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Tony W. Wilson

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54 papers

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YNICL Journal 2025 Journal Article

Adults with down syndrome exhibit altered somatosensory cortical inhibition

Jiraros Meejang
Morgan T. Busboom
Sarah E. Baker
Yasra Arif
Olyvia Kastner
Tony W. Wilson
Max J. Kurz

Down syndrome (DS) is a developmental genetic disorder that is associated with an accelerated aging profile and high probability of early incidence Alzheimer's disease like symptoms. It is well established that there are morphological differences in the brains of adults with DS, but the net impact of the genetic disruption on cortical function remains poorly understood. To address this knowledge gap, we used magnetoencephalographic (MEG) brain imaging to assess the somatosensory cortical activity elicited by a paired-pulse electrical stimulation of the right median nerve of adults with DS (N = 19; Age = 28.05 ± 7.9 yrs.) and neurotypical controls (NT) (N = 21; Age = 30.81 ± 8.2 yrs.). sLORETA was used to image neural responses to the somatosensory stimulation, which were centered on the left central sulcus posterior to the motor hand knob region. Our results revealed that adults with DS had weaker somatosensory cortical activity after the second electrical stimulation in the paired-pulse paradigm (DS = 594.1 ± 194.22 AU; NT = 750.48 ± 256.6; P = 0.038) and a pronounced hyper-gating response (DS = 78.9 ± 6.8 %; NT = 87.4 ± 9.9 %; P = 0.003). Together, these results suggest that adults with DS may have an imbalance in the excitatory/inhibitory ratio. These novel data enhance our understanding of the neurophysiological aberrations associated with DS and may hold promise in understanding the origins of Alzheimer's disease like symptoms in this population. Future studies should examine whether these inhibitory alterations are restricted to the sensorimotor cortices or extend across the brain.

YNIMG Journal 2025 Journal Article

Blending into naturalistic scenes: Cortical regions serving visual search are more strongly activated in congruent contexts

Ilenia Salsano
Nathan M. Petro
Giorgia Picci
Aubrie J. Petts
Ryan J. Glesinger
Lucy K. Horne
Anna T. Coutant
Grace C. Ende

Visual attention allows us to navigate complex environments by selecting behaviorally relevant stimuli while suppressing distractors, through a dynamic balance between top-down and bottom-up mechanisms. Extensive attention research has examined the object-context relationship. Some studies have shown that incongruent object-context associations are processed faster, likely due to semantic mismatch-related attentional capture, while others have suggested that schema-driven facilitation may enhance object recognition when the object and context are congruent. Beyond the conflicting findings, translation of this work to real world contexts has been difficult due to the use of non-ecological scenes and stimuli when investigating the object-context congruency relationship. To address this, we employed a goal-directed visual search task and naturalistic indoor scenes during functional MRI (fMRI). Seventy-one healthy adults searched for a target object, either congruent or incongruent within the scene context, following a word cue. We collected accuracy and response time behavioral data, and all fMRI data were processed following standard pipelines, with statistical maps thresholded at p < .05 following multiple comparisons correction. Our results indicated faster response times for incongruent relative to congruent trials, likely reflecting the so-called pop-out effect of schema violations in the incongruent condition. Our neural results indicated that congruent elicited greater activation than incongruent trials in the dorsal frontoparietal attention network and the precuneus, likely reflecting sustained top-down attentional control to locate the targets that blend more seamlessly into the context. These findings highlight the flexible interplay between top-down and bottom-up mechanisms in real-world visual search, emphasizing the dominance of schema-guided top-down processes in congruent contexts and rapid attention capture in incongruent contexts.

YNIMG Journal 2025 Journal Article

Chronic radon exposure is associated with developmental alterations to neural and behavioral indices of cognitive control

Haley R. Pulliam
Christine M. Embury
Maggie P. Rempe
Hannah J. Okelberry
Danielle L. Rice
Anna T. Coutant
Ryan Glesinger
Tony W. Wilson

Radon is a prevalent, naturally occurring gas which contributes to radiation within the environment and is the second-leading cause of lung cancer worldwide. Although many environmental toxins have been linked to maladaptive neurodevelopmental outcomes in children and adolescents, radon has seldom been examined for its effects on the developing brain. This study aimed to investigate the effects of chronic home radon exposure on top-down neural processes of cognitive control in youths. Fifty-nine participants (aged 6-14 years) completed a Simon interference task during magnetoencephalography (MEG), and radon levels were measured in their homes. MEG data were transformed into time-frequency space and significant oscillatory responses relative to baseline were imaged condition-wise and then subtracted to isolate the Simon interference effect (i.e., Simon-control). Whole-brain linear regressions indicated that children with greater radon exposure exhibited aberrant oscillatory activity in widespread networks related to attentional control. We also found that radon exposure moderated the developmental trajectory of theta and gamma oscillations underlying selective attention in frontoparietal cortices and other regions. Further, mediation analyses showed that the neural interference effects within cerebellar and extended motor cortices mediated the relationship between radon exposure and behavioral outcomes. Additionally, we found the mediating effects of neural interference within the left superior frontal gyrus and precuneus on the relationship between age and task accuracy were dependent on radon exposure. These data are among the first to demonstrate radon-related disruptions to the normative development of the neural substrates supporting cognitive control processes. Further, these disruptions have direct implications on observable behavior.

YNIMG Journal 2025 Journal Article

Developmental trajectory of neural activity underlying motor control differs by sequence complexity and motor stage

Thomas W. Ward
Jackson Derby
Jake J. Son
Peihan J. Huang
Danielle L. Rice
Grace C. Ende
Anna T. Coutant
Erica L. Steiner

Primary motor areas in the brain mature relatively early in development, yet the control of complex movements improves through early adulthood. Neural oscillations in higher-order regions are refined in adolescence and contribute to executive processes important for complex motor control, but the neural dynamics among these regions and primary motor cortices remain poorly understood in youth. We recorded magnetoencephalography during a motor sequencing task in 68 healthy youth from ten to 17 years of age. Significant changes in oscillatory activity relative to baseline were identified at the sensor level and source reconstructed with a beamformer. Whole-brain maps of beta (18-24 Hz) and gamma (74-84 Hz) oscillatory activity were subjected to voxel-wise repeated-measures ANCOVAs to identify brain areas in which the developmental trajectory of oscillatory power differed by sequence complexity (simple/complex) or motor stage (planning/execution). Beta activity in bilateral prefrontal cortices was weaker with age during the planning of complex movements. Across simple and complex conditions, older youth tended to have stronger beta in posterior areas during planning. Finally, gamma activity across conditions was stronger with age in occipital and weaker in temporal cortices. These results suggest that the functional refinement of association cortices may drive improvements in motor control by enabling more efficient attentional and inhibitory control during formulation of the motor plan.

YNIMG Journal 2025 Journal Article

Dual-montage high-definition transcranial direct current stimulation (HD-tDCS) modulates the neural dynamics serving working memory

Peihan J. Huang
Yasra Arif
Jake J. Son
Jason A. John
Maggie P. Rempe
Kellen M. McDonald
Lauren K. Webert
Grant M. Garrison

Verbal working memory (WM) is a critical cognitive construct supporting a broad range of daily functions. Neuroimaging studies have highlighted the involvement of prefrontal-occipital circuitry in WM, but specific regional contributions and possible laterality effects remain unclear. Transcranial direct current stimulation (tDCS) is an emerging technique that noninvasively modulates the excitability of neural populations, with studies showing stimulation effects on both local and distant but connected cortices. Herein, we utilized a novel dual-montage, high-definition tDCS (HD-tDCS) approach to evaluate the impact on functional brain dynamics and WM performance. Forty-five healthy adults underwent dual-montage HD-tDCS with 2.0 mA anodal stimulation applied over the midline occipital cortices and either the left or right dorsolateral prefrontal cortices (DLPFC) concurrently, or sham to both sites during three sessions. Following stimulation, participants completed a verbal WM task during magnetoencephalography (MEG). Whole-brain, voxel-wise maps were subjected to 1 × 3 repeated measure ANOVAs to probe stimulation effects. We found that left DLPFC-occipital stimulation induced stronger theta responses in the left superior temporal cortices, left supramarginal gyrus, left angular gyrus, and the right parietal cortices, while attenuated alpha responses were observed in the bilateral parietal cortices following right compared to left DLPFC-occipital stimulation and sham. Additionally, both active stimulation montages modulated oscillatory responses in the bilateral inferior frontal, the right lateral occipital cortices and other critical WM network regions during the encoding and maintenance phases. In conclusion, our results show that dual-montage anodal HD-tDCS differentially modulates spectrally and temporally distinct oscillatory responses, suggesting clear functional dissociations between left and right prefrontal regions during WM processing. These findings highlight the potential of tDCS in advancing our understanding of the unique contribution of each region in the network, which long-term could inform clinical interventions.

YNIMG Journal 2025 Journal Article

Neurochemical changes in GABA+, Glx, and the excitatory/inhibitory ratio in the calcarine cortex with healthy aging

Ilenia Salsano
Ryan J. Glesinger
Jason A. John
Grant M. Garrison
Lucy K. Horne
Grace C. Ende
Danielle L. Rice
Anna T. Coutant

Aging has been associated with widespread alterations in neural structure and function, but the underlying biochemical changes remain less understood despite recent neurophysiological work suggesting age-related alterations in the excitatory/inhibitory (E/I) balance. In the current study, we used ¹H-MRS to quantify levels of excitatory (Glx: glutamate + glutamine) and inhibitory (GABA+: GABA + macromolecules) neurotransmitters in the calcarine cortex in 187 healthy adults (19-79 years-old). These neurotransmitter estimates were used to compute the E/I ratio, and all three parameters were examined for aging effects. Given our large sample, we also conducted supplementary analyses to estimate the concentration of secondary metabolites commonly implicated in aging, including total creatine (tCr), total N-acetyl aspartate (tNAA), total choline (tCho), and myo-inositol (mI). Following best practices, metabolite concentrations were estimated relative to the unsuppressed water signal and corrected for voxel tissue composition (i.e., gray matter, white matter, CSF). Our results indicated significant age-related declines in both GABA+ and Glx, along with a reduction in the E/I ratio, suggesting diminished inhibitory and excitatory tone with advancing age. We also found a decline in tNAA and an increase in tCr with increasing age. In summary, we provide compelling evidence through one of the largest studies of its kind for age-related shifts in excitatory and inhibitory neurotransmitter levels in the visual cortex. These changes may be critical to well-known, age-related physiological changes, including reduced neural selectivity and processing efficiency. These findings provide novel evidence that neurochemical alterations may contribute to the functional declines in cortical processing seen in healthy aging.

