Spectral specificity of gamma-frequency transcranial alternating current stimulation over motor cortex during sequential movements.

Motor control requires the coordination of spatiotemporally precise neural oscillations in the beta and gamma range within the primary motor cortex (M1). Recent studies have shown that motor performance can be differentially modulated based on the spectral target of noninvasive transcranial alternating current stimulation (tACS), with gamma-frequency tACS improving motor performance. However, the spectral specificity for eliciting such improvements remains unknown. Herein, we derived the peak movement-related gamma frequency in 25 healthy adults using magnetoencephalography and a motor control paradigm. These individualized peak gamma frequencies were then used for personalized sessions of tACS. All participants completed 4 sessions of high-definition (HD)-tACS (sham, low-, peak-, and high-gamma frequency) over M1 for 20 min during the performance of sequential movements of varying complexity (e.g. tapping adjacent fingers or nonadjacent fingers). Our primary findings demonstrated that individualized tACS dosing over M1 leads to enhanced motor performance/learning (i.e. greatest reduction in time to complete motor sequences) compared to nonspecific gamma-tACS in humans, which suggests that personalized neuromodulation may be advantageous to optimize behavioral outcomes.

Neural oscillatory activity serving sensorimotor control is predicted by superoxide-sensitive mitochondrial redox environments.

Motor control requires a coordinated ensemble of spatiotemporally precise neural oscillations across a distributed motor network, particularly in the beta range (15 to 30 Hz) to successfully plan and execute volitional actions. While substantial evidence implicates beta activity as critical to motor control, the molecular processes supporting these microcircuits and their inherent oscillatory dynamics remain poorly understood. Among these processes are mitochondrial integrity and the associated redox environments, although their direct impact on human neurophysiological function is unknown. Herein, 40 healthy adults completed a motor sequence paradigm during magnetoencephalography (MEG). MEG data were imaged in the time-frequency domain using a beamformer to evaluate beta oscillatory profiles during distinct phases of motor control (i.e., planning and execution) and subsequent behavior. To comprehensively quantify features of the mitochondrial redox environment, we used state-of-the-art systems biology approaches including Seahorse Analyzer to assess mitochondrial respiration and electron paramagnetic resonance spectroscopy to measure superoxide levels in whole blood as well as antioxidant activity assays. Using structural equation modeling, we tested the relationship between mitochondrial function and sensorimotor brain-behavior dynamics through alterations in the redox environment (e.g., generation of superoxide and alteration in antioxidant defenses). Our results indicated that superoxide-sensitive but not hydrogen peroxide-sensitive features of the redox environment had direct and mediating effects on the bioenergetic-neural pathways serving motor performance in healthy adults. Importantly, our results suggest that alterations in the redox environment may directly impact behavior above and beyond mitochondrial respiratory capacities alone and further may be effective targets for age- and disease-related declines in cognitive-motor function.

Regular recreational Cannabis users exhibit altered neural oscillatory dynamics during attention reorientation.

BACKGROUND: Cannabis is the most widely used illicit drug in the United States and is often associated with changes in attention function, which may ultimately impact numerous other cognitive faculties (e.g. memory, executive function). Importantly, despite the increasing rates of cannabis use and widespread legalization in the United States, the neural mechanisms underlying attentional dysfunction in chronic users are poorly understood. METHODS: We used magnetoencephalography (MEG) and a modified Posner cueing task in 21 regular cannabis users and 32 demographically matched non-user controls. MEG data were imaged in the time-frequency domain using a beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying use-related aberrations in attentional reorienting, as well as the impact on spontaneous neural activity immediately preceding stimulus onset. RESULTS: Behavioral performance on the task (e.g. reaction time) was similar between regular cannabis users and non-user controls. However, the neural data indicated robust theta-band synchronizations across a distributed network during attentional reorienting, with activity in the bilateral inferior frontal gyri being markedly stronger in users relative to controls (p's < 0.036). Additionally, we observed significantly reduced spontaneous theta activity across this distributed network during the pre-stimulus baseline in cannabis users relative to controls (p's < 0.020). CONCLUSIONS: Despite similar performance on the task, we observed specific alterations in the neural dynamics serving attentional reorienting in regular cannabis users compared to controls. These data suggest that regular cannabis users may employ compensatory processing in the prefrontal cortices to efficiently reorient their attention relative to non-user controls.

