Brain and Behavior

The validation of objective neurophysiological monitoring of concussion from diagnosis to return to play has the potential to improve the clinical care of athletes. Extracted from event-related potentials (ERP), brain vital signs offer a non-invasive objective neurophysiological measure of three well established ERP responses that complement existing clinical assessments: 1) the N100 response related to auditory sensation; 2) the P300 response related to basic attention; and 3) the N400 response related to cognitive processing. The N400, in particular, has increasingly been demonstrated to be sensitive to head impact related cognitive impairment. Accordingly, brain vital sign measures were collected in n =165 rugby league players from two Australian professional National Rugby League clubs (NRL), with concussed players (n =26) being subsequently assessed over a total of five separate time points (Baseline, Day 2, Day 5, Day 10, and Day 42). This timeline aligned with acute (Day 2), NRL mandatory minimum return-to-play (RTP) guidelines (Day 10), and an extended post RTP period. Relative to baseline, the results revealed significant N400 cognitive processing latency delays at Day 2 post-concussion (p =0.002). The N400 latency delays persisted past day 5, significantly returning to baseline values at Day 10, consistent with the RTP mandatory minimum requirement. The findings indicated that neurophysiological recovery occurred in this cohort within an approximate 10-day time frame. Future studies monitoring brain vital sign changes across the trajectory of injury to recovery are needed in sports related concussion management.

Background and Objectives Transient ischemic attack (TIA) diagnosis is challenging because it relies mainly on clinical assessment and exclusion of common differential. Functional MRI (fMRI) may provide a diagnostic biomarker by detecting transient brain dysfunction not visible on conventional imaging. This pilot study aimed to characterize acute motor-task BOLD activation in patients with suspected DWI-negative TIA and compare functional patterns between confirmed TIA and alternative diagnoses. Secondary objectives were to assess longitudinal changes in activation and connectivity at 3 months. Methods In this prospective single-center study, adults presenting within 24 h of transient anterior-circulation neurological symptoms underwent conventional MRI and additional motor-task fMRI. Patients with acute DWI lesions were excluded. Final diagnosis was established after 3-month follow-up. Whole-brain analyses, individualized motor cortex region-of-interest (ROI) analyses, and generalized psychophysiological interaction (gPPI) connectivity analyses were performed during the acute phase and at 3 months. Results Eight patients were enrolled; six had complete longitudinal imaging data and were included in the final analyses. Final diagnoses were TIA (n=2), migraine aura (n=2), functional neurological disorder (n=1), and hypoglycemia (n=1). Whole-brain and ROI analyses showed reduced bilateral motor-related BOLD responses during the acute phase in both TIA patients and in the patient with hypoglycemia. In contrast, patients with migraine and functional neurological disorder exhibited less marked longitudinal changes. In TIA patients, motor cortex activation increased at 3 months, tending to normalize toward values observed in non-TIA participants. Connectivity analyses revealed heterogeneous patterns, but the 2 TIA patients demonstrated increased longitudinal connectivity between the motor cortex contralateral to symptoms and other sensorimotor regions, including supplementary motor, premotor, parietal, and postcentral cortices. Discussion These preliminary findings suggest that TIA may be associated with transient bilateral reductions in motor-network activity. Functional abnormalities appeared to improve over time, supporting the hypothesis of reversible network dysfunction. Although limited by the very small sample size, this study provides the first longitudinal assessment of emergency task-based fMRI in rigorously defined TIA and supports further investigation of acute functional MRI as a potential biomarker of transient cerebral dysfunction.

Transcranial magnetic stimulation (TMS) is widely used in both clinical and research settings to study and treat neurological and neuropsychiatric disorders, yet its underlying neural mechanisms remain unclear; particularly how stimulation influences both local and distant regional activity in relation to behavior. In this study, we combined single-pulse TMS with concurrent whole-head functional near-infrared spectroscopy (fNIRS) to examine hemodynamic and behavioral responses during a working memory task, with a focus on behavioral variability. Single TMS pulses were delivered to the left dorsolateral prefrontal cortex (DLPFC) while healthy participants rested; additionally, single pulses were delivered online to the left DLPFC while participants performed the working memory task. Across all participants, we observed a reliable load-dependent increase in hemodynamic activity associated with task. However, behavioral responses to TMS varied during the task. When participants were stratified into subgroups based on performance, a distinct topographic pattern emerged. During the task, TMS systematically modulated hemodynamic responses in regions including DLPFC, superior medial gyrus, precuneus, and parietal lobule, which are areas belonging to the default mode network. Moreover, the hemodynamic response during the single pulse alone sessions without any task was also found to be associated with the behavioral responses in a coherent pattern involving DLPFC, precuneus and parietal lobules. These findings suggest that variable behavioral outcomes during online TMS task are linked to distinct hemodynamic responses in a topographic pattern of local and distant regional areas.

