Differences In Brain Connectivity Research Articles

“Do You Know Where the Dragons Are?” - Introducing a Novel Enactive Framework to Map the Wide Unknown of Social Spaces With Neurodivergent Young People

Experiences of being are fundamentally different for neurodivergent young people. Differences in brain connectivity and function conferred by neurodivergence give rise to differences in construal processes underlying intersubjective engagement and shared meaning. Normative therapeutic and educational interventions refer to ‘social communication disorders’, ‘cognitive inflexibility’ and ‘social anxiety’. Peers call them ‘weird’. Parents struggle with guilt, exasperation and despair. The world demands social conformity. “Toby” (11yrs) requested a map and sword to slay the fearsome dragons lurking in the unknown spaces between himself and others- between here and there; intention and action; words and meaning; friend and foe. This paper describes a contextualizing model in a novel systematized approach to meeting the social engagement challenges of neurodivergent young people, devised in collaboration with those young people as Experts by Experience. The approach was formulated on the principle that social competence in neurodivergence should be shaped around self- discovery of authentic modes of being and relating, rather than imposed normative criteria. The 12 Social Spaces model integrates theoretical and clinical principles of Personal Construct Psychology, Enactivism, play theory, neurocognition and social competence, to provide a contextualizing framework of twelve interactional spaces to scaffold social cognition during evolving play between neurodivergent young people.

Resting-state Functional Connectivity of the Motor and Cognitive Areas is Preserved in Masters Athletes

Aging is characterized by a decline in physical and cognitive functions, often resulting in decreased quality of life. Physical activity has been suggested to potentially slow down various aspects of the aging process, a theory that has been supported by studies of Masters Athletes (MA). For example, MA usually have better cognitive and physical functions than age-matched sedentary and healthy older adults (OA), making them a valuable model to gain insights into mechanisms that promote physical and cognitive function with aging. The purpose of this study was to identify differences in resting-state functional connectivity (rs-FC) of motor and cognitive regions between MA and OA and determine if these differences in the resting brain are associated with differences in cognitive and physical performance between groups. Fifteen MA (9 males) and 12 age-matched OA (six males) were included. rs-FC images were compared to identify significant between-groups differences in brain connectivity. There was higher connectivity between the cognitive and motor networks for the OA group, whereas the MA group had stronger connectivity between different regions within the same network, both for the cognitive and the motor networks. These results are in line with the literature suggesting that aging reduces the segregation between functional networks and causes regions within the same network to be less strongly connected. High-level physical activity practiced by the MA most likely contributes to attenuating aging-related changes in brain functional connectivity, preserving clearer boundaries between different functional networks, which may ultimately favor maintenance of efficient cognitive and sensorimotor processing.

Functional Brain Connectivity Differences between Aphasic and Neurotypical Brains

Aphasia is a language disorder that can arise from brain damage, leading to difficulties in understanding, generating, or using language. Although the precise neural mechanisms are not fully elucidated, it is hypothesized that these disruptions involve altered communication and interaction among brain regions. In this study, functional magnetic resonance imaging (fMRI) was employed to assess functional connectivity in both individuals with aphasia and neurotypical individuals. Functional connectivity is a measure of the way that brain regions communicate and interact with each other. The study participants performed a series of language-processing tasks, while their fMRI data was collected. The study's findings showed that individuals with aphasia had unique functional brain connectivity patterns when compared to neurotypical individuals. These distinctions were most prominent in the left hemisphere, which is conventionally associated with language processing. In particular, individuals with aphasia demonstrated diminished functional connectivity between the language regions in the left hemisphere and other brain regions, including those in the right hemisphere and the frontal lobe. The study's findings suggest that differences in functional brain connectivity may contribute to language deficits in aphasia. The study's findings also hold significant implications for advancing our understanding of the neurological underpinnings of aphasia and the potential for improved diagnostic and therapeutic methods for individuals with this condition.

