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.

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.

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.

Age-related alterations in the oscillatory dynamics serving verbal working memory processing.

Working memory (WM) is a foundational cognitive function involving the temporary storage of information. Unfortunately, WM is also one of the most sensitive cognitive functions to the detrimental effects of aging. Expanding the field's understanding of age-related WM changes is critical to advancing the development of strategies to mitigate age-related WM declines. In the current study, we investigated the neural mechanisms serving WM function in seventy-eight healthy aging adults (range: 20.2-65.2 years) using magnetoencephalography (MEG) and a Sternberg WM task with letter stimuli. Neural activity during the different phases of the WM task (i.e., encoding, maintenance, and retrieval) were imaged using a time-frequency resolved beamformer and whole-brain statistics were performed. We found stronger increases in theta activity and stronger decreases in alpha and beta activity (i.e., more negative relative to baseline) as a function of healthy aging. Specifically, age-related increases in theta activity were detected during the encoding period in the primary visual and left prefrontal cortices. Additionally, alpha and beta oscillations were stronger (i.e., more negative) during both encoding and maintenance in the left prefrontal cortex in older individuals. Finally, alpha and beta oscillations during the retrieval phase were stronger (i.e., more negative) in older participants within the prefrontal, parietal, and temporal cortices. Together, these results indicate that healthy aging strongly modulates the neural oscillatory dynamics serving WM function.

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.

Piecing it together: atrophy profiles of hippocampal subfields relate to cognitive impairment along the Alzheimer's disease spectrum.

Introduction: People with Alzheimer's disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls. Methods: Participants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes. Results: Our results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory. Discussion: These findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum.

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.

Movement-related beta and gamma oscillations indicate parallels and disparities between Alzheimer's disease and HIV-associated neurocognitive disorder.

People with HIV (PWH) often develop HIV-related neurological impairments known as HIV-associated neurocognitive disorder (HAND), but cognitive dysfunction in older PWH may also be due to age-related disorders such as Alzheimer's disease (AD). Discerning these two conditions is challenging since the specific neural characteristics are not well understood and limited studies have probed HAND and AD spectrum (ADS) directly. We examined the neural dynamics underlying motor processing during cognitive interference using magnetoencephalography (MEG) in 22 biomarker-confirmed patients on the ADS, 22 older participants diagnosed with HAND, and 30 healthy aging controls. MEG data were transformed into the time-frequency domain to examine movement-related oscillatory activity and the impact of cognitive interference on distinct stages of motor programming. Both cognitively impaired groups (ADS/HAND) performed significantly worse on the task (e.g., less accurate and slower reaction time) and exhibited reductions in frontal and cerebellar beta and parietal gamma activity relative to controls. Disease-specific aberrations were also detected such that those with HAND exhibited weaker gamma interference effects than those on the ADS in frontoparietal and motor areas. Additionally, temporally distinct beta interference effects were identified, with ADS participants exhibiting stronger beta interference activity in the temporal cortex during motor planning, along with weaker beta interference oscillations dispersed across frontoparietal and cerebellar cortices during movement execution relative to those with HAND. These results indicate both overlapping and distinct neurophysiological aberrations in those with ADS disorders or HAND in key motor and top-down cognitive processing regions during cognitive interference and provide new evidence for distinct neuropathology.

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.

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 longitudinal trajectory of default mode network connectivity in healthy youth with subclinical depressive and posttraumatic stress symptoms.

The default mode network (DMN) plays a crucial role in internal self-processing, rumination, and social functions. Disruptions to DMN connectivity have been linked with early adversity and the emergence of psychopathology in adolescence and early adulthood. Herein, we investigate how subclinical psychiatric symptoms can impact DMN functional connectivity during the pubertal transition. Resting-state fMRI data were collected annually from 190 typically-developing youth (9-15 years-old) at three timepoints and within-network DMN connectivity was computed. We used latent growth curve modeling to determine how self-reported depressive and posttraumatic stress symptoms predicted rates of change in DMN connectivity over the three-year period. In the baseline model without predictors, we found no systematic changes in DMN connectivity over time. However, significant modulation emerged after adding psychopathology predictors; greater depressive symptomatology was associated with significant decreases in connectivity over time, whereas posttraumatic stress symptoms were associated with significant increases in connectivity over time. Follow-up analyses revealed that these effects were driven by connectivity changes involving the dorsal medial prefrontal cortex subnetwork. In conclusion, these data suggest that subclinical depressive and posttraumatic symptoms alter the trajectory of DMN connectivity, which may indicate that this network is a nexus of clinical significance in mental health disorders.

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.

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.

Oscillatory markers of neuroHIV-related cognitive impairment and Alzheimer's disease during attentional interference processing.

