Background and Purpose Functional magnetic resonance imaging (fMRI) studies could provide crucial information on the neural mechanisms of motor recovery in stroke patients. Resting-state fMRI is applicable to stroke patients who are not capable of proper performance of the motor task. In this study, we explored neural correlates of motor recovery in stroke patients by investigating longitudinal changes in resting-state functional connectivity of the ipsilesional primary motor cortex (M1). Methods A longitudinal observational study using repeated fMRI experiments was conducted in 12 patients with stroke. Resting-state fMRI data were acquired four times over a period of 6 months. Patients participated in the first session of fMRI shortly after onset, and thereafter in subsequent sessions at 1, 3, and 6 months after onset. Resting-state functional connectivity of the ipsilesional M1 was assessed and compared with that of healthy subjects. Results Compared with healthy subjects, patients demonstrated higher functional connectivity with the ipsilesional frontal and parietal cortices, bilateral thalamus, and cerebellum. Instead, functional connectivity with the contralesional M1 and occipital cortex were decreased in stroke patients. Functional connectivity between the ipsilesional and contralesional M1 showed the most asymmetry at 1 month after onset to the ipsilesional side. Functional connectivity of the ipsilesional M1 with the contralesional thalamus, supplementary motor area, and middle frontal gyrus at onset was positively correlated with motor recovery at 6 months after stroke. Conclusions Resting-state fMRI elicited distinctive but comparable results with previous task-based fMRI, presenting complementary and practical values for use in the study of stroke patients.

Background and Purpose-Aside from the primary motor cortex, the corticospinal tract (CST) also receives fibers from dorsal and ventral premotor cortices and supplementary motor area, all of which might potentially contribute to motor function after stroke. We sought to quantify the microstructural integrity of CST originating from the hand representations in these 4 motor cortices separately and examined how these values related to hand motor impairment. Methods-Probabilistic tractography from functional MRI-defined cortical sites demonstrated continuous CST originating from hand representations within each motor area in a group of healthy subjects. Microstructural integrity for each tract was calculated using fractional anisotropy at the level of the posterior limb of the internal capsule in a group of patients with chronic stroke. Results-Fractional anisotropy was reduced in all 4 CSTs in the affected hemisphere. Grip strength correlated with the integrity of the CSTs originating from primary motor and dorsal premotor cortices, whereas, in a multiple regression model, the latter improved the ability of primary motor cortex CST to explain variability in grip strength. Conclusion-Handgrip critically depends on the CST originating in primary motor cortex but microstructural integrity of CST originating from premotor cortices appears to play a role in supporting motor function after stroke. (Stroke. 2012; 43:2248-2251.)

These findings demonstrate the plasticity and training induced redistribution of the visuospatial attentional network in TBI patients.

Stroke results in reorganization of residual brain networks. The functional role of brain regions within these networks remains unclear, particularly those in the contralesional hemisphere. We studied 25 stroke patients with a range of motor impairment and 23 healthy age-matched controls using magnetoencephalography (MEG) and electromyography (EMG) to measure oscillatory signals from the brain and affected muscles simultaneously during a simple isometric hand grip, from which cortico-muscular coherence (CMC) was calculated. Peaks of cortico-muscular coherence in both the beta and gamma bands were found in the contralateral sensorimotor cortex in all healthy controls, but were more widespread in stroke patients, including some peaks found in the contralesional hemisphere (7 patients for beta coherence and 5 for gamma coherence). Neither the coherence value nor the distance of the coherence peak from the mean of controls correlated with impairment. Peak CMC in the contralesional hemisphere was found not only in some highly impaired patients, but also in some patients with good functional recovery. Our results provide evidence that a wide range of cortical brain regions, including some in the contralesional hemisphere, may have influence over EMG activity in the affected muscles after stroke thereby supporting functional recovery.