Diffusion tensor imaging in pediatric patients with dystonia

Background: Childhood-onset dystonia is often progressive and severely impairs a child´s life. The pathophysiology is very heterogeneous and treatment responses vary in patients with dystonia. Factors influencing treatment effects remain to be elucidated. We hypothesize that differences in brain connectivity and fiber coherence contribute to the heterogeneity in treatment response among pediatric patients with inherited and acquired dystonia.Methods: Twenty patients with childhood-onset dystonia were retrospectively recruited including twelve patients with inherited or idiopathic, and eight patients with acquired dystonia (mean age 10 years; 8 female/12 male). Fiber density between the internal part of the globus pallidus and selective target regions, as well as the diffusion measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed and compared between different etiologies.Results: Patients with acquired dystonia presented higher fiber density to the premotor cortex and putamen and lower FA values in the thalamus compared to patients with inherited/idiopathic dystonia. MD in the premotor cortex was higher in patients with acquired dystonia, while it was lower in the thalamus.Conclusion: Diffusion MRI reveals microstructural and network alterations in patients with dystonia of different etiologies.

Differences in Brain Network Topology Based on Alcohol Use History in Adolescents.

Approximately 6 million youth aged 12 to 20 consume alcohol monthly in the United States. The effect of alcohol consumption in adolescence on behavior and cognition is heavily researched; however, little is known about how alcohol consumption in adolescence may alter brain function, leading to long-term developmental detriments. In order to investigate differences in brain connectivity associated with alcohol use in adolescents, brain networks were constructed using resting-state functional magnetic resonance imaging data collected by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) from 698 youth (12-21 years; 117 hazardous drinkers and 581 no/low drinkers). Analyses assessed differences in brain network topology based on alcohol consumption in eight predefined brain networks, as well as in whole-brain connectivity. Within the central executive network (CEN), basal ganglia network (BGN), and sensorimotor network (SMN), no/low drinkers demonstrated stronger and more frequent connections between highly globally efficient nodes, with fewer and weaker connections between highly clustered nodes. Inverse results were observed within the dorsal attention network (DAN), visual network (VN), and frontotemporal network (FTN), with no/low drinkers demonstrating weaker connections between nodes with high efficiency and increased frequency of clustered nodes compared to hazardous drinkers. Cross-sectional results from this study show clear organizational differences between adolescents with no/low or hazardous alcohol use, suggesting that aberrant connectivity in these brain networks is associated with risky drinking behaviors.

Small vessel disease burden and functional brain connectivity in mild cognitive impairment

BackgroundThe role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing. MethodFunctional brain connectivity differences were analyzed between mild cognitive impairment individuals with absent or low (n = 34) and high (n = 34) small vessel disease burden using data from the Parelsnoer Institute, a Dutch multicenter study. Small vessel disease was characterized using an ordinal scale considering: lacunes, microbleeds, perivascular spaces in the basal ganglia, and white matter hyperintensities. Resting state functional MRI data using 3 Tesla scanners was analyzed with group-independent component analysis using the CONN toolbox. ResultsFunctional connectivity between areas of the cerebellum and between the cerebellum and the thalamus and caudate nucleus was higher in the absent or low small vessel disease group compared to the high small vessel disease group. ConclusionThese findings might suggest that functional connectivity of mild cognitive impairment individuals with low or absent small vessel disease burden is more intact than in mild cognitive impairment individuals with high small vessel disease. These brain areas are mainly responsible for motor, attentional and executive functions, domains which in previous studies were found to be mostly associated with small vessel disease markers. Our results support findings on the involvement of the cerebellum in cognitive functioning.

