Investigating predictive coding in younger and older children using MEG and a multi-feature auditory oddball paradigm.

There is mounting evidence for predictive coding theory from computational, neuroimaging, and psychological research. However, there remains a lack of research exploring how predictive brain function develops across childhood. To address this gap, we used pediatric magnetoencephalography to record the evoked magnetic fields of 18 younger children (M = 4.1 years) and 19 older children (M = 6.2 years) as they listened to a 12-min auditory oddball paradigm. For each child, we computed a mismatch field "MMF": an electrophysiological component that is widely interpreted as a neural signature of predictive coding. At the sensor level, the older children showed significantly larger MMF amplitudes relative to the younger children. At the source level, the older children showed a significantly larger MMF amplitude in the right inferior frontal gyrus relative to the younger children, P < 0.05. No differences were found in 2 other key regions (right primary auditory cortex and right superior temporal gyrus) thought to be involved in mismatch generation. These findings support the idea that predictive brain function develops during childhood, with increasing involvement of the frontal cortex in response to prediction errors. These findings contribute to a deeper understanding of the brain function underpinning child cognitive development.

Increased segregation of functional networks in developing brains.

A growing literature conceptualises typical brain development from a network perspective. However, largely due to technical and methodological challenges inherent in paediatric functional neuroimaging, there remains an important gap in our knowledge regarding the typical development of functional brain networks in "preschool" childhood (i.e., children younger than 6 years of age). In this study, we recorded brain oscillatory activity using age-appropriate magnetoencephalography in 24 children, including 14 preschool children aged from 4 to 6 years and 10 school children aged from 7 to 12 years. We compared the topology of the resting-state brain networks in these children, estimated using minimum spanning tree (MST) constructed from phase synchrony between beamformer-reconstructed time-series, with that of 24 adults. Our results show that during childhood the MST topology shifts from a star-like (centralised) toward a more line-like (de-centralised) configuration, indicating the functional brain networks become increasingly segregated. In addition, the increasing global network segregation is frequency-independent and accompanied by decreases in centrality (or connectedness) of cortical regions with age, especially in areas of the default mode network. We propose a heuristic MST model of "network space", which posits a clear developmental trajectory for the emergence of complex brain networks. Our results not only revealed topological reorganisation of functional networks across multiple temporal and spatial scales in childhood, but also fill a gap in the literature regarding neurophysiological mechanisms of functional brain maturation during the preschool years of childhood.

Atypical brain responses to auditory spatial cues in adults with autism spectrum disorder.

The auditory processing atypicalities experienced by many individuals on the autism spectrum disorder might be understood in terms of difficulties parsing the sound energy arriving at the ears into discrete auditory 'objects'. Here, we asked whether autistic adults are able to make use of two important spatial cues to auditory object formation - the relative timing and amplitude of sound energy at the left and right ears. Using electroencephalography, we measured the brain responses of 15 autistic adults and 15 age- and verbal-IQ-matched control participants as they listened to dichotic pitch stimuli - white noise stimuli in which interaural timing or amplitude differences applied to a narrow frequency band of noise typically lead to the perception of a pitch sound that is spatially segregated from the noise. Responses were contrasted with those to stimuli in which timing and amplitude cues were removed. Consistent with our previous studies, autistic adults failed to show a significant object-related negativity (ORN) for timing-based pitch, although their ORN was not significantly smaller than that of the control group. Autistic participants did show an ORN to amplitude cues, indicating that they do not experience a general impairment in auditory object formation. However, their P400 response - thought to indicate the later attention-dependent aspects of auditory object formation - was missing. These findings provide further evidence of atypical auditory object processing in autism with potential implications for understanding the perceptual and communication difficulties associated with the condition.

The relationship between spoken language and speech and nonspeech processing in children with autism: a magnetic event-related field study.

