UNASSIGNED: Adolescents with disrupted rest-activity rhythms (RAR) including shorter sleep duration, later sleep timing and low physical activity levels have higher risk for mental and behavioral problems. However, it remains unclear whether the same associations can be observed for within-subject changes in RAR.
UNASSIGNED: Our longitudinal investigation on RAR used Fitbit data from the Adolescent Brain Cognitive Development (ABCD) Study at the 2-year (FL2: aged 10-13 years) and 4-year follow-up (FL4: aged 13-16 years). 963 youths had good-quality Fitbit data at both time points. In this study we examined changes in RAR from FL2 to FL4, their environmental and demographic contributors as well as brain and behavioral correlates.
UNASSIGNED: From FL2 to FL4, adolescents showed decreases in sleep duration and physical activity as well as delayed sleep timing (Cohen\'s d .44-.75). The contributions of environmental and demographic factors to RAR changes were greatest to sleep timing (explained 10% variance) and least to sleep duration (explained 1% variance). Delays in sleep timing had stronger correlations with behavioral problems including greater impulsivity and poor academic performance than reductions in sleep duration or physical activity. Additionally, the various brain measures differed in their sensitivity to RAR changes. Reductions in sleep duration were associated with decreased brain functional connectivity between subcortical regions and sensorimotor and cingulo-opercular networks and with enhanced functional connectivity between sensorimotor, visual and auditory networks. Delays in sleep timing were mainly associated with grey matter changes in subcortical regions.
UNASSIGNED: The current findings corroborate the role of sleep and physical activity in adolescent\'s brain neurodevelopment and behavior problems. RAR might serve as biomarkers for monitoring behavioral problems in adolescents and to serve as potential therapeutic targets for mental disorders.

Cognitive flexibility is an executive functioning skill that develops in childhood, and when impaired, has transdiagnostic implications for psychiatric disorders. To identify how intrinsic neural architecture at rest is linked to cognitive flexibility performance, we used the data-driven method of independent component analysis (ICA) to investigate resting state networks (RSNs) and their whole-brain connectivity associated with levels of cognitive flexibility performance in children. We hypothesized differences by cognitive flexibility performance in RSN connectivity strength in cortico-striatal circuitry, which would manifest via the executive control network, right and left frontoparietal networks (FPN), salience network, default mode network (DMN), and basal ganglia network. We selected participants from the Adolescent Brain Cognitive Development (ABCD) Study who scored at the 25th, (\"CF-Low\"), 50th (\"CF-Average\"), or 75th percentiles (\"CF-High\") on a cognitive flexibility task, were early to middle puberty, and did not exhibit significant psychopathology (n = 967, 47.9% female; ages 9-10). We conducted whole-brain ICA, identifying 14 well-characterized RSNs. Groups differed in connectivity strength in the right FPN, anterior DMN, and posterior DMN. Planned comparisons indicated CF-High had stronger connectivity between right FPN and supplementary motor/anterior cingulate than CF-Low. CF-High had more anti-correlated connectivity between anterior DMN and precuneus than CF-Average. CF-Low had stronger connectivity between posterior DMN and supplementary motor/anterior cingulate than CF-Average. Post-hoc correlations with reaction time by trial type demonstrated significant associations with connectivity. In sum, our results suggest childhood cognitive flexibility performance is associated with DMN and FPN connectivity strength at rest, and that there may be optimal levels of connectivity associated with task performance that vary by network.

BACKGROUND: Brief interventions for alcohol use disorder (AUD) are generally efficacious, albeit with variability in response. Resting state functional connectivity (rsFC) may characterize neurobiological indicators that predict the response to brief interventions and is the focus of the current investigation.
METHODS: Forty-six individuals with AUD (65.2% female) completed a resting state functional magnetic resonance imaging (fMRI) scan immediately followed by a brief intervention aimed at reducing alcohol consumption. Positive clinical response was defined as a reduction in alcohol consumption by at least one World Health Organization (WHO) risk drinking level at 3-month follow-up. rsFC was analyzed using seed-to-voxel analysis with seed regions from four networks: salience network, reward network, frontoparietal network, and default mode network.
RESULTS: At baseline, responders had greater rsFC between the following seed regions in relation to voxel-based clusters than non-responders: (i) anterior cingulate cortex (ACC) in relation to left postcentral gyrus and right supramarginal gyrus (salience network); (ii) right posterior parietal cortex in relation to right ventral ACC (salience network); (iii) right interior frontal gyrus (IFG) pars opercularis in relation to right cerebellum and right occipital fusiform gyrus (frontoparietal); and (iv) right primary motor cortex in relation to left thalamus (default mode). Lower rsFC in responders vs. nonresponders was seen between the (i) right rostral prefrontal cortex in relation to left IFG pars triangularis (frontoparietal); (ii) right IFG pars triangularis in relation to right cerebellum (frontoparietal); (iii) right IFG pars triangularis in relation to right frontal eye fields and right angular gyrus (frontoparietal); and (iv) right nucleus accumbens in relation to right orbital frontal cortex and right insula (reward).
CONCLUSIONS: Resting state functional connectivity in the frontoparietal, salience, and reward networks predicts the response to a brief intervention in individuals with AUD and could reflect greater receptivity or motivation for behavior change.

