In this study, we investigated the impact of tempi variations (60, 100, 120, and 150 beats per minute) and major and minor modes on the perceived emotional content of music. To explore this, we created eight versions of five original compositions, resulting in 40 musical stimuli. Control stimuli included variants of white, brown, and pink noise, as well as six human voice recordings. A total of 1280 participants took part in an online survey. Participants were diverse, comprising 262 musicians (defined as individuals with over six years of instrument-playing experience who identified as amateur, semi-professional, or professional). Participants were asked to rate the perceived emotional content of the stimuli, using the second-order factors of the GEMS-9 framework: 'sublimity', 'unease', and 'vitality'. We employed a mixed between-within-subjects analysis of variance to analyse the data. Specifically examining the influence of the four tempi, the two modes, while controlling for musicianship, gender, age, and education level. Results showed that as tempi increased, compositions were consistently rated as less sublimity and more vitality, in both major and minor modes. A higher tempi in the major mode resulted in lower ratings of uneasiness. There were also several significant findings for musicianship, gender, and education level, although these mostly had small effect sizes. For age groups, there were two substantial differences between the groups with larger effect sizes. Overall, our findings suggest that tempi and mode significantly influence how compositions are rated for sublimity, unease, and vitality, as they interact.

The underlying mechanisms for neurodegeneration in multiple sclerosis are complex and incompletely understood. Multivariate and multimodal investigations integrating demographic, clinical, multi-omics, and neuroimaging data provide opportunities for nuanced analyses, aimed to define disease progression markers. We used data from a 12-year longitudinal cohort of 88 people with multiple sclerosis, to test the predictive value of multi-omics, MRI, clinical examinations, self-reports on quality of life, demographics, and general health-related variables for future functional and cognitive disability. Progressive functional loss beyond an Expanded Disability Status Scale score≥4 was used to define a functional loss group. A cognitive decline group was defined by a ≥25% decrease from the maximum (cognitive) Paced Auditory Serial Addition Test score. We used a multiverse approach to identify which baseline variables were most predictive for functional and cognitive loss group memberships, independent of analysis bias. We identified several factors predicting an increased risk of future functional loss (FLG) and cognitive decline groups (CDG) within the next 12 years from baseline: functional score (0-10, median Odds Ratio per baseline unit increase [mORFLG=2.15± 0.51; mORCDG=2.46± 1.60]), cognitive scores (1-60 [mORFLG=0.98± 0.03; mORCDG=0.91± 0.06]), the number of previous relapses [mORFLG=1.56± 0.26; mORCDG=1.44± 0.60], serum vitamin A levels (umol/l [mORFLG=0.92± 0.06; mORCDG=0.33± 0.36]), self-reported mental health (1-100 [mORFLG=0.96± 0.02; mORCDG=0.91± 0.09]) and physical functioning (1-100 [mORFLG=0.99± 0.01; mORCDG=0.97± 0.03]). Our results suggest that clinical assessment of physical function and cognition, self-reported mental health, and potentially vitamin A levels are the best predictors for risk-group stratifications of people with MS at baseline. While these findings are promising, we also want to underscore the observed analysis-choice induced variability which necessitates both an increase in transparency when reporting study findings as well as strategies which are robust to the many researcher degrees of freedom. ### Competing Interest Statement OAA has received a speaker's honorarium from Lundbeck, Janssen, Otsuka and Lilly, and is a consultant to Coretechs.ai and Precision Health. LTW is a minor shareholder of baba.vision. KMM has served on scientific advisory board for Alexion, received speaker honoraria from Biogen, Novartis, Roche and Sanofi, and has participated in clinical trials organized by Biogen, Merck, Novartis, Otivio, Roche and Sanofi. EAH received honoraria for advisory board activity from Sanofi-Genzyme, and his department has received honoraria for lecturing from Biogen and Merck. OT received speaker honoraria from and served on scientific advisory boards of Biogen, Sanofi-Aventis, Merck, and Novartis, and has participated in clinical trials organized by Merck, Novartis, Roche and Sanofi. The remaining authors declare no other competing interests. ### Funding Statement This project was funded by the Norwegian MS-union (no reference). Model training was performed on the Service for Sensitive Data (TSD) platform, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo IT-Department (USIT). Computations were performed using resources provided by UNINETT Sigma2 (#NS9666S) - the National Infrastructure for High Performance Computing and Data Storage in Norway, supported by the Norwegian Research Council (#223273). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Norwegian Regional Committees for Medical and Health Research Ethics (REK, 814351). The OFAMS-study and the 10-year follow-up were previously approved by REK (2016/1906) and registered as clinical trial (clinicaltrials.gov identifier: [NCT00360906][1]). Ethical approval for the different brain age training datasets was obtained (REK 567301, PVO 17/21624), as well as for the longitudinal validation set (Bergen Breakfast Scanning Club, REK 238310), and the cross-sectional MS data (REK 2011/1846, REK 2016/102). All participants gave their written informed consent according to the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Brain age model training data are available from the respective websites of the databases either openly or after application (see supplemental material). The main study data (OFAMS data) can be shared after receiving a new ethics approval upon reasonable request to the authors. Brain age models and analysis code are freely available at https://github.com/MaxKorbmacher/OFAMS\_Brain\_Age. [https://github.com/MaxKorbmacher/OFAMS\_Brain\_Age][2] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00360906&atom=%2Fmedrxiv%2Fearly%2F2025%2F02%2F12%2F2025.02.09.25321961.atom [2]: https://github.com/MaxKorbmacher/OFAMS_Brain_Age

