Brain Sciences

International concern regarding the association between repetitive neurotrauma in sport and long term concerns with ageing continues. While previous studies have reported older (i.e. over 50 years) our study describes corticomotor changes across the lifespan between retired contact sport athletes, between the ages of 30 and 70 years. Retired athletes, minimum five years retired, (n=152; 48.6{+/-}9.0 years) and age-matched controls (n=72; 47.8{+/-}9.5 years) were assessed using single and paired-pulse transcranial magnetic stimulation (TMS) for active motor threshold (aMT), motor evoked potential and cortical silent period duration (expressed as MEP:cSP ratio), and short- and long-interval intracortical inhibition (SICI and LICI). Age-matched controls showed significant moderate correlations for MEP:cSP ratios at 130% (rho=0.48), 150% (rho=0.49)and 170% aMT (rho=0.42; all p<0.001) and significant but small negative correlation for SICI (rho=-0.27; p=0.030), and moderate negative correlation for LICI (rho=-0.43; p<0.001). Further, group-wise correlation analysis shows significant stronger corelations (all p<0.05) in the control for each variable than in the retired players. This study is the first to characterise corticomotor differences between retired athletes and age matched controls across the lifespan. in those with a history of repetitive head trauma and provides a foundation for further work to utilise TMS as a prodromal marker useful in supplementing neuropsychological assessment for traumatic encephalopathy syndrome which currently lacks physiological biomarkers.

The neuromodulatory effects of repetitive transcranial magnetic stimulation (rTMS) are often described as inhibiting for low frequency and facilitating for high frequency protocols, leading to the lofi-hife heuristic. However, the data basis for this is inconsistent and reliability of rTMS is barely evaluated. The present study examines the validity of this lofi-hife heuristic at group and single subject level and the reliability of rTMS in a non-navigated setting close to clinical application. In 30 healthy participants, 1 Hz and 20 Hz rTMS were each administered twice over the left motor cortex resulting in four sessions/participant. Motor evoked potentials (MEPs) were measured before and after each session. Reliability measures were intraclass and Pearsons correlation coefficient (ICC and r). The heuristic was not evident at group level. At single-subject level four participants responded with heuristic-conform changes, i.e., concomitant decreases for 1 Hz and increases for 20 Hz sessions. ICCs and r were low to moderate. Within subgroups of less confounded measures, we found good r values for 20 Hz rTMS. Results demonstrate high inter- and intraindividual variability of rTMS questioning the lofi-hife heuristic. Methodological improvements for the usage of rTMS might help to increase validity and reliability of non-invasive brain stimulation.

Changes in the corticospinal (CSE) and cortico-cortical (CCE) excitability of the primary motor cortex (M1) may underlie the effect of mental fatigue on physical performance. To date, research on this subject has predominantly focused on the examination of CSE, with limited exploration of effects of mental fatigue on CCE. This study aims to investigate the influence of mental fatigue induced through prolonged cognitive activity on both CSE and CCE. Fifteen healthy adults (aged 29.13{+/-}7.15 years) participated in assessments of CSE (Motor evoked potential - MEP amplitude) and CCE (Intracortical facilitation - ICF, short-interval intracortical inhibition - SICI, and long-interval intracortical inhibition - LICI) before and after a 60-minute Stroop task (experimental condition) or watching a documentary (control condition). Subjective mental fatigue was measured using the mental fatigue visual analogue scale (M-VAS), and workload associated with the tasks was assessed using the National Aeronautics and Space Administration (NASA) task load index. Objective mental fatigue was defined by the time-related decline in Stroop task performance. The study results revealed no significant differences in M-VAS, CSE and CCE between the two conditions. Stroop task performance did not exhibit significant changes over time. However, participants perceived the Stroop task to be more mentally demanding and effortful than watching the documentary (p<0.05). Further analysis of Stroop task performance at individual participants level identified two sub-groups of participants: one exhibiting deteriorating performance with time (fatigued subgroup) and the other showing improved performance (non-fatigued subgroup). Descriptively, cortical inhibition increased (reduced SICI and ICF values) from pre to post Stroop task in the fatigued subgroup, while the non-fatigued group displayed an opposite pattern. The findings suggest that mental fatigue may lead to increased cortical inhibition, highlighting the need for further investigation with a larger sample size.