It has been proposed that language impairments in children with Autism Spectrum Disorders (ASD) stem from atypical neural processing of speech and/or nonspeech sounds. However, the strength of this proposal is compromised by the unreliable outcomes of previous studies of speech and nonspeech processing in ASD. The aim of this study was to determine whether there was an association between poor spoken language and atypical event-related field (ERF) responses to speech and nonspeech sounds in children with ASD (n = 14) and controls (n = 18). Data from this developmental population (ages 6-14) were analysed using a novel combination of methods to maximize the reliability of our findings while taking into consideration the heterogeneity of the ASD population. The results showed that poor spoken language scores were associated with atypical left hemisphere brain responses (200 to 400 ms) to both speech and nonspeech in the ASD group. These data support the idea that some children with ASD may have an immature auditory cortex that affects their ability to process both speech and nonspeech sounds. Their poor speech processing may impair their ability to process the speech of other people, and hence reduce their ability to learn the phonology, syntax, and semantics of their native language.

A frontotemporoparietal network common to initiating and responding to joint attention bids.

Joint attention is a fundamental cognitive ability that supports daily interpersonal relationships and communication. The Parallel Distributed Processing model (PDPM) postulates that responding to (RJA) and initiating (IJA) joint attention are predominantly supported by posterior-parietal and frontal regions respectively. It also argues that these neural networks integrate during development, supporting the parallel processes of self- and other-attention representation during interactions. However, direct evidence for the PDPM is limited due to a lack of ecologically valid experimental paradigms that can capture both RJA and IJA. Building on existing interactive approaches, we developed a virtual reality paradigm where participants engaged in an online interaction to complete a cooperative task. By including tightly controlled baseline conditions to remove activity associated with non-social task demands, we were able to directly contrast the neural correlates of RJA and IJA to determine whether these processes are supported by common brain regions. Both RJA and IJA activated broad frontotemporoparietal networks. Critically, a conjunction analysis identified that a subset of these regions were common to both RJA and IJA. This right-lateralised network included the dorsal portion of the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), middle temporal gyrus (MTG), precentral gyrus, posterior superior temporal sulcus (pSTS), temporoparietal junction (TPJ) and precuneus. Additional activation was observed in this network for IJA relative to RJA at MFG, IFG, TPJ and precuneus. This is the first imaging study to directly investigate the neural correlates common to RJA and IJA engagement, and thus support the assumption that a broad integrated network underlies the parallel aspects of both initiating and responding to joint attention.

Face processing in the brains of pre-school aged children measured with MEG.

There are two competing theories concerning the development of face perception: a late maturation account and an early maturation account. Magnetoencephalography (MEG) neuroimaging holds promise for adjudicating between the two opposing accounts by providing objective neurophysiological measures of face processing, with sufficient temporal resolution to isolate face-specific brain responses from those associated with other sensory, cognitive and motor processes. The current study used a customized child MEG system to measure M100 and M170 brain responses in 15 children aged three to six years while they viewed faces, cars and their phase-scrambled counterparts. Compared to adults tested using the same stimuli in a conventional MEG system, children showed significantly larger and later M100 responses. Children's M170 responses, derived by subtracting the responses to phase-scrambled images from the corresponding images (faces or cars) were delayed in latency but otherwise resembled the adult M170. This component has not been obtained in previous studies of young children tested using conventional adult MEG systems. However children did show a markedly reduced M170 response to cars in comparison to adults. This may reflect children's lack of expertise with cars relative to faces. Taken together, these data are in accord with recent behavioural and neuroimaging data that support early maturation of the basic face processing functions.

Development of effective connectivity in the core network for face perception.

This study measured effective connectivity within the core face network in young children using a paediatric magnetoencephalograph (MEG). Dynamic casual modeling (DCM) of brain responses was performed in a group of adults (N = 14) and a group of young children aged from 3 to 6 years (N = 15). Three candidate DCM models were tested, and the fits of the MEG data to the three models were compared at both individual and group levels. The results show that the connectivity structure of the core face network differs significantly between adults and children. Further, the relative strengths of face network connections were differentially modulated by experimental conditions in the two groups. These results support the interpretation that the core face network undergoes significant structural configuration and functional specialization between four years of age and adulthood.

