Brain Sciences

BackgroundAlcohol use disorder (AUD) is a chronic condition characterized by compulsive drinking and high relapse risk. Craving in early abstinence is a strong predictor of relapse, yet its underlying neurobiological mechanisms remain unclear. Guided by Menons Triple Network Model (TNM) of psychopathology, this study investigates whether altered connectivity between the salience (SN), default mode (DMN), and central executive (CEN) networks --previously implicated in alcohol-related behaviours -- underlies craving during early abstinence. MethodsA final cohort of 27 individuals with AUD recruited from an inpatient alcohol withdrawal program completed resting-state fMRI scans on day 1 of withdrawal and 18 days later. Additionally, 17 healthy controls underwent fMRI at two sessions spaced two weeks apart. Craving was assessed in the AUD group at both timepoints using the obsessive thoughts subscale of the Obsessive Compulsive Drinking Scale (OCDS). Functional connectivity between brain networks was computed by referencing each individuals between-network connectivity to normative models derived from large-scale reference data to generate scores reflecting their deviations from normative values. Proposed analysesPlanned analyses will leverage large-scale lifespan normative models to test associations between patient deviation scores in SN-DMN connectivity and craving during acute withdrawal, along with longitudinal associations during abstinence. Exploratory analyses will assess correlations between craving and connectivity of other network pairs of the TNM. ConclusionsThis report aims to identify functional neurobiological markers of craving during early abstinence in AUD employing normative models. Findings may advance understanding of relapse vulnerability and inform personalized interventions targeting large-scale brain network dysfunctions in AUD. This submission corresponds to Level 3 of the Peer Community In (PCI) Registered Report bias-control taxonomy: data were collected and pre-processed prior to hypothesis formulation, but key variables (subject-level values) have not been observed and no statistical analyses have been performed.

Spinal cord injury (SCI) is associated with cardiovascular deficits that affect cerebral blood flow, cerebral perfusion, and cerebrovascular control. While several studies use neuroimaging techniques such as functional magnetic resonance imaging (fMRI) to understand neuroplasticity following SCI, more work needs to be done to evaluate the cerebrovascular changes following SCI. Understanding these effects using neuroimaging is essential as these deficits also affect neurovascular coupling and how we interpret neuroplasticity measured based on neuroimaging. Hence, we conducted a pilot study in twelve healthy males and thirteen males with thoracolumbar SCI using functional near-infrared spectroscopy (fNIRS) to understand the effects of breath-holding induced hypercapnia on the hemodynamics of the sensorimotor cortex and prefrontal cortex (PFC) after SCI. Participants performed 30 seconds of regular breathing alternated by 15 seconds of breath-holding for 5 minutes. Compared to controls, the SCI group presented with a greater initial decrease in oxy-hemoglobin concentration change and a delayed subsequent increase in oxy-hemoglobin concentration change in response to hypercapnia at p<. Additionally, the net increase in oxy-hemoglobin concentration change following BH in the PFC was negatively correlated with the level of injury at p=0.005, where higher levels of injury were associated with a smaller increase in oxy-hemoglobin concentration following hypercapnia. These findings confirm that a) SCI, including lower levels of injury (below T6) are associated with cerebrovascular changes that are quantifiable using fNIRS, and b) fNIRS could be a robust tool to understand the neuroplastic and cerebrovascular changes in people with SCI.

