Back

Brain Sciences

○ MDPI AG

Preprints posted in the last 30 days, ranked by how well they match Brain Sciences's content profile, based on 55 papers previously published here. The average preprint has a 0.06% match score for this journal, so anything above that is already an above-average fit.

1
Technology-enhanced learning in undergraduate neuroscience education: tractography-based virtual dissection in psychology

Lopez-Barroso, D.; Torres-Prioris, M. J.

2026-09-23 scientific communication and education 10.64898/2026.09.21.753122 medRxiv
Top 0.1%
10.3%
Show abstract

Background: Neuroanatomy poses a significant challenge for Psychology students due to its spatial and conceptual complexity. Educational approaches that enhance the relevance and visualization of neuroanatomical content may improve students learning experiences. This study implemented a tractography-based activity focused on the virtual dissection of the arcuate fasciculus, a major white matter pathway, in undergraduate Psychology students and examined the relationships between perceived learning and students perceptions of utility, difficulty and handling, and organizational aspects of the activity. Methods: First-year undergraduate Psychology students participated in a two-session tractography-based activity combining instruction on white matter anatomy and diffusion tractography with a hands-on virtual dissection of the arcuate fasciculus using research-grade software routinely employed in neuroscience research. Following the activity, students completed an anonymous questionnaire assessing perceived learning, utility, difficulty and handling, and organizational aspects of the activity. Pearson correlations, multiple regression analyses, and relative importance analyses were performed. Results: Sixty-eight students completed the questionnaire. Students reported generally positive perceptions of the activity across the evaluated dimensions, with perceived learning receiving the highest mean score (M = 3.44, SD = .85). Perceived utility showed the strongest association with perceived learning (r = .64, p < .001). The regression model explained 41% of the variance in perceived learning (R2 = .41, adjusted R2 = .38, p < .001). Perceived utility was the only significant predictor in the model ({beta} = .59, p = .001), accounting for 67.9% of the explained variance. Conclusions: The findings support the feasibility of integrating authentic neuroimaging tools into undergraduate neuroanatomy teaching. Students who perceived the activity as more useful also reported higher perceived learning outcomes, with perceived utility emerging as the strongest predictor of perceived learning. In contrast, perceived difficulty and handling, and organizational aspects did not make significant independent contributions. These results suggest that students perceptions of educational relevance may play an important role in technology-enhanced STEM learning experiences.

2
Musical Aesthetic Experience Reveals Differential Effects of Professional Vocal Training on Female College Students' Brain Function

LI, H.; Gao, Y.; Ma, Y.; Sun, B.; Liu, Y.; Zhou, R.; Ren, A.; Yuan, T.; Huang, X.; Zhang, X.

2026-10-07 scientific communication and education 10.64898/2026.10.02.756189 medRxiv
Top 0.1%
9.2%
Show abstract

Musical aesthetic experience can reveal students' cognitive, aesthetic, and emotional responses to music. However, how professional vocal training alters brain functions in female college students with varying levels of musicianship to promote these is unknown. Here we applied fMRI, psychological measures and Goldsmiths musical sophistication index (Gold-MSI) assessments to study 27 non-music major female college students consisting of instrument group (normal pitch accuracy with instrumental training), general group (normal pitch accuracy without instrumental training) and poor-pitch group (poor pitch accuracy and without instrumental training). After 1 year of one-on-one instructional practice, we found that professional vocal training enhanced information processing related to musical cognition and pleasure during musical aesthetic experiences across all three groups, involving improvements in motor control of vocalization, auditory feedback processing, musical memory and attention together with musical pleasure. Specifically, instrument group showed activation of reward circuits, general group exhibited activation of laryngeal motor control circuits, and poor-pitch group displayed activation of sensory/sensorimotor/motor control circuits. Both pre- and post-training, the instrument group exhibited higher connectivity than the other two groups in the left amygdala-dorsal anterior cingulate cortex (dACC) and the right posterior superior temporal gyrus (pSTG)-left insula pathway. After professional vocal training, the general group showed higher connectivity in the left amygdala-dACC, whereas the poor-pitch group demonstrated increased connectivity in the right pSTG-left insula and dACC-nucleus accumbens pathways. Surprisingly, professional vocal training activated the bed nucleus of the stria terminalis (BNST), a subcortical emotion center, and connectivity with the medial prefrontal cortex associated with musical information processing. Thus, vocal training can significantly improve musical cognition and aesthetic pleasure, and facilitates neural modulation in the brain's emotional centers.

