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 (12-17 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 Covert semantic processing continues in neurotypical adolescents when explicit attention is withdrawn from sentence inputs.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.

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®) 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 (ß = -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 autism 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.

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

Humans rely on predictive and integrative mechanisms during visual processing to efficiently resolve incomplete or ambiguous sensory signals. Although initial low-level sensory data are conveyed by feedforward connections, feedback connections are believed to shape sensory processing through automatic conveyance of statistical probabilities 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 visual 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- to 17-yr-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 21 ms later in ASD, even though initial VEP afference was identical across groups. This suggests that feedforward information predominated during perceptual processing for 15% longer in ASD compared with 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 visual feedback.NEW & NOTEWORTHY Children 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 or putting together parts into a whole to help make sense of incoming new visual information. This provides empirical neural evidence to support theories of disrupted sensory perception mechanisms in autism.

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 (MMN) 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.

Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome.

BACKGROUND: In the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is "stationarity" of the underlying responses - i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary. METHODS: AEPs were recorded to simple 100 Hz tones from 18 RTT and 27 age-matched controls (Ages: 6-22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures. RESULTS: Substantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a "neural unreliability" account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident. CONCLUSIONS: To accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

Ventilation during COVID-19 in a school for students with intellectual and developmental disabilities (IDD).

BACKGROUND: This study examined the correlation of classroom ventilation (air exchanges per hour (ACH)) and exposure to CO2 ≥1,000 ppm with the incidence of SARS-CoV-2 over a 20-month period in a specialized school for students with intellectual and developmental disabilities (IDD). These students were at a higher risk of respiratory infection from SARS-CoV-2 due to challenges in tolerating mitigation measures (e.g. masking). One in-school measure proposed to help mitigate the risk of SARS-CoV-2 infection in schools is increased ventilation. METHODS: We established a community-engaged research partnership between the University of Rochester and the Mary Cariola Center school for students with IDD. Ambient CO2 levels were measured in 100 school rooms, and air changes per hour (ACH) were calculated. The number of SARS-CoV-2 cases for each room was collected over 20 months. RESULTS: 97% of rooms had an estimated ACH ≤4.0, with 7% having CO2 levels ≥2,000 ppm for up to 3 hours per school day. A statistically significant correlation was found between the time that a room had CO2 levels ≥1,000 ppm and SARS-CoV-2 PCR tests normalized to room occupancy, accounting for 43% of the variance. No statistically significant correlation was found for room ACH and per-room SARS-CoV-2 cases. Rooms with ventilation systems using MERV-13 filters had lower SARS-CoV-2-positive PCR counts. These findings led to ongoing efforts to upgrade the ventilation systems in this community-engaged research project. CONCLUSIONS: There was a statistically significant correlation between the total time of room CO2 concentrations ≥1,000 and SARS-CoV-2 cases in an IDD school. Merv-13 filters appear to decrease the incidence of SARS-CoV-2 infection. This research partnership identified areas for improving in-school ventilation.

Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome.

Background: In the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is "stationarity" of the underlying responses - i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary. Methods: AEPs were recorded to simple 100Hz tones from 18 RTT and 27 age-matched controls (Ages: 6-22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures. Results: Substantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a "neural unreliability" account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident. Conclusions: To accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome.

Background In the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is "stationarity" of the underlying responses - i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary. Methods AEPs were recorded to simple 100Hz tones from 18 RTT and 27 age-matched controls (Ages: 6-22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures. Results Substantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a "neural unreliability" account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident. Conclusions To accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

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.

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.

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.

Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): an auditory evoked potential study of the duration-evoked mismatch negativity (MMN).

BACKGROUND: We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of "duration" processing. Given decrements in auditory processing abilities associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials. METHODS: We employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system. RESULTS: Data from individuals with CLN3 disease (N = 21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N = 41; ages 6-26 years). CONCLUSIONS: Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.