Background and purpose: People after mild traumatic brain injury (mTBI) show persistent deficits in reactive balance. Cortical processes engaged during preparation and execution of balance reactions are reflected in distinct cortical activity signatures that can be measured with electroencephalography (EEG). The purpose of this study was to 1) compare preparatory cortical beta activity and evoked cortical N1 responses during balance recovery in people with mTBI and controls, and 2) explore relationships between preparatory and evoked cortical activity. Methods: Participants (age 21-35 years) with symptomatic mTBI (n=5, 27 +/- 13 days post-injury) and controls (n=5) completed the instrumented and modified push & release tests of reactive balance. Cortical activity was recorded using encephalography (EEG). Main outcome measures were 1) preparatory sensorimotor cortical beta-bust power and duration prior to balance perturbation onset (-1s-0s), and 2) cortical N1 response amplitude and latency during the post-perturbation balance recovery (50-250ms). Results: People with mTBI exhibited lower preparatory beta-burst power compared to controls (p=0.044, g=1.18). During balance recovery, cortical N1 responses occurred earlier in people with mTBI compared to controls (p=0.045, g=3.28). Relationships between preparatory and evoked cortical activity were altered after mTBI compared to controls; people after mTBI with greater beta-burst power and longer duration elicited shorter N1 latencies (r's>0.77, p's<0.010). Discussion and conclusion: The results serve as preliminary, hypothesis-generating observations to guide future research directions investigating neural signatures of reactive balance deficits in people after mTBI. The preparatory brain state before reactive balance recovery should be explored as a potential target for post-mTBI balance rehabilitation.

An increasing number of studies highlight the role of saccadic remodulation in compensatory mechanisms following vestibular injury, and the reappearance of SHIMP saccades correlates with symptom improvement measured by the Dizziness Handicap Inventory (DHI). To investigate the influence of attentional processes and working memory on visuo-vestibular interaction, three independent but interrelated experiments were conducted. In the first two experiments, healthy subjects and patients with unilateral or bilateral vestibular deficits underwent vHIT in SHIMP mode and the Functional Head Impulse Test (fHIT), performed first separately and subsequently simultaneously. Mean latency and clustering of SHIMP saccades, together with Landolt C recognition rates, were analyzed. Differences between separate and combined protocols were assessed, and, in patients, correlated with symptom severity measured by the DHI, to determine whether the near-simultaneous execution of tasks mediated by shared parietal cortical substrates influenced performance. In the third experiment, vHIT in HIMP mode and fHIT were performed using separate and combined protocols to evaluate whether recognition-related cognitive load affected recovery saccade latency and clustering. Results suggest that visual recognition modulates visuo-vestibular interaction, supporting integrated dual-task protocols for ecological balance assessment and helping explain clinical discrepancies.

(1) Background: Brain cancer is the ninth leading cause of cancer death in the US, with approximately 76,000 newly diagnosed cases annually. Studies show that at time of diagnosis, up to six-months post-treatment, 50%-80% of brain cancer survivors (BCS) report cognitive dysfunction. Mild cognitive impairment (MCI) has gained increasing attention as a persistent disability experienced by up to 75% of all BCS, which affects memory, concentration, executive function, etc. Studies show cognitive training with computerized gaming as improving cognitive function for patients with stroke, dementia, and Parkinsons. It is of significant clinical interest to develop innovative interventions that reduce MCI. Aim: To improve cognitive performance of BCS suffering with MCI by evaluating the feasibility, acceptability and effect of a Virtual Reality Cognitive Rehabilitation Training (VR-CRT) platform during four weeks of cognitive training. (2) Methods: We employed a quasi-experimental pretest/posttest non-randomized/non-blinded single-arm design for 4 weeks, with an experimental group (n=6, after attrition) using VR-CRT. Participants were selected based on convenience sampling using the electronic medical record to identify qualified patients, guided by inclusion/exclusion criteria. Feasibility was defined by retention as >80%, with usability testing using the System Usability Scale (SUS) and NASA-TLX surveys. The Hopkins Verbal Learning Test (HVLT), Controlled Oral Word Association (COWA) test, and Trail Making A-B (TM-A/B) test were used to measure cognitive performance, comparing baseline to post week-four. (3) Results: The feasibility criteria of >80% was met. All SUS and NASA scores were in the higher index, suggesting a high degree of usability, with low workload demand. For effect, the COWA findings showed a significant improvement (41.38%), with a paired sample T-Test confirming that the participants COWA scores improved significantly from pre- to post-intervention (p = 0.03), indicating enhanced verbal fluency and executive functioning after intervention. HVLT (combined) showed improvements of 18.75% for Form A and 11.32% for Form B, which also showed a significant improvement (p = .04) in the retention discrimination index from pre- to post-test. The TM-A/B test showed an improvement (25.97%), suggesting that the participants spent less time completing both parts A and B, but was not statistically significant. (4) Conclusion: This study fulfilled our aim to demonstrate modest to significant cognitive improvement using VR-CRT with brain cancer patients with MCI. Despite the small sample size, we believe the use of virtual reality will lead to important advances for patients with MCI, particularly the frontal lobe brain region, expressed in executive function.