Chemotherapy is a common treatment for women with ovarian cancer, and many women treated with chemotherapy experience cognitive dysfunction. However, few studies have investigated the mechanisms of chemotherapy-related cognitive impairment in women with ovarian cancer. The goal of this study was to assess the relationships among neurovascular coupling, iron levels and cognitive functions in women with ovarian cancer after first-line chemotherapy. Simultaneous fNIRS and EEG data were collected in women diagnosed with advanced stage ovarian cancer at baseline (N = 13) and after 3-9 rounds of chemotherapy (N = 8). The attentional network task (ANT) was administered for neurocognitive evaluation. Blood iron levels were measured using standard clinical assays. In parallel, similar concurrent fNIRS-EEG data were acquired in a group of 10 healthy participants in a test-retest design. Cognitive performance declined, as indicated by decreases in ANT sub scores after chemotherapy. Blood iron biomarkers indexing oxygen transport also declined and were related to decreases in the ANT sub scores. Both fNIRS and EEG data responses were shown to have excellent reliability in the healthy subjects, while cancer patients showed significant decreases in oxygenated hemoglobin response in fNIRS, despite no changes in EEG responses after chemotherapy. A significant dose relationship was also found in the changes of fNIRS responses. Our data indicate that chemotherapy produced cognitive deficits and decreases in the oxygenated hemoglobin response and that these may be related to reduced oxygen transport capacity. Results also suggest the utility of using fNIRS-EEG to monitor the progression of cognitive impairment and characterize those mechanisms.

Abstract Background The neuropsychiatric sequelae (cognitive deficits, anxiety and depression) post-COVID-19 exist as part of the spectrum of the multisystemic long COVID. People with these symptoms have been shown to have worse functional outcomes. Hence, this significantly impacts the economy, primarily due to productivity losses. Yet, the precise underlying pathogenesis remains unknown, as do any diagnostic or prognostic biomarkers. Aim This study aims to identify functionally impacted brain regions in those with post-COVID-19 neurological sequelae and to evaluate how alterations in brain function relate to acute serum inflammatory mediators and brain injury biomarkers. Methods The study will utilise data from the COVID-19 Clinical Neuroscience Study (CNS), a large UK multicentre study conducted during the pandemic. This sub-study will be a secondary analysis of the COVID-19 CNS, a prospective observational study that compared COVID-19-positive participants with negative controls. Participants had an MRI, blood tested for acute serum inflammatory mediators and brain injury biomarkers, and neuropsychiatric assessment (cognitron test, PHQ-9 and GAD-7) post-acutely and at follow-up. The DPABI (Data Processing & Analysis for Brain Imaging) toolbox will be used for pre-processing and analysis of the neuroimaging data (resting state functional MRI) to obtain regional homogeneity (ReHo). The association between ReHO and neuropsychiatric symptoms, acute inflammatory mediators and brain injury biomarkers will be explored. Regression models would be used to determine the risk and protective factors for developing these symptoms. Conclusion It is anticipated that the study will provide new insights into the functional basis of post-acute COVID-19 neuropsychiatric manifestations and identify new diagnostic biomarkers. Key words: Regional Homogeneity, COVID-19, functional MRI, neuropsychiatry, biomarkers

