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.

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.

Transdiagnostic indicators predict developmental changes in cognitive control resting-state networks.

Over the past decade, transdiagnostic indicators in relation to neurobiological processes have provided extensive insight into youth's risk for psychopathology. During development, exposure to childhood trauma and dysregulation (i.e., so-called AAA symptomology: anxiety, aggression, and attention problems) puts individuals at a disproportionate risk for developing psychopathology and altered network-level neural functioning. Evidence for the latter has emerged from resting-state fMRI studies linking mental health symptoms and aberrations in functional networks (e.g., cognitive control (CCN), default mode networks (DMN)) in youth, although few of these investigations have used longitudinal designs. Herein, we leveraged a three-year longitudinal study to identify whether traumatic exposures and concomitant dysregulation trigger changes in the developmental trajectories of resting-state functional networks involved in cognitive control (N = 190; 91 females; time 1 Mage = 11.81). Findings from latent growth curve analyses revealed that greater trauma exposure predicted increasing connectivity between the CCN and DMN across time. Greater levels of dysregulation predicted reductions in within-network connectivity in the CCN. These findings presented in typically developing youth corroborate connectivity patterns reported in clinical populations, suggesting there is predictive utility in using transdiagnostic indicators to forecast alterations in resting-state networks implicated in psychopathology.

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

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

The development of sensorimotor cortical oscillations is mediated by pubertal testosterone.

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

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

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

Differential impact of movement on the alpha and gamma dynamics serving visual processing.

Visual processing is widely understood to be served by a decrease in alpha activity in occipital cortices, largely concurrent with an increase in gamma activity. Although the characteristics of these oscillations are well documented in response to a range of complex visual stimuli, little is known about how these dynamics are impacted by concurrent motor responses, which is problematic as many common visual tasks involve such responses. Thus, in the current study, we used magnetoencephalography (MEG) and modified a well-established visual paradigm to explore the impact of motor responses on visual oscillatory activity. Thirty-four healthy adults viewed a moving gabor (grating) stimulus that was known to elicit robust alpha and gamma oscillations in occipital cortices. Frequency and power characteristics were assessed statistically for differences as a function of movement condition. Our results indicated that occipital alpha significantly increased in power during movement relative to no movement trials. No differences in peak frequency or power were found for gamma responses between the two movement conditions. These results provide valuable evidence of visuomotor integration and underscore the importance of careful task design and interpretation, especially in the context of complex visual processing, and suggest that even basic motor responses alter occipital visual oscillations in healthy adults.NEW & NOTEWORTHY Processing of visual stimuli is served by occipital alpha and gamma activity. Many studies have investigated the impact of visual stimuli on motor cortical responses, but few studies have systematically investigated the impact of motor responses on visual oscillations. We found that when participants are asked to move in response to a visual stimulus, occipital alpha power was modulated whereas gamma responses were unaffected. This suggests that these responses have dissociable roles in visuomotor integration.

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.

Left amygdala structure mediates longitudinal associations between exposure to threat and long-term psychiatric symptomatology in youth.

Traumatic experiences during childhood can have profound effects on stress sensitive brain structures (e.g., amygdala and hippocampus) and the emergence of psychiatric symptoms. Recent theoretical and empirical work has delineated dimensions of trauma (i.e., threat and deprivation) as having distinct neural and behavioral effects, although there are few longitudinal examinations. A sample of 243 children and adolescents were followed for three time points, with each assessment approximately 1 year apart (ages 9-15 years at Time 1; 120 males). Participants or their caregiver reported on youths' threat exposure, perceived stress (Time 1), underwent a T1-weighted structural high-resolution MRI scan (Time 2), and documented their subsequent psychiatric symptoms later in development (Time 3). The primary findings indicate that left amygdala volume, in particular, mediated the longitudinal association between threat exposure and subsequent internalizing and externalizing symptomatology. Greater threat exposure related to reduced left amygdala volume, which in turn differentially predicted internalizing and externalizing symptoms. Decreased bilateral hippocampal volume was related to subsequently elevated internalizing symptoms. These findings suggest that the left amygdala is highly threat-sensitive and that stress-related alterations may partially explain elevated psychopathology in stress-exposed adolescents. Uncovering potential subclinical and/or preclinical predictive biomarkers is essential to understanding the emergence, progression, and eventual targeted treatment of psychopathology following trauma exposure.

