The Fate of Injured Corticospinal Tracts in Patients with Intracerebral Hemorrhage: Diffusion Tensor Imaging Study

BACKGROUND AND PURPOSE: Little is known about the fate of the injured CST for a large number of patients with ICH. Using DTT, we investigated the longitudinal changes of injured CSTs in patients with an ICH

Regional cerebral blood perfusion changes in chronic stroke survivors as potential brain correlates of the functional outcome following gamiied home-based rehabilitation (IntelliRehab)—a pilot study

Background: Hospital-based stroke rehabilitation for stroke survivors in developing countries may be limited by staffing ratios and length of stay that could hamper recovery potential. Thus, a home-based, gamified rehabilitation system (i.e., IntelliRehab) was tested for its ability to increase cerebral blood flow (CBF), and the secondary impact of changes on the upper limb motor function and functional outcomes. Objective: To explore the effect of IntelliRehab on CBF in chronic stroke patients and its correlation with the upper limb motor function. Methods: Two-dimensional pulsed Arterial Spin Labelling (2D-pASL) was used to obtain CBF images of stable, chronic stroke subjects (n = 8) over 3-months intervention period. CBF alterations were mapped, and the detected differences were marked as regions of interest. Motor functions represented by Fugl-Meyer Upper Extremity Assessment (FMA) and Stroke Impact Scale (SIS) were used to assess the primary and secondary outcomes, respectively. Results: Regional CBF were significantly increased in right inferior temporal gyrus and left superior temporal white matter after 1-month (p = 0.044) and 3-months (p = 0.01) of rehabilitation, respectively. However, regional CBF in left middle fronto-orbital gyrus significantly declined after 1-month of rehabilitation (p = 0.012). Moreover, SIS-Q7 and FMA scores significantly increased after 1-month and 3-months of rehabilitation. There were no significant correlations, however, between CBF changes and upper limb motor function. Conclusions: Participants demonstrated improved motor functions, supporting the benefit of using IntelliRehab as a tool for home-based rehabilitation. However, within-participant improvements may have limited potential that suggests the need for a timely administration of IntelliRehab to get the maximum capacity of improvement

Brain plasticity following MI-BCI training combined with tDCS in a randomized trial in chronic subcortical stroke subjects: a preliminary study

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been used in stroke rehabilitation, though their combinatory effect is unknown. We investigated brain plasticity following a combined MI-BCI and tDCS intervention in chronic subcortical stroke patients with unilateral upper limb disability. Nineteen patients were randomized into tDCS and sham-tDCS groups. Diffusion and perfusion MRI, and transcranial magnetic stimulation were used to study structural connectivity, cerebral blood flow (CBF), and corticospinal excitability, respectively, before and 4 weeks after the 2-week intervention. After quality control, thirteen subjects were included in the CBF analysis. Eleven healthy controls underwent 2 sessions of MRI for reproducibility study. Whereas motor performance showed comparable improvement, long-lasting neuroplasticity can only be detected in the tDCS group, where white matter integrity in the ipsilesional corticospinal tract and bilateral corpus callosum was increased but sensorimotor CBF was decreased, particularly in the ipsilesional side. CBF change in the bilateral parietal cortices also correlated with motor function improvement, consistent with the increased white matter integrity in the corpus callosum connecting these regions, suggesting an involvement of interhemispheric interaction. The preliminary results indicate that tDCS may facilitate neuroplasticity and suggest the potential for refining rehabilitation strategies for stroke patients

On the Viability of Diffusion MRI-Based Microstructural Biomarkers in Ischemic Stroke

Recent tract-based analyses provided evidence for the exploitability of 3D-SHORE microstructural descriptors derived from diffusion MRI (dMRI) in revealing white matter (WM) plasticity. In this work, we focused on the main open issues left: (1) the comparative analysis with respect to classical tensor-derived indices, i.e., Fractional Anisotropy (FA) and Mean Diffusivity (MD); and (2) the ability to detect plasticity processes in gray matter (GM). Although signal modeling in GM is still largely unexplored, we investigated their sensibility to stroke-induced microstructural modifications occurring in the contralateral hemisphere. A more complete picture could provide hints for investigating the interplay of GM and WM modulations. Ten stroke patients and ten age/gender-matched healthy controls were enrolled in the study and underwent diffusion spectrum imaging (DSI). Acquisitions at three and two time points (tp) were performed on patients and controls, respectively. For all subjects and acquisitions, FA and MD were computed along with 3D-SHORE-based indices [Generalized Fractional Anisotropy (GFA), Propagator Anisotropy (PA), Return To the Axis Probability (RTAP), Return To the Plane Probability (RTPP), and Mean Square Displacement (MSD)]. Tract-based analysis involving the cortical, subcortical and transcallosal motor networks and region-based analysis in GM were successively performed, focusing on the contralateral hemisphere to the stroke. Reproducibility of all the indices on both WM and GM was quantitatively proved on controls. For tract-based, longitudinal group analyses revealed the highest significant differences across the subcortical and transcallosal networks for all the indices. The optimal regression model for predicting the clinical motor outcome at tp3 included GFA, PA, RTPP, and MSD in the subcortical network in combination with the main clinical information at baseline. Region-based analysis in the contralateral GM highlighted the ability of anisotropy indices in discriminating between groups mainly at tp1, while diffusivity indices appeared to be altered at tp2. 3D-SHORE indices proved to be suitable in probing plasticity in both WM and GM, further confirming their viability as a novel family of biomarkers in ischemic stroke in WM and revealing their potential exploitability in GM. Their combination with tensor-derived indices can provide more detailed insights of the different tissue modulations related to stroke pathology