UNASSIGNED: Alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonists have been developed to treat schizophrenia but failed in clinical trials due to rapid desensitization. GAT107, a type 2 allosteric agonist-positive allosteric modulator (ago-PAM) to the α7 nAChR was designed to activate the α7 nAChR while reducing desensitization. We hypothesized GAT107 would alter the activity of thalamocortical neural circuitry associated with cognition, emotion, and sensory perception.
UNASSIGNED: The present study used pharmacological magnetic resonance imaging (phMRI) to evaluate the dose-dependent effect of GAT107 on brain activity in awake male rats. Rats were given a vehicle or one of three different doses of GAT107 (1, 3, and 10 mg/kg) during a 35 min scanning session. Changes in BOLD signal and resting state functional connectivity were evaluated and analyzed using a rat 3D MRI atlas with 173 brain areas.
UNASSIGNED: GAT107 presented with an inverted-U dose response curve with the 3 mg/kg dose having the greatest effect on the positive BOLD volume of activation. The primary somatosensory cortex, prefrontal cortex, thalamus, and basal ganglia, particularly areas with efferent connections from the midbrain dopaminergic system were activated as compared to vehicle. The hippocampus, hypothalamus, amygdala, brainstem, and cerebellum showed little activation. Forty-five min post treatment with GAT107, data for resting state functional connectivity were acquired and showed a global decrease in connectivity as compared to vehicle.
UNASSIGNED: GAT107 activated specific brain regions involved in cognitive control, motivation, and sensory perception using a BOLD provocation imaging protocol. However, when analyzed for resting state functional connectivity there was an inexplicable, general decrease in connectivity across all brain areas.

This study examined the effects of human immunodeficiency virus (HIV) on resting state functional connectivity (RSFC) in a large cohort of people with HIV (PWH) and healthy controls without HIV (PWoH). Within PWH analyses focused on the effects of viral suppression and cognitive impairment on RSFC.
A total of 316 PWH on stable combination antiretroviral therapy and 209 demographically matched PWoH were scanned at a single institution. Effects of the virus were examined by grouping PWH by detectable (viral load > 20 copies/mL; VLD) and undetectable (VLU) viral loads and as being cognitively impaired (CI) (Global Deficit Score ≥ 0.5) or cognitively normal (CN). Regression analysis, object oriented data analysis, and spring embedded graph models were applied to RSFC measures from 298 established brain regions of interest comprising 13 brain networks to examine group differences.
No significant RSFC differences were observed between PWH and PWoH. Within PWH, there were no significant differences in RSFC between VLD and VLU subgroups and CI and CN subgroups.
There were no significant effects of HIV on RSFC in our relatively large cohort of PWH and PWoH. Future studies could increase the sample size and combine with other imaging modalities.

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Executive function deficits (EFD) in late life depression (LLD) are associated with poor outcomes. Dysfunction of the cognitive control network (CCN) has been posited in the pathophysiology of LLD with EFD.
Seventeen older adults with depression and EFD were randomized to iTBS or sham for 6 weeks. Intervention was delivered bilaterally using a recognized connectivity target.
A total of 89% (17/19) participants completed all study procedures. No serious adverse events occurred. Pre to post-intervention change in mean Montgomery-Asberg-depression scores was not different between iTBS or sham, p = 0.33. No significant group-by-time interaction for Montgomery-Asberg Depression rating scale scores (F 3, 44  = 0.51; p = 0.67) was found. No significant differences were seen in the effects of time between the two groups on executive measures: Flanker scores (F 1, 14  = 0.02, p = 0.88), Dimensional-change-card-sort scores F 1, 14  = 0.25, p = 0.63, and working memory scores (F 1, 14  = 0.98, p = 0.34). The Group-by-time interaction effect for functional connectivity (FC) within the Fronto-parietal-network was not significant (F 1, 14  = 0.36, p = 0.56). No significant difference in the effect-of-time between the two groups was found on FC within the Cingulo-opercular-network (F 1, 14  = 0, p = 0.98).
Bilateral iTBS is feasible in LLD. Preliminary results are unsupportive of efficacy on depression, executive function or target engagement of the CCN. A future Randomized clinical trial requires a larger sample size with stratification of cognitive and executive variables and refinement in the target engagement.

