Spontaneous cortical dynamics from the first years to the golden years.

In the largest and most expansive lifespan magnetoencephalography (MEG) study to date (n = 434, 6 to 84 y), we provide critical data on the normative trajectory of resting-state spontaneous activity and its temporal dynamics. We perform cutting-edge analyses to examine age and sex effects on whole-brain, spatially-resolved relative and absolute power maps, and find significant age effects in all spectral bands in both types of maps. Specifically, lower frequencies showed a negative correlation with age, while higher frequencies positively correlated with age. These correlations were further probed with hierarchical regressions, which revealed significant nonlinear trajectories in key brain regions. Sex effects were found in absolute but not relative power maps, highlighting key differences between outcome indices that are generally used interchangeably. Our rigorous and innovative approach provides multispectral maps indicating the unique trajectory of spontaneous neural activity across the lifespan, and illuminates key methodological considerations with the widely used relative/absolute power maps of spontaneous cortical dynamics.

Neuromodulatory effects of parietal high-definition transcranial direct-current stimulation on network-level activity serving fluid intelligence.

Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33 years) for 20 min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.

Multispectral brain connectivity during visual attention distinguishes controlled from uncontrolled hypertension.

Hypertension-related changes in brain function place individuals at higher risk for cognitive impairment and Alzheimer's disease. The existing functional neuroimaging literature has identified important neural and behavioural differences between normotensive and hypertensive individuals. However, previously-used methods (i.e. magnetic resonance imaging, functional near-infrared spectroscopy) rely on neurovascular coupling, which is a useful but indirect measure of neuronal activity. Furthermore, most studies fail to distinguish between controlled and uncontrolled hypertensive individuals, who exhibit significant behavioural and clinical differences. To partially remedy this gap in the literature, we used magnetoencephalography (MEG) to directly examine neuronal activity that is invariant to neurovascular coupling changes induced by hypertension. Our study included 52 participants (19 healthy controls, 15 controlled hypertensives, 18 uncontrolled hypertensives) who completed a modified flanker attention task during MEG. We identified significant oscillatory neural responses in two frequencies (alpha: 8-14 Hz, gamma: 48-60 Hz) for imaging and used grand-averaged images to determine seeds for whole-brain connectivity analysis. We then conducted Fisher-z tests for each pair of groups, using the relationship between the neural connectivity and behavioural attention effects. This highlighted a distributed network of regions associated with cognitive control and selective attention, including frontal-occipital and interhemispheric occipital connections. Importantly, the inferior frontal cortex exhibited a unique neurobehavioural relationship that distinguished the uncontrolled hypertensive group from the controlled hypertensive and normotensive groups. This is the first investigation of hypertension using MEG and identifies critical whole-brain connectivity differences based on hypertension profiles. KEY POINTS: Structural and functional changes in brain circuitry scale with hypertension severity and increase the risk of cognitive impairment and Alzheimer's disease. We harness the excellent spatiotemporal precision of magnetoencephalography (MEG) to directly quantify dynamic functional connectivity in healthy control, controlled hypertensive and uncontrolled hypertensive groups during a flanker task. In the first MEG study of hypertension, we show that there are neurobehavioural relationships that distinguish the uncontrolled hypertensive group from healthy and controlled hypertensive group in the prefrontal cortex. These results provide novel insights into the differential impact of hypertension on brain dynamics underlying selective attention.

Healthy aging alters the oscillatory dynamics and fronto-parietal connectivity serving fluid intelligence.

Fluid intelligence (Gf) involves logical reasoning and novel problem-solving abilities. Often, abstract reasoning tasks like Raven's progressive matrices are used to assess Gf. Prior work has shown an age-related decline in fluid intelligence capabilities, and although many studies have sought to identify the underlying mechanisms, our understanding of the critical brain regions and dynamics remains largely incomplete. In this study, we utilized magnetoencephalography (MEG) to investigate 78 individuals, ages 20-65 years, as they completed an abstract reasoning task. MEG data was co-registered with structural MRI data, transformed into the time-frequency domain, and the resulting neural oscillations were imaged using a beamformer. We found worsening behavioral performance with age, including prolonged reaction times and reduced accuracy. MEG analyses indicated robust oscillations in the theta, alpha/beta, and gamma range during the task. Whole brain correlation analyses with age revealed relationships in the theta and alpha/beta frequency bands, such that theta oscillations became stronger with increasing age in a right prefrontal region and alpha/beta oscillations became stronger with increasing age in parietal and right motor cortices. Follow-up connectivity analyses revealed increasing parieto-frontal connectivity with increasing age in the alpha/beta frequency range. Importantly, our findings are consistent with the parieto-frontal integration theory of intelligence (P-FIT). These results further suggest that as people age, there may be alterations in neural responses that are spectrally specific, such that older people exhibit stronger alpha/beta oscillations across the parieto-frontal network during abstract reasoning tasks.

