Activity flow under the manipulation of cognitive load and training.

Flexible cognitive functions, such as working memory (WM), usually require a balance between localized and distributed information processing. However, it is challenging to uncover how local and distributed processing specifically contributes to task-induced activity in a region. Although the recently proposed activity flow mapping approach revealed the relative contribution of distributed processing, few studies have explored the adaptive and plastic changes that underlie cognitive manipulation. In this study, we recruited 51 healthy volunteers (31 females) and investigated how the activity flow and brain activation of the frontoparietal systems was modulated by WM load and training. While the activation of both executive control network (ECN) and dorsal attention network (DAN) increased linearly with memory load at baseline, the relative contribution of distributed processing showed a linear response only in the DAN, which was prominently attributed to within-network activity flow. Importantly, adaptive training selectively induced an increase in the relative contribution of distributed processing in the ECN and also a linear response to memory load, which were predominantly due to between-network activity flow. Furthermore, we demonstrated a causal effect of activity flow prediction through training manipulation on connectivity and activity. In contrast with classic brain activation estimation, our findings suggest that the relative contribution of distributed processing revealed by activity flow prediction provides unique insights into neural processing of frontoparietal systems under the manipulation of cognitive load and training. This study offers a new methodological framework for exploring information integration versus segregation underlying cognitive processing.

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.

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.

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.

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.

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.

Dissociable Changes of Frontal and Parietal Cortices in Inherent Functional Flexibility across the Human Life Span.

UNLABELLED: Extensive evidence suggests that frontoparietal regions can dynamically update their pattern of functional connectivity, supporting cognitive control and adaptive implementation of task demands. However, it is largely unknown whether this flexibly functional reconfiguration is intrinsic and occurs even in the absence of overt tasks. Based on recent advances in dynamics of resting-state functional resonance imaging (fMRI), we propose a probabilistic framework in which dynamic reconfiguration of intrinsic functional connectivity between each brain region and others can be represented as a probability distribution. A complexity measurement (i.e., entropy) was used to quantify functional flexibility, which characterizes heterogeneous connectivity between a particular region and others over time. Following this framework, we identified both functionally flexible and specialized regions over the human life span (112 healthy subjects from 13 to 76 years old). Across brainwide regions, we found regions showing high flexibility mainly in the higher-order association cortex, such as the lateral prefrontal cortex (LPFC), lateral parietal cortex, and lateral temporal lobules. In contrast, visual, auditory, and sensory areas exhibited low flexibility. Furthermore, we observed that flexibility of the right LPFC improved during maturation and reduced due to normal aging, with the opposite occurring for the left lateral parietal cortex. Our findings reveal dissociable changes of frontal and parietal cortices over the life span in terms of inherent functional flexibility. This study not only provides a new framework to quantify the spatiotemporal behavior of spontaneous brain activity, but also sheds light on the organizational principle behind changes in brain function across the human life span. SIGNIFICANCE STATEMENT: Recent neuroscientific research has demonstrated that the human capability of adaptive task control is primarily the result of the flexible operation of frontal brain networks. However, it remains unclear whether this flexibly functional reconfiguration is intrinsic and occurs in the absence of an overt task. In this study, we propose a probabilistic framework to quantify the functional flexibility of each brain region using resting-state fMRI. We identify regions showing high flexibility mainly in the higher-order association cortex. In contrast, primary and unimodal visual and sensory areas show low flexibility. On the other hand, our findings reveal dissociable changes of frontal and parietal cortices in terms of inherent functional flexibility over the life span.

The plasticity of intrinsic functional connectivity patterns associated with rehabilitation intervention in chronic stroke patients.

