Brain state monitoring for the future prediction of migraine attacks.

BACKGROUND: Migraine attacks are unpredictable, precluding preemptive interventions and leading to lack of control over individuals' lives. Although there are neurophysiological changes 24-48 hours before migraine attacks, so far, they have not been used in patients' management. This study evaluates the applicability and the ability to identify pre-attack changes of daily "at home" electroencephalography obtained with a portable system for migraine patients. METHODS: Patients with episodic migraine fulfilling ICHD-3 beta criteria used a mobile system composed of a wireless EEG device (BrainStation®, Neuroverse®, Inc., USA) and mobile application (BrainVitalsM®, Neuroverse®, Inc., USA) to self-record their neural activity daily at home while resting and while performing an attention task, over the course of 2 weeks. Standard EEG spectral analysis and event-related brain potentials (ERP) methods were used and recordings were grouped by time from migraine attacks (i.e. "Interictal day", "24 h Before Migraine", "Migraine day" and "Post Migraine"). RESULTS: Twenty-four patients (22 women) recorded an average of 13.3 ± 1.9 days and had 2 ± 0.9 attacks. Twenty-four hours before attack onset, there was a statistically significant modulation of relative power in the delta (decrease) and beta (increase) frequency bands, at rest, and a significant reduction of the amplitude and inter-trial coherence measures of an attention event-related brain potential (P300). CONCLUSIONS: This proof-of-concept study shows that brain state monitoring, utilising an easy-to-use wearable EEG system to track neural modulations at home, can identify physiological changes preceding a migraine attack enabling valuable pre-symptom prediction and subsequent early intervention.

Brief Report: Cross-Modal Capture: Preliminary Evidence of Inefficient Filtering in Children with Autism Spectrum Disorder.

This study investigates how task-irrelevant auditory information is processed in children with autism spectrum disorder (ASD). Eighteen children with ASD and 19 age- and IQ-matched typically developing (TD) children were presented with semantically-congruent and incongruent picture-sound pairs, and in separate tasks were instructed to attend to only visual or both audio-visual sensory channels. Preliminary results showed that when required to attend to both modalities, both groups were equally slowed for semantically-incongruent compared to congruent pairs. However, when asked to attend to only visual information, children with ASD were disproportionally slowed by incongruent auditory information, suggesting that they may have more difficulty filtering task-irrelevant cross-modal information. Correlational analyses showed that this inefficient cross-modal attentional filtering was related to greater sociocommunicative impairment.

A New Foreperiod Effect on Intertrial Phase Coherence. Part I: Existence and Behavioral Relevance.

This letter makes scientific and methodological contributions. Scientifically, it demonstrates a new and behaviorally relevant effect of temporal expectation on the phase coherence of the electroencephalogram (EEG). Methodologically, it introduces novel methods to characterize EEG recordings at the single-trial level. Expecting events in time can lead to more efficient behavior. A remarkable finding in the study of temporal expectation is the foreperiod effect on reaction time, that is, the influence on reaction time of the delay between a warning signal and a succeeding imperative stimulus to which subjects are instructed to respond as quickly as possible. Here we study a new foreperiod effect in an audiovisual attention-shifting oddball task in which attention-shift cues directed the attention of subjects to impendent deviant stimuli of a given modality and therefore acted as warning signals for these deviants. Standard stimuli, to which subjects did not respond, were interspersed between warning signals and deviants. We hypothesized that foreperiod durations modulated intertrial phase coherence (ITPC, the degree of phase alignment across multiple trials) evoked by behaviorally irrelevant standards and that these modulations are behaviorally meaningful. Using averaged data, we first observed that ITPC evoked by standards closer to the warning signal was significantly different from that evoked by standards further away from it, establishing a new foreperiod effect on ITPC evoked by standards. We call this effect the standard foreperiod (SFP) effect on ITPC. We reasoned that if the SFP influences ITPC evoked by standards, it should be possible to decode the former from the latter on a trial-by-trial basis. We were able to do so showing that this effect can be observed in single trials. We demonstrated the behavioral relevance of the SFP effect on ITPC by showing significant correlations between its strength and subjects' behavioral performance.

A novel approach to training attention and gaze in ASD: A feasibility and efficacy pilot study.