Optimal gamma-band entrainment of visual cortex.

Visual entrainment is a powerful and widely used research tool to study visual information processing in the brain. While many entrainment studies have focused on frequencies around 14-16 Hz, there is renewed interest in understanding visual entrainment at higher frequencies (e.g., gamma-band entrainment). Notably, recent groundbreaking studies have demonstrated that gamma-band visual entrainment at 40 Hz may have therapeutic effects in the context of Alzheimer's disease (AD) by stimulating specific neural ensembles, which utilize GABAergic signaling. Despite such promising findings, few studies have investigated the optimal parameters for gamma-band visual entrainment. Herein, we examined whether visual stimulation at 32, 40, or 48 Hz produces optimal visual entrainment responses using high-density magnetoencephalography (MEG). Our results indicated strong entrainment responses localizing to the primary visual cortex in each condition. Entrainment responses were stronger for 32 and 40 Hz relative to 48 Hz, indicating more robust synchronization of neural ensembles at these lower gamma-band frequencies. In addition, 32 and 40 Hz entrainment responses showed typical patterns of habituation across trials, but this effect was absent for 48 Hz. Finally, connectivity between visual cortex and parietal and prefrontal cortices tended to be strongest for 40 relative to 32 and 48 Hz entrainment. These results suggest that neural ensembles in the visual cortex may resonate at around 32 and 40 Hz and thus entrain more readily to photic stimulation at these frequencies. Emerging AD therapies, which have focused on 40 Hz entrainment to date, may be more effective at lower relative to higher gamma frequencies, although additional work in clinical populations is needed to confirm these findings. PRACTITIONER POINTS: Gamma-band visual entrainment has emerged as a therapeutic approach for eliminating amyloid in Alzheimer's disease, but its optimal parameters are unknown. We found stronger entrainment at 32 and 40 Hz compared to 48 Hz, suggesting neural ensembles prefer to resonate around these relatively lower gamma-band frequencies. These findings may inform the development and refinement of innovative AD therapies and the study of GABAergic visual cortical functions.

Chronic cannabis use alters the spontaneous and oscillatory gamma dynamics serving cognitive control.

Regular cannabis use is associated with cortex-wide changes in spontaneous and oscillatory activity, although the functional significance of such changes remains unclear. We hypothesized that regular cannabis use would suppress spontaneous gamma activity in regions serving cognitive control and scale with task performance. Participants (34 cannabis users, 33 nonusers) underwent an interview regarding their substance use history and completed the Eriksen flanker task during magnetoencephalography (MEG). MEG data were imaged in the time-frequency domain and virtual sensors were extracted from the peak voxels of the grand-averaged oscillatory interference maps to quantify spontaneous gamma activity during the pre-stimulus baseline period. We then assessed group-level differences in spontaneous and oscillatory gamma activity, and their relationship with task performance and cannabis use metrics. Both groups exhibited a significant behavioral flanker interference effect, with slower responses during incongruent relative to congruent trials. Mixed-model ANOVAs indicated significant gamma-frequency neural interference effects in the left frontal eye fields (FEF) and left temporoparietal junction (TPJ). Further, a group-by-condition interaction was detected in the left FEF, with nonusers exhibiting stronger gamma oscillations during incongruent relative to congruent trials and cannabis users showing no difference. In addition, spontaneous gamma activity was sharply suppressed in cannabis users relative to nonusers in the left FEF and TPJ. Finally, spontaneous gamma activity in the left FEF and TPJ was associated with task performance across all participants, and greater cannabis use was associated with weaker spontaneous gamma activity in the left TPJ of the cannabis users. Regular cannabis use was associated with weaker spontaneous gamma in the TPJ and FEF. Further, the degree of use may be proportionally related to the degree of suppression in spontaneous activity in the left TPJ.

High-definition transcranial direct current stimulation of the parietal cortices modulates the neural dynamics underlying verbal working memory.

