Associations between spontaneous electroencephalogram oscillations and oxygen saturation across normobaric and hypobaric hypoxia.

High-altitude indoctrination (HAI) trains individuals to recognize symptoms of hypoxia by simulating high-altitude conditions using normobaric (NH) or hypobaric (HH) hypoxia. Previous studies suggest that despite equivalent inspired oxygen levels, physiological differences could exist between these conditions. In particular, differences in neurophysiological responses to these conditions are not clear. Our study aimed to investigate correlations between oxygen saturation (SpO2 ) and neural responses in NH and HH. We recorded 5-min of resting-state eyes-open electroencephalogram (EEG) and SpO2 during control, NH, and HH conditions from 13 participants. We applied a multivariate framework to characterize correlations between SpO2 and EEG measures (spectral power and multiscale entropy [MSE]), within each participant and at the group level. Participants were desaturating during the first 150 s of NH versus steadily desaturated in HH. We considered the entire time interval, first and second half intervals, separately. All the conditions were characterized by statistically significant participant-specific patterns of EEG-SpO2 correlations. However, at the group level, the desaturation period expressed a robust pattern of these correlations across frequencies and brain locations. Specifically, the first 150 s of NH during desaturation differed significantly from the other conditions with negative absolute alpha power-SpO2 correlations and positive MSE-SpO2 correlations. Once steadily desaturated, NH and HH had no significant differences in EEG-SpO2 correlations. Our findings indicate that the desaturating phase of hypoxia is a critical period in HAI courses, which would require developing strategies for mitigating the hypoxic stimulus in a real-world situation.

Alterations in Local Connectivity and Their Developmental Trajectories in Autism Spectrum Disorder: Does Being Female Matter?

Autism spectrum disorder (ASD) is diagnosed more often in males with a ratio of 1:4 females/males. This bias is even stronger in neuroimaging studies. There is a growing evidence suggesting that local connectivity and its developmental trajectory is altered in ASD. Here, we aim to investigate how local connectivity and its age-related trajectories vary with ASD in both males and females. We used resting-state fMRI data from the ABIDE I and II repository: males (n = 102) and females (n = 92) with ASD, and typically developing males (n = 104) and females (n = 92) aged between 6 and 26. Local connectivity was quantified as regional homogeneity. We found increases in local connectivity in participants with ASD in the somatomotor and limbic networks and decreased local connectivity within the default mode network. These alterations were more pronounced in females with ASD. In addition, the association between local connectivity and ASD symptoms was more robust in females. Females with ASD had the most distinct developmental trajectories of local connectivity compared with other groups. Overall, our findings of more pronounced local connectivity alterations in females with ASD could indicate a greater etiological load for an ASD diagnosis in this group congruent with the female protective effect hypothesis.

Multiple constrained minimum variance beamformer (MCMV) performance in connectivity analyses.

Functional brain connectivity is increasingly being seen as critical for cognition, perception and motor control. Magnetoencephalography and electroencephalography are modalities that offer noninvasive mapping of electrophysiological interactions among brain regions, yet suffer from signal leakage and signal cancellation when estimating brain activity. This leads to biased connectivity values which complicate interpretation. In this study, we test the hypothesis that a Multiple Constrained Minimum Variance beamformer (MCMV) outperforms the more traditional Linearly Constrained Minimum Variance beamformer (LCMV) for estimation of electrophysiological connectivity. To this end, MCMV and LCMV performance is compared in task related analyses with both simulated data and human MEG recordings of visual steady state signals, and in resting state analyses with simulated data and human MEG data of 89 subjects. In task related scenarios connectivity was estimated using coherence and phase locking values, whereas envelope correlations were used for the resting state data. We also introduce a novel Augmented Pairwise MCMV (APW-MCMV) approach for signal leakage suppression in resting state analyses and assess its performance against LCMV and more conventional MCMV approaches. We demonstrate that with MCMV effects of signal mixing and coherent source cancellation are greatly reduced in both task related and resting state conditions, while in contrast to other approaches 0- and short time lag interactions are preserved. In addition, we demonstrate that in resting state analyses, APW-MCMV strongly reduces spurious connections while better controlling for false negatives compared to more conservative measures such as symmetrical orthogonalization.