The underlying mechanisms for neurodegeneration in multiple sclerosis are complex and incompletely understood. Multivariate and multimodal investigations integrating demographic, clinical, multi-omics, and neuroimaging data provide opportunities for nuanced analyses, aimed to define disease progression markers. We used data from a 12-year longitudinal multicenter cohort of 88 people with multiple sclerosis, to test the predictive value of multi-omics, T1-weighted MRI (lesion count and volume, lesion-filled brain-predicted age), clinical examinations, self-reports on quality of life, demographics, and general health-related variables for future functional and cognitive disability. Systematic increases in Expanded Disability Status Scale (EDSS) scores were used to stratify a progressive disability group (PDG) from relatively stabile disability. A processing speed decline group (PSDG) was defined by a ≥ 20% decrease of Paced Auditory Serial Addition Test score from previous timepoints. We used a multiverse approach to identify which baseline variables were most predictive for PDG and PSDG memberships, considering multiple analysis paths. Future disability (median area under the curve: mAUC = 0.83 ± 0.04, median Brier score: mBS = 0.16 ± 0.02) and the loss of processing speed (mAUC = 0.89 ± 0.05, mBS = 0.10 ± 0.03) could be successfully classified across models. Varibles significantly (median p-values < 0.05) predicting stable disability included receiving disease modifying treatment at 12-year follow-up (median Odds Ratio: mORPDG = 7.44 ± 4.07, pmedian = 0.013, proportion of the OR’s directionality: PORSD = 100%), lower baseline EDSS for each 1-unit (mORPDG = 0.25 ± 0.11, pmedian = 0.013, PORSD = 100%), and counter-intuitively every year increase in baseline age (mORPDG = 1.12 ± 0.04, pmedian = 0.020, PORSD = 100%), and lower vitamin A per 1 umol/L (mORPDG = 0.10 ± 0.05, pmedian = 0.016, PORSD = 99.7%) and D levels per 1 nmol/L (mORPDG = 0.95 ± 0.02, pmedian = 0.025, PORSD = 100%). Variables significantly predicting stable processing speed were receiving disease modifying treatment at 12-year follow-up (mORPSDG = 0.10 ± 0.08, pmedian = 0.013, PORSD = 100%) and baseline PASAT score (mORPSDG = 0.86 ± 0.03, pmedian = 0.005, PORSD = 99.73%). These findings were supported by an additional simulation study. Concordant with the literature, disease modifying treatments influence disability progression, as well as a higher EDSS and PASAT scores at measurement start. Experimental and counterintuitive findings on vitamin A and D levels require further validation. The large variability across models suggests a strong influence of analytic flexibility, such as the selection of covariates.

