Activity flow mapping over probabilistic functional connectivity.

Emerging evidence indicates that activity flow over resting-state network topology allows the prediction of task activations. However, previous studies have mainly adopted static, linear functional connectivity (FC) estimates as activity flow routes. It is unclear whether an intrinsic network topology that captures the dynamic nature of FC can be a better representation of activity flow routes. Moreover, the effects of between- versus within-network connections and tight versus loose (using rest baseline) task contrasts on the prediction of task-evoked activity across brain systems remain largely unknown. In this study, we first propose a probabilistic FC estimation derived from a dynamic framework as a new activity flow route. Subsequently, activity flow mapping was tested using between- and within-network connections separately for each region as well as using a set of tight task contrasts. Our results showed that probabilistic FC routes substantially improved individual-level activity flow prediction. Although it provided better group-level prediction, the multiple regression approach was more dependent on the length of data points at the individual-level prediction. Regardless of FC type, we consistently observed that between-network connections showed a relatively higher prediction performance in higher-order cognitive control than in primary sensorimotor systems. Furthermore, cognitive control systems exhibit a remarkable increase in prediction accuracy with tight task contrasts and a decrease in sensorimotor systems. This work demonstrates that probabilistic FC estimates are promising routes for activity flow mapping and also uncovers divergent influences of connectional topology and task contrasts on activity flow prediction across brain systems with different functional hierarchies.

Pathway-Specific Mediation Effect Between Structure, Function, and Motor Impairment After Subcortical Stroke.

BACKGROUND AND OBJECTIVE: To investigate the pathway-specific correspondence between structural and functional changes resulting from focal subcortical stroke and their causal influence on clinical symptom. METHODS: In this retrospective, cross-sectional study, we mainly focused on patients with unilateral subcortical chronic stroke with moderate-severe motor impairment assessed by Fugl-Meyer Assessment (upper extremity) and healthy controls. All participants underwent both resting-state fMRI and diffusion tensor imaging. To parse the pathway-specific structure-function covariation, we performed association analyses between the fine-grained corticospinal tracts (CSTs) originating from 6 subareas of the sensorimotor cortex and functional connectivity (FC) of the corresponding subarea, along with the refined corpus callosum (CC) sections and interhemispheric FC. A mediation analysis with FC as the mediator was used to further assess the pathway-specific effects of structural damage on motor impairment. RESULTS: Thirty-five patients (mean age 52.7 ± 10.2 years, 27 men) and 43 healthy controls (mean age 56.2 ± 9.3 years, 21 men) were enrolled. Among the 6 CSTs, we identified 9 structurally and functionally covaried pathways, originating from the ipsilesional primary motor area (M1), dorsal premotor area (PMd), and primary somatosensory cortex (p < 0.05, corrected). FC for the bilateral M1, PMd, and ventral premotor cortex covaried with secondary degeneration of the corresponding CC sections (p < 0.05, corrected). Moreover, these covarying structures and functions were significantly correlated with the Fugl-Meyer Assessment (upper extremity) scores (p < 0.05, uncorrected). In particular, FC between the ipsilesional PMd and contralesional cerebellum (ß = -0.141, p < 0.05, CI = [-0.319 to -0.015]) and interhemispheric FC of the PMd (ß = 0.169, p < 0.05, CI = [0.015-0.391]) showed significant mediation effects in the prediction of motor impairment with structural damage of the CST and CC. DISCUSSIONS: This study reveals causal influence of structural and functional pathways on motor impairment after subcortical stroke and provides a promising way to investigate pathway-specific structure-function coupling. Clinically, our findings may offer a circuit-based evidence for the PMd as a critical neuromodulation target in more impaired patients with stroke and also suggest the cerebellum as a potential target.

Partial event coincidence analysis for distinguishing direct and indirect coupling in functional network construction.