Neuromagnetic activation and oscillatory dynamics of stimulus-locked processing during naturalistic viewing.

Naturalistic stimuli such as watching a movie while in the scanner provide an ecologically valid paradigm that has the potential of extracting valuable information on how the brain processes complex stimuli in realistic visual and auditory contexts. Naturalistic viewing is also easier to conduct with challenging participant groups including patients and children. Given the high temporal resolution of MEG, in the present study, we demonstrate how a short movie clip can be used to map distinguishable activation and connectivity dynamics underlying the processing of specific classes of visual stimuli such as face and hand manipulations, as well as contrasting activation dynamics for auditory words and non-words. MEG data were collected from 22 healthy volunteers (6 females, 3 left handed, mean age - 27.7 â€‹± â€‹5.28 years) during the presentation of naturalistic audiovisual stimuli. The MEG data were split into trials with the onset of the stimuli belonging to classes of interest (words, non-words, faces, hand manipulations). Based on the components of the averaged sensor ERFs time-locked to the visual and auditory stimulus onset, four and three time-windows, respectively, were defined to explore brain activation dynamics. Pseudo-Z, defined as the ratio of the source-projected time-locked power to the projected noise power for each vertex, was computed and used as a proxy of time-locked brain activation. Statistical testing using the mean-centered Partial Least Squares analysis indicated periods where a given visual or auditory stimuli had higher activation. Based on peak pseudo-Z differences between the visual conditions, time-frequency resolved analyses were performed to assess beta band desynchronization in motor-related areas, and inter-trial phase synchronization between face processing areas. Our results provide the first evidence that activation and connectivity dynamics in canonical brain regions associated with the processing of particular classes of visual and auditory stimuli can be reliably mapped using MEG during presentation of naturalistic stimuli. Given the strength of MEG for brain mapping in temporal and frequency domains, the use of naturalistic stimuli may open new techniques in analyzing brain dynamics during ecologically valid sensation and perception.

Sex differences in brain connectivity and male vulnerability in very preterm children.

Evidence indicates better cognitive and behavioral outcomes for females born very preterm (≤32 weeks gestation) compared to males, but the neurophysiology underlying this apparent resiliency of the female brain remains poorly understood. Here we test the hypothesis that very preterm males express more pronounced connectivity alterations as a reflection of higher male vulnerability. Resting state MEG recordings, neonatal and psychometric data were collected from 100 children at age 8 years: very preterm boys (n = 27), very preterm girls (n = 34), full-term boys (n = 15) and full-term girls (n = 24). Neuromagnetic source dynamics were reconstructed from 76 cortical brain regions. Functional connectivity was estimated using inter-regional phase-synchronization. We performed a series of multivariate analyses to test for differences across groups as well as to explore relationships between deviations in functional connectivity and psychometric scores and neonatal factors for very preterm children. Very preterm boys displayed significantly higher (p < .001) absolute deviation from average connectivity of same-sex full-term group, compared to very preterm girls versus full-term girls. In the connectivity comparison between very preterm and full-term groups separately for boys and girls, significant group differences (p < .05) were observed for boys, but not girls. Sex differences in connectivity (p < .01) were observed in very preterm children but not in full-term groups. Our findings indicate that very preterm boys have greater alterations in resting neurophysiological network communication than girls. Such uneven brain communication disruption in very preterm boys and girls suggests that stronger connectivity alterations might contribute to male vulnerability in long-term behavioral and cognitive outcome.

Idiosyncratic organization of cortical networks in autism spectrum disorder.

