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Although it is well appreciated that practicing a motor task updates the associated internal model, it is still unknown how the cortical oscillations linked with the motor action change with practice. The present study investigates the short-term changes (e.g., fast motor learning) in the α- and β-event-related desynchronizations (ERD) associated with the production of a motor action. To this end, we used magnetoencephalography to identify changes in the α- and β-ERD in healthy adults after participants practiced a novel isometric ankle plantarflexion target-matching task. After practicing, the participants matched the targets faster and had improved accuracy, faster force production, and a reduced amount of variability in the force output when trying to match the target. Parallel with the behavioral results, the strength of the β-ERD across the motor-planning and execution stages was reduced after practice in the sensorimotor and occipital cortexes. No pre/postpractice changes were found in the α-ERD during motor planning or execution. Together, these outcomes suggest that fast motor learning is associated with a decrease in β-ERD power. The decreased strength likely reflects a more refined motor plan, a reduction in neural resources needed to perform the task, and/or an enhancement of the processes that are involved in the visuomotor transformations that occur before the onset of the motor action. These results may augment the development of neurologically based practice strategies and/or lead to new practice strategies that increase motor learning. NEW & NOTEWORTHY We aimed to determine the effects of practice on the movement-related cortical oscillatory activity. Following practice, we found that the performance of the ankle plantarflexion target-matching task improved and the power of the β-oscillations decreased in the sensorimotor and occipital cortexes. These novel findings capture the β-oscillatory activity changes in the sensorimotor and occipital cortexes that are coupled with behavioral changes to demonstrate the effects of motor learning.

It is now generally accepted that diabetes increases the risk for cognitive impairment, but the precise mechanisms are poorly understood. A critical problem in linking diabetes to cognitive impairment is that patients often have multiple comorbidities (e.g., obesity, hypertension) that have been independently linked to cognitive deficits. In the study reported here we focused on young adults with and without type 1 diabetes who were virtually free of such comorbidities. The two groups were matched on major health and demographic factors, and all participants completed a verbal working memory task during magnetoencephalographic brain imaging. We hypothesized that patients would have altered neural dynamics in verbal working memory processing and that these differences would directly relate to clinical disease measures. Accordingly, we found that patients had significantly stronger neural responses in the superior parietal cortices during memory encoding and significantly weaker activity in parietal-occipital regions during maintenance compared with control subjects. Moreover, disease duration and glycemic control were both significantly correlated with neural responses in various brain regions. In conclusion, young healthy adults with type 1 diabetes already have aberrant neural processing relative to their peers without diabetes, using compensatory responses to perform the task, and glucose management and duration may play a central role., (© 2018 by the American Diabetes Association.)

The oscillatory dynamics serving spatial working memory (SWM), and how such dynamics relate to performance, are poorly understood. To address these topics, the present study recruited 22 healthy adults to perform a SWM task during magnetoencephalography (MEG). The resulting MEG data were transformed into the time-frequency domain, and significant oscillatory responses were imaged using a beamformer. Voxel time series data were extracted from the cluster peaks to quantify the dynamics, while whole-brain partial correlation maps were computed to identify regions where oscillatory strength varied with accuracy on the SWM task. The results indicated transient theta oscillations in spatially distinct subregions of the prefrontal cortices at the onset of encoding and maintenance, which may underlie selection of goal-relevant information. Additionally, strong and persistent decreases in alpha and beta oscillations were observed throughout encoding and maintenance in parietal, temporal, and occipital regions, which could serve sustained attention and maintenance processes during SWM performance. The neuro-behavioral correlations revealed that beta activity within left dorsolateral prefrontal control regions and bilateral superior temporal integration regions was negatively correlated with SWM accuracy. Notably, this is the first study to employ a whole-brain approach to significantly link neural oscillations to behavioral performance in the context of SWM.

Transcranial direct-current stimulation (tDCS) is now a widely used method for modulating the human brain, but the resulting physiological effects are not understood. Recent studies have combined magnetoencephalography (MEG) with simultaneous tDCS to evaluate online changes in occipital alpha and gamma oscillations, but no study to date has quantified the offline (i.e., after tDCS) alterations in these responses. Thirty-five healthy adults received active or sham anodal tDCS to the occipital cortices, and then completed a visual stimulation paradigm during MEG that is known to elicit robust gamma and alpha oscillations. The resulting MEG data were imaged and peak voxel time series were extracted to evaluate tDCS effects. We found that tDCS to the occipital increased the amplitude of local gamma oscillations, and basal alpha levels during the baseline. tDCS was also associated with network-level effects, including increased gamma oscillations in the prefrontal cortex, parietal, and other visual attention regions. Finally, although tDCS did not modulate peak gamma frequency, this variable was inversely correlated with gamma amplitude, which is consistent with a GABA-gamma link. In conclusion, tDCS alters gamma oscillations and basal alpha levels. The net offline effects on gamma activity are consistent with the view that anodal tDCS decreases local GABA.

The ability to reorient attention within the visual field is central to daily functioning, and numerous fMRI studies have shown that the dorsal and ventral attention networks (DAN, VAN) are critical to such processes. However, despite the instantaneous nature of attentional shifts, the dynamics of oscillatory activity serving attentional reorientation remain poorly characterized. In this study, we utilized magnetoencephalography (MEG) and a Posner task to probe the dynamics of attentional reorienting in 29 healthy adults. MEG data were transformed into the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Voxel time series were then extracted from peak voxels in the functional beamformer images. These time series were used to quantify the dynamics of attentional reorienting, and to compute dynamic functional connectivity. Our results indicated strong increases in theta and decreases in alpha and beta activity across many nodes in the DAN and VAN. Interestingly, theta responses were generally stronger during trials that required attentional reorienting relative to those that did not, while alpha and beta oscillations were more dynamic, with many regions exhibiting significantly stronger responses during non-reorienting trials initially, and the opposite pattern during later processing. Finally, stronger functional connectivity was found following target presentation (575-700 ms) between bilateral superior parietal lobules during attentional reorienting. In sum, these data show that visual attention is served by multiple cortical regions within the DAN and VAN, and that attentional reorienting processes are often associated with spectrally-specific oscillations that have largely distinct spatiotemporal dynamics., (© 2018 Wiley Periodicals, Inc.)