Neuromagnetic brain activity associated with anticipatory postural adjustments for bimanual load lifting.

During bimanual load lifting, the brain must anticipate the effects of unloading upon the load-bearing arm. Little is currently known about the neural networks that coordinate these anticipatory postural adjustments. We measured neuromagnetic brain activity with whole-head magnetoencephalography while participants performed a bimanual load-lifting task. Anticipatory adjustments were associated with reduction in biceps brachii muscle activity of the load-bearing arm and pre-movement desynchronization of the cortical beta rhythm. Beamforming analyses localized anticipatory brain activity to the precentral gyrus, basal ganglia, supplementary motor area, and thalamus, contralateral to the load-bearing arm. To our knowledge this is the first human neuroimaging study to directly investigate anticipatory postural adjustments and to explicitly partition the anticipatory and volitional aspects of brain activity in bimanual load lifting. These data contribute to our understanding of the neural systems supporting anticipatory postural adjustments in healthy adults.

Premovement brain activity in a bimanual load-lifting task.

Even the simplest volitional movements must be precisely coordinated with anticipatory postural adjustments. Little is currently known about the neural networks that coordinate these adjustments in healthy adults. We measured brain activity prior to movement during a bimanual load-lifting task, designed to elicit anticipatory adjustments in a restricted and well-defined set of musculature in the arm. Electroencephalography and magnetoencephalography brain measurements were obtained from eleven participants while they performed a bimanual load-lifting task that required precise inter-limb coordination. Anticipatory biceps brachii inhibition in the loaded arm was associated with a robust desynchronization of the beta rhythm. Beamforming analyses localized beta band responses to the parietal lobules, pre- and post-central gyri, middle and medial frontal gyri, basal ganglia and thalamus. The current study shows that premovement brain activity in a bimanual load-lifting task can be imaged with magnetoencephalography. Future experiments will partition out brain activity associated with anticipatory postural adjustments and volitional movements. The experimental paradigm will also be useful in the study of motor function in patients with developmental or degenerative disorders.

Specificity of impaired facial identity recognition in children with suspected developmental prosopagnosia.

Adults experiencing face recognition difficulties in the absence of known brain injury are described as cases of developmental prosopagnosia (DP), under the assumption that specific face recognition impairments have always been present. However, only five childhood cases of DP have been reported, and the majority had additional socio-communicative impairments consistent with an autism spectrum disorder (ASD). We tested face recognition skills of six 4- to 8-year-old children, who were suspected of having DP, and tested for ASD using established diagnostic tools. Two children met criteria for ASD. One child did not exhibit consistent face recognition impairments. The remaining three children were severely impaired on multiple tasks of unfamiliar face recognition despite normal cognitive functioning and no evidence of ASD. Two of these children were also impaired at object recognition suggesting more general visual recognition problems. The final child showed normal object recognition demonstrating apparently specific problems with facial identity recognition.

Toward an Individualized Neural Assessment of Receptive Language in Children.