Neuroimaging studies of Autism Spectrum Disorder (ASD) have yielded inconsistent results indicating either increases or decreases in functional connectivity, or both. Recent findings suggest that these seemingly divergent results might be underpinned by greater inter-individual variability in brain network connectivity in ASD. We tested the hypothesis that the spatial patterns of intrinsic connectivity networks (ICNs) are more idiosyncratic in ASD, and demonstrated that this increased variability is associated with symptomatology. We estimated whole brain functional connectivity based on resting state functional magnetic resonance imaging (fMRI) data obtained from the Autism Brain Imaging Data Exchange I & II (ABIDE I & II) repository: 422 (69 females) participants with ASD and 424 (59 females) typically developing (TD) participants between 6 and 30 years of age. We clustered individuals' patterns of resting state functional connectivity into seven networks, each representing an ICN, and assessed the heterogeneity of each vertex on the cortical surface across individuals in terms of its incorporation into a particular ICN. We found that the incorporation of individual anatomical locations (vertices) to a common network was less consistent across individuals in ASD, indicating a more idiosyncratic organization of ICNs in the ASD brain. This spatial shifting effect was particularly pronounced in the Sensory-Motor Network (SMN) and the Default Mode Network (DMN). We also found that this idiosyncrasy in large-scale brain network organization was correlated with ASD symptomatology (ADOS). These results support the view that idiosyncratic functional connectivity is a hallmark of the ASD brain. We provide the first evidence that the anatomical organization of ICNs is idiosyncratic in ASD, as well as providing evidence that such abnormalities in brain network organization may contribute to the symptoms of ASD.

Extreme male developmental trajectories of homotopic brain connectivity in autism.

It has been proposed that autism spectrum disorder (ASD) may be characterized by an extreme male brain (EMB) pattern of brain development. Here, we performed the first investigation of how age-related changes in functional brain connectivity may be expressed differently in females and males with ASD. We analyzed resting-state functional magnetic resonance imaging data of 107 typically developing (TD) females, 114 TD males, 104 females, and 115 males with ASD (6-26 years) from the autism brain imaging data exchange repository. We explored how interhemispheric homotopic connectivity and its maturational curvatures change across groups. Differences between ASD and TD and between females and males with ASD were observed for the rate of changes in connectivity in the absence of overall differences in connectivity. The largest portion of variance in age-related changes in connectivity was described through similarities between TD males, ASD males, and ASD females, in contrast to TD females. We found that shape of developmental curvature is associated with symptomatology in both males and females with ASD. We demonstrated that females and males with ASD tended to follow the male pattern of developmental changes in interhemispheric connectivity, supporting the EMB theory of ASD.

Cognitive loading via mental arithmetic modulates effects of blink-related oscillations on precuneus and ventral attention network regions.

Blink-related oscillations (BROs) have been linked with environmental monitoring processes associated with blinking, with cortical activations in the bilateral precuneus. Although BROs have been described under resting and passive fixation conditions, little is known about their characteristics under cognitive loading. To address this, we investigated BRO effects during both mental arithmetic (MA) and passive fixation (PF) tasks using magnetoencephalography (n =20), while maintaining the same sensory environment in both tasks. Our results confirmed the presence of BRO effects in both MA and PF tasks, with similar characteristics including blink-related increase in global field power and blink-related activation of the bilateral precuneus. In addition, cognitive loading due to MA also modulated BRO effects by decreasing BRO-induced cortical activations in key brain regions including the bilateral anterior precuneus. Interestingly, blinking during MA-but not PF-activated regions of the ventral attention network (i.e., right supramarginal gyrus and inferior frontal gyrus), suggesting possible recruitment of these areas for blink processing under cognitive loading conditions. Time-frequency analysis revealed a consistent pattern of BRO-related effects in the precuneus in both tasks, but with task-related functional segregation within the anterior and posterior subregions. Based on these findings, we postulate a potential neurocognitive mechanism for blink processing in the precuneus. This study is the first investigation of BRO effects under cognitive loading, and our results provide compelling new evidence for the important cognitive implications of blink-related processing in the human brain.

EEG before and after total corpus callosotomy for pharmacoresistant infantile spasms: Fast oscillations and slow-wave connectivity in hypsarrhythmia.

