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Neuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)-with its capability to improve neuronal function-may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC). Eleven PWH (47-69 years old, 2 females, 100% African Americans, disease duration 16-36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2-3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1. Compared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test-Part B (TMT-B) to TMT-Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS. Cingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.

Sleep disturbance is known to be associated with various mental disorders and often precedes the onset of mental disorders in youth. Given the increasingly acknowledged bidirectional influence between sleep disturbance and mental disorders, we aim to identify a shared neural mechanism that underlies sleep disturbance and mental disorders in preadolescents. We analyzed a dataset of 9,350 9–10 year‐old children, among whom 8,845 had 1‐year follow‐up data, from the Adolescent Brain Cognitive Development (ABCD) study. Linear mixed‐effects models, mediation analysis, and longitudinal mediation analysis were used to investigate the relationship between sleep disturbance, mental disorders, and resting‐state network connectivity. Out of 186 unique connectivities, the effect of total sleep disturbance (TSP, from Sleep Disturbance Scale) and mental problems (MP, from Child Behavior Checklist) converged in the default mode network (DMN) and the dorsal attention network (DAN). Within‐ and between‐network connectivities (DMN‐DAN, DMN‐DMN, DAN‐DAN) mediated the relationship between baseline TSD and MP at 1‐year follow‐up and the relationship between baseline MP and TSD at 1‐year follow‐up. The pathway model in which sleep disturbance and mental problems affect each other through two anticorrelated brain networks (DMN and DAN) suggests a common neural mechanism between them. Longitudinally, a less segregated DMN and DAN is associated with negative outcomes on mental well‐being and sleep disturbance a year later. These findings have important implications for the design of prevention and neurofeedback intervention for mental disorders and sleep problems. The impact of sleep disturbance and mental disorders on functional connectivity converges in default mode and dorsal attention networks. The relationship between sleep disturbance and mental disorders is mediated via a shared brain network mechanism. Sleep disturbance and mental disorders at baseline can each predict the other a year later through the identified network connectivities.

Sleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal connectivity to multiple prefrontal and default mode network regions, and disrupted the relationships between memory performance and hippocampal connectivity. Following TSD, two nights of recovery sleep restored hippocampal connectivity to baseline levels, but did not fully restore memory performance nor its associations with hippocampal connectivity. These findings suggest that more than two nights of recovery sleep are needed to fully restore memory function and hippocampal-memory associations after one night of total sleep loss.

Sleep deprivation significantly reduces the ability to maintain a consistent alertness level and impairs vigilant attention. Previous studies have shown that longer inter-stimulus interval (ISI) are associated with faster reaction times (RTs) on the Psychomotor Vigilance Test (PVT). However, whether and how sleep deprivation interacts with this ISI effect remains unclear. N = 70 healthy adults (age range 20-50 years, 41 males) participated in a 5-day and 4-night in-laboratory controlled sleep deprivation study, including N = 54 in the experimental group with one night of total sleep deprivation and N = 16 in the control group without sleep loss. All participants completed a neurobehavioral test battery every 2 hours while awake, including a 10-minute standard PVT (PVT-S, N = 1626) and a 3-minute brief PVT (PVT-B, N = 1622). The linear approach to threshold with ergodic rate (LATER) model was used to fit the RT data. RT decreased significantly with longer ISI on the PVT-S and PVT-B. Increased ISI effect was found for both PVT-S and PVT-B during sleep deprivation compared to baseline or recovery sleep in the experimental group, whereas no differences in the ISI effect were found in the control group. The LATER model fitting indicated that changes in perceptual sensitivity rather than threshold adjustment may underlie the ISI effect. Both standard and brief PVT showed a similar ISI effect on vigilant attention performance. Sleep deprivation increased the ISI effect on both PVT-S and PVT-B, which may be due to impaired temporal resolution and time estimation after sleep loss.

Depressive symptoms are more prevalent in persons with HIV (PWH) than HIV‐uninfected individuals. In HIV‐uninfected individuals, depression has been associated with atrophy in the hippocampus and other brain regions. In the present study, we investigated the impact of depression on brain structure in PWH. One hundred PWH participated in a cross‐sectional study (56.6 ± 6.4 yrs, range 41–70 yrs, 24 females, 63 African Americans). The Beck's Depression Inventory‐II (BDI‐II) was used to assess depressive symptoms. Structural MRI images were collected. Both the voxel‐based morphometry (VBM) technique and a region of interest (ROI) based approach were used to examine the relationship between hippocampal gray matter volume (GMv) and depressive symptoms. The impact of HIV CD4 nadir and antidepressants was also investigated. Both VBM and ROI approaches revealed that higher BDI‐II scores (implicating more severe depressive symptoms) were associated with loss of hippocampal GMv, especially in the right hippocampus and the right entorhinal cortex. Low CD4 nadir predicted additional hippocampal volume loss independent of depressive symptoms. Taking antidepressants did not have a detectable effect on hippocampal volume. In summary, having more depressive symptoms is associated with smaller hippocampal volume in PWH, and a history of severe immunosuppression (i.e., low CD4 nadir) correlates with additional hippocampal volume reduction. However, the impact of depression on hippocampal volume may be independent of HIV‐disease severity such as low CD4 nadir. In people with HIV infection, having more depressive symptoms is associated with smaller hippocampal volume. A history of severe immunosuppression (i.e., low CD4 nadir) correlates with additional hippocampal volume reduction. However, the impact of depression on hippocampal volume may be independent of HIV‐disease severity such as low CD4 nadir.

