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.

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.

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.

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.

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.

Theta oscillatory dynamics serving cognitive control index psychosocial distress in youth.

Background: Psychosocial distress among youth is a major public health issue characterized by disruptions in cognitive control processing. Using the National Institute of Mental Health's Research Domain Criteria (RDoC) framework, we quantified multidimensional neural oscillatory markers of psychosocial distress serving cognitive control in youth. Methods: The sample consisted of 39 peri-adolescent participants who completed the NIH Toolbox Emotion Battery (NIHTB-EB) and the Eriksen flanker task during magnetoencephalography (MEG). A psychosocial distress index was computed with exploratory factor analysis using assessments from the NIHTB-EB. MEG data were analyzed in the time-frequency domain and peak voxels from oscillatory maps depicting the neural cognitive interference effect were extracted for voxel time series analyses to identify spontaneous and oscillatory aberrations in dynamics serving cognitive control as a function of psychosocial distress. Further, we quantified the relationship between psychosocial distress and dynamic functional connectivity between regions supporting cognitive control. Results: The continuous psychosocial distress index was strongly associated with validated measures of pediatric psychopathology. Theta-band neural cognitive interference was identified in the left dorsolateral prefrontal cortex (dlPFC) and middle cingulate cortex (MCC). Time series analyses of these regions indicated that greater psychosocial distress was associated with elevated spontaneous activity in both the dlPFC and MCC and blunted theta oscillations in the MCC. Finally, we found that stronger phase coherence between the dlPFC and MCC was associated with greater psychosocial distress. Conclusions: Greater psychosocial distress was marked by alterations in spontaneous and oscillatory theta activity serving cognitive control, along with hyperconnectivity between the dlPFC and MCC.

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.

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 alterations in the neural oscillatory dynamics underlying attentional reorienting.

The neural and cognitive processes underlying the flexible allocation of attention undergo a protracted developmental course with changes occurring throughout adolescence. Despite documented age-related improvements in attentional reorienting throughout childhood and adolescence, the neural correlates underlying such changes in reorienting remain unclear. Herein, we used magnetoencephalography (MEG) to examine neural dynamics during a Posner attention-reorienting task in 80 healthy youth (6-14 years old). The MEG data were examined in the time-frequency domain and significant oscillatory responses were imaged in anatomical space. During the reorienting of attention, youth recruited a distributed network of regions in the fronto-parietal network, along with higher-order visual regions within the theta (3-7 Hz) and alpha-beta (10-24 Hz) spectral windows. Beyond the expected developmental improvements in behavioral performance, we found stronger theta oscillatory activity as a function of age across a network of prefrontal brain regions irrespective of condition, as well as more limited age- and validity-related effects for alpha-beta responses. Distinct brain-behavior associations between theta oscillations and attention-related symptomology were also uncovered across a network of brain regions. Taken together, these data are the first to demonstrate developmental effects in the spectrally-specific neural oscillations serving the flexible allocation of attention.

Oscillatory dynamics serving visual selective attention during a Simon task.

Selective attention is an important component of cognitive control and is essential for day-to-day functioning. The Simon task is a common test of visual selective attention that has been widely used to probe response selection, inhibition and cognitive control. However, to date, there is a dearth of literature that has focused on the oscillatory dynamics serving task performance in the selective attention component of this task. In this study, 32 healthy adults (mean age: 33.09 years, SD: 7.27 years) successfully completed a modified version of the Simon task during magnetoencephalography. All magnetoencephalographic data were pre-processed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach, and peak task-related neural activity was extracted to examine the temporal dynamics. Across both congruent and Simon conditions, our results indicated robust decreases in alpha (8-12 Hz) activity in the bilateral occipital regions and cuneus during task performance, while increases in theta (3-6 Hz) oscillatory activity were detected in regions of the dorsal frontoparietal attention network, including the dorsolateral prefrontal cortex, frontal eye fields and insula. Lastly, whole-brain condition-wise analyses showed Simon interference effects in the theta range in the superior parietal region and the alpha range in the posterior cingulate and inferior frontal cortices. These findings provide network-specific insights into the oscillatory dynamics serving visual selective attention.