3
Sustained Viral Suppression and its association with Psychiatric Morbidity and Sleep Quality among Older Adults with Human Immunodeficiency Virus: Evidence from a Retrospective Cohort in Ibadan, Nigeria.

Elugbadebo, O. O.; Akintade, F. M.; Oladeji, B. D.; Beach, L. B.; Kuhns, L. M.; Egbuna, C.; Awolude, O.; Omigbodun, O.; Gorelick, P. B.

2026-10-09 hiv aids 10.64898/2026.10.07.26364957 medRxiv
Top 0.1%
7.1%
Show abstract

Purpose Older adults with HIV are at risk of psychiatric disorders and poor sleep quality, but evidence from sub-Saharan Africa is limited, particularly regarding sustained viral suppression. This study examined the prevalence of psychiatric disorders and poor sleep quality symptoms and their association with sustained viral suppression among older adults with HIV in Nigeria. Methods: A retrospective cohort study was conducted among older adults receiving care at a tertiary HIV clinic in Ibadan, Nigeria. Viral load data from 2019-2023 were abstracted from medical records to determine sustained viral load suppression, while psychiatric morbidity and sleep quality were assessed cross-sectionally in 2023. Psychiatric assessments included major depressive disorder, anxiety disorder, bipolar disorder and mania. Mixed-effects logistic regression assessed changes in viral suppression over time and associations with psychiatric morbidity and sleep quality. Results: Among 400 participants, 63.5% were female and mean age was 58.2 years (S.D 6.5). A total of 25.8% had major depressive disorder, 17.5% had anxiety disorder, 29.3% had poor sleep quality, 3.3%, bipolar disorder, and 1.0% mania. Viral suppression improved significantly over the retrospective period. Sustained viral suppression was significantly associated with higher odds of good sleep quality (OR = 1.69, 95% CI: 1.07 to 2.66, p = 0.025), but not psychiatric morbidity. Conclusion: Psychiatric disorders and poor sleep quality are common among older adults with HIV in Nigeria. Sustained viral suppression was associated with better sleep quality but not psychiatric morbidity highlighting the importance of integrating mental health and sleep assessment into comprehensive HIV care for older adults.

4
Ecological momentary assessments predict clinical anxiety and depression status at 3 months post-stroke

Duttagupta, S.; Berthoz, S.; Sibon, I.

2026-10-09 neurology 10.64898/2026.10.07.26362727 medRxiv
Top 0.1%
4.8%
Show abstract

Background: Stroke survivors frequently experience post-stroke depression (PSD) and post-stroke anxiety (PSA), which may be underexamined by clinicians if patient mood status between discharge and follow-up is unknown. Digital monitoring may enable early identification of mood disturbances. Ecological momentary assessments (EMA) have been tested to capture mood fluctuations in patients regular environments, but no standardized procedure for monitoring PSA or PSD has been developed. Objective: Determine the feasibility and validity of EMA for evaluating subacute PSA and PSD in non-severe stroke patients. Methods: Patients with non-severe stroke discharged home responded to daily smartphone EMA questions concerning mood and activity for twelve weeks until follow-up. Questions based on symptoms of anxiety and depression were used to derive EMA Anx and EMA Dep indices, computed over five 15-day intervals. Convergent validity was assessed using follow-up Generalized Anxiety Disorder-7 (GAD-7) and Centre for Epidemiological Studies-Depression (CES-D) scores. Logistic regression models predicted PSA and PSD status at follow-up, with baseline models comprising stroke severity, age, sex, and mood status, to which EMA Anx or Dep were added. Results: Data from 118 patients were analyzed. EMA adherence was moderate, with 89 patients (75.4%) responding on 75 or more days. Correlations between EMA Anx and GAD-7 and between EMA Dep and CES-D generally strengthened at later intervals, with the average mood index generally showing the strongest associations. Adding EMA data from the third time interval (31-45 days) significantly improved model fit beyond the baseline models (Anxiety: {chi}-square = 7.08, p = 0.008, {delta}R-square = 0.060; Depression: {chi}-square = 28.0, p < 0.001, {delta}R-square = 0.256). Discussion: EMA is feasible in mild-to-moderate stroke patients and may facilitate early identification of post-stroke mood disturbances. Further analyses in more diverse populations are required to validate these findings.

5
Intracortical microstimulation evokes diverse electrode-specific phosphenes in the early visual cortex of blind individuals

Soo, L.; Rodil Doblado, A.; Grani, F.; Lopez Peco, R.; Villamarin-Ortiz, A.; Morollon Ruiz, R.; Waclawczyk, D.; Fine, I.; Gonzalez-Lopez, P.; Soto-Sanchez, C.; Alfaro, A.; Fernandez, E.

