Biology subjects

Foxe, J. J.

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

46 records · Page 3Linked to original sources

bioRxiv2021

Learning a new class of multisensory associations: High-density electrophysiological mapping of the temporal course of audio-visual object processing.

Multisensory objects that are frequently encountered in the natural environment lead to strong associations across a distributed sensory cortical network, with the end result experience of a unitary percept. Remarkably little is known, however, about the cortical processes sub-serving multisensory object formation and recognition. To advance our understanding in this important domain, the present study investigated the brain processes involved in learning and identification of novel visual-auditory objects. Specifically, we introduce and test a rudimentary three-stage model of multisensory object-formation and processing. Thirty adults were remotely trained for a week to recognize a novel class of multisensory objects (3D shapes paired to complex sounds), and high-density event related potentials (ERPs) were recorded to the corresponding unisensory (shapes or sounds only) and multisensory (shapes and sounds) stimuli, before and after intensive training. We identified three major stages of multisensory processing: 1) an early, multisensory, automatic effect (<100 ms) in occipital areas, related to the detection of simultaneous audiovisual signals and not related to multisensory learning 2) an intermediate object-processing stage (100-200 ms) in occipital and parietal areas, sensitive to the learned multisensory associations and 3) a late multisensory processing stage (>250 ms) that appears to be involved in both object recognition and possibly memory consolidation. Results from this study provide support for multiple stages of multisensory object learning and recognition that are subserved by an extended network of cortical areas.

neuroscience↗

bioRxiv2020

Oscillatory entrainment mechanisms and anticipatory predictive processes in Autism Spectrum Disorder (ASD)

Anticipating near-future events is fundamental to adaptive behavior, whereby neural processing of predictable stimuli is significantly facilitated relative to non-predictable inputs. 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 in daily life, and as such, a candidate neural mechanism may be failure to adequately entrain neural activity to repetitive environmental patterns. Here, we tested this hypothesis by interrogating rhythmic entrainment both behaviorally and electrophysiologically. We recorded high-density electroencephalography in children with ASD (n=31) and Typically Developing (TD) age- and IQ-matched controls (n=20), while they reacted to an auditory target as quickly as possible. This auditory event was either preceded by predictive rhythmic visual cues, or not. Results showed that while both groups presented highly comparable evoked responses to the visual stimuli, children with ASD showed reduced neural entrainment to the rhythmic visual cues, and altered anticipation of the occurrence of these stimuli. Further, in both groups, neuro-oscillatory phase coherence correlated with behavior. These results describe neural processes that may underlie impaired event anticipation in children with ASD, and support the notion that their perception of events is driven more by instantaneous sensory inputs and less by their temporal predictability.

neuroscience↗

bioRxiv2020

Individuals with autism have no detectable deficit in neural markers of prediction error when presented with auditory rhythms of varied temporal complexity

The brains ability to encode temporal patterns and predict upcoming events is critical for speech perception and other aspects of social communication. Deficits in predictive coding may contribute to difficulties with social communication and overreliance on repetitive predictable environments in individuals with autism spectrum disorder (ASD). Using a mismatch negativity (MMN) task involving rhythmic tone sequences of varying complexity, we tested the hypotheses that 1) individuals with ASD have reduced MMN response to auditory stimuli that deviate in presentation timing from expected patterns, particularly as pattern complexity increases and 2) amplitude of MMN signal is inversely correlated with level of impairment in social communication and repetitive behaviors. Electroencephalography was acquired as individuals (age 6-21years) listened to repeated five-rhythm tones that varied in the Shannon entropy of the rhythm across three conditions (zero, medium-1 bit) and high-2 bit entropy). The majority of the tones conformed to the established rhythm (standard tones); occasionally the 4th tone was temporally shifted relative to its expected time of occurrence (deviant tones). Social communication and repetitive behaviors were measured using the Social Responsiveness Scale and Repetitive Behavior Scale-Revised. Both neurotypical controls (n=19) and individuals with ASD (n=21) show stepwise decreases in MMN as a function of increasing entropy. Contrary to the result forecasted by a predictive coding hypothesis, individuals with ASD do not differ from controls in these neural mechanisms of prediction error to auditory rhythms of varied temporal complexity, and there is no relationship between these signals and social communication or repetitive behavior measures. Lay SummaryWe tested the idea that the brains ability to use previous experience to influence processing of sounds is weaker in individuals with autism spectrum disorder (ASD) than in neurotypical individuals. We found no difference between individuals with ASD and neurotypical controls in brain wave responses to sounds that occurred earlier than expected in either simple or complex rhythms. There was also no relationship between these brain waves and social communication or repetitive behavior scores.

neuroscience↗

bioRxiv2020

Atypical response inhibition and error processing in 22q11.2 Deletion Syndrome and Schizophrenia: Towards neuromarkers of disease progression and risk