Verbal working memory (vWM) is an essential limited-capacity cognitive system that spans the fronto-parietal network and utilizes the subprocesses of encoding, maintenance, and retrieval. With the recent widespread use of noninvasive brain stimulation techniques, multiple recent studies have examined whether such stimulation may enhance cognitive abilities such as vWM, but the findings to date remain unclear in terms of both behavior and critical brain regions. In the current study, we applied high-definition direct current stimulation to the left and right parietal cortices of 39 healthy adults in three separate sessions (left anodal, right anodal, and sham). Following stimulation, participants completed a vWM task during high-density magnetoencephalography (MEG). Significant neural responses at the sensor-level were imaged using a beamformer and whole-brain ANOVAs were used to identify the specific neuromodulatory effects of the stimulation conditions on neural responses serving distinct phases of vWM. We found that right stimulation had a faciliatory effect relative to left stimulation and sham on theta oscillations during encoding in the right inferior frontal, while the opposite pattern was observed for left supramarginal regions. Stimulation also had a faciliatory effect on theta in occipital regions and alpha in temporal regions regardless of the laterality of stimulation. In summary, our data suggest that parietal HD-tDCS both facilitates and interferes with neural responses underlying both the encoding and maintenance phases of vWM. Future studies are warranted to determine whether specific tDCS parameters can be tuned to accentuate the facilitation responses and attenuate the interfering aspects.

Disturbances in primary visual processing as a function of healthy aging.

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

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

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

Developmental changes in endogenous testosterone have sexually-dimorphic effects on spontaneous cortical dynamics.

The transition from childhood to adolescence is associated with an influx of sex hormones, which not only facilitates physical and behavioral changes, but also dramatic changes in neural circuitry. While previous work has shown that pubertal hormones modulate structural and functional brain development, few of these studies have focused on the impact that such hormones have on spontaneous cortical activity, and whether these effects are modulated by sex during this critical developmental window. Herein, we examined the effect of endogenous testosterone on spontaneous cortical activity in 71 typically-developing youth (ages 10-17 years; 32 male). Participants completed a resting-state magnetoencephalographic (MEG) recording, structural MRI, and provided a saliva sample for hormone analysis. MEG data were source-reconstructed and the power within five canonical frequency bands (delta, theta, alpha, beta, and gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially specific effects of testosterone and sex by testosterone interactions, while covarying out age. We found robust sex differences in the modulatory effects of testosterone on spontaneous delta, beta, and gamma activity. These interactions were largely confined to frontal cortices and exhibited a stark switch in the directionality of the correlation from the low (delta) to high frequencies (beta/gamma). For example, in the delta band, greater testosterone related to lower relative power in prefrontal cortices in boys, while the reverse pattern was found for girls. These data suggest testosterone levels are uniquely related to the development of spontaneous cortical dynamics during adolescence, and such levels are associated with different developmental patterns in males and females within regions implicated in executive functioning.

Regular cannabis use alters the neural dynamics serving complex motor control.

Cannabis is the most widely used recreational drug in the United States and regular use has been linked to deficits in attention and memory. However, the effects of regular use on motor control are less understood, with some studies showing deficits and others indicating normal performance. Eighteen users and 23 nonusers performed a motor sequencing task during high-density magnetoencephalography (MEG). The MEG data was transformed into the time-frequency domain and beta responses (16-24 Hz) during motor planning and execution phases were imaged separately using a beamformer approach. Whole-brain maps were examined for group (cannabis user/nonuser) and time window (planning/execution) effects. As expected, there were no group differences in task performance (e.g., reaction time, accuracy, etc.). Regular cannabis users exhibited stronger beta oscillations in the contralateral primary motor cortex compared to nonusers during the execution phase of the motor sequences, but not during the motor planning phase. Similar group-by-time window interactions were observed in the left superior parietal, right inferior frontal cortices, right posterior insular cortex, and the bilateral motor cortex. We observed differences in the neural dynamics serving motor control in regular cannabis users compared to nonusers, suggesting regular users may employ compensatory processing in both primary motor and higher-order motor cortices to maintain adequate task performance. Future studies will need to examine more complex motor control tasks to ascertain whether this putative compensatory activity eventually becomes exhausted and behavioral differences emerge.

Dehydroepiandrosterone mediates associations between trauma-related symptoms and anterior pituitary volume in children and adolescents.