The present study aimed to characterize microstate dynamics induced by non-reactive attention underlying mindfulness. Electroencephalogram signals from eighteen trained meditators and a matched non-meditators group were recorded before, during, and after a non-reactive attention meditation or during three resting periods respectively, while they were passively exposed to auditory stimulation. In a multimodal approach, microstate cluster decompositions, personality trait questionnaires, phenomenological ratings, and microstates sources localization were analyzed. Our results revealed that temporal parameters of microstates A and C at rest were negatively correlated to mindfulness traits across all participants. After meditation, the frequency of microstate A and C was decreased while microstate B was of longer duration, in meditators. Source localization analysis revealed that the non-reactive trait effect on microstate C at rest was explained by a modified activity of the salience network (identified by the anterior cingulate cortex, thalamus, and insula), while the non-reactive attentional state effect relied on a contribution of (anterior and posterior) cerebellum during meditation. Our results suggest that decreased microstates A and C reflect decreased mental state reactivity, while the increased microstate B relies on attention stability. These findings strongly encourage more research to assess the use of the microstate temporal parameters as a biomarker of the salience network activity, as well as objectify the brain changes induced by non-reactive attention training. HIGHLIGHTO_LIThe present study aimed to characterize microstate dynamics induced by non-reactive attention meditation, by the use of multimodal analysis including EEG microstate clusters decompositions, personality trait questionnaires, phenomenological reports, and source localization analysis. C_LIO_LIThe occurrence of microstate A, recognized to be related to phonological processing and depressive disorders, was negatively correlated to mindfulness trait and was decreased after non-reactive attention meditation. C_LIO_LIThe duration of microstate B, generally associated with the visual system, increases after meditation, in particular in meditators with a high non-reactivity trait. C_LIO_LITemporal parameters of microstate C, recognized to be related to default mode, were negatively correlated to the non-reactivity trait of meditators and were decreased after non-reactive attention meditation. Source analysis revealed that these trait and state effects reflect modified activities of the salient network. C_LI

PurposePersistent motor dysfunction after burn injury may be due to altered motor cortex and corticospinal tract function. This study examined manual dexterity, motor cortex neuroplasticity, and intracortical inhibition in former burn patients 1-3 years post-minor injury (<10% TBSA). MethodsThirty former burn patients (TBSA: 0.78 {+/-} 1.08%) and 30 non-injured controls participated. Manual dexterity was assessed using the Purdue Pegboard. Transcranial magnetic stimulation (TMS) was used to measure motor cortex excitability (motor evoked potential (MEP) amplitude) and short- and long-interval intracortical inhibition (SICI, LICI) before and after paired-associative stimulation (PAS) to induce neuroplasticity. ResultsFormer burn patients performed worse than controls on the bilateral assembly subtest of the Purdue Pegboard. PAS did not induce changes in MEP amplitude but increased LICI in both former burn patients and control participants. In former burn patients, greater baseline SICI and LICI were associated with better bilateral performance. ConclusionsThese findings suggest that poorer motor function persists following minor burn injury and is associated with reduced excitability of motor cortex inhibitory circuits. Further research should explore whether targeting motor cortex inhibitory circuits can improve motor performance following burn injury. HighlightsO_LIFormer burn patients 1-3 years post-minor injury had poorer manual dexterity than controls. C_LIO_LIPaired associative stimulation increased long-interval intracortical inhibition. C_LIO_LIGreater motor cortex inhibition at rest linked to better manual dexterity in former burn patients. C_LI

