Objective: Motor recovery after stroke depends on the integrity of ipsilesional motor circuits and interactions between the ipsilesional and contralesional hemispheres. In this sham-controlled randomized trial, we investigated whether noninvasive modulation of regional excitability of bilateral motor cortices in combination with physical and occupational therapy improves motor outcome after stroke. Methods:Twenty chronic stroke patients were randomly assigned to receive 5 consecutive sessions of either 1) bihemispheric transcranial direct current stimulation (tDCS) (anodal tDCS to upregulate excitability of ipsilesional motor cortex and cathodal tDCS to downregulate excitability of contralesional motor cortex) with simultaneous physical/occupational therapy or 2) sham stimulation with simultaneous physical/occupational therapy. Changes in motor impairment (Upper Extremity Fugl-Meyer) and motor activity (Wolf Motor Function Test) assessments were outcome measures while functional imaging parameters were used to identify neural correlates of motor improvement.

Objective: Motor impairment after stroke has been related to infarct size, infarct location, and integrity of motor tracts. To determine the value of diffusion tensor imaging (DTI) as a predictor of motor outcome and its role as a structural surrogate marker of impairment in chronic stroke, we tested correlations between motor impairment and DTI-derived measures of motor tract integrity.Methods: Thirty-five chronic stroke patients with varying degrees of recovery underwent DTI and motor impairment assessments. Fibers originating from the precentral gyrus were traced and separated into pyramidal tract (PT) and alternate motor fibers (aMF). Asymmetry indices of fiber number and regional fractional anisotropy (FA) values comparing lesional with nonlesional hemispheres were correlated with motor impairment scores and compared to an age-matched control group.Results: Fiber number and regional FA value asymmetry significantly differed between the groups with lower values in the patients' lesional hemispheres. Both measures significantly predicted motor impairment with stronger predictions when all motor tracts were combined as compared to predictions using only the PT. The pattern of motor tract damage (PT only vs PT and aMF) led to a classification of mild, moderate, or severe impairment with significant between-group differences in motor impairment scores.Conclusions: Diffusion tensor imaging-derived measures are valid structural markers of motor impairment. The integrity of all descending motor tracts, not merely the pyramidal tract, appears to account for stroke recovery. A 3-tier, hierarchical classification of impairment categories based on the pattern of motor tract damage is proposed that might be helpful in predicting recovery potential. Neurology Motor impairment after stroke has been related to lesion site and size, 1,2 amount of previous lesion burden, and other factors like age or comorbidities. 3,4 It has also been shown that the integrity of motor fibers, with the pyramidal tract (PT) as the main descending fiber bundle, but also the cortico-rubro-spinal or cortico-reticulo-spinal systems, 5,6 plays an important role for the degree of motor impairment which can be measured with standardized, reliable, and valid clinical assessments. 7,8 However, mere lesion location may not sufficiently demonstrate the extent to which motor fibers remain intact and a considerable amount of variance remains unexplained.Diffusion tensor imaging (DTI) allows for the visualization and quantitative examination of fiber tracts and their integrity in vivo 9 so that the topographic relation of lesion location and corticospinal fibers can be evaluated [10][11][12][13][14] and fiber degeneration can be revealed.

Electrophysiological and neuroimaging studies suggest that the integrity of ipsilesional and inter-hemispheric motor circuits is important for motor recovery after stroke. However, the extent to which each of these tracts contributes to the variance in outcome remains unclear. We examined whether diffusion tensor imaging (DTI)-derived measures of corticospinal and transcallosal tracts predict motor improvement in an experimental neurorehabilitation trial. 15 chronic stroke patients received bihemispheric transcranial direct current stimulation and simultaneous physical/occupational therapy for five consecutive days. Motor impairment was assessed prior to and after the intervention. At baseline, the patients underwent DTI; probabilistic fiber tracking was used to reconstruct the pyramidal tract (PT), alternate descending motor fibers (aMF) and transcallosal fibers connecting primary motor cortices (M1-M1). Ipsilesional corticospinal tracts (PT, aMF) and M1-M1 showed significantly decreased fractional anisotropy (FA) and increased directional diffusivities when compared to age-matched healthy controls. Partial correlations revealed that greater gains in motor functions were related to higher FA values and lower directional diffusivities of transcallosal and ipsilesional corticospinal tracts. M1-M1 diffusivity had the greatest predictive value. An additional slice-by-slice analysis of FA values along the corticospinal tracts demonstrated that the more the ipsilesional FA profiles of patients resembled those of healthy controls, the greater their functional improvement. In conclusion, our study shows that DTI-derived measures can be used to predict functional potential for subsequent motor recovery in chronic stroke patients. Diffusivity parameters of individual tracts and tract combinations may help in assessing a patient’s individual recovery potential and in determining optimal neurorehabilitative interventions.