INTRODUCTION: It has been demonstrated that rehabilitative interventions can promote motor function recovery in stroke patients. However, little is known regarding the neural mechanisms that underlie the rehabilitation treatments. The aim of this study was to investigate the plasticity of intrinsic functional connectivity patterns that are associated with rehabilitation intervention in chronic stroke patients. METHODS: Twelve chronic stroke patients with subcortical lesions in the left motor pathway participated in a 4-week rehabilitation intervention and underwent resting-state functional magnetic resonance imaging (fMRI) scanning before and after the intervention. Both functional connectivity analyses of the ipsilesional (left) primary motor cortex (M1) and measurements of the lateralization index of the connectivity patterns were performed in both the stroke patients and healthy controls (HC). RESULTS: Compared with the HC, the decreased connectivity of the ipsilesional M1 with the contralesional sensorimotor cortex (SMC), bilateral supplementary motor areas, and inferior parietal lobule due to stroke were remarkably restored after the intervention. More specifically, the lateralization index of the bilateral SMC tends to be the normal level. Moreover, comparing post- with pre-intervention, we observed significantly increased connectivity of ipsilesional M1 with the contralesional M1 and medial superior frontal gyrus (mSFG). Additionally, the index of pre-intervention connectivity with the contralesional mSFG was positively correlated with motor improvement. CONCLUSION: The impact of rehabilitation intervention on intrinsic functional connectivity patterns throughout the brain was measurable on resting-state fMRI, and systematic assessment of resting-state functional connectivity can provide prognostic insight for later motor improvement.

Abnormal functional connectivity of the amygdala-based network in resting-state FMRI in adolescents with generalized anxiety disorder.

BACKGROUND: We aimed to investigate the disruptions of functional connectivity of amygdala-based networks in adolescents with untreated generalized anxiety disorder (GAD). MATERIAL AND METHODS: A total of 26 adolescents with first-episode GAD and 20 normal age-matched volunteers underwent resting-state and T1 functional magnetic resonance imaging (fMRI). We analyzed the correlation of fMRI signal fluctuation between the amygdala and other brain regions. The variation of amygdala-based functional connectivity and its correlation with anxiety severity were investigated. RESULTS: Decreased functional connectivity was found between the left amygdala and left dorsolateral prefrontal cortex. An increased right amygdala functional connectivity with right posterior and anterior lobes of the cerebellum, insula, superior temporal gyrus, putamen, and right amygdala were found in our study. Negative correlations between GAD scores and functional connectivity of the right amygdala with the cerebellum were also observed in the GAD adolescents. CONCLUSIONS: Adolescents with GAD have abnormalities in brain regions associated with the emotional processing pathways.

Altered topological properties of the cortical motor-related network in patients with subcortical stroke revealed by graph theoretical analysis.

Cerebral neuroplasticity after stroke has been elucidated by functional neuroimaging. However, little is known concerning how topological properties of the cortical motor-related network evolved following subcortical stroke. In the present study, we investigated 24 subcortical stroke patients with only left motor pathway damaged and 24 matched healthy controls. A cortical motor-related network consisting of 20 brain regions remote from the primary lesion was constructed using resting-state functional MRI datasets. We subsequently used graph theoretical approaches to analyze the topological properties of this network in both stroke patients and healthy controls. In addition, we divided the stroke patients into two subgroups according to their outcomes in hand function to explore relationships between topological properties of this network and outcomes in hand function. Although we observed that the cortical motor-related network in both healthy controls and stroke patients exhibited small-world topology, the local efficiency of this network in stroke patients is higher than and global efficiency is lower than those in healthy controls. In addition, striking alterations in the betweenness centrality of regions were found in stroke patients, including the contralesional supplementary motor area, dorsolateral premotor cortex, and anterior inferior cerebellum. Moreover, we observed significant correlations between betweenness centrality of regions and Fugl-Meyer assessment scores. A tendency for the cortical motor-related network to be close to a regular configuration and altered betweenness centrality of regions were demonstrated in patients with subcortical stroke. This study provided insight into functional organization after subcortical stroke from the viewpoint of network topology.

A magnetic nanoparticle stabilized gas containing emulsion for multimodal imaging and triggered drug release.

PURPOSE: To develop a multimodal imaging guided and triggered drug delivery system based on a novel emulsion formulation composed of iron oxide nanoparticles, nanoscopic bubbles, and oil containing drugs. METHODS: Iron oxide paramagnetic nanoparticles were synthesized and modified with surface conjugation of polyethylenimide (PEI) or Bovine Serum Albumin (BSA). Both particles were used to disperse and stabilize oil in water emulsions containing coumarin-6 as the model drug. Sulfur hexafluoride was introduced into the oil phase to form nanoscopic bubbles inside the emulsions. The resulted gas containing emulsions were evaluated for their magnetic resonance (MR) and ultrasound (US) imaging properties. The drug release profile triggered by ultrasound was also examined. RESULTS: We have successfully prepared the highly integrated multi-component emulsion system using the surface modified iron oxide nanoparticles to stabilize the interfaces. The resulted structure had distinctive MR and US imaging properties. Upon application of ultrasound waves, the gas containing emulsion would burst and encapsulated drug could be released. CONCLUSION: The integrated emulsion formulation was multifunctional with paramagnetic, sono-responsive and drug-carrying characteristics, which may have potential applications for disease diagnosis and imaging guided drug release.