22q11.2 deletion syndrome (also known as DiGeorge syndrome or velo-cardio-facial syndrome) is characterized by increased vulnerability to neuropsychiatric symptoms, with approximately 30% of individuals with the deletion going on to develop schizophrenia. Clinically, deficits in executive function have been noted in this population, but the underlying neural processes are not well understood. Using a Go/No-Go response inhibition task in conjunction with high-density electrophysiological recordings (EEG), we sought to investigate the behavioral and neural dynamics of inhibition of a prepotent response (a critical component of executive function) in individuals with 22q11.2DS with and without psychotic symptoms, when compared to individuals with idiopathic schizophrenia and age-matched neurotypical controls. Twenty-eight participants diagnosed with 22q11.2DS (14-35 years old; 14 with at least one psychotic symptom), 15 individuals diagnosed with schizophrenia (18-63 years old) and two neurotypical control groups (one age-matched to the 22q11.2DS sample, the other age-matched to the schizophrenia sample) participated in this study. Analyses focused on the N2 and P3 no-go responses and error-related negativity (Ne) and positivity (Pe). Atypical inhibitory processing was shown behaviorally and by significantly reduced P3, Ne, and Pe responses in 22q11.2DS and schizophrenia. Interestingly, whereas P3 was only reduced in the presence of psychotic symptoms, Ne and Pe were equally reduced in schizophrenia and 22q11.2DS, regardless of the presence of symptoms. We argue that while P3 may be a marker of disease severity, Ne and Pe might be candidate markers of risk.

neuroscience↗

bioRxiv2019

Mobile Brain/Body Imaging of cognitive-motor impairment in multiple sclerosis: deriving EEG-based neuro-markers during a dual-task walking study

Individuals with a diagnosis of multiple sclerosis (MS) often present with deficits in the cognitive as well as the motor domain. The ability to perform tasks that rely on both domains may therefore be particularly impaired. Yet, behavioral studies designed to measure costs associated with performing two tasks at the same time such as dual-task walking have yielded mixed results. Patients may mobilize additional brain resources to sustain good levels of performance. To test this hypothesis, we acquired event-related potentials (ERP) in thirteen individuals with MS and fifteen healthy control (HC) participants performing a Go/NoGo response inhibition task while sitting (i.e., single task) or walking on a treadmill (i.e., dual-task). In previous work, we showed that the nogo-N2 elicited by the cognitive task was reduced when healthy adults are also asked to walk, and that nogo-N2 reduction was accompanied by sustained dual-task performance. We predicted that some MS patients, similar to their healthy peers, may mobilize N2-indexed brain resources and thereby reduce costs. Somewhat to our surprise, the HC group performed the Go/NoGo task more accurately while walking, thus showing a dual-task benefit, whereas, in line with expectation, the MS group showed a trend towards dual-task costs. The expected nogo-N2 reduction during dual-task walking was found in the HC group, but was not present at the group level in the MS group, suggesting that this group did not modulate the nogo-N2 process in response to higher task load. Regression analysis for the pooled sample revealed a robust link between nogo-N2 reduction and better dual-task performance. We conclude that impaired nogo-N2 adaptation reflects a neurophysiological marker of cognitive-motor dysfunction in MS.

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bioRxiv2019

Electrophysiological evidence for impaired auditory sensory memory in Cystinosis despite typical sensory processing: An MMN investigation

Cystinosis, a genetic rare disease characterized by cystine accumulation and crystallization, results in significant damage in a multitude of tissues and organs, such as the kidney, thyroid, eye, and brain. While Cystinosis impact on brain function is relatively mild compared to its effects on other organs, the increased lifespan of this population and thus potential for productive societal contributions have led to increased interest on the effects on brain function. Nevertheless, and despite some evidence of structural brain differences, the neural impact of the mutation is still not well characterized.\n\nHere, using a passive duration oddball paradigm (with different stimulus onset asynchronies (SOAs), representing different levels of demand on memory) and high-density electrophysiology, we tested basic auditory processing in a group of 22 children and adolescents diagnosed with Cystinosis (age range: 6-17 years old) and in neurotypical age-matched controls (N=24). We examined whether the N1 and mismatch negativity (MMN) significantly differed between the groups and if those neural measures correlated with verbal and non-verbal IQ. Individuals diagnosed with Cystinosis presented similar N1 responses to their age-matched peers, indicating typical basic auditory processing in this population. However, whereas both groups showed similar MMN responses for the shortest (450ms) SOA, suggesting intact change detection and sensory memory, individuals diagnosed with Cystinosis presented clearly reduced responses for the longer (900ms and 1800ms) SOAs. This could indicate reduced duration auditory sensory memory traces, and thus sensory memory impairment, in children and adolescents diagnosed with Cystinosis. Future work addressing other aspects of sensory and working memory is needed to understand the underlying bases of the differences described here, and their implication for higher order processing.

neuroscience↗

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↗