Changes In Brain Networks Research Articles

Multi-dimensional persistent feature analysis identifies connectivity patterns of resting-state brain networks in Alzheimer’s disease

Objective. The characterization of functional brain network is crucial to understanding the neural mechanisms associated with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Some studies have shown that graph theoretical analysis could reveal changes of the disease-related brain networks by thresholding edge weights. But the choice of threshold depends on ambiguous cognitive conditions, which leads to the lack of interpretability. Recently, persistent homology (PH) was proposed to record the persistence of topological features of networks across every possible thresholds, reporting a higher sensitivity than graph theoretical features in detecting network-level biomarkers of AD. However, most research on PH focused on zero-dimensional features (persistence of connected components) reflecting the intrinsic topology of the brain network, rather than one-dimensional features (persistence of cycles) with an interesting neurobiological communication pattern. Our aim is to explore the multi-dimensional persistent features of brain networks in the AD and MCI patients, and further to capture valuable brain connectivity patterns. Approach. We characterized the change rate of the connected component numbers across graph filtration using the functional derivative curves, and examined the persistence landscapes that vectorize the persistence of cycle structures. After that, the multi-dimensional persistent features were validated in disease identification using a K-nearest neighbor algorithm. Furthermore, a connectivity pattern mining framework was designed to capture the disease-specific brain structures. Main results. We found that the multi-dimensional persistent features can identify statistical group differences, quantify subject-level distances, and yield disease-specific connectivity patterns. Relatively high classification accuracies were received when compared with graph theoretical features. Significance. This work represents a conceptual bridge linking complex brain network analysis and computational topology. Our results can be beneficial for providing a complementary objective opinion to the clinical diagnosis of neurodegenerative diseases.

Specific Brain Reorganization Underlying Superior Upper Limb Motor Function After Spinal Cord Injury: A Multimodal MRI Study

Background We recently discovered that individuals with complete spinal cord injury (SCI) have a higher grip force control ability in their intact upper limbs than able-bodied subjects. However, the neural basis for this phenomenon is unknown. Objective This study aimed to investigate the neural basis of the higher grip force control in the brains of individuals with SCI using multimodal magnetic resonance imaging (MRI). Methods Eight SCI subjects and 10 able-bodied subjects performed hand grip force control tasks at 10%, 20%, and 30% of their maximal voluntary contraction during functional MRI (fMRI). Resting-state fMRI and T1-weighted structural images were obtained to investigate changes in brain networks and structures after SCI. Results SCI subjects showed higher grip force steadiness than able-bodied subjects (P < .05, corrected), smaller activation in the primary motor cortex (P < .05, corrected), and deactivation of the visual cortex (P < .001, uncorrected). Furthermore, SCI subjects had stronger functional connectivity between the superior parietal lobule and the left primary motor cortex (P < .001, uncorrected), as well as larger gray matter volume in the bilateral superior parietal lobule (P < .001, uncorrected). Conclusions The structural and functional reorganization observed in the superior parietal lobule of SCI subjects may represent the neural basis underlying the observed higher grip force control, and is likely responsible for the smaller activation in the primary motor cortex observed in these individuals. These findings could have applications in the fields of neurorehabilitation for improvement of intact limb functions after SCI.

Neural changes in youth at high risk for bipolar disorder undergoing family-focused therapy or psychoeducation.

Patients with mood disorders may benefit from psychosocial interventions through changes in brain networks underlying emotion processing. In this study, we used functional magnetic resonance imaging (fMRI) to investigate treatment-related changes in emotion processing networks in youth at familial high risk for bipolar disorder (BD). Youth, ages 9-17, were randomly assigned to family-focused therapy for high-risk youth (FFT-HR) or an active comparison treatment, Enhanced Care (EC). Before and after these 4-month treatments, participants underwent fMRI while viewing happy, fearful, and calm facial expressions. Twenty youth in FFT-HR and 20 in EC were included in analyses of pre- to post-treatment changes in activation across the whole brain. Significant clusters were assessed for correlation with mood symptom improvement. In the dorsolateral prefrontal cortex (DLPFC), activation increased from pre- to post-treatment in the FFT-HR group and decreased in the EC group. Insula activation decreased in the FFT-HR group and did not change in the EC group. Across both treatments, decreasing activation in the hippocampus and amygdala was correlated with pre- to post-treatment improvement in hypomania, while increasing activation in the DLPFC was correlated with pre- to post-treatment improvement in depression. Psychosocial treatment addresses abnormalities in emotion regulation networks in youth at high risk for BD. Increased prefrontal cortex activation suggests enhanced emotion regulation from pre- to post-treatment with FFT-HR. Improvements in family interactions may facilitate the development of prefrontal resources that provide protection against future mood episodes.