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 low-level processing of the temporal qualities of somatosensation remains poorly understood. The goal of the present study was to evaluate electrophysiological discrimination of parametric somatosensory stimuli to better understand how the brain processes the duration of tactile information. This research used a somatosensory mismatch negativity (sMMN) paradigm to evaluate electrophysiological sensitivity to differences in the duration of vibrotactile stimuli in healthy young adults. Specifically, a 100 ms standard vibration was presented 80% of the time while the remaining 20% of presentations were made up of deviant stimuli with one of the following durations: 115, 130, 145, or 160 ms. When a deviation from the anticipated tactile input is detected, the distinct electrophysiological signature of the sMMN is present. A companion behavioral task assessed individual thresholds for cognizant awareness of the standard and deviant vibrotactile stimuli. The results of the present study demonstrated a sMMN response when deviant stimuli were 130, 145, and 160 ms, but not when they were 115 ms. This suggests that on average the participants did not electrophysiologically discriminate between the 100 and 115 ms. Future work may apply this paradigm to better understand atypical tactile sensitivity in various clinical conditions.

No evidence for differential saccadic adaptation in children and adults with an autism spectrum diagnosis.

Background: Altered patterns of eye-movements during scene exploration, and atypical gaze preferences in social settings, have long been noted as features of the Autism phenotype. While these are typically attributed to differences in social engagement and interests (e.g., preferences for inanimate objects over face stimuli), there are also reports of differential saccade measures to non-social stimuli, raising the possibility that fundamental differences in visuo-sensorimotor processing may be at play. Here, we tested the plasticity of the eye-movement system using a classic saccade-adaptation paradigm to assess whether individuals with ASD make typical adjustments to their eye-movements in response to experimentally introduced errors. Saccade adaptation can be measured in infants as young as 10 months, raising the possibility that such measures could be useful as early neuro-markers of ASD risk. Methods: Saccade amplitudes were measured while children and adults with ASD (N = 41) and age-matched typically developing (TD) individuals (N = 68) made rapid eye-movements to peripherally presented targets. During adaptation trials, the target was relocated from 20-degrees to 15-degrees from fixation once a saccade to the original target location was initiated, a manipulation that leads to systematic reduction in saccade amplitudes in typical observers. Results: Neither children nor adults with ASD showed any differences relative to TD peers in their abilities to appropriately adapt saccades in the face of persistently introduced errors. Conclusion: Of the three studies to date of saccade adaptation in ASD, none have shown deficits in saccade adaptation that are sufficient to generalize to the whole or a subgroup of the ASD population. Unlike prior studies, we found no evidence for a slower adaptation rate during the early adaptation phase, and no of evidence greater variance of saccade amplitudes in ASD. In post hoc analysis, there was evidence for larger primary saccades to non-adapted targets, a finding requiring replication in future work.

Ventilation during COVID-19 in a school for students with intellectual and developmental disabilities (IDD).

Background: This study examined the correlation of classroom ventilation (air exchanges per hour (ACH)) and exposure to CO2 ≥1,000 ppm with the incidence of SARS-CoV-2 over a 20-month period in a specialized school for students with intellectual and developmental disabilities (IDD). These students were at a higher risk of respiratory infection from SARS-CoV-2 due to challenges in tolerating mitigation measures (e.g. masking). One in-school measure proposed to help mitigate the risk of SARS-CoV-2 infection in schools is increased ventilation. Methods: We established a community-engaged research partnership between the University of Rochester and the Mary Cariola Center school for students with IDD. Ambient CO2 levels were measured in 100 school rooms, and air changes per hour (ACH) were calculated. The number of SARS-CoV-2 cases for each room was collected over 20 months. Results: 97% of rooms had an estimated ACH ≤4.0, with 7% having CO2 levels ≥2,000 ppm for up to 3 hours per school day. A statistically significant correlation was found between the time that a room had CO2 levels ≥1,000 ppm and SARS-CoV-2 PCR tests normalized to room occupancy, accounting for 43% of the variance. No statistically significant correlation was found for room ACH and per-room SARS-CoV-2 cases. Rooms with ventilation systems using MERV-13 filters had lower SARS-CoV-2-positive PCR counts. These findings led to ongoing efforts to upgrade the ventilation systems in this community-engaged research project. Conclusions: There was a statistically significant correlation between the total time of room CO2 concentrations ≥1,000 and SARS-CoV-2 cases in an IDD school. Merv-13 filters appear to decrease the incidence of SARS-CoV-2 infection. This research partnership identified areas for improving in-school ventilation.