Mitochondrial redox environments predict sensorimotor brain-behavior dynamics in adults with HIV.

Despite virologic suppression, people living with HIV (PLWH) remain at risk for developing cognitive impairment, with aberrations in motor control being a predominant symptom leading to functional dependencies in later life. While the neuroanatomical bases of motor dysfunction have recently been illuminated, the underlying molecular processes remain poorly understood. Herein, we evaluate the predictive capacity of the mitochondrial redox environment on sensorimotor brain-behavior dynamics in 40 virally-suppressed PLWH and 40 demographically-matched controls using structural equation modeling. We used state-of-the-art approaches, including Seahorse Analyzer of mitochondrial function, electron paramagnetic resonance spectroscopy to measure superoxide levels, antioxidant activity assays and dynamic magnetoencephalographic imaging to quantify sensorimotor oscillatory dynamics. We observed differential modulation of sensorimotor brain-behavior relationships by superoxide and hydrogen peroxide-sensitive features of the redox environment in PLWH, while only superoxide-sensitive features were related to optimal oscillatory response profiles and better motor performance in controls. Moreover, these divergent pathways may be attributable to immediate, separable mechanisms of action within the redox environment seen in PLWH, as evidenced by mediation analyses. These findings suggest that mitochondrial redox parameters are important modulators of healthy and pathological oscillations in motor systems and behavior, serving as potential targets for remedying HIV-related cognitive-motor dysfunction in the future.

Elevated CRP and TNF-α levels are associated with blunted neural oscillations serving fluid intelligence.

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf. METHODS: Seventy adults between the ages of 20-66 years (Mean = 45.17 years, SD = 16.29, 21.4% female) completed an abstract reasoning task that probes Gf during magnetoencephalography (MEG) and provided a blood sample for inflammatory marker analysis. MEG data were imaged in the time-frequency domain, and whole-brain regressions were conducted using each individual's plasma CRP and TNF-α concentrations per oscillatory response, controlling for age, BMI, and education. RESULTS: CRP and TNF-α levels were significantly associated with region-specific neural oscillatory responses. In particular, elevated CRP concentrations were associated with altered gamma activity in the right inferior frontal gyrus and right cerebellum. In contrast, elevated TNF-α levels scaled with alpha/beta oscillations in the left anterior cingulate and left middle temporal, and gamma activity in the left intraparietal sulcus. DISCUSSION: Elevated inflammatory markers such as CRP and TNF-α were associated with aberrant neural oscillations in regions important for Gf. Linking inflammatory markers with regional neural oscillations may hold promise in identifying mechanisms of cognitive and psychiatric disorders.

Alpha oscillations in left perisylvian cortices support semantic processing and predict performance.

Semantic processing is the ability to discern and maintain conceptual relationships among words and objects. While the neural circuits serving semantic representation and controlled retrieval are well established, the neuronal dynamics underlying these processes are poorly understood. Herein, we examined 25 healthy young adults who completed a semantic relation word-matching task during magnetoencephalography (MEG). MEG data were examined in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Whole-brain statistical analyses were conducted to compare semantic-related to length-related neural oscillatory responses. Time series were extracted to visualize the dynamics and were linked to task performance using structural equation modeling. The results indicated that participants had significantly longer reaction times in semantic compared to length trials. Robust MEG responses in the theta (3-6 Hz), alpha (10-16 Hz), and gamma (64-76 Hz and 64-94 Hz) bands were observed in parieto-occipital and frontal cortices. Whole-brain analyses revealed stronger alpha oscillations in a left-lateralized network during semantically related relative to length trials. Importantly, stronger alpha oscillations in the left superior temporal gyrus during semantic trials predicted faster responses. These data reinforce existing literature and add novel temporal evidence supporting the executive role of the semantic control network in behavior.

A First Methodological Development and Validation of ReTap: An Open-Source UPDRS Finger Tapping Assessment Tool Based on Accelerometer-Data.