ObjectiveNicotinic acetylcholinergic receptors (nAChRs), comprising of and {beta} subunits are present in the brain and whole body. The less abundant 2-subunit is a fast-acting receptor subtype and plays an important role in cognition and learning. To understand cellular functional consequences, this study evaluated glucose metabolism using [18F]FDG PET/CT in 2 knockout (2KO) and 2 hypersensitive (2HS) mice. MethodsControl (CN; 4M, 4F), 2 knockout (2KO; 4M, 4F) and 2 hypersensitive (2HS; 4M,4F), 12-16 month old mice were used. Mice were fasted and injected with [18F]FDG (3-5 MBq) while awake. After 40 minutes they underwent whole body PET/CT. On a separate day, nicotine challenge [18F]FDG studies were done. Reconstructed images were analyzed to obtain standard uptake values (SUV) of [18F]FDG in brain and interscapular brown adipose tissue (IBAT). Statistical analysis was performed. ResultsThe 2HS male mice exhibited the largest brain increase in [18F]FDG compared to 2KO male mice. The rank order of brain [18F]FDG uptake in the 3 groups: 2HS[male]> CN[male]> 2KO[male]> CN[female]= 2KO[female][&ge;] 2HS[female]. Nicotine treatment reduced brain [18F]FDG uptake in all mice. Females had lower [18F]FDG uptake compared to males and were less sensitive to 2 nAChR. In the case of IBAT, 2KO mice had significantly higher baseline [18F]FDG uptake compared to the other two groups: 2KO[male]> 2KO[female]> 2HS[female]> 2HS[male]> CN[female]> CN[male]. Nicotine decreased IBAT in 2KO mice rather than increase as observed in CN and 2HS mice. Conclusions2 nAChRs plays a significant role in brain activation as exhibited by the increase in [18F]FDG in 2HS mice. In the absence of regulatory control by the 2 nAChR, the 2KO mice IBAT exhibited higher [18F]FDG IBAT compared to controls and 2HS mice. Female mice were less affected by nicotine compared to the male mice. Overall, 2 nAChRs played a significant role in glucose metabolism in the brain and IBAT.

This research demonstrates that the trans-aqueduct approach is a feasible, minimally invasive access pathway to the third ventricle, offering a potential route to the deep brain for therapeutic technologies. Further pre-clinical investigation is required to thoroughly evaluate physiological tolerance, trauma risk, and the long-term implications of intraventricular implantation. The third ventricle is a high-value site for neuromodulation due to its proximity to deep-brain targets, including the subthalamic nucleus (STN) and globus pallidus internus (GPi). This study defined the anatomical pathway; and evaluated the technical feasibility of retrograde access to the third ventricle via the cerebral aqueduct using minimally invasive interventional techniques. Evaluation was conducted in three phases using human MRI datasets (n=16; mean age 48.4 years) and cadaveric specimens (n=6; mean age 88.2 years). Phase 1 involved morphometric MRI analysis of the aqueduct and ventricles. Phase 2 tested trans-aqueduct access on cadaver specimens via fluoroscopically guided guidewires and catheters. Phase 3 utilized direct anatomical dissections on cadaver specimens (n=3) to morphometrically measure the third ventricular cavity and its relationship to deep-brain nuclei. Measurements across the sample groups showed a mean aqueduct diameter of 1.6 mm (SD=0.14). Third ventricle dimensions averaged 27.6 mm (ventral-dorsal), 19.9 mm (caudal-cranial), and 5.7 mm (lateral). Successful access to the third ventricle was achieved in 83% (5/6) of cadaveric specimens. The optimal technical configuration utilized a 0.018'' angled-tip guidewire and 5-6 Fr catheters; the aqueduct accommodated diameters up to 2.0 mm with minimal resistance. The STN and GPi were localized within 5-20 mm of the ventricular volumetric centroid. The trans-aqueduct approach is a technically feasible, minimally invasive pathway for accessing the third ventricle. This route offers a potential alternative for the delivery of therapeutic neurotechnologies. Further research is required to assess physiological tolerance, trauma risk, and the long-term safety of intraventricular implantation.

