Sleep, brain systems, and persistent stress in early adolescents during COVID-19: Insights from the ABCD study.

PURPOSE: The first year of the COVID-19 pandemic constituted a major life stress event for many adolescents, associated with disrupted school, behaviors, social networks, and health concerns. However, pandemic-related stress was not equivalent for everyone and could have been influenced by pre-pandemic factors including brain structure and sleep, which both undergo substantial development during adolescence. Here, we analyzed clusters of perceived stress levels across the pandemic and determined developmentally relevant pre-pandemic risk factors in brain structure and sleep of persistently high stress during the first year of the COVID-19 pandemic. METHODS: We investigated longitudinal changes in perceived stress at six timepoints across the first year of the pandemic (May 2020-March 2021) in 5559 adolescents (50 % female; age range: 11-14 years) in the United States (U.S.) participating in the Adolescent Brain Cognitive Development (ABCD) study. In 3141 of these adolescents, we fitted machine learning models to identify the most important pre-pandemic predictors from structural MRI brain measures and self-reported sleep data that were associated with persistently high stress across the first year of the pandemic. RESULTS: Patterns of perceived stress levels varied across the pandemic, with 5 % reporting persistently high stress. Our classifiers accurately detected persistently high stress (AUC > 0.7). Pre-pandemic brain structure, specifically cortical volume in temporal regions, and cortical thickness in multiple parietal and occipital regions, predicted persistent stress. Pre-pandemic sleep difficulties and short sleep duration were also strong predictors of persistent stress, along with more advanced pubertal stage. CONCLUSIONS: Adolescents showed variable stress responses during the first year of the COVID-19 pandemic, and some reported persistently high stress across the whole first year. Vulnerability to persistent stress was evident in several brain structural and self-reported sleep measures, collected before the pandemic, suggesting the relevance of other pre-existing individual factors beyond pandemic-related factors, for persistently high stress responses.

Influence of childhood trauma, HIV infection, alcohol use disorder, and resilience on health-related quality of life in adulthood.

Experience of childhood trauma, especially physical, emotional, and sexual abuse, carries a risk for developing alcohol use disorder (AUD) and engaging in risky behaviors that can result in HIV infection. AUD and HIV are associated with compromised self-reported health-related quality of life (HRQoL) possibly intersecting with childhood trauma. To determine whether poor HRQoL is heightened by AUD, HIV, their comorbidity (AUD + HIV), number of trauma events, or poor resilience, 108 AUD, 45 HIV, 52 AUD + HIV, and 67 controls completed the SF-21 HRQoL, Brief Resilience Scale (BRS), Ego Resiliency Scale (ER-89), and an interview about childhood trauma. Of the 272 participants, 116 reported a trauma history before age 18. Participants had a blood draw, AUDIT questionnaire, and interview about lifetime alcohol consumption. AUD, HIV, and AUD + HIV had lower scores on HRQoL and resilience composite comprising the BRS and ER-89 than controls. Greater resilience was a significant predictor of better quality of life in all groups. HRQoL was differentially moderated in AUD and HIV: more childhood traumas predicted poorer quality of life in AUD and controls, whereas higher T-lymphocyte count contributed to better quality of life in HIV. This study is novel in revealing a detrimental impact on HRQoL from AUD, HIV, and their comorbidity, with differential negative contribution from trauma and beneficial effect of resilience to quality of life. Channeling positive effects of resilience and reducing the incidence and negative impact of childhood trauma may have beneficial effects on health-related quality of life in adulthood independent of diagnosis.

Episodic memory deficit in HIV infection: common phenotype with Parkinson's disease, different neural substrates.

Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson's disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, assessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed with a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were examined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hippocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall trials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account for the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in HIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller thalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates in HIV and PD suggest different pathogenic mechanisms.

The distortions of the free water model for diffusion MRI data when assuming single compartment relaxometry and proton density.