2026-10-07 ophthalmology 10.64898/2026.10.05.26364412 medRxiv
Top 0.1%
4.3%
Show abstract

Purpose: Electrical stimulation of the occipital cortex evokes visual percepts known as phosphenes. To date, most human studies have examined phosphenes elicited by large surface or depth electrodes. These differ considerably from the small penetrating intracortical microelectrodes capable of stimulating highly localized cortical populations that are the basis of current next-generation devices. Here, we provide a detailed characterization of phosphenes evoked by such intracortical microelectrodes. Methods: As part of the CORTIVIS clinical trial, a Utah Electrode Array with 100 penetrating electrodes was implanted in the early visual cortex of four blind volunteers. Participants completed drawing and description tasks in response to single-electrode stimulation. Two participants also performed forced-choice tasks to determine whether phosphenes elicited by different electrodes could be reliably discriminated. Results: Single-electrode stimulation reliably evoked phosphenes in all participants. Most percepts appeared in the contralateral visual field, although two participants reported near-midline ipsilateral percepts. Phosphenes ranged from simple dots to elongated, textured, circular, or otherwise idiosyncratic forms. One participant reported distinguishable phosphene colors, which depended on electrode and amplitude structure and varied across sessions. The two participants tested on forced-choice discrimination could successfully identify electrode-specific phosphenes across multiple sessions. Conclusions: Intracortical microstimulation of the human visual cortex produces phosphenes with diverse, electrode-specific appearances that are recognizable across repeated trials. These findings indicate that penetrating microelectrodes often evoke more structured percepts than simple points or blobs, providing foundational evidence that electrode-specific encoding strategies will be necessary in future visual prosthetic devices.

6
Prenatal alcohol and cannabinoid co-exposure increases ethanol-seeking in adult offspring and produces sex-dependent medial prefrontal cannabinoid receptor 1 expression.

Rouzer, S. K.; Bowring, A.; George, A.; Domen, M.; Labbe, E.; Palacios, M.; Miranda, R.

2026-09-23 developmental biology 10.64898/2026.09.21.753297 medRxiv
Top 0.2%
3.3%
Show abstract

Background: Alcohol and cannabinoids are frequently used during pregnancy, however their combined effects on offspring outcomes are currently under-investigated. In this study, co-exposure was compared to single-drug and drug-free exposures for influences on adult alcohol-seeking and cannabinoid system proteomics. Methods: Pregnant C57BL/6J mice received ethanol vapor (ALC), CP-55,940 (0.75 mg/kg; CB), both (ALC+CB), or neither on gestational days 12-15. Beginning on Postnatal Day 200, male and female offspring underwent home-cage ethanol drinking (N=108) and operant self-administration, progressive-ratio, extinction, and reinstatement testing (N=96). CNR1 and CNRIP1 protein abundance was quantified in the medial prefrontal cortex (mPFC) and dorsomedial striatum (N=57) and compared to within-subject drinking behaviors. Results: Prenatal CB exposure increased cumulative home-cage ethanol intake, primarily in males. At 40% ethanol under progressive-ratio schedules, ALC+CB males consumed more than all other male groups, whereas all exposed female groups consumed more than controls. ALC+CB males also showed greater extinction responding than all other male groups and greater reinstatement intake relative to baseline than CON and ALC males. ALC+CB increased mPFC CNR1 in males relative to all other groups, whereas CB and ALC+CB reduced mPFC CNR1 in females. Higher mPFC CNR1 was associated with fixed-ratio and 40% progressive-ratio intake, extinction, and reinstatement exclusively in males. Conclusions: Prenatal co-exposure produced a persistent male phenotype of enhanced ethanol seeking that was distinct from either exposure alone and accompanied by elevated mPFC CNR1. This behavioral and molecular convergence justifies future investigations manipulating corticostriatal cannabinoid signaling to attenuate exposure-induced ethanol consumption in late adulthood.

7
Novel Cognitive Behavioral Therapy App for Depression in Mild Traumatic Brain Injury: A Randomized Controlled Trial

Emery, J. B.; Matheson, L.; Shaw, O.; Mannan, N.; Cota, M.; Fu, A.; Haight, T.; Brody, D. L.