Musical Expertise Shapes Functional and Structural Brain Networks Independent of Absolute Pitch Ability.

Professional musicians are a popular model for investigating experience-dependent plasticity in human large-scale brain networks. A minority of musicians possess absolute pitch, the ability to name a tone without reference. The study of absolute pitch musicians provides insights into how a very specific talent is reflected in brain networks. Previous studies of the effects of musicianship and absolute pitch on large-scale brain networks have yielded highly heterogeneous findings regarding the localization and direction of the effects. This heterogeneity was likely influenced by small samples and vastly different methodological approaches. Here, we conducted a comprehensive multimodal assessment of effects of musicianship and absolute pitch on intrinsic functional and structural connectivity using a variety of commonly used and state-of-the-art multivariate methods in the largest sample to date (n = 153 female and male human participants; 52 absolute pitch musicians, 51 non-absolute pitch musicians, and 50 non-musicians). Our results show robust effects of musicianship in interhemispheric and intrahemispheric connectivity in both structural and functional networks. Crucially, most of the effects were replicable in both musicians with and without absolute pitch compared with non-musicians. However, we did not find evidence for an effect of absolute pitch on intrinsic functional or structural connectivity in our data: The two musician groups showed strikingly similar networks across all analyses. Our results suggest that long-term musical training is associated with robust changes in large-scale brain networks. The effects of absolute pitch on neural networks might be subtle, requiring very large samples or task-based experiments to be detected.SIGNIFICANCE STATEMENT A question that has fascinated neuroscientists, psychologists, and musicologists for a long time is how musicianship and absolute pitch, the rare talent to name a tone without reference, are reflected in large-scale networks of the human brain. Much is still unknown as previous studies have reported widely inconsistent results based on small samples. Here, we investigate the largest sample of musicians and non-musicians to date (n = 153) using a multitude of established and novel analysis methods. Results provide evidence for robust effects of musicianship on functional and structural networks that were replicable in two separate groups of musicians and independent of absolute pitch ability.

Changes of Structural Brain Network Following Repetitive Transcranial Magnetic Stimulation in Children With Bilateral Spastic Cerebral Palsy: A Diffusion Tensor Imaging Study.

Introduction: Bilateral spastic cerebral palsy (BSCP) is the most common subtype of cerebral palsy (CP), which is characterized by various motor and cognitive impairments, as well as emotional instability. However, the neural basis of these problems and how repetitive transcranial magnetic stimulation (rTMS) can make potential impacts on the disrupted structural brain network in BSCP remain unclear. This study was aimed to explore the topological characteristics of the structural brain network in BSCP following the treatment of rTMS.Methods: Fourteen children with BSCP underwent 4 weeks of TMS and 15 matched healthy children (HC) were enrolled. Diffusion tensor imaging (DTI) data were acquired from children with bilateral spastic cerebral palsy before treatment (CP1), children with bilateral spastic cerebral palsy following treatment (CP2) and HC. The graph theory analysis was applied to construct the structural brain network. Then nodal clustering coefficient (Ci) and shortest path length (Li) were measured and compared among groups.Results: Brain regions with significant group differences in Ci were located in the left precental gyrus, middle frontal gyrus, calcarine fissure, cuneus, lingual gyrus, postcentral gyrus, inferior parietal gyri, angular gyrus, precuneus, paracentral lobule and the right inferior frontal gyrus (triangular part), insula, posterior cingulate gyrus, precuneus, paracentral lobule, pallidum. In addition, significant differences were detected in the Li of the left precental gyrus, lingual gyrus, superior occipital gyrus, middle occipital gyrus, superior parietal gyrus, precuneus and the right median cingulate gyrus, posterior cingulate gyrus, hippocampus, putamen, thalamus. Post hoc t-test revealed that the CP2 group exhibited increased Ci in the right inferior frontal gyrus, pallidum and decreased Li in the right putamen, thalamus when compared with the CP1 group.Conclusion: Significant differences of node-level metrics were found in various brain regions of BSCP, which indicated a disruption in structural brain connectivity in BSCP. The alterations of the structural brain network provided a basis for understanding of the pathophysiological mechanisms of motor and cognitive impairments in BSCP. Moreover, the right inferior frontal gyrus, putamen, thalamus could potentially be biomarkers for predicting the efficacy of TMS.