YNIMG Journal 2025 Journal Article

Oscillatory and evoked neural responses underlying gating in the primary somatosensory cortices: Evidence from optically-pumped magnetometry

Yasra Arif
Elizabeth Heinrichs-Graham
Alexa M. Wildy
Thomas W. Ward
Augusto Diedrich
Christine M. Embury
Maggie P. Rempe
Ryan J. Glesinger

Sensory gating (SG) is a protective mechanism that prevents sensory overload by attenuating neural responses to repeated stimuli while allowing allocation of neural resources to salient inputs. While studies using conventional, cryogenic magnetoencephalography (MEG) have provided a foundational understanding of the neurophysiological spectro-temporal profile of sensory gating in somatosensory cortices, its utility in diverse populations is constrained by technical limitations, including movement restriction and a one-size-fits-all helmet design. Recent developments in optically pumped magnetometry (OPM) aim to overcome these constraints by providing greater tolerance to movement and customizable helmet sizes. A small number of studies have documented the reliability of OPM in mapping somatosensory responses to median nerve stimulation using OPM; however, none have examined SG. In this study, we utilized a whole-head 128-channel OPM system and a paired-pulse median nerve stimulation paradigm to examine somato-SG and map the precise spectro-temporal cortical dynamics in a group of 31 healthy adults. Neural responses per stimulation were imaged in both the time-frequency and time domains, and voxel time series data were extracted to quantify the dynamics of somato-SG. Robust gating effects were observed in the peak and average neural responses within the primary somatosensory cortices, in both the oscillatory and time domains. These findings underscore OPM's ability to precisely resolve the spatiotemporal neural dynamics of somato-SG and stress the utility of OPM in examining somatosensory processes across developmental trajectories extending down to infants, as well as in clinical populations.

YNICL Journal 2025 Journal Article

Overground gait training improves the sensorimotor cortical dynamics and mobility of persons with cerebral palsy

Morgan T. Busboom
Rachel K. Spooner
Liana S. Chinen
Sarah E. Baker
Brad Corr
Katie L. Bemis
Kimberley Scott
Tony W. Wilson

OBJECTIVE: Persons with cerebral palsy (CP) exhibit aberrant sensorimotor cortical oscillations linked to uncharacteristic motor actions and mobility, but the key physical therapy ingredients needed to offset these aberrations and drive improvements in cortical function remain unclear. This study evaluated whether overground gait training results in mobility gains that are coupled to beneficial changes in sensorimotor cortical oscillations in persons with CP. 34 persons with CP (Age = 20.58 ± 7.61yrs; Gross Motor Functional Classification Scores I-III) and 32 neurotypical (NT) controls (Age = 23.06 ± 3.79yrs) participated. Persons with CP completed 24 overground gait training sessions (3 days/week for 8 weeks). A battery of clinical assessments were used to examine changes in functional mobility. Magnetoencephalographic (MEG) imaging was used to quantify sensorimotor cortical oscillations while performing a knee extension motor task pre- and post-therapy in the CP group. Only one MEG measurement was completed by NTs. Persons with CP improved their Functional Gait Assessment scores by 8.77 % (p 0.05). Notably, the persons with CP who exhibited the largest increases in sensorimotor beta oscillations tended to have greater improvements in the TUG (p = 0.025). Overground gait training enhanced sensorimotor cortical oscillations and yielded clinically meaningful mobility gains. These neuroplastic and functional improvements may stem from gait-related tasks emphasizing movement planning, execution, and problem-solving.

YNIMG Journal 2025 Journal Article

Regular cannabis use modulates gamma functional connectivity with V1 during visual processing

Lauren K. Webert
Nathan M. Petro
Seth D. Springer
Jason A. John
Lucy K. Horne
Molly E. Voller
Kyla R. De Luca
Olivia R. Carusi

Cannabis is a widely-used illicit substance in the United States, and heavy cannabis use has been linked to deficits across multiple cognitive domains. Mechanistically, cannabis affects endocannabinoid receptors densely distributed among GABAergic interneurons throughout the cortex and cerebellum. Such interneuronal networks are known to be crucial in the generation of fast neural gamma-band responses, which support perceptual and cognitive processing and have been frequently implicated in cannabis use. However, studies to date have tended to focus on higher-order processing supported by gamma oscillations, with limited work examining more fundamental aspects of gamma circuit integrity. Herein, 84 adults who regularly use cannabis and 90 demographically-matched nonusers underwent high-density magnetoencephalography during a visual entrainment task involving three gamma-band flicker frequencies (32, 40, and 48 Hz). The resulting data were imaged in the time-frequency domain and the dynamic neural time series were extracted and tested for effects of hemisphere, frequency, and group, and then used to compute whole-brain dynamic functional connectivity. Our results indicated strong gamma entrainment in the bilateral primary visual cortices (V1), with 32 Hz responses being the strongest across both groups (p < .001) and right V1 activity being stronger than left across groups and frequencies (p = .002). Additionally, there were group-by-condition interactions in connectivity maps (p < .005), with the cannabis group having elevated 32 Hz connectivity between V1 and higher-order visual regions relative to controls. These findings suggest that basic gamma circuitry remains intact despite heavy cannabis use, while gamma functional connectivity is preferentially affected and this may lead to the higher-order deficits.

YNIMG Journal 2025 Journal Article

Spatiotemporal dynamics of multispectral oscillatory activity underlying the processing of negative and positive emotional images

Nathan M. Petro
Mikki Schantell
Mia C. Lulli
Kellen M. McDonald
Chloe C. Casagrande
Christine M. Embury
Hannah J. Okelberry
Jason A. John

Behavioral and neural responses to visual scenes depicting potential threat or harm constitute core aspects of human behavior and can illuminate symptoms of internalizing disorders. Decades of research have shown that negative content undergoes facilitated processing across a distributed brain network whereby perception is facilitated, and cognitive systems appraise the stimulus to regulate emotions and plan motor action. However, relatively limited studies have examined the multispectral dynamics underlying the neural processing of negative emotional images, with mixed results among existing studies. Herein, we used magnetoencephalography (MEG) to derive dynamic functional maps of positive and negative image processing in healthy adults. Alpha (from 200 to 700 ms) and beta (from 200 to 550 ms) oscillations were stronger for negative images in primary and ventral visual regions, as well as parietal and prefrontal cortices (all ps < .005). Similarly, theta activation was stronger for negative images in ventral temporal cortex (p < .001) from 0 to 250 ms. Lastly, gamma oscillatory activity was stronger for negative images in the pre-supplementary motor area (p < .005) from 150 to 500 ms. These results are consistent with the literature in regard to the critical brain regions involved in emotional processing, but importantly also delineate the multispectral oscillatory dynamics within these regions that support the swift synthesis of low-level visual inputs, appraise emotional meaning, and guide appropriate motor system activation (as necessary) to avoid harm.

YNIMG Journal 2025 Journal Article

The polarity of high-definition transcranial direct current stimulation affects the planning and execution of movement sequences

Jake J. Son
Tara D. Erker
Thomas W. Ward
Yasra Arif
Peihan J. Huang
Jason A. John
Kellen M. McDonald
Nathan M. Petro

Noninvasive brain stimulation of the primary motor cortex has been shown to alter therapeutic outcomes in stroke and other neurological conditions, but the precise mechanisms remain poorly understood. Determining the impact of such neurostimulation on the neural processing supporting motor control is a critical step toward further harnessing its therapeutic potential in multiple neurological conditions affecting the motor system. Herein, we leverage the excellent spatio-temporal precision of magnetoencephalographic (MEG) imaging to identify the spectral, spatial, and temporal effects of high-definition transcranial direct current stimulation (HD-tDCS) on the neural responses supporting motor control. Participants (N = 67) completed three HD-tDCS visits (anode, cathode, sham), with each involving 20 min of left primary motor cortex stimulation and performance of a simple/complex motor sequencing task during MEG. Whole-brain statistical analyses of beta oscillatory responses revealed stimulation-by-task interaction effects in the left primary motor cortex, right occipitotemporal, and the right dorsolateral prefrontal cortices. Broadly, anodal stimulation induced significantly stronger beta oscillatory responses in these regions during simple movement sequences, while neural responses to complex sequences were not affected by stimulation. En masse, these data suggest that the beta oscillations serving motor planning (i.e., pre-movement) are particularly sensitive to the polarity of noninvasive stimulation and that the impact varies based on the difficulty of the movement sequence.

YNIMG Journal 2024 Journal Article

Explainable spatio-temporal graph evolution learning with applications to dynamic brain network analysis during development

Longyun Chen
Chen Qiao
Kai Ren
Gang Qu
Vince D. Calhoun
Julia M. Stephen
Tony W. Wilson
Yu-Ping Wang

Modeling dynamic interactions among network components is crucial to uncovering the evolution mechanisms of complex networks. Recently, spatio-temporal graph learning methods have achieved noteworthy results in characterizing the dynamic changes of inter-node relations (INRs). However, challenges remain: The spatial neighborhood of an INR is underexploited, and the spatio-temporal dependencies in INRs' dynamic changes are overlooked, ignoring the influence of historical states and local information. In addition, the model's explainability has been understudied. To address these issues, we propose an explainable spatio-temporal graph evolution learning (ESTGEL) model to model the dynamic evolution of INRs. Specifically, an edge attention module is proposed to utilize the spatial neighborhood of an INR at multi-level, i.e., a hierarchy of nested subgraphs derived from decomposing the initial node-relation graph. Subsequently, a dynamic relation learning module is proposed to capture the spatio-temporal dependencies of INRs. The INRs are then used as adjacent information to improve the node representation, resulting in comprehensive delineation of dynamic evolution of the network. Finally, the approach is validated with real data on brain development study. Experimental results on dynamic brain networks analysis reveal that brain functional networks transition from dispersed to more convergent and modular structures throughout development. Significant changes are observed in the dynamic functional connectivity (dFC) associated with functions including emotional control, decision-making, and language processing.

YNIMG Journal 2024 Journal Article

Neurotoxic effects of home radon exposure on oscillatory dynamics serving attentional orienting in children and adolescents

Haley R. Pulliam
Seth D. Springer
Danielle L. Rice
Grace C. Ende
Hallie J. Johnson
Madelyn P. Willett
Tony W. Wilson
Brittany K. Taylor

Radon is a naturally occurring gas that contributes significantly to radiation in the environment and is the second leading cause of lung cancer globally. Previous studies have shown that other environmental toxins have deleterious effects on brain development, though radon has not been studied as thoroughly in this context. This study examined the impact of home radon exposure on the neural oscillatory activity serving attention reorientation in youths. Fifty-six participants (ages 6-14 years) completed a classic Posner cuing task during magnetoencephalography (MEG), and home radon levels were measured for each participant. Time-frequency spectrograms indicated stronger theta (3-7 Hz, 300-800 ms), alpha (9-13 Hz, 400-900 ms), and beta responses (14-24 Hz, 400-900 ms) during the task relative to baseline. Source reconstruction of each significant oscillatory response was performed, and validity maps were computed by subtracting the task conditions (invalidly cued - validly cued). These validity maps were examined for associations with radon exposure, age, and their interaction in a linear regression design. Children with greater radon exposure showed aberrant oscillatory activity across distributed regions critical for attentional processing and attention reorientation (e.g., dorsolateral prefrontal cortex, and anterior cingulate cortex). Generally, youths with greater radon exposure exhibited a reverse neural validity effect in almost all regions and showed greater overall power relative to peers with lesser radon exposure. We also detected an interactive effect between radon exposure and age where youths with greater radon exposure exhibited divergent developmental trajectories in neural substrates implicated in attentional processing (e.g., bilateral prefrontal cortices, superior temporal gyri, and inferior parietal lobules). These data suggest aberrant, but potentially compensatory neural processing as a function of increasing home radon exposure in areas critical for attention and higher order cognition.