Background: Sports betting is one of the most popular, rapidly evolving, and attractive forms of gambling. It is associated with an increased risk of gambling-related harms, including relationship difficulties, crime, and physical and mental health problems. Understanding the subjective experiences of sports betting is essential for accurately defining problematic betting and avoiding the overpathologization of the behavior. Hence, this study explored the perceptions and experiences of young men involved in sports betting in Addis Ababa, Ethiopia. Methods: We employed a qualitative study design using a phenomenological approach. In-depth interviews were conducted with thirteen purposively selected participants in Addis Ababa. Participants were adults aged 18 years or older who had engaged in sports betting within the past 12 months. They were recruited from sports betting houses. All interviews were transcribed verbatim and translated into English. The data were imported into OpenCode software and analyzed using reflexive thematic analysis, in which themes were actively generated through an iterative and interpretative process by the research team. Findings: The data resulted in five major themes: reasons for engagement in sports betting, unique and attractive features of sports betting, experiences of problematic betting, subjective harms of sports betting, and coping and recovery. Young men engaged in sports betting for financial gain, peer influence, and as a way of spending time and coping with boredom. Participants described several features that made sports betting particularly appealing, including ease of access, the ability to bet with small amounts of money, reduced interpersonal confrontation, opportunities to gamble on football, the chance to test sporting knowledge, diverse betting options, and frequent rewards and reinforcement. Experiences suggestive of problematic betting included preoccupation and extensive planning, successive betting and increased risk-taking after losses, unsuccessful attempts to quit, concealment of betting behavior, social and occupational impairment, and negative emotional experiences. Conclusion: Sports betting emerged in participants' accounts as a growing behavioral practice among young men in Addis Ababa, Ethiopia, raising concerns about gambling-related harms. While often initiated as a leisure activity, participants' narratives suggested patterns that extended beyond casual engagement and shared features commonly associated with problematic gambling. Future studies should include women and employ large-scale quantitative designs to examine the population burden and distribution of sports betting-related harms and to inform appropriate prevention and intervention strategies.

Monoamine oxidase B (MAO-B) is a high-density protein located mainly in astrocytes that influences mitochondrial function and transition to astrogliosis. MAO-B produces hydrogen peroxide while metabolizing non-serotonergic monoamines. Elevated MAO-B level is implicated in the pathophysiology of several common neuropsychiatric diseases. The aims are to examine the effect of treatment resistant major depressive episodes, sex, and antidepressant treatment on MAO-B total distribution volume ([11C]SL25.1188 VT), index of MAO-B level. [11C]SL25.1188 PET was applied in 95 adults (29 with MDE and no history of treatment-resistance (NTR-MDE), 26 with MDE and history of treatment-resistance (TRD), and 40 healthy control (HC)). A subset of NTR-MDE and TRD (n=13) were scanned before and after treatment with phenelzine, rasagiline, or duloxetine. [11C]SL25.1188 VT was higher in grey matter regions in females (10%, p<.001). [11C]SL25.1188 VT was also higher in prefrontal cortex in TRD compared to HC (23%, p<.001) and TRD compared to NTR-MDE (6%, p=.033). Duloxetine had minimal effect on [11C]SL25.1188 VT, but occupancy of rasagiline and phenelzine was ~94%. This study discovered sex differences in MAO-B level, which may explain sex differences in prevalence or trajectory of illnesses with greater MAO-B level like Alzheimer's disease, traumatic brain injury and major depressive disorder. Given our findings of greater MAO-B level in prefrontal cortex of TRD and its insensitivity to serotonin reuptake inhibition, combined with potential harm of highly elevated MAO-B level, development of MAO-B inhibitors could be considered for a subset of TRD. Rasagiline and phenelzine demonstrate similarly potent occupancy in vivo at clinical dosage.

A single injection of a subanesthetic dose of ketamine, an NMDA receptor antagonist, induces schizophrenia-like behavior in mice. Previous studies investigated the effect of single injection of ketamine on behavior and c-Fos expression in mice dose-dependently. However, there has not been functional magnetic resonance imaging (fMRI) study to investigate the effect of ketamine in mice. Here, we used awake fMRI and investigated the dose-dependent effect of single injection of ketamine in awaked mice. The lower-dose (5 mg/kg) ketamine increased functional connectivity (FC) with the thalamus and the hypothalamic nuclei. Higher-dose (50 mg/kg) ketamine increased widespread FC with cerebral cortex as well as hippocampus and thalamic nuclei. Graph theory analysis reveals that several regions of hypothalamus and cerebral cortex are essential for the network change by ketamine injection. These results indicate that sub-anesthetic ketamine dose-dependently alters the brain and indues the abnormal behavior in mice.