White Matter Integrity as a Biomarker for Stroke Recovery: Implications for TMS Treatment

White matter consists of myelinated axons which integrate information across remote brain regions. Following stroke white matter integrity is often compromised leading to functional impairment and disability. Despite its prevalence among stroke patients the role of white matter in development of post-stroke rehabilitation has been largely ignored. Rehabilitation interventions like repetitive transcranial magnetic stimulation (rTMS) are promising but reports on its efficacy have been conflicting. By understanding the role of white matter integrity in post-stroke motor recovery, brain reorganization and TMS efficacy we may be able to improve the development of future interventions. In this dissertation we set out answer these questions by investigating the relationship between white matter integrity and 1) bimanual motor performance following stroke, 2) cortical laterality following stroke and 3) TMS signal propagation (in a group of cocaine users without stroke). We identified white matter integrity of the corpus callosum as a key structure influencing bimanual performance using kinematic measures of hand symmetry (Chapter 2). Second, we found that reduced white matter integrity of corpus callosum was correlated with loss of functional laterality of the primary motor cortex during movement of the affected hand (Chapter 3). Lastly, we found that reduced white matter tract integrity from the site of stimulation to a downstream subcortical target, was correlated to the ability to modulate that target (Chapter 4). Taken together these studies support white matter integrity as a valuable biomarker for future rTMS trials in stroke. To emphasize the implications of these findings, we provide an example of how to incorporate white matter integrity at multiple levels of rTMS study design

Indirect Structural Connectivity As a Biomarker for Stroke Motor Recovery

In this dissertation project, we demonstrated that diffusion magnetic resonance imaging and measures of indirect structural brain connectivity are sensitive to changes in fiber integrity and connectivity to remote regions in the brain after stroke. Our results revealed new insights into the effects local lesions have on global connectivity—in particular, the cerebellum—and how these changes in connectivity and integrity relate to motor impairment. We tested this methodology on two stroke groups—subacute and chronic—and were able to show that indirect connectivity is sensitive to differences in connectivity during stroke recovery. Our work can inform clinical methods for rehabilitating motor function in stroke individuals. By introducing methodology that extends local damage to remotely connected motor related areas, we can measure Wallerian degeneration in addition to providing the framework to predict improvements in motor impairment score based on structural connectivity at the subacute stage.We used diffusion magnetic resonance imaging (dMRI), probabilistic tractography, and novel graph theory metrics to quantify structural connectivity and integrity after stroke. In the first aim, we improved on a measure of indirect structural connectivity in order to detect remote gray matter regions with reduced connectivity after stroke. In a region-level analysis, we found that indirect connectivity was more sensitive to remote changes in connectivity after stroke than measures of direct connectivity, in particular in cortical, subcortical, and cerebellar gray matter regions that play a central role in sensorimotor function. Adding this information to the integrity of the corticospinal tract (CST) improved our ability to predict motor impairment. In the second aim, we investigated the relationship between white matter integrity, connectivity, and motor impairment by developing a unified measure of white matter structure that extends local changes in white matter integrity along remotely connected fiber tracks. Our measure uniquely identified damaged fiber tracks outside the CST, correlated with motor impairment in the CST better than the FA, and also was able to relate white matter structure in the superior cerebellar peduncle to motor impairment. Our final aim used a novel connectome similarity metric and the measure of indirect structural connectivity in order to identify cross-sectional differences in white matter structure between subacute and chronic stroke. We found more reductions in indirect connectivity in the chronic stroke cerebellar fibers than the subacute group, Additionally, the indirect connectivity of the superior cerebellar peduncle at the subacute stage correlated with the improvement in motor impairment score for the paired participants. In conclusion, indirect connectivity is an important measure of global brain damage and motor impairment after stroke, and can be a useful metric to relate to brain function and stroke recovery