Brain and Behavior

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.

Prehabilitation (PRH) is a preoperative process aimed at optimizing patients functional capacity to improve surgical outcomes and overall well-being. While its physical and cognitive benefits are increasingly documented, its emotional impact, particularly in neuro-oncology patients, remains less explored. This study assessed the psychological effects of a PRH program on 29 brain tumor patients. The primary outcome, emotional well-being, was measured using quality of life and emotional distress metrices. Secondary outcomes included perceived stress levels and control attitudes. Additionally, qualitative data from structured interviews provided further insights into the psychological effects of the intervention. The results indicated significant improvements in quality of life and reductions in emotional distress, particularly among women. While perceived stress levels remained stable, control attitudes showed an increase. Qualitative analysis further highlighted the positive changes in the control sense and identified additional factors, such as the importance of social support sources during the PRH process. Overall, these findings suggest that PRH interventions play a significant role in enhancing emotional well-being among neuro-oncological patients in the preoperative phase. These results underscore the importance of implementing comprehensive and personalized PRH approaches to optimize clinical status both before and after surgery, thereby promoting sustained psychological benefits in this population. This study is based on data collected at Institut Guttmann in Barcelona in the context of the Prehabilita project (ClinicalTrials.gov identifier: NCT05844605; registration date: 06/05/2023).

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.

Negative cognitive biases in depression are more pronounced in females than in males. This sex difference emerges during adolescence, a sensitive developmental stage when chronic stress exposure increases the risk of depression in adulthood. The neurobiology linking adolescent stress to sex-specific cognitive bias and resting-state network reorganization in adults remain poorly understood. The study aimed to investigate the longitudinal effects of chronic restraint stress (CRS) during adolescence on cognitive bias and functional connectome in emerging adulthood. 28 Wistar rats (sex-balanced; aged five weeks on arrival) were trained on a judgment bias task with distinct tactile cues signalling differential rewards. Cognitive bias was quantified from responses to ambiguous probe trials. Following training, animals were randomly and equally assigned to CRS or control groups (sex-balanced). Offline resting-state functional MRI scans were conducted at adolescent baseline (pre-CRS) and again in adulthood (post-CRS), followed by probe trials to assess neural and behavioural changes. Following CRS, females showed a greater tendency to shift toward negative bias than males (ratio of odds ratio=3.67). Furthermore, CRS significantly reduced functional connectivity between the left cerebellar-auditory and hypothalamic-thalamic networks only in females. Repeated-measures correlation between cognitive bias and network connectivity were not statistically significant across sex-by-group strata, potentially due to offline imaging and small sample size. However, intra-individual association revealed sex-specific trends, with CRS females showing moderately positive correlations and CRS males exhibiting a weak negative association. The results could inform stratified connectome-based interventions targeting adolescent stress exposures to potentially reduce the risk of adult depression. Six keywords: Resting-State Functional MRI, Chronic Restraint Stress, Judgement Bias, Open Field Test, Sex Differences

Background and Objectives: Normal appearing white matter (NAWM) may already harbor subtle microstructural alterations not yet visible on conventional MRI. Quantitative Multi-Parametric Mapping (qMPM) such as Magnetization Transfer saturation (MTsat), longitudinal relaxation rate (R1), and Proton Density (PD) offer new possibilities for analyzing NAWM which are sensitive to demyelination, axonal loss, and edema. We aimed to characterize these alterations within white matter hyperintensities (WMH) and the perilesional NAWM (pNAWM), to gain insights into the underlying process of lesion progression. We also investigated their association with cerebrovascular risk factors (CVRF) and long-term cognitive performance. Methods: This investigation included the cerebral MRI data of 245 participants from the prospective Berlin Longterm Observation of Vascular Events (BeLOVE) study. Furthermore, 121 participants cognitive performance was evaluated at baseline and longitudinally at 2 years follow-up using Montreal Cognitive Assessment (MoCA). Regions of interest (ROIs) of WMH, pNAWM at 1, 2, 3 mm were assessed in comparison to the mirrored contralesional white matter (cWM). Linear mixed effects models were employed to demonstrate the pairwise comparisons between each region using estimated marginal means and the association of MPM metrics with CVRFs. Linear regression was used to assess the association with cognitive performance. Results: In 245 participants, (mean age 62 years, SD: 12 years; 29.8% females), MPM metrics demonstrated a clear spatial gradient of microstructural injury. MTsat and R1 values were lower in WMH compared to cWM (lower case Greek beta = -0.48 (-0.52 - -0.44) and lower case Greek beta = -0.07 (-0.08 - -0.06), p<0.001, respectively) and showed gradual recovery with increasing distance indicating a microstructural gradient in pNAWM. Conversely, PD values were higher in WMH and decreased peripherally (lower case Greek beta = 2.32 (2.05 - 2.61, p<0.001). No substantial associations were found between MPM parameters and CVRFs in our cohort. At baseline and 2-year follow-up, cognitive performance was associated with higher pNAWM R1 values, whereas MTsat were only moderately associated. Discussion: Quantitative MPM reliably detects microstructural alterations not only within WMH, but also in pNAWM, confirming the high sensitivity of qMPM to subtle tissue pathology and support its utility as a promising biomarker for longitudinal studies and monitoring therapeutic effects.