YNIMG Journal 2024 Journal Article

Oscillatory activity in bilateral prefrontal cortices is altered by distractor strength during working memory processing

Megan C. Hall
Maggie P. Rempe
Ryan J. Glesinger
Lucy K. Horne
Hannah J. Okelberry
Jason A. John
Christine M. Embury
Elizabeth Heinrichs-Graham

28) who completed a Sternberg type WM task with high- and low-distractor conditions during magnetoencephalography (MEG). MEG data were transformed into the time-frequency domain and significant task-related oscillatory responses were imaged to identify the underlying anatomical areas. Whole-brain paired t-tests, with cluster-based permutation testing for multiple comparisons correction, were performed to assess differences between the low- and high-distractor conditions for each oscillatory response. Across conditions, we found strong alpha and beta oscillations (i.e., decreases relative to baseline) and increases in theta power throughout the encoding and maintenance periods. Whole-brain contrasts revealed significantly stronger alpha and beta oscillations in bilateral prefrontal regions during maintenance in high- compared to low-distractor trials, with the stronger beta oscillations being centered on the left dorsolateral prefrontal cortex and right inferior frontal gyrus, while those for alpha being within the right anterior prefrontal cortices and the right middle frontal gyrus. These findings suggest that alpha and beta oscillations in the bilateral prefrontal cortices play a major role in the inhibition of distracting information during WM maintenance. Our results also contribute to prior research on cognitive control and functional inhibition, in which prefrontal regions have been widely implicated.

YNIMG Journal 2023 Journal Article

Altered age-related alpha and gamma prefrontal-occipital connectivity serving distinct cognitive interference variants

Yasra Arif
Alex I. Wiesman
Nicholas Christopher-Hayes
Hannah J. Okelberry
Hallie J. Johnson
Madelyn P. Willett
Tony W. Wilson

The presence of conflicting stimuli adversely affects behavioral outcomes, which could either be at the level of stimulus (Flanker), response (Simon), or both (Multisource). Briefly, flanker interference involves conflicting stimuli requiring selective attention, Simon interference is caused by an incongruity between the spatial location of the task-relevant stimulus and prepotent motor mapping, and multisource is combination of both. Irrespective of the variant, interference resolution necessitates cognitive control to filter irrelevant information and allocate neural resources to task-related goals. Though previously studied in healthy young adults, the direct quantification of changes in oscillatory activity serving such cognitive control and associated inter-regional interactions in healthy aging are poorly understood. Herein, we used an adapted version of the multisource interference task and magnetoencephalography to investigate age-related alterations in the neural dynamics governing both divergent and convergent cognitive interference in 78 healthy participants (age range: 20-66 years). We identified weaker alpha connectivity between bilateral visual and right dorsolateral prefrontal cortices (DLPFC) and left dorsomedial prefrontal cortices (dmPFC), as well as weaker gamma connectivity between bilateral occipital regions and the right dmPFC during flanker interference with advancing age. Further, an age-related decrease in gamma power was observed in the left cerebellum and parietal region for Simon and differential interference effects (i.e., flanker-Simon), respectively. Moreover, the superadditivity model showed decreased gamma power in the right temporoparietal junction (TPJ) with increasing age. Overall, our findings suggest age-related declines in the engagement of top-down attentional control secondary to reduced alpha and gamma coupling between prefrontal and occipital cortices.

YNIMG Journal 2023 Journal Article

Disturbances in primary visual processing as a function of healthy aging

Seth D. Springer
Tara D. Erker
Mikki Schantell
Hallie J. Johnson
Madelyn P. Willett
Hannah J. Okelberry
Maggie P. Rempe
Tony W. Wilson

For decades, visual entrainment paradigms have been widely used to investigate basic visual processing in healthy individuals and those with neurological disorders. While healthy aging is known to be associated with alterations in visual processing, whether this extends to visual entrainment responses and the precise cortical regions involved is not fully understood. Such knowledge is imperative given the recent surge in interest surrounding the use of flicker stimulation and entrainment in the context of identifying and treating Alzheimer's disease (AD). In the current study, we examined visual entrainment in eighty healthy aging adults using magnetoencephalography (MEG) and a 15 Hz entrainment paradigm, while controlling for age-related cortical thinning. MEG data were imaged using a time-frequency resolved beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying the processing of the visual flicker stimuli. We found that, as age increased, the mean amplitude of entrainment responses decreased and the latency of these responses increased. However, there was no effect of age on the trial-to-trial consistency in phase (i.e., inter-trial phase locking) nor amplitude (i.e., coefficient of variation) of these visual responses. Importantly, we discovered that the relationship between age and response amplitude was fully mediated by the latency of visual processing. These results indicate that aging is associated with robust changes in the latency and amplitude of visual entrainment responses within regions surrounding the calcarine fissure, which should be considered in studies examining neurological disorders such as AD and other conditions associated with increased age.

YNIMG Journal 2022 Journal Article

Detecting abnormal connectivity in schizophrenia via a joint directed acyclic graph estimation model

Gemeng Zhang
Biao Cai
Aiying Zhang
Zhuozhuo Tu
Li Xiao
Julia M. Stephen
Tony W. Wilson
Vince D. Calhoun

Functional connectivity (FC) between brain region has been widely studied and linked with cognition and behavior of an individual. FC is usually defined as the correlation or partial correlation of fMRI blood oxygen level-dependent (BOLD) signals between two brain regions. Although FC has been effective to understand brain organization, it cannot reveal the direction of interactions. Many directed acyclic graph (DAG) based methods have been applied to study the directed interactions but their performance was limited by the small sample size while high dimensionality of the available data. By enforcing group regularization and utilizing samples from both case and control groups, we propose a joint DAG model to estimate the directed FC. We first demonstrate that the proposed model is efficient and accurate through a series of simulation studies. We then apply it to the case-control study of schizophrenia (SZ) with data collected from the MIND Clinical Imaging Consortium (MCIC). We have successfully identified decreased functional integration, disrupted hub structures and characteristic edges (CtEs) in SZ patients. Those findings have been confirmed by previous studies with some identified to be potential markers for SZ patients. A comparison of the results between the directed FC and undirected FC showed substantial differences in the selected features. In addition, we used the identified features based on directed FC for the classification of SZ patients and achieved better accuracy than using undirected FC or raw features, demonstrating the advantage of using directed FC for brain network analysis.

YNIMG Journal 2022 Journal Article

Eyes-closed versus eyes-open differences in spontaneous neural dynamics during development

Nathan M. Petro
Lauren R. Ott
Samantha H. Penhale
Maggie P. Rempe
Christine M. Embury
Giorgia Picci
Yu-Ping Wang
Julia M. Stephen

BACKGROUND: Assessing brain activity during rest has become a widely used approach in developmental neuroscience. Extant literature has measured resting brain activity both during eyes-open and eyes-closed conditions, but the difference between these conditions has not yet been well characterized. Studies, limited to fMRI and EEG, have suggested that eyes-open versus -closed conditions may differentially impact neural activity, especially in visual cortices. METHODS: Spontaneous cortical activity was recorded using MEG from 108 typically developing youth (9-15 years-old; 55 female) during separate sessions of eyes-open and eyes-closed rest. MEG source images were computed, and the strength of spontaneous neural activity was estimated in the canonical delta, theta, alpha, beta, and gamma bands, respectively. Power spectral density maps for eyes-open were subtracted from eyes-closed rest, and then submitted to vertex-wise regression models to identify spatially specific differences between conditions and as a function of age and sex. RESULTS: Relative alpha power was weaker in the eyes-open compared to -closed condition, but otherwise eyes-open was stronger in all frequency bands, with differences concentrated in the occipital cortex. Relative theta power became stronger in the eyes-open compared to the eyes-closed condition with increasing age in frontal cortex. No differences were observed between males and females. CONCLUSIONS: The differences in relative power from eyes-closed to -open conditions are consistent with changes observed in task-based visual sensory responses. Age differences occurred in relatively late developing frontal regions, consistent with canonical attention regions, suggesting that these differences could be reflective of developmental changes in attention processes during puberty. Taken together, resting-state paradigms using eyes-open versus -closed produce distinct results and, in fact, can help pinpoint sensory related brain activity.

YNIMG Journal 2022 Journal Article

Individual differences in amygdala volumes predict changes in functional connectivity between subcortical and cognitive control networks throughout adolescence

Brittany K. Taylor
Michaela R. Frenzel
Jacob A. Eastman
Christine M. Embury
Oktay Agcaoglu
Yu-Ping Wang
Julia M. Stephen
Vince D. Calhoun

Adolescence is a critical period of structural and functional neural maturation among regions serving the cognitive control of emotion. Evidence suggests that this process is guided by developmental changes in amygdala and striatum structure and shifts in functional connectivity between subcortical (SC) and cognitive control (CC) networks. Herein, we investigate the extent to which such developmental shifts in structure and function reciprocally predict one another over time. 179 youth (9-15 years-old) completed annual MRI scans for three years. Amygdala and striatum volumes and connectivity within and between SC and CC resting state networks were measured for each year. We tested for reciprocal predictability of within-person and between-person changes in structure and function using random-intercept cross-lagged panel models. Within-person shifts in amygdala volumes in a given year significantly and specifically predicted deviations in SC-CC connectivity in the following year, such that an increase in volume was associated with decreased SC-CC connectivity the following year. Deviations in connectivity did not predict changes in amygdala volumes over time. Conversely, broader group-level shifts in SC-CC connectivity were predictive of subsequent deviations in striatal volumes. We did not see any cross-predictability among amygdala or striatum volumes and within-network connectivity measures. Within-person shifts in amygdala structure year-to-year robustly predicted weaker SC-CC connectivity in subsequent years, whereas broader increases in SC-CC connectivity predicted smaller striatal volumes over time. These specific structure function relationships may contribute to the development of emotional control across adolescence.

YNIMG Journal 2022 Journal Article

Longitudinal changes in the neural oscillatory dynamics underlying abstract reasoning in children and adolescents

Brittany K. Taylor
Elizabeth Heinrichs-Graham
Jacob A. Eastman
Michaela R. Frenzel
Yu-Ping Wang
Vince D. Calhoun
Julia M. Stephen
Tony W. Wilson

Fluid reasoning is the ability to problem solve in the absence of prior knowledge and is commonly conceptualized as "non-verbal" intelligence. Importantly, fluid reasoning abilities rapidly develop throughout childhood and adolescence. Although numerous studies have characterized the neural underpinnings of fluid reasoning in adults, there is a paucity of research detailing the developmental trajectory of this neural processing. Herein, we examine longitudinal changes in the neural oscillatory dynamics underlying fluid intelligence in a sample of typically developing youths. A total of 34 participants age 10 to 16 years-old completed an abstract reasoning task during magnetoencephalography (MEG) on two occasions set one year apart. We found robust longitudinal optimization in theta, beta, and gamma oscillatory activity across years of the study across a distributed network commonly implicated in fluid reasoning abilities. More specifically, activity tended to decrease longitudinally in additional, compensatory areas such as the right lateral prefrontal cortex and increase in areas commonly utilized in mature adult samples (e.g., left frontal and parietal cortices). Importantly, shifts in neural activity were associated with improvements in task performance from one year to the next. Overall, the data suggest a longitudinal shift in performance that is accompanied by a reconfiguration of the functional oscillatory dynamics serving fluid reasoning during this important period of development.