Introduction: Aphasia is an acquired language disorder with a significant negative functional impact. Much of the research on aphasia has focused on word-level language comprehension and production. Further evaluation of discourse-level tasks, both at behavioral and neural levels, will allow for an ecologically valid understanding of the functional implications of language impairment in this population. Method: This study evaluated bilateral frontal, temporal, and parietal cortical activity during computer-based narrative production in 14 young neurotypical individuals, 17 individuals with post-stroke aphasia, and 15 age-matched neurotypical participants using functional near-infrared spectroscopy (fNIRS). Oxygenated hemoglobin (HbO) was measured during narrative production following short video clips and compared to HbO during counting aloud. In addition, behavioral measures quantifying in-task performance were correlated with averaged HbO values. Results: Young neurotypical individuals showed greater cortical activity in bilateral language regions for narrative production compared to counting aloud. In contrast, people with aphasia showed positive condition-related effects in the right frontal ROI and the age-matched group showed positive condition-related effects in the left frontal and right precentral ROIs. Each group showed different patterns in relationships between cortical activity and discourse performance measures. Conclusion: Overall, young participants showing more consistent condition-related effects for narrative discourse production than individuals with aphasia and age-matched controls. This study shows the potential for fNIRS to evaluate cortical activity for ecologically valid language tasks in individuals with post-stroke aphasia.

BACKGROUND: Dual task walking requires simultaneous management of cognitive and motor demands and is associated with changes in gait and cortical activation. However, the relationship between task related cortical recruitment and dual task related gait adjustments in healthy young adults remains unclear. This study aimed to investigate the effects of dual tasking on gait performance and cortical activation, and to examine the association between changes in cortical activity and dual-task costs. METHODS: This cross sectional study included 33 healthy young adults. Participants performed three conditions: single task walking, cognitive single task (verbal fluency), and dual task walking. Each condition was repeated 10 times using a repeated short block design with randomized trial presentation. Gait performance was assessed using an instrumented walkway, and cortical activation was measured using functional near infrared spectroscopy. Dual task costs were calculated for gait and cognitive outcomes. Statistical analysis included repeated measures analysis of variance (ANOVA) and Wilcoxon signed rank tests, with false discovery rate correction for multiple comparisons. Associations between changes in cortical activation and dual task costs were examined using correlation analyses. RESULTS: Dual task walking resulted in significant changes in gait, including reduced speed, step and stride length, and increased base of support, stance, and double support (all p < 0.05), while cognitive performance remained unchanged. Dual tasking was associated with increased cortical activation in left prefrontal and motor related regions. Greater increases in cortical activation were associated with lower dual task costs across most gait parameters, with significant correlations observed in the left dorsolateral prefrontal cortex (r {approx} 0.42 to 0.47 for speed and stride length; p < 0.05). Double support showed a distinct pattern, suggesting a specific temporal adjustment within the gait cycle. CONCLUSIONS: Dual task walking in young adults is associated with coordinated behavioral and cortical adaptations. Increased cortical recruitment is linked to reduced motor interference, suggesting that broader engagement of cortical networks may contribute to performance under cognitive motor load.

