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.

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.

Young adults who improve performance during dual-task walking show more flexible reallocation of cognitive resources: a mobile brain-body imaging (MoBI) study.

INTRODUCTION: In young adults, pairing a 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. This study investigates the preliminary finding of behavioral improvement in Go/NoGo response inhibition task performance during walking compared with sitting, which was observed at the piloting stage. MATERIALS AND METHODS: Mobile brain/body imaging (MoBI) was used to record electroencephalographic (EEG) activity, 3-dimensional (3D) gait kinematics and behavioral responses in the cognitive task, during sitting or walking on a treadmill. RESULTS: In a cohort of 26 young adults, 14 participants improved in measures of cognitive task performance while walking compared with sitting. These participants exhibited walking-related EEG amplitude reductions over frontal 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 with those who did not improve. In contrast, 12 participants who did not improve exhibited no EEG amplitude differences across physical condition. DISCUSSION: 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.

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.

Cued motor processing in autism and typical development: A high-density electrical mapping study of response-locked neural activity in children and adolescents.

Motor atypicalities are common in autism spectrum disorder (ASD) and are often evident prior to classical ASD symptoms. Despite evidence of differences in neural processing during imitation in autistic individuals, research on the integrity and spatiotemporal dynamics of basic motor processing is surprisingly sparse. To address this need, we analysed electroencephalography (EEG) data recorded from a large sample of autistic (n = 84) and neurotypical (n = 84) children and adolescents while they performed an audiovisual speeded reaction time (RT) task. Analyses focused on RTs and response-locked motor-related electrical brain responses over frontoparietal scalp regions: the late Bereitschaftspotential, the motor potential and the reafferent potential. Evaluation of behavioural task performance indicated greater RT variability and lower hit rates in autistic participants compared to typically developing age-matched neurotypical participants. Overall, the data revealed clear motor-related neural responses in ASD, but with subtle differences relative to typically developing participants evident over fronto-central and bilateral parietal scalp sites prior to response onset. Group differences were further parsed as a function of age (6-9, 9-12 and 12-15 years), sensory cue preceding the response (auditory, visual and bi-sensory audiovisual) and RT quartile. Group differences in motor-related processing were most prominent in the youngest group of children (age 6-9), with attenuated cortical responses observed for young autistic participants. Future investigations assessing the integrity of such motor processes in younger children, where larger differences may be present, are warranted.

Neural markers of proactive and reactive cognitive control are altered during walking: A Mobile Brain-Body Imaging (MoBI) study.

The processing of sensory information and the generation of motor commands needed to produce coordinated actions can interfere with ongoing cognitive tasks. Even simple motor behaviors like walking can alter cognitive task performance. This cognitive-motor interference (CMI) could arise from disruption of planning in anticipation of carrying out the task (proactive control) and/or from disruption of the execution of the task (reactive control). In young healthy adults, walking-induced interference with behavioral performance may not be readily observable because flexibility in neural circuits can compensate for the added demands of simultaneous loads. In this study, cognitive-motor loads were systematically increased during cued task-switching while underlying neurophysiologic changes in proactive and reactive mechanisms were measured. Brain activity was recorded from 22 healthy young adults using 64-channel electroencephalography (EEG) based Mobile Brain/Body Imaging (MoBI) as they alternately sat or walked during performance of cued task-switching. Walking altered neurophysiological indices of both proactive and reactive control. Walking amplified cue-evoked late fontal slow waves, and reduced the amplitude of target-evoked fronto-central N2 and parietal P3. The effects of walking on evoked neural responses systematically increased as the task became increasingly difficult. This may provide an objective brain marker of increasing cognitive load, and may prove to be useful in identifying seemingly healthy individuals who are currently able to disguise ongoing degenerative processes through active compensation. If, however, degeneration continues unabated these people may reach a compensatory limit at which point both cognitive performance and control of coordinated actions may decline rapidly.

Neural correlates of multisensory enhancement in audiovisual narrative speech perception: A fMRI investigation.