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.

Stroke is the third leading cause of death and disability combined worldwide and often results in hemiparesis. Functional magnetic resonance imaging (fMRI) is a non-invasive technique used to investigate changes in brain activations during tasks aimed at restoring the lost motor function. Participants with chronic stroke and residual hemiparesis in the upper extremity were recruited for a clinical intervention that included neurofeedback training and fMRI sessions with motor-execution and motor-imagery tasks. The present study provides a baseline characterization of brain activations prior to neurofeedback training. Since lesion site and volume varied across participants, two fMRI preprocessing pipelines were applied. The first one was used for twelve participants with lesions restricted to a single hemisphere and for one participant with small secondary lesions in the contralesional hemisphere, whereas the second one was used for two participants with large bilateral lesions. These were followed by quality control measures and statistical analysis. First-level (i.e., single-participant) analysis returned the strongest and most extensive activation across participants during motor-execution tasks, with clusters identified in the ipsilesional parietal lobe, bilateral occipital lobes, and cerebellum after Family-Wise Error correction. Second-level (i.e., group-level) analysis involving participants who underwent the first fMRI preprocessing pipeline revealed a significant cluster in the cerebellum after False Discovery Rate correction. These results are consistent with previous studies involving participants with chronic stroke performing motor-tasks. Cerebellar recruitment observed consistently across participants could reflect compensatory mechanisms supporting motor control after stroke.

BackgroundAlzheimers disease (AD) patients are characterized by an early decline of episodic memory due to hippocampal damage. Nonetheless, besides the classical negative symptoms related to episodic memory deficits, i.e. failure to retrieve information, it has been shown that AD patients can also suffer from positives symptoms, i.e. confabulations. Some theoretical accounts have been proposed to explain the cognitive mechanisms underlying confabulation. Yet, even if most of these models have lead to some research trying to validate cognitive deficits in some cognitive domains, in particular executive functions, to our knowledge, none has yet tried to determine the specific cognitive profile of confabulatory patients. In the present study the main aim is to characterize the specific cognitive profile of confabulatory patients. Thus, given that AD patients cognitive profile is well known and documented, we compare mild to moderate AD patients with and without confabulations. Methods37 healthy control (HC) and 35 individuals with mild to moderate AD were recruited at the Pitie Salpetriere University Hospital. All participants were evaluated on Dalla Barbas Confabulation Battery to determine their tendency to produce provoked confabulations. Thus, among AD patients, we distinguish between those who produced confabulations in episodic memory questions, and those who did not. Accordingly 27 AD patients were considered free of confabulations (ADC-), and 8 as confabulators (ADC+) (none HC met the criteria). All participants were assessed on a comprehensive neuropsychological battery. ResultsStatistical analyses showed a significant difference between HC participants and the two groups of AD patients, in almost all cognitive domains assessed. However, when comparing the two AD groups, they did not show distinct profiles. Moreover, regarding the type of confabulations, ADC+ produced significantly more confabulations to the Episodic questions (both concerning past and future). ConclusionsBy not demonstrating cognitive differences between patients with and without confabulations, our results cast doubts on some confabulation models, which assume a unique and sufficient cognitive (e.g. executive) deficit underlying the onset of confabulations. HighlightsO_LIAlzheimers disease patients with or without confabulations do not have otherwise distinct cognitive profiles. C_LIO_LIThe emergence of a confabulatory syndrome does not seem to be the result of a necessary and sufficient executive deficit C_LIO_LIAlzheimers disease patients mainly produce episodic memory confabulations, which involve both the past and the future dimension. C_LI