Numerous studies connect beta oscillations in the motor cortices to volitional movement, and beta is known to be aberrant in multiple movement disorders. However, the dynamic interplay between these beta oscillations, motor performance, and spontaneous beta power (e.g., during rest) in the motor cortices remains unknown. This study utilized magnetoencephalography (MEG) to investigate these three parameters and their lifespan trajectory in 57 healthy participants aged 9-75 years old. Movement-related beta activity was imaged using a beamforming approach, and voxel time series data were extracted from the peak voxels in the primary motor cortices. Our results indicated that spontaneous beta power during rest followed a quadratic lifespan trajectory, while movement-related beta oscillations linearly increased with age. Follow-on analyses showed that spontaneous beta power and the beta minima during movement, together, significantly predicted task performance above and beyond the effects of age. These data are the first to show lifespan trajectories among measures of beta activity in the motor cortices, and suggest that the healthy brain compensates for age-related increases in spontaneous beta activity by increasing the strength of beta oscillations within the motor cortices which, when successful, enables normal motor performance into later life., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Posttraumatic stress disorder (PTSD) is a major psychiatric disorder that is prevalent in combat veterans. Previous neuroimaging studies have found elevated amygdala activity in PTSD in response to threatening stimuli, but previous work has lacked the temporal specificity to study fast bottom-up fear responses involving the amygdala. Forty-four combat veterans, 28 with PTSD and 16 without, completed psychological testing and then a face-processing task during magnetoencephalography (MEG). The resulting MEG data were pre-processed, transformed into the time-frequency domain, and then imaged using a beamforming approach. We found that veterans with PTSD exhibited significantly stronger oscillatory activity from 50 to 450 ms in the left amygdala compared to veterans without PTSD while processing threatening faces. This group difference was not present while viewing neutral faces. The current study shows that amygdala hyperactivity in response to threatening cues begins quickly in PTSD, which makes theoretical sense as an adaptive bottom-up fear response., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Recent research indicates the relative benefits of computerized attention control treatment (ACT) and attention bias modification treatment (ABMT) for posttraumatic stress disorder (PTSD); however, neural changes underlying these therapeutic effects remain unknown. This study examines how these two types of attention training modulate neurological dysfunction in veterans with PTSD. A community sample of 46 combat veterans with PTSD participated in a randomized double-blinded clinical trial of ACT versus ABMT and 32 of those veterans also agreed to undergo resting-state magnetoencephalography (MEG) recordings. Twenty-four veterans completed psychological and MEG assessments at pre- and post-training to evaluate treatment effects. MEG data were imaged using an advanced Bayesian reconstruction method and examined using statistical parametric mapping. In this report, we focus on the neural correlates and the differential treatment effects observed using MEG; the results of the full clinical trial have been described elsewhere. Our results indicated that ACT modulated occipital and ABMT modulated medial temporal activity more strongly than the comparative treatment. PTSD symptoms decreased significantly from pre- to post-test. These initial neurophysiological outcome data suggest that ACT modulates visual pathways, while ABMT modulates threat-processing regions, but that both are associated with normalizing aberrant neural activity in veterans with PTSD., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The dynamic allocation of neural resources to discrete features within a visual scene enables us to react quickly and accurately to salient environmental circumstances. A network of bilateral cortical regions is known to subserve such visuospatial attention functions; however the oscillatory and functional connectivity dynamics of information coding within this network are not fully understood. Particularly, the coding of information within prototypical attention-network hubs and the subsecond functional connections formed between these hubs have not been adequately characterized. Herein, we use the precise temporal resolution of magnetoencephalography (MEG) to define spectrally specific functional nodes and connections that underlie the deployment of attention in visual space. Twenty-three healthy young adults completed a visuospatial discrimination task designed to elicit multispectral activity in visual cortex during MEG, and the resulting data were preprocessed and reconstructed in the time-frequency domain. Oscillatory responses were projected to the cortical surface using a beamformer, and time series were extracted from peak voxels to examine their temporal evolution. Dynamic functional connectivity was then computed between nodes within each frequency band of interest. We find that visual attention network nodes are defined functionally by oscillatory frequency, that the allocation of attention to the visual space dynamically modulates functional connectivity between these regions on a millisecond timescale, and that these modulations significantly correlate with performance on a spatial discrimination task. We conclude that functional hubs underlying visuospatial attention are segregated not only anatomically but also by oscillatory frequency, and importantly that these oscillatory signatures promote dynamic communication between these hubs. Hum Brain Mapp 38:5128-5140, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Shortly after movement termination, there is a strong increase or resynchronization of the beta rhythm (15-30 Hz) across the sensorimotor network of humans, known as the post-movement beta rebound (PMBR). This response has been associated with active inhibition of the motor network following the completion of a movement, sensory afferentation of the sensorimotor cortices, and other functions. However, studies that have directly probed the role of the PMBR in movement execution have reported mixed results, possibly due to differences in the amount of total motor output and/or movement complexity. Herein, we used magnetoencephalography during an isometric-force control task to examine whether alterations in the timing of motor termination demands modulate the PMBR, independent of differences in the motor output itself. Briefly, we manipulated the amount of time between the cue to initiate the force and the cue to terminate the force, such that participants were either forced to terminate quickly or slowly. We also performed a control experiment to test for temporal predictability effects. Our results indicated that the PMBR was stronger immediately following movement termination in the prefrontal cortices, supplementary motor area, left postcentral gyrus, paracentral lobule, and parietal cortex when participants were forced to terminate more quickly. These results were not attributable to the temporal predictability of each condition. These findings support the notion that the PMBR response at least partially serves motor inhibition, independent of the parameters within the motor output itself, and that particular nodes of the motor network may be differentially modulated by motor termination.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Multiple sclerosis (MS) is a demyelinating disease that results in a broad array of symptoms, including impaired motor performance. How such demyelination of fibers affects the inherent neurophysiological activity in motor circuits, however, remains largely unknown. Potentially, the movement errors associated with MS may be due to imperfections in the internal model used to make predictions of the motor output that will meet the task demands. Prior magnetoencephalographic (MEG) and electroencephalographic brain imaging experiments have established that the beta (15-30 Hz) oscillatory activity in the sensorimotor cortices is related to the control of movement. Specifically, it has been suggested that the strength of the post-movement beta rebound may indicate the certainty of the internal model. In this study, we used MEG to evaluate the neural oscillatory activity in the sensorimotor cortices of individuals with MS and healthy individuals during a goal-directed isometric knee force task. Our results showed no difference between the individuals with MS and healthy individuals in the beta activity during the planning and execution stages of movement. However, we did find that individuals with MS exhibited a weaker post-movement beta rebound in the pre/postcentral gyri relative to healthy controls. Additionally, we found that the behavioral performance of individuals with MS was aberrant, and related to the strength of the post-movement beta rebound. These results suggest that the internal model may be faulty in individuals with MS. Hum Brain Mapp 38:4009-4018, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

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.