Bradykinesia is a cardinal hallmark of Parkinson's disease (PD). Improvement in bradykinesia is an important signature of effective treatment. Finger tapping is commonly used to index bradykinesia, albeit these approaches largely rely on subjective clinical evaluations. Moreover, recently developed automated bradykinesia scoring tools are proprietary and are not suitable for capturing intraday symptom fluctuation. We assessed finger tapping (i.e., Unified Parkinson's Disease Rating Scale (UPDRS) item 3.4) in 37 people with Parkinson's disease (PwP) during routine treatment follow ups and analyzed their 350 sessions of 10-s tapping using index finger accelerometry. Herein, we developed and validated ReTap, an open-source tool for the automated prediction of finger tapping scores. ReTap successfully detected tapping blocks in over 94% of cases and extracted clinically relevant kinematic features per tap. Importantly, based on the kinematic features, ReTap predicted expert-rated UPDRS scores significantly better than chance in a hold out validation sample (n = 102). Moreover, ReTap-predicted UPDRS scores correlated positively with expert ratings in over 70% of the individual subjects in the holdout dataset. ReTap has the potential to provide accessible and reliable finger tapping scores, either in the clinic or at home, and may contribute to open-source and detailed analyses of bradykinesia.

High-definition transcranial direct current stimulation of the occipital cortices induces polarity dependent effects within the brain regions serving attentional reorientation.

Numerous brain stimulation studies have targeted the posterior parietal cortex, a key hub of the attention network, to manipulate attentional reorientation. However, the impact of stimulating brain regions earlier in the pathway, including early visual regions, is poorly understood. In this study, 28 healthy adults underwent three high-definition transcranial direct current stimulation (HD-tDCS) visits (i.e., anodal, cathodal, and sham). During each visit, they completed 20 min of occipital HD-tDCS and then a modified Posner task during magnetoencephalography (MEG). MEG data were transformed into the time-frequency domain and significant oscillatory events were imaged using a beamformer. Oscillatory response amplitude values were extracted from peak voxels in the whole-brain maps and were statistically compared. Behaviorally, we found that the participants responded slowly when attention reallocation was needed (i.e., the validity effect), irrespective of the stimulation condition. Our neural findings indicated that cathodal HD-tDCS was associated with significantly reduced theta validity effects in the occipital cortices, as well as reduced alpha validity effects in the left occipital and parietal cortices relative to anodal HD-tDCS. Additionally, anodal occipital stimulation significantly increased gamma amplitude in right occipital regions relative to cathodal and sham stimulation. Finally, we also found a negative correlation between the alpha validity effect and reaction time following anodal stimulation. Our findings suggest that HD-tDCS of the occipital cortices has a polarity dependent impact on the multispectral neural oscillations serving attentional reorientation in healthy adults, and that such effects may reflect altered local GABA concentrations in the neural circuitry serving attentional reorientation.

Cortisol changes in healthy children and adolescents during the COVID-19 pandemic.

The Coronavirus Disease 2019 (COVID-19) pandemic has caused massive disruptions to daily life in the United States, closing schools and businesses and increasing physical and social isolation, leading to deteriorations in mental health and well-being in people of all ages. Many studies have linked chronic stress with long-term changes in cortisol secretion, which has been implicated in many stress-related physical and mental health problems that commonly emerge in adolescence. However, the physiological consequences of the pandemic in youth remain understudied. Using hair cortisol concentrations (HCC), we quantified average longitudinal changes in cortisol secretion across a four-month period capturing before, during, and after the transition to pandemic-lockdown conditions in a sample of healthy youth (n = 49). Longitudinal changes in HCC were analyzed using linear mixed-effects models. Perceived levels of pandemic-related stress were measured and compared to the physiological changes in HCC. In children and adolescents, cortisol levels significantly increased across the course of the pandemic. These youth reported a multitude of stressors during this time, although changes in HCC were not associated with self-reported levels of COVID-19-related distress. We provide evidence that youth are experiencing significant physiological changes in cortisol activity across the COVID-19 pandemic, yet these biological responses are not associated with perceived stress levels. Youth may be especially vulnerable to the deleterious impacts of chronic cortisol exposure due to their current status in the sensitive periods for development, and the incongruency between biological and psychological stress responses may further complicate these developmental problems.

Movement-Related Gamma Synchrony Differentially Predicts Behavior in the Presence of Visual Interference Across the Lifespan.

