more easily overwhelmed by sounds, lights, or other stimuli. In this study, we looked at a type of brain activity called alpha rhythms, which help regulate how strongly the brain responds to incoming information. We found that, in autistic children, these alpha rhythms were not weaker when they occurred, but they lasted for a shorter time and happened less often. Siblings of autistic children showed an intermediate pattern. These results suggest that sensory differences in autism may be linked to less stable brain rhythms that normally help control sensory input. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/716324v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1be733dorg.highwire.dtl.DTLVardef@7fea49org.highwire.dtl.DTLVardef@1ee9124org.highwire.dtl.DTLVardef@17af139_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Frontal theta phase modulates asymmetric posterior neural mechanisms of spatial attention

Selective attention enables prioritization of behaviorally relevant information through coordinated control of neural excitability. Although theta-band (3-7 Hz) rhythms are implicated in top-down attentional sampling in non-human primates, how intrinsic theta phase organizes sensory gain and behavior in humans, and whether this control operates symmetrically across hemispheres, remains unknown. We recorded electroencephalography (EEG) and pupillometry in typically developing human participants (n = 21; 14.7 {+/-} 3.8 YO) performing a covert spatial attention task. Behaviorally, participants responded faster during leftward relative to rightward attention. This behavioral asymmetry was paralleled in the neural data: anticipatory modulation of parieto-occipital alpha and beta power emerged selectively during leftward attention, whereas rightward attention did not recruit comparable posterior oscillatory processes. Mechanistically, ipsilateral fronto-central theta phase emerged as a potential driver of this asymmetry. Intrinsic theta phase predicted trial-by-trial reaction time (RT) in a cue-direction-specific manner. During leftward attention, 3-Hz theta-phase over left fronto-central cortex modulated behavior and was significantly coupled to coordinated posterior alpha-band activity. In contrast, 6-7-Hz theta-phase over right fronto-central cortex modulated behavior during rightward attention but showed no relationship with alpha or beta modulation; instead, it modulated early sensory gain, indexed by P1 amplitude. Consistent with these distinct architectures, RT was jointly predicted by lower pre-stimulus alpha power and higher P1 amplitude over the attended hemisphere during leftward attention, whereas only P1 amplitude predicted performance during rightward attention. Resting-state alpha power did not differ across hemispheres, indicating that these effects were task-evoked rather than baseline spectral differences. Critically, older participants, who demonstrated enhanced behavioral performance, also exhibited a larger hemispheric asymmetry. Together, these findings reveal developmentally emerging, direction-specific neural control dynamics underlying human spatial attention. Significance StatementSpatial attention is often assumed to rely on symmetric neural mechanisms across left and right space. Using EEG in typically developing children and adolescents, we show that intrinsic theta rhythms organize attention through direction-specific control architectures. Leftward attention engages slower frontal theta (3-Hz) that coordinates posterior alpha and beta activity, consistent with oscillatory sensory gating. Rightward attention instead relies on faster theta (6-7-Hz) that modulates early sensory responses without coordinated alpha dynamics. These asymmetric mechanisms occur despite lack of hemispheric differences in resting alpha activity, indicating that they emerge during active control rather than reflecting baseline biases. These findings reveal that human attentional sampling is rhythmically organized but fundamentally asymmetric across space.

neuroscience↗

Neural oscillatory dynamics reveal altered top-down and integrative mechanisms during face processing in autistic children and unaffected siblings of autistic children

Face processing is fundamental to social communication and has been a major focus of autism research. While event-related potential (ERPs) studies of face processing have produced mixed results, little work has examined neuro-oscillatory dynamics, which may better capture the integrity of underlying networks. To address this gap, EEG was recorded from children aged 8-13 across three groups: autistic (n = 50), non-autistic (n = 38) and siblings of autistic children (n = 26), during a visual oddball task. In a blocked design, participants viewed faces and objects, presented upright and inverted (non-targets), to assess the face inversion effect (the FIE; a larger or earlier N170 to inverted than upright faces), and responded to infrequent shadow versions (targets). Analyses using permutation statistics and linear mixed models focused on non-target stimuli, quantifying face-related ERPs (P1, N170) and oscillatory activity associated with sensory and attentional processing (theta, alpha, gamma). Across groups, faces elicited earlier P1 and larger N170 amplitudes than objects, and showed a FIE. Furthermore, the rightward lateralization of the FIE was reduced for autistic participants. Analyses in the frequency domain revealed greater induced theta for inverted versus upright stimuli and for faces versus objects, revealing face specific effects, and stronger theta for inverted faces for the autistic and sibling groups, suggesting greater cognitive effort in processing these social stimuli. Gamma-band inter-trial phase coherence exhibited face selectivity only in the non-autistic group, pointing to differences in early network synchronization in autistic children relative to their non-autistic peers, whereas alpha event-related desynchronization did not vary by group or category. Altogether, these findings support altered neural synchronization/efficiency for autistic participants and siblings of autistic children, that is specific to face stimuli and seen despite largely typical sensory driven encoding. These data suggest that neural oscillatory assays are more sensitive to face processing differences in autism than broadband ERPs and that these oscillatory assays may be endophenotypic.