Auditory cognitive control is crucial for filtering relevant information from irrelevant distractions, a frequent challenge in noisy everyday environments. This study investigates the association between vagally mediated heart rate variability (HRV) and auditory cognitive control, employing the Bergen Dichotic Listening (BDL) task. We hypothesized that higher HRV would be associated with enhanced performance in the cognitively demanding forced-left (FL) condition of the BDL, which is a validated measure of auditory cognitive control. Our sample consisted of 63 healthy individuals (N = 35 women), who performed the BDL task in a laboratory setting, with resting HRV measurements taken, followed by real-life cognitive assessments with simultaneous ambulatory HRV monitoring conducted three times across different times of the day. The results confirmed a significant positive relationship between HRV and performance in the FL condition but not in the less demanding forced-right condition (FR). Furthermore, ambulatory measurements revealed that this relationship was influenced by circadian rhythms, showing stronger positive correlations during the night and morning. These findings highlight HRV as a promising biomarker for auditory cognitive control and underscore the impact of time of day on cognitive performance. This study broadens our understanding of the autonomic nervous system's role in cognitive functions and affirms the extension of laboratory findings to daily life settings.

Music therapy has long been recognized as a valuable approach for supporting autistic children, yet its individualized and improvisational nature has made it challenging to evaluate and articulate within research frameworks. This paper presents a neuroscience-informed framework that connects theory, research, and practice by describing how the inherent capacities of music can support sensory, emotional, and social development. Drawing on findings from developmental psychology and neuroscience, it outlines how processes such as auditory-motor coupling, neural synchrony, and experience-dependent plasticity may help explain the therapeutic effects of music. The framework also proposes a semi-structured intervention design that balances flexibility with consistency, offering a practical scaffold for both clinical implementation and research. Core therapeutic principles-such as rapport, attunement, joint play, and providing choices-are articulated as foundations for fostering engagement and communication. By integrating neuroscientific insight with therapeutic practice, this framework complements existing clinical approaches and clarifies how music therapy can be understood, adapted, and studied as a dynamic, child-centered intervention grounded in both developmental and neuroscientific knowledge.

INTRODUCTION:Generalised anxiety disorder (GAD) in older adults involves excessive worry and cognitive challenges. Verbal memory impairments is associated to hippocampal dysfunction, with cortisol and brain-derived neurotrophic factor (BDNF) being important in hippocampal integrity. Research on hippocampal volume and verbal memory in older adults with GAD is limited, with mixed findings. This study investigates verbal memory in older adults with GAD versus healthy controls, and relations with hippocampal volumes. METHODS:Participants included 49 adults with GAD (Mage = 65.82, SD = 3.94) and 49 controls (Mage = 67.73, SD = 4.11). Verbal memory was assessed using the California Verbal Learning Test Long Delay Free Recall, hippocampal volumes via MRI, BDNF from serum, and cortisol via saliva. We fitted a Bayesian multivariate linear regression with bilateral hippocampal volume as outcome measure, and predictors: age, gender, education, intracranial volume, IQ, BDNF, cortisol, SSRI use, CVLT Long Delay Free Recall (LD FR), CVLT Learning, and diagnostic status*CVLT LD FR interaction. RESULTS:A credible interaction showed better verbal memory associated to larger hippocampal volume in controls, but this relationship was attenuated in GAD. BDNF and cortisol were not credibly associated with hippocampal volume. CONCLUSION:Diagnostic status moderates verbal memory and hippocampal volume relations, suggesting a distinct neurocognitive profile in older adults with GAD compared to healthy controls.

Developmental stuttering is a disorder with a high degree of heterogeneity, both behaviourally and neurologically. Research from different perspectives of stuttering indicates that sex is a potentially differentiating factor. In our study we explored if sex is related to variability of grey matter volume (GMV) patterns in adults with developmental stuttering. We used MRI to collect data on GMV from 24 righthanded adults who stutter (9 women and 15 men) and 29 righthanded fluent controls (10 women and 19 men). We analysed the following for 24 ROIs of the language system: 1) whole-group differences between the stuttering group and controls and 2) interaction between group (adults with stuttering versus controls) and sex. Our explorative results indicate that differences in grey matter volume between adults with stuttering and fluent adults are sex-specific for several areas involved in speech and language processing. We found an interaction between group and sex for the right BA45. The interaction indicates that men who stutter have larger GMV in this area compared to fluent men while women who stutter have smaller GMV compared to fluent women. Further, we found indications of sex-specific patterns in other areas of the bilateral inferior frontal cortex, but not the BA44, as well as in the cerebellum and the striatum.