In addition to the social, communicative and behavioral symptoms that define the disorder, individuals with ASD have difficulty re-orienting attention quickly and accurately. Similarly, fast re-orienting saccadic eye movements are also inaccurate and more variable in both endpoint and timing. Atypical gaze and attention are among the earliest symptoms observed in ASD. Disruption of these foundation skills critically affects the development of higher level cognitive and social behavior. We propose that interventions aimed at these early deficits that support social and cognitive skills will be broadly effective. We conducted a pilot clinical trial designed to demonstrate the feasibility and preliminary efficacy of using gaze-contingent video games for low-cost in-home training of attention and eye movement. Eight adolescents with ASD participated in an 8-week training, with pre-, mid- and post-testing of eye movement and attention control. Six of the eight adolescents completed the 8 weeks of training and all six showed improvement in attention (orienting, disengagement) and eye movement control or both. All game systems remained intact for the duration of training and all participants could use the system independently. We delivered a robust, low-cost, gaze-contingent game system for home use that, in our pilot training sample, improved the attention orienting and eye movement performance of adolescent participants in 8 weeks of training. We are currently conducting a clinical trial to replicate these results and to examine what, if any, aspects of training transfer to more real-world tasks. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 546-554, 2018.

Autism, Attention, and Alpha Oscillations: An Electrophysiological Study of Attentional Capture.

BACKGROUND: Autism spectrum disorder (ASD) is associated with deficits in adaptively orienting attention to behaviorally-relevant information. Neural oscillatory activity plays a key role in brain function and provides a high-resolution temporal marker of attention dynamics. Alpha band (8-12 Hz) activity is associated with both selecting task-relevant stimuli and filtering task-irrelevant information. METHODS: The present study used electroencephalography (EEG) to examine alpha-band oscillatory activity associated with attentional capture in nineteen children with ASD and twenty-one age- and IQ-matched typically developing (TD) children. Participants completed a rapid serial visual presentation paradigm designed to investigate responses to behaviorally-relevant targets and contingent attention capture by task-irrelevant distractors, which either did or did not share a behaviorally-relevant feature. Participants also completed six minutes of eyes-open resting EEG. RESULTS: In contrast to their TD peers, children with ASD did not evidence posterior alpha desynchronization to behaviorally-relevant targets. Additionally, reduced target-related desynchronization and poorer target detection were associated with increased ASD symptomatology. TD children also showed behavioral and electrophysiological evidence of contingent attention capture, whereas children with ASD showed no behavioral facilitation or alpha desynchronization to distractors that shared a task-relevant feature. Lastly, children with ASD had significantly decreased resting alpha power, and for all participants increased resting alpha levels were associated with greater task-related alpha desynchronization. CONCLUSIONS: These results suggest that in ASD under-responsivity and impairments in orienting to salient events within their environment are reflected by atypical EEG oscillatory neurodynamics, which may signify atypical arousal levels and/or an excitatory/inhibitory imbalance.

Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial.

OBJECTIVE: No drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low-dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment-1 (SAT-1) trial was a double-blind, placebo-controlled, translational pilot study to examine the safety and activity of low-dose suramin in children with ASD. METHODS: Ten male subjects with ASD, ages 5-14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS-2 comparison scores and Expressive One-Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire. RESULTS: Blood levels of suramin were 12 ± 1.5 µmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 µmol/L after 6 weeks. The terminal half-life was 14.7 ± 0.7 days. A self-limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS-2 comparison scores improved by -1.6 ± 0.55 points (n = 5; 95% CI = -2.3 to -0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors. INTERPRETATION: The safety and activity of low-dose suramin showed promise as a novel approach to treatment of ASD in this small study.

Tracking the sensory environment: an ERP study of probability and context updating in ASD.

We recorded visual event-related brain potentials from 32 adult male participants (16 high-functioning participants diagnosed with autism spectrum disorder (ASD) and 16 control participants, ranging in age from 18 to 53 years) during a three-stimulus oddball paradigm. Target and non-target stimulus probability was varied across three probability conditions, whereas the probability of a third non-target stimulus was held constant in all conditions. P3 amplitude to target stimuli was more sensitive to probability in ASD than in typically developing participants, whereas P3 amplitude to non-target stimuli was less responsive to probability in ASD participants. This suggests that neural responses to changes in event probability are attention-dependant in high-functioning ASD. The implications of these findings for higher-level behaviors such as prediction and planning are discussed.