Understanding the immune response against HIV-1 and the natural resistance exhibited by HIV-exposed Seronegative Individuals (HESN) offers the possibility of proposing new control strategies. Several studies suggest an important role of HLA and KIR genes in protecting against HIV-1 infection. Moreover, there is an important gap in the knowledge of these genetic factors in seronegative Latin American men who have sex with men (MSM), a population largely underrepresented in HIV immunogenetic studies. This study aimed to identify HLA and KIR genetic profile associated with potential resistance to HIV-1 acquisition, in a cross-sectional study including a cohort of 60 HIV-1-seronegative Colombian MSM at low and high risk of HIV-1 infection. The high-risk group showed a higher frequency of the HLA-B*18 allele, and a lower frequency of the HLA*B35, which have been previously associated with protection and susceptibility to HIV-1 infection respectively. Likewise, the high-risk group exhibited a low frequency of Bx haplotypes, a higher frequency of one AA haplotype and differences in KIR gene profile, with a low frequency of the inhibitory KIR2DL5 and both activating KIR2DS1, KIR2DS2 and KIR2DS5 genes. These findings suggest that host immunogenetic factors may contribute to resistance to HIV-1 acquisition in highly exposed individuals.

This retrospective study aims to explore the interactive effects of biological maturation and relative age effect (RAE) on talent identification. 56 male elite soccer players matched for chronological age (15.08{+/-}0.41 years) were studied. Test items included anthropometry (height, body mass, sitting height, leg length, BMI and Quetelet index), physiology (power, speed, agility, speed endurance and aerobic performance), soccer-specific skills (passing, shooting and dribbling), psychology (achievement motivation, orientation and resilience) and biological maturation (APHV) tests. The test results were analyzed independent sample t-test, Pearson correlation analysis, and stratified regression. Conclusion: Biological maturation significantly influences anthropometry (height, weight and Quetelet index), lower limb explosive, and speed (single-leg jump, standing triple jump, and 30-m sprint) in U16 male elite soccer players in Shanghai. The relative age effect shows no significant impact on talent selection indicators, which is attributed to the accumulated training load effect. The mechanisms of biological maturation and RAE in youth soccer talent selection are distinct and operate independently.

Background: Spinal cord injury (SCI) is associated with widespread reorganisation of cortical sensorimotor circuits. Persistent complications such as spasticity and neuropathic pain suggest that homeostatic plasticity, which normally helps stabilise and constrain activity-dependent changes in sensorimotor circuits, may be disrupted after SCI. Homeostatic plasticity can be probed using repeated blocks of transcranial direct current stimulation (tDCS); in healthy individuals, two closely spaced excitatory blocks typically leads to an inhibitory response, reflected as a reduction in corticomotor excitability. Objective: To determine whether individuals with SCI show reduced homeostatic suppression of corticospinal excitability in response to repeated anodal tDCS, compared with healthy controls. Methods: Twenty adults with thoracic or below SCI and 20 healthy controls completed three counterbalanced sessions. Each session comprised two 10-minute blocks of 2 mA tDCS separated by 5 minutes, with the second block always being anodal tDCS over left primary motor cortex. The first block was either anodal, cathodal, or sham tDCS, yielding 3 condition types: anodal-anodal, cathodal-anodal, and sham-anodal. To assess corticomotor excitability, transcranial magnetic stimulation-evoked motor evoked potentials (MEPs) were elicited at baseline, after priming, and every 5 minutes for 60 minutes after the second block. The primary outcome was percent change in MEP amplitude from baseline. Results: In the anodal-anodal condition, the SCI group showed greater facilitation than controls over 0-30 minutes (estimate = 83.09, 95% CI 49.75 to 116.43, p < 0.001), suggestive of a weaker homeostatic response. The cathodal-anodal condition led to a significant overall facilitatory effect with no between-group difference, while the sham-anodal condition showed no change in MEP amplitude relative to baseline. Within the SCI group, exploratory subgroup analysis suggests that those with neuropathic pain and a traumatic injury showed greater facilitation in the anodal-anodal condition than those without these features, indicative of a weaker homeostatic response. Conclusions: SCI is associated with impairment in the homeostatic regulation of corticomotor excitability following repeated excitatory brain stimulation. Disrupted plasticity stabilisation may be relevant to persistent symptoms such as neuropathic pain.