The ability to allocate neural resources to task-relevant stimuli, while inhibiting distracting information in the surrounding environment (i.e., selective attention) is critical for high-level cognitive function, and declines in this ability have been linked to functional deficits in later life. Studies of age-related declines in selective attention have focused on frontal circuitry, with almost no work evaluating the contribution of motor cortical dynamics to successful task performance. Herein, we examined 69 healthy adults (23-72 years old) who completed a flanker task during magnetoencephalography (MEG). MEG data were imaged in the time-frequency domain using a beamformer to evaluate the contribution of motor cortical dynamics to age-related increases in behavioral interference effects. Our results showed that gamma oscillations in the contralateral motor cortex (M1) were a robust predictor of reaction time, regardless of interference level. Additionally, we observed condition-wise differences in gamma-by-age interactions, such that in younger adults, increases in M1 gamma power were predictive of faster reaction times during incongruent trials, while older adults did not receive this same behavioral benefit. Importantly, these data indicate that M1 gamma oscillations are differentially predictive of behavior in the presence, but not absence of visual interference, resulting in exhausted compensatory strategies with age.

Differences in Rhythmic Neural Activity Supporting the Temporal and Spatial Cueing of Attention.

The neural processes serving the orienting of attention toward goal-relevant stimuli are generally examined with informative cues that direct visual attention to a spatial location. However, cues predicting the temporal emergence of an object are also known to be effective in attentional orienting but are implemented less often. Differences in the neural oscillatory dynamics supporting these divergent types of attentional orienting have only rarely been examined. In this study, we utilized magnetoencephalography and an adapted Posner cueing task to investigate the spectral specificity of neural oscillations underlying these different types of attentional orienting (i.e., spatial vs. temporal). We found a spectral dissociation of attentional cueing, such that alpha (10-16 Hz) oscillations were central to spatial orienting and theta (3-6 Hz) oscillations were critical to temporal orienting. Specifically, we observed robust decreases in alpha power during spatial orienting in key attention areas (i.e., lateral occipital, posterior cingulate, and hippocampus), along with strong theta increases during temporal orienting in the primary visual cortex. These results suggest that the oscillatory dynamics supporting attentional orienting are spectrally and anatomically specific, such that spatial orienting is served by stronger alpha oscillations in attention regions, whereas temporal orienting is associated with stronger theta responses in visual sensory regions.

High-definition transcranial direct current stimulation modulates performance and alpha/beta parieto-frontal connectivity serving fluid intelligence.

Fluid intelligence (Gƒ) includes logical reasoning abilities and is an essential component of normative cognition. Despite the broad consensus that parieto-prefrontal connectivity is critical for Gƒ (e.g. the parieto-frontal integration theory of intelligence, P-FIT), the dynamics of such functional connectivity during logical reasoning remains poorly understood. Further, given the known importance of these brain regions for Gƒ, numerous studies have targeted one or both of these areas with non-invasive stimulation with the goal of improving Gƒ, but to date there remains little consensus on the overall stimulation-related effects. To examine this, we applied high-definition direct current anodal stimulation to the left and right dorsolateral prefrontal cortex (DLPFC) of 24 healthy adults for 20 min in three separate sessions (sham, left, and right active). Following stimulation, participants completed a logical reasoning task during magnetoencephalography (MEG). Significant neural responses at the sensor-level were imaged using a beamformer, and peak task-induced activity was subjected to dynamic functional connectivity analyses to evaluate the impact of distinct stimulation montages on network activity. We found that participants responded faster following right DLPFC stimulation vs. sham. Moreover, our neural findings followed a similar trajectory of effects such that left parieto-frontal connectivity decreased following right and left DLPFC stimulation compared to sham, with connectivity following right stimulation being significantly correlated with the faster reaction times. Importantly, our findings are consistent with P-FIT, as well as the neural efficiency hypothesis (NEH) of intelligence. In sum, this study provides evidence for beneficial effects of right DLPFC stimulation on logical reasoning. KEY POINTS: Logical reasoning is an indispensable component of fluid intelligence and involves multispectral oscillatory activity in parietal and frontal regions. Parieto-frontal integration is well characterized in logical reasoning; however, its direct neural quantification and neuromodulation by brain stimulation remain poorly understood. High-definition transcranial direct current stimulation of dorsolateral prefrontal cortex (DLPFC) had modulatory effects on task performance and neural interactions serving logical reasoning, with right stimulation showing beneficial effects. Right DLPFC stimulation led to a decrease in the response time (i.e. better task performance) and left parieto-frontal connectivity with a marginal positive association between behavioural and neural metrics. Other modes of targeted stimulation of DLPFC (e.g. frequency-specific) can be employed in future studies.