OBJECTIVE: We analyzed the features of fast oscillations (FOs) and connectivity in hypsarrhythmia to identify biomarkers for predicting seizure outcomes after total corpus callosotomy (TCC) in children with pharmacoresistant infantile spasms (IS). We hypothesize that the power of FOs and connectivity of slow waves in hypsarrhythmia would indicate the prognosis of IS. METHOD: We retrospectively identified 42 children with pharmacoresistant IS who underwent TCC from 2009 to 2014 at Nagasaki Medical Center. We collected preoperative hypsarrhythmia for 200 seconds from each child. Children were categorized into three groups with interictal epileptic discharges on EEG at 6 months after TCC: group A, no epileptic discharge; group B, lateralized epileptic discharges; and group C; bilateral epileptic discharges. We analyzed spectral power and phase synchronization in preoperative hypsarrhythmia among the three groups. RESULTS: We found 10 children in group A, 10 children in group B, and 22 children in group C. All group A and 1 in group B achieved seizure freedom after TCC. Six (67%) of 9 group B children who underwent further surgeries achieved seizure freedom. Ten (45%) of group C children had seizure reduction >50% after TCC, and 13 (87%) of 15 children who underwent further surgeries had residual seizures. The clinical profiles of the three groups did not differ significantly. The power of FOs (≥45 Hz) in hypsarrhythmia was significantly stronger in group C at the midline and temporal regions than in groups B and A (P = .014). The connectivity of theta (4-9 Hz) and FOs (29-70 Hz) tended to increase in group C, compared with the increased connectivity of 1-2 Hz in group A (P = .08). SIGNIFICANCE: The increased power and connectivity of FOs in hypsarrhythmia may correlate with pharmacoresistant and surgically resistant seizures in IS. The existence and connectivity of FOs are associated with unilateral/bilateral cortical epileptogenicity in hypsarrhythmia. Prominent slow waves and connectivity without FOs might correlate with seizure freedom after TCC. Modulation of the callosal system with subcortical/cortical epileptic discharges might play a role in generating hypsarrhythmia and IS.

Atypical resting state neuromagnetic connectivity and spectral power in very preterm children.

BACKGROUND: Children born very preterm often display selective cognitive difficulties at school age even in the absence of major brain injury. Alterations in neurophysiological activity underpinning such difficulties, as well as their relation to specific aspects of adverse neonatal experience, remain poorly understood. In the present study, we examined interregional connectivity and spectral power in very preterm children at school age, and their relationship with clinical neonatal variables and long-term outcomes (IQ, executive functions, externalizing/internalizing behavior, visual-motor integration). METHODS: We collected resting state magnetoencephalographic (MEG) and psychometric data from a cohort at the age of 8 years followed prospectively since birth, which included three groups: Extremely Low Gestational Age (ELGA, 24-28 weeks GA n = 24, age 7.7 ± 0.38, 10 girls), Very Low Gestational Age (VLGA, 29-32 weeks GA n = 37, age 7.7 ± 0.39, 24 girls), and full-term children (38-41 weeks GA n = 39, age 7.9 ± 1.02, 24 girls). Interregional phase synchrony and spectral power were tested for group differences, and associations with neonatal and outcome variables were examined using mean-centered and behavioral Partial Least Squares (PLS) analyses, respectively. RESULTS: We found greater connectivity in the theta band in the ELGA group compared to VLGA and full-term groups, primarily involving frontal connections. Spectral power analysis demonstrated overall lower power in the ELGA and VLGA compared to full-term group. PLS indicated strong associations between neurophysiological connectivity at school age, adverse neonatal experience and cognitive performance, and behavior. Resting spectral power was associated only with behavioral scores. CONCLUSIONS: Our findings indicate significant atypicalities of neuromagnetic brain activity and connectivity in very preterm children at school age, with alterations in connectivity mainly observed only in the ELGA group. We demonstrate a significant relationship between connectivity, adverse neonatal experience, and long-term outcome, indicating that the disruption of developing neurophysiological networks may mediate relationships between neonatal events and cognitive and behavioral difficulties at school age.

Developmental changes in neuromagnetic rhythms and network synchrony in autism.