Introduction: Glioblastoma multiforme (GBM) remains the most lethal primary brain tumor with median survival of 14-15 months. Current prognostic markers inadequately stratify patient outcomes. PINK1 (PTEN-induced putative kinase 1), a mitochondrial kinase regulating mitophagy and cellular stress responses, has emerged as a promising prognostic candidate. Our preliminary analysis of 20 GBM cases demonstrated significant PINK1 expression with correlation to aggressive phenotypes (Turizo Smith et al., 2025). This multicenter study aims to prospectively validate PINK1 as a prognostic biomarker for survival and functional outcomes in a Latin American cohort. Methods and analysis: PINK1-GBM Colombia is a multicenter, observational cohort study across four tertiary hospitals in Bogota, Colombia (Hospital de Kennedy, Hospital El Tunal, Hospital Santa Clara and Hospital Universitario de la Samaritana). We will enroll at least 26-50 adults (18+ years) with newly diagnosed IDH-wild type GBM undergoing surgical resection. PINK1 expression will be quantified by immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue using standardized protocols. Primary outcomes: overall survival (OS) and progression-free survival (PFS). Secondary outcomes: functional status trajectories (KPS/ECOG). Follow-up extends 24 months with clinical, imaging (RANO 2.0), and telephone assessments. Survival analyses will employ Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models adjusted for established prognostic factors. Ethics and dissemination: Approved by Universidad Nacional de Colombia Ethics Committee (Acta 001, February 5, 2026; Ref: 2.FM.1.002-CE-002-26), Subred Sur Occidente (P-AP-19-2025, July 11, 2025), and Subred Centro Oriente (CEI 067/2025, October 24, 2025). Conducted per Declaration of Helsinki and Colombian Resolution 8430/1993. Results will be disseminated via peer-reviewed publication, international conferences, and thesis submission.

IntroductionWe present here a methodology for morphometric analysis of the substantia nigra (SN), the ventral tegmental area (VTA), the dorsal raphe nucleus (DRN) and their respective structural brain circuits. MethodsOur analyses were based on multimodal T1-weighted MRI and diffusion MRI (dMRI) segmentation and tractography in 12 human subjects drawn from the Human Connectome Project (HCP) repository. ResultsWe were able to demonstrate strong connections of the SN, VTA and DRN with several brain regions, in particular the dorsolateral prefrontal cortex (DLPFC) and the cerebellum. More specifically, we created comprehensive visualizations of the SN and VTA dopaminergic as well as the DRN serotonergic structural circuits in the human brain, which, although preliminary, demonstrate the potential of multimodal neuroimaging to investigate these circuits quantitatively in clinical conditions. Finally, we created a pilot dataset for the most frequently observed structural connections, specifically those that were present more than 92% of the time among all subjects. Discussion This pilot morphometric report examines the structural circuits of the SN, VTA and DRN, which are critically involved in several biobehaviors and clinical conditions such as addiction, stress, Parkinsons disease (PD), schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder, mood disorders, COVID-19 and long COVID. Importantly, the strong structural connectivity of the DLPFC and cerebellum with the SN, VTA and DRN is expected to be a potential target of noninvasive neuromodulation treatments in neuropsychiatry. Our findings demonstrate the potential of current clinical multimodal neuroimaging to delineate the dopaminergic (DA) and serotonergic (5-HT) circuits in the human brain in clinical conditions.

Neuroendocrine stressors can disrupt the brains redox equilibrium by generating high levels of reactive oxygen species (ROS) that lead to oxidative stress. The magnitude of the effect of neuroendocrine stressors on brain redox equilibrium can be influenced by many internal and external factors. To what extent the relationship between neuroendocrine and oxidative stress is modulated by an individuals stress coping style is only beginning to be understood. To explore this, we subjected proactive and reactive zebrafish to an acute novelty stressor and subsequently quantified changes in behavior and whole brain biomarkers of oxidative stress and antioxidants (DNA damage, total glutathione (GSH), glutathione ratio, oxygen radical absorbance capacity (ORAC), and superoxide dismutase (SOD). Stressed fish had significantly higher total glutathione, trends higher ORAC, DNA damage, and glutathione ratio, and trend for lower SOD levels compared to controls. In addition, individuals with a reactive stress coping style exhibited significantly higher levels of SOD and glutathione ratio, and a trend for ORAC compared to proactive individuals. From a principal component analysis, we also found that the reactive individuals had significantly higher PC1 scores (antioxidant axis) compared to the proactive, and a trend for stressed fish having higher PC1 scores than control. The oxidative stress axis (PC2) showed that the stressed fish had a significantly higher PC2 score relative to control fish. Our results show that neuroendocrine stress-induced disruption of redox equilibrium in the brain differs by stress coping style. Those with a reactive stress coping style have elevated antioxidant capabilities and capacities. Overall, our findings suggest that elevated reactivity to neuroendocrine stressors commonly seen in reactive stress coping styles may be mitigated through the glutathione buffering system and other antioxidants.