A Graph Gaussian Embedding Method for Predicting Alzheimer's Disease Progression With MEG Brain Networks.

Characterizing the subtle changes of functional brain networks associated with the pathological cascade of Alzheimer's disease (AD) is important for early diagnosis and prediction of disease progression prior to clinical symptoms. We developed a new deep learning method, termed multiple graph Gaussian embedding model (MG2G), which can learn highly informative network features by mapping high-dimensional resting-state brain networks into a low-dimensional latent space. These latent distribution-based embeddings enable a quantitative characterization of subtle and heterogeneous brain connectivity patterns at different regions, and can be used as input to traditional classifiers for various downstream graph analytic tasks, such as AD early stage prediction, and statistical evaluation of between-group significant alterations across brain regions. We used MG2G to detect the intrinsic latent dimensionality of MEG brain networks, predict the progression of patients with mild cognitive impairment (MCI) to AD, and identify brain regions with network alterations related to MCI.

Post-Stroke Reorganization of Transient Brain Activity Characterizes Deficits and Recovery of Cognitive Functions

Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to assess spatial and temporal changes of brain networks after stroke. While large-scale spatial patterns of these networks were preserved after stroke, their durations were altered, with stroke subjects exhibiting a varied pattern of longer and shorter network activations compared to healthy individuals. These temporal alterations were associated with white matter damage and were behavior-specific. Specifically, restoration of healthy brain dynamics paralleled recovery of cognitive functions, but was not significantly correlated to motor recovery. These findings underscore the critical importance of network temporal properties in dissecting the pathophysiology of brain changes after stroke, thus shedding new light on the clinical potential of time-resolved methods for fMRI analysis.

Phase/Amplitude Synchronization of Brain Signals During Motor Imagery BCI Tasks.

In the last decade, functional connectivity (FC) has been increasingly adopted based on its ability to capture statistical dependencies between multivariate brain signals. However, the role of FC in the context of brain-computer interface applications is still poorly understood. To address this gap in knowledge, we considered a group of 20 healthy subjects during an EEG-based hand motor imagery (MI) task. We studied two well-established FC estimators, i.e. spectral- and imaginary-coherence, and we investigated how they were modulated by the MI task. We characterized the resulting FC networks by extracting the strength of connectivity of each EEG sensor and we compared the discriminant power with respect to standard power spectrum features. At the group level, results showed that while spectral-coherence based network features were increasing in the sensorimotor areas, those based on imaginary-coherence were significantly decreasing. We demonstrated that this opposite, but complementary, behavior was respectively determined by the increase in amplitude and phase synchronization between the brain signals. At the individual level, we eventually assessed the potential of these network connectivity features in a simple off-line classification scenario. Taken together, our results provide fresh insights into the oscillatory mechanisms subserving brain network changes during MI and offer new perspectives to improve BCI performance.