Video gaming often sparks controversy, though negative effects are mainly linked to gaming disorder, not gaming itself. Research shows that gaming disorder is associated with reduced executive functioning and greater reliance on habitual processes, while recreational gaming may relate to enhanced cognitive functions. However, comprehensive comparisons of cognitive profiles across gaming behaviors remain scarce. Therefore, we aimed to compare the cognitive functioning of non-gamers (NG), recreational gamers (RG), and gaming disorder risk individuals (GDR). Based on the Internet Gaming Disorder Test scores, 114 participants were classified into NG, RG, or GDR groups. Executive functions were assessed using the Go/No-Go, Counting Span, Digit Span, Card Sorting, 1-back and 2-back tasks. Habit learning was measured with the Alternating Serial Reaction Time task. The GDR group showed reduced working memory, performing worse on the Digit Span task than the NG group, and worse on the Counting Span task than both NG and RG groups. Conversely, the RG group displayed enhanced attention-related performance. No group differences emerged in other executive functions or overall habit learning. Interaction analyses revealed a negative relationship between habit learning and inhibitory control/updating across groups, supporting competition theory, while a positive link between working memory and habit learning in NG and GDR groups suggests possible compensatory mechanisms. Overall, this study underscores that cognitive impairments are linked to gaming disorder rather than gaming itself, while recreational gaming may offer cognitive benefits. These findings provide insights into the distinct cognitive profiles of recreational gamers and those at risk of gaming disorder. HighlightsO_LICognitive profiles differ for gaming disorder vs. recreational gaming. C_LIO_LIWorking memory is impaired in individuals at risk of gaming disorder. C_LIO_LIRecreational gaming is linked to enhanced attention-related performance. C_LIO_LIExecutive functions and habits compete with each other, regardless of gaming. C_LIO_LICognitive systems show both competitive and compensatory links. C_LI

Dance is an art form and simultaneously a form of exercise that provides pleasure to individuals who practise it regularly with subsequent improvements to motor and non-motor symptoms in people with Parkinsons disease (PD). Recent evidence suggests that dance promotes neuroplasticity and correlates with improvements of depression scores in individuals with PD. However, no neuroplasticity studies using fMRI and EEG have been conducted on people with Parkinsons disease (PwPD) who attend community dance programs. Thus, we present an observational examination across 7-years that explores the effects of non-motor symptoms of anxiety and depression. The study utilized multimodal recordings from functional MRI (fMRI), electroencephalogram (EEG) and measured affective state using the expanded version of the Positive and Negative Affect Schedule (PANAS-X) questionnaire. fMRI was performed at four time points in the first year (September, December, January, and May) where participants visualized/imagined the choreography they had learned in the dance studio while listening to the recording of the music in the MRI. Resting state EEG was recorded immediately before and after the dance class when the dancers volunteered over the 7 years. In addition, mood was monitored using the PANAS-X in conjunction with the EEG sessions. The PANAS-X was sorted by generalized anxiety disorder (positive and negative affect) symptoms, and major depressive disorder (positive and negative affect) symptoms, along with standard general negative affect (GNA) and general positive affect (GPA). This analysis reveals significant improvements in both symptoms after dance and across time. fMRI results show significant BOLD signal changes in the nucleus accumbens and anterior cingulate cortex, along with trends in other regions in the reward pathway such as the ventral tegmental area and the orbitofrontal cortex. rsEEG results show significant increases in alpha peak values after dance, in both EO and EC conditions. The findings support the idea that dance is a multimodal form of neurorehabilitation with beneficial effects on both motor and non-motor symptoms, including anxiety and depression.