Altered functional connectivity and oscillatory dynamics in polysubstance and cannabis only users during visuospatial processing.

RATIONALE AND OBJECTIVES: Cannabis use is often associated with the use of other psychoactive substances, which is subsequently linked to an increased risk for addiction. While there is a growing body of neuroimaging literature investigating the cognitive effect of long-term cannabis use, very little is known about the potential additive effects of cannabis polysubstance use. METHODS: Fifty-six adults composed of 18 polysubstance users (i.e., cannabis plus at least one other illicit substance), 19 cannabis-only users, and 19 nonusers completed a visuospatial attention task while undergoing magnetoencephalography. A data-driven approach was used to identify oscillatory neural responses, which were imaged using a beamforming approach. The resulting cortical regions were probed for group differences and used as seeds for whole-brain connectivity analysis. RESULTS: Participants exhibited robust theta, alpha, beta, and gamma responses during visuospatial processing. Statistical analyses indicated that the cannabis-only group had weaker occipital theta relative to the nonusers, and that both polysubstance and cannabis-only users had reduced spontaneous gamma in the occipital cortices during the pre-stimulus baseline period relative to nonusers. Finally, functional connectivity analyses revealed that polysubstance users had sharply reduced beta connectivity between occipital and prefrontal, as well as occipital and left temporal cortices. CONCLUSIONS: Cannabis use should be considered in a polysubstance context, as our correlational design suggests differences in functional connectivity among those who reported cannabis-only versus polysubstance use in occipital to prefrontal pathways critical to visuospatial processing and attention function. Future work should distinguish the effect of different polysubstance combinations and use more causal designs.

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.

Regular cannabis use modulates the impact of HIV on the neural dynamics serving cognitive control.

BACKGROUND: Cannabis use and HIV are independently associated with decrements in cognitive control. However, the combined effects of HIV and regular cannabis use on the brain circuitry serving higher-order cognition are unclear. AIMS: Investigate the interaction between cannabis and HIV on neural interference effects during the flanker task and spontaneous activity in regions underlying higher-order cognition. METHODS: The sample consisted of 100 participants, including people with HIV (PWH) who use cannabis, PWH who do not use cannabis, uninfected cannabis users, and uninfected nonusers. Participants 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 oscillatory maps depicting the neural flanker interference effect were probed for group differences. Voxel time series were then assessed for group-level differences in spontaneous activity. RESULTS: Group differences in behavioral performance were identified along with group differences in theta and alpha neural interference responses in higher-order regions across the cortex, with nonusers with HIV generally exhibiting the most aberrant responses. Likewise, time series analyses indicated that nonusers with HIV also had significantly elevated spontaneous alpha activity in the left inferior frontal and dorsolateral prefrontal cortices (dlPFC). Finally, we found that spontaneous and oscillatory alpha activity were significantly coupled in the inferior frontal cortex and dlPFC among cannabis users, but not nonusers. CONCLUSIONS: Regular cannabis use appears to suppress the impact of HIV on spontaneous and oscillatory alpha deficits in the left inferior frontal cortex and dlPFC.

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.

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.

Aberrant inhibitory processing in the somatosensory cortices of cannabis-users.