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric condition that is common in veterans returning from combat operations. While the symptoms of PTSD have been extensively characterized, the neural mechanisms that underlie PTSD are only vaguely understood. In this study, we examined the neurophysiology of PTSD using magnetoencephalography (MEG) in a sample of veterans with and without PTSD. Our primary hypothesis was that veterans with PTSD would exhibit aberrant activity across multiple brain networks, especially those involving medial temporal and frontal regions. To this end, we examined a total of 51 USA combat veterans with a battery of clinical interviews and tests. Thirty-one of the combat veterans met diagnostic criteria for PTSD and the remaining 20 did not have PTSD. All participants then underwent high-density MEG during an eyes-closed resting-state task, and the resulting data were analyzed using a Bayesian image reconstruction method. Our results indicated that veterans with PTSD had significantly stronger neural activity in prefrontal, sensorimotor and temporal areas compared to those without PTSD. Veterans with PTSD also exhibited significantly stronger activity in the bilateral amygdalae, parahippocampal and hippocampal regions. Conversely, healthy veterans had stronger neural activity in the bilateral occipital cortices relative to veterans with PTSD. In conclusion, these data suggest that veterans with PTSD exhibit aberrant neural activation in multiple cortical areas, as well as medial temporal structures implicated in affective processing.

A potential therapeutic role for immune transformation in Parkinson's disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson's disease patients. Both Parkinson's disease patients and controls were monitored for 2 months for baseline profiling. Parkinson's disease patients were then randomized into two equal groups to self-administer placebo (saline) or sargramostim subcutaneously at 6 μg/kg/day for 56 days. Adverse events for the sargramostim and placebo groups were 100% (10/10) and 80% (8/10), respectively. These included injection site reactions, increased total white cell counts, and upper extremity bone pain. One urticarial and one vasculitis reaction were found to be drug and benzyl alcohol related, respectively. An additional patient with a history of cerebrovascular disease suffered a stroke on study. Unified Parkinson's disease rating scale, Part III scores in the sargramostim group showed modest improvement after 6 and 8 weeks of treatment when compared with placebo. This paralleled improved magnetoencephalography-recorded cortical motor activities and Treg numbers and function compared with pretreated Parkinson's disease patients and non-Parkinsonian controls. Peripheral Treg transformation was linked to serum tryptophan metabolites, including L-kynurenine, quinolinic acid, and serotonin. These data offer a potential paradigm shift in modulating immune responses for potential therapeutic gain for Parkinson's disease. Confirmation of these early study results requires larger numbers of enrolled patients and further clinical investigation.

Transcranial direct-current stimulation (tDCS) is a noninvasive neuromodulatory method that involves delivering low amplitude, direct current to specific regions of the brain. While a wealth of literature shows changes in behavior and cognition following tDCS administration, the underlying neuronal mechanisms remain largely unknown. Neuroimaging studies have generally used fMRI and shown only limited consensus to date, while the few electrophysiological studies have reported mostly null or counterintuitive findings. The goal of the current investigation was to quantify tDCS-induced alterations in the oscillatory dynamics of visual processing. To this end, we performed either active or sham tDCS using an occipital-frontal electrode configuration, and then recorded magnetoencephalography (MEG) offline during a visual entrainment task. Significant oscillatory responses were imaged in the time-frequency domain using beamforming, and the effects of tDCS on absolute and relative power were assessed. The results indicated significantly increased basal alpha levels in the occipital cortex following anodal tDCS, as well as reduced occipital synchronization at the second harmonic of the stimulus-flicker frequency relative to sham stimulation. In addition, we found reduced power in brain regions near the cathode (e.g., right inferior frontal gyrus [IFG]) following active tDCS, which was absent in the sham group. Taken together, these results suggest that anodal tDCS of the occipital cortices differentially modulates spontaneous and induced activity, and may interfere with the entrainment of neuronal populations by a visual-flicker stimulus. These findings also demonstrate the importance of electrode configuration on whole-brain dynamics, and highlight the deceptively complicated nature of tDCS in the context of neurophysiology., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Key Points: Sensory gating is important for preventing excessive environmental stimulation from overloading neural resources. Gating in the human somatosensory cortices is a critically understudied topic, particularly in the lower extremities. We utilize the unique capabilities of magnetoencephalographic neuroimaging to quantify the normative neural population responses and dynamic functional connectivity of somatosensory gating in the lower extremities of healthy human participants. We show that somatosensory processing is subserved by a robust gating effect in the oscillatory domain, as well as a dynamic effect on interhemispheric functional connectivity between primary sensory cortices. These results provide novel insight into the dynamic neural mechanisms that underlie the processing of somatosensory information in the human brain, and will be vital in better understanding the neural responses that are aberrant in gait-related neurological disorders (e.g. cerebral palsy)., Abstract: Sensory gating (SG) is a phenomenon in which neuronal responses to subsequent similar stimuli are weaker, and is considered to be an important mechanism for preventing excessive environmental stimulation from overloading shared neural resources. Although gating has been demonstrated in multiple sensory systems, the neural dynamics and developmental trajectory underlying SG remain poorly understood. In the present study, we adopt a data-driven approach to map the spectrotemporal amplitude and functional connectivity (FC) dynamics that support gating in the somatosensory system (somato-SG) in healthy children and adolescents using magnetoencephalography (MEG). These data underwent time-frequency decomposition and the significant signal changes were imaged using a beamformer. Voxel time series were then extracted from the peak voxels and these signals were examined in the time and time-frequency domains, and then subjected to dynamic FC analysis. The results obtained indicate a significant decrease in the amplitude of the neural response following the second stimulation relative to the first in the primary somatosensory cortex (SI). A significant decrease in response latency was also found between stimulations, and each stimulation induced a sharp decrease in FC between somatosensory cortical areas. Furthermore, there were no significant correlations between somato-SG metrics and age. We conclude that somato-SG can be observed in SI in both the time and oscillatory domains, with rich dynamics and alterations in inter-hemispheric FC, and that this phenomenon has already matured by early childhood. A better understanding of these dynamics may provide insight to the numerous psychiatric and neurologic conditions that have been associated with aberrant SG across multiple modalities., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

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.