This fMRI study investigated the effect of seeing articulatory movements of a speaker while listening to a naturalistic narrative stimulus. It had the goal to identify regions of the language network showing multisensory enhancement under synchronous audiovisual conditions. We expected this enhancement to emerge in regions known to underlie the integration of auditory and visual information such as the posterior superior temporal gyrus as well as parts of the broader language network, including the semantic system. To this end we presented 53 participants with a continuous narration of a story in auditory alone, visual alone, and both synchronous and asynchronous audiovisual speech conditions while recording brain activity using BOLD fMRI. We found multisensory enhancement in an extensive network of regions underlying multisensory integration and parts of the semantic network as well as extralinguistic regions not usually associated with multisensory integration, namely the primary visual cortex and the bilateral amygdala. Analysis also revealed involvement of thalamic brain regions along the visual and auditory pathways more commonly associated with early sensory processing. We conclude that under natural listening conditions, multisensory enhancement not only involves sites of multisensory integration but many regions of the wider semantic network and includes regions associated with extralinguistic sensory, perceptual and cognitive processing.

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 ∼100-150 ms 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 paradig ms 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 (67 ms and 117 ms), 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.

Association between mild traumatic brain injury, brain structure, and mental health outcomes in the Adolescent Brain Cognitive Development Study.

BACKGROUND: Children that experience a mild traumatic brain injury (mTBI) are at an increased risk of neural alterations that can deteriorate mental health. We test the hypothesis that mTBI is associated with psychopathology and that structural brain metrics (e.g., volume, area) meaningfully mediate the relation in an adolescent population. METHODS: We analyzed behavioral and brain MRI data from 11,876 children who participated in the Adolescent Brain Cognitive Development (ABCD) Study. Mixed-effects models were used to examine the longitudinal association between mTBI and mental health outcomes. Bayesian methods were used to investigate brain regions that are intermediate between mTBI and symptoms of poor mental health. RESULTS: There were 199 children with mTBI and 527 with possible mTBI across the three ABCD Study visits. There was a 7% (IRR = 1.07, 95% CI: 1.01, 1.13) and 15% (IRR = 1.16, 95% CI: 1.05, 1.26) increased risk of emotional or behavioral problems in children that experienced possible mTBI or mTBI, respectively. Possible mTBI was associated with a 17% (IRR: 1.17, 95% CI: 0.99, 1.40) increased risk of experiencing distress following a psychotic-like experience. We did not find any brain regions that meaningfully mediated the relationship between mTBI and mental health outcomes. Analysis of volumetric measures found that approximately 2% to 5% of the total effect of mTBI on mental health outcomes operated through total cortical volume. Image intensity measure analyses determined that approximately 2% to 5% of the total effect was mediated through the left-hemisphere of the dorsolateral prefrontal cortex. CONCLUSION: Results indicate an increased risk of emotional and behavioral problems in children that experienced possible mTBI or mTBI. Mediation analyses did not elucidate the mechanisms underlying the association between mTBI and mental health outcomes.

Predicting alcohol dependence from multi-site brain structural measures.

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.

Oscillatory entrainment mechanisms and anticipatory predictive processes in children with autism spectrum disorder.