INTRODUCTION: The anterior pituitary gland (PG) is a potential locus of hypothalamic-pituitary-adrenal (HPA) axis responsivity to early life stress, with documented associations between dehydroepiandrosterone (DHEA) levels and anterior PG volumes. In adults, elevated anxiety/depressive symptoms are related to diminished DHEA levels, and studies have shown a positive relationship between DHEA and anterior pituitary volumes. However, specific links between responses to stress, DHEA levels, and anterior pituitary volume have not been established in developmental samples. METHODS: High-resolution T1-weighted MRI scans were collected from 137 healthy youth (9-17 years; Mage = 12.99 (SD = 1.87); 49% female; 85% White, 4% Indigenous, 1% Asian, 4% Black, 4% multiracial, 2% not reported). The anterior and posterior PGs were manually traced by trained raters. We examined the mediating effects of salivary DHEA on trauma-related symptoms (i.e., anxiety, depression, and posttraumatic) and PG volumes as well as an alternative model examining mediating effects of PG volume on DHEA and trauma-related symptoms. RESULTS: DHEA mediated the association between anxiety symptoms and anterior PG volume. Specifically, higher anxiety symptoms related to lower DHEA levels, which in turn were related to smaller anterior PG. CONCLUSIONS: These results shed light on the neurobiological sequelae of elevated anxiety in youth and are consistent with adult findings showing suppressed levels of DHEA in those with greater comorbid anxiety and depression. Specifically, adolescents with greater subclinical anxiety may exhibit diminished levels of DHEA during the pubertal window, which may be associated with disruptions in anterior PG growth.

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.

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.

Modulation of movement-related oscillatory signatures by cognitive interference in healthy aging.

Age-related changes in the neurophysiology underlying motor control are well documented, but whether these changes are specific to motor function or more broadly reflect age-related alterations in fronto-parietal circuitry serving attention and other higher-level processes remains unknown. Herein, we collected high-density magnetoencephalography (MEG) in 72 healthy adults (age 28-63 years) as they completed an adapted version of the multi-source interference task that involved two subtypes of cognitive interference (i.e., flanker and Simon) and their integration (i.e., multi-source). All MEG data were examined for age-related changes in neural oscillatory activity using a whole-brain beamforming approach. Our primary findings indicated robust behavioral differences in task performance based on the type of interference, as well as stronger beta oscillations with increasing age in the right dorsolateral prefrontal cortices (flanker and multi-source conditions), left parietal (flanker and Simon), and medial parietal regions (multi-source). Overall, these data indicate that healthy aging is associated with alterations in higher-order association cortices that are critical for attention and motor control in the context of cognitive interference.

Hypertension Impacts the Oscillatory Dynamics Serving the Encoding Phase of Verbal Working Memory.

BACKGROUND: Chronic hypertension is known to be a major contributor to cognitive decline, with executive function and working memory being among the domains most commonly affected. Despite the growing literature on such dysfunction in patients with hypertension, the underlying neural processes are poorly understood. METHODS: In this cross-sectional study, we examine these neural processes by having participants with controlled hypertension, uncontrolled hypertension, and healthy controls perform a verbal working memory task during magnetoencephalography. Neural oscillations associated with the encoding and maintenance components of the working memory task were imaged and statistically evaluated among the 3 groups. RESULTS: Differences related to hypertension emerged during the encoding phase, where the hypertension groups exhibited weaker α-ß oscillatory responses compared with controls in the left parietal cortices, whereas such oscillatory activity differed between the 2 hypertension groups in the right prefrontal regions. Importantly, these neural responses in the prefrontal and parietal cortices during encoding were also significantly associated with behavioral performance across all participants. CONCLUSIONS: Overall, our data suggest that hypertension is associated with neurophysiological abnormalities during working memory encoding, whereas the neural processes serving maintenance seem to be preserved. The right hemispheric neural responses likely reflected compensatory processing, which patients with controlled hypertension may use to achieve verbal working memory function at the level of controls, as opposed to the uncontrolled hypertension group where diminished resources may have limited such additional recruitment.

Regular cannabis use modulates gamma activity in brain regions serving motor control.

BACKGROUND: People who regularly use cannabis exhibit altered brain dynamics during cognitive control tasks, though the impact of regular cannabis use on the neural dynamics serving motor control remains less understood. AIMS: We sought to investigate how regular cannabis use modulates the neural dynamics serving motor control. METHODS: Thirty-four people who regularly use cannabis (cannabis+) and 33 nonusers (cannabis-) underwent structured interviews about their substance use history and performed the Eriksen flanker task to map the neural dynamics serving motor control during high-density magnetoencephalography (MEG). The resulting neural data were transformed into the time-frequency domain to examine oscillatory activity and were imaged using a beamforming approach. RESULTS: MEG sensor-level analyses revealed robust beta (16-24 Hz) and gamma oscillations (66-74 Hz) during motor planning and execution, which were imaged using a beamformer. Both responses peaked in the left primary motor cortex and voxel time series were extracted to evaluate the spontaneous and oscillatory dynamics. Our key findings indicated that the cannabis+ group exhibited weaker spontaneous gamma activity in the left primary motor cortex relative to the cannabis- group, which scaled with cannabis use and behavioral metrics. Interestingly, regular cannabis use was not associated with differences in oscillatory beta and gamma activity, and there were no group differences in spontaneous beta activity. CONCLUSIONS: Our findings suggest that regular cannabis use is associated with suppressed spontaneous gamma activity in the left primary motor cortex, which scales with the degree of cannabis use disorder symptomatology and is coupled to behavioral task performance.