Correctly identifying interaction patterns from multivariate time series presents an important step in functional network construction. In this context, the widespread use of bivariate statistical association measures often results in a false identification of links because strong similarity between two time series can also emerge without the presence of a direct interaction due to intermediate mediators or common drivers. In order to properly distinguish such direct and indirect links for the special case of event-like data, we present here a new generalization of event coincidence analysis to a partial version thereof, which is aimed at excluding possible transitive effects of indirect couplings. Using coupled chaotic systems and stochastic processes on two generic coupling topologies (star and chain configuration), we demonstrate that the proposed methodology allows for the correct identification of indirect interactions. Subsequently, we apply our partial event coincidence analysis to multi-channel EEG recordings to investigate possible differences in coordinated alpha band activity among macroscopic brain regions in resting states with eyes open (EO) and closed (EC) conditions. Specifically, we find that direct connections typically correspond to close spatial neighbors while indirect ones often reflect longer-distance connections mediated via other brain regions. In the EC state, connections in the frontal parts of the brain are enhanced as compared to the EO state, while the opposite applies to the posterior regions. In general, our approach leads to a significant reduction in the number of indirect connections and thereby contributes to a better understanding of the alpha band desynchronization phenomenon in the EO state.

Cognitive Dysfunction in Type 2 Diabetes Is Not a One-Way Process: Evidence From a Longitudinal Brain Connectivity Study.

Background: Cognitive dysfunction is an important comorbidity of diabetes characterized by brain functional hypo-connectivity. However, our recent study demonstrated an adaptive hyper-connectivity in young type 2 diabetes with cognitive decrements. This longitudinal study aimed to further explore the changes in functional connectivity and cognitive outcomes after regular glycemic control. Methods: At 18 months after recruitment, participants underwent a second cognitive assessment and magnetic resonance imaging. Three enhanced functional connectivities previously identified at baseline were followed up. Linear mixed-effects models were performed to compare the longitudinal changes of cognition and functional connectivity in patients with type 2 diabetes and non-diabetic controls. A linear regression model was used to investigate the association between changes in functional connectivity and changes in cognitive performance. Results: Improvements in multiple cognitive domains were observed in diabetes; however, the enhanced functional connectivity at baseline decreased significantly. Moreover, the decrease in hippocampal connectivity was correlated with an increase in the accuracy of Stroop task and the decrease in posterior cingulate cortex connectivity was correlated with an increase in Montreal Cognitive Assessment in diabetes. Conclusion: This study suggests diabetes-related cognitive dysfunction is not a one-way process and the early-stage enhancement of brain connectivity was a potential "window period" for cognitive reversal.

Common and Distinct Disruptions of Cortical Surface Morphology Between Autism Spectrum Disorder Children With and Without SHANK3 Deficiency.

SH3 and Multiple Ankyrin Repeat Domains 3 (SHANK3)-caused autism spectrum disorder (ASD) may present a unique opportunity to clarify the heterogeneous neuropathological mechanisms of ASD. However, the specificity and commonality of disrupted large-scale brain organization in SHANK3-deficient children remain largely unknown. The present study combined genetic tests, neurobehavioral evaluations, and magnetic resonance imaging, aiming to explore the disruptions of both local and networked cortical structural organization in ASD children with and without SHANK3 deficiency. Multiple surface morphological parameters such as cortical thickness (CT) and sulcus depth were estimated, and the graph theory was adopted to characterize the topological properties of structural covariance networks (SCNs). Finally, a correlation analysis between the alterations in brain morphological features and the neurobehavioral evaluations was performed. Compared with typically developed children, increased CT and reduced nodal degree were found in both ASD children with and without SHANK3 defects mainly in the lateral temporal cortex, prefrontal cortex (PFC), temporo-parietal junction (TPJ), superior temporal gyrus (STG), and limbic/paralimbic regions. Besides commonality, our findings showed some distinct abnormalities in ASD children with SHANK3 defects compared to those without. Locally, more changes in the STG and orbitofrontal cortex were exhibited in ASD children with SHANK3 defects, while more changes in the TPJ and inferior parietal lobe (IPL) in those without SHANK3 defects were observed. For the SCNs, a trend toward regular network topology was observed in ASD children with SHANK3 defects, but not in those without. In addition, ASD children with SHANK3 defects showed more alterations of nodal degrees in the anterior and posterior cingulate cortices and right insular, while there were more disruptions in the sensorimotor areas and the left insular and dorsomedial PFC in ASD without SHANK3 defects. Our findings indicate dissociable disruptions of local and networked brain morphological features in ASD children with and without SHANK3 deficiency. Moreover, this monogenic study may provide a valuable path for parsing the heterogeneity of brain disturbances in ASD.