Anticipating near-future events is fundamental to adaptive behavior, whereby neural processing of predictable stimuli is significantly facilitated relative to nonpredictable events. Neural oscillations appear to be a key anticipatory mechanism by which processing of upcoming stimuli is modified, and they often entrain to rhythmic environmental sequences. Clinical and anecdotal observations have led to the hypothesis that people with autism spectrum disorder (ASD) may have deficits in generating predictions, and as such, a candidate neural mechanism may be failure to adequately entrain neural activity to repetitive environmental patterns, to facilitate temporal predictions. We tested this hypothesis by interrogating temporal predictions and rhythmic entrainment using behavioral and electrophysiological approaches. We recorded high-density electroencephalography in children with ASD and typically developing (TD) age- and IQ-matched controls, while they reacted to an auditory target as quickly as possible. This auditory event was either preceded by predictive rhythmic visual cues or was not preceded by any cue. Both ASD and control groups presented comparable behavioral facilitation in response to the Cue versus No-Cue condition, challenging the hypothesis that children with ASD have deficits in generating temporal predictions. Analyses of the electrophysiological data, in contrast, revealed significantly reduced neural entrainment to the visual cues and altered anticipatory processes in the ASD group. This was the case despite intact stimulus-evoked visual responses. These results support intact behavioral temporal prediction in response to a cue in ASD, in the face of altered neural entrainment and anticipatory processes.NEW & NOTEWORTHY We examined behavioral and EEG indices of predictive processing in children with ASD to rhythmically predictable stimuli. Although behavioral measures of predictive processing and evoked neural responses were intact in the ASD group, neurophysiological measures of preparatory activity and entrainment were impaired. When sensory events are presented in a predictable temporal pattern, performance and neuronal responses in ASD may be governed more by the occurrence of the events themselves and less by their anticipated timing.

Using the MoBI motion capture system to rapidly and accurately localize EEG electrodes in anatomic space.

During mobile brain/body imaging (MoBI) experiments, electroencephalography and motion capture systems are used in concert to record high temporal resolution neural activity and movement kinematics while participants perform demanding perceptual and cognitive tasks in a naturalistic environment. A typical MoBI setup involves positioning multi-channel electrode caps based on anatomical fiducials as well as experimenter and participant intuition regarding the scalp midpoint location (i.e., Cz). Researchers often use the "template" electrode locations provided by the manufacturer, however, the "actual" electrode locations can vary based on each participant's head morphology. Accounting for differences in head morphologies could provide more accurate clinical diagnostic information when using MoBI to identify neurological deficits in patients with motor, sensory, or cognitive impairments. Here, we asked whether the existing motion capture system used in a MoBI setup could be easily adapted to improve spatial localization of electrodes across participants without requiring additional or specialized equipment that might impede clinical adoption. Using standard electrode configurations, infrared markers were placed on a subset of electrodes and anatomical fiducials, and the remaining electrode locations were estimated using spherical or ellipsoid models. We identified differences in event-related potentials between "template" and "actual" electrode locations during a Go/No-Go task (p < 9.8e-5) and an object-manipulation task (p < 9.8e-5). Thus, the motion capture system already used in MoBI experiments can be effectively deployed to accurately register and quantify the neural activity. Improving the spatial localization without needing specialized hardware or additional setup time to the workflow has important real-world implications for translating MoBI to clinical environments.

Aging-related changes in cortical mechanisms supporting postural control during base of support and optic flow manipulations.

Behavioral findings suggest that aging alters the involvement of cortical sensorimotor mechanisms in postural control. However, corresponding accounts of the underlying neural mechanisms remain sparse, especially the extent to which these mechanisms are affected during more demanding tasks. Here, we set out to elucidate cortical correlates of altered postural stability in younger and older adults. 3D body motion tracking and high-density electroencephalography (EEG) were measured while 14 young adults (mean age = 24 years, 43% women) and 14 older adults (mean age = 77 years, 50% women) performed a continuous balance task under four different conditions. Manipulations were applied to the base of support (either regular or tandem (heel-to-toe) stance) and visual input (either static visual field or dynamic optic flow). Standing in tandem, the more challenging position, resulted in increased sway for both age groups, but for the older adults, only this effect was exacerbated when combined with optic flow compared to the static visual display. These changes in stability were accompanied by neuro-oscillatory modulations localized to midfrontal and parietal regions. A cluster of electro-cortical sources localized to the supplementary motor area showed a large increase in theta spectral power (4-7 Hz) during tandem stance, and this modulation was much more pronounced for the younger group. Additionally, the older group displayed widespread mu (8-12 Hz) and beta (13-30 Hz) suppression as balance tasks placed more demands on postural control, especially during tandem stance. These findings may have substantial utility in identifying early cortical correlates of balance impairments in otherwise healthy older adults.

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study.

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Cognitive load reduces the effects of optic flow on gait and electrocortical dynamics during treadmill walking.