Impairments in working memory are among the most prevalent features of HIV-associated neurocognitive disorders (HAND), yet their origins are unknown, with some studies arguing that encoding operations are disturbed and others supporting deficits in memory maintenance. The current investigation directly addresses this issue by using a dynamic mapping approach to identify when and where processing in working memory circuits degrades. HIV-infected older adults and a demographically-matched group of uninfected controls performed a verbal working memory task during magnetoencephalography (MEG). Significant oscillatory neural responses were imaged using a beamforming approach to illuminate the spatiotemporal dynamics of neuronal activity. HIV-infected patients were significantly less accurate on the working memory task and their neuronal dynamics indicated that encoding operations were preserved, while memory maintenance processes were abnormal. Specifically, no group differences were detected during the encoding period, yet dysfunction in occipital, fronto-temporal, hippocampal, and cerebellar cortices emerged during memory maintenance. In addition, task performance in the controls covaried with occipital alpha synchronization and activity in right prefrontal cortices. In conclusion, working memory impairments are common and significantly impact the daily functioning and independence of HIV-infected patients. These impairments likely reflect deficits in the maintenance of memory representations, not failures to adequately encode stimuli., Competing Interests: Drs. Wilson, Heinrichs-Graham and Fox report no disclosures. Ms. Proskovec and Ms. O’Neill report no disclosures. Dr. Robertson serves as a consultant for Abbott and GlaxoSmithKline. Dr. Swindells reports receiving grant support to the University of Nebraska Medical Center from GlaxoSmithKline, Merck, and Pfizer for research unrelated to this study.

Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory (WM). Recent studies suggest that attention training reduces PTSD symptomatology, but the underlying neural mechanisms are unknown. We used high-density magnetoencephalography (MEG) to evaluate whether attention training modulates brain regions serving WM processing in PTSD. Fourteen veterans with PTSD completed a WM task during a 306-sensor MEG recording before and after 8 sessions of attention training treatment. A matched comparison sample of 12 combat-exposed veterans without PTSD completed the same WM task during a single MEG session. To identify the spatiotemporal dynamics, each group's data were transformed into the time-frequency domain, and significant oscillatory brain responses were imaged using a beamforming approach. All participants exhibited activity in left hemispheric language areas consistent with a verbal WM task. Additionally, veterans with PTSD and combat-exposed healthy controls each exhibited oscillatory responses in right hemispheric homologue regions (e.g., right Broca's area); however, these responses were in opposite directions. Group differences in oscillatory activity emerged in the theta band (4-8 Hz) during encoding and in the alpha band (9-12 Hz) during maintenance and were significant in right prefrontal and right supramarginal and inferior parietal regions. Importantly, following attention training, these significant group differences were reduced or eliminated. This study provides initial evidence that attention training improves aberrant neural activity in brain networks serving WM processing.

We examined two groups of combat veterans, one with post-traumatic stress disorder (PTSD) (n = 27) and another without PTSD (n = 16), using an emotional Stroop task (EST) with word lists matched across a series of lexical variables (e.g. length, frequency, neighbourhood size, etc.). Participants with PTSD exhibited a strong EST effect (longer colour-naming latencies for combat-relevant words as compared to neutral words). Veterans without PTSD produced no such effect, t < .918, p > .37. Participants with PTSD then completed eight sessions of attention training (Attention Control Training or Attention Bias Modification Training) with a dot-probe task utilising threatening and neutral faces. After training, participants-especially those undergoing Attention Control Training-no longer produced longer colour-naming latencies for combat-related words as compared to other words, indicating normalised attention allocation processes after treatment.

There is currently a void in the scientific literature on the cortical beta oscillatory activity that is associated with the production of leg motor actions. In addition, we have limited data on how these cortical oscillations may progressively change as a function of development. This study began to fill this vast knowledge gap by using high-density magnetoencephalography to quantify the beta cortical oscillatory activity over a cross-section of typically developing children as they performed an isometric knee target matching task. Advanced beamforming methods were used to identify the spatiotemporal changes in beta oscillatory activity during the motor planning and motor action time frames. Our results showed that a widespread beta event-related desynchronization (ERD) was present across the pre/postcentral gyri, supplementary motor area, and the parietal cortices during the motor planning stage. The strength of this beta ERD sharply diminished across this fronto-parietal network as the children initiated the isometric force needed to match the target. Rank order correlations indicated that the older children were more likely to initiate their force production sooner, took less time to match the targets, and tended to have a weaker beta ERD during the motor planning stage. Lastly, we determined that there was a relationship between the child's age and the strength of the beta ERD within the parietal cortices during isometric force production. Altogether our results suggest that there are notable maturational changes during childhood and adolescence in beta cortical oscillatory activity that are associated with the planning and execution of leg motor actions.

Purpose: This study examined the effects of stimulus type and hearing status on speech recognition and listening effort in children with normal hearing (NH) and children with mild bilateral hearing loss (MBHL) or unilateral hearing loss (UHL)., Method: Children (5-12 years of age) with NH (Experiment 1) and children (8-12 years of age) with MBHL, UHL, or NH (Experiment 2) performed consonant identification and word and sentence recognition in background noise. Percentage correct performance and verbal response time (VRT) were assessed (onset time, total duration)., Results: In general, speech recognition improved as signal-to-noise ratio (SNR) increased both for children with NH and children with MBHL or UHL. The groups did not differ on measures of VRT. Onset times were longer for incorrect than for correct responses. For correct responses only, there was a general increase in VRT with decreasing SNR., Conclusions: Findings indicate poorer sentence recognition in children with NH and MBHL or UHL as SNR decreases. VRT results suggest that greater effort was expended when processing stimuli that were incorrectly identified. Increasing VRT with decreasing SNR for correct responses also supports greater effort in poorer acoustic conditions. The absence of significant hearing status differences suggests that VRT was not differentially affected by MBHL, UHL, or NH for children in this study.

