Biology subjects

Freedman, E. G.

Publications and source records attributed to Freedman, E. G..

At least 19 recordsLinked to original sources

bioRxiv2026

Functional ultrasound imaging reveals pathway-specific visual system reorganization in young Cln3-/- mice

CLN3 disease, or juvenile Batten disease, is a neurodegenerative lysosomal storage disorder in which visual impairment is typically the earliest clinical manifestation. Although retinal pathology has been extensively studied, functional alterations within central visual pathways remain poorly understood. Here, we used functional ultrasound (fUS) imaging to characterize visually evoked activity across central visual circuits in young Cln3 knockout (Cln3-/-) mice before the onset of severe retinal degeneration. Visually evoked hemodynamic responses were quantified in regions spanning the geniculostriate and extrageniculate visual pathways, including cortical, thalamic, and midbrain regions. To assess regional pathological burden, accumulation of subunit c of mitochondrial ATP synthase (SCMAS), a pathological marker of CLN3 disease, was examined using immunohistochemistry. We found that Cln3-/- mice exhibited pathway-specific alterations in visually evoked activity. Regions along the extrageniculate pathway, including the midbrain, posterior thalamus, and anterior secondary visual cortex, showed enhanced activation relative to wild-type controls. In contrast, activation within the geniculostriate pathway was reduced in the anterior thalamus and remained unchanged in the primary and posterior secondary visual cortex. SCMAS accumulation was elevated across all examined visual regions in Cln3-/- mice relative to wild-type controls, with greater accumulation observed in geniculostriate regions than in extrageniculate regions. These findings demonstrate early pathway-specific functional and pathological alterations in the visual system of Cln3-/- mice, suggesting pathway-level reorganization of central visual processing. This study advances understanding of central visual dysfunction in CLN3 disease and highlights fUS imaging as a sensitive approach for detecting early functional abnormalities in neurodegenerative disorders.

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bioRxiv2026

Atypical somatosensory adaptation in adults on the autism spectrum: a high-density electrophysiological (EEG) mapping study.

Adaptation to repetitive sensory inputs promotes efficient neural processing by attenuating responses to redundant information and reallocating resources to novel stimuli. Reduced adaptation has been proposed to contribute to atypical sensory reactivity in autism, but the physiological mechanisms underlying tactile adaptation remain poorly understood. Here, we examined short-term adaptation to repetitive vibrotactile stimulation in autistic and neurotypical adults using high-density electrophysiological recordings. Fifty participants (18-44 years; 25 autistic; 25 neurotypical), received sequences of four brief vibrations to the index fingertip while viewing silent videos. Neural responses were analyzed for an early negative deflection (N1, [~]100 milliseconds) indexing basic stimulus recognition, and a later positive deflection (P2, [~]200-300 milliseconds) indexing higher-order contextual and attentional processing. Adaptation was quantified as changes in response magnitude across the four vibrations. The N1 did not differ between groups, showing minimal change across repetitions, indicating comparable processing of basic tactile features. In contrast, the P2 was significantly larger overall in the autistic group. Across both groups, responses to the first vibration in each sequence were greater than responses to subsequent vibrations, reflecting re-sensitization following the inter-sequence interval. Autistic participants exhibited consistently amplified P2 responses to initial vibrations, suggesting heightened re-sensitization rather than impaired within-sequence adaptation. Associations between neural responses and clinical measures of autistic traits and tactile sensitivity were modest. These findings indicate that autistic adults show amplified higher-order neural responses to tactile input alongside preserved short-term adaptation. Heightened re-sensitization to repeated touch may reflect shortened refractory periods, contributing to sensory hyper-reactivity and increased perceptual load.

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bioRxiv2026

Neural markers of visual working memory during an upper extremity movement-coupled task: a mobile brain-body imaging (MOBI) study.