Generalized anxiety disorder (GAD) is a severe and prevalent disorder among older adults. Cognitive behaviour therapy (CBT) is recommended treatment for GAD, but older adults benefit less than younger peers. Physical exercise has been suggested to improve treatment efficacy. We aimed to determine the efficacy of augmenting CBT with physical exercise for older adults with GAD. This randomised controlled trial included 50 participants (mean [SD] age 66.52 [4.09] years; 39 [78%] female) with GAD. Participants received individual CBT and were randomised to either physical exercise or telephone attention placebo. The main outcome measure was self-reported worry on the Penn State Worry Questionnaire (PSWQ). Secondary outcome measures were clinician-rated remission and self-reported symptoms of anxiety, depression, and quality of life. Although the interaction between time and condition was statistically nonsignificant, moderation analysis revealed that this interaction was significant for participants with low treatment credibility to CBT at baseline. Participants randomised to physical exercise were five times more likely to achieve reliable long-term worry-reduction than placebo control. We found significant differences in favour of physical exercise for secondary measures of depression and anxiety. Participants with better cognitive inhibition at baseline were more likely to achieve clinician-rated remission. Findings suggest that physical exercise augments CBT for older adults with GAD.

Cumulative cultural evolution (CCE) is a fundamental aspect of human cognition, enabling the refinement and transmission of complex skills across generations. This study explores the cognitive abilities supporting CCE through a transmission chain design using a knot-tying task combined with brain imaging to examine how skills are acquired over successive learning and transmission stages. We obtained data from two chains of multiple generations of participants. Our results revealed generational modifications in knot-tying techniques accompanied by increased prefrontal cortex activation in later generations of learners, possibly suggesting that loss of information due to imperfect copying fidelity increases cognitive demands for working memory. Our study further shows the potential of brain imaging as a viable technique for investigating CCE. By applying functional MRI to track neural activity during the acquisition of knot-tying skills, we provide a novel approach for understanding the cognitive mechanisms that underlie cultural knowledge transfer. Further research integrating neuroimaging with behavioral studies could help clarify how cognitive and neural processes contribute to the accumulation and refinement of cultural knowledge over time.

BackgroundMaintaining quality of life (QoL) and identifying contributing factors is an important aspect of treatment for glioma patients. Little is known about to what extent language function and psychological distress impact QoL before surgery.AimsThe aim of the present study was to investigate the impact of subjective and objective language function, as well as psychological distress on domains of QoL before surgery.Methods and proceduresTwenty-seven patients (52% female) with a suspected glioma, grade 1-3 based on symptoms and MRI imaging diagnostics were assessed pre-surgery. Subjective language concerns, psychological distress and QoL were investigated with self-reported questionnaires. A Subjective language index was calculated, based on items addressing word-finding, expression of thoughts, reading and writing. Objective language function was assessed with tasks of naming (The Boston Naming Test), verbal comprehension (Vocabulary and Similarities), verbal fluency (Semantic and Phonemic fluency) and verbal short-term and working memory (Digit span forward and backward). The strength of associations was determined using Spearman's rho correlations. Linear regression analyses were used to examine predictors for QoL.Outcomes and ResultsClinically significant reductions in QoL were found in 48% of the sample. Subjective language concerns were highly common, with 85% reporting some degree of difficulty. Group means on objective language tests were within normative range on the included measures. The Subjective language index correlated significantly with several QoL domains, whereas objective performance mainly correlated with functional well-being. Psychological distress was a strong predictor for QoL.ConclusionsThe findings demonstrate that reductions in QoL may occur during the diagnostic phase, even before glioma treatment starts. Subjective language concerns and psychological distress contributed to all aspects of QoL and highlight the importance of acknowledging patient-reported information. The results suggest a comprehensive multi-modal assessment of glioma patients pre-surgery, to establish a base-line and facilitate patient-centered treatment planning.

