Postural control processes during standing and step initiation in autism spectrum disorder

This work is licensed under a Creative Commons Attribution 4.0 International License.Background Individuals with autism spectrum disorder (ASD) show a reduced ability to maintain postural stability, though motor control mechanisms contributing to these issues and the extent to which they are associated with other gross motor activities (e.g., stepping) are not yet known. Methods Seventeen individuals with ASD and 20 typically developing (TD) controls (ages 6–19 years) completed three tests of postural control during standing. During the neutral stance, individuals stood with their feet shoulder width apart. During the Romberg one stance, they stood with feet close together. During the circular sway, participants stood with feet shoulder width apart and swayed in a circular motion. The standard deviation (SD) of their center of pressure (COP) in the mediolateral (ML) and anteroposterior (AP) directions and the COP trajectory length were examined for each stance. We also assessed mutual information (MI), or the shared dependencies between COP in the ML and AP directions. Participants also completed a stepping task in which they stepped forward from one force platform to an adjacent platform. The amplitude and duration of anticipatory postural adjustments (APAs) were examined, as were the maximum lateral sway, duration, and velocity of COP adjustments following the initial step. We examined stepping variables using separate one-way ANCOVAs with height as a covariate. The relationships between postural control and stepping measures and ASD symptom severity were assessed using Spearman correlations with scores on the Autism Diagnostic Observation Schedule–Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R). Results Individuals with ASD showed increased COP trajectory length across stance conditions (p = 0.05) and reduced MI during circular sway relative to TD controls (p = 0.02). During stepping, groups did not differ on APA amplitude (p = 0.97) or duration (p = 0.41), but during their initial step, individuals with ASD showed reduced ML sway (p = 0.06), reduced body transfer duration (p < 0.01), and increased body transfer velocity (p = 0.02) compared to controls. Greater neutral stance COPML variability (r = 0.55, p = 0.02) and decreased lateral sway (r = − 0.55, p = 0.02) when stepping were associated with more severe restricted and repetitive behaviors in participants with ASD. Conclusions We found that individuals with ASD showed reduced MI during circular sway suggesting a reduced ability to effectively coordinate joint movements during dynamic postural adjustments. Additionally, individuals with ASD showed reduced lateral sway when stepping indicating that motor rigidity may interfere with balance and gait. Postural control and stepping deficits were related to repetitive behaviors in individuals with ASD indicating that motor rigidity and key clinical issues in ASD may represent overlapping pathological processes

Reduced habituation of auditory evoked potentials indicate cortical hyper-excitability in Fragile X Syndrome

Sensory hypersensitivities are common, clinically distressing features of Fragile X Syndrome (FXS). Preclinical evidence suggests this abnormality may result from synaptic hyper-excitability in sensory systems. This model predicts reduced sensory habituation to repeated stimulus presentation. Fourteen adolescents and adults with FXS and 15 age-matched controls participated in a modified auditory gating task using trains of 4 identical tones during dense array electroencephalography (EEG). Event-related potential and single trial time–frequency analyses revealed decreased habituation of the N1 event-related potential response in FXS, and increased gamma power coupled with decreases in gamma phase-locking during the early-stimulus registration period. EEG abnormalities in FXS were associated with parent reports of heightened sensory sensitivities and social communication deficits. Reduced habituation and altered gamma power and phase-locking to auditory cues demonstrated here in FXS patients parallels preclinical findings with Fmr1 KO mice. Thus, the EEG abnormalities seen in FXS patients support the model of neocortical hyper-excitability in FXS, and may provide useful translational biomarkers for evaluating novel treatment strategies targeting its neural substrate

Precision Sensorimotor Control in Aging FMR1 Gene Premutation Carriers.

Background: Individuals with premutation alleles of the Materials and Methods: 26 Results: Relative to controls, premutation carriers showed reduced rates of initial force generation during rapid motor actions and longer durations of their initial pressing with their dominant hand. During sustained force, premutation carriers demonstrated reduced force complexity, though this effect was specific to younger premutation carries during dominant hand pressing and was more severe for younger relative to older premutation carriers at low and medium force levels. Increased reaction time and lower sustained force complexity each were associated with greater CGG repeat length for premutation carriers. Increased reaction time and increased sustained force variability were associated with more severe clinically rated FXTAS symptoms. Conclusion: Overall our findings suggest multiple sensorimotor processes are disrupted in aging premutation carriers, including initial force control guided by feedforward mechanisms and sustained sensorimotor behaviors guided by sensory feedback control processes. Results indicating that sensorimotor issues in aging premutation carriers relate to both greater CGG repeat length and clinically rated FXTAS symptoms suggest that quantitative tests of precision sensorimotor ability may serve as key targets for monitoring FXTAS risk and progression

Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome

Background Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS. Methods EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0–100 Hz over 2 s. Results Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits. Conclusions This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics

Familiality of behavioral flexibility and response inhibition deficits in autism spectrum disorder (ASD)

This work is licensed under a Creative Commons Attribution 4.0 International License.Background Diminished cognitive control, including reduced behavioral flexibility and behavioral response inhibition, has been repeatedly documented in autism spectrum disorder (ASD). We evaluated behavioral flexibility and response inhibition in probands and their parents using a family trio design to determine the extent to which these cognitive control impairments represent familial traits associated with ASD. Methods We examined 66 individuals with ASD (probands), 135 unaffected biological parents, and 76 typically developing controls. Participants completed a probabilistic reversal learning task (PRL) and a stop-signal task (SST) to assess behavioral flexibility and response inhibition respectively. Rates of PRL and SST errors were examined across groups, within families, and in relation to clinical and subclinical traits of ASD. Based on prior findings that subclinical broader autism phenotypic (BAP) traits may co-segregate within families and reflect heritable risk factors, we also examined whether cognitive control deficits were more prominent in families in which parents showed BAP features (BAP+). Results Probands and parents each showed increased rates of PRL and SST errors relative to controls. Error rates across tasks were not related. SST error rates inter-correlated among probands and their parents. PRL errors were more severe in BAP+ parents and their children relative to BAP− parents and their children. For probands of BAP+ parents, PRL and SST error rates were associated with more severe social-communication abnormalities and repetitive behaviors, respectively. Conclusion Reduced behavioral flexibility and response inhibition are present among probands and their unaffected parents, but represent unique familial deficits associated with ASD that track with separate clinical issues. Specifically, behavioral response inhibition impairments are familial in ASD and manifest independently from parental subclinical features. In contrast, behavioral flexibility deficits are selectively present in families with BAP characteristics, suggesting they co-segregate in families with parental subclinical social, communication, and rigid personality traits. Together, these findings provide evidence that behavioral flexibility and response inhibition impairments track differentially with ASD risk mechanisms and related behavioral traits

Postural orientation and equilibrium processes associated with increased postural sway in autism spectrum disorder (ASD)

Background: Increased postural sway has been repeatedly documented in children with autism spectrum disorder (ASD). Characterizing the control processes underlying this deficit, including postural orientation and equilibrium, may provide key insights into neurophysiological mechanisms associated with ASD. Postural orientation refers to children’s ability to actively align their trunk and head with respect to their base of support, while postural equilibrium is an active process whereby children coordinate ankle dorsi-/plantar-flexion and hip abduction/adduction movements to stabilize their upper body. Dynamic engagement of each of these control processes is important for maintaining postural stability, though neither postural orientation nor equilibrium has been studied in ASD. Methods: Twenty-two children with ASD and 21 age and performance IQ-matched typically developing (TD) controls completed three standing tests. During static stance, participants were instructed to stand as still as possible. During dynamic stances, participants swayed at a comfortable speed and magnitude in either anterior-posterior (AP) or mediolateral (ML) directions. The center of pressure (COP) standard deviation and trajectory length were examined to determine if children with ASD showed increased postural sway. Postural orientation was assessed using a novel virtual time-to-contact (VTC) approach that characterized spatiotemporal dimensions of children’s postural sway (i.e., body alignment) relative to their postural limitation boundary, defined as the maximum extent to which each child could sway in each direction. Postural equilibrium was quantified by evaluating the amount of shared or mutual information of COP time series measured along the AP and ML directions. Results: Consistent with prior studies, children with ASD showed increased postural sway during both static and dynamic stances relative to TD children. In regard to postural orientation processes, children with ASD demonstrated reduced spatial perception of their postural limitation boundary towards target directions and reduced time to correct this error during dynamic postural sways but not during static stance. Regarding postural equilibrium, they showed a compromised ability to decouple ankle dorsi-/plantar-flexion and hip abduction/adduction processes during dynamic stances. Conclusions: These results suggest that deficits in both postural orientation and equilibrium processes contribute to reduced postural stability in ASD. Specifically, increased postural sway in ASD appears to reflect patients’ impaired perception of their body movement relative to their own postural limitation boundary as well as a reduced ability to decouple distinct ankle and hip movements to align their body during standing. Our findings that deficits in postural orientation and equilibrium are more pronounced during dynamic compared to static stances suggests that the increased demands of everyday activities in which children must dynamically shift their COP involve more severe postural control deficits in ASD relative to static stance conditions that often are studied. Systematic assessment of dynamic postural control processes in ASD may provide important insights into new treatment targets and neurodevelopmental mechanisms