YNICL Journal 2022 Journal Article

Retrospective comparison of motor and somatosensory MEG mapping—Considerations for better clinical applications

Rachel K. Spooner
Deepak Madhavan
Michele R. Aizenberg
Tony W. Wilson

While magnetoencephalography (MEG) has proven to be a valuable and reliable tool for presurgical functional mapping of eloquent cortices for at least two decades, widespread use of this technique by clinicians has remained elusive. This modest application may be attributable, at least in part, to misunderstandings regarding the success rate of such mapping procedures, as well as the primary sources contributing to mapping failures. To address this, we conducted a retrospective comparison of sensorimotor functional mapping success rates in 141 patients with epilepsy and 75 tumor patients from the Center for MEG in Omaha, NE. Neurosurgical candidates either completed motor mapping (i.e., finger tapping paradigm), somatosensory mapping (i.e., peripheral stimulation paradigm), or both motor and somatosensory protocols during MEG. All MEG data underwent subsequent time-domain averaging and source localization of left and right primary motor (M1) and somatosensory (S1) cortices was conducted using a single equivalent dipole model. Successful mapping was determined based on dipole goodness of fit metrics ∼ 95%, as well as an accurate and conceivable spatial correspondence to precentral and postcentral gyri for M1 and S1, respectively. Our results suggest that mapping M1 in epilepsy and tumor patients was on average 94.5% successful, when patients only completed motor mapping protocols. In contrast, mapping S1 was successful 45-100% of the time in these patient groups when they only completed somatosensory mapping paradigms. Importantly, Z-tests for independent proportions revealed that the percentage of successful S1 mappings significantly increased to ∼ 94% in epilepsy patients who completed both motor/somatosensory mapping protocols during MEG. Together, these data suggest that ordering more comprehensive mapping procedures (e.g., both motor and somatosensory protocols for a collective sensorimotor network) may substantially increase the accuracy of presurgical functional mapping by providing more extensive data from which to base interpretations. Moreover, clinicians and magnetoencephalographers should be considerate of the major contributors to mapping failures (i.e., low SNR, excessive motion and magnetic artifacts) in order to further increase the percentage of cases achieving successful mapping of eloquent cortices.

YNIMG Journal 2022 Journal Article

Spontaneous sensorimotor beta power and cortical thickness uniquely predict motor function in healthy aging

Maggie P. Rempe
Brandon J. Lew
Christine M. Embury
Nicholas J. Christopher-Hayes
Mikki Schantell
Tony W. Wilson

BACKGROUND: Spontaneous beta activity in the primary motor cortices has been shown to increase in amplitude with advancing age, and that such increases are tightly coupled to stronger motor-related beta oscillations during movement planning. However, the relationship between these age-related changes in spontaneous beta in the motor cortices, local cortical thickness, and overall motor function remains unclear. METHODS: We collected resting-state magnetoencephalography (MEG), high-resolution structural MRI, and motor function scores using a neuropsychological battery from 126 healthy adults (56 female; age range = 22-72 years). MEG data were source-imaged and a whole-brain vertex-wise regression model was used to assess age-related differences in spontaneous beta power across the cortex. Cortical thickness was computed from the structural MRI data and local beta power and cortical thickness values were extracted from the sensorimotor cortices. To determine the unique contribution of age, spontaneous beta power, and cortical thickness to the prediction of motor function, a hierarchical regression approach was used. RESULTS: There was an increase in spontaneous beta power with age across the cortex, with the strongest increase being centered on the sensorimotor cortices. Sensorimotor cortical thickness was not related to spontaneous beta power, above and beyond age. Interestingly, both cortical thickness and spontaneous beta power in sensorimotor regions each uniquely contributed to the prediction of motor function when controlling for age. DISCUSSION: This multimodal study showed that cortical thickness and spontaneous beta activity in the sensorimotor cortices have dissociable contributions to motor function across the adult lifespan. These findings highlight the complexity of interactions between structure and function and the importance of understanding these interactions in order to advance our understanding of healthy aging and disease.

YNIMG Journal 2022 Journal Article

The development of sensorimotor cortical oscillations is mediated by pubertal testosterone

Madison H. Fung
Elizabeth Heinrichs-Graham
Brittany K. Taylor
Michaela R. Frenzel
Jacob A. Eastman
Yu-Ping Wang
Vince D. Calhoun
Julia M. Stephen

Puberty is a period of substantial hormonal fluctuations, and pubertal hormones can modulate structural and functional changes in the developing brain. Many previous studies have characterized the neural oscillatory responses serving movement, which include a beta event-related desynchronization (ERD) preceding movement onset, gamma and theta responses coinciding with movement execution, and a post-movement beta-rebound (PMBR) response following movement offset. While a few studies have investigated the developmental trajectories of these neural oscillations serving motor control, the impact of pubertal hormone levels on the maturation of these dynamics has not yet been examined. Since the timing and tempo of puberty varies greatly between individuals, pubertal hormones may uniquely impact the maturation of motor cortical oscillations distinct from other developmental metrics, such as age. In the current study we quantified these oscillations using magnetoencephalography (MEG) and utilized chronological age and measures of endogenous testosterone as indices of development during the transition from childhood to adolescence in 69 youths. Mediation analyses revealed complex maturation patterns for the beta ERD, in which testosterone predicted both spontaneous baseline and ERD power through direct and indirect effects. Age, but not pubertal hormones, predicted motor-related theta, and no relationships between oscillatory responses and developmental metrics were found for gamma or PMBR responses. These findings provide novel insight into how pubertal hormones affect motor-related oscillations, and highlight the continued development of motor cortical dynamics throughout the pubertal period.

YNICL Journal 2021 Journal Article

Altered neural oscillations during complex sequential movements in patients with Parkinson’s disease

Marie C. McCusker
Alex I. Wiesman
Rachel K. Spooner
Pamela M. Santamaria
Jennifer McKune
Elizabeth Heinrichs-Graham
Tony W. Wilson

The sequelae of Parkinson's disease (PD) includes both motor- and cognitive-related symptoms. Although traditionally considered a subcortical disease, there is increasing evidence that PD has a major impact on cortical function as well. Prior studies have reported alterations in cortical neural function in patients with PD during movement, but to date such studies have not examined whether the complexity of multicomponent movements modulate these alterations. In this study, 23 patients with PD (medication "off" state) and 27 matched healthy controls performed simple and complex finger tapping sequences during magnetoencephalography (MEG), and the resulting MEG data were imaged to identify the cortical oscillatory dynamics serving motor performance. The patients with PD were significantly slower than controls at executing the sequences overall, and both groups took longer to complete the complex sequences than the simple. In terms of neural differences, patients also exhibited weaker beta complexity-related effects in the right medial frontal gyrus and weaker complexity-related alpha activity in the right posterior and inferior parietal lobules, suggesting impaired motor sequence execution. Characterizing the cortical pathophysiology of PD could inform current and future therapeutic interventions that address both motor and cognitive symptoms.

YNICL Journal 2021 Journal Article

Gray matter volumes discriminate cognitively impaired and unimpaired people with HIV

Mikki Schantell
Brittany K. Taylor
Brandon J. Lew
Jennifer L. O'Neill
Pamela E. May
Susan Swindells
Tony W. Wilson

BACKGROUND: Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses. METHODS: A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could accurately distinguish the three groups using linear discriminant analysis. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, area under the curve (AUC), and accuracy were computed for each model using the classification results based on GMV compared to the neuropsychological assessment. RESULTS: The best performing model was comprised of bilaterally combined GMV and was stratified by sex. Among males, sensitivity was 85.2% (95% CI: 66.3%-95.8%), specificity was 97.0% (95% CI: 91.6%-99.4%), and the AUC was 0.91 (95% CI: 0.83-0.99). Among females, sensitivity was 100.0% (95% CI: 83.9%-100.0%), specificity was 98.8% (95% CI: 93.4%-100.0%), and the AUC was 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: GMV accurately discriminated HAND from unimpaired PWH and controls. Measures of GMV may be highly sensitive to HAND, and revisions to the Frascati criteria should consider including GMV in conjunction with a neuropsychological assessment to diagnose HAND.

JBHI Journal 2021 Journal Article

Multi-Paradigm fMRI Fusion via Sparse Tensor Decomposition in Brain Functional Connectivity Study

Yipu Zhang
Li Xiao
Gemeng Zhang
Biao Cai
Julia M. Stephen
Tony W. Wilson
Vince D. Calhoun
Yu-Ping Wang

Functional magnetic resonance imaging (fMRI) is a powerful technique with the potential to estimate individual variations in behavioral and cognitive traits. Joint learning of multiple datasets can utilize their complementary information so as to improve learning performance, but it also gives rise to the challenge for data fusion to effectively integrate brain patterns elicited by multiple fMRI data. However, most of the current data fusion methods analyze each single dataset separately and further infer the relationship among them, which fail to utilize the multidimensional structure inherent across modalities and may ignore complex but important interactions. To address this issue, we propose a novel sparse tensor decomposition method to integrate multiple task-stimulus (paradigm) fMRI data. Seeing each paradigm fMRI as one modality, our proposed method considers the relationships across subjects and modalities simultaneously. In specific, a third-order tensor is first modeled by using the functional network connectivity (FNC) of subjects in multiple fMRI paradigms. A novel sparse tensor decomposition with the regularization terms is designed to factorize the tensor into a series of rank-one components, which can extract the shared components across modalities as the embedded features. The L 2, 1 -norm regularizer (i. e. , group sparsity) is enforced to select a few common features among multiple subjects. Validation of the proposed method is performed on realistic three paradigm fMRI datasets from the Philadelphia Neurodevelopmental Cohort (PNC) study, for the study of the relationship between the FNC and human cognitive abilities. Experimental results show our method outperforms several other competing methods in the prediction of individuals with different cognitive behaviors via the wide range achievement test (WRAT). Furthermore, our method discovers the FNC related to the cognitive behaviors, such as the connectivity associated with the default mode network (DMN) for three paradigms, and the connectivity between DMN and visual (VIS) domains within the emotion task.

YNIMG Journal 2021 Journal Article

Response certainty during bimanual movements reduces gamma oscillations in primary motor cortex

Alex I. Wiesman
Nicholas J. Christopher-Hayes
Jacob A. Eastman
Elizabeth Heinrichs-Graham
Tony W. Wilson

Even when movement outputs are identical, the neural responses supporting them might differ substantially in order to adapt to changing environmental contexts. Despite the essential nature of this adaptive capacity of the human motor system, little is known regarding the effects of contextual response (un)certainty on the neural dynamics known to serve motor processing. In this study, we use a novel bimanual motor task and neuroimaging with magnetoencephalography (MEG) to examine the effects of contextual response certainty on the dynamic neural responses that are important for proper movement. Significant neural responses were identified in the time-frequency domain at the sensor-level and imaged to the cortex using a spectrally resolved beamformer. Combined frequentist and Bayesian statistical testing between neural motor responses under certain and uncertain conditions indicated evidence for no conditional effect on the peri-movement beta desynchronization (18 - 28 Hz; -100 to 300 ms). In contrast, the movement-related gamma synchronization (MRGS; 66 - 86 Hz; -50 to 150 ms) exhibited a robust effect of motor certainty, such that increased contextual response certainty reduced the amplitude of this response. Interestingly, the peak frequency of the MRGS was unaffected by response certainty. These findings both advance our understanding of the neural processes required to adapt our movements under altered environmental contexts, and support the growing conceptualization of the MRGS as being reflective of ongoing higher cognitive processes during movement execution.