Dissociable functional responses along the posterior-anterior gradient of the frontal and parietal cortices revealed by parametric working memory and training.

While the storage capacity is limited, accumulating studies have indicated that working memory (WM) can be improved by cognitive training. However, understanding how exactly the brain copes with limited WM capacity and how cognitive training optimizes the brain remains inconclusive. Given the hierarchical functional organization of WM, we hypothesized that the activation profiles along the posterior-anterior gradient of the frontal and parietal cortices characterize WM load and training effects. To test this hypothesis, we recruited 51 healthy volunteers and adopted a parametric WM paradigm and training method. In contrast to exclusively strengthening the activation of posterior areas, a broader range of activation concurrently occurred in the anterior areas to cope with increased memory load for all subjects at baseline. Moreover, there was an imbalance in the responses of the posterior and anterior areas to the same increment of 1 item at different load levels. Although a general decrease in activation after adaptive training, the changes in the posterior and anterior areas were distinct at different memory loads. Particularly, we found that the activation gradient between the posterior and anterior areas was significantly increased at load 4-back after adaptive training, and the changes were correlated with improvement in WM performance. Together, our results demonstrate a shift in the predominant role of posterior and anterior areas in the frontal and parietal cortices when approaching WM capacity limits. Additionally, the training-induced performance improvement likely benefits from the elevated neural efficiency reflected in the increased activation gradient between the posterior and anterior areas.

Resting-state functional MRI: functional connectivity analysis of the visual cortex in primary open-angle glaucoma patients.

PURPOSE: To analyze functional connectivity (FC) of the visual cortex using resting-state functional MRI in human primary open-angle glaucoma (POAG) patients. MATERIALS AND METHODS: Twenty-two patients with known POAG and 22 age-matched controls were included in this IRB-approved study. Subjects were evaluated by 3 T MR using resting-state blood oxygenation level dependent and three-dimensional brain volume imaging (3D-BRAVO) MRI. Data processing was performed with standard software. FC maps were generated from Brodmann areas (BA) 17/18/19/7 in a voxel-wise fashion. Region of interest analysis was used to specifically examine FC among each pair of BA17/18/19/7. RESULTS: Voxel-wise analyses demonstrated decreased FC in the POAG group between the primary visual cortex (BA17) and the right inferior temporal, left fusiform, left middle occipital, right superior occipital, left postcentral, right precentral gyri, and anterior lobe of the left cerebellum. Increased FC was found between BA17 and the left cerebellum, right middle cerebellar peduncle, right middle frontal gyrus, and extra-nuclear gyrus (P < 0.05). In terms of the higher visual cortices (BA18/19), positive FC was disappeared with the cerebellar vermis, right middle temporal, and right superior temporal gyri (P < 0.05). Negative FC was disappeared between BA18/19 and the right insular gyrus (P < 0.05). Region of interest analysis demonstrated no statistically significant differences in FC between the POAG patients relative to the controls (P > 0.05). CONCLUSION: Changes in FC of the visual cortex are found in patients with POAG. These include alterations in connectivity between the visual cortex and associative visual areas along with disrupted connectivity between the primary and higher visual areas.

Whole-brain voxel-based analysis of diffusion tensor MRI parameters in patients with primary open angle glaucoma and correlation with clinical glaucoma stage.