The hippocampal CA1 subregion supports learning, memory formation, and spatial navigation. Although its three-layered architecture has been described in ex-vivo investigations, the in-vivo microstructural profile of CA1 and its relation to individual variations in memory performance remain poorly characterized. In this study, we used ultra-high field structural MRI at 7 Tesla to investigate the depth-dependent myelination patterns (measured by quantitative T1) of CA1 in younger adults, their relation to the local arterial architecture, and their association with individual differences in cognitive functions, specifically memory performance. Results show that left and right CA1 present depth-dependent patterns of myelination, with the outer and inner compartments showing higher myelination than the middle compartment. No significant relationship between layer-specific myelination of CA1 and distance to the nearest artery was observed. Right CA1 was found to be more myelinated than left CA1. Pairwise correlations and regression models showed that higher left CA1 myelination is linked to higher accuracy in object localization. Together, our data demonstrates the feasibility of describing the three layered myelin architecture of CA1 in vivo, and provides information on how alterations in the architecture of CA1 may relate to alterations in cognitive performance in younger adults.

Phasic increase of frontal midline theta (Fm theta) has been described as a key indicator of cognitive processing, while relatively lower task-related Fm theta is associated with reduced cognitive strain, reflecting less intensive cognitive processing. In a previous investigation, reduced task-related Fm theta in relation to higher expertise, as well as higher setting anticipation performance in the domain of volleyball was identified. In the present study a single-session sham-controlled neurofeedback training (NFT) intervention was conducted to investigate the feasibility of Fm theta downregulation for the improvement of volleyball setting anticipation. A total of 24 volleyball novices was allocated to "Real" (n = 12) and "Sham" (n = 12) Fm theta downregulation NFT groups. NFT-related Fm theta, pre-/post-NFT setting anticipation task performance and task-related Fm theta, as well as resting EEG activity were analyzed. Incongruous with our expectations, the Real NFT group showed a tendency toward stronger Fm theta synchronization compared with the Sham group during NFT. Anticipation task performance did not change significantly from before to after NFT in both groups, yet a significant reduction of task-related Fm theta was observed in the Real NFT group following NFT. A post-NFT rebound of Fm theta could be responsible for this result. With our findings we provide further evidence for the existence of an apparent paradox of Fm theta downregulation, in which cognitive control mechanisms, associated with oscillatory Fm theta activity, appear to hinder explicit downregulation of Fm theta through classical neurofeedback learning mechanisms.

Traumatic brain injury (TBI), particularly sports- and recreational activity related mild TBI (mTBI), is common in young adults and can be followed by persistent attentional and executive complaints. This study investigated chronic ([&ge;]6 months post-injury) structural brain alterations in gray matter (GM) and white matter (WM) and their associations with self-reported inattentive and hyperactive/impulsive symptoms, with a focus on sex-differentiated patterns. Structural brain properties in gray matter (GM) and white matter (WM) were acquired from 44 subjects with TBI and 45 matched controls, by utilizing structural MRI and diffusion tensor imaging techniques. Behavioral measures assessing severities of post TBI inattentive and hyperactive/impulsive symptoms were collected from each participant. Between-group and sex-specific differences of these brain and behavioral measures were conducted. Interactions among the TBI-induced significant brain- and behavioral-alterations, and their sex-specific patterns, were assessed as well. Male-dominated pattern of increased cortical thickness in superior parietal lobule (SPL) and female-dominated pattern of higher superior longitudinal fasciculus and superior fronto-occipital fasciculus (sFOF) fractional anisotropy (FA) were observed in the TBI group, when compared to controls. In males with TBI, greater SPL cortical thickness was significantly correlated with increased inattentive behaviors. In females with TBI, higher FA of sFOF was significantly correlated with decreased hyperactive/impulsive behaviors. Findings suggest that TBI-induced superior parietal cortical GM abnormalities may significantly cause attention deficits in patients with TBI, especially in males; while optimal post-TBI WM recovery in sFOF significantly contributes to maintenance of inhibitive control in patients with TBI, especially in females.