Objective.To document the bias of thesimplifiedfree water model of diffusion MRI (dMRI) signal vis-à-vis aspecificmodel which, in addition to diffusion, incorporates compartment-specific proton density (PD), T1 recovery during repetition time (TR), and T2 decay during echo time (TE).Approach.Both models assume that volume fractionfof the total signal in any voxel arises from the free water compartment (fw) such as cerebrospinal fluid or edema, and the remainder (1-f) from hindered water (hw) which is constrained by cellular structures such as white matter (WM). Thespecificandsimplifiedmodels are compared on a synthetic dataset, using a range of PD, T1 and T2 values. We then fit the models to anin vivohealthy brain dMRI dataset. For bothsyntheticandin vivodata we use experimentally feasible TR, TE, signal-to-noise ratio (SNR) and physiologically plausible diffusion profiles.Main results.From the simulations we see that the difference between the estimatedsimplified fandspecific fis largest for mid-range ground-truthf, and it increases as SNR increases. The estimation of volume fractionfis sensitive to the choice of model,simplifiedorspecific, but the estimated diffusion parameters are robust to small perturbations in the simulation.Specific fis more accurate and precise thansimplified f. In the white matter (WM) regions of thein vivoimages,specific fis lower thansimplified f.Significance.In dMRI models for free water, accounting for compartment specific PD, T1 and T2, in addition to diffusion, improves the estimation of model parameters. This extra model specification attenuates the estimation bias of compartmental volume fraction without affecting the estimation of other diffusion parameters.

Detecting negative valence symptoms in adolescents based on longitudinal self-reports and behavioral assessments.

BACKGROUND: Given the high prevalence of depressive symptoms reported by adolescents and associated risk of experiencing psychiatric disorders as adults, differentiating the trajectories of the symptoms related to negative valence at an individual level could be crucial in gaining a better understanding of their effects later in life. METHODS: A longitudinal deep learning framework is presented, identifying self-reported and behavioral measurements that detect the depressive symptoms associated with the Negative Valence System domain of the NIMH Research Domain Criteria (RDoC). RESULTS: Applied to the annual records of 621 participants (age range: 12 to 17 years) of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), the deep learning framework identifies predictors of negative valence symptoms, which include lower extraversion, poorer sleep quality, impaired executive control function and factors related to substance use. LIMITATIONS: The results rely mainly on self-reported measures and do not provide information about the underlying neural correlates. Also, a larger sample is required to understand the role of sex and other demographics related to the risk of experiencing symptoms of negative valence. CONCLUSIONS: These results provide new information about predictors of negative valence symptoms in individuals during adolescence that could be critical in understanding the development of depression and identifying targets for intervention. Importantly, findings can inform preventive and treatment approaches for depression in adolescents, focusing on a unique predictor set of modifiable modulators to include factors such as sleep hygiene training, cognitive-emotional therapy enhancing coping and controllability experience and/or substance use interventions.

A Longitudinal Examination of Alcohol-Related Blackouts as a Predictor of Changes in Learning, Memory, and Executive Function in Adolescents.