2026-09-27 neurology 10.64898/2026.09.24.26363933 medRxiv
Top 0.2%
3.3%
Show abstract

Background: Depression symptoms following traumatic brain injury (TBI) are common and strongly associated with adverse overall outcomes in military service members, veterans, and civilians. Cognitive behavioral therapy for depression (CBT-D) is considered a first-line treatment for depression symptoms in many contexts. However, costs associated with CBT-D can be substantial, and there are insufficient numbers of providers trained to perform CBT-D. In contradistinction, digital therapeutic interventions such as smartphone apps have virtually unlimited availability and low per-patient costs. However, evidence for efficacy of digital interventions providing CBT-D in the context of TBI is limited. The aims of this study were to design, develop, and test a novel smartphone app to provide CBT-D intended for military service members with depression symptoms and history of mild TBI. Results: We designed a novel smartphone app featuring digital avatar coaches to provide CBT-D intended for military service members with depression symptoms and history of mild TBI. Key features and goals of the 12 weekly CBT lessons included stigma minimization, personal engagement, and 1-2 hours per week of personal challenge homework assignments. We performed a randomized controlled trial initially involving military service members and veterans. Inclusion criteria were later relaxed to allow for civilian participation due to practical constraints . The control group received an app providing educational lessons about concussions and depression which did not include the therapeutic components of CBT. There was no difference between the groups randomized to CBT-D (n=19) vs. educational app control (n=23) in self-reported depression symptoms. Nevertheless, there was a statistically significant benefit of the CBT-D intervention in self-reported insomnia severity at the 16-week follow-up (four weeks post intervention) assessment (Cohens D=0.45, p=0.0064). There were also statistically significant positive correlations (r= 0.46 to 0.76, p=0.046 to 0.001) between changes over time in depression symptoms and changes over time in both insomnia and PTSD symptoms in the CBT-D group. There were no such correlations in the control group. Participants reported higher therapeutic alliance (p=0.0001) and overall mobile application user rating (p=0.036) for the CBT-D app than for the control education app. More favorable therapeutic alliance and mobile application user ratings correlated significantly with greater improvements in depression symptoms in the CBT-D group (r=0.53 to 0.66, p=0.02 to 0.002). However, dropout was substantial (40/59 in the CBT-D group and 31/54 in the control group) and results may not be fully representative of the population at risk. Conclusions: There remains a major unmet need for widely available, low-cost, effective interventions for depression symptoms in the context of mild TBI. The challenges of designing and rigorously assessing the effects such interventions remain formidable. However, the lessons learned from this study and indications of benefit in a highly relevant secondary outcome measure (insomnia) suggest that remote app-based interventions remain therapeutically viable. Trial Registration: clinicaltrials.gov NCT05147506, submitted 20 July 2021, posted 7 December 2021.

8
Biological aging markers in South African women with HIV and variable exposure to childhood maltreatment

Maloka, K. M. S.; Spies, G.; du Plessis, S.; Hemmings, S. M. J.; Letendre, S.; Seedat, S.; Womersley, J. S.

2026-10-16 hiv aids 10.64898/2026.10.15.26365601 medRxiv
Top 0.2%
3.3%
Show abstract

Introduction: HIV and childhood maltreatment (CM) are both chronic stressors that disproportionately affect women, with each contributing to accelerated biological aging. Whether biological aging markers are convergent and associate with HIV and CM is unclear. Methods: We studied 238 women (122 with HIV), characterised for CM severity, and assessed biological aging using absolute telomere length (aTL), mitochondrial DNA copy number (mtDNAcn), magnetic resonance imaging-based brain-predicted age difference (MRI-BPAD), and DNA methylation age (DNAmAge) clocks. CM was measured with the Childhood Trauma Questionnaire-Short Form total score. We examined intercorrelations among biological aging markers to assess convergence and conducted linear regression models to test moderation by HIV status and CM severity. Results: PWH had shorter aTL, lower MRI-BPAD, and higher Horvath age acceleration (HorvathAA), HannumAA, PhenoAA, and extrinsic epigenetic age acceleration (EEAA). CM had limited associations with biological aging markers. Absolute TL correlated weakly with mtDNAcn (p = 0.36), PhenoAA (p = -0.18), and EEAA (p = -0.18), while MRI-BPAD correlated weakly with PhenoAA (r = 0.20). DNAmAge clocks were moderately to strongly intercorrelated (r = 0.35 - 0.93). No robust two- or three-way moderation effects were observed after false discovery rate correction. Conclusion: Our findings support a multidimensional pattern of biological aging, with substantial convergence among epigenetic aging measures but limited relationships across different markers, largely independent of HIV status and CM severity. Longitudinal approaches are needed to clarify how distinct biological aging markers relate to one another and to health outcomes over time in vulnerable populations.