The structural integrity of the corticospinal tract (CST) after stroke is closely linked to the degree of motor impairment. Simple and reliable methods of assessing white matter integrity within the CST would facilitate the use of this measure in routine clinical practice. Commonly, diffusion tensor imaging is used to measure voxel-wise fractional anisotropy (FA) in a variety of regions of interest (ROIs) representing the CST. Several methods are currently in use with no consensus about which approach is best. ROIs are usually either the whole CST or the posterior limb of the internal capsule (PLIC). These are created manually on brain images or with reference to an individual's CST determined by tractography. Once the ROI has been defined, the FA can be reported as an absolute measure from the ipsilesional side or as a ratio in comparison to the contralesional side. Both corticospinal tracking and manual ROI definition in individual stroke patients are time consuming and subject to bias. Here, we investigated whether using a CST template derived from healthy volunteers was a feasible method for defining the appropriate ROI within which to measure changes in FA. We reconstructed the CST connecting the primary motor cortex to the ipsilateral pons in 23 age-matched control subjects and 21 stroke patients. An average healthy CST template was created from the 23 control subjects. For each patient, FA values were then calculated for both the template CST and for their own CST. We compared patients' FA metrics between the two tracts by considering four measures (FA in the ipsilesional side, FA in the contralesional side, FA ratio of the ipsilesional side to the contralesional side and FA asymmetry between the two sides) and in two tract-based ROIs (whole tract and tract section traversing the PLIC). There were no significant differences in FA metrics for either method, except for contralesional FA. Furthermore, we found that FA metrics relating to CST damage all correlated with motor ability post-stroke equally well. These results suggest that the healthy CST template could be a surrogate structure for defining tract-based ROIs with which to measure stroke patients' FA metrics, avoiding the necessity for CST tracking in individual patients. CST template-based automated quantification of structural integrity would greatly facilitate implementation of practical clinical applications of diffusion tensor imaging.

Background The ability to predict outcome after stroke is clinically important for planning treatment and for stratification in restorative clinical trials. In relation to the upper limbs, the main predictor of outcome is initial severity, with patients who present with mild to moderate impairment regaining about 70% of their initial impairment by 3 months post-stroke. However, in those with severe presentations, this proportional recovery applies in only about half, with the other half experiencing poor recovery. The reasons for this failure to recover are not established although the extent of corticospinal tract damage is suggested to be a contributory factor. In this study, we investigated 30 patients with chronic stroke who had presented with severe upper limb impairment and asked whether it was possible to differentiate those with a subsequent good or poor recovery of the upper limb based solely on a T1-weighted structural brain scan. Methods A support vector machine approach using voxel-wise lesion likelihood values was used to show that it was possible to classify patients as good or poor recoverers with variable accuracy depending on which brain regions were used to perform the classification. Results While considering damage within a corticospinal tract mask resulted in 73% classification accuracy, using other (non-corticospinal tract) motor areas provided 87% accuracy, and combining both resulted in 90% accuracy. Conclusion This proof of concept approach highlights the relative importance of different anatomical structures in supporting post-stroke upper limb motor recovery and points towards methodologies that might be used to stratify patients in future restorative clinical trials.

Background Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain. Objective The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain. Methods Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale. Results Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders. Conclusion Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network.

Brain activity during motor performance becomes more widespread and less lateralized with advancing age in response to ongoing degenerative processes. In this study, we were interested in the mechanism by which this change in the pattern of activity supports motor performance with advancing age. We used both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to assess age related changes in motor system connectivity during isometric hand grip. Paired pulse TMS was used to measure the change in interhemispheric inhibition (IHI) from contralateral M1 (cM1) to ipsilateral M1 (iM1) during right hand grip. Dynamic Causal Modelling (DCM) of fMRI data was used to investigate the effect of age on causal interactions throughout the cortical motor network during right hand grip. Bayesian model selection was used to identify the causal model that best explained the data for all subjects. Firstly, we confirmed that the TMS and DCM measures both demonstrated a less inhibitory/more facilitatory influence of cM1 on iM1 during hand grip with advancing age. These values correlated with one another providing face validity for our DCM measures of connectivity. We found increasing reciprocal facilitatory influences with advancing age (i) between all ipsilateral cortical motor areas and (ii) between cortical motor areas of both hemispheres and iM1. There were no differences in the performance of our task with ageing suggesting that the ipsilateral cortical motor areas, in particular iM1, play a central role in maintaining performance levels with ageing through increasingly facilitatory cortico-cortical influences.