Dissociable plasticity of visual-motor system in functional specialization and flexibility in expert table tennis players.

Specialization and flexibility are two basic attributes of functional brain organization, enabling efficient cognition and behavior. However, it is largely unknown what plastic changes in specialization and flexibility in visual-motor areas occur in support of extraordinary motor skills in expert athletes and how the selective adaptability of the visual-motor system affects general perceptual or cognitive domains. Here, we used a dynamic network framework to investigate intrinsic functional specialization and flexibility of visual-motor system in expert table tennis players (TTP). Our results showed that sensorimotor areas increased intrinsic functional flexibility, whereas visual areas increased intrinsic functional specialization in expert TTP compared to nonathletes. Moreover, the flexibility of the left putamen was positively correlated with skill level, and that of the left lingual gyrus was positively correlated with behavioral accuracy of a sport-unrelated attention task. This study has uncovered dissociable plasticity of the visual-motor system and their predictions of individual differences in skill level and general attention processing. Furthermore, our time-resolved analytic approach is applicable across other professional athletes for understanding their brain plasticity and superior behavior.

Understanding neural flexibility from a multifaceted definition.

Flexibility is a hallmark of human intelligence. Emerging studies have proposed several flexibility measurements at the level of individual regions, to produce a brain map of neural flexibility. However, flexibility is usually inferred from separate components of brain activity (i.e., intrinsic/task-evoked), and different definitions are used. Moreover, recent studies have argued that neural processing may be more than a task-driven and intrinsic dichotomy. Therefore, the understanding to neural flexibility is still incomplete. To address this issue, we propose a multifaceted definition of neural flexibility according to three key features: broad cognitive engagement, distributed connectivity, and adaptive connectome dynamics. For these three features, we first review the advances in computational approaches, their functional relevance, and their potential pitfalls. We then suggest a set of metrics that can help us assign a flexibility rating to each region. Subsequently, we present an emergent probabilistic view for further understanding the functional operation of individual regions in the unified framework of intrinsic and task-driven states. Finally, we highlight several areas related to the multifaceted definition of neural flexibility for future research. This review not only strengthens our understanding of flexible human brain, but also suggests that the measure of neural flexibility could bridge the gap between understanding intrinsic and task-driven brain function dynamics.

Brain connectivity abnormalities and treatment-induced restorations in patients with cervical dystonia.

BACKGROUND: The relationship between brain abnormalities and phenotypic characteristics in cervical dystonia (CD) patients has not been fully established, and little is known about the neuroplastic changes induced by botulinum toxin type A (BoNT-A) treatment. METHODS: Ninety-two CD patients presenting with rotational torticollis and 45 healthy controls from our database were retrospectively screened. After clinical assessment, the 92 patients underwent baseline magnetic resonance imaging (MRI) followed by a single-dose injection of BoNT-A. Four weeks later, 76 out of the 92 patients were re-evaluated with the Tsui scale for dystonia severity, and 33 out of 76 patients completed post-treatment MRI scanning. Data-driven global brain connectivity and regional homogeneity in tandem with seed-based connectivity analyses were used to examine the functional abnormalities in CD and longitudinal circuit alterations that scaled with clinical response to BoNT-A. Multiple regression models were employed for the prediction analysis of treatment efficacy. RESULTS: Cervical dystonia patients exhibited elevated baseline connectivity of the right postcentral gyrus with the left dorsomedial prefrontal cortex and right caudate nucleus, which was associated with their symptom severity. BoNT-A reduced excessive functional connectivity between the sensorimotor cortex and right superior frontal gyrus, which was significantly correlated with changes in Tsui score. Moreover, pre-treatment regional homogeneity of the left middle frontal gyrus was linearly related to varied response to treatment. CONCLUSIONS: Our findings unravel dissociable connectivity of the sensorimotor cortex underlying the pathology of CD and central effects of BoNT-A therapy. Furthermore, baseline regional homogeneity with the left middle frontal gyrus may represent a potential evidence-based marker of patient stratification for BoNT-A therapy in CD.