BackgroundWord-finding difficulties are a common self-reported concern in glioma patients known to negatively affect social participation and life satisfaction. Discrepancies between self-reported difficulties and performance on objective tests have been reported, but studies are seldom conducted longitudinally.AimsThe aim of the present study was to examine the occurrence of self-reported word-finding difficulties before and during the first year after glioma surgery. In addition, we investigated whether self-reported word-finding difficulties were predicted by standardized language tests and psychological distress.Methods and proceduresTwenty-three patients with gliomas (grade 1-3) were assessed pre-surgery, at six and twelve months follow-up. Self-reported word-finding difficulties were addressed with the item I am able to find the right word(s) to say what I mean, from the Functional Assessment of Cancer Therapy - Brain (FACT-Br). Confrontation naming was tested with the Boston Naming Test (BNT), word production with a semantic fluency test and word knowledge with a vocabulary test. Self-reported measures of psychological distress were assessed with the Hospital Anxiety and Depression Scale (HADS). Ordinal regression models were used to examine predictors of self-reported word-finding difficulties.Outcomes and resultsWord-finding difficulties were reported by 68% of the patients pre-surgery, increasing to 90% and 85% at the following assessments. Significant changes were observed in the magnitude of reported concerns between pre-surgery assessment and six months follow-up. Regression analyses demonstated that self-reported word-finding difficulties were predicted by psychological distress and vocabulary pre-surgery and vocabulary at six months follow-up, whereas confrontation naming and semantic fluency did not become significant in any of the assessments.ConclusionOur results indicate that self-reported word-finding difficulties occurred in a high percentage of glioma patients throughout the first year of illness. Patients reported increased difficulties after surgery that were not predicted by confrontation naming or semantic fluency but by vocabulary performance. The results imply further that psychological distress is a factor that should be taken into account. Self-reported function is an important supplement to objective testing and can provide indications about mental health status and the patients` perspective on language related challenges in everyday life.

AbstractThis lesson intends to provide a brief introduction to some central neuroimaging methods that are relevant for studying the human brain. The lesson starts with a brief introduction to cognitive neuroscience as the basis of all cognitive processes, followed by a description of methods that can be used to measure brain responses.

Executive functions (EF) decline with age and this decline in older adults with generalised anxiety disorder (GAD) may be influenced by heart rate variability (HRV), brain-derived neurotrophic factor (BDNF), and physical fitness. Understanding these relationships is important for tailored treatments in this population. In this study, 51 adults with GAD (M age = 66.46, SD = 4.08) and 51 healthy controls (M age = 67.67, SD = 4.04) were assessed on cognitive inhibition (Stroop task), shifting (Trails part 4), flexibility (Wisconsin Card Sorting Test - Perseverative errors), working memory (Digit Span Backwards), IQ (Wechsler Abbreviated Scale of Intelligence), high frequency HRV, serum mature BDNF levels, and VO2 max. Results indicated that participants with GAD exhibited better cognitive inhibition compared to controls, with no general reduction in EF. Cognitive inhibition was predicted by gender, HRV, and BDNF levels, while cognitive shifting was predicted by gender and IQ, and cognitive flexibility and working memory by IQ. The enhanced cognitive inhibition in GAD participants might stem from maladaptive use of this function, characteristic of GAD, or protection from EF decline due to normal HRV. Increased BDNF levels, possibly due to good fitness, or compensatory mechanisms related to the disorder, might also play a role. These findings highlight the complexity of EF and related mechanisms in GAD, highlighting the need for interventions that consider both cognitive and physiological factors for optimal outcomes.

Citation: Wang M-Y, Zöllner HJ, Yücel MA and Specht K (2024) Editorial: Variability and reproducibility of brain imaging. Front. Psychol. 15:1386948. doi: 10.3389/fpsyg.2024.1386948

With the feature of noninvasively monitoring the human brain, magnetic resonance imaging (MRI) has become a ubiquitous means to understand how the brain works. Specifically, T1-weighted (T1w) imaging is widely used to examine the brain structure where the cortical thickness, surface area, and brain volumes have been investigated. These T1w-derived phenotypes undergo radical changes during childhood and adolescence, while remaining relatively stable during adulthood. However, stability over a short time (e.g. one year) during adulthood is still unknown. Additionally, how environmental factors such as time-of-day and different daylight lengths could impact the structural brain is also elusive. The main purpose of this study, therefore, was to assess the stability of T1w-derived phenotypes, i.e., cortical thickness, surface area, and brain volumes including subcortical volumes, and to explore the time-of-day and daylight length effects. Accordingly, three subjects in their late 20s, and early 30s and 40s were scanned repeatedly on the same scanner over one year from which a deep brain imaging dataset was constructed with 38, 40, and 25 sessions for subjects 1, 2, and 3, respectively. The T1w-derived phenotypes demonstrated percentage changes within 5% and CVs (coefficients of variance) within 2% for the majority of brain regions. However, several brain regions did show larger variations with percentage changes around 10% and CVs around 5%, such as the temporal pole, the frontal pole, and the entorhinal cortex. More importantly, there were no significant effects of time-of-day and daylight length. Moreover, cortical thickness change was strongly and positively correlated with that of volume while being negatively correlated with that of surface area, illustrating their distinct roles in brain anatomy. Additionally, it was found that apparent head motion causes cortical thickness and volume to be underestimated and surface area to be overestimated. These results indicate that T1w-derived phenotypes are reasonably stable regardless of time-of-day or daylight length, but that head motion should be taken into consideration. Significance Assessing the measurement precision and within-subject stability of T1w-derived phenotypes is crucial for accurately estimating brain changes induced by treatments or interventions. Furthermore, understanding within-subject variation enhances our ability to predict behavior and associations with brain phenotypes, which rely heavily on between-subject variation. ### Competing Interest Statement The authors have declared no competing interest.

