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.

Associative memory, the ability to bind and retrieve relationships between unrelated elements, is a cornerstone of human cognition and a primary target for neurorehabilitation. Vagus nerve stimulation (VNS) has emerged as a promising method to modulate the locus coeruleus-norepinephrine (LC-NE) system and hippocampal-prefrontal circuits essential for memory. However, the comparative efficacy of non-invasive modalities such as electrical (E-taVNS) and the emerging field of ultrasound (U-taVNS) remains poorly understood in the context of active recall. In this study, participants performed a crossmodal video-word associative memory task before and after receiving either E-taVNS or U-taVNS in active and sham conditions. We investigated whether these modalities enhance cued recall accuracy and retrieval reaction time. Our results revealed that neither E-taVNS nor U-taVNS significantly improved recall accuracy. However, E-taVNS significantly accelerated response times specifically for correctly recalled items. These findings suggest that while taVNS may not increase the likelihood of recalling associative memories, electrical stimulation may enhances the efficiency in which we do so. These findings suggest that electrical taVNS is a viable tool for facilitating memory search processes, though further research is required to optimize ultrasound parameters and validate mechanistic pathways through physiological monitoring.

Early life stress (ELS) in primates alters dopamine function, contributing to addiction, hyperactivity, cognitive deficits, aggression, and social subordinance. To assess whether dopamine receptor densities are affected by ELS, male juvenile rhesus monkeys (Macaca mulatta) were either mother-reared (MR, N=6) in a semi-natural environment or nursery-reared (NR, N=6) with peers in a laboratory. At 1 [1/2] years of age, subjects were sacrificed and the left prefrontal cortex (PFC), striatum (caudate and putamen), nucleus accumbens (NAcc), and claustrum (CLA) were explored through quantitative autoradiographic studies of dopamine receptor-1 (DRD1) and -2 (DRD2) conducted using [125I]-(+)-SCH 23982 and 125I-Epidepride, which have high affinity and selectivity for DRD1 and DRD2, respectively. No group differences emerged in striatal or NAcc receptor binding. However, MR monkeys exhibited significantly greater DRD1 binding in the left orbital PFC and significantly greater DRD2 binding in both the left medial PFC and right CLA compared to NR. These findings implicate the medial PFC (stress vulnerability, cognition), orbital PFC (reward valuation), and CLA (anxiety modulation) as critical sites disrupted by maternal deprivation. Therefore, we propose that nursery-rearing induces a hypodopaminergic prefrontal-claustral ecophenotype, underlying the cognitive, affective, and social impairments observed in NR monkeys.

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.

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.

Ketamine, an N-Methyl-D-aspartate receptor (NMDAR) antagonist, is used clinically as an anesthetic and antidepressant, and is also known for its psychotomimetic effects. Its impact on brain dynamics and behavior varies significantly with dosage likely via a dose-dependent modulation of the NMDARergic transmission. Currently, it is unclear how molecular changes at the microscopic level of NMDAR antagonism lead to large-scale changes in brain dynamics. We implement a dose-dependent NMDAR antagonism based on ketamines disinhibition theory into a biophysically grounded mean-field model within The Virtual Brain (TVB) framework to replicate ketamines key signatures across its dose spectrum. Our results imply that in low doses ketamine preferentially impairs excito-inhibitory neurotransmission while in higher doses antagonism on excito-excitatory connections plays a role. These findings highlight the utility of computational modeling for disentangling dose-specific mechanisms of action and provide a framework for exploring NMDAR-related interventions. Author summaryKetamine is a dissociative anesthetic at high doses, but at lower, sub-anesthetic doses, it has garnered significant interest for its rapid-acting antidepressant and anxiolytic effects. Despite its growing clinical use in psychiatric conditions, the precise neural mechanisms underlying ketamines dose-dependent effects remain incompletely understood. Ketamine primarily acts as a non-competitive antagonist of the NMDAR, which is expressed on both excitatory and inhibitory neurons throughout the cortex. One of the leading hypotheses explaining its antidepressant effects is the disinhibition theory which proposes that low doses of ketamine preferentially block NMDARs on inhibitory interneurons, resulting in increased cortical excitability. At high doses ketamine exerts anesthetic effects potentially through more widespread NMDAR antagonism including on excitatory neurons. In this study, we used a computational model to explore how selective NMDAR antagonism at different doses affects large-scale brain dynamics. A key novelty of our work is the integration of ketamines full dose spectrum within a single computational modeling framework, allowing us to relate distinct neural effects from disinhibition to anesthesia to experimental findings. This modeling approach contributes to a deeper understanding of how ketamine modulates cortical activity across different contexts.