Brain network functional connectivity changes in patients with anterior knee pain: a resting-state fMRI exploratory study

BackgroundThis study investigates the functional brain connectivity in patients with anterior knee pain (AKP). While biomechanical models are frequently employed to investigate AKP, it is important to recognize that pain can manifest even in the absence of structural abnormalities. Leveraging the capabilities of functional magnetic resonance imaging (fMRI), this research aims to investigate the brain mechanisms present in AKP patients.MethodsForty-five female subjects (24 AKP patients, 21 controls) underwent resting-state fMRI and T1-weighted structural MRI. Functional brain connectivity patterns were analyzed, focusing on pain network areas, and the influence of catastrophizing thoughts was evaluated.ResultsComparing patients and controls, several findings emerged. First, patients with AKP exhibited increased correlation between the right supplementary motor area and cerebellum I, as well as decreased correlation between the right insula and the left rostral prefrontal cortex and superior frontal gyrus. Second, in AKP patients with catastrophizing thoughts, there was increased correlation of the left lateral parietal cortex with two regions of the right cerebellum (II and VII) and the right pallidum, and decreased correlation between the left medial frontal gyrus and the right thalamus. Furthermore, the correlation between these regions showed promising results for discriminating AKP patients from controls, achieving a cross-validation accuracy of 80.5%.ConclusionsResting-state fMRI revealed correlation differences in AKP patients compared to controls and based on catastrophizing thoughts levels. These findings shed light on neural correlates of chronic pain in AKP, suggesting that functional brain connectivity alterations may be linked to pain experience in this population.Relevance statementEtiopathogenesis of pain in anterior knee pain patients might not be limited to the knee, but also to underlying alterations in the central nervous system: cortical changes might lead a perpetuation of pain.Key points• Anterior knee pain patients exhibit distinct functional brain connectivity compared to controls, and among catastrophizing subgroups.• Resting-state fMRI reveals potential for discriminating anterior knee pain patients with 80.5% accuracy.• Functional brain connectivity differences improve understanding of pain pathogenesis and objective anterior knee pain identification.Graphical

Predicting an individual's cerebellar activity from functional connectivity fingerprints

The cerebellum is gaining scientific attention as a key neural substrate of cognitive function; however, individual differences in the cerebellar organization have not yet been well studied. Individual differences in functional brain organization can be closely tied to individual differences in brain connectivity. ‘Connectome Fingerprinting’ is a modeling approach that predicts an individual's brain activity from their connectome. Here, we extend ‘Connectome Fingerprinting’ (CF) to the cerebellum. We examined functional MRI data from 160 subjects (98 females) of the Human Connectome Project young adult dataset. For each of seven cognitive task paradigms, we constructed CF models from task activation maps and resting-state cortico-cerebellar functional connectomes, using a set of training subjects. For each model, we then predicted task activation in novel individual subjects, using their resting-state functional connectomes. In each cognitive paradigm, the CF models predicted individual subject cerebellar activity patterns with significantly greater precision than did predictions from the group average task activation. Examination of the CF models revealed that the cortico-cerebellar connections that carried the most information were those made with the non-motor portions of the cerebral cortex. These results demonstrate that the fine-scale functional connectivity between the cerebral cortex and cerebellum carries important information about individual differences in cerebellar functional organization. Additionally, CF modeling may be useful in the examination of patients with cerebellar dysfunction, since model predictions require only resting-state fMRI data which is more easily obtained than task fMRI.

Sex-dependent differences in connectivity patterns are related to episodic memory recall.

Previous studies have shown that females typically outperform males on episodic memory tasks. In this study, we investigated if (1) there are differences between males and females in their connectome characteristics, (2) if these connectivity patterns are associated with memory performance, and (3) if these brain connectome characteristics contribute to the differences in episodic memory performance between sexes. In a sample of 655 healthy young subjects (n = 391 females; n = 264 males), we derived brain network characteristics from diffusion-weighted imaging (DWI) data using models of crossing fibers within each voxel of the brain and probabilistic tractography (graph strength, shortest path length, global efficiency, and weighted transitivity). Group differences were analysed with linear models and mediation analyses were used to explore how connectivity patterns might relate to sex-dependent differences in memory performance. Our results show significant sex-dependent differences in weighted transitivity (d = 0.42), with males showing higher values. Further, we observed a negative association between weighted transitivity and memory performance (r = -0.12). Finally, these distinct connectome characteristics partially mediated the observed differences in memory performance (effect size of the indirect effect r = 0.02). Our findings indicate a higher interconnectedness in females compared to males. Additionally, we demonstrate that the sex-dependent differences in episodic memory performance can be partially explained by the differences in this connectome measure. These results further underscore the importance of sex-dependent differences in brain connectivity and their impact on cognitive function.

Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis.

Changes in brain connectivity occur in patients with multiple sclerosis (MS), even in patients under disease-modifying therapies. Using magnetic resonance imaging (MRI) to asses patients treated with disease-modifying therapies, such as natalizumab, can elucidate the mechanisms involved in clinical deterioration in MS. To evaluate differences in resting-state functional connectivity among MS patients treated with natalizumab, MS patients not treated with natalizumab, and controls. Single-center retrospective cross-sectional study. Twenty-three MS patients being treated with natalizumab were retrospectively compared with 23 MS patients who were naïve for natalizumab, and were using first-line medications (interferon-β and/or glatiramer acetate), and 17 gender- and age-matched control subjects. The MS patient groups were also matched for time since diagnosis and hyperintense lesion volume on FLAIR. All participants underwent brain MRI using a 3Tesla scanner. Independent component analysis and dual regression were used to identify resting-state functional connectivity using the FMRIB Software Library. In comparison to controls, the MS patients treated with natalizumab presented decreased connectivity in the left orbitofrontal cortex, in the anterior cingulate and orbitofrontal cortex network. The patients not treated with natalizumab presented increased connectivity in the secondary visual, sensorimotor, and ventral attention networks in comparison to controls.Compared to patients treated with natalizumab, the patients not using natalizumab presented increased connectivity in the left Heschl's gyrus and in the right superior frontal gyrus in the ventral attention network. Differences in brain connectivity between MS patients not treated with natalizumab, healthy controls, and patients treated with natalizumab may be secondary to suboptimal neuronal compensation due to prior less efficient treatments, or due to a compensation in response to maladaptive plasticity.

Connective differences between patients with depression with and without ASD: A case-control study.

Researchers find it difficult to distinguish between depression with ASD (Depress-wASD) and without ASD (Depression) in adult patients. We aimed to clarify the differences in brain connectivity between patients with depression with ASD and without ASD. From April 2017 to February 2019, 22 patients with suspected depression were admitted to the hospital for diagnosis or follow-up and met the inclusion criteria. The diagnosis was determined according to the Diagnostic and Statistical Manual of Mental Disorders-5 by skilled psychiatrists. The Hamilton Depression Rating Scale (HAM-D), Young Mania Raging Scale (YMRS), Mini-International Neuropsychiatric Interview, Parent-interview ASD Rating Scale-Text Revision (PARS-TR), and Autism-Spectrum Quotient-Japanese version (AQ-J) were used to assess the patients' background and help with diagnosis. Resting-state functional magnetic resonance imaging (rs-fMRI) was performed using the 3-T-MRI system. rs-fMRI was processed using the CONN functional connectivity toolbox. Voxel-based morphometry was performed using structural images. No significant difference was observed between the Depress-wASD and Depression groups using the HAM-D, YMRS, AQ-J, Intelligence Quotient (IQ), and verbal IQ results. rs-fMRI for the Depress-wASD group indicated a positive connection between the salience network (SN) and right supramarginal gyrus (SMG) and a negative connection between the SN and hippocampus and para-hippocampus than that for the Depression group. No significant structural differences were observed between the groups. We identified differences in the SN involving the SMG and hippocampal regions between the Depress-wASD and Depression groups.

Sex differences in cognition and structural covariance-based morphometric connectivity: evidence from 28,000+ UK Biobank participants.

There is robust evidence for sex differences in domain-specific cognition, where females typically show an advantage for verbal memory, whereas males tend to perform better in spatial memory. Sex differences in brain connectivity are well documented and may provide insight into these differences. In this study, we examined sex differences in cognition and structural covariance, as an index of morphometric connectivity, of a large healthy sample (n = 28,821) from the UK Biobank. Using T1-weighted magnetic resonance imaging scans and regional cortical thickness values, we applied jackknife bias estimation and graph theory to obtain subject-specific measures of structural covariance, hypothesizing that sex-related differences in brain network global efficiency, or overall covariance, would underlie cognitive differences. As predicted, females demonstrated better verbal memory and males showed a spatial memory advantage. Females also demonstrated faster processing speed, with no observed sex difference in executive functioning. Males showed higher global efficiency, as well as higher regional covariance (nodal strengths) in both hemispheres relative to females. Furthermore, higher global efficiency in males mediated sex differences in verbal memory and processing speed. Findings contribute to an improved understanding of how biological sex and differences in cognition are related to morphometric connectivity as derived from graph-theoretic methods.