Prefrontal Multielectrode Transcranial Direct Current Stimulation Modulates Performance and Neural Activity Serving Visuospatial Processing.

The dorsolateral prefrontal cortex (DLPFC) is known to play a critical role in visuospatial attention and processing, but the relative contribution of the left versus right DLPFC remains poorly understood. We applied multielectrode transcranial direct-current stimulation (ME-tDCS) to the left and right DLPFC to investigate its net impact on behavioral performance and population-level neural activity. The primary hypothesis was that significant laterality effects would be observed in regard to behavior and neural oscillations. Twenty-five healthy adults underwent three visits (left, right, and sham ME-tDCS). Following stimulation, participants completed a visuospatial processing task during magnetoencephalography (MEG). Statistically significant oscillatory events were imaged, and time series were then extracted from the peak voxels of each response. Behavioral findings indicated differences in reaction time and accuracy, with left DLPFC stimulation being associated with slower responses and decreased accuracy compared to right stimulation. Left DLPFC stimulation was also associated with increases in spontaneous theta and decreases in gamma within occipital cortices relative to both right and sham stimulation, while connectivity among DLPFC and visual cortices was generally increased contralateral to stimulation. These data suggest spectrally specific modulation of spontaneous cortical activity at the network-level by ME-tDCS, with distinct outcomes based on the laterality of stimulation.

Multielectrode Transcranial Electrical Stimulation of the Left and Right Prefrontal Cortices Differentially Impacts Verbal Working Memory Neural Circuitry.

Recent studies have examined the effects of conventional transcranial direct current stimulation (tDCS) on working memory (WM) performance, but this method has relatively low spatial precision and generally involves a reference electrode that complicates interpretation. Herein, we report a repeated-measures crossover study of 25 healthy adults who underwent multielectrode tDCS of the left dorsolateral prefrontal cortex (DLPFC), right DLPFC, or sham in 3 separate visits. Shortly after each stimulation session, participants performed a verbal WM (VWM) task during magnetoencephalography, and the resulting data were examined in the time-frequency domain and imaged using a beamformer. We found that after left DLPFC stimulation, participants exhibited stronger responses across a network of left-lateralized cortical areas, including the supramarginal gyrus, prefrontal cortex, inferior frontal gyrus, and cuneus, as well as the right hemispheric homologues of these regions. Importantly, these effects were specific to the alpha-band, which has been previously implicated in VWM processing. Although stimulation condition did not significantly affect performance, stepwise regression revealed a relationship between reaction time and response amplitude in the left precuneus and supramarginal gyrus. These findings suggest that multielectrode tDCS targeting the left DLPFC affects the neural dynamics underlying offline VWM processing, including utilization of a more extensive bilateral cortical network.

High-definition transcranial direct current stimulation dissociates fronto-visual theta lateralization during visual selective attention.

KEY POINTS: Visual attention involves discrete multispectral oscillatory responses in visual and 'higher-order' prefrontal cortices. Prefrontal cortex laterality effects during visual selective attention are poorly characterized. High-definition transcranial direct current stimulation dynamically modulated right-lateralized fronto-visual theta oscillations compared to those observed in left fronto-visual pathways. Increased connectivity in right fronto-visual networks after stimulation of the left dorsolateral prefrontal cortex resulted in faster task performance in the context of distractors. Our findings show clear laterality effects in theta oscillatory activity along prefrontal-visual cortical pathways during visual selective attention. ABSTRACT: Studies of visual attention have implicated oscillatory activity in the recognition, protection and temporal organization of attended representations in visual cortices. These studies have also shown that higher-order regions such as the prefrontal cortex are critical to attentional processing, but far less is understood regarding prefrontal laterality differences in attention processing. To examine this, we selectively applied high-definition transcranial direct current stimulation (HD-tDCS) to the left or right dorsolateral prefrontal cortex (DLPFC). We predicted that HD-tDCS of the left versus right prefrontal cortex would differentially modulate performance on a visual selective attention task, and alter the underlying oscillatory network dynamics. Our randomized crossover design included 27 healthy adults that underwent three separate sessions of HD-tDCS (sham, left DLPFC and right DLPFC) for 20 min. Following stimulation, participants completed an attention protocol during magnetoencephalography. The resulting oscillatory dynamics were imaged using beamforming, and peak task-related neural activity was subjected to dynamic functional connectivity analyses to evaluate the impact of stimulation site (i.e. left and right DLPFC) on neural interactions. Our results indicated that HD-tDCS over the left DLPFC differentially modulated right fronto-visual functional connectivity within the theta band compared to HD-tDCS of the right DLPFC and further, specifically modulated the oscillatory response for detecting targets among an array of distractors. Importantly, these findings provide network-specific insight into the complex oscillatory mechanisms serving visual selective attention.