9
Delay in antiretroviral therapy initiation is associated with worse mood symptoms in adults with chronic HIV disease

Lee, H.; O'Connor, C.; Hanly, G.; Chen, L.; Mahmood, D.; Moore, D. J.; Ellis, R. J.; Jiang, X.

2026-10-08 hiv aids 10.64898/2026.10.07.26364968 medRxiv
Top 0.2%
3.2%
Show abstract

Background. In the era of successful antiretroviral therapy (ART), mood disturbance remains highly prevalent in people with HIV (PWH). In the present study, we investigated the long-term legacy effects of long delay in ART initiation and low nadir CD4 count on mood symptoms in adults with HIV. The impacts of demographic and other HIV clinical factors were also examined. Methods. A total of 109 PWH (disease duration: 24.6{+/-}9.3 years) and 42 demographically matched healthy participants (people without HIV, or PWoH) participated in a cross-sectional study (41-70 years old (55.6{+/-}6.8), 62.9% African Americans, 27.2% female, 14.3{+/-}2.9 years of education). Mood symptoms were assessed with the Beck Depression Inventory-II (BDI-II) and the Profile of Mood States (POMS). A comprehensive neuropsychological test battery was administered to assess neurocognitive function. Results. Despite largely comparable neurocognitive performance between PWH and PWoH , PWH had worse mood symptoms than PWoH, including higher total BDI-II (p<.001) and total POMS scores (p=.002), as well as higher score in all POMS sub-scores (p<.007), except Vigor (p=.724). Within the PWH group, longer delays in ART initiation, lower nadir CD4 count, and lower educational attainment were associated with worse mood symptoms. By contrast, current plasma CD4+ cell count, plasma detectable viral load, and HIV disease duration were not associated with either BDI-II or POMS score. Conclusion. Mood disturbance is highly prevalent in PWH on ART. The long-term legacy effects of delay in ART initiation and low nadir CD4 count on mood management reinforce the necessity of early ART initiation in clinical practice.

10
Optimizing Intermittent Theta-Burst Stimulation: The Effects of Pulse Parameters on Corticospinal Excitability

Proulx, B.; Hasani, S. A.; Frechette, A.-J.; Hamel, R.; Tremblay, S.; Cote, S.; Lepage, J.-F.

2026-10-12 neuroscience 10.64898/2026.10.05.756785 medRxiv
Top 0.3%
3.1%
Show abstract

Objective. Intermittent theta burst stimulation (iTBS) is a repetitive transcranial magnetic stimulation (rTMS) protocol used in clinical settings to alleviate symptoms of psychiatric disorders. Although the pulse parameters currently used in iTBS have remained unchanged since the first treatments, recent controllable TMS devices allow for the personalization of pulse shape and duration, opening the possibility of testing the efficacy of other pulse parameters in modulating corticospinal excitability (CSE). Methods. In a repeated-measures design, changes in CSE were induced by the administration of iTBS over the left primary motor cortex under three different conditions: long bidirectional pulse (L-Bi), long quasi-unidirectional pulse (L-QU), and a control short quasi-unidirectional pulse (S-QU). We assessed TMS-induced motor evoked potentials before and up to 70 minutes after iTBS. We hypothesized that L-QU pulses would induce greater facilitation than other conditions. Results. A mixed linear model showed that all conditions induced increased MEPs compared to baseline. However, the L-Bi pulse led to a larger and more sustained MEP increase than both unidirectional pulses, while the S-QU pulse appeared less effective in modulating CSE. We observed large within- and between-subject variability in responsiveness to the iTBS protocols. Conclusion. These results suggest that L-Bi pulses in iTBS protocols are more potent than unidirectional pulses in inducing CSE changes in the cortex of healthy adults. The individual variability in response to iTBS and the potential clinical relevance of these findings are discussed.

11
EEG mu rhythms and trait empathy during observation of a romantic partner's pain with and without consoling touch

Love, S.; Rowden, L.; Ballenger, B.; Harris Bozer, A.