YNIMG Journal 2021 Journal Article

Spontaneous cortical MEG activity undergoes unique age- and sex-related changes during the transition to adolescence

Lauren R. Ott
Samantha H. Penhale
Brittany K. Taylor
Brandon J. Lew
Yu-Ping Wang
Vince D. Calhoun
Julia M. Stephen
Tony W. Wilson

BACKGROUND: While numerous studies have examined the developmental trajectory of task-based neural oscillations during childhood and adolescence, far less is known about the evolution of spontaneous cortical activity during this time period. Likewise, many studies have shown robust sex differences in task-based oscillations during this developmental period, but whether such sex differences extend to spontaneous activity is not understood. METHODS: Herein, we examined spontaneous cortical activity in 111 typically-developing youth (ages 9-15 years; 55 male). Participants completed a resting state magnetoencephalographic (MEG) recording and a structural MRI. MEG data were source imaged and the power within five canonical frequency bands (delta, theta, alpha, beta, gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially-specific effects of age, sex, and their interaction. RESULTS: We found robust increases in power with age in all frequencies except delta, which decreased over time, with findings largely confined to frontal cortices. Sex effects were distributed across frontal and temporal regions; females tended to have greater delta and beta power, whereas males had greater alpha. Importantly, there was a significant age-by-sex interaction in theta power, such that males exhibited decreasing power with age while females showed increasing power with age in the bilateral superior temporal cortices. DISCUSSION: These data suggest that the strength of spontaneous activity undergoes robust change during the transition from childhood to adolescence (i.e., puberty onset), with intriguing sex differences in some cortical areas. Future developmental studies should probe task-related oscillations and spontaneous activity in parallel.

YNIMG Journal 2021 Journal Article

Stairway to memory: Left-hemispheric alpha dynamics index the progressive loading of items into a short-term store

Alex I. Wiesman
Nicholas J. Christopher-Hayes
Tony W. Wilson

The encoding, maintenance, and subsequent retrieval of memories over short time intervals is an essential cognitive function. Load effects on the neural dynamics supporting the maintenance of short-term memories have been well studied, but experimental design limitations have hindered the study of similar effects during the encoding of information into online memory stores. Theoretically, the active encoding of complex visual stimuli into memory must also recruit neural resources in a manner that scales with memory load. Understanding the neural systems supporting this encoding load effect is of particular importance, as some patient populations exhibit difficulties specifically with the encoding, and not the maintenance, of short-term memories. Using magnetoencephalography, a visual sequence memory paradigm, and a novel encoding slope analysis, we provide evidence for a left-lateralized network of regions, oscillating in the alpha frequency range, that exhibit a progressive loading effect of complex visual stimulus information during memory encoding. This progressive encoding load effect significantly tracked the eventual retrieval of item-order memories at the single trial level, and neural activity in these regions was functionally dissociated from that of earlier visual networks. These findings suggest that the active encoding of stimulus information into short-term stores recruits a left-lateralized network of frontal, parietal, and temporal regions, and might be susceptible to modulation (e.g., using non-invasive stimulation) in the alpha band.

YNIMG Journal 2021 Journal Article

Three-year reliability of MEG resting-state oscillatory power

Brandon J. Lew
Emily E. Fitzgerald
Lauren R. Ott
Samantha H. Penhale
Tony W. Wilson

INTRODUCTION: Resting-state oscillatory activity has been extensively studied across a wide array of disorders. Establishing which spectrally- and spatially-specific oscillatory components exhibit test-retest reliability is essential to move the field forward. While studies have shown short-term reliability of MEG resting-state activity, no studies have examined test-retest reliability across an extended period of time to establish the stability of these signals, which is critical for reproducibility. METHODS: We examined 18 healthy adults age 23 - 61 who completed three visits across three years. For each visit, participants completed both a resting state MEG and structural MRI scan. MEG data were source imaged, and the cortical power in canonical frequency bands (delta, theta, alpha, beta, low gamma, high gamma) was computed. Intra-class correlation coefficients (ICC) were then calculated across the cortex for each frequency band. RESULTS: Over three years, power in the alpha and beta bands displayed the highest reliability estimates, while gamma showed the lowest estimates of three-year reliability. Spatially, delta, alpha, and beta all showed the highest degrees of reliability in the parietal cortex. Interestingly, the peak signal for each of these frequency bands was located outside of the parietal cortex, suggesting that reliability estimates were not solely dependent on the signal-to-noise ratio. CONCLUSION: Oscillatory resting-state power in parietal delta, posterior beta, and alpha across most of the cortex are reliable across three years and future MEEG studies may focus on these measures for the development of specific markers.

YNIMG Journal 2020 Journal Article

Attention modulates the gating of primary somatosensory oscillations

Alex I. Wiesman
Tony W. Wilson

Sensory gating (SG) is a well-studied phenomenon in which neural responses are reduced to identical stimuli presented in succession, and is thought to represent the functional inhibition of primary sensory information that is redundant in nature. SG is traditionally considered pre-attentive, but little is known about the effects of attentional state on this process. In this study, we investigate the impact of directed attention on somatosensory SG using magnetoencephalography. Healthy young adults (n = 26) performed a novel somato-visual paired-pulse oddball paradigm, in which attention was directed towards or away from paired-pulse stimulation of the left median nerve. We observed a robust evoked (i.e., phase-locked) somatosensory response in the time domain, and three stereotyped oscillatory responses in the time-frequency domain including an early theta response (4-8 Hz), and later alpha (8-14 Hz) and beta (20-26 Hz) responses across attentional states. The amplitudes of the evoked response and the theta and beta oscillations were gated for the second stimulus, however, only the gating of the oscillatory responses was altered by attention. Specifically, directing attention to the somatosensory domain enhanced SG of the early theta response, while reducing SG of the later alpha and beta responses. Further, prefrontal alpha-band coherence with the primary somatosensory cortex was greater when attention was directed towards the somatosensory domain, supporting a frontal modulatory effect on the alpha response in primary somatosensory regions. These findings highlight the dynamic effects of attentional modulation on somatosensory processing, and the importance of considering attentional state in studies of SG.

YNIMG Journal 2020 Journal Article

Beta and gamma oscillations index cognitive interference effects across a distributed motor network

Alex I. Wiesman
Sam M. Koshy
Elizabeth Heinrichs-Graham
Tony W. Wilson

The planning and execution of an efficient motor plan is essential to everyday cognitive function, and relies on oscillatory neural responses in both the beta (14-30 Hz) and gamma (>30 Hz) bands. Such motor control requires not only the integration of salient information from the environment, but also the inhibition of irrelevant or distracting inputs that often manifest as forms of cognitive interference. While the effects of cognitive interference on motor neural dynamics has been an area of increasing interest recently, it remains unclear whether different subtypes of interference differentially impact these dynamics. We address this issue using magnetoencephalography and a novel adaptation of the Multi-Source Interference Task, wherein two common subtypes of cognitive interference are each presented in isolation, as well as simultaneously. We find evidence for the subtype-invariant indexing of cognitive interference across a widely distributed set of motor regions oscillating in the beta range, including the bilateral primary motor and posterior parietal cortices. Further, we find that superadditive effects of cognitive interference subtypes on behavior are paralleled by gamma oscillations in the contralateral premotor cortex, and determine that these gamma oscillations also predict the superadditive effects on behavior.

YNICL Journal 2020 Journal Article

Beyond the eye: Cortical differences in primary visual processing in children with cerebral palsy

Jacy R. VerMaas
Christine M. Embury
Rashelle M. Hoffman
Michael P. Trevarrow
Tony W. Wilson
Max J. Kurz

Despite the growing clinical recognition of visual impairments among people with cerebral palsy (CP), very few studies have evaluated the neurophysiology of the visual circuitry. To this end, the primary aim of this investigation was to use magnetoencephalography and beamforming methods to image the relative change in the alpha-beta and gamma occipital cortical oscillations induced by a spatial grating stimulus (e.g., visual contrast) that was viewed by a cohort of children with CP and typically-developing (TD) children. Our results showed that the high-contrast, visual gratings stimuli induced a decrease in alpha-beta (10 - 20 Hz) activity, and an increase in both low (40 - 56 Hz) and high (60 - 72 Hz) gamma oscillations in the occipital cortices. Compared with the TD children, the strength of the frequency specific cortical oscillations were significantly weaker in the children with CP, suggesting that they had deficient processing of the contrast stimulus. Although CP is largely perceived as a musculoskeletal centric disorder, our results fuel the growing impression that there may also be prominent visual processing deficiencies. These visual processing deficits likely impact the ability to perceive visual changes in the environment.

YNIMG Journal 2020 Journal Article

Development and sex modulate visuospatial oscillatory dynamics in typically-developing children and adolescents

Abraham D. Killanin
Alex I. Wiesman
Elizabeth Heinrichs-Graham
Boman R. Groff
Michaela R. Frenzel
Jacob A. Eastman
Yu-Ping Wang
Vince D. Calhoun

Visuospatial processing is a cognitive function that is critical to navigating one's surroundings and begins to develop during infancy. Extensive research has examined visuospatial processing in adults, but far less work has investigated how visuospatial processing and the underlying neurophysiology changes from childhood to early adolescence, which is a critical period of human development that is marked by the onset of puberty. In the current study, we examined behavioral performance and the oscillatory dynamics serving visuospatial processing using magnetoencephalography (MEG) in a cohort of 70 children and young adolescents aged 8–15 years. All participants performed a visuospatial processing task during MEG, and the resulting oscillatory responses were imaged using a beamformer and probed for developmental and sex-related differences. Our findings indicated that reaction time on the task was negatively correlated with age, and that the amplitude of theta oscillations in the medial occipital cortices increased with age. Significant sex-by-age interactions were also detected, with female participants exhibiting increased theta oscillatory activity in the right prefrontal cortex with increasing age, while male participants exhibited theta increases in the left parietal lobe/left precuneus and left supplementary motor area with increasing age. These data indicate that different nodes of the visuospatial processing network develop earlier in males compared to females (and vice versa) in this age range, which may have major implications for the developmental trajectory of behavioral performance and executive function more generally during the transition through puberty.

YNIMG Journal 2020 Journal Article

Local cortical thickness predicts somatosensory gamma oscillations and sensory gating: A multimodal approach

Amy L. Proskovec
Rachel K. Spooner
Alex I. Wiesman
Tony W. Wilson

Two largely distinct bodies of research have demonstrated age-related alterations and disease-specific aberrations in both local gamma oscillations and patterns of cortical thickness. However, seldom has the relationship between gamma activity and cortical thickness been investigated. Herein, we combine the spatiotemporal precision of magnetoencephalography (MEG) with high-resolution magnetic resonance imaging and surface-based morphometry to characterize the relationships between somatosensory gamma oscillations and the thickness of the cortical tissue generating the oscillations in 94 healthy adults (age range: 22–72). Specifically, a series of regressions were computed to assess the relationships between thickness of the primary somatosensory cortex (S1), S1 gamma response power, peak gamma frequency, and somatosensory gating of identical stimuli. Our results indicated that increased S1 thickness significantly predicted greater S1 gamma response power, reduced peak gamma frequency, and improved somatosensory gating. Furthermore, peak gamma frequency significantly and partially mediated the relationship between S1 thickness and the magnitude of the S1 gamma response. Finally, advancing age significantly predicted reduced S1 thickness and decreased gating of redundant somatosensory stimuli. Notably, this is the first study to directly link somatosensory gamma oscillations to local cortical thickness. Our results demonstrate a multi-faceted relationship between structure and function, and have important implications for understanding age- and disease-related deficits in basic sensory processing and higher-order inhibitory function.