The influence of sex steroid treatment on insular connectivity in gender dysphoria

BackgroundSex-specific differences in brain connectivity were found in various neuroimaging studies, though little is known about sex steroid effects on insular functioning. Based on well-characterized sex differences in emotion regulation, interoception and higher-level cognition, gender-dysphoric individuals receiving gender-affirming hormone therapy represent an interesting cohort to investigate how sex hormones might influence insular connectivity and related brain functions. MethodsTo analyze the potential effect of sex steroids on insular connectivity at rest, 11 transgender women, 14 transgender men, 20 cisgender women, and 11 cisgender men were recruited. All participants underwent two magnetic resonance imaging sessions involving resting-state acquisitions separated by a median time period of 4.5 months and also completed the Bermond-Vorst alexithymia questionnaire at the initial and final examination. Between scans, transgender subjects received gender-affirming hormone therapy. ResultsA seed based functional connectivity analysis revealed a significant 2-way interaction effect of group-by-time between right insula, cingulum, left middle frontal gyrus and left angular gyrus. Post-hoc tests demonstrated an increase in connectivity for transgender women when compared to cisgender men. Furthermore, spectral dynamic causal modelling showed reduced effective connectivity from the posterior cingulum and left angular gyrus to the left middle frontal gyrus as well as from the right insula to the left middle frontal gyrus. Alexithymia changes were found after gender-affirming hormone therapy for transgender women in both fantasizing and identifying. ConclusionThese findings suggest a considerable influence of estrogen administration and androgen suppression on brain networks implicated in interoception, own-body perception and higher-level cognition.

Precision functional MRI mapping reveals distinct connectivity patterns for depression associated with traumatic brain injury.

Depression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to conventional treatments. Brain connectivity differences between the dorsal attention network (DAN), default mode network (DMN), and subgenual cingulate have been implicated in TBI and MDD. To characterize these distinctions, we applied precision functional mapping of brain network connectivity to resting-state functional magnetic resonance imaging data from five published patient cohorts, four discovery cohorts (n = 93), and one replication cohort (n = 180). We identified a distinct brain connectivity profile in TBI-associated depression that was independent of TBI, MDD, posttraumatic stress disorder (PTSD), depression severity, and cohort. TBI-associated depression was independently associated with decreased DAN-subgenual cingulate connectivity, increased DAN-DMN connectivity, and the combined effect of both. This effect was stronger when using precision functional mapping relative to group-level network maps. Our results support the possibility of a physiologically distinct "TBI affective syndrome," which may benefit from individualized neuromodulation approaches to target its distinct neural circuitry.

Differences in Intrinsic Gray Matter Connectivity and Their Genomic Underpinnings in Autism Spectrum Disorder

BackgroundAutism is a heterogeneous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differences in intrinsic (i.e., gray matter) connections in autism. Intrinsic connections may be assessed in vivo via so-called intrinsic global and local wiring costs. MethodsHere, we examined intrinsic global and local wiring costs in the brain of 359 individuals with autism and 279 healthy control participants ages 6 to 30 years from the EU-AIMS LEAP (Longitudinal European Autism Project). FreeSurfer was used to derive surface mesh representations to compute the estimated length of connections required to wire the brain within the gray matter. Vertexwise between-group differences were assessed using a general linear model. A gene expression decoding analysis based on the Allen Human Brain Atlas was performed to link neuroanatomical differences to putative underpinnings. ResultsGroup differences in global and local wiring costs were predominantly observed in medial and lateral prefrontal brain regions, in inferior temporal regions, and at the left temporoparietal junction. The resulting neuroanatomical patterns were enriched for genes that had been previously implicated in the etiology of autism at genetic and transcriptomic levels. ConclusionsBased on intrinsic gray matter connectivity, the current study investigated the complex neuroanatomy of autism and linked between-group differences to putative genomic and/or molecular mechanisms to parse the heterogeneity of autism and provide targets for future subgrouping approaches.

