Relevance of Structural Brain Connectivity to Learning and Recovery from Stroke

The physical structure of white matter fiber bundles constrains their function. Any behavior that relies on transmission of signals along a particular pathway will therefore be influenced by the structural condition of that pathway. Diffusion-weighted magnetic resonance imaging provides localized measures that are sensitive to white matter microstructure. In this review, we discuss imaging evidence on the relevance of white matter microstructure to behavior. We focus in particular on motor behavior and learning in healthy individuals and in individuals who have suffered a stroke. We provide examples of ways in which imaging measures of structural brain connectivity can inform our study of motor behavior and effects of motor training in three different domains: (1) to assess network degeneration or damage with healthy aging and following stroke, (2) to identify a structural basis for individual differences in behavioral responses, and (3) to test for dynamic changes in structural connectivity with learning or recovery

Occasional essay: upper motor neuron syndrome in amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) requires recognition of both lower (LMN) and upper motor neuron (UMN) dysfunction.1 However, classical UMN signs are frequently difficult to identify in ALS.2 LMN involvement is sensitively detected by electromyography (EMG)3 but, as yet, there are no generally accepted markers for monitoring UMN abnormalities,4 the neurobiology of ALS itself, and disease spread through the brain and spinal cord,.5 Full clinical assessment is therefore necessary to exclude other diagnoses and to monitor disease progression. In part, this difficulty regarding detection of UMN involvement in ALS derives from the definition of ‘the UMN syndrome’. Abnormalities of motor control in ALS require reformulation within an expanded concept of the UMN, together with the neuropathological, neuro-imaging and neurophysiological abnormalities in ALS. We review these issues here

Degree of corticospinal tract damage correlates with motor function after stroke

Objectives: Direct injury to the corticospinal tract (CST) is a major factor defining motor impairment after stroke. Diffusion tensor imaging (DTI) tractography allows definition of the CST. We sought to determine whether DTI-based assessment of the degree of CST damage correlates with motor impairment at each phase of ischemic stroke. Methods: We evaluated patients at the acute (3–7 days), subacute (30 days), and chronic (90 days) phases of ischemic stroke with DTI and clinical motor scores (upper extremity Fugl-Myer test [UE-FM], motor items of the National Institutes of Health Stroke Scale [mNIHSS]). The CST was identified and virtual fiber numbers (FN) were calculated for the affected and contralateral CST. We used Spearman correlation to study the relationship of FN ratio (FNr) (affected/unaffected CST) with motor scores at each time point, and the regression model to study the association of the acute parameters with chronic motor scores. Results: We studied 23 patients. Mean age was 66.7 (±12) years. FNr correlated with UE-FM score in the acute (r = 0.50, P = 0.032), subacute (r = 0.57, P = 0.007), and chronic (r = 0.67, P = 0.0008) phase, and with mNIHSS in the acute (r = −0.48, P = 0.043), subacute (r = −0.58, P = 0.006), and chronic (r = −0.75, P = 0.0001) phase. The combination of acute NIHSS and FNr significantly predicted chronic UE-FM score (r = 0.74, P = 0.0001). Interpretation DTI-defined degree of CST injury correlates with motor impairment at each phase of ischemic stroke. The combination of baseline FNr and NIHSS predicts motor outcome. DTI-derived CST assessment could become a surrogate marker of motor impairment in the design of neurorestorative clinical trials

Network mechanisms underlying motor control after ischemic stroke

Motor impairment is one of the most common symptoms after ischemic stroke. While many patients partially regain lost functions due to plastic changes to the structural and functional architecture of brain networks, recovery is often incomplete, making stroke a leading cause of long-term disability worldwide. Thus, a better mechanistic understanding of motor recovery seems crucial to inform future plasticity-enhancing treatment approaches. The studies summarized in the present thesis therefore aimed at furthering our mechanistic insights into motor network reorganization in acute and chronic stroke patients. In study 1, we focused on the role of different descending motor pathways on distinct aspects of motor control. Study 2 addressed the role of corticospinal output fibers descending from the primary motor cortex (M1) and various premotor areas. In study 3, we assessed cortico-cortical structural connectivity and its differential association with basal and complex motor functions. Finally, study 4 utilized fMRI-data from acute stroke patients to conduct the first direct comparison of resting-state functional and task-related effective connectivity. Taken together, our findings offer novel insights into mechanisms underlying motor control after stroke and hold important implications for therapeutic interventions