Dorsal attention network centrality increases during recovery from acute stress exposure

Stress is a major risk factor for the development of almost all psychiatric disorders. In addition to the acute stress response, an efficient recovery in the aftermath of stress is important for optimal resilience. Increased stress vulnerability across psychiatric disorders may therefore be related to altered trajectories during the recovery phase following stress. Such recovery trajectories can be quantified by changes in functional brain networks. This study therefore evaluated longitudinal functional network changes related to stress in healthy individuals (N = 80), individuals at risk for psychiatric disorders (healthy siblings of schizophrenia patients) (N = 39), and euthymic bipolar I disorder (BD) patients (N = 36). Network changes were evaluated before and at 20 and 90 min after onset of an experimental acute stress task (Trier Social Stress Test) or a control condition. Whole-brain functional networks were analyzed using eigenvector centrality as a proxy for network importance, centrality change over time was related to the acute stress response and recovery for each group. In healthy individuals, centrality of the dorsal attention network (DAN; p = 0.007) changed over time in relation to stress. More specifically, DAN centrality increased during the recovery phase after acute stress exposure (p = 0.020), while no DAN centrality change was observed during the initial stress response (p = 0.626). Such increasing DAN centrality during stress recovery was also found in healthy siblings (p = 0.016), but not in BD patients (p = 0.554). This study highlights that temporally complex and precise changes in network configuration are vital to understand the response to and recovery from stress.

Altered brain structural connectivity in patients with longstanding gut inflammation is correlated with psychological symptoms and disease duration

ObjectiveWe aimed to identify differences in network properties of white matter microstructure between asymptomatic ulcerative colitis (UC) participants who had a history of chronic gut inflammation, healthy controls (HCs) and a disease control group without gut inflammation (irritable bowel syndrome; IBS). DesignDiffusion weighted imaging was conducted in age and sex-matched participants with UC, IBS, and HCs (N = 74 each), together with measures of gastrointestinal and psychological symptom severity. Using streamline connectivity matrices and graph theory, we aimed to quantify group differences in brain network connectivity. Regions showing group connectivity differences were correlated with measures showing group behavioral and clinical differences. ResultsUC participants exhibited greater centrality in regions of the somatosensory network and default mode network, but lower centrality in the posterior insula and globus pallidus compared to HCs (q < 0.05). Hub analyses revealed compromised hubness of the pallidus in UC and IBS compared to HCs which was replaced by increased hubness of the postcentral sulcus. Surprisingly, few differences in network matrices between UC and IBS were identified. In UC, centrality measures in the secondary somatosensory cortex were associated with depression (q < 0.03), symptom related anxiety (q < 0.04), trait anxiety (q < 0.03), and symptom duration (q < 0.05). ConclusionA history of UC is associated with neuroplastic changes in several brain networks, which are associated with symptoms of depression, trait and symptom-related anxiety, as well as symptom duration. When viewed together with the results from IBS subjects, these findings suggest that chronic gut inflammation as well as abdominal pain have a lasting impact on brain network organization, which may play a role in symptoms reported by UC patients, even when gut inflammation has subsided.

Connectivity changes in major depressive disorder after rTMS: a review of functional and structural connectivity data

Abstract Aims In the search for effective therapeutic strategies for depression, repetitive transcranial magnetic stimulation (rTMS) emerged as a non-invasive, promising treatment. This is because the antidepressant effect of rTMS might be related to neuronal plasticity mechanisms possibly reverting connectivity alterations often observed in depression. Therefore, in this review, we aimed at providing an overview of the findings reported by studies investigating functional and structural connectivity changes after rTMS in depression. Methods A bibliographic search was conducted on PubMed, including studies that used unilateral, excitatory (⩾10 Hz) rTMS treatment targeted on the left dorsolateral prefrontal cortex (DLPFC) in unipolar depressed patients. Results The majority of the results showed significant TMS-induced changes in functional connectivity (FC) between areas important for emotion regulation, including the DLPFC and the subgenual anterior cingulate cortex, and among regions that are part of the major resting-state networks, such as the Default Mode Network, the Salience Networks and the Central Executive Network. Finally, in diffusion tensor imaging studies, it has been reported that rTMS appeared to increase fractional anisotropy in the frontal lobe. Limitations The small sample size, the heterogeneity of the rTMS stimulation parameters, the concomitant use of psychotropic drugs might have limited the generalisability of the results. Conclusions Overall, rTMS treatment induces structural and FC changes in brain regions and networks implicated in the pathogenesis of unipolar depression. However, whether these changes underlie the antidepressant effect of rTMS still needs to be clarified.