Guidelines and best practices for electrophysiological data collection, analysis and reporting in autism.

The EEG reflects the activation of large populations of neurons that act in synchrony and propagate to the scalp surface. This activity reflects both the brain's background electrical activity and when the brain is being challenged by a task. Despite strong theoretical and methodological arguments for the use of EEG in understanding the neural correlates of autism, the practice of collecting, processing and evaluating EEG data is complex. Scientists should take into consideration both the nature of development in autism given the life-long, pervasive course of the disorder and the disability of altered or atypical social, communicative, and motor behaviors, all of which require accommodations to traditional EEG environments and paradigms. This paper presents guidelines for the recording, analyzing, and interpreting of EEG data with participants with autism. The goal is to articulate a set of scientific standards as well as methodological considerations that will increase the general field's understanding of EEG methods, provide support for collaborative projects, and contribute to the evaluation of results and conclusions.

Motor skill in autism spectrum disorders: a subcortical view.

The earliest observable symptoms of autism spectrum disorders (ASDs) involve motor behavior. There is a growing awareness of the developmental importance of impaired motor function in ASD and its association with social skill. Compromised motor function requires increased attention, leaving fewer resources available for processing environmental stimuli and learning. This knowledge suggests that the motor system-which we know to be trainable-may be a gateway to improving outcomes of individuals living with ASD. In this review, we suggest a framework borrowed from machine learning to examine where, why, and how motor skills are different in individuals with ASD.

Detection and classification of subject-generated artifacts in EEG signals using autoregressive models.

We examine the problem of accurate detection and classification of artifacts in continuous EEG recordings. Manual identification of artifacts, by means of an expert or panel of experts, can be tedious, time-consuming and infeasible for large datasets. We use autoregressive (AR) models for feature extraction and characterization of EEG signals containing several kinds of subject-generated artifacts. AR model parameters are scale-invariant features that can be used to develop models of artifacts across a population. We use a support vector machine (SVM) classifier to discriminate among artifact conditions using the AR model parameters as features. Results indicate reliable classification among several different artifact conditions across subjects (approximately 94%). These results suggest that AR modeling can be a useful tool for discriminating among artifact signals both within and across individuals.

Brain oscillations in switching vs. focusing audio-visual attention.

Selective attention contributes to perceptual efficiency by modulating cortical activity according to task demands. The majority of attentional research has focused on the effects of attention to a single modality, and little is known about the role of attention in multimodal sensory processing. Here we employ a novel experimental design to examine the electrophysiological basis of audio-visual attention shifting. We use electroencephalography (EEG) to study differences in brain dynamics between quickly shifting attention between modalities and focusing attention on a single modality for extended periods of time. We also address interactions between attentional effects generated by the attention-shifting cue and those generated by subsequent stimuli. The conclusions from these examinations address key issues in attentional research, including the supramodal theory of attention, or the role of attention in foveal vision. The experimental design and analysis methods used here may suggest new directions in the study of the physiological basis of attention.

Assisting autistic children with wireless EOG technology.

We propose a novel intervention to train the speed and accuracy of attention orienting and eye movements in Autism Spectrum Disorder (ASD). Training eye movements and attention could not only affect those important functions directly, but could also result in broader improvement of social communication skills. To this end we describe a system that would allow ASD children to improve their fixation skills while playing a computer game controlled by an eye tracker. Because this intervention will probably be time consuming, this system should be designed to be used at homes. To make this possible, we propose an implementation based on wireless and dry electrooculography (EOG) technology. If successful, this system would develop an approach to therapy that would improve clinical and behavioral function in children and adults with ASD. As our initial steps in this direction, here we describe the design of a computer game to be used in this system, and the predictions of gaze position from EOG data recorded while a subject played this game.

Medial prefrontal theta bursts precede rapid motor responses during visual selective attention.

After visual target stimuli presented infrequently at a covertly attended location, quicker speeded button presses immediately followed a larger positive (P3f) ramp in averaged electroencephalographic (EEG) recordings from the forehead. We show this peak in the mean response time locked to the button press to be principally composed of triphasic, primarily low-theta band (4.5 Hz) complexes preceding but only partially phase-locked to the button press, with larger complexes preceding quicker motor responses. For 10 of 15 subjects, independent component analysis of the unaveraged 31-channel data identified a temporally independent medial frontal EEG process contributing to these phenomena. Low-resolution tomographic modeling localized related components of two 253-channel data sets to medial frontal polar cortex (BA32/10). The far-frontal low-theta complexes and concomitant mean P3f positivity may index cortical activity induced by paralimbic processes involved in disinhibiting impulsive motor responses to rewarding or goal-fulfilling stimuli or events.

