Search

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting “Biotypes of CNS Complications in People Living with HIV,” held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.

Resting-state functional magnetic resonance imaging (rs-fMRI)-derived functional connectivity (FC) patterns have been extensively used to delineate global functional organization of the human brain in healthy development and neuropsychiatric disorders. In this paper, we investigate how FC in males and females differs in an age prediction framework.We first estimate FC between regions-of-interest (ROIs) using distance correlation instead of Pearson's correlation. Distance correlation, as a multivariate statistical method, explores spatial relations of voxel-wise time courses within individual ROIs and measures both linear and nonlinear dependence, capturing more complex between-ROI interactions. Then, we propose a novel non-convex multi-task learning (NC-MTL) model to study age-related gender differences in FC, where age prediction for each gender group is viewed as one task, and a composite regularizer with a combination of the non-convex lWe validate the effectiveness of our NC-MTL model with distance correlation-based FC derived from rs-fMRI for predicting ages of both genders. The experimental results on the Philadelphia Neurodevelopmental Cohort demonstrate that our NC-MTL model outperforms several other competing MTL models in age prediction. We also compare the age prediction performance of our NC-MTL model using FC estimated by Pearson's correlation and distance correlation, which shows that distance correlation-based FC is more discriminative for age prediction than Pearson's correlation-based FC.This paper presents a novel framework for functional connectome developmental studies, characterizing developmental gender differences in FC patterns.

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

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

Background: Motor control requires a reciprocal volley between somatosensory and motor systems, with somatosensory feedback being essential for the online updating of motor commands to achieve behavioral outcomes. However, this dynamic interplay among sensorimotor brain systems serving motor control remains poorly understood. Methods: To address this, we designed a novel somatosensory entrainment-movement task, which 25 adults completed during magnetoencephalography (MEG). Specifically, participants completed a quasi-paced finger-tapping paradigm while subthreshold electrical stimulation was applied to the right median nerve at a sensorimotor-relevant frequency (15 Hz) and during a second condition where no electrical stimulation was applied. The MEG data were transformed into the time-frequency domain and imaged by using a beamformer to evaluate the effect of somatosensory feedback (i.e., entrainment) on movement-related oscillations and motor performance at the single trial level. Results: Our results indicated spectrally specific reductions in movement-related oscillatory power (i.e., theta, gamma) during 15 Hz stimulation in the contralateral motor cortex during motor execution. In addition, we observed robust cross-frequency coupling within the motor cortex and further, stronger theta-gamma coupling was predictive of faster reaction times, irrespective of condition (i.e., stim vs. no stim). Finally, in the presence of electrical stimulation, cross-frequency coupling of movement-related oscillations was reduced, and the stronger the entrained neuronal populations (i.e., increased oscillatory power) were before movement onset, the weaker the inherent theta-gamma coupling became in the motor cortex. Discussion: This novel exogenous manipulation paradigm provides key insights on how the somatosensory system modulates the motor cortical oscillations required for volitional movement in the normative sensorimotor system.

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.

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

Poor glycemic control in type 2 diabetes has been associated with accentuated age-related cognitive decline, although the underlying neural mechanisms are not well understood. The current study sought to identify the impact of glycemic control on the neural dynamics serving working memory in adults with type 2 diabetes. Participants (n = 34, ages = 55–73) performed a working memory task while undergoing MEG. Significant neural responses were examined relative to poorer (A1c > 7.0%) or tighter glycemic control (A1c

BackgroundCannabis 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.MethodsWe 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.ResultsBehavioral 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).ConclusionsDespite 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.

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

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

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.