Network Analysis of Induced Neural Plasticity Post-Acceptance and Commitment Therapy for Chronic Pain.

Chronic musculoskeletal pain is a costly and prevalent condition that affects the lives of over 50 million individuals in the United States. Chronic pain leads to functional brain changes in those suffering from the condition. Not only does the primary pain network transform as the condition changes from acute to persistent pain, a state of hyper-connectivity also exists between the default mode, frontoparietal, and salience networks. Graph theory analysis has recently been used to investigate treatment-driven brain network changes. For example, current research suggests that Acceptance and Commitment Therapy (ACT) may reduce the chronic pain associated hyper-connectivity between the default mode, frontoparietal, and salience networks, as well as within the salience network. This study extended previous work by examining the associations between the three networks above and a meta-analytically derived pain network. Results indicate decreased connectivity within the pain network (including left putamen, right insula, left insula, and right thalamus) in addition to triple network connectivity changes after the four-week Acceptance and Commitment Therapy intervention.

Seizure Prediction Using Directed Transfer Function and Convolution Neural Network on Intracranial EEG.

Automatic seizure prediction promotes the development of closed-loop treatment system on intractable epilepsy. In this study, by considering the specific information exchange between EEG channels from the perspective of whole brain activities, the convolution neural network (CNN) and the directed transfer function (DTF) were merged to present a novel method for patient-specific seizure prediction. Firstly, the intracranial electroencephalogram (iEEG) signals were segmented and the information flow features of iEEG signals were calculated by using the DTF algorithm. Then, these features were reconstructed as the channel-frequency maps according to channel pairs and the frequency of information flow. Finally, these maps were fed into the CNN model and the outputs were post-processed by the moving average approach to predict the epileptic seizures. By the evaluation of cross-validation method, the proposed algorithm achieved the averaged sensitivity of 90.8%, the averaged false prediction rate of 0.08 per hour. Compared to the random predictor and other existing algorithms tested on the Freiburg EEG dataset, our proposed method achieved better performance for seizure prediction in all patients. These results demonstrated that the proposed algorithm could provide an robust seizure prediction solution by using deep learning to capture the brain network changes of iEEG signals from epileptic patients.

Dynamic Changes of Brain Networks during Working Memory Tasks in Schizophrenia

Electroencephalograph (EEG) signals and graph theory measures have been widely used to characterize the brain functional networks of healthy individuals and patients by calculating the correlations between different electrodes over an entire time series. Although EEG signals have a high temporal resolution and can provide relatively stable results, the process of constructing and analyzing brain functional networks is inevitably complicated by high time complexity. Our goal in this research was to distinguish the brain function networks of schizophrenia patients from those of healthy participants during working memory tasks. Consequently, we utilized a method involving microstates, which are each characterized by a unique topography of electric potentials over an entire channel array, to reduce the dimension of the EEG signals during working memory tasks and then compared and analyzed the brain functional networks using the microstates time series (MTS) and original time series (OTS) of the schizophrenia patients and healthy individuals. We found that the right frontal and parietal-occipital regions neurons of the schizophrenia patients were less active than those of the healthy participants during working memory tasks. Notably, compared with OTS, the time needed to construct the brain functional networks was significantly reduced by using MTS. In conclusion, our results show that, like OTS, MTS can well distinguish the brain functional network of schizophrenia patients from those of healthy individuals during working memory tasks while greatly decreasing time complexity. MTS can thus provide a method for characterizing the original time series for the construction and analysis of EEG brain functional networks.

Effects of Head Motion on the Evaluation of Age-related Brain Network Changes Using Resting State Functional MRI.