Hyperlipidemia has been proposed as a risk factor of dementia and cognitive decline. However, the findings of the relationship between cholesterol level and cognitive/brain function have been inconsistent. Here, using a well-controlled sample from the Parkinson's Progression Markers Initiative (PPMI), we investigated the probable non-linear relationship between plasma total cholesterol (TC) level, gray matter volume (GMv), and cognitive performance in 117 non-demented subjects (mean age, 61.5 ± 8.9 years), including 67 Parkinson's disease (PD) patients and 50 demographically matched controls. A quadratic relationship between semantic fluency (SF) performance and TC levels was identified. Within the subjects with a desirable TC level (TC < 200 mg/dl), low TC (lTC) levels were associated with reduced SF performance, as well as reduced GMv in three medial temporal regions [including bilateral anterior hippocampus (HIP)]. In contrast, no significant relationship between TC and cognition performance/GMv was found in individuals with a high cholesterol level (i.e., TC ≥ 200 mg/dl). Further region of interest (ROI)-based analysis showed that individuals with TC levels ranging from 100 to 160 mg/dl had the lowest GMv in the medial temporal regions. These findings suggest that low-normal TC level may be associated with reduced cognitive function and brain atrophy in regions implicated in neurodegenerative diseases, adding to a growing body of literature supporting a probable non-linear relationship between cholesterol level and brain health. However, this finding needs to be verified with other large public cohort data that do not include PD patients.

[This corrects the article DOI: 10.1371/journal.pone.0269491.].

Understanding the function of sleep requires studying the dynamics of brain activity across whole-night sleep and their transitions. However, current gold standard polysomnography (PSG) has limited spatial resolution to track brain activity. Additionally, previous fMRI studies were too short to capture full sleep stages and their cycling. To study whole-brain dynamics and transitions across whole-night sleep, we used an unsupervised learning approach, the Hidden Markov model (HMM), on two-night, 16 hr fMRI recordings of 12 non-sleep-deprived participants who reached all PSG-based sleep stages. This method identified 21 recurring brain states and their transition probabilities, beyond PSG-defined sleep stages. The HMM trained on one night accurately predicted the other, demonstrating unprecedented reproducibility. We also found functionally relevant subdivisions within rapid eye movement (REM) and within non-REM 2 stages. This study provides new insights into brain dynamics and transitions during sleep, aiding our understanding of sleep disorders that impact sleep transitions.

Arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) is increasingly used to assess regional brain activity and cerebrovascular function in both healthy and clinical populations. ASL perfusion imaging provides a quantitative measure of regional brain activity by determining absolute cerebral blood flow (CBF) values at a resting state or during task performance. However, the comparative reliability of these ASL measures is not well characterized. It is also unclear whether the test-retest reliability of absolute CBF or task-induced CBF change measures would be comparable to the reliability of task performance. In this study, fifteen healthy participants were scanned three times in a strictly controlled in-laboratory study while at rest and during performing a simple and reliable psychomotor vigilance test (PVT). The reliability of absolute CBF and task-induced CBF changes was evaluated using the intraclass correlation coefficient (ICC) and compared to that of task performance. Absolute CBF showed excellent test-retest reliability across the three scans for both resting and PVT scans. The reliability of regional absolute CBF was comparable to that of behavioral measures of PVT performance, and was slightly higher during PVT scans as compared with resting scans. Task-induced regional CBF changes demonstrated only poor to moderate reliability across three scans. These findings suggest that absolute CBF measures are more reliable than task-induced CBF changes for characterizing regional brain function, especially for longitudinal and clinical studies. •Absolute CBF showed excellent test-retest reliability for both resting and task scans across three days.•Reliability of absolute CBF during the PVT across three scans is comparable to PVT performance reliability.•Reliability of absolute CBF during the PVT is slightly higher than that at a resting state.•Task-induced CBF changes have poor reliability as compared with absolute CBF measures and PVT performance.•Introduction.

Background Neuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)—with its capability to improve neuronal function—may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC). Methods Eleven PWH (47–69 years old, 2 females, 100% African Americans, disease duration 16–36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2–3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1. Results Compared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test—Part B (TMT-B) to TMT—Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS. Conclusions Cingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.