Purpose We aimed to develop a noninvasive neural test of language comprehension to use with nonspeaking children for whom standard behavioral testing is unreliable (e.g., minimally verbal autism). Our aims were threefold. First, we sought to establish the sensitivity of two auditory paradigms to elicit neural responses in individual neurotypical children. Second, we aimed to validate the use of a portable and accessible electroencephalography (EEG) system, by comparing its recordings to those of a research-grade system. Third, in light of substantial interindividual variability in individuals' neural responses, we assessed whether multivariate decoding methods could improve sensitivity. Method We tested the sensitivity of two child-friendly covert N400 paradigms. Thirty-one typically developing children listened to identical spoken words that were either strongly predicted by the preceding context or violated lexical-semantic expectations. Context was given by a cue word (Experiment 1) or sentence frame (Experiment 2), and participants either made an overall judgment on word relatedness or counted lexical-semantic violations. We measured EEG concurrently from a research-grade system, Neuroscan's SynAmps2, and an adapted gaming system, Emotiv's EPOC+. Results We found substantial interindividual variability in the timing and topology of N400-like effects. For both paradigms and EEG systems, traditional N400 effects at the expected sensors and time points were statistically significant in around 50% of individuals. Using multivariate analyses, detection rate increased to 88% of individuals for the research-grade system in the sentences paradigm, illustrating the robustness of this method in the face of interindividual variations in topography. Conclusions There was large interindividual variability in neural responses, suggesting interindividual variation in either the cognitive response to lexical-semantic violations and/or the neural substrate of that response. Around half of our neurotypical participants showed the expected N400 effect at the expected location and time points. A low-cost, accessible EEG system provided comparable data for univariate analysis but was not well suited to multivariate decoding. However, multivariate analyses with a research-grade EEG system increased our detection rate to 88% of individuals. This approach provides a strong foundation to establish a neural index of language comprehension in children with limited communication. Supplemental Material https://doi.org/10.23641/asha.12606311.

Eye-movement patterns are associated with communicative competence in autistic spectrum disorders.

BACKGROUND: Investigations using eye-tracking have reported reduced fixations to salient social cues such as eyes when participants with autism spectrum disorders (ASD) view social scenes. However, these studies have not distinguished different cognitive phenotypes. METHODS: The eye-movements of 28 teenagers with ASD and 18 typically developing peers were recorded as they watched videos of peers interacting in familiar situations. Within ASD, we contrasted the viewing patterns of those with and without language impairments. The proportion of time spent viewing eyes, mouths and other scene details was calculated, as was latency of first fixation to eyes. Finally, the association between viewing patterns and social-communicative competence was measured. RESULTS: Individuals with ASD and age-appropriate language abilities spent significantly less time viewing eyes and were slower to fixate the eyes than typically developing peers. In contrast, there were no differences in viewing patterns between those with language impairments and typically developing peers. Eye-movement patterns were not associated with social outcomes for either language phenotype. However, increased fixations to the mouth were associated with greater communicative competence across the autistic spectrum. CONCLUSIONS: Attention to both eyes and mouths is important for language development and communicative competence. Differences in fixation time to eyes may not be sufficient to disrupt social competence in daily interactions. A multiple cognitive deficit model of ASD, incorporating different language phenotypes, is advocated.

Responding to joint attention bids in schizophrenia: An interactive eye-tracking study.

This study investigated social cognition in schizophrenia using a virtual reality paradigm to capture the dynamic processes of evaluating and responding to eye gaze as an intentional communicative cue. A total of 21 patients with schizophrenia and 21 age-, gender-, and IQ-matched healthy controls completed an interactive computer game with an on-screen avatar that participants believed was controlled by an off-screen partner. On social trials, participants were required to achieve joint attention by correctly interpreting and responding to gaze cues. Participants also completed non-social trials in which they responded to an arrow cue within the same task context. While patients and controls took equivalent time to process communicative intent from gaze shifts, patients made significantly more errors than controls when responding to the directional information conveyed by gaze, but not arrow, cues. Despite no differences in response times to gaze cues between groups, patients were significantly slower than controls when responding to arrow cues. This is the opposite pattern of results previously observed in autistic adults using the same task and suggests that, despite general impairments in attention orienting or oculomotor control, patients with schizophrenia demonstrate a facilitation effect when responding to communicative gaze cues. Findings indicate a hyper-responsivity to gaze cues of communicative intent in schizophrenia. The possible effects of self-referential biases when evaluating gaze direction are discussed, as are clinical implications.

Do individuals with autism process words in context? Evidence from language-mediated eye-movements.