The impact of pubertal DHEA on the development of visuospatial oscillatory dynamics.

The adolescent brain undergoes tremendous structural and functional changes throughout puberty. Previous research has demonstrated that pubertal hormones can modulate sexually dimorphic changes in cortical development, as well as age-related maturation of the neural activity underlying cognitive processes. However, the precise impact of pubertal hormones on these functional changes in the developing human brain remains poorly understood. In the current study, we quantified the neural oscillatory activity serving visuospatial processing using magnetoencephalography, and utilized measures of dehydroepiandrosterone (DHEA) as an index of development during the transition from childhood to adolescence (i.e., puberty). Within a sample of typically developing youth (ages 9-15), a novel association between pubertal DHEA and theta oscillatory activity indicated that less mature children exhibited stronger neural responses in higher-order prefrontal cortices during the visuospatial task. Theta coherence between bilateral prefrontal regions also increased with increasing DHEA, such that network-level theta activity became more distributed with more maturity. Additionally, significant DHEA-by-sex interactions in the gamma range were centered on cortical regions relevant for attention processing. These findings suggest that pubertal DHEA may modulate the development of neural oscillatory activity serving visuospatial processing and attention functions during the pubertal period.

Reliability of the NIH toolbox cognitive battery in children and adolescents: a 3-year longitudinal examination.

BACKGROUND: The Cognitive Battery of the National Institutes of Health Toolbox (NIH-TB) is a collection of assessments that have been adapted and normed for administration across the lifespan and is increasingly used in large-scale population-level research. However, despite increasing adoption in longitudinal investigations of neurocognitive development, and growing recommendations that the Toolbox be used in clinical applications, little is known about the long-term temporal stability of the NIH-TB, particularly in youth. METHODS: The present study examined the long-term temporal reliability of the NIH-TB in a large cohort of youth (9-15 years-old) recruited across two data collection sites. Participants were invited to complete testing annually for 3 years. RESULTS: Reliability was generally low-to-moderate, with intraclass correlation coefficients ranging between 0.31 and 0.76 for the full sample. There were multiple significant differences between sites, with one site generally exhibiting stronger temporal stability than the other. CONCLUSIONS: Reliability of the NIH-TB Cognitive Battery was lower than expected given early work examining shorter test-retest intervals. Moreover, there were very few instances of tests meeting stability requirements for use in research; none of the tests exhibited adequate reliability for use in clinical applications. Reliability is paramount to establishing the validity of the tool, thus the constructs assessed by the NIH-TB may vary over time in youth. We recommend further refinement of the NIH-TB Cognitive Battery and its norming procedures for children before further adoption as a neuropsychological assessment. We also urge researchers who have already employed the NIH-TB in their studies to interpret their results with caution.

Amount of Hearing Aid Use Impacts Neural Oscillatory Dynamics Underlying Verbal Working Memory Processing for Children With Hearing Loss.