Introduction: In adolescents, the relationship between alcohol-related blackouts (ARBs) and distinct cognitive changes lasting beyond intoxication is unclear. We examined ARBs as a predictor of persistent changes in the development of learning, memory, and executive function in participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. Methods: Descriptive analyses of the NCANDA sample (N = 831, 50.9% female, 12-21 years at baseline) identified ARB patterns within participants with an ARB history (n = 106). Latent growth curve modeling evaluated ARB-related performance changes on four neuropsychological measures across five years, excluding baseline data to reduce the magnitude of practice effects over time (n = 790). Measures included the Penn Conditional Exclusion Test (PCET), Penn Letter N-back Test (PLBT), Penn Facial Memory Test immediate (PFMTi), and delayed (PFMTd) recognition trials, and the Rey Complex Figure Test copy (RCFTc), immediate recall (RCFTi), and delayed recall (RCFTd) trials. Multivariate models were fit for raw accuracy scores from each measure, with ARB history (i.e., presence of past-year ARBs) as the main independent variable. Age, sex, race, socioeconomic status, assessment site, and alcohol use (i.e., past-year frequency) were included as covariates. Interaction effects between ARB history and alcohol use frequency were tested. Results: By year five, 16% of participants had experienced at least one ARB (59% of whom reported > 1 ARB and 57% of whom had an ARB lasting > 1 h). After controlling for demographics and alcohol use, ARB history predicted attenuated PFMTd performance growth at year one. Interaction effects between ARB history and alcohol use frequency predicted attenuated PFMTd performance growth at years one and two. ARB history predicted attenuated RCFTi and RCFTd performance growth by year four, but not PCET or PLBT performance over time. By contrast, greater past-year alcohol use predicted attenuated PFMTi and PFMTd performance growth between years two and four in adolescents without an ARB history. Conclusion: We found that ARBs predict distinct, lasting changes in learning and memory for visual information, with results suggesting that the developing brain is vulnerable to ARBs during adolescence and emerging adulthood.

Disruption of cerebellar-cortical functional connectivity predicts balance instability in alcohol use disorder.

BACKGROUND: A neural substrate of alcohol-related instability of gait and balance is the cerebellum. Whether disruption of neural communication between cerebellar and cortical brain regions exerts an influence on ataxia in alcohol use disorder (AUD) was the focus of this study. METHODS: Study groups comprised 32 abstinent AUD participants and 22 age- and sex-matched healthy controls (CTL). All participants underwent clinical screening, motor testing, and resting-state functional MR imaging analyzed for functional connectivity (FC) among 90 regions across the whole cerebrum and cerebellum. Ataxia testing quantified gait and balance with the Fregly-Graybiel Ataxia Battery conducted with and without vision. RESULTS: The AUD group achieved lower scores than the CTL group on balance performance, which was disproportionately worse for eyes open than eyes closed in the AUD relative to the CTL group. Differences in ataxia were accompanied by differences in FC marked by cerebellar-frontal and cerebellar-parietal hyperconnectivity and cortico-cortical hypoconnectivity in the AUD relative to the control group. Lifetime alcohol consumption correlated significantly with AUD-related FC aberrations, which explained upwards of 69% of the AUD ataxia score variance. CONCLUSION: Heavy, chronic alcohol consumption is associated with disorganized neural communication among cerebellar-cortical regions and contributes to ataxia in AUD. Ataxia, which is known to accelerate with age and be exacerbated with AUD, can threaten functional independence. Longitudinal studies are warranted to address whether extended sobriety quells ataxia and normalizes aberrant FC contributing to instability.

Neurofunctional characteristics of executive control in older people with HIV infection: a comparison with Parkinson's disease.

Expression of executive dysfunctions is marked by substantial heterogeneity in people living with HIV infection (PLWH) and attributed to neuropathological degradation of frontostriatal circuitry with age and disease. We compared the neurophysiology of executive function in older PLWH and Parkinson's disease (PD), both affecting frontostriatal systems. Thirty-one older PLWH, 35 individuals with PD, and 28 older healthy controls underwent executive task-activated fMRI, neuropsychological testing, and a clinical motor exam. fMRI task conditions distinguished cognitive control operations, invoking a lateral frontoparietal network, and motor control operations, activating a cerebellar-precentral-medial prefrontal network. HIV-specific findings denoted a prominent sensorimotor hypoactivation during cognitive control and striatal hypoactivation during motor control related to CD4+ T cell count and HIV disease duration. Activation deficits overlapped for PLWH and PD, relative to controls, in dorsolateral frontal, medial frontal, and middle cingulate cortices for cognitive control, and in limbic, frontal, parietal, and cerebellar regions for motor control. Thus, despite well-controlled HIV infection, frontostriatal and sensorimotor activation deficits occurred during executive control in older PLWH. Overlapping activation deficits in posterior cingulate and hippocampal regions point toward similarities in mesocorticolimbic system aberrations among older PLWH and PD. The extent of pathophysiology in PLWH was associated with variations in immune system health, neural signature consistent with subclinical parkinsonism, and mild neurocognitive impairment. The failure to adequately engage these pathways could be an early sign for cognitive and motor functional decline in the aging population of PLWH.