It is widely argued that people with autism have difficulty processing ambiguous linguistic information in context. To investigate this claim, we recorded the eye-movements of 24 adolescents with autism spectrum disorder and 24 language-matched peers as they monitored spoken sentences for words corresponding to objects on a computer display. Following a target word, participants looked more at a competitor object sharing the same onset than at phonologically unrelated objects. This effect was, however, mediated by the sentence context such that participants looked less at the phonological competitor if it was semantically incongruous with the preceding verb. Contrary to predictions, the two groups evidenced similar effects of context on eye-movements. Instead, across both groups, the effect of sentence context was reduced in individuals with relatively poor language skills. Implications for the weak central coherence account of autism are discussed.

Cumulative plasma HIV burden disparities among adults in HIV care: implications for HIV transmission in the era of treatment as prevention.

OBJECTIVE: To characterize disparities in cumulative plasma HIV burden in a sample of adults accessing HIV care in San Francisco, California. DESIGN: Observational cohort and supplemental HIV surveillance data. METHODS: Data from the San Francisco Medical Monitoring Project 2012-2014 cycles and HIV surveillance data were used to create an analytic cohort followed for 2 years. Matched HIV viral load test results from HIV surveillance were used to create five viral outcome measures: any unsuppressed viral load (>200 copies/ml), any transmittable viral load (>1500 copies/ml), person-time spent unsuppressed, person-time spent transmittable, and 2-year viremia copy-years, a measure of cumulative plasma HIV burden. Rao-Scott chi-squares and analysis of variance examined differences in durable suppression and mean percentage time spent unsuppressed and transmittable. Weighted linear regression was used to describe differences in cumulative HIV burden. RESULTS: Adults receiving HIV care spent approximately 12% of the 2-year time period with an unsuppressed viral load and approximately 7% of the time at a transmittable viral level. Factors independently associated with higher cumulative HIV viremia in an adjusted model included trans women identity, younger age, lower CD4 cell count, and a history of homelessness, incarceration, not taking ART, and nonadherence to ART. CONCLUSION: Although 95% of the cohort of adults in HIV care in San Francisco self-reported ART use during MMP interview, they spent on average almost 1 month per year at a transmittable viral level. We identified characteristics of those who were more likely to have higher viral burden, highlighting priorities for resource allocation to reduce onward HIV transmission.

Joint attention difficulties in autistic adults: An interactive eye-tracking study.

Joint attention - the ability to coordinate attention with a social partner - is critical for social communication, learning and the regulation of interpersonal relationships. Infants and young children with autism demonstrate impairments in both initiating and responding to joint attention bids in naturalistic settings. However, little is known about joint attention abilities in adults with autism. Here, we tested 17 autistic adults and 17 age- and nonverbal intelligence quotient-matched controls using an interactive eye-tracking paradigm in which participants initiated and responded to joint attention bids with an on-screen avatar. Compared to control participants, autistic adults completed fewer trials successfully. They were also slower to respond to joint attention bids in the first block of testing but performed as well as controls in the second block. There were no group differences in responding to spatial cues on a non-social task with similar attention and oculomotor demands. These experimental results were mirrored in the subjective reports given by participants, with some commenting that they initially found it challenging to communicate using eye gaze, but were able to develop strategies that allowed them to achieve joint attention. Our study indicates that for many autistic individuals, subtle difficulties using eye-gaze information persist well into adulthood.

Disordered connectivity in the autistic brain: challenges for the "new psychophysiology".