Optimal goal-directed behavior in everyday life involves the appropriate coupling of cognition and movement. In this study we employed a mobile brain-body imaging (MoBI) system that integrated time-synchronized high-density electroencephalography with 3-dimensional motion capture during a touchscreen visual working memory task requiring dynamic upper extremity reach responses. Using this framework we examined how increasing memory load (i.e. from 1-disc to 4-discs) influences behavior and scalp-recorded neural activity when cognitive and motor processes are coupled within a single task and whether these effects are modulated by handedness. Increasing memory load reliably degraded working memory task performance and slowed motor preparation, while core movement execution measures remained largely preserved. Regarding electroencephalography data, parieto-occipital activity increased with load during both the early visual-evoked N1 and the delay period. However, load-related modulation reached a plateau at the 3-disc condition during the delay period only. Posterior-frontal engagement also strengthened as load increased, consistent with demands on attentional control, memory maintenance, and sensorimotor planning. Brain-behavior associations were most robust at a moderate level (2-disc), where contralateral delay activity correlated with both cognitive and motor performance measures. Finally, although handedness exerted selective behavioral effects, it did not modulate load-related parieto-occipital neural activity. Together, these findings demonstrate that a multimodal MoBI approach captures integrated cognitive-motor dynamics during working memory-guided actions, providing a more comprehensive characterization of behavior and underlying neural signatures than either modality alone. This framework offers a translational approach for studying cognitive-motor interactions and their potential disruption in neurological conditions such as Parkinsons disease.

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bioRxiv2025

Longitudinal Exploration of Auditory Sensory-Perceptual Processing in CLN3 Disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): A High-Density Auditory Evoked Potential (AEP) Study.

BackgroundThere is currently limited information about sensory and perceptual abilities across the progression of CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis; Batten disease), a recessively inherited lysosomal storage disorder and a leading cause of childhood neurodegeneration. Clinical symptoms include vision loss, motor impairments, and cognitive challenges, making it difficult to accurately assess neurocognitive and perceptual abilities. Thus, there is a critical need to identify objective biomarkers that can be used to inform disease progression and track treatment response in this population. MethodsThis exploratory study investigates longitudinal changes in auditory sensory perceptual processing in a small sample of individuals with genetically confirmed CLN3 disease (N=4; 3 male) compared to a cross-sectional sample of 60 neurotypical (NT) controls using high-density electroencephalography (EEG). We utilized a duration mismatch negativity (MMN) paradigm, identical to what has been used in our previous cross-sectional study. We examined the auditory evoked potentials (AEPs) of the standard tones across three different stimulus onset asynchrony conditions and examined the N1 and P2 components of the AEP. ResultsWe found age related differences in the amplitudes of the N1 and P2 components in individuals with CLN3 disease relative to NT controls. These amplitude differences were most notable in CLN3 disease when participants were presented with standard tones that had the slowest presentation rate. Specifically, N1 and P2 amplitudes were more negative than NT controls in childhood and adolescence and as CLN3 disease participants aged, the amplitude of the AEPs was greater than controls. Further, a more positive N1 amplitude during the longest stimulus presentation condition was associated with both reduced verbal intelligence and working memory abilities in CLN3 disease participants. ConclusionsOur preliminary findings parallel recently published work in a mouse model of CLN3 disease that showed both sex- and age-dependent disruptions in central auditory processing. Taken together, we demonstrate the utility of auditory EEG measures as a sensitive, objective and translational measure in CLN3 disease that may serve as a potential outcome measure useful in tracking disease progression. Continued work is needed in humans focused on sex-based differences and longitudinal changes of auditory processing in CLN3 disease.

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bioRxiv2025

Processing of Emotional Faces Has Unique Functional and Cytoarchitectural Associations in those with an Autism Spectrum Diagnosis.