neuroscience↗

Testing the auditory steady-state response (ASSR) to 40-Hz and 27-Hz click trains in children with autism spectrum disorder and their first-degree biological relatives: A high-density electroencephalographic (EEG) study

MotivationAltered auditory processing likely contributes to core social and attentional impairments in autism spectrum disorder (ASD). The auditory steady-state response (ASSR)-- a neural measure of auditory processing and cortical excitatory-inhibitory balance--has yielded mixed results in ASD. This study uses high density electroencephalography (EEG) to evaluate ASSR in ASD and unaffected siblings to clarify neural mechanisms underlying auditory deficits in autism. MethodsHigh-density 70-channel EEG was recorded in children (8-12 years, IQ >80) with ASD (n=53), typically developing (TD) peers (n=35), and unaffected biological siblings (n=26) during 500-ms binaural click trains (27- and 40-Hz) in an active oddball task. ResultsNo group differences were observed in frequency-following responses (FFR) to 27- or 40-Hz stimuli, although higher 40-Hz power was associated with older age and better behavioral performance in ASD. The broad-band response from 180-250 ms was reduced in ASD for both stimulation frequencies--particularly in the low-frequency (<8 Hz) range--and significantly correlated with IQ and age. Siblings showed intermediate broad-band responses. DiscussionWhile FFRs appeared intact in ASD, we observed reduced broad-band response in the transition period to the steady state FFR, which was specific to low (<8-Hz) frequencies--potentially reflecting reduced synchronization at timescales that correspond with slower, syllabic rhythms ([~]4-8 Hz) occurring in natural speech. Intermediate responses in first-degree relatives suggest that this is related to genetic vulnerability for ASD and highlights its clinical relevance. These findings suggest intact sensory processing in ASD alongside possible top-down auditory feedback deficits, which may serve as heritable neurophysiological markers. Lay AbstractChildren with autism may process sounds differently, which could contribute to challenges with attention and communication. Here, electroencephalography (EEG) measured how the brain responds to rapidly repeating sounds and found that, while basic sound processing was intact, children with autism showed significantly reduced low-frequency responses that may reflect difficulty tracking speech rhythm. Interestingly, unaffected siblings showed an intermediate response, suggesting this may be a heritable marker of neural differences in autism.

neuroscience↗

Gait-level analysis of mouse open field behavior using deep learning-based pose estimation

1Gait and whole body posture are sensitive measures of the proper functioning of numerous neural circuits, and are often perturbed in many neurological, neuromuscular, and neuropsychiatric illnesses. Rodents provide a tractable model for elucidating disease mechanisms and interventions, however, studying gait and whole body posture in rodent models requires specialized methods and remains challenging. Here, we develop a simple assay that allows adoption of the commonly used open field apparatus for gait and whole body posture analysis. We leverage modern neural networks to abstract a mouse into keypoints and extract gait and whole body coordination metrics of the animal. Gait-level analysis allows us to detect every step of the animals movement and provides high resolution information about the animals behavior. We quantitate gait and whole body posture with high precision and accuracy across 62 highly visually diverse strains of mice. We apply our approach to characterize four genetic mutants with known gait deficits. In extended analysis, we demonstrate that multiple autism spectrum disorder (ASD) models show gait and posture deficits, implying this is a general feature of ASD. We conduct a large strain survey of 1898 mice, and find that gait and whole body posture measures are highly heritable in the laboratory mouse, and fall into three classes. Furthermore, the reference mouse strain, C57BL/6J, has a distinctly different gait and posture compared to other standard laboratory and wild-derived strains. We conduct a genome wide association study (GWAS) to define the genetic architecture of mouse movement in the open field. In sum, we describe a simple, sensitive, accurate, scalable, and ethologically relevant method of mouse gait and whole body posture analysis for behavioral neurogenetics. These results provide one of the largest laboratory mouse gait-level data resources for the research community and show the utility of automated machine learning approaches for deriving biological insights.

animal behavior and cognition↗