People with HIV (PWH) frequently experience mild cognitive decline, which is typically attributed to HIV-associated neurocognitive disorder (HAND). However, such declines could also be a sign of early Alzheimer's disease (AD) in older PWH. Distinguishing these two pathologies in PWH is exceedingly difficult, as there is a major knowledge gap regarding their neural and neuropsychological bases. In the current study, we begin to address this knowledge gap by recording magnetoencephalography (MEG) during a flanker interference task in 31 biomarker-confirmed patients on the AD spectrum (ADS), 25 older participants with HAND, and 31 cognitively-normal controls. MEG data was examined in the time-frequency domain using a data-driven approach. Our results indicated that the clinical groups (ADS/HAND) performed significantly worse than controls on the task and exhibited aberrations in interference-related theta and alpha oscillations, some of which were disease-specific. Specifically, patients (ADS/HAND) exhibited weaker interference activity in frontoparietal and cingulate cortices compared to controls, while the ADS group exhibited stronger theta interference than those with HAND in frontoparietal, occipital, and temporal cortices. These results reveal overlapping and distinct patterns of neurophysiological alterations among those with ADS and HAND in attentional processing centers and suggest the existence of unique oscillatory markers of each condition.

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.

Convergent and divergent oscillatory aberrations during visuospatial processing in HIV-related cognitive impairment and Alzheimer's disease.

Adults with HIV frequently develop a form of mild cognitive impairment known as HIV-associated neurocognitive disorder (HAND), but presumably cognitive decline in older persons with HIV could also be attributable to Alzheimer's disease (AD). However, distinguishing these two conditions in individual patients is exceedingly difficult, as the distinct neural and neuropsychological features are poorly understood and most studies to date have only investigated HAND or AD spectrum (ADS) disorders in isolation. The current study examined the neural dynamics underlying visuospatial processing using magnetoencephalography (MEG) in 31 biomarker-confirmed patients on the ADS, 26 older participants who met criteria for HAND, and 31 older cognitively normal controls. MEG data were examined in the time-frequency domain, and a data-driven approach was utilized to identify the neural dynamics underlying visuospatial processing. Both clinical groups (ADS/HAND) were significantly less accurate than controls on the task and exhibited stronger prefrontal theta oscillations compared to controls. Regarding disease-specific alterations, those with HAND exhibited stronger alpha oscillations than those on the ADS in frontoparietal and temporal cortices. These results indicate both common and unique neurophysiological alterations among those with ADS disorders and HAND in regions serving visuospatial processing and suggest the underlying neuropathological features are at least partially distinct.

Epigenetic aging is associated with aberrant neural oscillatory dynamics serving visuospatial processing in people with HIV.

BACKGROUND: Despite effective antiretroviral therapy, cognitive impairment and other aging-related comorbidities are more prevalent in people with HIV (PWH) than in the general population. Previous research examining DNA methylation has shown PWH exhibit accelerated biological aging. However, it is unclear how accelerated biological aging may affect neural oscillatory activity in virally suppressed PWH, and more broadly how such aberrant neural activity may impact neuropsychological performance. METHODS: In the present study, participants (n = 134) between the ages of 23 - 72 years underwent a neuropsychological assessment, a blood draw to determine biological age via DNA methylation, and a visuospatial processing task during magnetoencephalography (MEG). Our analyses focused on the relationship between biological age and oscillatory theta (4-8 Hz) and alpha (10 - 16 Hz) activity among PWH (n=65) and seronegative controls (n = 69). RESULTS: PWH had significantly elevated biological age when controlling for chronological age relative to controls. Biological age was differentially associated with theta oscillations in the left posterior cingulate cortex (PCC) and with alpha oscillations in the right medial prefrontal cortex (mPFC) among PWH and seronegative controls. Stronger alpha oscillations in the mPFC were associated with lower CD4 nadir and lower current CD4 counts, suggesting such responses were compensatory. Participants who were on combination antiretroviral therapy for longer had weaker theta oscillations in the PCC. CONCLUSIONS: These findings support the concept of interactions between biological aging and HIV status on the neural oscillatory dynamics serving visuospatial processing. Future work should elucidate the long-term trajectory and impact of accelerated aging on neural oscillatory dynamics in PWH.

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.

Spontaneous sensorimotor beta power and cortical thickness uniquely predict motor function in healthy aging.

BACKGROUND: Spontaneous beta activity in the primary motor cortices has been shown to increase in amplitude with advancing age, and that such increases are tightly coupled to stronger motor-related beta oscillations during movement planning. However, the relationship between these age-related changes in spontaneous beta in the motor cortices, local cortical thickness, and overall motor function remains unclear. METHODS: We collected resting-state magnetoencephalography (MEG), high-resolution structural MRI, and motor function scores using a neuropsychological battery from 126 healthy adults (56 female; age range = 22-72 years). MEG data were source-imaged and a whole-brain vertex-wise regression model was used to assess age-related differences in spontaneous beta power across the cortex. Cortical thickness was computed from the structural MRI data and local beta power and cortical thickness values were extracted from the sensorimotor cortices. To determine the unique contribution of age, spontaneous beta power, and cortical thickness to the prediction of motor function, a hierarchical regression approach was used. RESULTS: There was an increase in spontaneous beta power with age across the cortex, with the strongest increase being centered on the sensorimotor cortices. Sensorimotor cortical thickness was not related to spontaneous beta power, above and beyond age. Interestingly, both cortical thickness and spontaneous beta power in sensorimotor regions each uniquely contributed to the prediction of motor function when controlling for age. DISCUSSION: This multimodal study showed that cortical thickness and spontaneous beta activity in the sensorimotor cortices have dissociable contributions to motor function across the adult lifespan. These findings highlight the complexity of interactions between structure and function and the importance of understanding these interactions in order to advance our understanding of healthy aging and disease.