Those with an autism spectrum diagnosis (ASD) have been found to process emotional faces differently than other populations. Processing of emotional faces requires engagement of temporal, frontal, occipital, and limbic brain regions. Functional activity has been shown to differ in those with an ASD, particularly in the amygdala, inferior frontal cortex (IFC), and temporal brain regions. However, the consistency and direction of these associations have been inconsistent across studies. Recent findings have demonstrated that measures of neuron density differ in those with an ASD. Some of these regional differences in cytoarchitecture coincide with regions important to emotional facial processing. Therefore, the interaction between cytoarchitecture and functional activity may be important in elucidating unique neurophysiology in ASD. The present study uses diffusion weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) data from the Adolescent Brain Cognitive Developmentsm (ABCD(R)) study to investigate the relationship between cytoarchitecture and functional activity during emotional face processing in those with an ASD. 75 individuals with a reported ASD and 6,396 individuals with no reported diagnosis of an ASD (nASD) were identified. The emotional n-back (EN-Back) task was administered during fMRI acquisition, activating regions of the brain associated with processing emotional faces. Neuron cell body density was positively correlated with functional activation in the left amygdala in the ASD group but not the nASD group. These findings suggest that a unique relationship may exist between neuron cell body density in the left amygdala and functional activity while processing emotional faces in those with an ASD.

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bioRxiv2025

Sex-specific and age-related progression of auditory neurophysiological deficits in the Cln3 mouse model of Batten disease

CLN3 disease is a prevalent form of Neuronal Ceroid Lipofuscinosis (NCL) caused by inherited mutations in the CLN3 gene, with symptoms such as vision loss, language impairment, and cognitive decline. The early onset of visual deficits complicates neurological assessment of brain pathophysiology underlying cognitive decline, while the small number of CLN3 mutation cases in humans hinders the study of sex differences. Building on our recent progress in assessing auditory neurophysiological changes in CLN3 patients, we developed a parallel approach using electroencephalography arrays in Cln3 knockout (Cln3-/-) mice to investigate the longitudinal progression of auditory processing deficits in both sexes. We employed a duration mismatch negativity (MMN) paradigm, similar to that used in our CLN3 patient studies, to assess the automatic detection of pattern changes in a sequence of stimuli. Wild-type mice of both sexes showed robust duration MMN responses when assessed longitudinally in the same subjects from 3 to 9 months of age. In contrast, female Cln3-/- mice developed consistent MMN deficits throughout this age range, while male Cln3-/- mice exhibited MMN deficits at younger ages that were mitigated at older ages. Analyses of auditory brainstem responses indicate that MMN abnormalities in Cln3-/- mice are not due to peripheral hearing loss. Instead, these deficits originate centrally from sex-specific and age-related changes in auditory evoked potentials elicited by standard and deviant stimuli. Our findings reveal a sex-specific progression of central auditory processing deficits in Cln3-/- mice, supporting auditory duration MMN as a translational neurophysiological biomarker for mechanistic studies and therapeutic development. Significance StatementCLN3 disease is an inherited neurodegenerative disorder with progressive decline in cognitive functioning and verbal abilities. The neuropathophysiological mechanisms underlying this decline remain poorly understood, highlighting the urgent need for objective neurological biomarkers to advance mechanistic insights and therapeutic development. Our identification of central auditory processing and change detection deficits in Cln3-/- mice, mirroring findings from our recent studies in CLN3 patients, validates auditory MMN as a translational neurophysiological biomarker bridging pre-clinical and clinical research. Moreover, our discovery of sex-specific, non-linear progression of MMN deficits emphasizes the necessity of developing disease management strategies tailored to each sex. This finding also provides a foundation for investigating both pathogenic and compensatory neural mechanisms to inform the development of individualized treatments.

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bioRxiv2024

Neurophysiological measures of covert semantic processing in neurotypical adolescents actively ignoring spoken sentence inputs: A high-density event-related potential (ERP) study.