Cognitive impairment is a prevalent, disabling manifestation of Long COVID, but whether cognitive rehabilitation alters neural network organization is unknown. We examined whether a 12-week cognitive rehabilitation intervention modified resting-state connectivity within the central-executive (CEN), default-mode (DMN), and salience (SN) networks, and whether connectivity changes associated with cognitive performance. Participants were adults with prior SARS-CoV-2 infection, persistent Long COVID symptoms ([&ge;]3 months), and objectively confirmed mild-to-moderate cognitive impairment. Of 58 participants randomized, 39 (mean age 46.4; 69% women) completed neuroimaging (19 intervention, 20 control). The 12-week intervention combined virtual cognitive rehabilitation and small-group and individual sessions with computerized cognitive training. No significant group, time, or group-by-time interaction effects were observed for within- or between-network connectivity (all P > 0.22). Exploratory analyses identified nominal associations (P < 0.05) between connectivity changes and cognition; improved processing speed associated with increased CEN-DMN connectivity, greater SN-DMN connectivity associated with worse performance across processing speed, working memory, and executive function. None survived correction for multiple comparisons. Cognitive rehabilitation was not associated with detectable changes in resting-state network connectivity in long COVID-related cognitive impairment. SN-DMN connectivity may represent a marker of reduced network segregation underlying cognitive dysfunction, warranting study in larger, multimodal trials. Trial registration: NCT05498493.

Background Classical psychedelics induce profound changes in brain function, yet the temporal organization of these effects remains incompletely understood. Methods We investigated the effects of acute lysergic acid diethylamide (LSD) on large-scale brain connectivity in nine male Long-Evans rats using resting-state functional magnetic resonance imaging. Following a 15-min baseline acquisition, rats received LSD (500 g/kg, i.p.), and imaging continued during two consecutive 15-min post-injection periods. Network reorganization was assessed using independent component analysis (ICA), seed-to-voxel mapping, stationary seed-to-seed connectivity, dynamic graph-based metrics, and dynamic causal modeling. Results LSD produced widespread but regionally heterogeneous changes across default mode network related, cortical, striatal, thalamic, sensory, and limbic systems. During the early post-injection window, ICA revealed a predominance of increased functional coupling, while dynamic analyses showed prominent fluctuations in hippocampal coupling strength and medial frontal network centrality. Dynamic causal modeling identified a false discovery rate-corrected reduction in retrosplenial-to-infralimbic influence, accompanied by a broader descriptive pattern of reduced posterior- and hippocampal-to-frontal coupling. During the later window, ICA showed a relative shift toward connectivity decreases, while complementary analyses revealed more selective hippocampal and parahippocampal involvement. Conclusions Across complementary analyses, acute LSD induced a temporally structured reorganization of brain hierarchy, characterized by an early weakening of directed cortical interactions followed by a later shift toward hippocampal-centered network control. These findings identify a dynamic shift in effective network organization and provide a mechanistic framework for psychedelic-induced default mode network reconfiguration.

Dietary iron deficiency in the absence of anemia (IDNA) affects numerous people worldwide, with a wide range of negative effects on brain functioning and cognition. Although studies employing electroencephalography (EEG) have revealed a number of negative effects of IDNA in both the time- and frequency domains, to date there have been no attempts to characterize the effects of IDNA on the temporal dynamics of whole brain interactions. To address this issue, we applied multiscale entropy (MSE) analysis to resting-state EEG data collected from IDNA (n = 21) and iron sufficient (IS, n = 21) women. The MSE analysis on this data revealed that entropy was higher overall for the IS than the IDNA group, with significant differences appearing primarily at longer time scales and under right frontal and left and right parietal electrodes. These results suggest that IDNA may negatively affect long-distance interactions among brain regions and that this could conceivably be a source of diminished cognitive function and neural resilience in IDNA.