Imaging human EEG dynamics using independent component analysis.

This review discusses the theory and practical application of independent component analysis (ICA) to multi-channel EEG data. We use examples from an audiovisual attention-shifting task performed by young and old subjects to illustrate the power of ICA to resolve subtle differences between evoked responses in the two age groups. Preliminary analysis of these data using ICA suggests a loss of task specificity in independent component (IC) processes in frontal and somatomotor cortex during post-response periods in older as compared to younger subjects, trends not detected during examination of scalp-channel event-related potential (ERP) averages. We discuss possible approaches to component clustering across subjects and new ways to visualize mean and trial-by-trial variations in the data, including ERP-image plots of dynamics within and across trials as well as plots of event-related spectral perturbations in component power, phase locking, and coherence. We believe that widespread application of these and related analysis methods should bring EEG once again to the forefront of brain imaging, merging its high time and frequency resolution with enhanced cm-scale spatial resolution of its cortical sources.

The functional neuroanatomy of spatial attention in autism spectrum disorder.

This study investigated the functional neuroanatomical correlates of spatial attention impairments in autism spectrum disorders (ASD) using an event-related functional magnetic resonance imaging (FMRI) design. Eight ASD participants and 8 normal comparison (NC) participants were tested with a task that required stimulus discrimination following a spatial cue that preceded target presentation by 100 msec (short interstimulus interval [ISI]) or 800 msec (long ISI). The ASD group showed significant behavioral spatial attention impairment in the short ISI condition. The FMRI results showed a reduction in activity within frontal, parietal, and occipital regions in ASD relative to the NC group, most notably within the inferior parietal lobule. ASD behavioral performance improved in the long ISI condition but was still impaired relative to the NC group. ASD FMRI activity in the long ISI condition suggested that the rudimentary framework of normal attention networks were engaged in ASD including bilateral activation within the frontal, parietal, and occipital lobes. Notable activation increases were observed in the superior parietal lobule and extrastriate cortex. No reliable activation was observed in the posterior cerebellar vermis in ASD participants during either long or short ISI conditions. In addition, no frontal activation during short ISI and severely reduced frontal activation during long ISI was observed in the ASD group. Taken together, these findings suggest a dysfunctional cerebello-frontal spatial attention system in ASD. The pattern of findings suggests that ASD is associated with a profound deficit in automatic spatial attention abilities and abnormal voluntary spatial attention abilities. This article also describes a method for reducing the contribution of physical eye movements to the blood-oxygenation level dependent activity in studies of ASD.

Electroencephalographic brain dynamics following manually responded visual targets.

Scalp-recorded electroencephalographic (EEG) signals produced by partial synchronization of cortical field activity mix locally synchronous electrical activities of many cortical areas. Analysis of event-related EEG signals typically assumes that poststimulus potentials emerge out of a flat baseline. Signals associated with a particular type of cognitive event are then assessed by averaging data from each scalp channel across trials, producing averaged event-related potentials (ERPs). ERP averaging, however, filters out much of the information about cortical dynamics available in the unaveraged data trials. Here, we studied the dynamics of cortical electrical activity while subjects detected and manually responded to visual targets, viewing signals retained in ERP averages not as responses of an otherwise silent system but as resulting from event-related alterations in ongoing EEG processes. We applied infomax independent component analysis to parse the dynamics of the unaveraged 31-channel EEG signals into maximally independent processes, then clustered the resulting processes across subjects by similarities in their scalp maps and activity power spectra, identifying nine classes of EEG processes with distinct spatial distributions and event-related dynamics. Coupled two-cycle postmotor theta bursts followed button presses in frontal midline and somatomotor clusters, while the broad postmotor "P300" positivity summed distinct contributions from several classes of frontal, parietal, and occipital processes. The observed event-related changes in local field activities, within and between cortical areas, may serve to modulate the strength of spike-based communication between cortical areas to update attention, expectancy, memory, and motor preparation during and after target recognition and speeded responding.