Language comprehension requires semantic processing of individual words and their context within a sentence. Well-characterized event-related potential (ERP) components (the N400 and late positivity component (LPC/P600)) provide neuromarkers of semantic processing, and are robustly evoked when semantic errors are introduced into sentences. These measures are useful for evaluating semantic processing in clinical populations, but it is not known whether they can be evoked in more severe neurodevelopmental disorders where explicit attention to the sentence inputs cannot be objectively assessed (i.e., when sentences are passively listened to). We evaluated whether N400 and LPC/P600 could be detected in adolescents who were explicitly ignoring sentence inputs. Specifically, it was asked whether explicit attention to spoken inputs was required for semantic processing, or if a degree of automatic processing occurs when the focus of attention is directed elsewhere? High-density ERPs were acquired from twenty-two adolescents (7-12 years), under two experimental conditions: 1) individuals actively determined whether the final word in a sentence was congruent or incongruent with sentence context, or 2) passively listened to background sentences while watching a video. When sentences were ignored, N400 and LPC/P600 were robustly evoked to semantic errors, albeit with reduced amplitudes and protracted/delayed latencies. Statistically distinct topographic distributions during passive versus active paradigms pointed to distinct generator configurations for semantic processing as a function of attention. Covert semantic processing continues in neurotypical adolescents when explicit attention is withdrawn from sentence inputs. As such, this approach could be used to objectively investigate semantic processing in populations with communication deficits.

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bioRxiv2024

Intact Somatosensory Temporal Sensitivity in Adults on the Autism Spectrum: A High-Density Electrophysiological Mapping Study Using the Mismatch Negativity (MMN) Sensory Memory Paradigm.

Atypical reactivity to somatosensory inputs is common in autism spectrum disorder and carries considerable impact on downstream social communication and quality of life. While behavioral and survey work have established differences in the perception of somatosensory information, little has been done to elucidate the underlying neurophysiological processes that drive these characteristics. Here, we implemented a duration-based somatosensory mismatch negativity paradigm to examine the role of temporal sensitivity and sensory memory in the processing of vibrotactile information in autistic (n=30) and neurotypical (n=30) adults. To capture the variability in responses between groups across a range of duration discrepancies, we compared the electrophysiological responses to frequent standard vibrations (100 ms) and four infrequent deviant vibrations (115, 130, 145, and 160 ms). The same stimuli were used in a follow-up behavioral task to determine active detection of the infrequent vibrations. We found no differences between the two groups with regard to discrimination between standard and deviant vibrations, demonstrating comparable neurologic and behavioral temporal somatosensory perception. However, exploratory analyses yielded subtle differences in amplitude at the N1 and P220 time points. Together, these results indicate that the temporal mechanisms of somatosensory discrimination are conserved in adults on the autism spectrum, though more general somatosensory processing may be affected. We discuss these findings in the broader context of the MMN literature in autism, as well as the potential role of cortical maturity in somatosensory mechanisms.

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bioRxiv2024

Reduced Proactive and Reactive Cognitive Flexibility in Older Adults Underlies Performance Costs During Dual-Task Walking: A Mobile Brain/Body Imaging (MoBI) Study

Age-related reductions in cognitive flexibility may limit modulation of control processes during systematic increases to cognitive-motor demands, exacerbating dual-task costs. In this study, behavioral and neurophysiologic changes to proactive and reactive control during progressive cognitive-motor demands were compared across older and younger adults to explore the basis for age-differences in cognitive-motor interference (CMI). 19 younger (19 - 29 years old, mean age = 22.84 +/- 2.75 years, 6 male, 13 female) and 18 older (60 - 77 years old, mean age = 67.89 +/- 4.60 years, 9 male, 9 female) healthy adults completed cued task-switching while alternating between sitting and walking on a treadmill. Gait kinematics, task performance measures, and brain activity were recorded using electroencephalography (EEG) based Mobile Brain/Body Imaging (MoBI). Response accuracy on easier trial types improved in younger, but not older adults when they walked while performing the cognitive task. As difficulty increased, walking provoked accuracy costs in older, but not younger adults. Both groups registered faster responses and reduced gait variability during dual-task walking. Older adults exhibited lower amplitude modulations of proactive and reactive neural activity as cognitive-motor demands systematically increased, which may reflect reduced flexibility for progressive preparatory and reactive adjustments over behavioral control.