In 2002, we published a paper [Brock, J., Brown, C., Boucher, J., Rippon, G., 2002. The temporal binding deficit hypothesis of autism. Development and Psychopathology 142, 209-224] highlighting the parallels between the psychological model of 'central coherence' in information processing [Frith, U., 1989. Autism: Explaining the Enigma. Blackwell, Oxford] and the neuroscience model of neural integration or 'temporal binding'. We proposed that autism is associated with abnormalities of information integration that is caused by a reduction in the connectivity between specialised local neural networks in the brain and possible overconnectivity within the isolated individual neural assemblies. The current paper updates this model, providing a summary of theoretical and empirical advances in research implicating disordered connectivity in autism. This is in the context of changes in the approach to the core psychological deficits in autism, of greater emphasis on 'interactive specialisation' and the resultant stress on early and/or low-level deficits and their cascading effects on the developing brain [Johnson, M.H., Halit, H., Grice, S.J., Karmiloff-Smith, A., 2002. Neuroimaging of typical and atypical development: a perspective from multiple levels of analysis. Development and Psychopathology 14, 521-536]. We also highlight recent developments in the measurement and modelling of connectivity, particularly in the emerging ability to track the temporal dynamics of the brain using electroencephalography (EEG) and magnetoencephalography (MEG) and to investigate the signal characteristics of this activity. This advance could be particularly pertinent in testing an emerging model of effective connectivity based on the balance between excitatory and inhibitory cortical activity [Rubenstein, J.L., Merzenich M.M., 2003. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behavior 2, 255-267; Brown, C., Gruber, T., Rippon, G., Brock, J., Boucher, J., 2005. Gamma abnormalities during perception of illusory figures in autism. Cortex 41, 364-376]. Finally, we note that the consequence of this convergence of research developments not only enables a greater understanding of autism but also has implications for prevention and remediation.

Human agency beliefs influence behaviour during virtual social interactions.

In recent years, with the emergence of relatively inexpensive and accessible virtual reality technologies, it is now possible to deliver compelling and realistic simulations of human-to-human interaction. Neuroimaging studies have shown that, when participants believe they are interacting via a virtual interface with another human agent, they show different patterns of brain activity compared to when they know that their virtual partner is computer-controlled. The suggestion is that users adopt an "intentional stance" by attributing mental states to their virtual partner. However, it remains unclear how beliefs in the agency of a virtual partner influence participants' behaviour and subjective experience of the interaction. We investigated this issue in the context of a cooperative "joint attention" game in which participants interacted via an eye tracker with a virtual onscreen partner, directing each other's eye gaze to different screen locations. Half of the participants were correctly informed that their partner was controlled by a computer algorithm ("Computer" condition). The other half were misled into believing that the virtual character was controlled by a second participant in another room ("Human" condition). Those in the "Human" condition were slower to make eye contact with their partner and more likely to try and guide their partner before they had established mutual eye contact than participants in the "Computer" condition. They also responded more rapidly when their partner was guiding them, although the same effect was also found for a control condition in which they responded to an arrow cue. Results confirm the influence of human agency beliefs on behaviour in this virtual social interaction context. They further suggest that researchers and developers attempting to simulate social interactions should consider the impact of agency beliefs on user experience in other social contexts, and their effect on the achievement of the application's goals.

Detecting communicative intent in a computerised test of joint attention.

The successful navigation of social interactions depends on a range of cognitive faculties-including the ability to achieve joint attention with others to share information and experiences. We investigated the influence that intention monitoring processes have on gaze-following response times during joint attention. We employed a virtual reality task in which 16 healthy adults engaged in a collaborative game with a virtual partner to locate a target in a visual array. In the Search task, the virtual partner was programmed to engage in non-communicative gaze shifts in search of the target, establish eye contact, and then display a communicative gaze shift to guide the participant to the target. In the NoSearch task, the virtual partner simply established eye contact and then made a single communicative gaze shift towards the target (i.e., there were no non-communicative gaze shifts in search of the target). Thus, only the Search task required participants to monitor their partner's communicative intent before responding to joint attention bids. We found that gaze following was significantly slower in the Search task than the NoSearch task. However, the same effect on response times was not observed when participants completed non-social control versions of the Search and NoSearch tasks, in which the avatar's gaze was replaced by arrow cues. These data demonstrate that the intention monitoring processes involved in differentiating communicative and non-communicative gaze shifts during the Search task had a measurable influence on subsequent joint attention behaviour. The empirical and methodological implications of these findings for the fields of autism and social neuroscience will be discussed.