Neuroanatomical Substrates and Predictors of Response to Capsulotomy in Intractable Obsessive-Compulsive Disorder.

BACKGROUND: Anterior capsulotomy that surgically targets fiber tracts connecting prefrontal cortex and subcortical nuclei is a therapeutic option for a subgroup of patients with treatment-refractory obsessive-compulsive disorder. The goal of this study was to investigate neural correlates to anterior capsulotomy and find predictors of clinical improvement following this procedure. METHODS: Structural and diffusion imaging data and clinical evaluation were acquired from 31 patients with refractory obsessive-compulsive disorder who underwent anterior capsulotomy. Of the 31 patients, 16 were clinical responders defined by a ≥35% reduction in the Yale-Brown Obsessive Compulsive Scale scores. Analysis of variance was applied on 2 levels (surgery and response) to examine alterations of gray matter volume and fiber tract integrity (measured by generalized fractional anisotropy). The correlation between preoperative data and clinical response was further investigated. RESULTS: After surgery, generalized fractional anisotropy was significantly decreased in the bilateral anterior limb of the internal capsule and anterior thalamic radiation, accompanied by a decrease in gray matter volume in the prefrontal cortex, anterior cingulate cortex, striatum, thalamus, and cerebellum. Moreover, atrophy of the right caudate was greater in responders than in nonresponders, which correlated with alteration in Yale-Brown Obsessive Compulsive Scale score. In addition, preoperative gray matter volume in the right inferior frontal gyrus and generalized fractional anisotropy in the left superior longitudinal fasciculus and right cingulum predicted improved response. More anterior location of the lesion area predicted better clinical response. CONCLUSIONS: These results demonstrate that reduced volume of the right caudate might be associated with therapeutic response of capsulotomy and might offer a potential predictor of treatment outcome and a guide for lesion site.

Neuroplastic changes in resting-state functional connectivity after rTMS intervention for methamphetamine craving.

Amphetamine-type stimulants are the second most commonly abused illicit drug worldwide, with no effective medical treatments currently available. Previous studies have demonstrated that high frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) reduced cue-induced craving in patients with methamphetamine dependence. However, the neuroplastic mechanism underlying rTMS intervention in methamphetamine users remains to be elucidated. Sixty participants (40 males) with severe methamphetamine use disorder according to DSM-5 were randomized to receive either intermittent theta burst protocols (iTBS) (short bursts of 50 Hz rTMS repeated at a rate in the theta range (5 Hz), 2-sec on, 8-sec off for 5 min; 900 pulses) or sham rTMS over the DLPFC over four weeks (20 daily sessions). Resting state functional connectivity magnetic resonance imaging was acquired before and after rTMS intervention. Participants received drug related cue exposure and rated their craving before and after stimulation. Seed-based functional connectivity analysis was performed to probe rTMS-induced neuroplastic reorganization of brain functional networks. Results showed that twenty daily rTMS sessions decreased craving, increased functional connectivity between left DLPFC and inferior parietal lobule, and decreased functional connectivity between insula and inferior parietal lobule, medial temporal lobe and precuneus. Moreover, the increase of functional connectivity between DLPFC and inferior parietal lobule correlated with craving reduction. This study suggests that neuroplastic changes of frontoparietal functional connectivity contributes to craving reduction, shedding light on the therapeutic effect of rTMS on methamphetamine use disorder. This article is part of the special issue on Stress, Addiction and Plasticity.

A graph representation of functional diversity of brain regions.