Persons with cerebral palsy (CP) have impaired mobility that has been attributed to changes in structure and function within the nervous system. The brainstem is a region that plays a critical role in locomotion by connecting the cortex and cerebellum to the spinal cord, yet this region has been largely unstudied in persons with CP. The objective of this investigation was to use high-resolution structural MRI and biomechanical analyses to examine whether the volume of the whole brainstem and its constituent elements are altered in CP, and if these alterations relate to the mobility impairments within this population. We assessed the volume of the pons, midbrain, medulla, and superior cerebellar peduncle (SCP) in a cohort of persons with CP (N = 26; Age = 16.3 ± 1.0 yrs; GMFCS levels I-IV, Females = 12) and a cohort of neurotypical (NT) controls (N = 38; Age = 14.3 ± 0.4 yrs, Females = 14) using structural MR imaging of the brainstem. Outside the scanner, a digital mat was used to quantify the spatiotemporal gait biomechanics of these individuals. Our MRI results revealed that there was a significant decrease in volume of the total brainstem, midbrain, and pons in persons with CP in comparison to the NT controls. Furthermore, we found that the altered volumes were related to reduced gait velocity and step length. These results suggest that there are structural changes in the brainstems of persons with CP that may contribute to the mobility impairments that are ubiquitous within this population.

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.

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.

Alcohol and cannabis use disorder (AUD/CUD) are two of the most common addictive disorders. While studies are beginning to understand the neural changes related to acute and chronic use, few studies have examined the independent effects of AUD and CUD on neural oscillatory activity. We examined 45 adults who reported current use of both cannabis and alcohol. Participants underwent the SCID-V to determine whether they met criteria for AUD and/or CUD. Participants also completed a visual-spatial processing task while undergoing magnetoencephalography (MEG). ANCOVA with a 2 × 2 design was then used to identify the main effects of AUD and CUD on source-level oscillatory activity. Of the 45 adults, 17 met criteria for AUD, and 26 met criteria for CUD. All participants, including comparison groups, reported use of both cannabis and alcohol. Statistical analyses showed a main effect of AUD, such that participants with AUD displayed a blunted occipital alpha (8–16 Hz) response. Post-hoc testing showed this decreased alpha response was related to increased AUD symptoms, above and beyond amount of use. No effects of AUD or CUD were identified in visual theta or gamma activity. In conclusion, AUD was associated with reduced alpha responses and scaled with increasing severity, independent of CUD. These findings indicate that alpha oscillatory activity may play an integral part in networks affected by alcohol addiction.

Background: Cannabis is one of the most commonly used substances in the United States. Prior literature using task-based functional magnetic resonance imaging (fMRI) has identified that individuals with Cannabis use disorder (CUD) show impairments in emotion processing circuitry. However, whether the functional networks involving these regions are also altered in CUD remains poorly understood. Aims: Investigate changes in resting-state functional connectivity (rsFC) in regions related to emotional processing in CUD. Methods: Sixty-two participants completed resting-state fMRI, including 21 with CUD, 20 with histories of illicit substance use but no current CUD diagnosis, and 21 with no history of illicit substance use. Whole-brain seed-based connectivity analyses were performed and one-way analyses of covariance (ANCOVAs) were conducted to detect group differences in the bilateral amygdalae, hippocampi, and the anterior and posterior cingulate cortices. Results: The CUD group exhibited significant reductions in rsFC between the amygdala and the cuneus, paracentral lobule, and supplementary motor area, and between the cingulate cortices and the occipital and temporal lobes. There were no significant group differences in hippocampal functional connectivity. In addition, CUD symptom counts based on the Structured Clinical Interview for DSM-5 (SCID) and the Cannabis Use Disorders Identification Test (CUDIT) significantly correlated with multiple connectivity metrics. Conclusion: These data expand on emerging literature indicating that CUD is associated with dysfunction in the neural circuits underlying emotion processing. Dysfunction in emotion processing circuits may play a role in the behavioral impairments seen in emotion processing tasks in individuals with CUD, and the severity of CUD symptoms appears to be directly related to the degree of dysfunction in these circuits.

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.