The resting-state infraslow oscillation (ISO) of the cerebral cortex reflects the neurophysiological state of the human brain. ISO results from distinct vasomotion with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. Quantification of prefrontal ISO in cortical hemodynamics and metabolism in the resting human brain may facilitate the identification of objective features that are characteristic of certain brain disorders. The goal of this study was to explore and quantify the prefrontal ISO of the cortical concentration changes of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics in all 3 E/N/M bands. Two-channel broadband near-infrared spectroscopy (2-bbNIRS) enabled measurements of the forehead of 26 healthy young participants in a resting state once a week for 5 weeks. After quantifying the ISO spectral amplitude (SA) and coherence at each E/N/M band, several key and statistically reliable metrics were obtained as features: (i) SA of Δ[HbO] at all E/N/M bands, (ii) SA of Δ[CCO] in the M band, (iii) bilateral connectivity of hemodynamics and metabolism across the E and N bands, and (iv) unilateral hemodynamic-metabolic coupling in each of the E and M bands. These features have promising potential to be developed as objective biomarkers for clinical applications in the future.

The establishment of test-retest reliability and reproducibility (TRR) is an important part of validating any research tool, including functional magnetic resonance imaging (fMRI). The primary objective of this study is to investigate the reliability of pseudo-Continuous Arterial Spin Labeling (pCASL) and Blood Oxygen Level Dependent (BOLD) fMRI data acquired across two different scanners in a sample of healthy adults. While single site/single scanner studies have shown acceptable repeatability, TRR of both in a practical multisite study occurring in two facilities spread out across the country with weeks to months between scans is critically needed.
Ten subjects were imaged with similar 3 T MRI scanners at the University of Pittsburgh and Massachusetts General Hospital. Finger-tapping and Resting-state data were acquired for both techniques. Analysis of the resting state data for functional connectivity was performed with the Functional Connectivity Toolbox, while analysis of the finger tapping data was accomplished with FSL. pCASL Blood flow data was generated using AST Toolbox. Activated areas and networks were identified via pre-defined atlases and dual-regression techniques. Analysis for TRR was conducted by comparing pCASL and BOLD images in terms of Intraclass correlation coefficients, Dice Similarity Coefficients, and repeated measures ANOVA.
Both BOLD and pCASL scans showed strong activation and correlation between the two locations for the finger tapping tasks. Functional connectivity analyses identified elements of the default mode network in all resting scans at both locations. Multivariate repeated measures ANOVA showed significant variability between subjects, but no significant variability for location. Global CBF was very similar between the two scanning locations, and repeated measures ANOVA showed no significant differences between the two scanning locations.
The results of this study show that when similar scanner hardware and software is coupled with identical data analysis protocols, consistent and reproducible functional brain images can be acquired across sites. The variability seen in the activation maps is greater for pCASL versus BOLD images, as expected, however groups maps are remarkably similar despite the low number of subjects. This demonstrates that multi-site fMRI studies of task-based and resting state brain activity is feasible.

Magnetic Resonance-guided high-intensity Focused Ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus (Vim) for tremor has increasingly gained interest as a new non-invasive alternative to standard neurosurgery. Resting state functional connectivity (rs-FC) correlates of MRgFUS have not been extensively investigated yet. A region of interest (ROI)-to-ROI rs-FC MRI \"connectomic\" analysis focusing on brain regions relevant for tremor was conducted on 15 tremor-dominant patients with Parkinson\'s disease who underwent MRgFUS. We tested whether rs-FC between tremor-related areas was modulated by MRgFUS at 1 and 3 months post-operatively, and whether such changes correlated with individual clinical outcomes assessed by the MDS-UPDRS-III sub items for tremor. Significant increase in FC was detected within bilateral primary motor (M1) cortices, as well as between bilateral M1 and crossed primary somatosensory cortices, and also between pallidum and the dentate nucleus of the untreated hemisphere. Correlation between disease duration and FC increase at 3 months was found between the putamen of both cerebral hemispheres and the Lobe VI of both cerebellar hemispheres, as well as between the Lobe VI of untreated cerebellar hemisphere with bilateral supplementary motor area (SMA). Drop-points value of MDS-UPDRS at 3 months correlated with post-treatment decrease in FC, between the anterior cingulate cortex and bilateral SMA, as well as between the Lobe VI of treated cerebellar hemisphere and the interpositus nucleus of untreated cerebellum. Tremor improvement at 3 months, expressed as percentage of intra-subject MDS-UPDRS changes, correlated with FC decrease between bilateral occipital fusiform gyrus and crossed Lobe VI and Vermis VI. Good responders (≥50% of baseline tremor improvement) showed reduced FC between bilateral SMA, between the interpositus nucleus of untreated cerebellum and the Lobe VI of treated cerebellum, as well as between the untreated SMA and the contralateral putamen. Good responders were characterized at baseline by crossed hypoconnectivity between bilateral putamen and M1, as well as between the putamen of the treated hemisphere and the contralateral SMA. We conclude that MRgFUS can effectively modulate brain FC within the tremor network. Such changes are associated with clinical outcome. The shifting mode of integration among the constituents of this network is, therefore, susceptible to external redirection despite the chronic nature of PD.