BackgroundThe present study examined neurocognitive differences between Perinatally HIV (PHIV)-infected-youth and age and gender matched healthy controls. Despite early, long-term anti-viral treatment (ART), significant neurocognitive deficiencies remain for PHIV-infected-youth reaching adulthood compared to controls. MethodsParticipants were assessed with a comprehensive neuropsychological battery. An Overall Neurocognitive Composite Score and a Global Deficit Score (GDS) were created. Sleep, depression, and developmental level of intellectual functioning were also examined. ResultsPHIV-youth performed more poorly than controls in all neurocognitive domains. Very large effect sizes were observed for the Overall Neurocognitive Composite Score and GDS. PHIV-infected-youth appear to be significantly more depressed compared to controls, but there were no differences in amount or type of sleep observed. ConclusionDespite early, long-term anti-viral treatment (ART), neurocognitive deficiencies remain for PHIV-infected-young-adults. The verbal learning domain was significantly impaired with implications for functioning. The PHIV-infected-youth were also depressed and not receiving treatment for depression.

Smoking is a severe addictive health risk behavior and notorious for the high likelihood of relapse after attempted cessation. Such an addictive pattern in smoking has been associated with neurobiological changes in the brain. However, little is known whether the neural changes associated with chronic smoking persist after a long period of successful abstinence. To address this question, we examined resting state EEG (rsEEG) in heavy smokers who have been smoking for 20 years or more, past-smokers who have been successfully abstaining for 20 years or more, and non-smokers. Compared with chronic current- or past-smokers, non-smokers showed higher relative power in theta frequency band, showcasing long-lasting effects of smoking on the brain. A few rsEEG features in alpha frequency band also revealed reversible impacts of smoking, such that only current-smokers, but not past-smokers, showed distinctively higher patterns than non-smokers in their relative power, EEG reactivity--power changes between eyes-closed and eyes-open conditions--, and coherence between channels. Furthermore, rsEEG feature differences between current- and past-smokers were accounted for by individuals self-reported smoking history and nicotine dependence. These data suggest long-lasting impacts of chronic smoking on the brain that are dissociable from the neural changes reversible with long-term abstinence.

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.

Transcranial direct current stimulation (tDCS) might modulate neural activity and promote neural plasticity. This factorial randomized clinical trial compared a-tDCS on the left dorsolateral prefrontal cortex (l-DLPFC) or sham (s-tDCS), and a-tDCS or s-tDCS on the primary motor cortex (M1) in the connectivity analyses in eight regions of interest (ROIs) across eight resting-state electroencephalography (EEG) frequencies. We included 48 women with fibromyalgia, aged 30 to 65, randomly assigned to 2:1:2:1 to receive 20 sessions during 20 minutes of a-tDCS 2mA or s-tDCS at home, over l-DLPFC or M1, respectively. EEG recordings were obtained before and after treatment with eyes open (EO) and eyes closed (EC). In the EC condition, comparing pre to post-treatment, the a-tDCS on l-DLPFC decreased the lagged coherence connectivity in the delta frequency band between the right insula and left anterior cingulate cortex (ACC) (t=-3.542, p=.048). The l-DLPFC a-tDCS compared to s-tDCS decreased the lagged coherence connectivity in the delta frequency band between the right insula and left ACC (t=-4.000, p=.017). In the EO condition, the l-DLPFC a-tDCS compared to M1 s-tDCS increased the lagged coherence connectivity between the l-DLPFC and left ACC in the theta band (t=-4.059, p=.048). Regression analysis demonstrated that the a-tDCS effect on the l-DLPFC was positively correlated with sleep quality, while a-tDCS on l-DLPFC and M1 s-tDCS were positively correlated with pain catastrophizing. The application of a-tDCS over the l-DLPFC has modulated the connectivity between various brain regions involved in the affective-attentional aspects of pain, especially at lower EEG frequencies during the resting state. These findings suggest that the effects of a-tDCS on neural oscillations could serve as a neural marker associated with its impact on fibromyalgia symptoms.