Acute spinal cord injury is a condition with a poor prognosis, leading to reduced quality of life and high economic costs for both patients and health systems, and only a minority of patients with this injury can achieve a meaningful recovery. Given the high frequency of traumatic events such as vehicle collisions and falls, research aimed at limiting injury extension, promoting neuronal recovery, and improving prognosis is essential. It has been shown that ketone bodies have anti-inflammatory properties and also mediate the Nrf2 pathway, exerting antioxidant effects. The aim was to identify any alternative to mitigate the extension and progression of secondary injury by using 1,3 butanediol as a {beta}-hydroxybutyrate source. An experimental model (n= 60) of clinically healthy male Wistar rats were used, divided into five groups (n=12) as a control group, while the remaining rats were subjected to extradural spinal cord clipping according to the following groups (n=12): Spinal Cord Injury (SCI); endogenous ketosis + methylprednisolone (Endo-K+MP); exogenous ketosis + methylprednisolone (Exo-K+MP), and methylprednisolone (MP). After 8 hours of spinal cord injury, tissue was collected, immunohistochemistry and PCR analyses were carried out. Nrf2 and 3NT for the antioxidant pathway, and HIF-1, NFkB, NLRP3, TNF-[a] and IL-1{beta} for inflammation were analyzed. Results demonstrated that the groups thrown into a ketosis state had better outcomes, and, according to the Exo-k+MP and Endo-k+MP groups, increased Nrf2 and decreased 3NT (p < 0.05), which resulted in an upregulation of antioxidant pathways. According to HIF-1 and NF{kappa}B, Endo-K+MP showed better outcomes p<0.05 and proinflammatory cytokines showed the same pattern as the standard treatment (MP) p<0.05). Overall, our results also demonstrated a downregulation of inflammatory pathways. Author SummarySpinal cord injury is a devastating condition that frequently results in permanent neurological damage, reduced quality of life, and high social and healthcare costs. Current treatments are limited and mainly focus on reducing inflammation after injury, with methylprednisolone being one of the most commonly used therapies despite its associated adverse effects. Previous studies have shown that ketosis, a metabolic state characterized by increased ketone bodies, has anti-inflammatory and antioxidant properties in several neurological conditions. In this study, we investigated whether inducing ketosis could improve early outcomes after acute spinal cord injury. Using a rat model, we compared the effects of endogenous ketosis (induced by fasting) and exogenous ketosis (induced by ketone precursors), alone or in combination with methylprednisolone. We analyzed inflammatory and oxidative stress pathways using immunohistochemistry and molecular techniques. Our findings show that ketosis enhances the anti-inflammatory and antioxidant effects of methylprednisolone, leading to reduced activation of inflammatory pathways and increased antioxidant responses during the first hours after injury. These results suggest that metabolic interventions such as ketosis may represent a promising complementary strategy to improve early management of spinal cord injury.

Developing scientific reading skills is critical for undergraduate STEM students due to scientific literatures unique formatting and use of specialized jargon. Generative AI tools such as ChatGPT offer students the ability to ask questions about what they are reading interactively. Previously, we reported the development of a ChatGPT-assisted reading guide that combined structured, active reading strategies with using ChatGPT to clarify unfamiliar words and concepts in real time. In the initial study, undergraduates found the use of the ChatGPT-assisted reading guide helpful in their understanding of an abstract and introduction of a journal article. Here, the ChatGPT-assisted reading guide was used in a journal club assignment for an undergraduate chemistry course. ChatGPT transcripts were analyzed for common types of interactions, and students were surveyed about their experience. Overall, students reported that using the ChatGPT-assisted reading guide was helpful in understanding the article and helped them have more productive class discussions. However, some students also expressed skepticism about using AI tools, citing concerns about accuracy of AI-generated information and the effect of using AI on their own learning.

Anorexia nervosa is an eating disorder disproportionately found in female human teens and young adults. It is often resistant to treatment, has a significant chance of relapse and is more lethal than other eating disorders, such as bulimia nervosa or Avoidant/Restrictive Food Intake Disorder (ARFID). There is no specific medication for the treatment of anorexia nervosa. Treatment consists of psychosocial means, psychotherapy, psychoeducation, and nutritional counseling. Medication is usually used for treating comorbidities such as anxiety or to decrease obsessive-compulsive tendencies. These medications cannot help the patient regain weight or treat core symptoms. Metabotropic 2/3-glutamate (mGluR2/3) receptor agonist (LY379268) and antagonist (LY341495) are promising pharmacological agents to treat psychiatric disorders. Both agonists and antagonists have been reported to have anxiolytic effects in different animal models of anxiety, while antagonists have shown antidepressant-like effects in preclinical studies. The activity-based anorexia (ABA) paradigm is used to model anorexia nervosa. It consists of giving mice access to a running wheel and restricting their feeding time. This causes mice to exercise more than mice without feeding time restriction and to eat less than mice without access to a moving running wheel. In this study, we subcutaneously injected female ABA model mice with a metabotropic 2/3-glutamate receptor agonist (LY379268) and antagonist (LY341495) in two experiments. Both compounds exacerbated weight loss by decreasing food intake as well as increasing physical activity. It can be concluded that the manipulation of mGluR2/3 receptors is detrimental for the ABA model and likely for anorexia nervosa as well. HighlightsO_LImGluR2/3 agonist LY379268 decreases food intake and body weight of the ABA model C_LIO_LImGluR2/3 antagonist LY341495 decreases food intake and body weight of the ABA model C_LIO_LIBoth agonist and antagonist produce the effect within 48 hours C_LIO_LIBoth the agonist and antagonist are detrimental to the ABA-model C_LI

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