Purpose:The estimation of functional connectivity (FC) measures using resting state functional MRI (fMRI) is often affected by head motion during functional imaging scans. Head motion is more common in the elderly than in young participants and could therefore affect the evaluation of age-related changes in brain networks. Thus, this study aimed to investigate the influence of head motion in FC estimation when evaluating age-related changes in brain networks.Methods:This study involved 132 healthy volunteers divided into 3 groups: elderly participants with high motion (OldHM, mean age (±SD) = 69.6 (±5.31), N = 44), elderly participants with low motion (OldLM, mean age (±SD) = 68.7 (±4.59), N = 43), and young adult participants with low motion (YugLM, mean age (±SD) = 27.6 (±5.26), N = 45). Head motion was quantified using the mean of the framewise displacement of resting state fMRI data. After preprocessing all resting state fMRI datasets, several resting state networks (RSNs) were extracted using independent component analysis (ICA). In addition, several network metrics were also calculated using network analysis. These FC measures were then compared among the 3 groups.Results:In ICA, the number of voxels with significant differences in RSNs was higher in YugLM vs. OldLM comparison than in YugLM vs. OldHM. In network analysis, all network metrics showed significant (P < 0.05) differences in comparisons involving low vs. high motion groups (OldHM vs. OldLM and OldHM vs. YugLM). However, there was no significant (P > 0.05) difference in the comparison involving the low motion groups (OldLM vs. YugLM).Conclusion:Our findings showed that head motion during functional imaging could significantly affect the evaluation of age-related brain network changes using resting state fMRI data.

The Structural and Functional Neuroanatomy of Post-Stroke Depression and Executive Dysfunction: A Review of Neuroimaging Findings and Implications for Treatment.

Post-stroke depression and executive dysfunction co-occur and are highly debilitating. Few treatments alleviate both depression and executive dysfunction after stroke. Understanding the brain network changes underlying post-stroke depression with executive dysfunction can inform the development of targeted and efficacious treatment. In this review, we synthesize neuroimaging findings in post-stroke depression and post-stroke executive dysfunction and highlight the network commonalities that may underlie this comorbidity. Structural and functional alterations in the cognitive control network, salience network, and default mode network are associated with depression and executive dysfunction after stroke. Specifically, post-stroke depression and executive dysfunction are both linked to changes in intrinsic functional connectivity within resting state networks, functional over-connectivity between the default mode and salience/cognitive control networks, and reduced cross-hemispheric frontoparietal functional connectivity. Cognitive training and noninvasive brain stimulation targeted at these brain network abnormalities and specific clinical phenotypes may help advance treatment for post-stroke depression with executive dysfunction.

Increased ALFF and functional connectivity of the right striatum in bipolar disorder patients

BackgroundBipolar disorder (BD) is a serious neuropsychiatric disorder characterized by alternating periods of mania, depression, and euthymia. Abnormal spontaneous brain activity within the cortical-striatal neural circuits has been observed in patients with BD. However, whether the abnormality appears in patients with BD while not in a manic mood state is unclear. MethodsThis study collected resting-state fMRI data from 65 patients with BD who were not in a manic mood state and 85 matched healthy controls. First, we examined differences in amplitude of low-frequency fluctuations (ALFF) between the patients with BD and the healthy controls to identify regions that show abnormal local spontaneous activity in the patients. Based on the ALFF results, we conducted seed-based resting-state functional connectivity (rsFC) analysis to identify the changes in brain networks that are centered on the regions showing abnormal local spontaneous activity in the patients. Finally, we repeated these analyses in a sub-sample comprising euthymic BD patients (N = 37) and between the euthymic BD patients and all the other patients who had at least mild depressive symptoms. ResultsBD patients exhibited increased ALFF in the right caudate/putamen and increased rsFC in the right caudate/putamen with the right inferior parietal lobe (cluster-level FWE p < 0.05). Further analyses showed that the euthymic BD patients showed similar abnormalities in ALFF and rsFC maps as found in all patients with BD. And the euthymic BD patients were comparable with all the other patients who had at least mild depressive symptoms in ALFF values. ConclusionsOur results indicated the important role of the right striatum in the baseline brain function of BD patients and suggested that the abnormality of spontaneous brain activity in the cortical-striatal neural circuits may be a trait-like variant in patients with BD. The results deepen our understanding of the neurobiological mechanisms associated with BD etiology.

Indirect Structural Connectivity Identifies Changes in Brain Networks After Stroke.