Altered white matter connectivity associated with visual hallucinations following occipital stroke

Introduction: Visual hallucinations that arise following vision loss stem from aberrant functional activity in visual cortices and an imbalance of activity across associated cortical and subcortical networks subsequent to visual pathway damage. We sought to determine if structural changes in white matter connectivity play a role in cases of chronic visual hallucinations associated with visual cortical damage. Methods: We performed diffusion tensor imaging (DTI) and probabilistic fiber tractography to assess white matter connectivity in a patient suffering from continuous and disruptive phosphene (simple) visual hallucinations for more than 2 years following right occipital stroke. We compared these data to that of healthy age-matched controls. Results: Probabilistic tractography to reconstruct white matter tracts suggests regeneration of terminal fibers of the ipsilesional optic radiations in the patient. However, arrangement of the converse reconstruction of these tracts, which were seeded from the ipsilesional visual cortex to the intrahemispheric lateral geniculate body, remained disrupted. We further observed compromised structural characteristics, and changes in diffusion (measured using diffusion tensor indices) of white matter tracts in the patient connecting the visual cortex with frontal and temporal regions, and also in interhemispheric connectivity between visual cortices. Conclusions: Cortical remapping and the disruption of communication between visual cortices and remote regions are consistent with our previous functional magnetic resonance imaging (fMRI) data showing imbalanced functional activity of the same regions in this patient (Rafique et al, 2016, Neurology, 87, 1493–1500). Long-term adaptive and disruptive changes in white matter connectivity may account for the rare nature of cases presenting with chronic and continuous visual hallucinations.York University Librarie

Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study

Background: Our understanding of the effect of ataxia-telangiectasia mutated gene mutations on brain structure and function is limited. In this study, white matter motor pathway integrity was investigated in ataxia telangiectasia patients using diffusion MRI and probabilistic tractography

Dynamic diffusion tensor imaging reveals structural changes in the bilateral pyramidal tracts after brain stem hemorrhage in rats

Background and Purpose: Few studies have concentrated on pyramidal tract (PY) changes after brain stem hemorrhage (BSH). In this study, we used a diffusion tensor imaging (DTI) technique and histologic identification to investigate longitudinal PY changes on both the contralateral and ipsilateral sides after experimental BSH. Methods: BSH was induced in 61 Sprague-Dawley rats by infusing 30 μl of autogenous tail blood into each rat’s right pons. DTI and motor function examinations were performed repeatedly on days 1, 3, 7, 14, and 28 after surgery. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were measured in the bilateral PYs. The axon and myelin injury in the PY were evaluated by histologic study. Results: As compared with normal controls, the bilateral PYs in rats with induced BSH showed an early decrease and a late increase in fractional anisotropy and an early increase and a late decrease in mean diffusivity. A progressive decrease in axial diffusivity with dramatic axon loss from day 1 to day 28 after BSH was found bilaterally. The bilateral PYs showed an early increase and a late decrease in radial diffusivity. Early myelin injury and late repair were also detected pathologically in the bilateral PYs of rats with BSH. Thus, the early motor function deficits of rats with BSH began to improve on day 14 and had almost completely disappeared by day 28. Conclusions: DTI revealed dynamic changes in the bilateral PYs after BSH, which was confirmed by histologic findings and which correlated with motor function alteration. These findings support the idea that quantitative DTI can track structural changes in the bilateral PYs and that DTI may serve as a noninvasive tool to predict the prognoses of patients with BSH

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