Depression and treatment-resistant depression (TRD) are significant public health issues, but the associated network-level neurobiological mechanisms remain poorly understood. This study used magnetoencephalography (MEG) to identify altered resting-state connectivity within the default mode (DMN), executive control (ECN), salience (SN), dorsal attention (DAN), motor (MN), and visual (VN) networks as potential biomarkers of depression and treatment resistance. The study recruited 168 participants (80 healthy volunteers (HVs) and 88 currently experiencing a major depressive episode (74 with TRD and 14 without TRD (noTRD))). Data Integration Analysis for Biomarker Discovery using Latent Variable Approaches for Omics Studies (DIABLO) was used to differentiate the depression, TRD, and HV subgroups and identify neural markers of depression and treatment resistance. For differentiating the depression and HV groups, the triple network model (area under the receiver operating curve (AUROC): 0.759-0.787) - which includes the DMN, ECN, and SN - outperformed the six-network model (AUROC: 0.747-0.762) across different bandwidths. For differentiating the TRD and HV groups, the triple network model demonstrated reasonable prediction across different bandwidths (AUROC: 0.737-0.807); potential within-network connectivity differences distinguished those with TRD from HVs, especially DMN within-network connectivity between the inferior parietal lobule and precuneus in the beta band (FDR-corrected p<.05). Hyperconnectivity within the SN (superior parietal lobule and frontal operculum in the alpha band) and DMN (inferior parietal lobule and lateral prefrontal cortex in the beta band) was associated with number of treatment failures (ps<.05). These findings highlight key brain regions and connectivity patterns, advancing our understanding of neural mechanisms underlying depression and treatment resistance.

Exposure to armed conflict can leave persistent effects on mental health, yet its neurophysiological correlates remain poorly characterized, particularly in populations exposed to prolonged violence outside narrowly defined post traumatic stress disorder samples. Here we examined resting state electroencephalographic activity in 122 Colombian adults, including 74 participants exposed to armed conflict and 48 controls. Eyes closed EEG was analysed for 240 seconds per participant. We quantified absolute and relative spectral power across delta, theta, alpha and beta bands and regional functional connectivity using weighted phase lag index in theta, alpha and beta. Group comparisons were adjusted for age, education, sex and assessment year, with correction across 78 EEG contrasts. Median occipital and global alpha power was lower in exposed participants, although adjusted estimates were close to the null and confidence intervals were broad. Temporal theta relative power was lower in exposed participants at nominal significance, but this association did not survive Holm correction. No spectral power or regional connectivity contrast remained significant after multiple testing correction. Exploratory associations between EEG measures and MoCA performance were modest in participants with confirmed scores. These findings provide a systematic characterization of resting EEG after exposure to armed conflict in a population shaped by prolonged violence and displacement. They also indicate that large or widespread alterations in resting spectral power and connectivity were not detectable with the current sample and analytical framework, while defining candidate signals and methodological priorities for larger studies of conflict related brain health.

Hypoxia impairs cognitive function, yet its effects on navigation and intrinsic brain activity remain poorly understood. This study investigated whether a continuous exposure to hypoxia (CH) or an intermittent exposure to hypoxia (IH) differentially influence navigation performance and resting-state electroencephalography (EEG) in healthy young adults. Seventy-two participants completed sham (FiO2 = .209) and hypoxia (FiO2 = .13) sessions during either a one hour of CH or IH intervention. Navigation was assessed using the Spatial Performance Assessment for Cognitive Evaluation (SPACE), while resting-state EEG was recorded before and after the intervention in a subset of participants (n = 40). EEG spectra were parameterised into periodic (alpha and beta power and central frequency) and aperiodic (exponent and offset) components. Aligned rank transform (ART) analyses of variance examined effects of hypoxia and intervention group, while linear regression determined whether reductions in peripheral oxygen saturation (SpO2) predicted changes in navigation or EEG. Hypoxia impaired multiple components of navigation, increasing path integration distance error and egocentric pointing angle error irrespective of intervention group, while mapping accuracy was preferentially impaired following IH and perspective taking performance following CH. Hypoxia also reduced alpha and beta power, beta central frequency, and aperiodic exponent, while aperiodic offset and alpha central frequency remained stable. The reduction in aperiodic exponent was primarily evident following IH, suggesting that the temporal pattern of oxygen delivery may influence specific neurophysiological responses. Contrary to our hypothesis, SpO2 reduction did not predict individual differences in navigation performance or EEG activity. These findings demonstrate that brief, moderate hypoxic exposure can disrupt allocentric and egocentric components of spatial navigation while selectively altering periodic and aperiodic features of intrinsic brain activity.