Background/Purpose: The purpose of this study was (1) to identify changes in structural connectivity after stroke and (2) to relate changes in indirect connectivity to post-stroke impairment. Methods: A novel measure of indirect connectivity was implemented to assess the impact of stroke on brain connectivity. Probabilistic tractography was performed on 13 chronic stroke and 16 control participants to estimate connectivity between gray matter (GM) regions. The Fugl-Meyer assessment of motor impairment was measured for stroke participants. Network measures of direct and indirect connectivity were calculated, and these measures were linearly combined with measures of white matter integrity to predict motor impairment. Results: We found significantly reduced indirect connectivity in the frontal and parietal lobes, ipsilesional subcortical regions, and bilateral cerebellum after stroke. When added to the regression analysis, the volume of GM with reduced indirect connectivity significantly improved the correlation between image parameters and upper extremity motor impairment (R2 = 0.71, p < 0.05). Conclusion: This study provides evidence of changes in indirect connectivity in regions remote from the lesion, particularly in the cerebellum and regions in the fronto-parietal cortices, and these changes correlate with upper extremity motor impairment. These results highlight the value of using measures of indirect connectivity to identify the effect of stroke on brain networks. Impact statement Changes in indirect structural connectivity occur in regions distant from a lesion after stroke, highlighting the impact that stroke has on brain functional networks. Specifically, losses in indirect structural connectivity occur in hubs with high centrality, including the fronto-parietal cortices and cerebellum. These losses in indirect connectivity more accurately reflect motor impairments than measures of direct structural connectivity. As a consequence, indirect structural connectivity appears to be important to recovery after stroke and imaging biomarkers that incorporate indirect structural connectivity might improve prognostication of stroke outcomes.

A Whole-Brain and Cross-Diagnostic Perspective on Functional Brain Network Dysfunction.

A wide variety of mental disorders have been associated with resting-state functional network alterations, which are thought to contribute to the cognitive changes underlying mental illness. These observations appear to support theories postulating large-scale disruptions of brain systems in mental illness. However, existing approaches isolate differences in network organization without putting those differences in a broad, whole-brain perspective. Using a graph distance approach-connectome-wide similarity-we found that whole-brain resting-state functional network organization is highly similar across groups of individuals with and without a variety of mental diseases. This similarity was observed across autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Nonetheless, subtle differences in network graph distance were predictive of diagnosis, suggesting that while functional connectomes differ little across health and disease, those differences are informative. These results suggest a need to reevaluate neurocognitive theories of mental illness, with a role for subtle functional brain network changes in the production of an array of mental diseases. Such small network alterations suggest the possibility that small, well-targeted alterations to brain network organization may provide meaningful improvements for a variety of mental disorders.

Brain Network Modularity Predicts Improvements in Cognitive and Scholastic Performance in Children Involved in a Physical Activity Intervention.

Introduction: Brain network modularity is a principle that quantifies the degree to which functional brain networks are divided into subnetworks. Higher modularity reflects a greater number of within-module connections and fewer connections between modules, and a highly modular brain is often interpreted as a brain that contains highly specialized brain networks with less integration between networks. Recent work in younger and older adults has demonstrated that individual differences in brain network modularity at baseline can predict improvements in performance after cognitive and physical interventions. The use of brain network modularity as a predictor of training outcomes has not yet been examined in children.Method: In the present study, we examined the relationship between baseline brain network modularity and changes (post-intervention performance minus pre-intervention performance) in cognitive and academic performance in 8- to 9-year-old children who participated in an after-school physical activity intervention for 9 months (N = 78) as well as in children in a wait-list control group (N = 72).Results: In children involved in the after-school physical activity intervention, higher modularity of brain networks at baseline predicted greater improvements in cognitive performance for tasks of executive function, cognitive efficiency, and mathematics achievement. There were no associations between baseline brain network modularity and performance changes in the wait-list control group.Discussion: Our study has implications for biomarkers of cognitive plasticity in children. Understanding predictors of cognitive performance and academic progress during child development may facilitate the effectiveness of interventions aimed to improve cognitive and brain health.