AimsDue to the multifaceted nature of "impulsivity", its measurement remains fragmented. Here, we developed the Risky Social Choices task to provide evidence for its validity and reliability, while testing the hypothesis that impaired access to implicit knowledge of negative long-term consequences is of distinct importance for "impulsive" decision-making in a general population sample. MethodsForty participants chose whether to engage in risk-taking behaviors, which combined web-based AI-generated videos with narrated hypothetical scenarios and measured worries related to negative long-term consequences, approach-related motivation for short-term rewards, response time to and accuracy of recognizing degraded auditory prime words denoting negative long-term consequences. ResultsA pre-registered multi-step regression model was constructed with worry, motivation, response time and accuracy as predictors and percentage of risky choices as the outcome. Among all predictors, only prime word recognition accuracy was significantly negatively associated with risky choices, confirming our hypothesis of the role of reduced implicit access to negative long-term consequences in risk-taking decisions. In contrast, approach-related motivation for rewards was the only predictor significantly positively related to percentage of risky choices. DiscussionAs predicted, the negative association between risky choices and implicit access to negative long-term consequences supports its role as a distinct aspect of "impulsivity". The novel task successfully captured this aspect, paving the way for a more precise neurocognitive characterization of clinical conditions where "impulsivity" plays a key role. The findings unveil the importance of implicit social sequential knowledge for impulsivity in neurotypical populations, so far only investigated in patients with brain lesions.

There is a predicted increase in older adults presenting with mild to severe cognitive impairment. Screening tools with high sensitivity are the first frontier in identifying a cognitive pathology; however, to ensure that they are measuring the intended concept or criterion, thorough psychometric procedures should be followed. In this study, convergent criterion validity of Riga Cognitive Screening Task was measured, using cortical thickness of regions of interest as the criterion. 106 older adults (Mage = 70.49, SD =8.08, 35.8% male) with varying levels of cognitive functioning were involved in the study. All participants underwent cognitive assessment with the screening task and a 3T MRI. Cortical thickness of selected temporal and parietal regions was used as a brain measure. Behavioural Partial Least Squares Correlation was conducted and one latent variable was extracted. The results confirmed that Riga Cognitive Screening Task shows good criterion validity, suggesting successful use for screening.

An inflammatory subtype of major depressive disorder (MDD) is associated with treatment resistance pointing to an unmet need for adjunctive treatments. To evaluate treatment-related changes in brain inflammation, diffusion basis spectrum imaging (DBSI) is a promising non-radiation-based technique for longitudinal designs which has been verified with histopathology. However, its use as an endpoint in clinical trials is dependent on its individual-level reliability to robustly track changes. Here, we evaluated two DBSI runs acquired in 94 participants (including 43 participants with MDD) on the same day about 1.5 h apart to assess short-term test-retest reliability. Fiber fraction (reflecting axonal/dendrite density) and hindered fraction (reflecting edema) showed moderate to high test-retest reliability in both gray and white matter regions, whereas restricted fraction (reflecting cellularity) showed lower values in gray and white matter. Group-level reliability was similar in participants with MDD, except for lower reliability of hindered fraction in gray matter. Re-identification rates of individual brain maps were higher using voxel-level white matter signatures compared to gray matter regions of interest (ROIs) (p<.001). Crucially, participants with MDD showed reduced fiber fraction (tmax=4.68, k=38) and elevated hindered fraction (tmax=4.74, k=32) in the cingulate bundle, consistent with increased white matter inflammation, while gray matter ROI-based classification failed to identify cases. We conclude that DBSI is a promising technique to track inflammatory signatures in MDD, particularly in white matter tracts. Since several frontal and subcortical gray matter ROIs showed insufficient reliability, their assessment would require multiple DBSI runs to provide robust estimates.