Magnetoencephalography (MEG) is a noninvasive, silent, and totally passive neurophysiological imaging method with excellent temporal resolution (∼1 ms) and good spatial precision (∼3-5 mm). In a typical experiment, MEG data are acquired as healthy controls or patients with neurologic or psychiatric disorders perform a specific cognitive task, or receive sensory stimulation. The resulting data are generally analyzed using standard electrophysiological methods, coupled with advanced image reconstruction algorithms. To date, the total number of MEG instruments and associated users is significantly smaller than comparable human neuroimaging techniques, although this is likely to change in the near future with advances in the technology. Despite this small base, MEG research has made a significant impact on several areas of translational neuroscience, largely through its unique capacity to quantify the oscillatory dynamics of activated brain circuits in humans. This review focuses on the clinical areas where MEG imaging has arguably had the greatest impact in regard to the identification of aberrant neural dynamics at the regional and network level, monitoring of disease progression, determining how efficacious pharmacologic and behavioral interventions modulate neural systems, and the development of neural markers of disease. Specifically, this review covers recent advances in understanding the abnormal neural oscillatory dynamics that underlie Parkinson's disease, autism spectrum disorders, human immunodeficiency virus (HIV)-associated neurocognitive disorders, cerebral palsy, attention-deficit hyperactivity disorder, cognitive aging, and post-traumatic stress disorder. MEG imaging has had a major impact on how clinical neuroscientists understand the brain basis of these disorders, and its translational influence is rapidly expanding with new discoveries and applications emerging continuously., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a common neurodegenerative disorder characterized primarily by motor symptoms such as bradykinesia, muscle rigidity, and resting tremor. It is now broadly accepted that these motor symptoms frequently co-occur with cognitive impairments, with deficits in working memory and attention being among the most common cognitive sequelae associated with PD. While these cognitive impairments are now recognized, the underlying neural dynamics and precise regions involved remain largely unknown. To this end, we examined the oscillatory dynamics and interregional functional connectivity that serve working memory processing in a group of unmedicated adults with PD and a matched group without PD. Each participant completed a high-load, Sternberg-type working memory task during magnetoencephalography (MEG), and we focused on the encoding and maintenance phases. All data were transformed into the time-frequency domain and significant oscillatory activity was imaged using a beamforming approach. Phase-coherence (connectivity) was also computed among the brain subregions exhibiting the strongest responses. Our most important findings were that unmedicated patients with PD had significantly diminished working memory performance (i.e., accuracy), and reduced functional connectivity between left inferior frontal cortices and left supramarginal-superior temporal cortices compared to participants without PD during the encoding phase of working memory processing. We conclude that patients with PD have reduced neural interactions between left prefrontal executive circuits and temporary verbal storage centers in the left supramarginal/superior temporal cortices during the stimulus encoding phase, which may underlie their diminished working memory function. Hum Brain Mapp 37:3224-3235, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In humans, there is a strong beta (15-30 Hz) event-related desynchronization (ERD) that begins before movement, which has been tentatively linked to motor planning operations. The dynamics of this response are strongly modulated by whether a pending movement is cued and the inherent parameters of the cue. However, previous studies have focused on the information content of cues and not on parameters such as the timing of the cue relative to other events. Variations in such timing are critical, as they directly impact the amount of time that participants have to plan pending movements. In this study, participants performed finger-tapping sequences during magnetoencephalography, and we manipulated the amount of time (i.e., "long" vs. "short") between the presentation of the to-be-executed sequence and the cue to initiate the sequence. We found that the beta ERD was stronger immediately after the cue to move in the contralateral postcentral gyrus and bilateral parietal cortices during the short compared with long planning time condition. During movement execution, the beta ERD was stronger in the premotor cortex and the SMA in the short relative to long condition. Finally, peak latency in the SMA significantly correlated with RT, such that the closer the peak beta ERD was to the cue to move, the quicker the participant responded. The results of this study establish that peri-movement beta ERD activity across the cortical motor circuit is highly sensitive to cue-related temporal factors, with a direct link to motor performance.

Background: Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory. In this study, we examined the neural dynamics of working memory processing in veterans with PTSD and a matched healthy control sample using magnetoencephalography (MEG)., Methods: Our sample of recent combat veterans with PTSD and demographically matched participants without PTSD completed a working memory task during a 306-sensor MEG recording. The MEG data were preprocessed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach to identify spatiotemporal dynamics., Results: Fifty-one men were included in our analyses: 27 combat veterans with PTSD and 24 controls. Across all participants, a dynamic wave of neural activity spread from posterior visual cortices to left frontotemporal regions during encoding, consistent with a verbal working memory task, and was sustained throughout maintenance. Differences related to PTSD emerged during early encoding, with patients exhibiting stronger α oscillatory responses than controls in the right inferior frontal gyrus (IFG). Differences spread to the right supramarginal and temporal cortices during later encoding where, along with the right IFG, they persisted throughout the maintenance period., Limitations: This study focused on men with combat-related PTSD using a verbal working memory task. Future studies should evaluate women and the impact of various traumatic experiences using diverse tasks., Conclusion: Posttraumatic stress disorder is associated with neurophysiological abnormalities during working memory encoding and maintenance. Veterans with PTSD engaged a bilateral network, including the inferior prefrontal cortices and supramarginal gyri. Right hemispheric neural activity likely reflects compensatory processing, as veterans with PTSD work to maintain accurate performance despite known cognitive deficits associated with the disorder.

Working memory is central to the execution of many daily functions and is typically divided into three phases: encoding, maintenance, and retrieval. While working memory performance has been repeatedly shown to decline with age, less is known regarding the underlying neural processes. We examined age-related differences in the neural dynamics that serve working memory by recording high-density magnetoencephalography (MEG) in younger and older adults while they performed a modified, high-load Sternberg working memory task with letters as stimuli. MEG data were evaluated in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. A hierarchical regression was performed to investigate whether age moderated the relationship between oscillatory activity and accuracy on the working memory task. Our results indicated that the spatiotemporal dynamics of oscillatory activity in language-related areas of the left fronto-temporal cortices were similar across groups. Age-related differences emerged during early encoding in the right-hemispheric homologue of Wernicke's area. Slightly later, group differences emerged in the homologue of Broca's area and these persisted throughout memory maintenance. Additionally, occipital alpha activity during maintenance was stronger, occurred earlier, and involved more cortical tissue in older adults. Finally, age significantly moderated the relationship between accuracy and neural activity in the prefrontal cortices. In younger adults, as prefrontal activity decreased, accuracy tended to increase. Our results are consistent with predictions of the compensation-related utilization of neural circuits hypothesis (CRUNCH). Such differences in the oscillatory dynamics could reflect compensatory mechanisms, which would aid working memory performance in older age. Hum Brain Mapp 37:2348-2361, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Cortical oscillatory dynamics are known to be critical for human movement, although their functional significance remains unclear. In particular, there is a strong beta (15-30 Hz) desynchronization that begins before movement onset and continues during movement, before rebounding after movement termination. Several studies have connected this response to motor planning and/or movement selection operations, but to date such studies have examined only the early aspects of the response (i.e., before movement) and a limited number of parameters. In this study, we used magnetoencephalography (MEG) and a novel motor sequence paradigm to probe how motor plan complexity modulates peri-movement beta oscillations, and connectivity within activated circuits. We also examined the dynamics by imaging beta activity before and during movement execution and extracting virtual sensors from key regions. We found stronger beta desynchronization during complex relative to simple sequences in the right parietal and left dorsolateral prefrontal cortex (DLPFC) during movement execution. There was also an increase in functional connectivity between the left DLPFC and right parietal shortly after movement onset during complex but not simple sequences, which produced a significant conditional effect (i.e., complex > simple) that was not attributable to differences in response amplitude. This study is the first to demonstrate that complexity modulates the dynamics of the peri-movement beta ERD, which provides crucial new data on the functional role of this well-known oscillatory motor response. These data further suggest that execution of complex motor behavior may recruit key regions of the fronto-parietal network, in addition to traditional sensorimotor regions., (© 2015 Wiley Periodicals, Inc.)

Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder prevalent in combat veterans. Previous neuroimaging studies have demonstrated that patients with PTSD exhibit abnormal responses to non-threatening visual and auditory stimuli, but have not examined somatosensory processing. Thirty male combat veterans, 16 with PTSD and 14 without, completed a tactile stimulation task during a 306-sensor magnetoencephalography (MEG) recording. Significant oscillatory neural responses were imaged using a beamforming approach. Participants also completed clinical assessments of PTSD, combat exposure, and depression. We found that veterans with PTSD exhibited significantly reduced activity during early (0-125 ms) tactile processing compared with combat controls. Specifically, veterans with PTSD had weaker activity in the left postcentral gyrus, left superior parietal area, and right prefrontal cortex in response to nonthreatening tactile stimulation relative to veterans without PTSD. The magnitude of activity in these brain regions was inversely correlated with symptom severity, indicating that those with the most severe PTSD had the most abnormal neural responses. Our findings are consistent with a resource allocation view of perceptual processing in PTSD, which directs attention away from nonthreatening sensory information., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Many electrophysiology studies have examined neural oscillatory activity during the encoding, maintenance, and/or retrieval phases of various working memory tasks. Together, these studies have helped illuminate the underlying neural dynamics, although much remains to be discovered and some findings have not replicated in subsequent work. In this study, we examined the oscillatory dynamics that serve visual working memory operations using high-density magnetoencephalography (MEG) and advanced time-frequency and beamforming methodology. Specifically, we recorded healthy adults while they performed a high-load, Sternberg-type working memory task, and focused on the encoding and maintenance phases. We found significant 9-16 Hz desynchronizations in the bilateral occipital cortices, left dorsolateral prefrontal cortex (DLPFC), and left superior temporal areas throughout the encoding phase. Our analysis of the dynamics showed that the left DLPFC and superior temporal desynchronization became stronger as a function of time during the encoding period, and was sustained throughout most of the maintenance phase until sharply decreasing in the milliseconds preceding retrieval. In contrast, desynchronization in occipital areas became weaker as a function of time during encoding and eventually evolved into a strong synchronization during the maintenance period, consistent with previous studies. These results provide clear evidence of dynamic network-level processes during the encoding and maintenance phases of working memory, and support the notion of a dynamic pattern of functionally-discrete subprocesses within each working memory phase. The presence of such dynamic oscillatory networks may be a potential source of inconsistent findings in this literature, as neural activity within these networks changes dramatically with time., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The noted disruption of thalamocortical connections and abnormalities in tactile sensory function has resulted in a new definition of cerebral palsy (CP) that recognizes the sensorimotor integration process as central to the motor impairments seen in these children. Despite this updated definition, the connection between a child's motor impairments and somatosensory processing remains almost entirely unknown. In this investigation, we explored the relationship between the magnitude of neural activity within the somatosensory cortices, the strength of the ankle plantarflexors, and the gait spatiotemporal kinematics of a group of children with CP and a typically developing matched cohort. Our results revealed that the magnitude of somatosensory cortical activity in children with CP had a strong positive relationship with the ankle strength, step length, and walking speed. These results suggest that stronger activity within the somatosensory cortices in response to foot somatosensations was related to enhanced ankle plantarflexor strength and improved mobility in the children with CP. These results provide further support for the notion that children with CP exhibit, not only musculoskeletal deficits, but also somatosensory deficits that potentially contribute to their overall functional mobility and strength limitations., (Copyright © 2015 the American Physiological Society.)

Combination antiretroviral therapy transformed human immunodeficiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker., (© 2014 Wiley Periodicals, Inc.)

Previous electrophysiological investigations have evaluated movement-related beta (14-28 Hz) 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 16:00 h 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: This investigation used magnetoencephalography (MEG) to examine the neural oscillatory responses of the sensorimotor cortices during the motor planning and movement execution stages of children with typical development and children with cerebral palsy (CP)., Method: The study involved 13 children with CP (nine males, four females; mean [SD] age 14y 3mo [9mo], range 10-18y; height 1.61m [0.08m]; weight 52.65kg [13kg]), and 13 age- and sex-matched typically developing children (height 1.64m [0.06m]; weight 56.88kg [10kg]). The experiment required the children to extend their knee joint as whole-head MEG recordings were acquired. Beamformer imaging methods were employed to quantify the source activity of the beta-frequency (14-28Hz) event-related desynchronization (ERD) that occurs during the motor planning period, and the gamma-frequency (~50Hz) event-related synchronization (ERS) that occurs at the motor execution stage., Results: The children with CP had a stronger mean beta ERD during the motor planning phase and reduced mean gamma ERS at the onset of movement., Interpretation: The uncharacteristic beta ERD in the children with CP suggests that they may have greater difficulty planning knee joint movements. We suggest that these aberrant beta ERD oscillations may have a cascading effect on the gamma ERS, which ultimately affects the execution of the motor command., (© 2014 Mac Keith Press.)

Parkinson's disease (PD) is a progressive debilitating neurodegenerative disorder clinically manifest by motor, posture and gait abnormalities. Human neurophysiological studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchrony throughout the basal ganglia-thalamic-cortical motor network in PD. Notably, suppression of this pathological beta synchrony by dopamine replacement therapy or deep-brain stimulation has been associated with improved motor function. However, due to the invasive nature of these studies, it remains unknown whether this "pathological beta" is actually stronger than that observed in healthy demographically matched controls. We used magnetoencephalography to investigate neuronal synchrony and oscillatory amplitude in the beta range and lower frequencies during the resting state in patients with PD and a matched group of patients without neurological disease. Patients with PD were studied both in the practically defined drug "OFF" state, and after administration of dopamine replacements. We found that beta oscillatory amplitude was reduced bilaterally in the primary motor regions of unmedicated patients with PD compared with controls. Administration of dopaminergic medications significantly increased beta oscillatory activity, thus having a normalizing effect. Interestingly, we also found significantly stronger beta synchrony (i.e., hypersynchrony) between the primary motor regions in unmedicated patients with PD compared with controls, and that medication reduced this coupling which is in agreement with the intraoperative studies. These results are consistent with the known functionality of the basal ganglia-thalamic-cortical motor circuit and the likely consequences of beta hypersynchrony in the subthalamic nucleus of patients with PD., (Copyright © 2014 the American Physiological Society.)