Regular cannabis use has been associated with alterations in reward-related neural processes, yet findings remain inconsistent and the relationship between neural activity and behavioural performance is not fully understood. The present study aimed to characterise neural and behavioural correlates of reward processing in regular cannabis users (CU) compared with matched non-users (NU) using the Monetary Incentive Delay Task (MIDT). Firstly, we assessed behavioural performance through reaction times, accuracy and monetary earnings to determine whether potential neural alterations were reflected in task performance. Secondly, focusing on reward-related brain regions, we examined group differences in BOLD functional MRI activity during anticipation and outcome phases separately for monetary win and loss conditions. Finally, we explored the association between behavioural performance and neural activation. Our findings indicate that regular cannabis use is associated with altered engagement of key nodes within the mesocorticolimbic circuit during both anticipatory and outcome phases of reward processing, accompanied by impaired behavioural performance. Particularly, compared with NU, CU showed (I) lower striatal activity during anticipation of monetary win and higher ventral striatum and frontal pole activity during anticipation of monetary loss; (II) greater VTA activation during outcome of successful monetary win and loss avoidance and lower frontal pole activity during outcome of unsuccessful loss avoidance; (III) impaired behavioural performance, reflected in lower monetary rewards and a trend towards slower reaction times and reduced accuracy; (IV) disrupted brain-behaviour coupling. Results from this study may help inform future research on the neurobiological mechanisms underlying changes in reward function and the resultant behavioural consequences of cannabis use.

IntroductionHere, we create a conditional Adra2a line and use it to show that sedative, hypnotic, and hypothermic effects of 2-agonists are neuronally mediated via the 2A adrenergic receptor. MethodsWe generated mice with loxP sites flanking Adra2a using CRISPR/Cas9 gene targeting. This line was crossed with lines encoding Cre recombinase (Cre) under the control of the Vgat, Snap25, and Dbh promoters. Cell-specific knockout was confirmed using fluorescent in-situ hybridization demonstrating targeted reduction in Adra2a mRNA in the appropriate cell types. Mice were given intraperitoneal dexmedetomidine (0.3 or 1 mg/kg) or saline, and 20 minutes later righting reflex was assessed, followed by 3 rounds of rotarod testing, with fall time and end temperature recorded. Spontaneous activity was recorded using beam break for an hour after. Mice of each genotype were implanted with EEG leads and recorded while given 0.3 mg/kg IP dexmedetomidine. ResultsWe created a conditional knockout and demonstrated cell-type specific reduction of Adra2a mRNA in crossed lines with cell-specific Cre. The pan-neuronal Adra2a knockout showed resistance to all temperature, sedative, and hypnotic effect endpoints in response to the 2-agonist dexmedetomidine. Adrenergic knockout demonstrated resistance to 2-agonist hypnosis and moderate resistance to hypothermia and impaired coordination with forced movement. GABAergic knockout showed resistance only to impairment of spontaneous movement by 2-agonists. Spectral analysis of the EEG showed an increase in proportion of delta power with a sedative dose of dexmedetomidine in all lines except the pan-neuronal Adra2a knockout. DiscussionFuture studies will pursue both the specific subtype(s) and location of neuronal populations responsible for sedative, hypnotic, and hypothermic effects of 2-agonists.