Motor control requires the adaptive updating of internal models to successfully target desired outcomes. This adaptive control can be proactive, such that imminent actions and corresponding sensorimotor programmes are anticipated prior to movement, or reactive, such that online error correction is necessary to adjust to sudden changes. While substantial evidence implicates a distributed cortical network serving adaptive control when behavioural changes are required (e.g. response inhibition), the neural dynamics serving such control when the target motor commands are to remain intact are poorly understood. To address this, we developed a novel proactive–reactive cued finger tapping paradigm that was performed during magnetoencephalography by 25 healthy adults. Importantly, to ensure condition-wise differences in adaptive cueing were not attributable to changes in movement kinematics, motor selection and planning processes were held constant despite changes in task demands. All data were imaged in the time-frequency domain using a beamformer to evaluate the effect of proactive and reactive cues on movement-related oscillations and subsequent performance. Our results indicated spectrally specific increases in low (i.e. theta) and high (i.e. gamma) frequency oscillations during motor execution as a function of adaptive cueing. Additionally, we observed robust cross-frequency coupling of theta and gamma oscillatory power in the contralateral motor cortex and further, the strength of this theta–gamma coupling during motor execution was differentially predictive of behavioural improvements and decrements during reactive and proactive trials, respectively. These data indicate that functional oscillatory coupling may govern the adaptive control of movement in the healthy brain and importantly, may serve as effective proxies for characterizing declines in motor function in clinical populations in the future.

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.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).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.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.

Background Trait dissociation has not been examined from a structural human brain mapping perspective in healthy adults or children. Non-pathological dissociation shares some features with daydreaming and mind-wandering, but also involves subtle disruptions in affect and autobiographical memory. Aims To identify neurostructural biomarkers of trait dissociation in healthy children. Method Typically developing 9- to 15-year-olds (n = 180) without psychological or behavioural disorders were enrolled in the Developmental Chronnecto-Genomics (DevCoG) study of healthy brain development and completed psychological assessments of trauma exposure and dissociation, along with a structural T1-weighted magnetic resonance imaging. We conducted univariate ANCOVA generalised linear models for each region of the default mode network examining the effects of trait dissociation, including scanner site, age, gender and trauma as covariates and correcting for multiple comparison. Results We found that the precuneus was significantly larger in children with higher levels of trait dissociation but this was not related to trauma exposure. The inferior parietal volume was smaller in children with higher levels of trauma but was not related to dissociation. No other regions of interest, including frontal and limbic structures, were significantly related to trait dissociation even before multiple comparison correction. Conclusions Trait dissociation reflects subtle cognitive disruptions worthy of study in healthy people and warrants study as a potential risk factor for psychopathology. This neurostructural study of trait dissociation in healthy children identified the precuneus as an essential brain region to consider in future dissociation research.

People with HIV (PWH) use cannabis at a higher rate than the general population, but the influence on neural activity is not well characterized. Cannabis use among PWH may have a beneficial effect, as neuroinflammation is known to be a critical problem in PWH and cannabis use has been associated with a reduction in proinflammatory markers. Thus, it is important to understand the net impact of cannabis use on brain and cognitive function in PWH. In this study, we collected magnetoencephalographic (MEG) brain imaging data on 81 participants split across four demographically matched groups (i.e., PWH using cannabis, controls using cannabis, non‐using PWH, and non‐using controls). Participants completed a visuospatial processing task during MEG. Time–frequency resolved voxel time series were extracted to identify the dynamics of oscillatory and pre‐stimulus baseline neural activity. Our results indicated strong theta (4–8 Hz), alpha (10–16 Hz), and gamma (62–72 Hz) visual oscillations in parietal–occipital brain regions across all participants. PWH exhibited significant behavioral deficits in visuospatial processing, as well as reduced theta oscillations and elevated pre‐stimulus gamma activity in visual cortices, all of which replicate prior work. Strikingly, chronic cannabis use was associated with a significant reduction in pre‐stimulus gamma activity in the visual cortices, such that PWH no longer statistically differed from controls. These results provide initial evidence that cannabis use may normalize some neural aberrations in PWH. This study fills an important gap in understanding the impact of cannabis use on brain and cognitive function in PWH., This work used a visuospatial processing paradigm in combination with magnetoencephalographic (MEG) imaging. Voxel‐level timeseries analyses were applied to study the impact of cannabis use on behavior and neural activity in people with HIV (PWH).