OBJECTIVE: There is gathering consensus that altered connectivity is a hallmark of the autistic brain. This includes atypical neural oscillations and their coordination across brain regions, which are understood to mediate information processing and integration. It remains unclear whether and how connectivity in various neurophysiological frequency ranges develops atypically in autism spectrum disorder (ASD). METHODS: To address this in a cross-sectional sample, we recorded resting-state magnetoencephalography from 134 children and adolescents with and without ASD, and calculated resting spectral power and inter-regional synchrony (functional connectivity). RESULTS: Although no overall group differences were observed, significant alterations in linear and nonlinear age-related changes in resting oscillatory power and network synchrony were found. These differences were frequency- and region-specific and implicated brain systems thought to play a prominent role in ASD, such as the frontal cortex and cerebellum. We also found correlations between Autism Diagnostic Observation Schedule scores and the degree to which connectivity in cerebellar networks is "idiosyncratic" in an individual with autism. INTERPRETATION: We provide the first evidence that it is the curvatures of maturational changes in neurophysiological oscillations and synchrony, rather than disturbances in a particular direction, that characterize the brain function in individuals with ASD. Moreover, the patterns of idiosyncratic distortions of network synchrony relative to the group curve are associated with behavioral symptoms of ASD. Ann Neurol 2017;81:199-211.

Post-Traumatic Stress Constrains the Dynamic Repertoire of Neural Activity.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising from exposure to a traumatic event. Although primarily defined in terms of behavioral symptoms, the global neurophysiological effects of traumatic stress are increasingly recognized as a critical facet of the human PTSD phenotype. Here we use magnetoencephalographic recordings to investigate two aspects of information processing: inter-regional communication (measured by functional connectivity) and the dynamic range of neural activity (measured in terms of local signal variability). We find that both measures differentiate soldiers diagnosed with PTSD from soldiers without PTSD, from healthy civilians, and from civilians with mild traumatic brain injury, which is commonly comorbid with PTSD. Specifically, soldiers with PTSD display inter-regional hypersynchrony at high frequencies (80-150 Hz), as well as a concomitant decrease in signal variability. The two patterns are spatially correlated and most pronounced in a left temporal subnetwork, including the hippocampus and amygdala. We hypothesize that the observed hypersynchrony may effectively constrain the expression of local dynamics, resulting in less variable activity and a reduced dynamic repertoire. Thus, the re-experiencing phenomena and affective sequelae in combat-related PTSD may result from functional networks becoming "stuck" in configurations reflecting memories, emotions, and thoughts originating from the traumatizing experience. SIGNIFICANCE STATEMENT: The present study investigates the effects of post-traumatic stress disorder (PTSD) in combat-exposed soldiers. We find that soldiers with PTSD exhibit hypersynchrony in a circuit of temporal lobe areas associated with learning and memory function. This rigid functional architecture is associated with a decrease in signal variability in the same areas, suggesting that the observed hypersynchrony may constrain the expression of local dynamics, resulting in a reduced dynamic range. Our findings suggest that the re-experiencing of traumatic events in PTSD may result from functional networks becoming locked in configurations that reflect memories, emotions, and thoughts associated with the traumatic experience.

Detecting Mild Traumatic Brain Injury Using Resting State Magnetoencephalographic Connectivity.

Accurate means to detect mild traumatic brain injury (mTBI) using objective and quantitative measures remain elusive. Conventional imaging typically detects no abnormalities despite post-concussive symptoms. In the present study, we recorded resting state magnetoencephalograms (MEG) from adults with mTBI and controls. Atlas-guided reconstruction of resting state activity was performed for 90 cortical and subcortical regions, and calculation of inter-regional oscillatory phase synchrony at various frequencies was performed. We demonstrate that mTBI is associated with reduced network connectivity in the delta and gamma frequency range (>30 Hz), together with increased connectivity in the slower alpha band (8-12 Hz). A similar temporal pattern was associated with correlations between network connectivity and the length of time between the injury and the MEG scan. Using such resting state MEG network synchrony we were able to detect mTBI with 88% accuracy. Classification confidence was also correlated with clinical symptom severity scores. These results provide the first evidence that imaging of MEG network connectivity, in combination with machine learning, has the potential to accurately detect and determine the severity of mTBI.

Development of Network Synchronization Predicts Language Abilities.

Synchronization of oscillations among brain areas is understood to mediate network communication supporting cognition, perception, and language. How task-dependent synchronization during word production develops throughout childhood and adolescence, as well as how such network coherence is related to the development of language abilities, remains poorly understood. To address this, we recorded magnetoencephalography while 73 participants aged 4-18 years performed a verb generation task. Atlas-guided source reconstruction was performed, and phase synchronization among regions was calculated. Task-dependent increases in synchronization were observed in the theta, alpha, and beta frequency ranges, and network synchronization differences were observed between age groups. Task-dependent synchronization was strongest in the theta band, as were differences between age groups. Network topologies were calculated for brain regions associated with verb generation and were significantly associated with both age and language abilities. These findings establish the maturational trajectory of network synchronization underlying expressive language abilities throughout childhood and adolescence and provide the first evidence for an association between large-scale neurophysiological network synchronization and individual differences in the development of language abilities.