Embodied interoception refers to the perception of the bodys state and is a multidimensional cognitive process. It is proposed that the experience of pain also feeds interoceptive networks with information from the state of the body, and the subjective experience of pain would be influenced by an individuals trait embodied interoceptive profile. Here we developed and validated the Intero-10, a questionnaire designed to specifically evaluate embodied interoception based on trait interoceptive channels. Healthy adults (n=381) and people with neuropathic pain (n=86) were enrolled. The relationship between trait and state interoceptive responses was examined during experimentally evoked interoceptive psychophysics tasks, which were specific for each interoceptive channel. During these tests, embodied interoceptive state scores only correlated with trait ones for unpleasantness (P<0.05), but not for intensity rating, suggesting that the predicted negative valence of lived experience provided lower prediction errors than intensity estimations. The Intero-10 final version included embodied interoceptive perception intensity (heartbeat, heat, itching, dyspnea, sleep, muscle fatigue, and anguish) and unpleasantness (heartbeat, dyspnea, and nausea) categories. Intero-10 demonstrated adequate content validity, good internal consistency (Cronbachs alpha=0.81), good reliability (>0.75), and a single-factor structure. Patients with neuropathic pain filled in the Intero-10 alongside traditional pain, mood, sleep, and quality of life assessments. Embodied interoception scores correlated with mood, and quality of life, and partially mediated the correlation between pain interference and quality of life ({beta}=-0.0093). The specific assessment of embodied interoceptive channels may broaden our current assessment of people with chronic pain and of those at risk to develop it.

BackgroundMajor depressive disorder (MDD) with suicidality represents a significant public health concern, as suicide ranks among the leading causes of death worldwide. While electroencephalography (EEG) has shown promise in depression diagnosis, its utility in identifying suicidal risk remains underexplored. This study aims to develop and validate a Suicidal Risk Index (SR Index) using EEG biomarkers and machine learning (ML) algorithms for distinguishing between MDD patients with and without suicidality. MethodsIn this retrospective observational study, resting-state EEG data were collected using Stress EEG Assessment (SEA) system. SR Index was developed by integrating the PHQ-9 scale with EEG-derived features, including band power, coherence, and fractal dimension, optimized using ML algorithms to enhance accuracy. ResultsThe study included 268 participants (159 without suicidality, 109 with suicidality). The SR Index demonstrated robust discriminative ability with an AUC of 0.8117 (p=2.63x10-18). At the optimal cutoff value of 8, the model achieved 88.99% sensitivity, 57.23% specificity, 67.86% positive predictive value, and 78.85% negative predictive value, with a balanced accuracy of 73.11%. ConclusionsThe SR Index shows promise as an objective tool for identifying suicidality in MDD patients, potentially complementing traditional clinical assessments. This approach may enhance early detection and risk stratification in clinical settings, potentially improving suicide prevention strategies. HighlightsO_LINovel EEG- and ML-based Suicidal Risk Index distinguishes MDD patients with and without suicidality. C_LIO_LISR Index achieves 88.99% sensitivity and 73.11% balanced accuracy in identifying suicidal risk. C_LI

Cognitive function can decline irreversibly with age, potentially progressing to dementia. Intervention during the preclinical stage is considered effective, but evaluation often requires large-scale equipment and tests. A decline in inhibitory function precedes and is involved in a general decline in higher-order brain functions, making its assessment a key target for early detection. We focused on error-related negativity (ERN) to capture the neural network of inhibitory function. While larger ERN amplitudes indicate higher error detection ability and correlate with inhibitory function, the causal relationship, mutual influences, and age-related effects in older adults remain unclear. This study measured brain activity during an inhibitory task in young and older adults to examine the neural networks related to error detection and inhibitory function. We used LORETA iCoh Full Vector Field analysis to verify directional connectivity. In the elderly group, during error responses, we observed significantly stronger beta-band directionality from the ventral anterior cingulate cortex (ACC) to the left frontal pole. Between the ventral and dorsal ACC, we also found significantly stronger directionality in the theta, alpha, and beta bands. During correct responses, they showed significantly stronger alpha and beta-band directionality from the left dorsolateral prefrontal cortex (DLPFC) to the right frontal pole. Compared to the elderly, the young group exhibited significantly stronger mutual directionality between the ventral and dorsal prefrontal cortices in the alpha and beta bands. They also showed widespread, significantly strong directionality among the ACC, bilateral DLPFC, and frontal poles. These results suggest that error detection ability is important for the normal functioning of inhibitory control in older adults. Furthermore, an age-related decline in metacognitive abilities may be associated with impaired inhibitory function. The insights from this study can contribute to developing risk prediction models for cognitive decline and establishing effective preventive strategies.