Inhibitory control is an essential executive function that encompasses both the stopping of an action in response to an unexpected stop signal (reactive response inhibition) and slowing of responses in anticipation of stopping (proactive response inhibition). Fronto-basal-ganglia circuits are thought to differentially contribute to response inhibition, with the indirect pathway implicated in proactive inhibition. Given the high expression of dopamine D2 receptors in the indirect pathway, pharmacological blockade of D2 receptors is expected to impact proactive inhibition, as indicated by response times on Go trials. The current study aimed to investigate this experimentally and study the effect of 600 mg of sulpiride, a D2 receptor antagonist, on behavioural and electrophysiological measures of proactive and reactive inhibition in humans. Human participants (N=24) completed an anticipated response version of the stop-signal task on either sulpiride or placebo in a double-blind within-subjects design. Sulpiride led to increased variability of Go response times and attenuation of the frontocentral negativity/readiness potential, considered to be a signature of proactive inhibition. In contrast, sulpiride had no effect on stop-signal reaction time or event-related potential components associated with reactive inhibition. These findings suggest that D2 receptor blockade selectively alters processes involved in proactive inhibition while leaving reactive inhibition unaffected, consistent with a key role for the indirect basal ganglia pathway in proactive response inhibition.

Background: Balance control is essential for independence in activities of daily living, and its impairment is a leading contributor to falls in stroke survivors. Stroke-induced brain reorganization alters cortical activation patterns; however, localized changes do not reveal the underlying network dynamics critical for the exchange of task-related information. How stroke affects balance-related cortical network dynamics remains unclear. Methods: We studied cortical functional connectivity during a challenging balance task in fifteen chronic stroke survivors and fifteen age- and gender-matched healthy adults. Whole-head electroencephalography (EEG) was recorded while participants performed a balance sway-referenced task. Balance-related cortical sources were localized to the supplementary motor area/premotor area (SMA-PM), posterior cingulate cortex (PCC), and bilateral lateral prefrontal cortex (LPFC). Directed task-related functional connectivity was estimated across multiple frequency bands. Results: Stroke participants demonstrated elevated gamma-band SMA-PM to PCC connectivity, ipsilesional LPFC to SMA-PM connectivity, and SMA-PM to contralesional LPFC connectivity compared to healthy participants. Stroke participants also showed poorer performance on both the clinical Berg Balance Scale (BBS) and the laboratory-based balance task. Stronger SMA-PM to contralesional LPFC connectivity, but not SMA-PM to PCC connectivity, was associated with better BBS scores in stroke survivors. Conclusions: These findings suggest less reliable SMA-PM to PCC sensorimotor pathways and a compensatory recruitment of SMA-PM to contralesional LPFC pathway for the control of balance post-stroke. Cortical network reorganization after stroke leads to directional connectivity changes adaptive to functional needs, with implications for designing targeted interventions to reduce fall risk in stroke survivors.

Background: Determining the cause of death in electrocution is often challenging at autopsy, particularly when characteristic external electrical marks are absent. Reliable internal markers are scarce, and the neuropathological changes associated with electrocution remain underexplored. Objective: To identify and characterize histopathological alterations in the brain in cases of fatal electrocution and evaluate their diagnostic utility. Methods: A prospective observational study was conducted on 12 autopsy cases, including 7 confirmed electrocution deaths and 5 non-electrocution deaths (control). Brain tissue samples from multiple regions were processed using H&E and Golgi Cox staining. Histopathological parameters, including neuronal morphology, vascular changes, haemorrhage, and dendritic architecture, were evaluated. Results: Electrocution cases demonstrated neuronal destruction, axonal ballooning, focal hemorrhages, and dendritic disruption. Cerebellar involvement with Purkinje cell damage. Conclusion: Comprehensive neurohistological technique may helpful in evaluation neuronal damage in electrocution death. Neuropathological findings, particularly neuronal and dendritic injury, may serve as supportive evidence in determining cause of death when external signs are absent. Keywords: Electrocution, Neuropathology, Golgi Cox stain, Forensic histopathology, death.