Top-down alpha oscillatory network interactions during visuospatial attention orienting.

Neuroimaging and lesion studies indicate that visual attention is controlled by a distributed network of brain areas. The covert control of visuospatial attention has also been associated with retinotopic modulation of alpha-band oscillations within early visual cortex, which are thought to underlie inhibition of ignored areas of visual space. The relation between distributed networks mediating attention control and more focal oscillatory mechanisms, however, remains unclear. The present study evaluated the hypothesis that alpha-band, directed, network interactions within the attention control network are systematically modulated by the locus of visuospatial attention. We localized brain areas involved in visuospatial attention orienting using magnetoencephalographic (MEG) imaging and investigated alpha-band Granger-causal interactions among activated regions using narrow-band transfer entropy. The deployment of attention to one side of visual space was indexed by lateralization of alpha power changes between about 400ms and 700ms post-cue onset. The changes in alpha power were associated, in the same time period, with lateralization of anterior-to-posterior information flow in the alpha-band from various brain areas involved in attention control, including the anterior cingulate cortex, left middle and inferior frontal gyri, left superior temporal gyrus, and right insula, and inferior parietal lobule, to early visual areas. We interpreted these results to indicate that distributed network interactions mediated by alpha oscillations exert top-down influences on early visual cortex to modulate inhibition of processing for ignored areas of visual space.

Desynchronization of fronto-temporal networks during working memory processing in autism.

BACKGROUND: Mounting evidence suggests that autism is a network disorder, characterized by atypical brain connectivity, especially in the context of high level cognitive processes such as working memory (WM). Accordingly, atypical WM processes have been related to the social and cognitive deficits observed in children with autism spectrum disorder (ASD). METHODS: We used magnetoencephalography (MEG) to investigate connectivity differences during a high memory load (2-back) WM task between 17 children with ASD and 20 age-, sex-, and IQ-matched controls. RESULTS: We identified reduced inter-regional alpha-band (9-15 Hz) phase synchronization in children with ASD during the WM task. Reduced WM-related brain synchronization encompassed fronto-temporal networks (ps < 0.04 corrected) previously associated with challenging high-level conditions (i.e. the left insula and the anterior cingulate cortex (ACC)) and memory encoding and/or recognition (i.e. the right middle temporal gyrus and the right fusiform gyrus). Additionally, we found that reduced connectivity processes related to the right fusiform were correlated with the severity of symptoms in children with ASD, suggesting that such atypicalities could be directly related to the behavioural deficits observed. DISCUSSION: This study provides new evidence of atypical long-range synchronization in children with ASD in fronto-temporal areas that crucially contribute to challenging WM tasks, but also emotion regulation and social cognition processes. Thus, these results support the network disorder hypothesis of ASD and argue for a specific pathophysiological contribution of brain processes related to working memory and executive functions on the symptomatology of autism.

Altered resting-state functional connectivity in cognitively preserved pediatric-onset MS patients and relationship to structural damage and cognitive performance.

OBJECTIVE: To evaluate resting-state functional connectivity (FC) and relationship to brain volumes and cognition in a sample of cognitively preserved pediatric-onset multiple sclerosis (MS) patients. METHODS: Sixteen cognitively intact pediatric-onset MS patients and 15 healthy age- and sex-matched controls underwent cognitive testing and 3T anatomical and functional MRI. Resting-state FC patterns were examined using region-of-interest-based timeseries correlations. RESULTS: Compared to controls, pediatric-onset MS patients demonstrated higher FC of the precuneus, particularly with the anterior cingulate cortex (z=4.21, p<.001), frontal medial cortex (z=3.48, p<.001), and cerebellum (z=3.72, p<.001). Greater T2 lesion volume and lower normalized thalamic volume were associated with reduced FC of the thalamus, especially for FC with the right superior occipital region (t=-2.87, p=.0123 and t=2.27, p=.04 respectively). FC of the left frontal medial cortex was negatively correlated with composite cognitive z-score in the pediatric-onset MS group (p<.05). CONCLUSIONS: Greater resting-state FC between posterior and anterior brain regions is present in pediatric-onset MS. With greater disease-related structural pathology, there is a disruption of thalamo-cortical FC. In the absence of actual cognitive impairment, heightened FC of the frontal medial cortex was associated with lower cognitive performance, suggesting that greater functional resources are recruited during resting-state in patients with reduced cognitive efficiency.

