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J. Christopher Edgar

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11 papers

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YNIMG Journal 2023 Journal Article

Maturation of auditory cortex neural responses during infancy and toddlerhood

Yuhan Chen
Heather L. Green
Mary E. Putt
Olivia Allison
Emily S. Kuschner
Mina Kim
Lisa Blaskey
Kylie Mol

The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by ∼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left–right hemisphere P2m maturation is associated with language performance.

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YNIMG Journal 2019 Journal Article

Magnetoencephalography and the infant brain

Yu-Han Chen
Joni Saby
Emily Kuschner
William Gaetz
J. Christopher Edgar
Timothy P.L. Roberts

Magnetoencephalography (MEG) is a non-invasive neuroimaging technique that provides whole-head measures of neural activity with millisecond temporal resolution. Over the last three decades, MEG has been used for assessing brain activity, most commonly in adults. MEG has been used less often to examine neural function during early development, in large part due to the fact that infant whole-head MEG systems have only recently been developed. In this review, an overview of infant MEG studies is provided, focusing on the period from birth to three years. The advantages of MEG for measuring neural activity in infants are highlighted (See Box 1), including the ability to assess activity in brain (source) space rather than sensor space, thus allowing direct assessment of neural generator activity. Recent advances in MEG hardware and source analysis are also discussed. As the review indicates, efforts in this area demonstrate that MEG is a promising technology for studying the infant brain. As a noninvasive technology, with emerging hardware providing the necessary sensitivity, an expected deliverable is the capability for longitudinal infant MEG studies evaluating the developmental trajectory (maturation) of neural activity. It is expected that departures from neuro-typical trajectories will offer early detection and prognosis insights in infants and toddlers at-risk for neurodevelopmental disorders, thus paving the way for early targeted interventions.

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YNICL Journal 2016 Journal Article

Maturation of auditory neural processes in autism spectrum disorder — A longitudinal MEG study

Russell G. Port
J. Christopher Edgar
Matthew Ku
Luke Bloy
Rebecca Murray
Lisa Blaskey
Susan E. Levy
Timothy P.L. Roberts

BACKGROUND: Individuals with autism spectrum disorder (ASD) show atypical brain activity, perhaps due to delayed maturation. Previous studies examining the maturation of auditory electrophysiological activity have been limited due to their use of cross-sectional designs. The present study took a first step in examining magnetoencephalography (MEG) evidence of abnormal auditory response maturation in ASD via the use of a longitudinal design. METHODS: Initially recruited for a previous study, 27 children with ASD and nine typically developing (TD) children, aged 6- to 11-years-old, were re-recruited two to five years later. At both timepoints, MEG data were obtained while participants passively listened to sinusoidal pure-tones. Bilateral primary/secondary auditory cortex time domain (100 ms evoked response latency (M100)) and spectrotemporal measures (gamma-band power and inter-trial coherence (ITC)) were examined. MEG measures were also qualitatively examined for five children who exhibited "optimal outcome", participants who were initially on spectrum, but no longer met diagnostic criteria at follow-up. RESULTS: M100 latencies were delayed in ASD versus TD at the initial exam (~ 19 ms) and at follow-up (~ 18 ms). At both exams, M100 latencies were associated with clinical ASD severity. In addition, gamma-band evoked power and ITC were reduced in ASD versus TD. M100 latency and gamma-band maturation rates did not differ between ASD and TD. Of note, the cohort of five children that demonstrated "optimal outcome" additionally exhibited M100 latency and gamma-band activity mean values in-between TD and ASD at both timepoints. Though justifying only qualitative interpretation, these "optimal outcome" related data are presented here to motivate future studies. CONCLUSIONS: Children with ASD showed perturbed auditory cortex neural activity, as evidenced by M100 latency delays as well as reduced transient gamma-band activity. Despite evidence for maturation of these responses in ASD, the neural abnormalities in ASD persisted across time. Of note, data from the five children whom demonstrated "optimal outcome" qualitatively suggest that such clinical improvements may be associated with auditory brain responses intermediate between TD and ASD. These "optimal outcome" related results are not statistically significant though, likely due to the low sample size of this cohort, and to be expected as a result of the relatively low proportion of "optimal outcome" in the ASD population. Thus, further investigations with larger cohorts are needed to determine if the above auditory response phenotypes have prognostic utility, predictive of clinical outcome.