INTRODUCTION: Modern network science techniques are popularly used to characterize the functional organization of the brain. A major challenge in network neuroscience is to understand how functional characteristics and topological architecture are related in the brain. Previous task-based functional neuroimaging studies have uncovered a core set of brain regions (e.g., frontal and parietal) supporting diverse cognitive tasks. However, the graph representation of functional diversity of brain regions remains to be understood. METHODS: Here, we present a novel graph measure, the neighbor dispersion index, to test the hypothesis that the functional diversity of a brain region is embodied by the topological dissimilarity of its immediate neighbors in the large-scale functional brain network. RESULTS: We consistently identified in two independent and publicly accessible resting-state functional magnetic resonance imaging datasets that brain regions in the frontoparietal and salience networks showed higher neighbor dispersion index, whereas those in the visual, auditory, and sensorimotor networks showed lower neighbor dispersion index. Moreover, we observed that human fluid intelligence was associated with the neighbor dispersion index of dorsolateral prefrontal cortex, while no such association for the other metrics commonly used for characterizing network hubs was noticed even with an uncorrected p < .05. CONCLUSIONS: This newly developed graph theoretical method offers fresh insight into the topological organization of functional brain networks and also sheds light on individual differences in human intelligence.

Brain Map of Intrinsic Functional Flexibility in Anesthetized Monkeys and Awake Humans.

Emerging neuroimaging studies emphasize the dynamic organization of spontaneous brain activity in both human and non-human primates, even under anesthesia. In a recent study, we were able to characterize the heterogeneous architecture of intrinsic functional flexibility in the awake, resting human brain using time-resolved analysis and a probabilistic model. However, it is unknown whether this organizational principle is preserved in the anesthetized monkey brain, and how anesthesia affects dynamic and static measurements of spontaneous brain activity. To investigate these issues, we collected resting-state functional magnetic resonance imaging (fMRI) datasets from 178 awake humans and 11 anesthetized monkeys (all healthy). Our recently established method, a complexity measurement (i.e., Shannon entropy) of dynamic functional connectivity patterns of each brain region, was used to map the intrinsic functional flexibility across the cerebral cortex. To further explore the potential effects of anesthesia, we performed time series analysis and correlation analysis between dynamic and static measurements within awake human and anesthetized monkey brains, respectively. We observed a heterogeneous profile of intrinsic functional flexibility in the anesthetized monkey brain, which showed some similarities to that of awake humans (r = 0.30, p = 0.007). However, we found that brain activity in anesthetized monkeys generally shifted toward random fluctuations. Moreover, there is a negative correlation between nodal entropy for the distribution of dynamic functional connectivity patterns and static functional connectivity strength in anesthetized monkeys, but not in awake humans. Our findings indicate that the heterogeneous architecture of intrinsic functional flexibility across cortex probably reflects an evolutionarily conserved aspect of functional brain organization, which persists across levels of cognitive processing (states of consciousness). The coupling between nodal entropy for the distribution of dynamic functional connectivity patterns and static functional connectivity strength may serve as a potential signature of anesthesia. This study not only offers fresh insight into the evolution of brain functional architecture, but also advances our understanding of the dynamics of spontaneous brain activity.

Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes.

CONTEXT: Middle-aged to elderly patients with type 2 diabetes mellitus (T2DM) exhibit reduced functional connectivity and brain atrophy underlying cognitive decrements; however, little is known about brain abnormalities in young patients. OBJECTIVE: To detect brain anatomical and functional changes in young patients with T2DM during the early disease stage. DESIGN: Case-control study. SETTING: Tertiary referral hospital. PARTICIPANTS: Thirty-five young patients with T2DM (<40 years of age) with no detectable microangiopathy and 32 nondiabetic control subjects. INTERVENTION: None. MAIN OUTCOME MEASURES: Subjects underwent neuropsychological assessments and structural and resting-state functional MRI. Both voxel-based morphometry and resting-state functional connectivity analyses were performed. RESULTS: No significant differences in brain volume were observed between the patients with T2DM and the controls after controlling for age, sex, education, and body mass index. Compared with the controls, the patients showed greater connectivity of the left hippocampus with the left inferior frontal gyrus and the left inferior parietal lobule. Moreover, the enhanced functional connectivity of left hippocampus with the left inferior frontal gyrus significantly correlated with disease severity (urinary albumin-to-creatinine ratio) (r = 0.613, P < 0.001) and executive function (completion time of Stroop Color and Word Test) (r = -0.461, P = 0.005) after false discovery rate correction. CONCLUSIONS: Our findings suggest an adaptive compensation of brain function to counteract the insidious cognitive decrements during the early stage of T2DM. Additionally, the functional alterations occurring before changes in brain structure and peripheral microangiopathy might serve as early biomarkers related to cognitive decrements.