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bioRxiv2024

It's all in the timing: Delayed feedback in autism may weaken predictive mechanisms during contour integration

Humans rely on predictive mechanisms during visual processing to efficiently resolve incomplete or ambiguous sensory signals. While initial low-level sensory data are conveyed by feedforward connections, feedback connections are believed to shape sensory processing through conveyance of statistical predictions based on prior exposure to stimulus configurations. Individuals with autism spectrum disorder (ASD) show biases in stimulus processing toward parts rather than wholes, suggesting their sensory processing may be less shaped by statistical predictions acquired through prior exposure to global stimulus properties. Investigations of illusory contour (IC) processing in neurotypical (NT) adults have established a well-tested marker of contour integration characterized by a robust modulation of the visually evoked potential (VEP) - the IC-effect - that occurs over lateral occipital scalp during the timeframe of the N1 component. Converging evidence strongly supports the notion that this IC-effect indexes a signal with significant feedback contributions. Using high-density VEPs, we compared the IC-effect in 6-17-year-old children with ASD (n=32) or NT development (n=53). Both groups of children generated an IC-effect that was equivalent in amplitude. However, the IC-effect notably onset 21ms later in ASD, even though timing of initial VEP afference was identical across groups. This suggests that feedforward information predominated during perceptual processing for 15% longer in ASD compared to NT children. This delay in the feedback dependent IC-effect, in the context of known developmental differences between feedforward and feedback fibers, suggests a potential pathophysiological mechanism of visual processing in ASD, whereby ongoing stimulus processing is less shaped by statistical prediction mechanisms. SIGNIFICANCE STATEMENTChildren with autism often present with an atypical visual perceptual style that emphasizes parts or details over the whole. Using electroencephalography (EEG), this study identifies delays in the visual feedback from higher order sensory brain areas to primary sensory regions. Because this type of visual feedback is thought to carry information about prior sensory experiences, individuals with autism may have difficulty efficiently using prior experience and predictions to help make sense of incoming new visual information. This provides empirical neural evidence to support theories of disrupted sensory perception mechanisms in autism.

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bioRxiv2023

Maintaining task performance levels under cognitive load while walking requires widespread reallocation of neural resources: A Mobile Brain-Body Imaging (MoBI) study.

The neural underpinnings of increasing cognitive load during walking, despite being ubiquitous in everyday life, is still not fully understood. This study elucidates the neural mechanisms underlying increased cognitive load while walking, by employing 2 versions of a Go/NoGo response inhibition task, namely the 1-back Go/NoGo task and the more cognitively demanding 2-back Go/NoGo task, during sitting or walking on a treadmill. By using the Mobile Brain/Body Imaging (MoBI) modality, electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and task-related behavioral responses were collected from 34 young adults for the 1-back Go/NoGo task and 34 young adults for the 2-back Go/NoGo task. Interestingly, increasing cognitive-inhibitory load from 1-back to 2-back Go/NoGo during walking was not associated with any detectable costs in response accuracy, response speed, or gait consistency; however, it came with attenuations in walking-related EEG amplitude changes during both successful inhibitions (correct rejections) and successful executions (hits) of the Go motor response. During correct rejections, such attenuations were detected over frontal regions, during latencies related to sensory gain control, conflict monitoring and working memory storage and processing. During hits, attenuations were found over left-parietal regions, during latencies related to orienting attention to and selecting the Go motor plan, as well as over central regions, during latencies linked to executing the Go motor response. The pattern of attenuation in walking-related EEG amplitude changes, manifested by the 2-back Go/NoGo group, is thought to reflect more effortful recalibration of the above neural processes, a mechanism which might be a key driver of performance maintenance in the face of increased cognitive demands while walking. Overall, the present findings shed light on the extent of the neurocognitive capacity of young adults, thus revealing the employed methodology as promising for better understanding how factors such as aging or neurological disorders could impinge on this capacity.