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YNICL Journal 2014 Journal Article

Cortical thickness as a contributor to abnormal oscillations in schizophrenia?

J. Christopher Edgar
Yu-Han Chen
Matthew Lanza
Breannan Howell
Vivian Y. Chow
Kory Heiken
Song Liu
Cassandra Wootton

INTRODUCTION: Although brain rhythms depend on brain structure (e.g., gray and white matter), to our knowledge associations between brain oscillations and structure have not been investigated in healthy controls (HC) or in individuals with schizophrenia (SZ). Observing function-structure relationships, for example establishing an association between brain oscillations (defined in terms of amplitude or phase) and cortical gray matter, might inform models on the origins of psychosis. Given evidence of functional and structural abnormalities in primary/secondary auditory regions in SZ, the present study examined how superior temporal gyrus (STG) structure relates to auditory STG low-frequency and 40 Hz steady-state activity. Given changes in brain activity as a function of age, age-related associations in STG oscillatory activity were also examined. METHODS: Thirty-nine individuals with SZ and 29 HC were recruited. 40 Hz amplitude-modulated tones of 1 s duration were presented. MEG and T1-weighted sMRI data were obtained. Using the sources localizing 40 Hz evoked steady-state activity (300 to 950 ms), left and right STG total power and inter-trial coherence were computed. Time-frequency group differences and associations with STG structure and age were also examined. RESULTS: Decreased total power and inter-trial coherence in SZ were observed in the left STG for initial post-stimulus low-frequency activity (~ 50 to 200 ms, ~ 4 to 16 Hz) as well as 40 Hz steady-state activity (~ 400 to 1000 ms). Left STG 40 Hz total power and inter-trial coherence were positively associated with left STG cortical thickness in HC, not in SZ. Left STG post-stimulus low-frequency and 40 Hz total power were positively associated with age, again only in controls. DISCUSSION: Left STG low-frequency and steady-state gamma abnormalities distinguish SZ and HC. Disease-associated damage to STG gray matter in schizophrenia may disrupt the age-related left STG gamma-band function-structure relationships observed in controls.

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YNIMG Journal 2014 Journal Article

MEG source imaging method using fast L1 minimum-norm and its applications to signals with brain noise and human resting-state source amplitude images

Ming-Xiong Huang
Charles W. Huang
Ashley Robb
Annemarie Angeles
Sharon L. Nichols
Dewleen G. Baker
Tao Song
Deborah L. Harrington

The present study developed a fast MEG source imaging technique based on Fast Vector-based Spatio-Temporal Analysis using a L1-minimum-norm (Fast-VESTAL) and then used the method to obtain the source amplitude images of resting-state magnetoencephalography (MEG) signals for different frequency bands. The Fast-VESTAL technique consists of two steps. First, L1-minimum-norm MEG source images were obtained for the dominant spatial modes of sensor-waveform covariance matrix. Next, accurate source time-courses with millisecond temporal resolution were obtained using an inverse operator constructed from the spatial source images of Step 1. Using simulations, Fast-VESTAL's performance was assessed for its 1) ability to localize multiple correlated sources; 2) ability to faithfully recover source time-courses; 3) robustness to different SNR conditions including SNR with negative dB levels; 4) capability to handle correlated brain noise; and 5) statistical maps of MEG source images. An objective pre-whitening method was also developed and integrated with Fast-VESTAL to remove correlated brain noise. Fast-VESTAL's performance was then examined in the analysis of human median-nerve MEG responses. The results demonstrated that this method easily distinguished sources in the entire somatosensory network. Next, Fast-VESTAL was applied to obtain the first whole-head MEG source-amplitude images from resting-state signals in 41 healthy control subjects, for all standard frequency bands. Comparisons between resting-state MEG sources images and known neurophysiology were provided. Additionally, in simulations and cases with MEG human responses, the results obtained from using conventional beamformer technique were compared with those from Fast-VESTAL, which highlighted the beamformer's problems of signal leaking and distorted source time-courses.

