Biology subjects

Foxe, J. J.

Publications and source records attributed to Foxe, J. J..

4 recordsLinked to original sources

bioRxiv2019

Auditory processing atypicalities for pure tones and complex speech sounds in Rett Syndrome: towards neuromarkers of disease progression.

Due to severe motor impairments and the lack of expressive language abilities seen in most patients with Rett Syndrome (RTT), it has proven extremely difficult to obtain accurate measures of auditory processing capabilities in this population. Here, we examined early auditory cortical processing of pure tones and more complex phonemes females with confirmed mutation of the MECP2 gene. We recorded high-density auditory evoked potentials (AEP), which allow for objective evaluation of the timing and severity of processing deficits along the auditory processing hierarchy. We compared AEPs of 12 females with RTT to those of 21 typically developing (TD) peers aged 4-21 years, interrogating the first four major components of the AEP (P1: 60-90ms; N1: 100-130ms; P2: 135-165ms; N2: 245-275ms). Atypicalities were evident in RTT at the initial stage of processing. Whereas the initial P1 showed increased amplitude to phonemic inputs relative to tones in TD participants, this modulation by stimulus complexity was absent in RTT. Interestingly, the subsequent N1 did not differ between groups, whereas the following P2 was hugely diminished in RTT, regardless of stimulus complexity. The N2 was similarly smaller in RTT, and did not differ as a function of stimulus type. The P2 effect was remarkably robust in differentiating between groups with near perfect separation between the two groups despite the wide age range of our samples. Given this robustness, along with the observation that P2 amplitude was significantly associated with RTT symptom severity, the P2 has the potential to serve as a biomarker of treatment efficacy.\n\nSignificance statementOur study points to dramatic reduction of the P2 component of the auditory evoked potential (AEP) as a potentially reliable biomarker of Rett Syndrome severity, with prospective applicability as an objective readout (neuromarker) of change in functional brain activity following therapeutic interventions administered in the context of clinical trials. Compellingly, the reduction of P2 amplitude in patients with RTT mimics findings in animal models of RTT, providing a translational bridge between pre-clinical and human research.

neuroscience↗

bioRxiv2019

Dissociable neural circuits underlie the resolution of three discrete sources of competition during task-switching.

Humans perform sub-optimally when juggling more than one task, but are nonetheless required to multitask during many daily activities. Rapidly and effectively switching attentional focus between tasks is fundamental to navigating complex environments. Task-switching paradigms in conjunction with neuroimaging have identified brain networks underpinning flexible reallocation of cognitive resources and a core network of neural regions is repeatedly implicated (i.e., posterior parietal, inferior frontal, anterior cingulate, and middle frontal cortex). Performance costs such as reduced accuracy and slowed responses accompany the first execution of a task following a task-switch. These costs stem from three main sources of competition: 1) the need to reconfigure task-rules, 2) the immediate history of motor responding, and 3) whether inputs to be acted upon provide congruent or incongruent information regarding the appropriate motor response, relative to the recently \"switched-away-from\" task. Here, we asked whether both common (domain-general) and non-overlapping (dissociable) neural circuits were involved in resolving these three distinct sources of competition under high-demand task-switching conditions. Dissociable neural circuits were active in resolving each of the three sources of competition. No domain-general regions were implicated in all three. Rather, two regions were common across rule-switching and stimulus incongruence, and five regions to incongruence and response-switching. Each source of conflict elicited activation from many regions including the posterior cingulate, thalamus, and cerebellum, regions not commonly implicated in the task-switching literature. These results suggest that dissociable neural networks are principally responsible for resolving different sources of competition, but with partial interaction of some overlapping domain-general circuitry.

neuroscience↗

bioRxiv2019

Auditory sensory memory span for duration is severely curtailed in females with Rett Syndrome.

Rett syndrome (RTT), a rare neurodevelopmental disorder caused by mutations in the MECP2 gene, is typified by profound cognitive impairment and severe language impairment, rendering it very difficult to accurately measure auditory processing capabilities behaviorally in this population. Here we leverage the mismatch negativity (MMN) component of the event-related potential to measure the ability of RTT patients to decode and store occasional duration deviations in a stream of auditory stimuli. Sensory memory for duration, crucial for speech comprehension, has not been studied in RTT.\n\nHigh-density EEG was successfully recorded in 18 females with RTT and 27 age-matched typically developing (TD) controls (aged 6-22 years). Data from 7 RTT and 3 TD participants were excluded for excessive noise. Stimuli were 1kHz tones with a standard duration of 100ms and deviant duration of 180ms. To assess the sustainability of sensory memory, stimulus presentation rate was varied with stimulus onset asynchronies (SOAs) of 450, 900 and 1800ms. MMNs with maximum negativity over fronto-central scalp and a latency of 220-230ms were clearly evident for each presentation rate in the TD group, but only for the shortest SOA in the RTT group. Repeated-measures ANOVA revealed a significant group by SOA interaction. MMN amplitude correlated with age in the TD group only. MMN amplitude was not correlated with the Rett Syndrome Severity Scale. This study indicates that while RTT patients can decode deviations in auditory duration, the span of this sensory memory system is severely foreshortened, with likely implications for speech decoding abilities.

neuroscience↗

bioRxiv2019

Developmental Recovery of Impaired Multisensory Processing in Autism and the Cost of Switching Sensory Modality

Children with autism spectrum disorder (ASD) are often impaired in their ability to cope with and process multisensory information, which may contribute to some of the social and communicative deficits that are prevalent in this population. Amelioration of such deficits in adolescence has been observed for ecologically-relevant stimuli such as speech. However, it is not yet known if this recovery generalizes to the processing of nonsocial stimuli such as more basic beeps and flashes, typically used in cognitive neuroscience research. We hypothesize that engagement of different neural processes and lack of environmental exposure to such artificial stimuli leads to protracted developmental trajectories in both neurotypical (NT) individuals and individuals with ASD, thus delaying the age at which we observe this "catch up". Here, we test this hypothesis using a bisensory detection task by measuring human response times to randomly presented auditory, visual and audiovisual stimuli. By measuring the behavioral gain afforded by an audiovisual signal, we show that the multisensory deficit previously reported in children with ASD recovers in adulthood by the mid-twenties. In addition, we examine the effects of switching between sensory modalities and show that teenagers with ASD incur less of a behavioral cost than their NT peers. Computational modelling reveals that multisensory information interacts according to different rules in children and adults, and that sensory evidence is weighted differently too. In ASD, weighting of sensory information and allocation of attention during multisensory processing differs to that of NT individuals. Based on our findings, we propose a theoretical framework of multisensory development in NT and ASD individuals.

neuroscience↗