BackgroundHealthy older adults show a decrease in motor learning capacity as well as in working memory (WM) performance. WM has been suggested to be involved in motor learning processes, such as sequence learning. Correlational evidence has shown the involvement of the fronto-parietal network (FPN), a network underlying WM processes, in motor sequence learning. However, causal evidence is currently lacking. Non-invasive brain stimulation (NIBS) studies have focused so far predominantly on motor related areas to enhance motor sequence learning while areas associated with more cognitive aspects of motor learning have not yet been addressed. HypothesisIn this study, we aim to provide causal evidence for the involvement of WM processes and the underlying FPN in successful motor sequence learning by using a theta transcranial alternating current stimulation (tACS) paradigm targeting the FPN during motor sequence learning. MethodsIn a cohort of 20 healthy older adults, we applied bifocal tACS in the theta range to the FPN during a sequence learning task. With the use of a double-blind, cross-over design, we tested the efficacy of active compared with sham stimulation. Two versions of the motor task were used: one with high and one with low WM load, to explore the efficacy of stimulation on tasks differing in WM demand. Additionally, the effects of stimulation on WM performance were addressed using an N-back task. The tACS frequency was personalized by means of EEG measuring the individual theta peak frequency during the N-back task. ResultsThe application of personalized theta tACS to the FPN improved performance on the motor sequence learning task with high WM load (p <.001), but not with low WM load. Active stimulation significantly improved both speed (p <.001), and accuracy (p =.03) during the task with high WM load. In addition, the stimulation paradigm improved performance on the N-back task for the 2-back task (p = .013), but not for 1-back and 3-back. ConclusionMotor sequence learning can be enhanced with the use of personalized bifocal theta tACS to the FPN when WM load is high. This indicates that the efficacy of this stimulation paradigm is dependent on the cognitive demand during the learning task and provides further causal evidence for the critical involvement of WM processes and the FPN in motor sequence learning in healthy older adults. These findings open new exciting possibilities to counteract the age-related decline in motor learning capacity and WM performance.