Anterior pituitary gland volume mediates associations between pubertal hormones and changes in transdiagnostic symptoms in youth.

The pituitary gland (PG) plays a central role in the production and secretion of pubertal hormones, with documented links to the emergence and increase in mental health symptoms known to occur during adolescence. Although much of the literature has focused on examining whole PG volume, recent findings suggest that there are associations among pubertal hormone levels, including dehydroepiandrosterone (DHEA), subregions of the PG, and elevated mental health symptoms (e.g., internalizing symptoms) during adolescence. Surprisingly, studies have not yet examined associations among these factors and increasing transdiagnostic symptomology, despite DHEA being a primary output of the anterior PG. Therefore, the current study sought to fill this gap by examining whether anterior PG volume specifically mediates associations between DHEA levels and changes in dysregulation symptoms in an adolescent sample ( N = 114, 9 - 17 years, M age = 12.87, SD = 1.88). Following manual tracing of the anterior and posterior PG, structural equation modeling revealed that greater anterior, not posterior, PG volume mediated the association between greater DHEA levels and increasing dysregulation symptoms across time, controlling for baseline dysregulation symptom levels. These results suggest specificity in the role of the anterior PG in adrenarcheal processes that may confer risk for psychopathology during adolescence. This work not only highlights the importance of separately tracing the anterior and posterior PG, but also suggests that transdiagnostic factors like dysregulation are useful in parsing hormone-related increases in mental health symptoms in youth.

The neural oscillations serving task switching are altered in cannabis users.

BACKGROUND: Regular cannabis is known to impact higher-order cognitive processes such as attention, but far less is known regarding cognitive flexibility, a component of executive function. Moreover, whether such changes are related to aberrations in the neural oscillatory dynamics serving flexibility remains poorly understood. AIMS: Quantify the neural oscillatory dynamics serving cognitive flexibility by having participants complete a task-switching paradigm during magnetoencephalography (MEG). Probe whole-brain maps to identify alterations in chronic cannabis users relative to nonusers and determine how these alterations relate to the degree of cannabis use involvement. METHODS: In all, 25 chronic cannabis users and 30 demographically matched nonuser controls completed neuropsychological testing, an interview regarding their substance use, a urinalysis, and a task switch paradigm during MEG. Time-frequency windows of interest were identified using a data-driven statistical approach and these were imaged using a beamformer. Whole-brain neural switch cost maps were computed by subtracting the oscillatory maps of the no-switch condition from the switch condition per participant. These were examined for group differences. RESULTS: Cannabis users had weaker theta switch cost responses in the dorsolateral and dorsomedial prefrontal cortices, while nonusers showed the typical pattern of greater recruitment during switch relative to no switch trials. In addition, theta activity in the dorsomedial prefrontal cortex was significantly correlated with cannabis use involvement. CONCLUSIONS: Cannabis users exhibited altered theta switch cost activity compared to nonusers in prefrontal cortical regions, which are critical for cognitive flexibility. This activity scaled with cannabis use involvement, indicating a link between cannabis use and aberrant oscillatory activity underlying cognitive flexibility.

Developmentally sensitive multispectral cortical connectivity profiles serving visual selective attention.

Throughout childhood and adolescence, the brain undergoes significant structural and functional changes that contribute to the maturation of multiple cognitive domains, including selective attention. Selective attention is crucial for healthy executive functioning and while key brain regions serving selective attention have been identified, their age-related changes in neural oscillatory dynamics and connectivity remain largely unknown. We examined the developmental sensitivity of selective attention circuitry in 91 typically developing youth aged 6 - 13 years old. Participants completed a number-based Simon task while undergoing magnetoencephalography (MEG) and the resulting data were preprocessed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach, and task-related peak voxels in the occipital, parietal, and cerebellar cortices were used as seeds for subsequent whole-brain connectivity analyses in the alpha and gamma range. Our key findings revealed developmentally sensitive connectivity profiles in multiple regions crucial for selective attention, including the temporoparietal junction (alpha) and prefrontal cortex (gamma). Overall, these findings suggest that brain regions serving selective attention are highly sensitive to developmental changes during the pubertal transition period.