Somatosensory cortical activity is altered in individuals with cerebral palsy (CP). However, previous studies have focused on the lower extremities in children with CP and have given less attention to structural changes that may contribute to these alterations. We used a multimodal neuroimaging approach to investigate the relationship between somatosensory cortical activity and cortical thickness in 17 adults with CP (age = 32.8 ± 9.3 years) and 18 healthy adult controls (age = 30.7 ± 9.8 years). Participants performed a median nerve paired-pulse stimulation paradigm while undergoing magnetoencephalography (MEG) to investigate somatosensory cortical activity and sensory gating. Participants also underwent magnetic resonance imaging to evaluate cortical thickness within the area of the somatosensory cortex that generated the MEG response. We found that the somatosensory responses were attenuated in the adults with CP (P = 0.004). The adults with CP also hypergated the second stimulation (P = 0.030) and had decreased cortical thickness in the somatosensory cortex (P = 0.015). Finally, the strength of the somatosensory response was significantly correlated with the cortical thickness (P = 0.023). These findings demonstrate that the aberrant somatosensory cortical activity in adults with CP extends to the upper extremities and appears to be related to cortical thickness.

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.

Healthy aging is typically associated with some level of cognitive decline, but there is substantial variation in such decline among older adults. The mechanisms behind such heterogeneity remain unclear but some have suggested a role for cognitive reserve. In this work, we propose the “person-based similarity index” for cognition (PBSI-Cog) as a proxy for cognitive reserve in older adults, and use the metric to quantify similarity between the cognitive profiles of healthy older and younger participants. In the current study, we computed this metric in 237 healthy older adults (55–88 years) using a reference group of 156 younger adults (18–39 years) taken from the Cambridge Center for Ageing and Neuroscience dataset. Our key findings revealed that PBSI-Cog scores in older adults were: 1) negatively associated with age (rho = −0.25, P = 10−4) and positively associated with higher education (t = 2.4, P = 0.02), 2) largely explained by fluid intelligence and executive function, and 3) predicted more by functional connectivity between lower- and higher-order resting-state networks than brain structural morphometry or education. Particularly, we found that higher segregation between the sensorimotor and executive networks predicted higher PBSI-Cog scores. Our results support the notion that brain network functional organization may underly variability in cognitive reserve in late adulthood.

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

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.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.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.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.

The Coronavirus Disease 2019 (COVID-19) pandemic has spread across the world and resulted in over 5 million deaths to date, as well as countless lockdowns, disruptions to daily life, and extended period of social distancing and isolation. The impacts on youth in particular are astounding, with shifts in learning platforms, limited social outlets, and prolonged uncertainty about the future. Surveys have shown that mental health among youth has severely suffered during the pandemic. However, limited research to date has reported on physiological indices of stress surrounding the pandemic, such as cortisol. Cortisol is a stress hormone that typically increases during stressful situations and can have deleterious effects on mental and physical health when chronically heightened. The present study leveraged hair cortisol concentration measurements, which allowed the retrospectiveinvestigation of circulating cortisol prior to- versus after pandemic-related local lockdowns during the first wave of the pandemic. A final sample of 44 youth ages 10- to 18-years-old provided hair samples and reported on their perceived affective well-being and level of concern regarding pandemic-related stressors between May and June of 2020. We found significant levels of concern and decreases in affective well-being following local lockdowns. Moreover, we saw that cortisol robustly increased following local lockdowns, and those increases were predictive of changes in affect. These findings provide critical insights into the underlying neuroendocrinology of stress during the pandemic and support the need for resources to support youths’ mental health and well-being during this globally significant event.