Substance use disorder (SUD) recovery typically requires transformative change and prioritizing long-term healthy goals. Unfortunately, successful recovery is threatened by relapse rates that often exceed 50% in the first year. We previously reported on an experiential virtual reality (VR) SUD recovery intervention using personalized future self-avatars that produced emotional engagement and positive behavioral change, ie, stronger connection with the future self and future rewards and reduced craving. Here, we used fMRI to identify brain engagement to a future self experience with divergent futures. Twenty adults (14 male, 33 years old) in early SUD recovery (<1 year) interacted with age-progressed versions of themselves in two different VR future realities: an SUD Future Self and a Recovery Future Self. Vivid lifelike visual and audio animation was augmented with a personalized narrative concerning future drug use and recovery. MRI immediately followed. Participants viewed videos of their future selves in the virtual environment and were directed to contemplate what they were seeing. Viewing and contemplating the future selves elicited activation in midline default mode regions (posterior cingulate and ventromedial prefrontal cortices), visual regions including the occipital and fusiform face areas, and left middle frontal gyrus. The Recovery Future Self produced significant left occipital face area activation compared with the SUD Future Self. Midline default mode activation correlated with VR-induced increases in delayed reward preference, and also with greater trait perseverance. Using digital selves as therapeutic agents reveals an entirely novel set of possible interventions and opens exciting new frontiers in behavior change methodology. Future studies targeting decision-making and future behavior could be informed by evaluating increased midline default mode engagement, with uniquely self-focused mechanisms signaled by executive network and face area coactivation. New hope for treatment-resistant mental health conditions is offered by the nearly limitless range of therapeutic experiences enabled by immersive digital therapeutics. Plain Language SummaryHigh relapse rates in early recovery remains a serious challenge. To promote better outcomes, our team recently developed a virtual reality experience where people interacted with future versions of themselves. We used magnetic resonance imaging (MRI) to understand how the brain activated to this experience, and what brain responses were linked to positive outcomes. We worked with 20 adults in early recovery. Each person used virtual reality to interact with two different future selves: one who had returned to substance use, and one who had stayed in recovery. These digital future selves looked and sounded like the participants and were paired with a personalized story about future drug use and recovery. Right after the virtual reality session, participants brains were scanned while they watched videos of these future selves and were asked to think about what they were seeing. When people viewed and reflected on their future selves, brain areas involved in self-reflection and imagining the future became more active, along with regions that process faces. The future selves triggered brain activation in "self-focused" brain networks and in face-processing regions. Activity in key "self-focused" brain regions was linked to choosing larger, delayed rewards over smaller, immediate ones, and to lower impulsivity. These findings suggest that lifelike digital versions of peoples future selves engage brain systems that support thinking ahead, persistence, and valuing long-term outcomes. This creates a promising new avenue for immersive digital therapeutic experiences to encourage lasting behavior change in early recovery from substance use disorder.

For stroke participants undergoing motor rehabilitation, brain-machine/computer interfaces (BMI/BCI) can potentially improve the efficacy of robotic or exoskeleton-based therapies by ensuring patient engagement and active participation, through monitoring of motor intent. In such interventions, exploring the network-level understanding of the source space, in terms of various cognitive dimensions such as executive control versus reward processing is fruitful in both improving the existing therapy protocols as well as understanding the subject-level differences. This contrasts to traditional approaches that predominantly investigate rehabilitation from resting state data. Moreover, conventional BMIs used for stroke rehabilitation barely accommodate people suffering from moderate to severe cognitive impairments. In this first-of-the-kind study, we explore the cognitive dimensions of a BMI trial by probing the networks that are core to the BMI performance and propose a network connectivity-based measurement with the potential to characterize the cognitive impairments in patients for closed-loop intervention. Specifically, we tease apart the extent of cognitive evaluation versus executive control aspects of impairments in these patients, by measuring the activation power of a major cognitive evaluation network-the Cingulo-Opercular Network (CON) and a major executive control circuit-the Fronto-Parietal network (FPN), and the connectivity between FPN-CON. We test our hypothesis in a previously collected dataset of electroencephalography (EEG) and structural imaging performed on stroke patients with upper limb impairments, while they underwent an exoskeleton-based BMI intervention for about 12 sessions over 4 weeks. Our logistic regression modeling results suggest that the connectivity between FPN and CON networks and their source powers predict trial failure accurately to about 84.2%. In the future, we aim to integrate these observations into a closed-loop design to adaptively control the cognitive difficulty and passively increase the subjects motivation and attention factor for effective BMI learning.