Parkinson's disease (PD) is a neurodegenerative disorder associated with debilitating motor, posture, and gait abnormalities. Human studies recording local field potentials within the subthalamic nucleus and scalp-based electroencephalography have shown pathological beta synchronization throughout the cortical-basal ganglia motor network in PD. Suppression of such pathological beta synchronization has been associated with improved motor function, which may explain the effectiveness of deep-brain stimulation. We used magnetoencephalography (MEG) to investigate neural population-level beta responses, and other oscillatory activity, during a motor task in unmedicated patients with PD and a matched group of healthy adults. MEG is a noninvasive neurophysiological technique that permits the recording of oscillatory activity during movement planning, execution, and termination phases. Each of these phases was independently examined using beamforming to distinguish the brain areas and movement phases, where pathological oscillations exist during motor control. Patients with PD exhibited significantly diminished beta desynchronization compared with controls prior to and during movement, which paralleled reduced alpha desynchronization. This study is the first to systematically investigate neural oscillatory responses in PD during distinct stages of motor control (e.g. planning, execution, and termination) and indicates that these patients have significant difficulty suppressing cortical beta synchronization during movement planning, which may contribute to their diminished movement capacities., (© The Author 2013. Published by Oxford University Press.)

The ability to attend to particular stimuli while ignoring others is crucial in goal-directed activities and has been linked with prefrontal cortical regions, including the dorsolateral prefrontal cortex (DLPFC). Both hyper- and hypo-activation in the DLPFC has been reported in patients with attention-deficit/hyperactivity disorder (ADHD) during many different cognitive tasks, but the network-level effects of such aberrant activity remain largely unknown. Using magnetoencephalography (MEG), we examined functional connectivity between regions of the DLPFC and the modality-specific auditory cortices during an auditory attention task in medicated and un-medicated adults with ADHD, and those without ADHD. Participants completed an attention task in two separate sessions (medicated/un-medicated), and each session consisted of two blocks (attend and no-attend). All MEG data were coregistered to structural MRI, corrected for head motion, and projected into source space. Subsequently, we computed the phase coherence (i.e., functional connectivity) between DLPFC regions and the auditory cortices. We found that un-medicated adults with ADHD exhibited greater phase coherence in the beta (14-30Hz) and gamma frequency (30-56Hz) range in attend and no-attend conditions compared to controls. Stimulant medication attenuated these differences, but did not fully eliminate them. These results suggest that aberrant bottom-up processing may engulf executive resources in ADHD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Cerebral palsy (CP) results from a perinatal brain injury that often results in sensory impairments and greater errors in motor performance. Although these impairments have been well catalogued, the relationship between sensory processing networks and errors in motor performance has not been well explored. Children with CP and typically developing age-matched controls participated in this investigation. We used high-density magnetoencephalography to measure event-related oscillatory changes in the somatosensory cortices following tactile stimulation to the bottom of the foot. In addition, we quantified the amount of variability or errors in the isometric ankle joint torques as these children attempted to match a target. Our results showed that neural populations in the somatosensory cortices of children with CP were desynchronized by the tactile stimulus, whereas those of typically developing children were clearly synchronized. Such desynchronization suggests that children with CP were unable to fully integrate the external stimulus into ongoing sensorimotor computations. Our results also indicated that children with CP had a greater amount of errors in their motor output when they attempted to match the target force, and this amount of error was negatively correlated with the degree of synchronization present in the somatosensory cortices. These results are the first to show that the motor performance errors of children with CP are linked with neural synchronization within the somatosensory cortices.

The introduction of combination antiretroviral therapy significantly reduced the prevalence of the most severe form of HIV-associated neurocognitive disorders (HAND). Despite this decline, 35-70 % of HIV-infected patients continue to develop mild motor and cognitive impairments. Although neuropsychological studies have shown that HAND affects a wide array of cognitive functions, a formal diagnosis is still based on the exclusion of opportunistic infections and other common ailments, as no specific tests or biomarkers are currently available. In this study, we used magnetoencephalography (MEG) to measure neural activity during the resting-state in 15 HIV-infected older patients and a demographically matched group of 15 uninfected controls. MEG is a noninvasive and direct measure of neural activity with excellent spatiotemporal resolution. All MEG data were coregistered to structural magnetic resonance images, corrected for head motion, fitted to a regional-level source model, and subjected to spectral analyses to quantify population-level neural oscillatory activity. We found that HIV-infected persons exhibited decreased beta oscillations in the supplementary motor area bilaterally, paracentral lobule, posterior cingulate, and bilateral regions of the superior parietal lobule relative to healthy controls. Beta oscillations in the posterior cingulate, a critical component of the default mode network, were also positively correlated with patient scores on the memory recall aspect of the Hopkins Verbal Learning Test-Revised. These results demonstrate that chronic HIV infection does not uniformly disturb cortical function, and that neuronal populations in dorsomedial motor and parietal cortices are especially affected. These findings also suggest that resting-state MEG recordings may hold significant promise as a functional biomarker for identifying HAND and monitoring disease progression.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a common and extensively treated psychiatric disorder in children, which often persists into adulthood. The core diagnostic symptoms include inappropriate levels of hyperactivity, impulsivity, and/or pervasive inattention. Another crucial aspect of the disorder involves aberrations in temporal perception, which have been well documented in behavioral studies and, recently, have been the focus of neuroimaging studies. These functional magnetic resonance imaging studies have shown reduced activation in anterior cingulate and prefrontal cortices in ADHD using a time-interval discrimination task, whereby participants distinguish intervals differing by only hundreds of milliseconds., Method: We used magnetoencephalography (MEG) to evaluate the cortical network serving temporal perception during a continuous, long-duration (in minutes) time estimation experiment. Briefly, medicated and unmedicated persons with ADHD, and a control group responded each time they estimated 60 s had elapsed for an undisclosed amount of time in two separate MEG sessions. All MEG data were transformed into regional source activity, and subjected to spectral analyses to derive amplitude estimates of gamma-band activity., Results: Compared to controls, unmedicated patients were less accurate time estimators and had weaker gamma activity in the anterior cingulate, supplementary motor area, and left prefrontal cortex. After medication, these patients exhibited small but significant increases in gamma across these same neural regions and significant improvements in time estimation accuracy, which correlated with the gamma activity increases., Conclusion: We found deficient gamma activity in brain areas known to be crucial for timing functions, which may underlie the day-to-day abnormalities in time perception that are common in ADHD., (PsycINFO Database Record (c) 2013 APA, all rights reserved.)