A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome

(A) Scalp topographies of “local coupling”, showing correlations in each electrode between relative power of activity in the theta, and lower and upper alpha power bands and gamma power for male FXS and male healthy control participants, with significant group differences presented in the bottom row (p < 0.05, corrected), with dark blue reflecting no group difference. (B) Mean and standard error of correlations for all electrodes showing group differences as are plotted in A. * denotes correlations of spectral power in theta and upper alpha bands with gamma band power that are significantly different from zero based on the results of permutation analyses at p < 0.05. (TIF 4297 kb

Developmental Effects on Auditory Neural Oscillatory Synchronization Abnormalities in Autism Spectrum Disorder

Previous studies have found alterations in 40 Hz oscillatory activity in response to auditory stimuli in adults with Autism Spectrum Disorder (ASD). The current study sought to examine the specificity and developmental trajectory of these findings by driving the cortex to oscillate at a range of frequencies in both children and adults with and without ASD. Fifteen participants with ASD (3 female, aged 6–23 years) and 15 age-matched controls (4 female, aged 6–25 years) underwent dense-array EEG as they listened to a carrier tone amplitude-modulated by a sinusoid linearly increasing in frequency from 0–100 Hz over 2 s. EEG data were analyzed for inter-trial phase coherence (ITPC) and single-trial power (STP). Older participants with ASD displayed significantly decreased ability to phase-lock to the stimulus in the low gamma frequency range relative to their typically developing (TD) counterparts, while younger ASD and TD did not significantly differ from each other. An interaction between age and diagnosis suggested that TD and ASD also show different developmental trajectories for low gamma power; TD showed a significant decrease in low gamma power with age, while ASD did not. Regardless of age, increased low gamma STP was significantly correlated with increased clinical scores for repetitive behaviors in the ASD group, particularly insistence on sameness. This study contributes to a growing body of evidence supporting alterations in auditory processing in ASD. Older ASD participants showed more pronounced low gamma deficits than younger participants, suggesting an altered developmental trajectory for neural activity contributing to auditory processing deficits that may also be more broadly clinically relevant. Future studies are needed employing a longitudinal approach to confirm findings of this cross-sectional study.Open Access fees paid for in whole or in part by the University of Oklahoma LibrariesYe

Increased Force Variability Is Associated with Altered Modulation of the Motorneuron Pool Activity in Autism Spectrum Disorder (ASD)

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Force control deficits have been repeatedly documented in autism spectrum disorder (ASD). They are associated with worse social and daily living skill impairments in patients suggesting that developing a more mechanistic understanding of the central and peripheral processes that cause them may help guide the development of treatments that improve multiple outcomes in ASD. The neuromuscular mechanisms underlying force control deficits are not yet understood. Seventeen individuals with ASD and 14 matched healthy controls completed an isometric index finger abduction test at 60% of their maximum voluntary contraction (MVC) during recording of the first dorsal interosseous (FDI) muscle to determine the neuromuscular processes associated with sustained force variability. Central modulation of the motorneuron pool activation of the FDI muscle was evaluated at delta (0–4 Hz), alpha (4–10 Hz), beta (10–35 Hz) and gamma (35–60 Hz) frequency bands. ASD patients showed greater force variability than controls when attempting to maintain a constant force. Relative to controls, patients also showed increased central modulation of the motorneuron pool at beta and gamma bands. For controls, reduced force variability was associated with reduced delta frequency modulation of the motorneuron pool activity of the FDI muscle and increased modulation at beta and gamma bands. In contrast, delta, beta, and gamma frequency oscillations were not associated with force variability in ASD. These findings suggest that alterations of central mechanisms that control motorneuron pool firing may underlie the common and often impairing symptoms of ASD