Identification of informative signatures from electrophysiological signals is important for understanding brain developmental patterns, where techniques such as magnetoencephalography (MEG) are particularly useful. However, less attention has been given to fully utilizing the multidimensional nature of MEG data for extracting components that describe these patterns. Tensor factorizations of MEG yield components that encapsulate the data's multidimensional nature, providing parsimonious models identifying latent brain patterns for meaningful summarization of neural processes. To address the need for meaningful MEG signatures for studies of pediatric cohorts, we propose a tensor-based approach for extracting developmental signatures of multi-subject MEG data. We employ the canonical polyadic (CP) decomposition for estimating latent spatiotemporal components of the data, and use these components for group level statistical inference. Using CP decomposition along with hierarchical clustering, we were able to extract typical early and late latency event-related field (ERF) components that were discriminative of high and low performance groups ([Formula: see text]) and significantly correlated with major cognitive domains such as attention, episodic memory, executive function, and language comprehension. We demonstrate that tensor-based group level statistical inference of MEG can produce signatures descriptive of the multidimensional MEG data. Furthermore, these features can be used to study group differences in brain patterns and cognitive function of healthy children. We provide an effective tool that may be useful for assessing child developmental status and brain function directly from electrophysiological measurements and facilitate the prospective assessment of cognitive processes.

Multi-paradigm deep learning models show great potential for dynamic functional connectivity (dFC) analysis by integrating complementary information. However, many of them cannot use information from different paradigms effectively and have poor explainability, that is, the ability to identify significant features that contribute to decision making. In this paper, we propose a multi-paradigm fusion-based explainable deep sparse autoencoder (MF-EDSAE) to address these issues. Considering explainability, the MF-EDSAE is constructed based on a deep sparse autoencoder (DSAE). For integrating information effectively, the MF-EDASE contains the nonlinear fusion layer and multi-paradigm hypergraph regularization. We apply the model to the Philadelphia Neurodevelopmental Cohort and demonstrate it achieves better performance in detecting dynamic FC (dFC) that differ significantly during brain development than the single-paradigm DSAE. The experimental results show that children have more dispersive dFC patterns than adults. The function of the brain transits from undifferentiated systems to specialized networks during brain development. Meanwhile, adults have stronger connectivities between task-related functional networks for a given task than children. As the brain develops, the patterns of the global dFC change more quickly when stimulated by a task.

Longitudinal studies can provide more precise measure of brain development, as they focus on within-subject variability, as opposed to cross-sectional studies. In this study, we track longitudinal changes in resting state fMRI data using spectrum of time-courses generated via group independent component analysis (gICA), in a multi time point dataset containing healthy children 8-18 years old, collected on both eyes open and eyes closed resting state conditions. Clinical Relevance - Tracking normal brain development and identifying biomarkers of healthy brain development are critically important to diagnose mental disorders at early ages. We found increased spectral power in low frequencies and decreased spectral power in high frequencies in children with typical development in both the eyes open and eyes closed conditions though the eyes closed condition showed greater changes with development mostly in the visual networks. Results are also replicated on an independent dataset.

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

Recent research has indicated that rhythmic visual entrainment may be useful in clearing pathological protein deposits in the central nervous system of mouse models of Alzheimer’s disease. However, visual entrainment studies in human patients with Alzheimer’s disease are rare, and as such the degree to which these patients exhibit aberrations in the neural tracking of rhythmic visual stimuli is unknown. To fill this gap, we recorded magnetoencephalography during a 15 Hz visual entrainment paradigm in amyloid-positive patients on the Alzheimer’s disease spectrum and compared their neural responses to a demographically matched group of biomarker-negative healthy controls. Magnetoencephalography data were imaged using a beamformer and virtual sensor data were extracted from the peak visual entrainment responses. Our results indicated that, relative to healthy controls, participants on the Alzheimer’s disease spectrum exhibited significantly stronger 15 Hz entrainment in primary visual cortices relative to a pre-stimulus baseline period. However, the two groups exhibited comparable absolute levels of neural entrainment, and higher absolute levels of entertainment predicted greater Mini-mental Status Examination scores, such that those patients whose absolute entrainment amplitude was closer to the level seen in controls had better cognitive function. In addition, 15 Hz periodic activity, but not aperiodic activity, during the pre-stimulus baseline period was significantly decreased in patients on the Alzheimer’s disease spectrum. This pattern of results indicates that patients on the Alzheimer’s disease spectrum exhibited increased visual entrainment to rhythmic stimuli and that this increase is likely compensatory in nature. More broadly, these results show that visual entrainment is altered in patients with Alzheimer’s disease and should be further examined in future studies, as changes in the capacity to entrain visual stimuli may prove useful as a marker of Alzheimer’s disease progression.