Associations between neuroanatomical abnormality and motor symptoms in paroxysmal kinesigenic dyskinesia.

INTRODUCTION: The pathophysiologic mechanism of paroxysmal kinesigenic dyskinesia (PKD) is largely unclear. Basal ganglia-thalamo-cortical circuit involvement is thought to underlie PKD pathophysiology. However, microstructural alternations in the motor circuit of PKD require further elucidation. METHODS: Diffusion tensor imaging and high-resolution T1-weighted imaging were performed on 30 PKD patients (15 PRRT2 carriers, 15 PRRT2 non-carriers) and 15 matched healthy controls. Tract-based spatial statistics were conducted on diffusion indices to examine microstructural integrity of white matter. Voxel-based morphometry analysis was used to examine volumetric changes of gray matter. Multiple regression was employed to test the contribution of demography, disease duration, and PRRT2 status to pathological changes in brain structure. RESULTS: Six (including two novel) PRRT2 mutations were identified in PKD patients who exhibited significantly reduced mean diffusivity mainly along the left corticospinal tract, and reduced gray matter volume in pre-supplementary motor area (preSMA) and right opercular part of inferior frontal gyrus (IFGoperc), compared to healthy controls. Both gray matter volume reductions in preSMA and diffusion indices of abnormal white matter negatively correlated with disease duration. Genotype-phenotype analysis revealed that PRRT2 mutation carriers had earlier onset age, longer attacks, and a larger proportion of bilateral symptoms than non-carriers. CONCLUSIONS: We observed that PRRT2 mutations were associated with disease severity, while neuroanatomical abnormality was associated with disease duration in patients with PKD. Aberrant microstructural changes in preSMA and IFG areas, independent of mutation status, point to dysregulated motor inhibition in patients and provide new insights into neurobiological mechanisms underlying motor symptoms of PKD.

Dual integrin αvß 3 and NRP-1-Targeting Paramagnetic Liposome for Tumor Early Detection in Magnetic Resonance Imaging.

Enhanced MRI (magnetic resonance imaging) plays a vital role in the early detection of tumor but with low specificity. Molecular imaging of angiogenesis could efficiently deliver contrast agents to the tumor site by specific targeted carriers. We designed and synthesized dual-targeted paramagnetic liposomes functionalized with two angiogenesis-targeting ligands, the αVß3 integrin-specific RGD (Arg-Gly-Asp) and the neuropilin-1 (NRP-1) receptor-specific ATWLPPR (Ala-Thr-Trp-Leu-Pro-Pro-Arg) (A7R). These liposomes were proved to be in the nanoparticle range and demonstrated to effectively encapsulate paramagnetic MRI contrast agents Gd-DTPA (gadolinium-diethylenetriamine pentaacetic acid). T1 relaxivity of various liposome formulations was lower than pure Gd-DTPA but with no statistically significant difference. In vitro cellular uptake and competitive inhibition assay showed the higher binding affinity of dual-targeted liposomes to HUVECs (human umbilical vein endothelial cells) and A549 cells compared with pure Gd-DTPA, non-targeted, and single-targeted liposomes, which was proved to be mediated by the binding of RGD/ανß3-integrin and A7R/NRP1. For MR imaging of mice bearing A549 cells in vivo, dual-targeted liposomes reached the highest SER (signal enhancement rate) value with a significant difference at all experimental time points. It was about threefold increase compared to pure Gd-DTPA and non-targeted liposomes and was 1.5-fold of single-targeted liposomes at 2 h post injection. The SER was lowered gradually and decreased only by 40% of the peak value in 6 h. Dual-targeted liposomes were likely to exert a synergistic effect and the specificity of delivering Gd-DTPA to the tumor site. Therefore, dual-ανß3-integrin-NRP1-targeting paramagnetic liposome with a RGD-ATWLPPR heterodimeric peptide might be a potent system for molecular imaging of tumor.