The Pandemic's Toll on Young Adolescents: Prevention and Intervention Targets to Preserve Their Mental Health.

PURPOSE: Adolescence is characterized by dramatic physical, social, and emotional changes, making teens particularly vulnerable to the mental health effects of the COVID-19 pandemic. This longitudinal study identifies young adolescents who are most vulnerable to the psychological toll of the pandemic and provides insights to inform strategies to help adolescents cope better in times of crisis. METHODS: A data-driven approach was applied to a longitudinal, demographically diverse cohort of more than 3,000 young adolescents (11-14 years) participating in the ongoing Adolescent Brain Cognitive Development Study in the United States, including multiple prepandemic visits and three assessments during the COVID-19 pandemic (May-August 2020). We fitted machine learning models and provided a comprehensive list of predictors of psychological distress in individuals. RESULTS: Positive affect, stress, anxiety, and depressive symptoms were accurately detected with our classifiers. Female sex and prepandemic internalizing symptoms and sleep problems were strong predictors of psychological distress. Parent- and youth-reported pandemic-related psychosocial factors, including poorer quality and functioning of family relationships, more screen time, and witnessing discrimination in relation to the pandemic further predicted youth distress. However, better social support, regular physical activities, coping strategies, and healthy behaviors predicted better emotional well-being. DISCUSSION: Findings highlight the importance of social connectedness and healthy behaviors, such as sleep and physical activity, as buffering factors against the deleterious effects of the pandemic on adolescents' mental health. They also point to the need for greater attention toward coping strategies that help the most vulnerable adolescents, particularly girls and those with prepandemic psychological problems.

Alcohol Use Disorder and Its Comorbidity With HIV Infection Disrupts Anterior Cingulate Cortex Functional Connectivity.

BACKGROUND: Individuals with alcohol use disorder (AUD) have a heightened risk of contracting HIV infection. The effects of these two diseases and their comorbidity on brain structure have been well described, but their effects on brain function have never been investigated at the scale of whole-brain connectomes. METHODS: In contrast with prior studies that restricted analyses to specific brain networks or examined relatively small groups of participants, our analyses are based on whole-brain functional connectomes of 292 participants. RESULTS: Relative to participants without AUD, the functional connectivity between the anterior cingulate cortex and orbitofrontal cortex was lower for participants with AUD. Compared with participants without AUD+HIV comorbidity, the functional connectivity between the anterior cingulate cortex and hippocampus was lower for the AUD+HIV participants. Compromised connectivity between these pairs was significantly correlated with greater total lifetime alcohol consumption; the effects of total lifetime alcohol consumption on executive functioning were significantly mediated by the functional connectivity between the pairs. CONCLUSIONS: Taken together, our results suggest that the functional connectivity of the anterior cingulate cortex is disrupted in individuals with AUD alone and AUD with HIV infection comorbidity. Moreover, the affected connections are associated with deficits in executive functioning, including heightened impulsiveness.

Growth trajectories of cognitive and motor control in adolescence: How much is development and how much is practice?