YNIMG Journal 2020 Journal Article

Methodological considerations for a better somatosensory gating paradigm: The impact of the inter-stimulus interval

Rachel K. Spooner
Jacob A. Eastman
Alex I. Wiesman
Tony W. Wilson

Sensory gating (SG) is a neurophysiological phenomenon whereby the response to the second stimulus in a repetitive pair is attenuated. This filtering of irrelevant or redundant information is thought to preserve neural resources for more behaviorally-relevant stimuli and thereby reflect the functional inhibition of sensory input. Developing a SG paradigm in which optimal suppression of sensory input is achieved requires investigators to consider numerous parameters such as stimulus intensity, time between stimulus pairs, and the inter-stimulus interval (ISI) within each pair. While these factors have been well defined for the interrogation of auditory gating, the precise parameters for eliciting optimal gating in the somatosensory domain are far less understood. To address this, we investigated the impact of varying the ISI within each identical pair of stimuli on gating using magnetoencephalography (MEG). Specifically, 25 healthy young adults underwent paired-pulse electrical stimulation of the median nerve with increasing ISIs between 100 and 1000 ms (in 100 ms increments). Importantly, for correspondence with previous studies of somatosensory gating, both time-domain and oscillatory neural responses to somatosensory stimulation were evaluated. Our results indicated that gating of somatosensory input was optimal (i. e. , best suppression) for trials with an ISI of 200–220 ms, as evidenced by the smallest gating ratios and through statistical modeling estimations of optimal suppression. Importantly, this was true irrespective of whether oscillatory or evoked neural activity was used to calculate SG. Interestingly, oscillatory metrics of gating calculated using peak gamma (30-75 Hz) power and frequency revealed more robust gating (i. e. , smaller ratios) than those calculated using time-domain neural responses, suggesting that high frequency oscillations may provide a more sensitive measure of SG. These findings have important implications for the development of optimal protocols and analysis pipelines to interrogate SG and inhibitory processing with a higher degree of sensitivity and accuracy.

YNIMG Journal 2020 Journal Article

Multi-spectral oscillatory dynamics serving directed and divided attention

Marie C. McCusker
Alex I. Wiesman
Mikki D. Schantell
Jacob A. Eastman
Tony W. Wilson

Attention-related amplification of neural representations of external stimuli has been well documented in the visual domain, however, research concerning the oscillatory dynamics of such directed attention is relatively sparse in humans. Specifically, it is unknown which spectrally-specific neural responses are mainly impacted by the direction and division of attention, as well as whether the effects of attention on these oscillations are spatially disparate. In this study, we use magnetoencephalography and a visual-somatosensory oddball task to investigate the whole-brain oscillatory dynamics of directed (Experiment 1; N = 26) and divided (Experiment 2; N = 34) visual attention. Sensor-level data were transformed into the time-frequency domain and significant responses from baseline were imaged using a frequency-resolved beamformer. We found that multi-spectral cortical oscillations were stronger when attention was sustained in the visual space and that these effects exhibited informative spatial distributions that differed by frequency. More specifically, we found stronger frontal theta (4–8 Hz), frontal and occipital alpha (8–14 Hz), occipital beta (16–22 Hz), and frontal gamma (74–84 Hz) responses when visual attention was sustained than when it was directed away from the visual domain. Similarly, in the divided attention condition, we observed stronger fronto-parietal theta activity and temporo-parietal alpha and beta oscillations when visual attention was sustained toward the visual stimuli than divided between the visual and somatosensory domains. Investigating how attentional gain is implemented in the human brain is essential for better understanding how this process is degraded in disease, and may provide useful targets for future therapies.

YNICL Journal 2019 Journal Article

Altered motor dynamics in type 1 diabetes modulate behavioral performance

Christine M. Embury
Elizabeth Heinrichs-Graham
Grace H. Lord
Andjela T. Drincic
Cyrus V. Desouza
Tony W. Wilson

Type 1 diabetes (T1D) has been linked to alterations in both brain structure and function. However, the neural basis of the most commonly reported neuropsychological deficit in T1D, psychomotor speed, remains severely understudied. To begin to address this, the current study focuses on the neural dynamics underlying motor control using magnetoencephalographic (MEG) imaging. Briefly, 40 young adults with T1D who were clear of common comorbidities (e.g., vascular disease, retinopathy, etc.) and a demographically-matched group of 40 controls without T1D completed an arrow-based flanker movement task during MEG. The resulting signals were examined in the time-frequency domain and imaged using a beamforming approach, and then voxel time series were extracted from peak responses to evaluate the dynamics. The resulting time series were statistically examined for group and conditional effects using a rigorous permutation testing approach. Our primary hypothesis was that participants with T1D would have altered beta and gamma oscillatory dynamics within the primary motor cortex during movement, and that these alterations would reflect compensatory processing to maintain adequate performance. Our results indicated that the group with T1D had a significantly stronger post-movement beta rebound (PMBR) contralateral to movement compared to controls, and a smaller neural flanker effect (i.e., difference in neural activity between conditions). In addition, a significant group-by-condition interaction was observed in the ipsilateral beta event-related desynchronization (bERD) and the ipsilateral PMBR. We also examined the relationship between oscillatory motor response amplitude and reaction time, finding a differential effect of the driving oscillatory responses on behavioral performance by group. Overall, our findings suggest compensatory activity in the motor cortices is detectable early in the disease in a relatively healthy sample of adults with T1D. Future studies are needed to examine how these subtle effects on neural activity in young, otherwise healthy patients affect outcomes in aging.

YNICL Journal 2019 Journal Article

Children with cerebral palsy display altered neural oscillations within the visual MT/V5 cortices

Jacy R. VerMaas
James E. Gehringer
Tony W. Wilson
Max J. Kurz

Cortical visual processing in visual MT/V5 is necessary for tracking movement and performing reliable visuomotor transformations. Although the role of this cortical area is well recognized, the activity of the visual MT/V5 cortical area in children with cerebral palsy (CP) has not been examined nor has its potential role in the atypical motor actions of these children been considered. This study used magnetoencephalography to image the neural activity in the motion-sensitive MT/V5 cortices of typically developing (TD) children (n = 21; mean age 14 yrs. ± 2, 12 males) and children with CP (n = 21; mean age 16 yrs. ± 4, 13 males) as they viewed a horizontally moving stimulus. Behavioral measures of visual perception were additionally assessed by having the participants press a button when the visual stimulus changed to moving in vertical direction. Our results showed that the horizontal movement of the visual stimulus evoked changes in the strength of the theta-alpha (5-10 Hz) and alpha-beta (8-20 Hz) oscillations in the visual MT/V5 area of all participants. Compared with the TD children, the children with CP had weaker alpha-beta oscillations in the visual MT/V5 cortices. In addition, the children with CP took longer to perceive a directional change of the visual stimulus and made more errors in detecting the change. Lastly, weaker alpha-beta oscillations were correlated with slower detection of the change in motion direction and less accuracy in identifying the change. This study shows that the uncharacteristic neural oscillations in the visual MT/V5 cortical area may partially account for the abnormal perceptions and motor decisions seen in children with CP.

YNIMG Journal 2019 Journal Article

Load modulates the alpha and beta oscillatory dynamics serving verbal working memory

Amy L. Proskovec
Elizabeth Heinrichs-Graham
Tony W. Wilson

A network of predominantly left-lateralized brain regions has been linked to verbal working memory (VWM) performance. However, the impact of memory load on the oscillatory dynamics serving VWM is far less understood. To further investigate this, we had 26 healthy adults perform a high-load (6 letter) and low-load (4 letter) variant of a VWM task while undergoing magnetoencephalography (MEG). MEG data were evaluated in the time-frequency domain and significant oscillatory responses spanning the encoding and maintenance phases were reconstructed using a beamformer. To determine the impact of load on the neural dynamics, the resulting images were examined using paired-samples t-tests and virtual sensor analyses. Our results indicated stronger increases in frontal theta activity in the high- relative to low-load condition during early encoding. Stronger decreases in alpha/beta activity were also observed during encoding in bilateral posterior cortices during the high-load condition, and the strength of these load effects increased as encoding progressed. During maintenance, stronger decreases in alpha activity in the left inferior frontal gyrus, middle temporal gyrus, supramarginal gyrus, and inferior parietal cortices were detected during high- relative to low-load performance, with the strength of these load effects remaining largely static throughout maintenance. Finally, stronger increases in occipital alpha activity were observed during maintenance in the high-load condition, and the strength of these effects grew stronger with time during the first half of maintenance, before dissipating during the latter half of maintenance. Notably, this was the first study to utilize a whole-brain approach to statistically evaluate the temporal dynamics of load-related oscillatory differences during encoding and maintenance processes, and our results highlight the importance of spatial, temporal, and spectral specificity in this regard.

YNIMG Journal 2019 Journal Article

Neural dynamics of verbal working memory processing in children and adolescents

Christine M. Embury
Alex I. Wiesman
Amy L. Proskovec
Mackenzie S. Mills
Elizabeth Heinrichs-Graham
Yu-Ping Wang
Vince D. Calhoun
Julia M. Stephen

Development of cognitive functions and the underlying neurophysiology is evident throughout childhood and adolescence, with higher order processes such as working memory (WM) being some of the last cognitive faculties to fully mature. Previous functional neuroimaging studies of the neurodevelopment of WM have largely focused on overall regional activity levels rather than the temporal dynamics of neural component recruitment. In this study, we used magnetoencephalography (MEG) to examine the neural dynamics of WM in a large cohort of children and adolescents who were performing a high-load, modified verbal Sternberg WM task. Consistent with previous studies in adults, our findings indicated left-lateralized activity throughout the task period, beginning in the occipital cortices and spreading anterior to include temporal and prefrontal cortices during later encoding and into maintenance. During maintenance, the occipital alpha increase that has been widely reported in adults was found to be relatively weak in this developmental sample, suggesting continuing development of this component of neural processing, which was supported by correlational analyses. Intriguingly, we also found sex-specific developmental effects in alpha responses in the right inferior frontal region during encoding and in parietal and occipital cortices during maintenance. These findings suggested a developmental divergence between males and females in the maturation of neural circuitry serving WM during the transition from childhood to adolescence.

YNIMG Journal 2019 Journal Article

The developmental trajectory of sensorimotor cortical oscillations

Michael P. Trevarrow
Max J. Kurz
Timothy J. McDermott
Alex I. Wiesman
Mackenzie S. Mills
Yu-Ping Wang
Vince D. Calhoun
Julia M. Stephen

Numerous studies of motor control have confirmed beta and gamma oscillations in the primary motor cortices during basic movements. These responses include a robust beta decrease that precedes and extends through movement onset, a transient gamma response that coincides with the movement, and a post-movement beta rebound (PMBR) response that occurs after movement offset. While the existence of these responses has been confirmed by many studies, very few studies have examined their developmental trajectory. In the current study, we utilized magnetoencephalography (MEG) to investigate age-related changes in sensorimotor cortical oscillations in a large cross-section of children and adolescents (n = 94; age range = 9 -15 years-old). All participants performed a stimulus detection task with their right finger and the resulting MEG data were examined using oscillatory analysis methods and imaged using a beamformer. Consistent with adult studies, these youth participants exhibited characteristic beta (16–24 Hz) decreases prior to and during movement, as well as PMBR responses following movement offset, and a transient gamma (74–84 Hz) response during movement execution. Our primary findings were that the strength of the PMBR increased with age, while the strength of the gamma synchronization decreased with chronological age. In addition, the strength of each motor-related oscillatory response was significantly correlated with the power of spontaneous activity in the same frequency range and same voxel. This was the case for all three oscillatory responses. In conclusion, we investigated motor-related oscillatory activity in the largest cohort of children and adolescents reported to date, and our results indicated that beta and gamma cortical oscillations continue to develop as children transition into adolescents, and that these responses may not be fully matured until young to middle adulthood.