Compared to full-term (FT) born peers, children who were born very preterm (VPT; <32 weeks gestation) are likely to display more cognitive and behavioural difficulties, including inattention, anxiety and socio-communication problems. In the published literature, such difficulties tend to be studied independently, thus failing to account for how different aspects of child development interact. The current study aimed to investigate childrens cognitive and behavioural outcomes as interconnected, dynamically related facets of development that influence one another. Participants were 93 VPT and 55 FT children (median age 8.79 years). IQ was evaluated with the Wechsler Intelligence Scale for Children - 4th edition (WISC-IV), autism spectrum condition (ASC) traits with the Social Responsiveness Scale - 2nd edition (SRS-2), behavioural and emotional problems with the Strengths and Difficulties Questionnaire (SDQ), temperament with the Temperament in Middle Childhood Questionnaire (TMCQ) and executive function with the Behaviour Rating Inventory of Executive Functioning (BRIEF-2). Outcome measures were studied in VPT and FT children using Network Analysis, a method that graphically represents partial correlations between variables and yields information on each variables propensity to form a bridge between other variables. Results showed that VPT and FT children exhibited marked topological differences. Bridges (i.e., the variables most connected to others) in the VPT group network were: SDQ Conduct Problems scale and BRIEF-2 Organisation of Materials scale. In the FT group network, the most important bridges were: the BRIEF-2 Initiate, SDQ Emotional Problems and SDQ Prosocial Behaviours scales. These findings highlight the importance of targeting different aspects of development to support VPT and FT children in person-based interventions.

Measurement of the adverse outcomes of repeated head trauma in contact sport athletes is often achieved using tests where the comparator is the score or the accuracy obtained. While it is expected that ex-athletes would perform worse than controls, previous studies have shown inconsistent results. Here we have attempted to address these inconsistencies from a different perspective by quantifying not only accuracy, but also the time of motor responses (response time). We tested age-matched control subjects who have never experienced head trauma (n=20; 41.8 {+/-} 14.4 years), and two cohorts of retired contact sport athletes with a history of head trauma and concussions; one with self-reported concerns (n=36; 45.4 {+/-} 12.6 years), and another with no ongoing concerns (n=19; 43.1 {+/-} 13.5 years). Participants performed cognitive (Cogstate) and somatosensory (Cortical Metrics) testing and both accuracy and response time were recorded. Transcranial magnetic stimulation (TMS) was undertaken to investigate corticospinal conduction and excitability. Results showed that in both test batteries there was little difference between groups when considering only accuracy scores. By contrast, response times in all but one test revealed that ex-athletes with self-reported concerns were significantly slower compared to no concern ex-athlete or control groups (p ranges 0.031 to <0.001). TMS latency showed significantly increased conduction time (p=0.008) in the group with ongoing concerns. These findings suggest that incorporating response times in cognitive and somatosensory testing is more informative than considering accuracy scores alone when assessing cognitive processing ability in retired contact sport athletes with ongoing brain health concerns.

BackgroundIn the era following combined antiretroviral therapy (cART), asymptomatic neurocognitive impairment (ANI) has become the primary stage of HIV-associated neurocognitive disorder (HAND). As a potentially reversible phase, precise identification of ANI is crucial. Multimodal MRI, with its non-invasiveness and high sensitivity, can reveal potential changes in brain network function and structure, providing significant support for exploring biomarkers of HAND and optimizing intervention strategies.This study aims to explore the dynamic changes in the functional network, structural network, and functional-structural coupling in ANI patients using multimodal MRI combined with large-scale brain network analysis. MethodsA total of 95 participants were included, consisting of a healthy control group (HC, n=48) and an ANI patient group (n=47). Functional and structural connectivity matrices were constructed using resting-state fMRI (rs-fMRI) and diffusion tensor imaging (DTI), and graph theory analysis was used to evaluate global metrics, node characteristics, and functional-structural coupling changes. ResultsStructural Network: No significant changes were observed in the global or local topological properties of the structural network in ANI patients. Functional Network: Significant reorganization was observed in several key regions, including the visual network, executive control network, and default mode network. Functional-Structural Coupling: The functional-structural coupling in the occipital and frontal networks was significantly enhanced. Clinical Relevance: Changes in the functional network and functional-structural coupling were associated with the patients immune status, duration of infection, and cognitive performance. ConclusionThe reorganization of the functional network and enhancement of functional-structural coupling during the ANI phase may reflect early manifestations of microscopic pathological changes (such as synaptic and dendritic damage). These changes hold promise as early warning signals in the progression of HAND and provide sensitive biomarkers and important research perspectives for precise diagnosis and early intervention.