Brain anomaly networks uncover heterogeneous functional reorganization patterns after stroke.

Stroke has a large physical, psychological, and financial burden on patients, their families, and society. Based on functional networks (FNs) constructed from resting state fMRI data, network connectivity after stroke is commonly conjectured to be more randomly reconfigured. We find that this hypothesis depends on the severity of stroke. Head movement-corrected, resting-state fMRI data were acquired from 32 patients after stroke, and 37 healthy volunteers. We constructed anomaly FNs, which combine time series information of a patient with the healthy control group. We propose data-driven techniques to automatically identify regions of interest that are stroke relevant. Graph analysis based on anomaly FNs suggests consistently that strong connections in healthy controls are broken down specifically and characteristically for brain areas that are related to sensorimotor functions and frontoparietal control systems, but new links in stroke patients are rebuilt randomly from all possible areas. Entropic measures of complexity are proposed for characterizing the functional connectivity reorganization patterns, which are correlated with hand and wrist function assessments of stroke patients and show high potential for clinical use.

Frequency-specific alterations of regional homogeneity in subcortical stroke patients with different outcomes in hand function.

Emerging evidence has suggested that abnormalities in regional spontaneous brain activity following stroke may be detected by intrinsic low-frequency oscillations (LFO) in resting-state functional MRI (R-fMRI). However, the relationship between hand function outcomes following stroke and local LFO synchronization in different frequency bands is poorly understood. In this study, we performed R-fMRI to examine the regional homogeneity (ReHo) at three different frequency bands (slow-5: .01-.027 Hz; slow-4: .027-.08 Hz; and typical band: .01-.1 Hz) in 26 stroke patients with completely paralyzed hands (CPH) and 26 matched patients with partially paralyzed hands (PPH). Compared to the PPH group, decreased ReHo in the bilateral cerebellum posterior lobes and the contralesional cerebellum anterior lobe was observed in the slow-5 band and the slow-4 band in the CPH group, respectively. The mean ReHo values in these regions were positively correlated with the Fugl-Meyer assessment (FMA) scores. In contrast, increased ReHo in the contralesional supplementary motor area and the contralesional superior temporal gyrus was observed in the slow-4 band and the slow-5 band, respectively. The mean ReHo values in these regions were negatively correlated with the FMA scores. Importantly, significant interactions were identified between the frequency bands and the subgroups of patients in the contralesional precentral gyrus and middle frontal gyrus. These findings indicate that frequency-dependent R-fMRI patterns may serve as potential biomarkers of the neural substrates associated with hand function outcomes following stroke.

Functional network changes in the hippocampus contribute to depressive symptoms in epilepsy.