2026-10-01 neuroscience 10.64898/2026.09.26.754722 medRxiv
Top 0.3%
2.6%
Show abstract

Introduction: Observation of a partner in pain elicits empathy-related cortical responses and social support can modulate pain. Objective: The aim of this study was to investigate empathy and the cortical response during observation of a romantic partner in pain with and without consoling touch. Methods: A total of 40 participants (20 couples) completed validated measures of handedness, pain and empathy. Each member of the couple was randomly assigned to be either the recipient of cold pressor pain or the consoling partner undergoing EEG. EEG activity was recorded from the consoling partner during baseline and pain conditions (with and without consoling touch) to investigate how observation of a partner in pain could alter mu rhythms. Results: Observing a romantic partner in pain significantly enhanced mu at electrodes C4 and Cz, yet addition of consoling touch did not significantly change mu rhythms. Personal Distress was positively associated with mu rhythm enhancement at electrode C4 during pain without consoling touch (r = .576, p = .008). Conclusion: Viewing a romantic partner in pain significantly increased mu rhythms, that was not further changed by offering consoling touch. The association between increases in mu rhythms and Personal Distress in the current study suggests that self-oriented distress may be especially relevant to sensorimotor cortex responses when witnessing a partner in pain, particularly when consoling touch is not possible. Keywords: pain; empathy, EEG, mu rhythms, cold pressor

12
Adults experiences of comorbid insomnia and pain: Entangled vicious cycle, driven by four primary factors

Albertsdottir, A.; Islind, A. S.; Skuladottir, H.; Halldorsdottir, S.; Olafsdottir, K. A.; Bjornsdottir, E.; Vikingsson, A.; Pires, G. N.; Arnardottir, E. S.

2026-09-30 public and global health 10.64898/2026.09.29.26364320 medRxiv
Top 0.4%
2.5%
Show abstract

Chronic pain and insomnia are common, each has serious consequences and they often coexist [1-5]. This novel study employed a phenomenological method to explore adults lived experiences of the core and meaning of comorbid insomnia and pain, here conceptualized as COMIP. The empirical data is based on 22 semi-structured interviews with adults with COMIP. Each interview was analysed, developing themes and analytical frameworks for all participants, which were then compared to construct one main analytical framework. The consolidated criteria for reporting qualitative research were used [6]. The essence of COMIP was: A vicious cycle of insomnia and pain driven by four intertwined primary factors with cross effects, which reduced sleep quality and quality of life. Four main themes emerged: Firstly, insomnia with hyperarousal like racing thoughts, and difficulties with finding comfortable sleeping positions due to pain, disturbed sleep and decreased sleep quality. Secondly, daytime symptoms like reduced energy, with reduced daytime function and reduced quality of life. Thirdly, 24-hour hyperarousal, stress and distressing experiences such as suffering. Finally, contextual factors like treatment reduced and/or increased COMIP. The main contribution of this research is three-fold; mapping of the experiences of living with COMIP, the conceptualization of COMIP, and introduction of novel concepts. Our findings indicate that, when evaluating patients with COMIP, there is value in exploring the four COMIP factors. Although, it varies between individuals which factor/s is central to their COMIP experience, we emphasize that COMIP is distressing, and patients are likely to need emotional support and validation. Keywords: COMIP, sleep, phenomenology, disability, rehabilitation, ICF.

13
Fibromyalgia, Chronic Fatigue Syndrome, and Multiple Sclerosis are associated with lower translocator protein binding affinity genotypes

Jones, C. L.; Younger, J. W.

2026-10-21 neurology 10.64898/2026.10.19.26365953 medRxiv
Top 0.4%
2.4%
Show abstract

Introduction: Neuroinflammation is a known pathophysiologic mechanism in multiple sclerosis and a proposed mechanism in fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Positron Emission Tomography (PET) imaging of the translocator protein (TSPO) has been widely used to measure neuroinflammation, though second-generation ligands are highly sensitive to a single nucleotide polymorphism, rs6971, resulting in high, mixed, and low affinity binders. It is unknown whether this polymorphism is associated with neuroinflammatory disorders. Materials and Methods: Eighty-six total participant genotypes for TSPO binding affinity were identified through Sanger sequencing (30 fibromyalgia, 21 ME/CFS, 11 multiple sclerosis, and 24 healthy controls). Associations between patient group and genotype were assessed with Fishers Exact test. Associations between genotype and symptom severity from self-report questionnaires were assessed with Kruskal-Wallis tests. Results: In the present study individuals with fibromyalgia, (ME/CFS), or multiple sclerosis were more likely to have a mixed- or low-affinity genotypes compared to healthy controls. Presence of the low or mixed genotypes were also associated with greater self-reported fatigue severity and depressive symptoms. Discussion: These findings should be confirmed in larger samples but suggest functional consequences of rs6971 polymorphism that may be related to the pathophysiology of pain and fatigue illnesses.

14
Resting-State Functional Connectivity and Cognitive Performance in Long COVID: A Randomized Controlled Trial

O'Connor, D.; Watson, E.; Reich, D. L.; Carnavali, F.; Mcveety, M.; Gwalani, P.; Wisnivesky, J. P.; Becker, J. H.