Despite the availability of combination antiretroviral therapy, at least mild cognitive dysfunction is commonly observed in HIV-infected patients, with an estimated prevalence of 35-70 %. Neuropsychological studies of these HIV-associated neurocognitive disorders (HAND) have documented aberrations across a broad range of functional domains, although the basic pathophysiology remains unresolved. Some of the most common findings have been deficits in fine motor control and reduced psychomotor speed, but to date no neuroimaging studies have evaluated basic motor control in HAND. In this study, we used magnetoencephalography (MEG) to evaluate the neurophysiological processes that underlie motor planning in older HIV-infected adults and a matched, uninfected control group. MEG is a noninvasive and direct measure of neural activity with good spatiotemporal precision. During the MEG recording, participants fixated on a central crosshair and performed a finger-tapping task with the dominant hand. All MEG data was corrected for head movements, preprocessed, and imaged in the time-frequency domain using beamforming methodology. All analyses focused on the pre-movement beta desynchronization, which is known to be an index of movement planning. Our results demonstrated that HIV-1-infected patients have deficient beta desynchronization relative to controls within the left/right precentral gyri, and the supplementary motor area. In contrast, HIV-infected persons showed abnormally strong beta responses compared to controls in the right dorsolateral prefrontal cortex and medial prefrontal areas. In addition, the amplitude of beta activity in the primary and supplementary motor areas correlated with scores on the Grooved Pegboard test in HIV-infected adults. These results demonstrate that primary motor and sensory regions may be particularly vulnerable to HIV-associated damage, and that prefrontal cortices may serve a compensatory role in maintaining motor performance levels in infected patients.

Background: Dysfunction in the default mode network (DMN), a group of cortical areas more active during the resting state, has been linked to attentional deficits and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Prior imaging studies have shown decreased functional connectivity between DMN nodes in patients with ADHD, primarily between anterior and posterior regions. Using magnetoencephalography (MEG), we evaluated phase coherence (i.e., functional connectivity) among regions of the DMN in healthy controls and adults with ADHD before and after stimulant therapy., Methods: We obtained a resting-state MEG recording for all participants. Magnetoencephalography data were transformed into a ~30 node regional source model using inverse spatial filtering, including regions corresponding to the DMN. We computed the zero-lag phase coherence between these regions pairwise for 5 distinct frequency bands, and we assessed group and medication effects., Results: Twelve adults with and 13 without ADHD participated in our study. Functional connectivity was stronger between particular node pairs and showed frequency-specific effects. Unmedicated patients showed reduced phase locking between posterior cingulate/precuneus regions (PCC) and right inferior parietal cortices (RIPL), and between medial prefrontal regions (MPFC) and the left inferior parietal region (LIPL) and the PCC. Unmedicated patients had increased phase locking between the RIPL and LIPL regions compared with controls. Administration of stimulants improved phase locking abnormalities along the MPFC-PCC and LIPL-RIPL pathways in patients with ADHD., Limitations: Modest sample size and lack of duration of patient treatment history may limit the generalizability of our findings., Conclusion: Adults with ADHD exhibit hyper- and hypoconnectivity between regions of the DMN during rest, which were suppressed after stimulant medication administration.

Objective: Shortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation., Methods: High-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming., Results: Uninfected controls had increased neuronal synchronization in the 6-12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions., Conclusions: MEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health.

The analysis of interictal epileptiform discharges (IEDs) using magnetoencephalography (MEG) is utilized for the localization of seizure onset zones in the presurgical planning of epilepsy patients. Additionally, resting-state functional connectivity analyses using the IED area may provide novel insight into the underlying brain networks. In this study, we evaluate whether chronicity of seizures is related to whole-brain functional connectivity metrics using the area of IED generation (derived from MEG) as the seed region. We found a positive correlation between the duration of seizures and beta-band functional connectivity between the epileptogenic zone and other brain areas. This suggests the presence of inhibitory GABAergic modulation of distal brain regions in response to chronic epileptiform activity., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Previous investigations of the default-mode network (DMN) in persons with attention-deficit/hyperactivity disorder (ADHD) have shown reduced functional connectivity between the anterior and posterior aspects. This finding was originally demonstrated in adults with ADHD, then in youth with ADHD, and has been tentatively linked to ultra low frequency oscillations within the DMN. The current study evaluates the specificity of DMN abnormalities to neuronal oscillations in the ultra low frequency range, and examines the regional specificity of these DMN aberrations in medicated and unmedicated adults with, and those without ADHD. An individually matched sample of adults with and without ADHD completed 6-minute sessions of resting-state magnetoencephalography (MEG). Participants with ADHD were known responders to stimulant medications and completed two sessions (predrug/postdrug). MEG data were coregistered to the participant's MRI, corrected for head motion, fitted to a regional-level source model, and subjected to spectral analyses to extract neuronal population activity in regions of the DMN. The unmedicated adults with ADHD exhibited broadband deficits in medial prefrontal cortices (MPFC), but not other DMN regions compared to adults without ADHD. Unmedicated patients also showed abnormal cross-frequency coupling in the gamma range between the MPFC and posterior cingulate areas, and disturbed balance within the DMN as activity in posterior regions was stronger than frontal regions at beta and lower frequencies, which dissipated at higher γ-frequencies. Administration of pharmacotherapy significantly increased prefrontal alpha activity (8-14 Hz) in adults with ADHD, and decreased the cross-frequency gamma coupling. These results indicate that neurophysiological aberrations in the DMN of patients with ADHD are not limited to ultra slow oscillations, and that they may be primarily attributable to abnormal broadband activity in the MPFC., (Copyright © 2011 Wiley Periodicals, Inc.)

Visual neurons are known to synchronize their firing with stimuli that flicker at a constant rate (e.g. 12Hz). These so-called visual steady-state responses (VSSR) are a well-studied phenomenon, yet the underlying mechanisms are widely disagreed upon. Furthermore, there is limited evidence that visual neurons may simultaneously synchronize at harmonics of the stimulation frequency. We utilized magnetoencephalography (MEG) to examine synchronization at harmonics of the visual stimulation frequency (18Hz). MEG data were analyzed for event-related-synchronization (ERS) at the fundamental frequency, 36, 54, and 72Hz. We found strong ERS in all bands. Only 31% of participants showed maximum entrainment at the fundamental; others showed stronger entrainment at either 36 or 54Hz. The cortical foci of these responses indicated that the harmonics involved cortices that were partially distinct from the fundamental. These findings suggest that spatially-overlapping subpopulations of neurons are simultaneously entrained at different harmonics of the stimulus frequency., (Copyright © 2012 Elsevier B.V. All rights reserved.)