INTRODUCTION: Glaucoma is the second leading cause of blindness worldwide. The purpose of this study is to identify areas of neurodegeneration in glaucoma utilizing 3 T magnetic resonance (MR) diffusion tensor imaging (DTI) parameters with whole-brain voxel-based analysis (VBA) and determine whether these parameters correlate with disease severity. METHODS: Twenty-five glaucoma patients and 25 age-matched healthy volunteers were prospectively examined. Clinical glaucoma severity was assessed utilizing static threshold visual field parameters. All subjects underwent 3 T MRI utilizing a DTI sequence (repetition time/echo time 13,000/68.9 ms, maximal b value 800 s/mm(2) along 30 directions) and an anatomic sequence to provide structural information. All data sets were processed by VBA. Brain fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were compared in the two groups. Correlation between DTI parameters and glaucoma stage were determined. RESULTS: The bilateral optic radiations and chiasma of glaucoma patients demonstrated statistically significantly lower fractional anisotropy (p < 0.05). Optic radiation RD was similarly decreased in glaucoma patients (p < 0.05). There were no statistically significant differences noted in MD or AD between the two groups (p > 0.05). Optic chiasm fractional anisotropy values were negatively correlated with glaucoma stage (r = -0.53, p < 0.05) and optic radiation RD values positively correlated (left r = 0.45, p < 0.05; right = 0.38, p = 0.06). CONCLUSION: DTI parameters fractional anisotropy and RD are altered in the optic chiasm and radiations of glaucoma patients. As fractional anisotropy and RD also correlate with glaucoma stage, these values could serve as potential noninvasive markers of disease severity.

Functional reorganization associated with outcome in hand function after stroke revealed by regional homogeneity.

INTRODUCTION: Previous studies of task-based functional neuroimaging have shown that various patterns of functional reorganization underlie motor recovery following stroke. However, the mechanisms underlying functional reorganization that contribute to outcome differences in hand function after stroke have not been completely characterized. We, for the first time, investigate subgroups of stroke patients with different outcomes in hand function using a resting-state fMRI approach. METHODS: We selected 24 patients with subcortical stroke and divided them into two subgroups: completely paralyzed hands (CPH, 12 patients) and partially paralyzed hands (PPH, 12 patients). Twenty-four healthy controls (HCs) matched for age and handedness were also recruited. We used regional homogeneity (ReHo) method to map regional spontaneous activity across the whole brain and performed a two-sample t test between each pair of the three diagnostic groups. RESULTS: Compared to HCs, we found increased ReHo in the ipsilesional hemisphere in PPH and, conversely, increased ReHo in the contralesional hemisphere in CPH. Moreover, we detected decreased ReHo in the ipsilesional primary sensorimotor cortex and superior temporal gyrus, in addition to increased ReHo in the contralesional premotor cortex and ipsilesional medial frontal gyrus in CPH compared to PPH. Additionally, the ReHo index of these regions significantly correlated with the Fugl-Meyer assessment scores (hand + wrist) across all stroke patients. CONCLUSIONS: Our study offers a new insight into relationships between functional reorganization and outcomes in hand function after subcortical stroke, and the ReHo method can provide an effective tool for evaluating the efficiency of rehabilitative therapies following stroke.

Cortical reorganization after motor imagery training in chronic stroke patients with severe motor impairment: a longitudinal fMRI study.

INTRODUCTION: Despite its clinical efficacy, few studies have examined the neural mechanisms of motor imagery training (MIT) in stroke. Our objective was to find the cortical reorganization patterns after MIT in chronic stroke patients. METHODS: Twenty stroke patients with severe motor deficits were randomly assigned to the MIT or conventional rehabilitation therapy (CRT) group, but two lost in the follow-up. All 18 patients received CRT 5 days/week for 4 weeks. Nine subjects in the MIT group received 30-min MIT 5 days/week for 4 weeks. Before and after the interventions, the upper limb section of the Fugl-Meyer Scale (FM-UL) was blindly evaluated, and functional magnetic resonance imaging was administered while the patients executed a passive fist clutch task. RESULTS: Two cortical reorganization patterns were found. One pattern consisted of the growth in activation in the contralateral sensorimotor cortex (cSMC) for most patients (six in the MIT group, five in the CRT group), and the other consisted of focusing of the activation in the cSMC with increasing of the laterality index of the SMC for a small portion of patients (three in the MIT group, one in the CRT group). When we applied correlation analyses to the variables of relative ΔcSMC and ΔFM-UL in the 11 patients who experienced the first pattern, a positive relationship was detected. CONCLUSIONS: Our results indicate that different cortical reorganization patterns (increases in or focusing of recruitment to the cSMC region) exist in chronic stroke patients after interventions, and patients may choose efficient patterns to improve their motor function.

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.

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.

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.