2026-10-08 neurology 10.64898/2026.10.05.26364531 medRxiv
Top 0.4%
2.4%
Show abstract

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.

15
EasyCog: a fast and effective numerical tool for the self-assessment of cognitive functions

Hadri, L.; Lejczak, S.; Fabian, X.; Martinie, O.; Justin, G.; Lithfous, S.; Salvat, E.; Nizard, J.; Poisbeau, P.

2026-09-24 pain medicine 10.64898/2026.09.23.26363767 medRxiv
Top 0.5%
2.2%
Show abstract

Many pathological conditions, including chronic pain (CP), can impair cognitive functions. These functions are essential for adapting and evolving in concordance with the environment, which are key processes for coping with CP. However, in CP centers, cognitive assessment is rarely included in CP patient follow-up due to a lack of time, appropriate tools, or trained health professionals. To fill this gap, our team developed EasyCog, a digital tool that enables rapid self-assessment of cognitive functions. It enables cognitive evaluation without an experimenter's help, thanks to speech recognition powered by an artificial neural network. In the initial validation steps, we established normative values for 7 cognitive functions on a cohort of 76 healthy subjects. Because EasyCog includes tests comparable to the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), we assessed its reliability against available normative values. To assess its specificity, we compared data from healthy subjects with 15 subjects with mild cognitive impairment (MCI) and 15 age-matched CP patients selected from a medical center. Finally, we tested EasyCog's test-retest reliability by repeating sessions at different time intervals. EasyCog showed excellent sensitivity to age-related decline, similar to MoCA normative values. Several cognitive functions were significantly and differentially impaired in MCI subjects and CP patients compared to normative values in healthy subjects, confirming good specificity. Finally, test-retest analysis showed no effect at a 4-month interval. In conclusion, EasyCog appears to be a convenient and reliable numeric tool for rapidly assessing and monitoring cognitive functions in patients.

16
Compensatory drive and sleep-related phantom limb pain: the moderating role of autonomic reserve

Aranis, N.; Holmes, M.; Gianlorenco, A. L.; Sparrow, D.; Crandell, D.; Caumo, W.; Fregni, F.

2026-10-08 neurology 10.64898/2026.10.06.26364856 medRxiv
Top 0.5%
2.1%
Show abstract

Phantom limb pain (PLP) is common after amputation, yet why poor sleep becomes pain in only some individuals is unknown. We hypothesized that a regulatory response is interpretable only against the reserve sustaining it, and thus we tested whether autonomic capacity relative to demand moderates the sleep-pain relationship in 121 amputee adults. Sleep was assessed with the Pittsburgh Sleep Quality Index; PLP, residual limb pain (RLP), and phantom limb sensation (PLS) on 0-10 scales. Heart rate variability was summarized as autonomic reserve (log-transformed SDNN, RMSSD, total and high-frequency power) and autonomic drive (normalized low-frequency power). Poorer sleep was associated with greater PLP and RLP, but not PLS. No single HRV index moderated these associations, but the sleep x reserve x drive interaction did for PLP (b =-0.51, p = 0.026). Poor sleep predicted pain most strongly under high drive with reduced reserve. PLP vulnerability reflects autonomic capacity relative to demand, instead of any single HRV marker alone.

17
REM sleep EEG slowing signals basal forebrain integrity in older adults with subjective and mild cognitive impairment

Lam, A.; Espinosa, N.; Matar, E.; Cross, N.; Fripp, J.; Xia, Y.; Andre, C.; Coulson, E.; Taranto, R.; Grunstein, R.; D'Rozario, A. L.; Naismith, S. L.

2026-10-02 neurology 10.64898/2026.09.30.26363850 medRxiv
Top 0.6%
1.9%
Show abstract

Introduction The basal forebrain is an early site of pathology in Alzheimer's disease (AD). Within this region, the nucleus basalis of Meynert (NbM) provides the primary cholinergic input to the neocortex and supports cortical activation during rapid eye movement (REM) sleep. REM electroencephalography (EEG) slowing is observed in older adults with AD and amnestic mild cognitive impairment (MCI). This study examined the relationship between REM EEG slowing and NbM volume, and whether it differed by cognitive status, sex, or sleep apnea severity. Methods Participants aged [&le;] 60 years with cognitive concerns underwent neuropsychological and medical assessments, polysomnography, and magnetic resonance imaging (MRI). REM EEG slowing was quantified as the ratio of delta and theta (<8Hz) to alpha, sigma, and beta (8-32Hz) power. Bilateral NbM and Ch1-3 volume were derived from T1-weighted MRI images. Multiple linear regression and moderation analyses adjusted for age, sex, and sleep apnea severity. Exploratory analyses examined associations between NbM volume, sleep macroarchitecture, and memory. Results The sample comprised 116 participants (59.5% female; mean age = 70.5 years, 64.7% MCI). Greater REM EEG slowing was associated with smaller NbM volume (all p < 0.05). Although moderation effects were not significant after FDR correction, within-group analyses suggested a stronger relationship in MCI. Smaller NbM volume was associated with longer sleep latency and poorer episodic memory (all p < 0.05). Discussion REM EEG slowing may reflect early NbM degeneration and provide a non-invasive biomarker of basal forebrain integrity in older adults with cognitive concerns. Longitudinal studies are required to establish its prognostic value.