OBJECTIVE: Executive control continues to develop throughout adolescence and is vulnerable to alcohol use. Although longitudinal assessment is ideal for tracking executive function development and onset of alcohol use, prior testing experience must be distinguished from developmental trajectories. METHOD: We used the Stroop Match-to-Sample task to examine the improvement of processing speed and specific cognitive and motor control over 4 years in 445 adolescents. The twice-minus-once-tested method was used and expanded to four test sessions to delineate prior experience (i.e., learning) from development. A General Additive Model evaluated the predictive value of age and sex on executive function development and potential influences of alcohol use on development. RESULTS: Results revealed strong learning between the first two assessments. Adolescents significantly improved their speed processing over 4 years. Compared with boys, girls enhanced ability to control cognitive interference and motor reactions. Finally, the influence of alcohol use initiation was tested over 4 years for development in 110 no/low, 110 moderate/heavy age- and sex-matched drinkers; alcohol effects were not detected in the matched groups. CONCLUSIONS: Estimation of learning effects is crucial for examining developmental changes longitudinally. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The effects of mood and cognition on daily functioning and quality of life in older people living with HIV and people with Parkinson's disease.

OBJECTIVE: In light of the increased longevity of people living with HIV infection (PLWH) undergoing antiretroviral therapy (ART), the present study aimed to determine the effects of mood disturbances alongside cognitive and motor symptoms on activities of daily living (ADLs) and quality of life (QOL) in older PLWH in comparison to an aging control sample without notable medical history (CTL) and individuals with Parkinson's disease (PD). METHOD: Forty-one PLWH, 41 individuals with PD, and 37 CTL, aged 45-79 years, underwent neuropsychological, psychological, and neurological assessment including depressive and anxiety symptoms, physical (ADL-p) and instrumental (ADL-i) daily activities, Unified Parkinson's Disease Rating Scale motor ADLs (ADL-UPDRS-II), QOL, and cognitive and motor functions. Hierarchical regression analyses assessed the relative contribution of predictors including demographics, disease-related factors, comorbid conditions, and mood-related factors for ADL and QOL scales. RESULTS: PLWH and PD participants reported more depressive symptoms and higher anxiety and worse QOL and ADL-i than CTL. The PD group had greater ADL-p and motor-related ADL-UPDRS-II difficulties than PLWH and CTL groups. In PLWH, medical comorbidities and alcohol use disorder (AUD)/substance use disorder (SUD) histories significantly contributed to poor physical and motor ADLs. Mood scores, particularly depressive symptoms, were independent predictors of poor QOL and most ADLs in both clinical groups, above the contribution of cognitive compromise. CONCLUSIONS: Mood symptoms contribute significantly to poor ADLs and QOL in people aging with chronic diseases such as long-term HIV infection and PD. Comprehensive assessment and treatment of mood symptoms are recommended for ensuring optimal functional independence and life quality. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Adolescent alcohol use disrupts functional neurodevelopment in sensation seeking girls.

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.

Cognitive and motor deficits in older adults with HIV infection: Comparison with normal ageing and Parkinson's disease.

Despite the life-extending success of antiretroviral pharmacotherapy in HIV infection (HIV), the prevalence of mild cognitive impairment in HIV remains high. Near-normal life expectancy invokes an emerging role for age-infection interaction and a potential synergy between immunosenescence and HIV-related health factors, increasing risk of cognitive and motor impairment associated with degradation in corticostriatal circuits. These neural systems are also compromised in Parkinson's disease (PD), which could help model the cognitive deficit pattern in HIV. This cross-sectional study examined three groups, age 45-79 years: 42 HIV, 41 PD, and 37 control (CTRL) participants, tested at Stanford University Medical School and SRI International. Neuropsychological tests assessed executive function (EF), information processing speed (IPS), episodic memory (MEM), visuospatial processing (VSP), and upper motor (MOT) speed and dexterity. The HIV and PD deficit profiles were similar for EF, MEM, and VSP. Although only the PD group was impaired on MOT compared with CTRL, MOT scores were related to cognitive scores in HIV but not PD. Performance was not related to depressive symptoms, socioeconomic status, or CD4+ T-cell counts. The overlap of HIV-PD cognitive deficits implicates frontostriatal disruption in both conditions. The motor-cognitive score relation in HIV provides further support for the hypothesis that these processes share similar underlying mechanisms in HIV infection possibly expressed with or exacerbated by ageing.