Task-based attentional and default mode connectivity associated with science and math anxiety profiles among university physics students

PurposeAttentional control theory (ACT) posits that elevated anxiety increases the probability of re-allocating cognitive resources needed to complete a task to processing anxiety-related stimuli. This process impairs processing efficiency and can lead to reduced performance effectiveness. Science, technology, engineering, and math (STEM) students frequently experience anxiety about their coursework, which can interfere with learning and performance and negatively impact student retention and graduation rates. The objective of this study was to extend the ACT framework to investigate the neurobiological associations between science and math anxiety and cognitive performance among 123 physics undergraduate students. ProceduresLatent profile analysis (LPA) identified four profiles of science and math anxiety among STEM students, including two profiles that represented the majority of the sample (Low Science and Math Anxiety; 59.3% and High Math Anxiety; 21.9%) and two additional profiles that were not well represented (High Science and Math Anxiety; 6.5% and High Science Anxiety; 4.1%). Students underwent a functional magnetic resonance imaging (fMRI) session in which they performed two tasks involving physics cognition: the Force Concept Inventory (FCI) task and the Physics Knowledge (PK) task. FindingsNo significant differences were observed in FCI or PK task performance between High Math Anxiety and Low Science and Math Anxiety students. During the three phases of the FCI task, we found no significant brain connectivity differences during scenario and question presentation, yet we observed significant differences during answer selection within and between the dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN). Further, we found significant group differences during the PK task were limited to the DAN, including DAN-VAN and within-DAN connectivity. ConclusionsThese results highlight the different cognitive processes required for physics conceptual reasoning compared to physics knowledge retrieval, provide new insight into the underlying brain dynamics associated with anxiety and physics cognition, and confirm the relevance of ACT theory for science and math anxiety.

N°247 – Resting-state brain connectivity differences between epileptic and non-epileptic first events

N°247 – Resting-state brain connectivity differences between epileptic and non-epileptic first events

Enhancing the network specific individual characteristics in rs‐fMRI functional connectivity by dictionary learning

Most fMRI inferences are based on analyzing the scans of a cohort. Thus, the individual variability of a subject is often overlooked in these studies. Recently, there has been a growing interest in individual differences in brain connectivity also known as individual connectome. Various studies have demonstrated the individual specific component of functional connectivity (FC), which has enormous potential to identify participants across consecutive testing sessions. Many machine learning and dictionary learning-based approaches have been used to extract these subject-specific components either from the blood oxygen level dependent (BOLD) signal or from the FC. In addition, several studies have reported that some resting-state networks have more individual-specific information than others. This study compares four different dictionary-learning algorithms that compute the individual variability from the network-specific FC computed from resting-state functional Magnetic Resonance Imaging (rs-fMRI) data having 10 scans per subject. The study also compares the effect of two FC normalization techniques, namely, Fisher Z normalization and degree normalization on the extracted subject-specific components. To quantitatively evaluate the extracted subject-specific component, a metric named is proposed, and it is used in combination with the existing differential identifiability metric. It is based on the hypothesis that the subject-specific FC vectors should be similar within the same subject and different across different subjects. Results indicate that Fisher Z transformed subject-specific fronto-parietal and default mode network extracted using Common Orthogonal Basis Extraction (COBE) dictionary learning have the best features to identify a participant.