18
Hippocampal and large-scale functional connectivity reorganization following freediving training, and relationships with episodic memory

Micaux, J.; Troudi Habibi, A.; Mauconduit, F.; boumezbeur, f.; Chiron, C.; Noulhiane, M.

2026-09-29 neuroscience 10.64898/2026.09.24.753809 medRxiv
Top 0.6%
1.9%
Show abstract

The hippocampus is particularly vulnerable to hypoxia, yet freedivers, who repeatedly undergo voluntary breath-hold hypoxia, do not appear to show the memory impairments commonly reported after involuntary hypoxic exposure. We investigated whether freediving training is associated with functional connectivity reorganization at the whole-brain and hippocampal levels, and whether hippocampal connectivity relates to preserved episodic memory performance. Seventeen male recreational freedivers underwent fMRI before and after a 7-month standardized training period, and 20 matched aerobic-trained controls were assessed at baseline. Functional connectivity analyses examined (i) whole-brain ROI-to-ROI connectivity, (ii) seed-to-voxel connectivity from the bilateral hippocampus and selected cortical seeds, and (iii) associations between hippocampal connectivity and episodic memory. Compared with controls, freedivers showed distinct connectivity patterns during apnea and rest. After training, whole-brain analyses revealed reorganization involving salience, frontoparietal, sensorimotor, visual, and cerebellar systems. Hippocampal analyses showed reduced connectivity with sensorimotor and default mode regions, alongside increased connectivity with cerebellar and visual areas, with stronger effects after training. In freedivers, specific post-training hippocampal connectivity was associated with episodic memory performance. These findings suggest that repeated voluntary hypoxia during freediving training is associated with selective functional reorganization of hippocampal and large-scale brain networks. This pattern may reflect adaptive neuroplasticity linked to preserved episodic memory under intermittent hypoxic exposure.

19
Functional connectivity correlates of post-acute covid 19 cognitive and neuropsychiatric complications

Auwal, A. M.; Keller, S.; Bullmore, E.; Ellul, M.; Michael, B. D.

2026-10-01 neurology 10.64898/2026.09.24.26363490 medRxiv
Top 0.6%
1.9%
Show abstract

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

20
The Context of Recovery Among Adults Who Recover from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Condition Following Mind-Body Approaches: A Qualitative Descriptive Study Protocol

Cordovani, L.; Almazyad, L.; Zeraatkar, D.; Busse, J. W.

2026-09-25 pain medicine 10.64898/2026.09.24.26363855 medRxiv
Top 0.6%
1.8%
Show abstract

Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-COVID condition are complex, debilitating illnesses characterized by persistent fatigue and post-exertional malaise. Recovery is uncommon without targeted intervention; however, emerging clinical reports suggest that a subset of patients experience full resolution of symptoms after engaging in mind-body approaches. Patient perspectives on these interventions are divided, and qualitative evidence exploring successful recovery pathways is rare. This protocol outlines a study to investigate the contextual factors and patient-constructed explanations surrounding full recovery from ME/CFS or post-COVID condition using mind-body approaches. Methods and analysis We will employ a qualitative descriptive design rooted in a constructivist paradigm. Purposive and snowball sampling will be used to recruit approximately 20 adults from established infection-associated fatigue networks who self-report full recovery (lasting three months or more) from ME/CFS or post-COVID condition following a mind-body approach. Data will be collected through semi-structured interviews conducted via Zoom, and investigator reflexivity will be reported. Demographic information, including comorbidities, will be documented to contextualize the sample. Data will be analyzed inductively using reflexive thematic analysis. To ensure research rigor and reporting transparency, the study will adhere to the 15-point checklist of criteria for good thematic analysis proposed by Braun and Clarke. Dissemination We will publish our findings in a peer-reviewed, open-access journal and present at relevant academic conferences. A lay summary of the results will also be shared directly with participating patient recovery networks.