PURPOSE: Our study aimed to investigate the functional connectivity (FC) between the hippocampus and other brain regions in epilepsy patients with depressive symptoms. METHODS: Epilepsy patients with and without depressive symptoms, assessed using the 17-item Hamilton Depression Rating Scale scores, were enrolled. Healthy volunteers were recruited as the control group. Resting state functional magnetic resonance imaging was performed, and the data were processed using Resting-State fMRI (DPARSFA2.0) software. The regional homogeneity (ReHo) values and the FC between the right hippocampus and other brain regions were analysed. RESULTS: The ReHo value of the cerebellum (particularly the left cerebellar hemisphere) was significantly lower in epilepsy patients than in healthy controls, and was lower in epilepsy patients with depressive symptoms (EP + DS group) than in those without depressive symptoms (EP-DS group, p < 0.05). Additionally, the FC between the right hippocampus and the bilateral cerebellum was significantly greater in the EP + DS group than in the EP-DS group (p < 0.05). Moreover, abnormal ReHo values in the bilateral frontal lobes, including the right anterior cingulate cortex, and changes in the FC between the right hippocampus and the bilateral frontal lobes were found in the EP + DS group. Minor changes in the FC between the temporal and parietal lobes were also found in the epilepsy patients. CONCLUSION: The functional right hippocampus-cerebellum circuit might contribute to the pathogenesis of depressive symptoms in epilepsy, with the exception of brain areas associated with emotion such as the frontal and temporal lobes. Modulating the hippocampus-cerebellum circuit is a potential therapeutic strategy for epilepsy patients with depressive symptoms.

Dissociable Frontostriatal Connectivity: Mechanism and Predictor of the Clinical Efficacy of Capsulotomy in Obsessive-Compulsive Disorder.

BACKGROUND: Little is known about the neural mechanism and response variability underlying neurosurgical interventions for intractable obsessive-compulsive disorder (OCD). METHODS: Of 81 OCD patients screened for capsulotomy identified in our institutional database, 36 patients with clinical assessment before and after capsulotomy and imaging data (9 of 36 patients without postoperative imaging data used as an independent test group), and 29 healthy control subjects were retrospectively recruited. Twenty of 36 patients (56%) responded to the lesion procedure (determined as a ≥35% reduction in Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score). Seed-based (i.e., ventral and dorsal caudate, medial dorsal thalamus, and ventral and dorsal putamen) resting-state functional connectivity was used to examine alterations in frontostriatal circuitry after capsulotomy. RESULTS: The Y-BOCS score significantly decreased (p < .001) after capsulotomy in OCD patients. Functional connectivity between the ventral striatum/nucleus accumbens and the dorsal anterior cingulate cortex was reduced (p < .05, corrected) after the surgical procedure. Moreover, change in connectivity significantly correlated with alteration in Y-BOCS score (r = .41, p = .033). In addition, preoperative connectivity between the dorsal caudate and the dorsal anterior cingulate cortex could differentiate nonresponders from responders and predict changes in Y-BOCS score (R2 = .23, F1,25 = 7.56, p = .011), which was generalized in an independent test group. CONCLUSIONS: We demonstrated that restoration of ventral frontostriatal connectivity was associated with clinical improvement in refractory OCD, suggesting a therapeutic mechanism of capsulotomy. Moreover, preoperative variations in dorsal frontostriatal connectivity predicted clinical response, which may offer a predictor of treatment outcome.

Altered intra- and inter-network functional coupling of resting-state networks associated with motor dysfunction in stroke.

Motor functions are supported through functional integration across the extended motor system network. Individuals following stroke often show deficits on motor performance requiring coordination of multiple brain networks; however, the assessment of connectivity patterns after stroke was still unclear. This study aimed to investigate the changes in intra- and inter-network functional connectivity (FC) of multiple networks following stroke and further correlate FC with motor performance. Thirty-three left subcortical chronic stroke patients and 34 healthy controls underwent resting-state functional magnetic resonance imaging. Eleven resting-state networks were identified via independent component analysis (ICA). Compared with healthy controls, the stroke group showed abnormal FC within the motor network (MN), visual network (VN), dorsal attention network (DAN), and executive control network (ECN). Additionally, the FC values of the ipsilesional inferior parietal lobule (IPL) within the ECN were negatively correlated with the Fugl-Meyer Assessment (FMA) scores (hand + wrist). With respect to inter-network interactions, the ipsilesional frontoparietal network (FPN) decreased FC with the MN and DAN; the contralesional FPN decreased FC with the ECN, but it increased FC with the default mode network (DMN); and the posterior DMN decreased FC with the VN. In sum, this study demonstrated the coexistence of intra- and inter-network alterations associated with motor-visual attention and high-order cognitive control function in chronic stroke, which might provide insights into brain network plasticity following stroke.