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bioRxiv2023

Probing the neurophysiology of temporal sensitivity in the somatosensory system using the mismatch negativity (MMN) sensory memory paradigm.

Duration is an amodal feature common to all sensory experiences, but current understanding of sensory-perceptual processing of the temporal qualities of somatosensation remains incomplete. The goal here was to better understand how the brain processes the duration of vibrotactile information, which was assessed by parametrically varying the extent of duration deviance in a somatosensory mismatch negativity (sMMN) paradigm while high-density event-related potential (ERP) recordings were acquired. Healthy young adults (N = 20; aged 18-31 years) received stimulation of the right index fingertip with a 100 ms vibro-tactile input on 80% of trials while the other 20% of trials consisted of deviant stimuli with one of the following durations: 115, 130, 145, or 160 ms. Deviant conditions were presented in separate blocks with deviants pseudo-randomly distributed amongst the 100 ms standards. Participants ignored these inputs while watching a silent movie. Robust sMMN responses, with a dipolar field over the left antero-superior parietal cortex, were detected when deviant stimuli were 130, 145, and 160 ms, but not when they were 115 ms. The amplitudes of the sMMN correlated with individuals subsequent abilities to detect duration deviants when actively attempting to discriminate their presence. This simple-to-execute sMMN paradigm holds promise for the assessment of tactile processing differences in clinical populations where tactile sensitivities are a common aspect of the phenotype (e.g., Autism, Fragile-X syndrome).

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bioRxiv2023

Autism is Associated with in vivo Changes in Gray Matter Neurite Architecture.

Postmortem investigations in autism have identified anomalies in neural cytoarchitecture across limbic, cerebellar, and neocortical networks. These anomalies include narrow cell mini-columns and variable neuron density. However, difficulty obtaining sufficient post-mortem samples has often prevented investigations from converging on reproducible measures. Recent advances in processing magnetic resonance diffusion weighted images (DWI) make in vivo characterization of neuronal cytoarchitecture a potential alternative to post-mortem studies. Using extensive DWI data from the Adolescent Brain Cognitive Developmentsm (ABCD(R)) study 142 individuals with an Autism diagnosis were compared with 8971 controls using a restriction spectrum imaging (RSI) framework that characterized total neurite density (TND), its component restricted normalized directional diffusion (RND), and restricted normalized isotropic diffusion (RNI). A significant decrease in TND was observed in Autism in the right cerebellar cortex ({beta}=-0.005, SE =0.0015, p=0.0267), with significant decreases in RNI and significant increases in RND found diffusely throughout posterior and anterior aspects of the brain, respectively. Furthermore, these regions remained significant in post-hoc analysis when the ASD sample was compared against a subset of 1404 individuals with other psychiatric conditions (pulled from the original 8971). These findings highlight the importance of characterizing neuron cytoarchitecture in Autism and the significance of their incorporation as physiological covariates in future studies. Lay abstractChildren with autism have differences in neuron structure unique from the general population and populations with attention, anxiety, and depression disorders. Brain imaging data on over 11,000 children was acquired at ages 9 and 11 years-of-age. Estimates of neuron density were derived from brain imaging data using recently validated techniques and comparative groups were composed using parent reported diagnosis of autism and other common psychiatric disorders. Consistent macro-structural changes in brain have been difficult to replicate and micro-structural changes have been historically difficult to acquire with other methodologies. We identified regional differences in the density of neuron cell bodies, neuron branching, and total neuron density in those with a reported diagnosis of ASD. Findings were consistent when compared against those with other psychiatric disorders in post-hoc analysis. These findings demonstrate the viability and importance of investigating in vivo changes to neurons in those with autism to advance our current understanding of related physiology.