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YNICL Journal 2014 Journal Article

Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

Ming-Xiong Huang
Sharon Nichols
Dewleen G. Baker
Ashley Robb
Annemarie Angeles
Kate A. Yurgil
Angela Drake
Michael Levy

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1-4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1-4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI.

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YNICL Journal 2013 Journal Article

Frontal and superior temporal auditory processing abnormalities in schizophrenia

Yu-Han Chen
J. Christopher Edgar
Mingxiong Huang
Michael A. Hunter
Emerson Epstein
Breannan Howell
Brett Y. Lu
Juan Bustillo

BACKGROUND: Although magnetoencephalography (MEG) studies show superior temporal gyrus (STG) auditory processing abnormalities in schizophrenia at 50 and 100 ms, EEG and corticography studies suggest involvement of additional brain areas (e.g., frontal areas) during this interval. Study goals were to identify 30 to 130 ms auditory encoding processes in schizophrenia (SZ) and healthy controls (HC) and group differences throughout the cortex. METHODS: The standard paired-click task was administered to 19 SZ and 21 HC subjects during MEG recording. Vector-based Spatial-temporal Analysis using L1-minimum-norm (VESTAL) provided 4D maps of activity from 30 to 130 ms. Within-group t-tests compared post-stimulus 50 ms and 100 ms activity to baseline. Between-group t-tests examined 50 and 100 ms group differences. RESULTS: Bilateral 50 and 100 ms STG activity was observed in both groups. HC had stronger bilateral 50 and 100 ms STG activity than SZ. In addition to the STG group difference, non-STG activity was also observed in both groups. For example, whereas HC had stronger left and right inferior frontal gyrus activity than SZ, SZ had stronger right superior frontal gyrus and left supramarginal gyrus activity than HC. CONCLUSIONS: Less STG activity was observed in SZ than HC, indicating encoding problems in SZ. Yet auditory encoding abnormalities are not specific to STG, as group differences were observed in frontal and SMG areas. Thus, present findings indicate that individuals with SZ show abnormalities in multiple nodes of a concurrently activated auditory network.

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YNIMG Journal 2010 Journal Article

The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control

Rebecca Levin Silton
Wendy Heller
David N. Towers
Anna S. Engels
Jeffrey M. Spielberg
J. Christopher Edgar
Sarah M. Sass
Jennifer L. Stewart

A network of brain regions has been implicated in top-down attentional control, including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC). The present experiment evaluated predictions of the cascade-of-control model (Banich, 2009), which predicts that during attentionally-demanding tasks, LDLPFC imposes a top-down attentional set which precedes late-stage selection performed by dACC. Furthermore, the cascade-of-control model argues that dACC must increase its activity to compensate when top-down control by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense-array ERP data collected from the same 80 participants in separate sessions. fMRI results guided ERP source modeling to characterize the time course of activity in LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity distinguished congruent and incongruent conditions on the Stroop task. Furthermore, when LDLPFC activity was low, the level of dACC activity was related to performance outcome. These results demonstrate that dACC responds to attentional demand in a flexible manner that is dependent on the level of LDLPFC activity earlier in a trial. Overall, results were consistent with the temporal course of regional brain function proposed by the cascade-of-control model.