BACKGROUND: Delta-9 tetrahydrocannabinol (THC) is a major exogenous psychoactive agent, which acts as a partial agonist on cannabinoid (CB1) receptors. THC is known to inhibit presynaptic neurotransmission and has been repeatedly linked to acute decrements in cognitive function across multiple domains. Previous electrophysiological studies of sensory gating have shown specific deficits in inhibitory processing in cannabis-users, but to date these findings have been limited to the auditory cortices, and the degree to which these aberrations extend to other brain regions remains largely unknown. METHODS: We used magnetoencephalography (MEG) and a paired-pulse somatosensory stimulation paradigm to probe inhibitory processing in 29 cannabis-users (i.e. at least four times per month) and 41 demographically matched non-user controls. MEG responses to each stimulation were imaged in both the oscillatory and time domain, and voxel time-series data were extracted to quantify the dynamics of sensory gating, oscillatory gamma activity, evoked responses, and spontaneous neural activity. RESULTS: We observed robust somatosensory responses following both stimulations, which were used to compute sensory gating ratios. Cannabis-users exhibited significantly impaired gating relative to non-users in somatosensory cortices, as well as decreased spontaneous neural activity. In contrast, oscillatory gamma activity did not appear to be affected by cannabis use. CONCLUSIONS: We observed impaired gating of redundant somatosensory information and altered spontaneous activity in the same cortical tissue in cannabis-users compared to non-users. These data suggest that cannabis use is associated with a decline in the brain's ability to properly filter repetitive information and impairments in cortical inhibitory processing.

Stress-induced aberrations in sensory processing predict worse cognitive outcomes in healthy aging adults.

It is well recognized that not all individuals age equivalently, with functional dependence attributable, at least in part, to stress accumulated across the lifespan. Amongst these dependencies are age-related declines in cognitive function, which may be the result of impaired inhibitory processing (e.g., sensory gating). Herein, we examined the unique roles of life and biological stress on somatosensory gating dynamics in 74 adults (22-72 years old). Participants completed a sensory gating paired-pulse electrical stimulation paradigm of the right median nerve during magnetoencephalography (MEG) and data were subjected to advanced oscillatory and time-domain analysis methods. We observed separable mechanisms by which increasing levels of life and biological stress predicted higher oscillatory gating ratios, indicative of age-related impairments in inhibitory function. Specifically, elevations in life stress significantly modulated the neural response to the first stimulation in the pair, while elevations in biological stress significantly modulated the neural response to the second stimulation in the pair. In contrast, neither elevations in life nor biological stress significantly predicted the gating of time-domain neural activity in the somatosensory cortex. Finally, our study is the first to link stress-induced decline in sensory gating to cognitive dysfunction, suggesting that gating paradigms may hold promise for detecting discrepant functional trajectories in age-related pathologies in the future.

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.

The age-related trajectory of visual attention neural function is altered in adults living with HIV: A cross-sectional MEG study.

BACKGROUND: Despite living a normal lifespan, at least 35% of persons with HIV (PWH) in resource-rich countries develop HIV-associated neurocognitive disorder (HAND). This high prevalence of cognitive decline may reflect accelerated ageing in PWH, but the evidence supporting an altered ageing phenotype in PWH has been mixed. METHODS: We examined the impact of ageing on the orienting of visual attention in PWH using dynamic functional mapping with magnetoencephalography (MEG) in 173 participants age 22-72 years-old (94 uninfected controls, 51 cognitively-unimpaired PWH, and 28 with HAND). All MEG data were imaged using a state-of-the-art beamforming approach and neural oscillatory responses during attentional orienting were examined for ageing, HIV, and cognitive status effects. FINDINGS: All participants responded slower during trials that required attentional reorienting. Our functional mapping results revealed HIV-by-age interactions in left prefrontal theta activity, alpha oscillations in the left parietal, right cuneus, and right frontal eye-fields, and left dorsolateral prefrontal beta activity (p<.005). Critically, within PWH, we observed a cognitive status-by-age interaction, which revealed that ageing impacted the oscillatory gamma activity serving attentional reorienting differently in cognitively-normal PWH relative to those with HAND in the left temporoparietal, inferior frontal gyrus, and right prefrontal cortices (p<.005). INTERPRETATION: This study provides key evidence supporting altered ageing trajectories across vital attention circuitry in PWH, and further suggests that those with HAND exhibit unique age-related changes in the oscillatory dynamics serving attention function. Additionally, our neural findings suggest that age-related changes in PWH may serve a compensatory function. FUNDING: National Institutes of Health, USA.