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bioRxiv2022

Paradoxical improvement of cognitive control in older adults under dual-task walking conditions is associated with more flexible reallocation of neural resources: A Mobile Brain-Body Imaging (MoBI) study.

Combining walking with a demanding cognitive task is traditionally expected to elicit decrements in gait and/or cognitive task performance. However, it was recently shown that, in a cohort of young adults, most participants paradoxically improved performance when walking was added to performance of a Go/NoGo response inhibition task. The present study aims to extend these previous findings to an older adult cohort, to investigate whether this paradoxical improvement when dual-tasking is observed in healthy older adults. Mobile Brain/Body Imaging (MoBI) was used to record electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and behavioral responses in the Go/NoGo task, during sitting or walking on a treadmill, in 34 young adults and 37 older adults. Increased response accuracy during walking, independent of age, was found to correlate with slower responses to stimuli and with walking-related EEG amplitude modulations over latencies and topographies related to the cognitive component of inhibition. On the other hand, aging, independent of response accuracy during walking, was found to correlate with slower treadmill walking speeds and attenuation in walking-related EEG amplitude modulations over latencies and topographies associated with the motor component of inhibition. Older adults whose response accuracy improved during walking manifested neural signatures of both behavioral improvement and aging, suggesting that their flexibility in reallocating neural resources while walking might be maintained for the cognitive but not for the motor inhibitory component. These distinct neural signatures of aging and behavior can potentially be used to identify super-agers, or individuals at risk for cognitive decline due to aging or neurodegenerative disease.

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bioRxiv2022

The strength of feedback processing is associated with resistance to visual backward masking during illusory contour processing in adult humans.

Re-entrant feedback processing is a key mechanism of visual object-recognition, especially under compromised viewing conditions where only sparse information is available and object features must be interpolated. Illusory contour stimuli are commonly used in conjunction with visual evoked potentials (VEP) to study these filling-in processes, with characteristic modulation of the VEP in the ~100-150ms timeframe associated with this re-entrant processing. Substantial inter-individual variability in timing and amplitude of feedback-related VEP modulation is observed, raising the question whether this variability might underlie inter-individual differences in the ability to form strong perceptual gestalts. Backward masking paradigms have been used to study inter-individual variance in the ability to form robust object perceptions before processing of the mask interferes with object-recognition. Some individuals recognize objects when the time between target object and mask is extremely short, whereas others struggle to do so even at longer target-to-mask intervals. We asked whether timing and amplitude of feedback-related VEP modulations were associated with individual differences in resistance to backward masking. Participants (N=40) showed substantial performance variability in detecting illusory contours at intermediate target-to-mask intervals (67ms and 117ms), allowing us to use kmeans clustering to divide the population into four performance groups (poor, low-average, high-average, superior). There was a clear relationship between the amplitude (but not the timing) of feedback-related VEP modulation and illusory contour detection during backward masking. We conclude that individual differences in the strength of feedback processing in neurotypical humans lead to differences in the ability to quickly establish perceptual awareness of incomplete visual objects.

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bioRxiv2022

Young adults who improve performance during dual-task walking show more flexible reallocation of cognitive resources: A Mobile Brain-Body Imaging (MoBI) study.

In young adults, pairing a taxing cognitive task with walking can have different effects on gait and cognitive task performance. In some cases, performance clearly declines whereas in others compensatory mechanisms maintain performance even under dual-task conditions. This study set out to investigate the preliminary finding of behavioral improvement in Go-NoGo response inhibition task performance during walking compared to sitting, which was observed at the piloting stage. Mobile Brain/Body Imaging (MoBI) was used to record electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and behavioral responses in the cognitive task, during sitting or walking on a treadmill. In a cohort of twenty-six (26) young adults, fourteen (14) participants improved in measures of cognitive task performance while walking compared to sitting. These participants exhibited walking-related EEG amplitude reductions over frontal brain scalp regions during key stages of inhibitory control (conflict monitoring, control implementation and pre-motor stages), accompanied by reduced stride-to-stride variability and faster responses to stimuli compared to those who did not improve. In contrast, the twelve (12) participants who did not improve exhibited no EEG amplitude differences across physical condition. The neural activity changes associated with performance improvement during dual tasking hold promise as cognitive flexibility markers that can potentially help assess cognitive decline in aging and neurodegeneration.