BackgroundExercise therapy reduces depressive and anxiety symptoms, but its neural mechanisms are not fully understood. We examined whether and how running therapy reorganizes dynamic brain functional connectivity in affective disorders. MethodsAt baseline, resting-state fMRI was collected from 66 healthy controls and 50 individuals with affective disorders. Co-activation patterns analyses (CAPs) identified recurring whole-brain network states characterized by spatial patterns of regional co-activation/codeactivation patterns and their temporal occurrence rates. We compared CAPs between groups at baseline. Participants with affective disorders then received 16 weeks of running therapy or antidepressant treatment. We examined: (1) treatment-induced changes in brain CAPs and clinical symptoms, (2) brain-symptom associations at baseline versus post-treatment, and (3) associations between network reorganization and symptom improvement. ResultsAt baseline, individuals with affective disorders showed fewer occurrences of the visual-somatomotor-subcortical network state (VS-SCCAP) than controls (F=5.4, P=0.02, {superscript 2}=0.04). Running therapy significantly altered the temporal dynamics of two brain systems: the default mode (DMCAP: {beta} = -0.88, P = 0.006, d =- 0.88) and VS-SCCAP ({beta} = 0.87, P = 0.006, d = 0.85). These reorganizations were accompanied by significant improvements in depressive and anxiety symptoms (IDS: {beta} = -1.23, P < 0.001, d = -1.15; BAI: {beta} = - 0.98, P = 0.008, d = -0.93). DMCAP-symptom coupling changed significantly from baseline to post-treatment ({Delta}RHO=-0.48, Z{approx}-2.0, P<0.05). ConclusionsRunning therapy altered dynamic brain networks in association with clinical symptom improvement. These findings provide neurobiological evidence for exercise-induced therapeutic effects through transient brain-state reorganization, demonstrating the utility of dynamic connectivity approaches for characterizing neural mechanisms in affective disorders.

ObjectiveTo evaluate central and peripheral correlates of motor control using functional magnetic resonance imaging (fMRI) and surface electromyography (EMG), with a focus on the added value of EMG-informed analysis during movement of the lower limb in healthy controls. MethodsTwenty participants performed dorsi-/plantarflexion of the ankle (Ankle) and gait imagery (GI) in a block design during fMRI. Accelerometry (Acc) and surface EMG from tibialis anterior (TA) activity were recorded and included as regressors in five analysis models, either with or without temporal derivative (TD) to account for time shift in the task regressor. Voxel-wise analyses complemented by post-hoc region-of-interest (ROI) analyses were performed to compare the amount of variability explained by the models. ResultsInclusion of either Acc or EMG on top of the task regressor explained robustly fMRI signal variability in the primary sensorimotor cortices. On top of Acc, EMG additionally explained activation variability mainly in the contralateral thalamus and the secondary somatosensory cortex (S2). This effect was, however, mainly driven by spontaneous signal fluctuations at rest and during imagery. Comparisons between models with and without TD revealed consistent differences in the cerebellum and thalamus across tested models, suggesting that subcortical structures may involve transient signal changes when switching between movement and rest. ConclusionIncluding EMG in fMRI analysis enhances specificity in detecting motor-related brain activity and enables differentiation of spontaneous or unpredicted motor behavior. TD improved signal detection in the primary sensorimotor cortices, but may have a detrimental effect on signal detection in other, mostly subcortical regions, likely reflecting their different temporal signal dynamics.

ImportancePain is inherently aversive but provides emotional relief for individuals engaging in non-suicidal self-injury (NSSI). Despite the high prevalence and severity of NSSI, the neural mechanisms underlying pain processing in individuals with NSSI remain poorly understood. ObjectiveTo compare brain structure and functional connectivity between individuals with NSSI and controls and to relate brain function to pain inhibition. DesignCross-sectional, experimental. SettingMR Center at the Karolinska University Hospital in Stockholm, Sweden. ParticipantsWomen aged 18-35 years with NSSI (n=41) or matched healthy controls (n=40). ExposuresEngagment in self-injury [&ge;] 5 days during the last year. Main outcomes and measuresMagnetic Resonance Imaging (MRI) was used to examine brain structure and function related to pain regulation in individuals with NSSI (n=41) and healthy controls (n=40). The experimental pain test Conditioned Pain Modulation (CPM) was used to determine descending pain inhibition. ResultsWe found higher connectivity between the brains somatomotor networks and subcortical areas during resting-state functional MRI in NSSI compared to controls (P=.009; Bonferroni corrected), particularly involving the thalamus and caudate nucleus. The connectivity was linked to the level of descending pain inhibition during CPM. There was no difference between NSSI and controls regarding brain morphometry. Conclusions and relevanceOur findings suggest that individuals with NSSI may rely more on sensory-motor activations to regulate emotions. This study provides the first evidence linking specific brain circuits to pain regulation and self-injury behavior, highlighting potential pathways for more effective treatments for NSSI and related mental health conditions.