During navigation of complex environments, the brain must continuously adapt to both external demands, such as fluctuating sensory inputs, and internal demands, such as engagement in a cognitively demanding task. Previous studies have demonstrated changes in behavior and gait with increased sensory and cognitive load, but the underlying cortical mechanisms remain largely unknown. In the present study, in a mobile brain/body imaging (MoBI) approach, 16 young adults walked on a treadmill with high-density EEG while 3-dimensional (3D) motion capture tracked kinematics of the head and feet. Visual load was manipulated with the presentation of optic flow with and without continuous mediolateral perturbations. The effects of cognitive load were assessed by the performance of a go/no-go task on half of the blocks. During increased sensory load, participants walked with shorter and wider strides, which may indicate a more restrained pattern of gait. Interestingly, cognitive task engagement attenuated these effects of sensory load on gait. Using an independent component analysis and dipole-fitting approach, we found that cautious gait was accompanied by neuro-oscillatory modulations localized to frontal (supplementary motor area, anterior cingulate cortex) and parietal (inferior parietal lobule, precuneus) areas. Our results show suppression in alpha/mu (8-12 Hz) and beta (13-30 Hz) rhythms, suggesting enhanced activation of these regions with unreliable sensory inputs. These findings provide insight into the neural correlates of gait adaptation and may be particularly relevant to older adults who are less able to adjust to ongoing cognitive and sensory demands while walking. NEW & NOTEWORTHY The neural underpinnings of gait adaptation in humans are poorly understood. To this end, we recorded high-density EEG combined with three-dimensional body motion tracking as participants walked on a treadmill while exposed to full-field optic flow stimulation. Perturbed visual input led to a more cautious gait pattern with neuro-oscillatory modulations localized to premotor and parietal regions. Our findings show a possible brain-behavior link that might further our understanding of gait and mobility impairments.

Eye movements, sensorimotor adaptation and cerebellar-dependent learning in autism: toward potential biomarkers and subphenotypes.

Because of the wide range of symptoms expressed in individuals with autism spectrum disorder (ASD) and their idiosyncratic severity, it is unlikely that a single remedial approach will be universally effective. Resolution of this dilemma requires identifying subgroups within the autism spectrum, based on symptom set and severity, on an underlying neuro-structural difference, and on specific behavioral dysfunction. This will provide critical insight into the disorder and may lead to better diagnoses, and more targeted remediation in these subphenotypes of people with ASD. In this review, we discuss findings that appear to link the structure of the cerebellar vermis and plasticity of the saccadic eye-movement system in people with an autism spectrum disorder (ASD). Differences in cerebellar vermis structure in ASD could critically impact visuo-sensorimotor development in early infancy, which may in turn manifest as the visual orienting, communication and social interaction differences often seen in this population. It may be possible to distinguish a subpopulation of children with vermal hypoplasia, to establish whether this group manifests more severe deficits in visual orienting and in adaptation to persistent visual errors, and to establish whether this putative subphenotype of ASD is associated with a specific and distinct clinical symptom profile.

An Examination of the Neural Unreliability Thesis of Autism.

An emerging neuropathological theory of Autism, referred to here as "the neural unreliability thesis," proposes greater variability in moment-to-moment cortical representation of environmental events, such that the system shows general instability in its impulse response function. Leading evidence for this thesis derives from functional neuroimaging, a methodology ill-suited for detailed assessment of sensory transmission dynamics occurring at the millisecond scale. Electrophysiological assessments of this thesis, however, are sparse and unconvincing. We conducted detailed examination of visual and somatosensory evoked activity using high-density electrical mapping in individuals with autism (N = 20) and precisely matched neurotypical controls (N = 20), recording large numbers of trials that allowed for exhaustive time-frequency analyses at the single-trial level. Measures of intertrial coherence and event-related spectral perturbation revealed no convincing evidence for an unreliability account of sensory responsivity in autism. Indeed, results point to robust, highly reproducible response functions marked for their exceedingly close correspondence to those in neurotypical controls.