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bioRxiv2022

Evoking the N400 Event-Related Potential (ERP) Component Using a Publicly Available Novel Set of Sentences with Semantically Incongruent or Congruent Eggplants (Endings).

During speech comprehension, the ongoing context of a sentence is used to predict sentence outcome by limiting subsequent word likelihood. Neurophysiologically, violations of context-dependent predictions result in amplitude modulations of the N400 event-related potential (ERP) component. While N400 is widely used to measure semantic processing and integration, no publicly-available auditory stimulus set is available to standardize approaches across the field. Here, we developed an auditory stimulus set of 404 sentences that utilized the semantic anomaly paradigm, provided cloze probability for all stimuli, and was developed for both children and adults. With 20 neurotypical adults, we validated that this set elicits robust N400s, as well as two additional semantically-related ERP components: the late positivity component and the recognition potential. This stimulus set and the 20 high-density (128-channel) electrophysiological datasets are made publicly available here to promote data sharing and reuse. Future studies that use this stimulus set to investigate sentential semantic comprehension in both control and clinical populations may benefit from the increased comparability and reproducibility within this field of research.

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bioRxiv2022

Enhanced anticipatory biasing of visuospatial attention in deaf native-signing adults indexed by alpha-band (8-14 Hz) oscillatory neural activity

Deaf people show increased visuospatial attention abilities, especially towards peripheral inputs, but the neural mechanisms of these heightened abilities are not yet understood. In hearing individuals, topographically-specific alpha-band oscillatory activity (8-14 Hz) over parieto-occipital regions has been associated with active suppression of irrelevant locations. Here, we asked whether increases in this spatially-specific anticipatory oscillatory mechanism might underpin enhanced visuospatial attention abilities in deaf individuals, on the premise that deaf people might be more adept at transiently engaging and disengaging attentional processes involved in processing peripheral inputs. An alternative hypothesis was that deaf individuals might not produce lateralized alpha-band activity, because of the need to continuously monitor the periphery due to the absence of an auxiliary auditory spatial alerting system. High-density electroencephalography was recorded from 20 deaf native signers and 20 hearing non-signers performing a cued covert visuospatial attention task. Deaf participants responded significantly more rapidly and accurately and showed highly typical alpha-band lateralization during the cue-target interval of the task. Topographic analysis showed a greater extent of alpha-band anticipatory activity over right parietal scalp, suggesting sequestration of extra-visual attentional circuits (i.e., unused auditory regions), and post-hoc analysis pointed to substantially earlier onset of this activity during the cue-target interval. The presence of cue-evoked anticipatory alpha lateralization in deaf participants suggests that they are rapidly engaging and disengaging attentional processes involved in orienting attention to the periphery. The earlier and more extensive engagement of these anticipatory oscillatory processes may contribute to the improved visuospatial performance observed in these individuals. Significance StatementPrior to this study, it was not known whether deaf people demonstrate lateralization of alpha-band oscillatory electroencephalographic (EEG) activity over the posterior region of the brain, which plays a role in the suppression of uncued regions of space during cued visuospatial attention tasks. We found that this lateralized pattern was observable in deaf participants and was not significantly different from that seen in hearing participants, except that alpha activity onsets earlier in deaf participants. However, when cue directions were collapsed, the scalp topographies of deaf participants showed a greater distribution of alpha activity, suggesting that they recruited a brain region typically reserved for audiospatial attentional control during the visuospatial attention task. Additionally, deaf participants responded significantly more quickly and accurately compared to hearing participants, demonstrating increased visuospatial attention abilities.

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