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

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 â€‹ms (in 100 â€‹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 â€‹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 â€‹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.

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

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.

Utilizing transcranial alternating current stimulation and functional neuroimaging to investigate human sensory adaptation.

Sensory adaptation is the reduction of neural activity after repeated exposure to a stimulus. In a recent study, Kar et al. (Kar K, Ito T, Cole MW, Krekelberg B. J Neurophysiol 123: 428-438, 2020) found that implementation of 10-Hz transcranial alternating current stimulation (tACS) to the human middle temporal cortex (hMT+) decreased sensory adaptation and increased functional connectivity. We explain the relevance of neuroimaging utilization with tACS and suggest different methods. Additionally, future directions are provided by introducing task-relevant oscillatory frequencies for tACS related to other sensory processes that undergo adaptation.

Prefrontal theta modulates sensorimotor gamma networks during the reorienting of attention.

The ability to execute a motor plan involves spatiotemporally precise oscillatory activity in primary motor (M1) regions, in concert with recruitment of "higher order" attentional mechanisms for orienting toward current task goals. While current evidence implicates gamma oscillatory activity in M1 as central to the execution of a movement, far less is known about top-down attentional modulation of this response. Herein, we utilized magnetoencephalography (MEG) during a Posner attention-reorienting task to investigate top-down modulation of M1 gamma responses by frontal attention networks in 63 healthy adult participants. MEG data were evaluated in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Robust increases in theta activity were found in bilateral inferior frontal gyri (IFG), with significantly stronger responses evident in trials that required attentional reorienting relative to those that did not. Additionally, strong gamma oscillations (60-80 Hz) were detected in M1 during movement execution, with similar responses elicited irrespective of attentional reorienting. Whole-brain voxel-wise correlations between validity difference scores (i.e., attention reorienting trials-nonreorienting trials) in frontal theta activity and movement-locked gamma oscillations revealed a robust relationship in the contralateral sensorimotor cortex, supplementary motor area, and right cerebellum, suggesting modulation of these sensorimotor network gamma responses by attentional reorienting. Importantly, the validity difference effect in this distributed motor network was predictive of overall motor function measured outside the scanner and further, based on a mediation analysis this relationship was fully mediated by the reallocation response in the right IFG. These data are the first to characterize the top-down modulation of movement-related gamma responses during attentional reorienting and movement execution.

Rhythmic Spontaneous Activity Mediates the Age-Related Decline in Somatosensory Function.

Sensory gating is a neurophysiological process whereby the response to a second stimulus in a pair of identical stimuli is attenuated, and it is thought to reflect the capacity of the CNS to preserve neural resources for behaviorally relevant stimuli. Such gating is observed across multiple sensory modalities and is modulated by age, but the mechanisms involved are not understood. In this study, we examined somatosensory gating in 68 healthy adults using magnetoencephalography (MEG) and advanced oscillatory and time-domain analysis methods. MEG data underwent source reconstruction and peak voxel time series data were extracted to evaluate the dynamics of somatosensory gating, and the impact of spontaneous neural activity immediately preceding the stimulation. We found that gating declined with increasing age and that older adults had significantly reduced gating relative to younger adults, suggesting impaired local inhibitory function. Most importantly, older adults had significantly elevated spontaneous activity preceding the stimulation, and this effect fully mediated the impact of aging on sensory gating. In conclusion, gating in the somatosensory system declines with advancing age and this effect is directly tied to increased spontaneous neural activity in the primary somatosensory cortices, which is likely secondary to age-related declines in local GABA inhibitory function.