Introduction: Functional Neurological Disorder (FND) affects women approximately three times more often than men. This disparity has largely been attributed to higher trauma prevalence and diagnostic bias, while the potential contribution of hormonal influences has received little attention. Methods: An online questionnaire was distributed through FND clinics in thirteen countries, assessing self-reported symptom change across five hormonal events: hormonal contraception, pregnancy, the menstrual cycle, menopause, and gender-affirming hormone therapy. Eligible participants were cisgender women with a diagnosis of FND, or gender minority individuals (transgender or non-binary). Perceived symptom change was rated on a five-point scale ranging from large improvement to large worsening. Results: Among 262 respondents (96% female; mean age 39 years), several hormonal contexts were associated with self-reported symptom changes. Overall, hormonal contraception and pregnancy were frequently associated with worsening of motor and cognitive symptoms, and menopause with worsening across all symptom domains. Menstrual cycle analysis revealed a phase-dependent pattern: worsening was most frequently reported during menstruation and the luteal phase, whereas improvement was most frequent during the follicular phase. Reported changes were not uniform, with a substantial proportion of participants describing no change or improvement. Conclusion: Self-reported FND symptom severity appears to vary with hormonal context, with motor and cognitive symptoms most consistently affected. Given the retrospective, self-report design, these findings are hypothesis-generating and support prospective research into the role of hormonal transitions in FND.

Disorders of consciousness (DoC) are characterised by marked reductions in cerebral glucose metabolism, but the specific cellular and neurochemical processes driving this impairment remain unclear. To elucidate these mechanisms, a multimodal imaging approach combining [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance spectroscopy (MRS) was applied to the posterior medial cortex (PMC) in 15 DoC patients and 14 healthy controls. Regional FDG metabolic index (FDG-MI) values and MRS concentration estimates of glutamate plus glutamine (Glx), {gamma}-aminobutyric acid (GABA+), total N-acetylaspartate (tNAA), total creatine (tCr), and total choline (tCho) were compared between groups and evaluated against Coma Recovery Scale-Revised (CRS-R) scores at baseline and follow-up (mean 127 days). Patients demonstrated reductions within the PMC in Glx, tCr, and tNAA concentrations, as well as a reduced Glx/GABA+ ratio. Local FDG-MI was substantially reduced in patients and correlated positively with tNAA and tCr. Furthermore, baseline tCho concentrations positively predicted long-term clinical recovery, as indexed by changes in CRS-R scores at follow-up. These findings suggest that macroscopic glucose hypometabolism in DoC may be linked to disrupted intracellular mitochondrial energy production pathways and a shift towards relative synaptic inhibition in the PMC. Moreover, the association between choline levels and behavioural recovery may point to the relevance of retained structural synthesis capacity for functional outcomes.

Abstract: Objective: Post-traumatic epilepsy (PTE) is a common sequela of traumatic brain injury (TBI). Research indicates that individuals with PTE tend to experience greater cognitive difficulties compared to those with TBI alone. However, it is plausible that a distinct cognitive profile exists that distinguishes between TBI cases with and without PTE. We aimed to identify longitudinal changes in cognitive measures among TBI patients to better assess the changes associated with developing PTE. Setting: Outpatient. Participants: Prospective subjects who had suffered TBI within 6 months post-injury (TBI-6M, n=32), retrospective subjects with pre-existing PTE diagnoses (PTE, n=20), and healthy control subjects (HC, n=41). Design: We examined cognitive performance for TBI patients within 6 months post-injury, then again within 12 months (TBI-12M, n=26), and within 18-months (TBI-18M, n=25), and compared this with cognitive performance among HC and PTE. Main Measures: Cognitive tests administered yielded 15 test components for analysis. We utilized linear mixed effects modeling to examine cohort-level differences cognitive function. Results: 11/15 tests showed a significant performance deficit in the PTE subjects compared to HC. TBI-6M was not significantly different from the PTE subjects; with time, 9/15 tests showed some degree of recovery in TBI subjects. Tests for information processing speed/working memory and executive function showed strong recovery (TBI-6M vs. TBI-18M, SDMT written: p<0.0001, SDMT oral and COWAT: p<0.001). Tests for visual attention/working memory also showed a smaller but significant recovery (TBI-18M vs. PTE, p<0.05). By contrast, tests for verbal memory [HVLT-R Delayed Recall] showed chronic impairment in TBI (TBI-18M vs HC, p<0.0001). TBI subjects generally trend towards recovery in cognitive performance post-TBI. Conclusions: Information processing speed/working memory are strong indicators for TBI recovery, while auditory learning/memory shows chronic impairment. The stagnation of recovery in cognitive domains typically characterized by robust recovery may correlate with an elevated risk of developing PTE.