Alterations of Brain Signal Oscillations in Older Individuals with HIV Infection and Parkinson's Disease.

More than 30 years after the human immunodeficiency virus (HIV) epidemic, HIV patients are now aging due to the advances of antiretroviral therapy. With immunosenescence and the susceptibility of dopamine-rich basal ganglia regions to HIV-related injury, older HIV patients may show neurofunctional deficits similar to patients with Parkinson's disease (PD). We examined the amplitudes of low frequency fluctuations (ALFF) across different frequency bands of the BOLD signal in 30 older HIV-infected individuals, 33 older healthy controls, and 36 PD patients. Participants underwent resting-state fMRI, neuropsychological testing, and a clinical motor exam. HIV patients mainly showed abnormalities in cortical ALFF with reduced prefrontal amplitudes and enhanced sensorimotor and inferior temporal amplitudes. Frontal hypoactivation was overlapping for HIV and PD groups and different from controls. PD patients further exhibited reduced pallidum amplitudes compared to the other groups. In the HIV group, lower pallidum amplitudes were associated with lower CD4+ nadir and CD4+ T cell counts. Abnormalities in ALFF dynamics were largely associated with cognitive and motor functioning in HIV and PD groups. The disruption of neurofunctional frequency dynamics in subcortical-cortical circuits could contribute to the development of cognitive and motor dysfunction and serve as a biomarker for monitoring disease progression with immunosenescence. Graphical Abstract.

Quantitative Digitography Measures Fine Motor Disturbances in Chronically Treated HIV Similar to Parkinson's Disease.

Introduction: Motor and cognitive deficits were compared in aging, chronically treated human immunodeficiency virus (HIV) people, people with mild-to-moderate stage Parkinson's disease (PD), and healthy controls. Methods: Groups consisted of 36 people with PD, 28 with HIV infection, and 28 healthy controls. Motor function was assessed with the Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) and a rapid alternating finger tapping (RAFT) task on an engineered keyboard known as Quantitative Digitography (QDG). Executive function, verbal memory, and visuospatial processing were assessed using standard neuropsychological tests. Results: HIV demonstrated RAFT deficits similar to PD such as reduced amplitude (P = 0.023) and greater amplitude variability (P = 0.019) in the index finger when compared to controls. This fine motor disturbance correlated with HIV's immune health, measured by their CD4+ T cell count (P < 0.01). The UPDRS did not yield motor differences between HIV and controls. Executive function and verbal memory were impaired in HIV (P = 0.006, P = 0.016, respectively), but not in PD; visuospatial processing was similarly impaired in HIV and PD (P < 0.05) although motor deficits predominated in PD. Conclusions: Fine motor bradykinesia measured quantitatively by QDG RAFT holds promise as a marker of motor decline related to current immune health in aging HIV patients and may be useful in longitudinal studies regarding mechanisms of immunosenescence vs. potential toxicity of combination antiretroviral therapy (cART) in this population. Additionally, motor and cognitive networks in HIV may be affected differently as the disease progresses as observed in the differential patterns of impairment between HIV and PD, providing insight into the mechanisms of brain deterioration in HIV.

Effects of age, sex, and puberty on neural efficiency of cognitive and motor control in adolescents.

Critical changes in adolescence involve brain cognitive maturation of inhibitory control processes that are essential for a myriad of adult functions. Cognitive control advances into adulthood as there is more flexible integration of component processes, including inhibitory control of conflicting information, overwriting inappropriate response tendencies, and amplifying relevant responses for accurate execution. Using a modified Stroop task with fMRI, we investigated the effects of age, sex, and puberty on brain functional correlates of cognitive and motor control in 87 boys and 91 girls across the adolescent age range. Results revealed dissociable brain systems for cognitive and motor control processes, whereby adolescents flexibly adapted neural responses to control demands. Specifically, when response repetitions facilitated planning-based action selection, frontoparietal-insular regions associated with cognitive control operations were less activated, whereas cortical-pallidal-cerebellar motor regions associated with motor skill acquisition, were more activated. Attenuated middle cingulate cortex activation occurred with older adolescent age for both motor control and cognitive control with automaticity from repetition learning. Sexual dimorphism for control operations occurred in extrastriate cortices involved in visuo-attentional selection: While boys enhanced extrastriate selection processes for motor control, girls activated these regions more for cognitive control. These sex differences were attenuated with more advanced pubertal stage. Together, our findings show that brain cognitive and motor control processes are segregated, demand-specific, more efficient in older adolescents, and differ between sexes relative to pubertal development. Our findings advance our understanding of how distributed brain activity and the neurodevelopment of automaticity enhances cognitive and motor control ability in adolescence.