ObjectiveFinding indicators of early response to antidepressant treatment in EEG signals recorded from patients suffering from major depressive disorder. MethodsFunctional brain connectivity networks based on weighted imaginary coherence and weighted imaginary mean phase coherence were computed for 176 patients for 6 different EEG frequency bands. Cross-hemispheric connectivity (CH) and lateral asymmetry (LA) were estimated from these networks based on EEG signals recorded before the beginning of treatment (V is1) and one week after the start of the treatment (V is2). Repeated measures ANOVA was used to check for statistically significant changes in connectivity based on these measures at V is2 w.r.t. V is1. Post-hoc analysis was performed with multiple pairwise comparison tests to determine which group means were significantly different. ResultsIt was found that CHV is2 was significantly reduced w.r.t. CHV is1 in the {beta}1 [12.5 - 17.5 Hz] frequency band for the responders to treatment. Also, LAV is2 was significantly increased w.r.t. LAV is1 in the {beta}1 frequency band for the responders. No such significant changes were observed for the non-responders. Brain networks constructed using both weighted imaginary coherence and weighted imaginary mean phase coherence were found to exhibit these results. For the CH connectivity changes, binarized networks and for the LA connectivity changes, weighted networks were found to be more reliable. ConclusionsResponders were found to show a reduction in cross-hemispheric connectivity and an increase in lateral asymmetry, both in the {beta}1 band while no such change was observed for the non-responders. SignificanceDecrease in cross-hemispheric connectivity and increase in lateral asymmetry in the {beta}1 band may represent candidate neurophysiological indicators of early treatment response, but they require independent replication before any clinical application can be considered.

Preclinical evidence indicates that cocaine exerts acute and chronic effects on astrocyte functioning, which in turn modulate cocaine-related impacts on neural integrity and brain function. However, human evidence for astrocytic involvement in cocaine users (CU) remains limited. Glial fibrillary acidic protein (GFAP) is a marker of astrocyte activation with promising clinical utility in neurological conditions, yet its relevance in the addiction field is unclear. Hence, we investigated plasma GFAP levels in chronic CU (n=41) and cocaine-naive controls (HC; n=34) at baseline and after a 4-month follow-up. GFAP was assessed alongside plasma neurofilament light chain (NfL) levels, a marker of neuroaxonal injury previously associated with cocaine use in the same sample. Contrary to our hypothesis, we found no group differences in plasma GFAP concentrations between CU and HC. Neither cross-sectional nor longitudinal associations between GFAP levels and objective indices of cocaine use (derived from hair testing) were detected. However, exploratory analyses revealed higher plasma GFAP levels among CU with recent cocaine consumption (within the last 7 days), suggesting transient astrocytic responses following acute exposure. Additionally, GFAP and NfL were positively correlated across participants, supporting their functional association. Overall, these findings suggest that while GFAP might not be chronically elevated in CU, it may exhibit transient increases related to recent cocaine use. Further research is warranted to characterize the temporal dynamics and biological significance of these glial responses.

The present study aimed at evaluating the impact of high-definition transcranial random noise stimulation (HD-tRNS) applied to the right dorsolateral prefrontal cortex (DLPFC) on direct learning in computer-based complex tasks, and potential far transfer effects to a flight simulator task. Thirty young pilots in general aviation participated in a double-blind 11-week protocol that included a two-hour baseline session (week 1), 10 one-hour training sessions (weeks 2 to 6), a short-term (week 7) and a long-term (week 11) evaluations. Both stimulated, and sham groups exhibited improvements in trained (MATB and Space Fortress video game) and untrained (Flight Simulator) tasks from baseline to the first and last evaluation sessions. No significant differences between groups have been found either in terms of direct (trained tasks) or transfer (flight simulator and associated mental workload) effects. These findings contribute to the ongoing debate on the efficacy of transcranial brain stimulation for enhancing learning in healthy participants. Specifically, the present study demonstrates that the applied stimulation protocol yields no measurable benefit to learning processes, underscoring the need to explore alternative stimulation parameters and methodological approaches.