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YNIMG Journal 2009 Journal Article

The temporal dynamics of insula activity to disgust and happy facial expressions: A magnetoencephalography study

Yu-Han Chen
Jürgen Dammers
Frank Boers
Susanne Leiberg
J. Christopher Edgar
Timothy P.L. Roberts
Klaus Mathiak

The insula has consistently been shown to be involved in processing stimuli that evoke the emotional response of disgust. Recently, its specificity for processing disgust has been challenged and a broader role of the insula in the representation of interoceptive information has been suggested. Studying the temporal dynamics of insula activation during emotional processing can contribute valuable information pertaining to this issue. Few studies have addressed the insula's putative specificity to disgust and the dynamics of its underlying neural processes. In the present study, neuromagnetic responses of 13 subjects performing an emotional continuous performance task (CPT) to faces with disgust, happy, and neutral expressions were obtained. Magnetic field tomography extracted the time course of bilateral insula activities. Right insula activation was stronger to disgust and happy than neutral facial expressions at about 200 ms after stimulus onset. Later only at about 350 ms after stimulus onset the right insula was activated stronger to disgust than happy facial expressions. Thus, the early right insula response reflects activation to emotionally arousing stimuli regardless of valence, and the later right insula response differentiates disgust from happy facial expressions. Behavioral performance but not the insula activity differed between 100 ms and 1000 ms presentation conditions. Present findings support the notion that the insula is involved in the representation of interoceptive information.

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YNIMG Journal 2008 Journal Article

Time–frequency discriminant analysis of MEG signals

Moon-Ho Ringo Ho
Hernando Ombao
J. Christopher Edgar
Jose M. Cañive
Gregory A. Miller

This paper introduces a novel statistical method that can identify relevant time–frequency features in brain signals to distinguish between groups. The feature of interest is the spectrum which characterizes the distribution of a given signal's variance (or power) across frequency oscillations. Brain signals are generally nonstationary in that the distribution of the signals' power across frequency changes over time. The classical Fourier analysis is not formally suitable for time series signals with time-varying spectra. This paper utilizes the SLEX (Smooth Localized Complex EXponentials) basis function to capture the transient features of brain signals. The SLEX basis consists of a set of localized orthogonal Fourier-like waveforms with a built-in mechanism for representing localized spectral features. The best basis is first chosen that maximizes group dissimilarity in the time-varying spectra. However, not all spectral features extracted from the best basis may be useful for discrimination and classification purpose. A thresholding scheme is further developed to remove irrelevant features from the best basis to improve accuracy for classification. In simulations the proposed SLEX-thresholding discriminant method was able to consistently identify the most discriminant time–frequency features and was able to correctly classify signals at a high rate. The method was then applied to magnetoencephalographic data from a standard paired-click paradigm. Discrimination between individuals with schizophrenia and a healthy comparison group confirmed the utility of the method.

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YNIMG Journal 2005 Journal Article

A parietal–frontal network studied by somatosensory oddball MEG responses, and its cross-modal consistency

Ming-Xiong Huang
Roland R. Lee
Gregory A. Miller
Robert J. Thoma
Faith M. Hanlon
Kim M. Paulson
Kimberly Martin
Deborah L. Harrington

Previous studies using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) of the brain have found that a distributed parietal–frontal neuronal network is activated in normals during both auditory and visual oddball tasks. The common cortical regions in this network are inferior parietal lobule (IPL)/supramarginal gyrus (SMG), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). It is not clear whether the same network is activated by oddball tasks during somatosensory stimulation. The present study addressed this question by testing healthy adults as they performed a novel median-nerve oddball paradigm while undergoing magnetoencephalography (MEG). An automated multiple dipole analysis technique, the Multi-Start Spatio-Temporal (MSST) algorithm, localized multiple neuronal generators, and identified their time-courses. IPL/SMG, ACC, and DLPFC were reliably localized in the MEG median-nerve oddball responses, with IPL/SMG activation significantly preceding ACC and DLPFC activation. Thus, the same parietal–frontal neuronal network that shows activation during auditory and visual oddball tests is activated in a median-nerve oddball paradigm. Regions uniquely related to somatosensory oddball responses (e. g. , primary and secondary somatosensory, dorsal premotor, primary motor, and supplementary motor areas) were also localized. Since the parietal–frontal network supports attentional allocation during performance of the task, this study may provide a novel method, as well as normative baseline data, for examining attention-related deficits in the somatosensory system of patients with neurological or psychiatric disorders.

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