Brain activation to cannabis- and alcohol-related words in alcohol use disorder.

Cannabis abuse commonly co-occurs with alcohol use disorder (AUD). With increased acceptance and accessibility to cannabis in the US, it is imperative to understand the psychological and neural mechanisms of concurrent alcohol and cannabis use. We hypothesized that neural alcohol-cue conditioning may extent to other drug-related stimuli, such as cannabis, and underwrite the loss of control over reward-driven behavior. Task-activated fMRI examined the neural correlates of alcohol- and cannabis-related word cues in 21 abstinent AUD and 18 control subjects. Relative to controls, AUD showed behavioral attentional biases and frontal hypoactivation to both alcohol- and cannabis-related words. This cue-elicited prefrontal hypoactivation was related to higher lifetime alcohol consumption (pcorrected < 0.02) and modulated by past cannabis use histories (p ≦ 0.001). In particular, frontal hypoactivation to both alcohol and cannabis cues was pronounced in AUD without prior cannabis exposure. Overall, frontal control mechanisms in abstinent AUD were not sufficiently engaged to override automatic alcohol and cannabis-related intrusions, enhancing the risk for relapse and potentially for alcohol and cannabis co-use with the increased social acceptance and accessibility in the US.

Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson's disease.

Recent evidence has advanced our understanding of the function of sleep to include removal of neurotoxic protein aggregates via the glymphatic system. However, most research on the glymphatic system utilizes animal models, and the function of waste clearance processes in humans remains unclear. Understanding glymphatic function offers new insight into the development of neurodegenerative diseases that result from toxic protein inclusions, particularly those characterized by neuropathological sleep dysfunction, like Parkinson's disease (PD). In PD, we propose that glymphatic flow may be compromised due to the combined neurotoxic effects of alpha-synuclein protein aggregates and deteriorated dopaminergic neurons that are linked to altered REM sleep, circadian rhythms, and clock gene dysfunction. This review highlights the importance of understanding the functional role of glymphatic system disturbance in neurodegenerative disorders and the subsequent clinical and neuropathological effects on disease progression. Future research initiatives utilizing noninvasive brain imaging methods in human subjects with PD are warranted, as in vivo identification of functional biomarkers in glymphatic system functioning may improve clinical diagnosis and treatment of PD.

Longitudinally consistent estimates of intrinsic functional networks.

Increasing numbers of neuroimaging studies are acquiring data to examine changes in brain architecture by investigating intrinsic functional networks (IFN) from longitudinal resting-state functional MRI (rs-fMRI). At the subject level, these IFNs are determined by cross-sectional procedures, which neglect intra-subject dependencies and result in suboptimal estimates of the networks. Here, a novel longitudinal approach simultaneously extracts subject-specific IFNs across multiple visits by explicitly modeling functional brain development as an essential context for seeking change. On data generated by an innovative simulation based on real rs-fMRI, the method was more accurate in estimating subject-specific IFNs than cross-sectional approaches. Furthermore, only group-analysis based on longitudinally consistent estimates identified significant developmental effects within IFNs of 246 adolescents from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. The findings were confirmed by the cross-sectional estimates when the corresponding group analysis was confined to the developmental effects. Those effects also converged with current concepts of neurodevelopment.