Maintaining Task Performance Levels Under Cognitive Load While Walking Requires Widespread Reallocation of Neural Resources.

This study elucidates the neural mechanisms underlying increasing cognitive load while walking by employing 2 versions of a response inhibition task, the '1-back' version and the more cognitively demanding '2-back' version. By using the Mobile Brain/Body Imaging (MoBI) modality, electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and task-related behavioral responses were collected while young adults (n = 61) performed either the 1-back or 2-back response inhibition task. Interestingly, increasing inhibitory difficulty from 1-back to 2-back during walking was not associated with any detectable costs in response accuracy, response speed, or gait consistency. However, the more difficult cognitive task was associated with distinct EEG component changes during both successful inhibitions (correct rejections) and successful executions (hits) of the motor response. During correct rejections, ERP changes were found over frontal regions, during latencies related to sensory gain control, conflict monitoring and working memory storage and processing. During hits, ERP changes were found over left-parietal regions during latencies related to orienting attention and subsequent selection and execution of the motor plan. The pattern of attenuation in walking-related EEG amplitude changes, during 2-back task performance, is thought to reflect more effortful recalibration of 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 and may lead to a better understanding of how factors such as aging or neurological disorders could impinge on this capacity.

Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): An auditory evoked potential study of the duration-evoked mismatch negativity (MMN).

Background: We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of "duration" processing, a critical cue in speech perception. Given decrements in speech and language skills associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials. Methods: We employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system. Results: Data from individuals with CLN3 disease (N=21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N=41; ages 6-26 years). Conclusions: Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.

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 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 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 (r = 0.44) and with walking-related EEG amplitude modulations over frontocentral regions (r = 0.47) during the sensory gating (N1) and conflict monitoring (N2) stages of inhibition, and over left-lateralized prefrontal regions (r = 0.47) during the stage of inhibitory control implementation (P3). These neural activity changes are related to the cognitive component of inhibition, and they were interpreted as signatures of behavioral improvement during walking. On the other hand, aging, independent of response accuracy during walking, was found to correlate with slower treadmill walking speeds (r = -0.68) and attenuation in walking-related EEG amplitude modulations over left-dominant frontal (r = -0.44) and parietooccipital regions (r = 0.48) during the N2 stage, and over centroparietal regions (r = 0.48) during the P3 stage. These neural activity changes are related to the motor component of inhibition, and they were interpreted as signatures of aging. Older adults whose response accuracy 'paradoxically' 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.

Severely Attenuated Visual Feedback Processing in Children on the Autism Spectrum.

Individuals on the autism spectrum often exhibit atypicality in their sensory perception, but the neural underpinnings of these perceptual differences remain incompletely understood. One proposed mechanism is an imbalance in higher-order feedback re-entrant inputs to early sensory cortices during sensory perception, leading to increased propensity to focus on local object features over global context. We explored this theory by measuring visual evoked potentials during contour integration as considerable work has revealed that these processes are largely driven by feedback inputs from higher-order ventral visual stream regions. We tested the hypothesis that autistic individuals would have attenuated evoked responses to illusory contours compared with neurotypical controls. Electrophysiology was acquired while 29 autistic and 31 neurotypical children (7-17 years old, inclusive of both males and females) passively viewed a random series of Kanizsa figure stimuli, each consisting of four inducers that were aligned either at random rotational angles or such that contour integration would form an illusory square. Autistic children demonstrated attenuated automatic contour integration over lateral occipital regions relative to neurotypical controls. The data are discussed in terms of the role of predictive feedback processes on perception of global stimulus features and the notion that weakened "priors" may play a role in the visual processing anomalies seen in autism.SIGNIFICANCE STATEMENT Children on the autism spectrum differ from typically developing children in many aspects of their processing of sensory stimuli. One proposed mechanism for these differences is an imbalance in higher-order feedback to primary sensory regions, leading to an increased focus on local object features rather than global context. However, systematic investigation of these feedback mechanisms remains limited. Using EEG and a visual illusion paradigm that is highly dependent on intact feedback processing, we demonstrated significant disruptions to visual feedback processing in children with autism. This provides much needed experimental evidence that advances our understanding of the contribution of feedback processing to visual perception in autism spectrum disorder.