Measures of Brain Connectivity and Cognition by Sex in US Children

The neurobiological underpinnings underlying sex differences in cognition during adolescence are largely unknown. To examine sex differences in brain circuitry and their association with cognitive performance in US children. This cross-sectional study analyzed behavioral and imaging data from 9- to 11-year-old children from the Adolescent Brain Cognitive Development (ABCD) study between August 2017 and November 2018. The ABCD study is an open-science, multisite study following up more than 11 800 youths into early adulthood for 10 years with annual laboratory-based assessments and biennial magnetic resonance imaging (MRI). The selection of ABCD study children for the current analysis was based on the availability of functional and structural MRI data sets in ABCD Brain Imaging Data Structure Community Collection format. Five hundred and sixty participants who had excessive level of head motion (>50% of time points with framewise displacement >0.5 mm) during resting-state functional MRI were excluded from the analyses. Data were analyzed between January and August 2022. The main outcomes were the sex differences in (A) global functional connectivity density at rest and (B) mean water diffusivity (MD) and (C) the correlation of these metrics with total cognitive scores. A total of 8961 children (4604 boys and 4357 girls; mean [SD] age, 9.92 [0.62] years) were included in this analysis. Girls had higher functional connectivity density in default mode network hubs than boys, predominantly in the posterior cingulate cortex (Cohen d = -0.36), and lower MD and transverse diffusivity, predominantly in the superior corticostriatal white matter bundle (Cohen d = 0.3). Age-corrected fluid and total composite scores were higher for girls than for boys (Cohen d = -0.08 [fluid] and -0.04 [total]; P = 2.7 × 10-5). Although total mean (SD) brain volume (1260 [104] mL in boys and 1160 [95] mL in girls; t = 50; Cohen d = 1.0; df = 8738) and the proportion of white matter (d = 0.4) were larger for boys than for girls, the proportion of gray matter was larger for girls than for boys (d = -0.3; P = 2.2 × 10-16). The findings of this cross-sectional study on sex differences in brain connectivity and cognition are relevant to the future creation of brain developmental trajectory charts to monitor for deviations associated with impairments in cognition or behavior, including those due to psychiatric or neurological disorders. They could also serve as a framework for studies investigating the differential contribution of biological vs social or cultural factors in the neurodevelopmental trajectories of girls and boys.

Sex differences in the neural underpinnings of unimanual and bimanual control in adults.

While many of the movements we make throughout our day involve just one upper limb, most daily movements require a certain degree of coordination between both upper limbs. Historically, sex differences in eye-hand coordination have been observed. As well, there are demonstrated sex-specific differences in hemisphere symmetry, interhemispheric connectivity, and motor cortex organization. While it has been suggested that these anatomical differences may underlie sex-related differences in performance, sex differences in the functional neural correlate underlying bimanual performance have not been explicitly investigated. In the current study we tested the hypothesis that the functional connectivity underlying bimanual movement control differed depending on the sex of an individual. Participants underwent MRI scanning to acquire anatomical and functional brain images. During the functional runs, participants performed unimanual and bimanual coordination tasks using two button boxes. The tasks included pressing the buttons in time to an auditory cue with either their left or their right hand individually (unimanual), or with both hands simultaneously (bimanual). The bimanual task was further divided into either an in-phase (mirror/symmetrical) or anti-phase (parallel/asymmetrical) condition. Participants were provided with extensive training to ensure task comprehension, and performance error rates were found to be equivalent between men and women. A generalized psychophysiological interaction (gPPI) analysis was implemented to examine how functional connectivity in each condition was modulated by sex. In support of our hypothesis, women and men demonstrated differences in the neural correlates underlying unimanual and bimanual movements. In line with previous literature, functional connectivity patterns showed sex-related differences for right- vs left-hand movements. Sex-specific functional connectivity during bimanual movements was not a sum of the functional connectivity underlying right- and left-hand unimanual movements. Further, women generally showed greater interhemispheric functional connectivity across all conditions compared to men and had greater connectivity between task-related cortical areas, while men had greater connectivity involving the cerebellum. Sex differences in brain connectivity were associated with both unimanual and bimanual movement control. Not only do these findings provide novel insight into the fundamentals of how the brain controls bimanual movements in both women and men, they also present potential clinical implications on how bimanual movement training used in rehabilitation can best be tailored to the needs of individuals.