YNIMG Journal 2019 Journal Article

The impact of age and sex on the oscillatory dynamics of visuospatial processing

Alex I. Wiesman
Tony W. Wilson

The ability to dynamically allocate neural resources within the visual space is supported by a number of spectrally-specific oscillatory responses, and such visuospatial processing has been found to decline moderately with age and differ by sex. However, the direct effects of age and sex on these oscillatory dynamics remains poorly understood. Using magnetoencephalography (MEG), structural magnetic resonance imaging, and advanced source reconstruction and statistical methods, we investigated the impact of aging and sex on behavioral performance and the underlying neural dynamics during visuospatial processing. In a large sample spanning a broad age range, we find that a number of prototypical attention and perception network components, both spectrally- and spatially-defined, exhibit complex and uniquely informative relationships with age and sex. Specifically, neural responses in the theta range (4–10 Hz) were found to covary with chronological age in prefrontal and motor cortices, signifying a possible relationship between age and cognitive control. Further, we found that beta (18–24 Hz) activity covaried with age across a large swath of the somato-motor strip, supporting previous findings of motor planning and execution deficits with increasing age. Finally, gamma-frequency (48–70 Hz) oscillations were found to exhibit robust covariance with age in superior parietal and temporo-parietal areas, indicating that the mapping of saliency in visual space is modulated by the normal aging process. Interestingly, behavioral performance and some of these oscillatory neural responses also exhibited interactions between age and sex, indicating sex differences in the evolution of the neural coding of visual perception as age increases. In particular, men were found to have stronger correlations between age and neural oscillatory responses during task performance than women in lateral occipital and superior temporal regions in the alpha band and in dorsolateral prefrontal cortex in the gamma band, while women exhibited more robust covariance between age and neural responses than men in inferior temporal and medial prefrontal cortex in the theta range.

YNIMG Journal 2019 Journal Article

The strength of alpha and gamma oscillations predicts behavioral switch costs

Amy L. Proskovec
Alex I. Wiesman
Tony W. Wilson

Cognitive flexibility is often examined using task-switch paradigms, whereby individuals either switch between tasks or repeat the same task on successive trials. The behavioral costs of switching in terms of accuracy and reaction time are well-known, but the oscillatory dynamics underlying such costs are poorly understood. Herein, we examined 25 healthy adults who performed a task-switching paradigm during magnetoencephalography (MEG). All MEG data were transformed into the time-frequency domain and significant oscillatory responses were imaged separately per condition (i. e. , switch, repeat) using a beamformer. To determine the impact of task-switching on the neural dynamics, the resulting images were examined using paired-samples t-tests. Whole-brain correlations were also computed using the switch-related difference images (switch – repeat) and the switch-related behavioral data (i. e. , switch costs). Our key results indicated stronger decreases in alpha and beta activity, and greater increases in gamma activity in nodes of the cingulo-opercular and fronto-parietal networks during switch relative to repeat trials. In addition, behavioral switch costs were positively correlated with switch-related differences in right frontal and inferior parietal alpha activity, and negatively correlated with switch effects in anterior cingulate and right temporoparietal gamma activity. In other words, participants who had a greater decrease in alpha or increase in gamma in these respective regions had smaller behavioral switch costs, which suggests that these oscillations are critical to supporting cognitive flexibility. In sum, we provide novel data linking switch effects and gamma oscillations, and employed a whole-brain approach to directly link switch-related oscillatory differences with switch-related performance differences.

YNICL Journal 2018 Journal Article

Aberrant oscillatory dynamics during somatosensory processing in HIV-infected adults

Rachel K. Spooner
Alex I. Wiesman
Mackenzie S. Mills
Jennifer O'Neill
Kevin R. Robertson
Howard S. Fox
Susan Swindells
Tony W. Wilson

While the arrival of combination antiretroviral therapy significantly decreased the prevalence of HIV-associated dementia, between 35 and 70% of all infected adults continue to develop some form of cognitive impairment. These deficits appears to affect multiple neural subsystems, but the mechanisms and extent of damage are not fully understood. In the current study, we utilized magnetoencephalography (MEG), advanced oscillatory analysis methods, and a paired-pulse somatosensory stimulation paradigm to interrogate pre-attentive inhibitory processing in 43 HIV-infected adults and 28 demographically-matched uninfected controls. MEG responses were imaged using a beamformer, and time series data were extracted from the peak voxel in grand-averaged functional brain images to quantify the dynamics of sensory gating, oscillatory power, spontaneous power, and other neural indices. We found a significantly weakened response to the second stimulation compared to the first across groups, indicating significant sensory gating irrespective of HIV-infection. Interestingly, HIV-infected participants exhibited reduced neural responses in the 20-75 Hz gamma range to each somatosensory stimulation compared to uninfected controls, and exhibited significant alterations in peak gamma frequency in response to the second stimulation. Finally, HIV-infected participants also had significantly stronger spontaneous activity in the gamma range (i.e., 20-75 Hz) during the baseline period before stimulation onset. In conclusion, while HIV-infected participants had the capacity to efficiently gate somatosensory input, their overall oscillatory responses were weaker, spontaneous baseline activity was stronger, and their response to the second stimulation had an altered peak gamma frequency. We propose that this pattern of deficits suggests dysfunction in the somatosensory cortices, which is potentially secondary to accelerated aging.

YNIMG Journal 2018 Journal Article

The peak frequency of motor-related gamma oscillations is modulated by response competition

Elizabeth Heinrichs-Graham
Joslynn M. Hoburg
Tony W. Wilson

Movement execution generally occurs in an environment with numerous distractors, and requires the selection of a motor plan from multiple possible alternatives. However, the impact of such distractors on cortical motor function during movement remains largely unknown. Previous studies have identified two movement-related oscillatory responses that are critical to motor planning and execution, and these responses include the peri-movement beta event-related desynchronization (ERD) and the movement-related gamma synchronization (MRGS). In the current study, we investigate how visual distractors cuing alternative movements modulate the beta ERD and MRGS responses. To this end, we recorded magnetoencephalography (MEG) during an arrow-based version of the Eriksen flanker task in 42 healthy adults. All MEG data were transformed in to the time-frequency domain and the beta ERD and MRGS responses were imaged using a beamformer. Virtual sensors (voxel time series) were then extracted from the peak voxels of each response for the congruent and incongruent flanker conditions separately, and these data were examined for conditional differences during the movement. Our results indicated that participants exhibited the classic “flanker effect, ” as they responded significantly slower during incongruent relative to congruent trials. Our most important MEG finding was a significant increase in the peak frequency of the MRGS in the incongruent compared to the congruent condition, with no conditional effect on response amplitude. In addition, we found significantly stronger peri-movement beta ERD responses in the ipsilateral motor cortex during incongruent compared to congruent trials, but no conditional effect on frequency. These data are the first to show that the peak frequency of the MRGS response is linked to the task parameters, and varies from trial to trial in individual participants. More globally, these data suggest that beta and gamma oscillations are modulated by visual distractors causing response competition.

YNICL Journal 2017 Journal Article

Children with cerebral palsy have altered oscillatory activity in the motor and visual cortices during a knee motor task

Max J. Kurz
Amy L. Proskovec
James E. Gehringer
Elizabeth Heinrichs-Graham
Tony W. Wilson

The neuroimaging literature on cerebral palsy (CP) has predominantly focused on identifying structural aberrations within the white matter (e.g., fiber track integrity), with very few studies examining neural activity within the key networks that serve the production of motor actions. The current investigation used high-density magnetoencephalography to begin to fill this knowledge gap by quantifying the temporal dynamics of the alpha and beta cortical oscillations in children with CP (age = 15.5 ± 3 years; GMFCS levels II-III) and typically developing (TD) children (age = 14.1 ± 3 years) during a goal-directed isometric target-matching task using the knee joint. Advanced beamforming methods were used to image the cortical oscillations during the movement planning and execution stages. Compared with the TD children, our results showed that the children with CP had stronger alpha and beta event-related desynchronization (ERD) within the primary motor cortices, premotor area, inferior parietal lobule, and inferior frontal gyrus during the motor planning stage. Differences in beta ERD amplitude extended through the motor execution stage within the supplementary motor area and premotor cortices, and a stronger alpha ERD was detected in the anterior cingulate. Interestingly, our results also indicated that alpha and beta oscillations were weaker in the children with CP within the occipital cortices and visual MT area during movement execution. These altered alpha and beta oscillations were accompanied by slower reaction times and substantial target matching errors in the children with CP. We also identified that the strength of the alpha and beta ERDs during the motor planning and execution stages were correlated with the motor performance. Lastly, our regression analyses suggested that the beta ERD within visual areas during motor execution primarily predicted the amount of motor errors. Overall, these data suggest that uncharacteristic alpha and beta oscillations within visuomotor cortical networks play a prominent role in the atypical motor actions exhibited by children with CP.

YNIMG Journal 2017 Journal Article

Spatiotemporal oscillatory dynamics of visual selective attention during a flanker task

Timothy J. McDermott
Alex I. Wiesman
Amy L. Proskovec
Elizabeth Heinrichs-Graham
Tony W. Wilson

The flanker task is a test of visual selective attention that has been widely used to probe error monitoring, response conflict, and related constructs. However, to date, few studies have focused on the selective attention component of this task and imaged the underlying oscillatory dynamics serving task performance. In this study, 21 healthy adults successfully completed an arrow-based version of the Eriksen flanker task during magnetoencephalography (MEG). All MEG data were pre-processed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach, and voxel time series were extracted from the peak responses to identify the temporal dynamics. Across both congruent and incongruent flanker conditions, our results indicated robust decreases in alpha (9–12Hz) activity in medial and lateral occipital regions, bilateral parietal cortices, and cerebellar areas during task performance. In parallel, increases in theta (3–7Hz) oscillatory activity were detected in dorsal and ventral frontal regions, and the anterior cingulate. As per conditional effects, stronger alpha responses (i. e. , greater desynchronization) were observed in parietal, occipital, and cerebellar cortices during incongruent relative to congruent trials, whereas the opposite pattern emerged for theta responses (i. e. , synchronization) in the anterior cingulate, left dorsolateral prefrontal, and ventral prefrontal cortices. Interestingly, the peak latency of theta responses in these latter brain regions was significantly correlated with reaction time, and may partially explain the amplitude difference observed between congruent and incongruent trials. Lastly, whole-brain exploratory analyses implicated the frontal eye fields, right temporoparietal junction, and premotor cortices. These findings suggest that regions of both the dorsal and ventral attention networks contribute to visual selective attention processes during incongruent trials, and that such differential processes are transient and fully completed shortly after the behavioral response in most trials.