Abstract Many autistic children suffer from social communication problems, reduced participation, and mental health issues. Music therapy has beneficial but heterogeneous effects; its mechanisms are incompletely understood. The Music for Autism (M4A) trial aims to replicate and expand a previous trial examining brain mechanisms and clinical outcomes of music versus play-based therapy for autistic children. This paper presents M4A’s design and implementation; we examine feasibility of this replication trial based on the first wave of recruitment. M4A is a crossover randomised controlled trial currently conducted at two sites (Bergen, Norway; Vienna, Austria). Children aged 6-12 years diagnosed with autism spectrum disorder will be randomised to a sequence of weekly individual music and play-based therapy (3 months for each intervention; 3-month washout period). Outcomes assessed before and after each intervention period include communication (blinded, assessed by teachers); functional brain connectivity (from functional magnetic resonance imaging, fMRI); and further behavioural and biological outcomes. The planned total sample size of 80 will ensure adequate power. Recruitment in the first wave (14 randomised) was below expectations. Baseline characteristics were similar to the previous study, but some variables (severity, functioning) were difficult to assess and compare. A range of functioning levels were included. Interventions were well accepted; fidelity was adequate. Timing of interventions and assessments was challenging when blinded assessors were hard to reach. Blinding was successful. Movement in fMRI was an issue in some children, but we developed preparation strategies to help also low-functioning children to successfully complete the scans. No study-related adverse events occurred. M4A has a strong design, appears feasible, and promises important new insights into the mechanisms and outcomes of music therapy for ASD. Multinational replicability of controlled trials of complex psychosocial interventions in ASD combining clinical and brain imaging outcomes can be challenging and requires careful planning. Trial registration: Clinicaltrials.gov NCT04936048 * AGr and MR contributed equally to this work and share first authorship. CG, GS, and KS contributed equally to this work and share last authorship.

Background The aim of the present study was to investigate the associations stroke severity, aphasia severity, lesion location and lesion size in acute stroke, and aphasia severity in the subacute and chronic stages post stroke. We hypothesized that initial stroke severity and aphasia severity were associated with the patient’s aphasia severity in the subacute and chronic stages of stroke. We expected to find that lesions within the left frontotemporal regions of the brain were associated with aphasia severity post-stroke.Methods Thirty-three patients with aphasia were included in the study. They were assessed with a standardized aphasia test at admission to the hospital (T1), after 3 months (T2) and finally after 12 months (T3). Stroke severity, initial physical impairment, and initial functional independence were also assessed at T1. Diffusion-weighted magnetic resonance imaging was performed as clinical-routine at admission. Voxel-based lesion symptom mapping and a region of interest analysis (ROI) was performed to analyze MRI-findings.Results & Outcomes Initial lesion size and aphasia severity were associated with aphasia severity at T2. Initial stroke severity, aphasia severity, and lesion size were not associated with aphasia severity at T3, but the patients’ aphasia severity at T2 predicted aphasia severity at T3. Lesion analysis showed that lesions within the left postcentral gyrus and the left inferior parietal gyrus were significantly associated with aphasia severity at T3. The ROI-analysis did not yield any significant regions of interest to explain the total variance of the patients’ change in scores on the aphasia test from T1 to T3.Conclusion Lesions within the postcentral gyrus and the inferior parietal gyrus are associated with aphasia severity at T3. Lesion size in the acute stages of stroke is associated with aphasia severity at T1 and T2, but not T3. However, neither initial aphasia severity nor stroke severity was associated with aphasia severity at T3. Aphasia severity in T2 is however strongly associated with aphasia severity in T3.