Coordinated Information Generation and Mental Flexibility: Large-Scale Network Disruption in Children with Autism.

Autism spectrum disorder (ASD) includes deficits in social cognition, communication, and executive function. Recent neuroimaging studies suggest that ASD disrupts the structural and functional organization of brain networks and, presumably, how they generate information. Here, we relate deficits in an aspect of cognitive control to network-level disturbances in information processing. We recorded magnetoencephalography while children with ASD and typically developing controls performed a set-shifting task designed to test mental flexibility. We used multiscale entropy (MSE) to estimate the rate at which information was generated in a set of sources distributed across the brain. Multivariate partial least-squares analysis revealed 2 distributed networks, operating at fast and slow time scales, that respond completely differently to set shifting in ASD compared with control children, indicating disrupted temporal organization within these networks. Moreover, when typically developing children engaged these networks, they achieved faster reaction times. When children with ASD engaged these networks, there was no improvement in performance, suggesting that the networks were ineffective in children with ASD. Our data demonstrate that the coordination and temporal organization of large-scale neural assemblies during the performance of cognitive control tasks is disrupted in children with ASD, contributing to executive function deficits in this group.

Minimum variance beamformer weights revisited.

Adaptive minimum variance beamformers are widely used analysis tools in MEG and EEG. When the target brain activity presents in the form of spatially localized responses, the procedure usually involves two steps. First, positions and orientations of the sources of interest are determined. Second, the filter weights are calculated and source time courses reconstructed. This last step is the object of the current study. Despite different approaches utilized at the source localization stage, basic expressions for the weights have the same form, dictated by the minimum variance condition. These classic expressions involve covariance matrix of the measured field, which includes contributions from both the sources of interest and the noise background. We show analytically that the same weights can alternatively be obtained, if the full field covariance is replaced with that of the noise, provided the beamformer points to the true sources precisely. In practice, however, a certain mismatch is always inevitable. We show that such mismatch results in partial suppression of the true sources if the traditional weights are used. To avoid this effect, the "alternative" weights based on properly estimated noise covariance should be applied at the second, source time course reconstruction step. We demonstrate mathematically and using simulated and real data that in many situations the alternative weights provide significantly better time course reconstruction quality than the traditional ones. In particular, they a) improve source-level SNR and yield more accurately reconstructed waveforms; b) provide more accurate estimates of inter-source correlations; and c) reduce the adverse influence of the source correlations on the performance of single-source beamformers, which are used most often. Importantly, the alternative weights come at no additional computational cost, as the structure of the expressions remains the same.

Altered Network Oscillations and Functional Connectivity Dynamics in Children Born Very Preterm.

Structural brain connections develop atypically in very preterm children, and altered functional connectivity is also evident in fMRI studies. Such alterations in brain network connectivity are associated with cognitive difficulties in this population. Little is known, however, about electrophysiological interactions among specific brain networks in children born very preterm. In the present study, we recorded magnetoencephalography while very preterm children and full-term controls performed a visual short-term memory task. Regions expressing task-dependent activity changes were identified using beamformer analysis, and inter-regional phase synchrony was calculated. Very preterm children expressed altered regional recruitment in distributed networks of brain areas, across standard physiological frequency ranges including the theta, alpha, beta and gamma bands. Reduced oscillatory synchrony was observed among task-activated brain regions in very preterm children, particularly for connections involving areas critical for executive abilities, including middle frontal gyrus. These findings suggest that inability to recruit neurophysiological activity and interactions in distributed networks including frontal regions may contribute to difficulties in cognitive development in children born very preterm.