YNICL Journal 2017 Journal Article

The cortical signature of symptom laterality in Parkinson's disease

Elizabeth Heinrichs-Graham
Pamela M. Santamaria
Howard E. Gendelman
Tony W. Wilson

Patients with Parkinson's disease (PD) often present with unilateral motor symptoms that eventually spread to the other side. This symptom lateralization is diagnostically important, as it serves to distinguish PD from other motor disorders with overlapping symptom profiles. Further, recent studies have shown that the side of symptom onset is important for prognosis, as there are differences in the rate of disease progression and the incidence of secondary symptoms between right- and left-dominant (RD, LD) patients. Physiologically, previous studies have shown asymmetrical decline in structure and metabolism throughout the basal ganglia, although connecting this directly to motor function has been difficult. To identify the neurophysiological basis of symptom laterality in PD, we recorded magnetoencephalography (MEG) during left- and right-hand movement paradigms in patients with PD who exhibited either RD or LD symptomatology. The beta oscillations serving these movements were then imaged using beamforming methods, and we extracted the time series of the peak voxel in the left and right primary motor cortices for each movement. In addition, each patient's symptom asymmetry was quantitated using the Unified Parkinson's Disease Rating Scale (UPDRS), which allowed the relationship between symptom asymmetry and neural asymmetry to be assessed. We found that LD patients had stronger beta suppression during movement, as well as greater post-movement beta rebound compared to patients with RD symptoms, independent of the hand that was moved. Interestingly, the asymmetry of beta activity during right-hand movement uniquely correlated with symptom asymmetry, such that the more LD the symptom profile, the more left-lateralized (i.e., contralateral to movement) the beta response; conversely, the more RD the symptom profile, the more right-lateralized (i.e., ipsilateral to movement) the beta response. This study is the first to directly probe the relationship between symptom asymmetry and the laterality of neural activity during movement in patients with PD, and suggests that LD patients have a fundamentally different and more "healthy" oscillatory pattern relative to RD patients.

YNIMG Journal 2016 Journal Article

Is an absolute level of cortical beta suppression required for proper movement? Magnetoencephalographic evidence from healthy aging

Elizabeth Heinrichs-Graham
Tony W. Wilson

Previous research has connected a specific pattern of beta oscillatory activity to proper motor execution, but no study to date has directly examined how resting beta levels affect motor-related beta oscillatory activity in the motor cortex. Understanding this relationship is imperative to determining the basic mechanisms of motor control, as well as the impact of pathological beta oscillations on movement execution. In the current study, we used magnetoencephalography (MEG) and a complex movement paradigm to quantify resting beta activity and movement-related beta oscillations in the context of healthy aging. We chose healthy aging as a model because preliminary evidence suggests that beta activity is elevated in older adults, and thus by examining older and younger adults we were able to naturally vary resting beta levels. To this end, healthy younger and older participants were recorded during motor performance and at rest. Using beamforming, we imaged the peri-movement beta event-related desynchronization (ERD) and extracted virtual sensors from the peak voxels, which enabled absolute and relative beta power to be assessed. Interestingly, absolute beta power during the pre-movement baseline was much stronger in older relative to younger adults, and older adults also exhibited proportionally large beta desynchronization (ERD) responses during motor planning and execution compared to younger adults. Crucially, we found a significant relationship between spontaneous (resting) beta power and beta ERD magnitude in both primary motor cortices, above and beyond the effects of age. A similar link was found between beta ERD magnitude and movement duration. These findings suggest a direct linkage between beta reduction during movement and spontaneous activity in the motor cortex, such that as spontaneous beta power increases, a greater reduction in beta activity is required to execute movement. We propose that, on an individual level, the primary motor cortices have an absolute threshold of beta power that must be reached in order to move, and that an inability to suppress beta power to this threshold results in an increase in movement duration.

YNIMG Journal 2014 Journal Article

Circadian modulation of motor-related beta oscillatory responses

Tony W. Wilson
Elizabeth Heinrichs-Graham
Katherine M. Becker

Previous electrophysiological investigations have evaluated movement-related beta (14–28Hz) oscillatory activity in healthy participants. These studies have described an abrupt decrease in beta activity that starts before movement onset, and a sharp increase in beta power that peaks after movement termination. These neural responses have been respectively termed the event-related beta desynchronization or pre-movement beta ERD, and the post-movement beta rebound (PMBR). Previous studies have shown that a variety of movement parameters and demographic factors (e. g. , age) modulate the amplitude of these oscillatory responses, and in the current study we evaluated whether the amplitudes follow a biological temporal rhythm (e. g. , circadian), as it is known that spontaneous beta levels increase from morning to afternoon in some brain areas. To this end, we used magnetoencephalography (MEG) to evaluate oscillatory activity during a right hand finger-tapping task in four participants who were recorded at three different times (09: 00, 12: 00, 16: 00) on three consecutive days (i. e. , 36 total MEG sessions). All MEG data were corrected for head motion and examined in the time–frequency domain using beamforming methods. We found a significant linear increase in beta ERD amplitude from 09: 00 to 16: 00h in the left precentral gyrus, left premotor cortices, left supplementary motor area (SMA), and right precentral and postcentral gyri. In contrast, the amplitude of the PMBR was very steady across the day in all brain regions except the left SMA, which exhibited a linear increase from morning to afternoon. Finally, beta levels during the baseline period also increased from 09: 00 to 16: 00 in most regions of the cortical sensorimotor network. These data show that both the pre-movement beta ERD and spontaneous beta levels strongly increase from morning to afternoon in the motor cortices, which may indicate that the amplitude of the beta ERD response is determined by the spontaneous beta level during the motor planning period.

YNIMG Journal 2014 Journal Article

Functional specialization within the supplementary motor area: A fNIRS study of bimanual coordination

Tony W. Wilson
Max J. Kurz
David J. Arpin

Bimanual movements can be performed by flexing and extending the target effectors (e. g. , hand muscles) in unison, or by flexing units on one side in unison with extension of the same units on the opposite side. The former movement patterns are generally referred to as in-phase or parallel, whereas the latter patterns are often termed anti-phase movements. It is well known that anti-phase patterns are unstable and tend to spontaneously transition to in-phase movements at higher repetition rates, but the mechanisms and brain regions involved are not fully understood. In the current study, we utilized functional near-infrared spectroscopy (fNIRS) to evaluate whether anterior/posterior subdivisions of the supplementary motor complex (SMA) have distinct functional roles in maintaining in-phase and anti-phase movement patterns. Twelve healthy adult participants completed a bimanual coordination task comprised of anti-phase and in-phase trials as 24-channel fNIRS data was recorded from dorsal-medial motor areas. We examined the relative concentrations of oxygenated and deoxygenated hemoglobin in the channels that were located over the anterior SMA (e. g. , pre-SMA) and the SMA proper. Our most interesting results indicated that oxygenated hemoglobin responses were greater in the anterior SMA during performance of anti-phase compared to in-phase movements. In the SMA proper, oxygenated hemoglobin responses did not differ between the two movement patterns. These data suggest that the anterior SMA is critical to programming and maintaining the less stable anti-phase movement patterns, and support the conceptual framework of an anterior-directed gradient of progressively more complex functionality in the SMA.

YNIMG Journal 2012 Journal Article

Stride-time variability and sensorimotor cortical activation during walking

Max J. Kurz
Tony W. Wilson
David J. Arpin

The time it takes between consecutive foot contacts from the same leg is referred to as the stride-time interval. Several investigations have shown that the variations that are present in the stride time intervals are linked to walking balance. In this study, functional near infrared spectroscopy (fNIRS) was utilized to evaluate whether activation in the medial sensorimotor cortices reflects the amount of variations seen in the stride-time intervals. Thirteen healthy adults (Age=23. 7±1. 4yrs.) walked forwards and backwards on a programmable treadmill. Each walking condition consisted of two sessions, with each being comprised of five alternating blocks of standing still or walking at 0. 45m/s. Activation in the medial sensorimotor cortices was measured using an fNIRS system, which consisted of a 4×4 grid of infrared optode emitter/detector pairs. The optodes were positioned on the participant's head using the International 10/20 system with Cz located beneath the center of the front two rows of optodes. We evaluated the block-wise changes in the amount of oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) in the channels that were located over the supplementary motor area, pre-central gyrus, post-central gyrus and superior parietal lobule. Throughout the experiment, a footswitch system was used to concurrently measure the amount of variation present in the stride-time intervals. Our results showed that oxyHb was greater in the supplementary motor area, pre-central gyrus, and superior parietal lobule when participants walked backwards rather than forwards, which suggests that backward walking presents more of a challenge to the nervous system as it controls the stepping pattern. Additionally, there was a significant decrease in the amount of deoxyHb present in the supplementary motor area while walking backward. Consistent with previous investigations, we noted that the amount of variability present in the stride-time intervals was greater during backward walking compared to forward walking. In addition, the amount of variation in the stride-time intervals while walking forward was positively correlated with the maximum oxyHb response found in the pre-central gyrus and supplementary motor area, which has not been previously shown. This neurobehavioral relationship supports the notion that the subtle variations found in the stride-time intervals are partly associated with processing demands by the motor cortices for regulating the forward temporal kinematics.

YNIMG Journal 2009 Journal Article

A MEG investigation of somatosensory processing in the rhesus monkey

Tony W. Wilson
Dwayne W. Godwin
Paul W. Czoty
Michael A. Nader
Robert A. Kraft
Nancy C. Buchheimer
James B. Daunais

The use of minimally and non-invasive neuroimaging methods in animal models has sharply increased over the past decade. Such studies have enhanced understanding of the neural basis of the physical signals quantified by these tools, and have addressed an assortment of fundamental and otherwise intractable questions in neurobiology. To date, these studies have almost exclusively utilized positron-emission tomography or variants of magnetic resonance based imaging. These methods provide largely indirect measures of brain activity and are strongly reliant on intact vasculature and normal blood-flow, which is known to be compromised in many clinical conditions. The current study provides the first demonstration of whole-head magnetoencephalography (MEG), a non-invasive and direct measure of neuronal activity, in a rhesus monkey, and in the process supplies the initial data on systems-level dynamics in somatosensory cortices. An adult rhesus monkey underwent three separate studies of tactile stimulation on the pad of the right second or fifth digit as whole-head MEG data were acquired. The neural generators of the primary neuromagnetic components were localized using an equivalent-current-dipole model. Second digit stimulation produced an initial cortical response peaking ∼16 ms after stimulus onset in the contralateral somatosensory cortices, with a later response at ∼96 ms in an overlapping or nearby neural area with a roughly orthogonal orientation. Stimulation of the fifth digit produced similar results, the main exception being a substantially weaker later response. We believe the 16 ms response is likely the monkey homologue of the human M50 response, as both are the earliest cortical response and localize to the contralateral primary somatosensory area. Thus, these data suggest that mechanoreception in nonhuman primates operates substantially faster than that in adult humans. More broadly, these results demonstrate that it is feasible to use current human whole-head MEG instrumentation to record neuromagnetic responses in adult rhesus monkeys. Nonhuman primate models of human disease provide the closest phylogenetic link to humans. The present, non-invasive imaging study could promote exciting translational integration of invasive animal studies and non-invasive human studies, allowing experimentally induced deficits and pharmacological treatments to be interpreted in light of resulting brain network interactions.