OBJECTIVES: Children with hearing loss (CHL) may exhibit spoken language delays and may also experience deficits in other cognitive domains including working memory. Consistent hearing aid use (i.e., more than 10 hours per day) ameliorates these language delays; however, the impact of hearing aid intervention on the neural dynamics serving working memory remains unknown. The objective of this study was to examine the association between the amount of hearing aid use and neural oscillatory activity during verbal working memory processing in children with mild-to-severe hearing loss. DESIGN: Twenty-three CHL between 8 and 15 years-old performed a letter-based Sternberg working memory task during magnetoencephalography (MEG). Guardians also completed a questionnaire describing the participants' daily hearing aid use. Each participant's MEG data was coregistered to their structural MRI, epoched, and transformed into the time-frequency domain using complex demodulation. Significant oscillatory responses corresponding to working memory encoding and maintenance were independently imaged using beamforming. Finally, these whole-brain source images were correlated with the total number of hours of weekly hearing aid use, controlling for degree of hearing loss. RESULTS: During the encoding period, hearing aid use negatively correlated with alpha-beta oscillatory activity in the bilateral occipital cortices and right precentral gyrus. In the occipital cortices, this relationship suggested that with greater hearing aid use, there was a larger suppression of occipital activity (i.e., more negative relative to baseline). In the precentral gyrus, greater hearing aid use was related to less synchronous activity (i.e., less positive relative to baseline). During the maintenance period, hearing aid use significantly correlated with alpha activity in the right prefrontal cortex, such that with greater hearing aid use, there was less right prefrontal maintenance-related activity (i.e., less positive relative to baseline). CONCLUSIONS: This study is the first to investigate the impact of hearing aid use on the neural dynamics that underlie working memory function. These data show robust relationships between the amount of hearing aid use and phase-specific neural patterns during working memory encoding and maintenance after controlling for degree of hearing loss. Furthermore, our data demonstrate that wearing hearing aids for more than ~8.5 hours/day may serve to normalize these neural patterns. This study also demonstrates the potential for neuroimaging to help determine the locus of variability in outcomes in CHL.

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.

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

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

Resting-state functional connectivity of the human hippocampus in periadolescent children: Associations with age and memory performance.

The hippocampus is necessary for declarative (relational) memory, and the ability to form hippocampal-dependent memories develops through late adolescence. This developmental trajectory of hippocampal-dependent memory could reflect maturation of intrinsic functional brain networks, but resting-state functional connectivity (rs-FC) of the human hippocampus is not well-characterized for periadolescent children. Measuring hippocampal rs-FC in periadolescence would thus fill a gap, and testing covariance of hippocampal rs-FC with age and memory could inform theories of cognitive development. Here, we studied hippocampal rs-FC in a cross-sectional sample of healthy children (N = 96; 59 F; age 9-15 years) using a seed-based approach, and linked these data with NIH Toolbox measures, the Picture-Sequence Memory Test (PSMT) and the List Sorting Working Memory Test (LSWMT). The PSMT was expected to rely more on hippocampal-dependent memory than the LSWMT. We observed hippocampal rs-FC with an extensive brain network including temporal, parietal, and frontal regions. This pattern was consistent with prior work measuring hippocampal rs-FC in younger and older samples. We also observed novel, regionally specific variation in hippocampal rs-FC with age and hippocampal-dependent memory but not working memory. Evidence consistent with these findings was observed in a second, validation dataset of similar-age healthy children drawn from the Philadelphia Neurodevelopment Cohort. Further, a cross-dataset analysis suggested generalizable properties of hippocampal rs-FC and covariance with age and memory. Our findings connect prior work by describing hippocampal rs-FC and covariance with age and memory in typically developing periadolescent children, and our observations suggest a developmental trajectory for brain networks that support hippocampal-dependent memory.

Pubertal Testosterone Tracks the Developmental Trajectory of Neural Oscillatory Activity Serving Visuospatial Processing.

Puberty is a period of substantial hormonal fluctuations that induce dramatic physical, neurological, and behavioral changes. Previous research has demonstrated that pubertal hormones modulate cortical development, as well as sex- and age-specific patterns of cognitive development during childhood and adolescence. However, the influence of pubertal hormones on the brain's functional development, specifically neural oscillatory dynamics, has yet to be fully examined. Thus, in the current study, we used magnetoencephalography to investigate the oscillatory dynamics serving visuospatial perception and attention, and testosterone levels and chronological age as measures of development. Within a sample of typically developing youth, age was associated with changes in alpha, theta, and gamma oscillatory activity. Novel testosterone-by-sex interactions in the gamma range were identified in critical areas of the visual and attention networks. Females had increased gamma activity with increasing testosterone in the right temporal-parietal junction and occipital cortices, while males showed increased gamma activity in the right insula with increasing testosterone. These findings reveal robust developmental alterations in the oscillatory dynamics serving visuospatial processing during childhood and adolescence and provide novel insight into the hormonal basis of sexually dimorphic patterns of functional brain development during the pubertal transition that is at least partially mediated by endogenous testosterone.

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.

Multi-spectral oscillatory dynamics serving directed and divided attention.

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

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

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