INTRODUCTION:Brain age, the estimation of a person's age from magnetic resonance imaging (MRI) parameters, has been used as a general indicator of health. The marker requires however further validation for application in clinical contexts. Here, we show how brain age predictions perform for the same individual at various time points and validate our findings with age-matched healthy controls. METHODS:We used densely sampled T1-weighted MRI data from four individuals (from two densely sampled datasets) to observe how brain age corresponds to age and is influenced by acquisition and quality parameters. For validation, we used two cross-sectional datasets. Brain age was predicted by a pretrained deep learning model. RESULTS:We found small within-subject correlations between age and brain age. We also found evidence for the influence of field strength on brain age which replicated in the cross-sectional validation data and inconclusive effects of scan quality. CONCLUSION:The absence of maturation effects for the age range in the presented sample, brain age model bias (including training age distribution and field strength), and model error are potential reasons for small relationships between age and brain age in densely sampled longitudinal data. Clinical applications of brain age models should consider of the possibility of apparent biases caused by variation in the data acquisition process.

The notion of a connection between autism and music is as old as the first reported cases of autism, and music has been used as a therapeutic tool for many decades. Music therapy holds promise as an intervention for individuals with autism, harnessing their strengths in music processing to enhance communication and expression. While previous randomized controlled trials have demonstrated positive outcomes in terms of global improvement and quality of life, their reliance on psychological outcomes restricts our understanding of underlying mechanisms. This paper introduces the protocol for the Music for Autism study, a randomized crossover trial designed to investigate the effects of a 12-week music therapy intervention on a range of psychometric, neuroimaging, and biological outcomes in school-aged children with autism. The protocol builds upon previous research and aims to both replicate and expand upon findings that demonstrated improvements in social communication and functional brain connectivity following a music intervention. The primary objective of this trial is to determine whether music therapy leads to improvements in social communication and functional brain connectivity as compared to play-based therapy. In addition, secondary aims include exploring various relevant psychometric, neuroimaging, and biological outcomes. To achieve these objectives, we will enroll 80 participants aged 6-12 years in this international, assessor-blinded, crossover randomized controlled trial. Each participant will be randomly assigned to receive either music therapy or play-based therapy for a period of 12 weeks, followed by a 12-week washout period, after which they will receive the alternate intervention. Assessments will be conducted four times, before and after each intervention period. The protocol of the Music for Autism trial provides a comprehensive framework for studying the effects of music therapy on a range of multidimensional outcomes in children with autism. The findings from this trial have the potential to contribute to the development of evidence-based interventions that leverage strengths in music processing to address the complex challenges faced by individuals with autism.Clinical Trial Registration: Clinicaltrials.gov identifier NCT04936048.

Populational brain imaging methods based on group averages provide valuable insights into the general functions of the brain. However, they often overlook the inherent inter- and intra-subject variability, limiting our understanding of individual differences. To address this limitation, researchers have turned to big datasets and deep brain imaging datasets. Big datasets enable the exploration of inter-subject variations, while deep brain imaging datasets, involving repeated scanning of multiple subjects over time, offer detailed insights into intra-subject variability. Despite the availability of numerous big datasets, the number of deep brain imaging datasets remains limited. In this article, we present a deep brain imaging dataset derived from the Bergen Breakfast Scanning Club (BBSC) project. The dataset comprises data collected from three subjects who underwent repeated scanning over the course of approximately one year. Specifically, three types of data chunks were collected: behavioral data, functional brain data, and structural brain data. Functional brain images, encompassing magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI), along with their anatomical reference T1-weighted brain images, were collected twice a week during the data collection period. In total, 38, 40, and 25 sessions of functional data were acquired for subjects 1, 2, and 3, respectively. On the other hand, structural brain images, including T2-weighted brain images, diffusion-weighted images (DWI), and fluid-attenuated inversion recovery (FLAIR) images, were obtained once a month. A total of 10, 9, and 6 sessions were collected for subjects 1, 2, and 3, respectively. The primary objective of this article is to provide a comprehensive description of the data acquisition protocol employed in the BBSC project, as well as detailed insights into the preprocessing steps applied to the acquired data.