Astrocytes are the most abundant glial cells in the brain and an integrative component of the neural network. Studies have shown that ethanol altered expression of an astrocyte marker, i.e., glial fibrillary acidic protein (GFAP), in two key corticolimbic regions, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). These regions comprise anatomically and functionally different subregions, i.e., the prelimbic (PL) and infralimbic (IL) cortex of the mPFC, the shell and core subregions of the NAc. However, ethanol effects on GFAP expression within these subregions remain largely unknown. In addition, effects of pharmacological manipulation of astrocytes on alcohol drinking have been understudied. Western blot was conducted to determine GFAP expression in subregions of the mPFC and NAc after chronic ethanol drinking. Fluorocitrate, an astrocyte-specific metabolic inhibitor, was administered to inhibit astrocytes and was tested on ethanol drinking. Ethanol drinking enhanced GFAP protein expression in the PL cortex and NAc core, but not in the IL cortex or NAc shell. Intra-ventricular administration of fluorocitrate reduced ethanol intake and preference, but increased water consumption during choice ethanol drinking. In addition, fluorocitrate did not affect total fluid consumption or basal locomotor activity. These results indicate that chronic ethanol drinking induced GFAP elevation in a subregion-specific manner within the mPFC and NAc, and that metabolic inhibition of astrocytes selectively attenuated ethanol drinking without non-specific effects on water drinking or general activity. Together, these results suggest that astrocytes may play an important role in ethanol drinking. HighlightsO_LIEthanol drinking enhanced GFAP levels in the PL cortex and NAc core. C_LIO_LIFluorocitrate inhibition of astrocytes reduced intermittent ethanol drinking. C_LIO_LIFluorocitrate did not alter total fluid consumption or basal locomotor activity. C_LI

The amplitude of motor-evoked potentials (MEPs) elicited using transcranial magnetic stimulation (TMS) has been shown to decrease in the short interval prior to response initiation. The cause of this premovement MEP suppression is currently unclear and has been attributed to various processes such as preparation-related inhibition preventing the premature release of planned action or increasing signal-to-noise ratio to facilitate rapid response initiation. The present study explored whether the decrease in MEP amplitude is affected by the task requirements, using reaction time (RT) paradigms that differ in the timeline of preparation and initiation of a motor response. Participants completed simple RT (SRT), choice RT (CRT), and go/no-go (GNG) tasks, while TMS was applied at various times between the warning signal and go-signal. It was hypothesized that if MEP suppression relates to preparation level, the greatest suppression would be observed during the SRT and GNG tasks, as these paradigms encourage advance preparation and response inhibition. Conversely, if the reduction in corticospinal excitability is associated with facilitating response initiation processes, then suppression would be expected for all tasks, including the CRT paradigm in which preparation does not occur until presentation of the go-signal. Results showed MEP amplitudes decreased for all tasks as the go-signal approached; however, both the SRT and GNG had significantly greater MEP suppression 50 ms prior to, and coincident with the go-signal. These results indicate that the nature and origin of the suppression is likely multifactorial and relates to both preparatory and initiation-related processes, with the timeline and magnitude of suppression dependent on the nature of the task being executed. Impact StatementTranscranial magnetic stimulation was used to elicit motor-evoked potentials to examine the timeline of corticospinal activation during the instructed delay period for choice, simple and go/no-go reaction time tasks. For all tasks, corticospinal excitability was initially elevated compared to baseline, followed by a similar magnitude of early suppression. However, just prior to the go-signal, those tasks that allowed advance preparation showed additional suppression, providing novel information linking pre-movement corticospinal suppression to preparatory and inhibition processes.

Excessive screen use is associated with childhood behavioral problems, but whether associations differ between typically developing (TD) children and those with autism spectrum disorder (ASD) is unclear. Our cross-sectional study included 108 children aged 5-9 years (61 TD, 47 ASD). ASD was diagnosed using standardized clinical instruments. Measures included parent-reported screen time (excluding TV/DVD), cognitive ability (K-ABC), and behavioral problems (Vineland-II). Screen time and externalizing problems were associated in the TD group (Spearmans {rho} = 0.361, p < 0.01), but not in the ASD group. In the regression model, screen time ({beta} = 0.40, t = 2.60, p < 0.05), ASD status ({beta} = 0.70, t = 8.30, p < 0.001), and their interaction ({beta} = -0.34, t = -2.06, p < 0.05) significantly predicted externalizing problems. Considering the diversity within the autism spectrum, future studies with larger sample sizes should consider individual heterogeneity when examining the association between behavioral outcomes and screen time.