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

Objective This investigation used magnetoencephalography (MEG) to identify the neurophysiological mechanisms contributing to the altered cognition seen in adults with cerebral palsy (CP). Methods Adults with CP (GMFCS levels I-IV) and demographically-matched controls completed a Sternberg-type working memory task during MEG. Secondarily, they completed the National Institutes of Health (NIH) cognitive toolbox. Beamforming was used to image the significant MEG oscillatory responses and the resulting images were examined using statistical parametric mapping to identify cortical activity that differed between groups. Results Both groups had a left-lateralized decrease in alpha–beta (11–16 Hz) power across the occipital, temporal, and prefrontal cortices during encoding, as well as an increase in alpha (9–13 Hz) power across the occipital cortices during maintenance. The strength of alpha–beta oscillations in the prefrontal cortices were weaker in those with CP during encoding. Weaker alpha–beta oscillation within the prefrontal cortex was associated with poorer performance on the NIH toolbox and a higher GMFCS level. Conclusions Alpha-beta aberrations may impact the basic encoding of information in adults with CP, which impacts their overall cognition. Altered alpha–beta oscillation might be connected with gross motor function. Significance This experimental work highlights the aberrant alpha–beta during encoding as possible neurophysiological mechanism of the cognitive deficiencies.

HIV‐infection has been associated with widespread alterations in brain structure and function, although few studies have examined whether such aberrations are co‐localized and the degree to which clinical and cognitive metrics are related. We examine this question in the somatosensory system using high‐resolution structural MRI (sMRI) and magnetoencephalographic (MEG) imaging of neural oscillatory activity. Forty‐four participants with HIV (PWH) and 55 demographically‐matched uninfected controls completed a paired‐pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. MEG data were transformed into the time‐frequency domain; significant sensor level responses were imaged using a beamformer. Virtual sensor time series were derived from the peak responses. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. The T1‐weighted sMRI data were processed using morphological methods to derive cortical thickness values across the brain. From these, the cortical thickness of the tissue coinciding with the peak response was estimated. Our findings indicated both PWH and control exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls. Follow‐up analyses indicated that the reduction in cortical thickness was significantly correlated with CD4 nadir and mediated the relationship between HIV and spontaneous cortical activity within the left postcentral gyrus. These data indicate that PWH have abnormally strong spontaneous cortical activity in the left postcentral gyrus and such elevated activity is driven by locally reduced cortical gray matter thickness., Forty‐four participants with HIV (PWH) and 55 demographically‐matched uninfected controls completed a paired‐pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. Our findings indicated both PWH and controls exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls.

People with HIV (PWH) may be particularly vulnerable to the psychological impacts of COVID-19. To assess this, participants were recruited from two established cohorts of PWH and HIV− adults with the available pre-pandemic baseline data and completed the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Alcohol Use Identification Test (AUDIT), National Institute on Drug Abuse Quick Screen (NIDA-QS), and Pittsburgh Sleep Quality Index (PSQI) at two distinct intra-pandemic time periods. All outcomes were evaluated using generalized linear mixed models. In total, 87 participants completed all the questionnaires; 45 were PWH and 42 were HIV−. The pre-pandemic mean BDI-II, BAI, AUDIT and PSQI scores were higher in the PWH cohort. After the onset of the pandemic, the mean BDI-II, AUDIT and PSQI scores increased within the sample as a whole (p < 0.001, p = 0.029 and p = 0.046, respectively). The intra-pandemic mean BDI-II scores fell slightly for both groups and the AUDIT scores increased slightly for the PWH group and fell slightly for the HIV− group, but not significantly. The intra-pandemic PSQI scores increased sharply for both groups. The percentage of PWH and HIV− participants who moved into a more severe category of depression was identical (18%), but more PWH met the criteria for clinical evaluation. The BAI and NIDA-QS scores did not increase significantly. In conclusion, the measures of mental health symptoms and alcohol use increased in both groups after the onset of the pandemic. Although there were no significant differences in the changes between the groups, the PWH had higher baseline scores and the changes in this group had more clinical impacts.