The rising proportion of elderly people worldwide will yield an increased incidence of age-associated cognitive impairments, imposing major burdens on societies. Consequently, growing interest emerged to evaluate new strategies to delay or counteract cognitive decline in aging. Here, we assessed immediate effects of anodal transcranial direct current stimulation (atDCS) on cognition and previously described detrimental changes in brain activity attributable to aging. Twenty healthy elderly adults were assessed in a crossover shamcontrolled design using functional magnetic resonance imaging (fMRI) and concurrent transcranial DCS administered to the left inferior frontal gyrus. Effects on performance and task-related brain activity were evaluated during overt semantic word generation, a task that is negatively affected by advanced age. Task-absent resting-state fMRI (RS-fMRI) assessed atDCS-induced changes at the network level independent of performance. Twenty matched younger adults served as controls. During sham stimulation, task-related fMRI demonstrated that enhanced bilateral prefrontal activity in older adults was associated with reduced performance. RS-fMRI revealed enhanced anterior and reduced posterior functional brain connectivity. atDCS significantly improved performance in older adults up to the level of younger controls; significantly reduced task-related hyperactivity in bilateral prefrontal cortices, the anterior cingulate gyrus, and the precuneus; and induced a more "youth-like" connectivity pattern during RS-fMRI. Our results provide converging evidence from behavioral analysis and two independent functional imaging paradigms that a single session of atDCS can temporarily reverse nonbeneficial effects of aging on cognition and brain activity and connectivity. These findings may translate into novel treatments to ameliorate cognitive decline in normal aging in the future.

Background and Purpose-Previous studies have shown motor impairment after a stroke relates to lesion size and location, but unexplained variability in recovery still exists. In this study, we used lesion-mapping techniques in combination with diffusion tensor imaging to quantitatively test the hypothesis that motor recovery in patients with chronic stroke is inversely related to the proportion of the corticospinal tract (CST) affected by the lesion. Methods-We studied 50 patients with chronic stroke, all of whom presented with moderate to severe motor impairments in the acute stage, using high-resolution anatomic MRI. We evaluated the degree of motor impairment with the Upper Extremity module of the Fugl-Meyer Assessment. To analyze the relationship between CST damage and impairment scores, we calculated a CST-lesion load for each patient by overlaying the patient's lesion map with a probabilistic tract derived from diffusion tensor images of age-matched healthy subjects. Results-CST-lesion load was a significant predictor of motor deficit. Infarct size, despite correlating with motor scores, did not significantly predict impairment. Conclusions-Our results show the degree of functional motor deficit after a stroke is highly dependent on the overlap of the lesion with the CST and not lesion size per se. In the future, automated calculation of CST-lesion load may allow more precise prediction of motor impairment after stroke. (Stroke. 2010;41:910-915.)

Excitatory anodal transcranial direct current stimulation (atDCS) can improve human cognitive functions, but neural underpinnings of its mode of action remain elusive. In a cross-over placebo ("sham") controlled study we used functional magnetic resonance imaging (fMRI) to investigate neurofunctional correlates of improved language functions induced by atDCS over a core language area, the left inferior frontal gyrus (IFG). Intrascanner transcranial direct current stimulation-induced changes in overt semantic word generation assessed behavioral modulation; task-related and task-independent (resting-state) fMRI characterized language network changes. Improved word-retrieval during atDCS was paralleled by selectively reduced task-related activation in the left ventral IFG, an area specifically implicated in semantic retrieval processes. Under atDCS, resting-state fMRI revealed increased connectivity of the left IFG and additional major hubs overlapping with the language network. In conclusion, atDCS modulates endogenous low-frequency oscillations in a distributed set of functionally connected brain areas, possibly inducing more efficient processing in critical task-relevant areas and improved behavioral performance.

Transcranial direct current stimulation has shown promise to improve recovery in patients with post-stroke aphasia, but previous studies have only assessed stimulation effects on impairment parameters, and evidence for long-term maintenance of transcranial direct current stimulation effects from randomized, controlled trials is lacking. Moreover, due to the variability of lesions and functional language network reorganization after stroke, recent studies have used advanced functional imaging or current modelling to determine optimal stimulation sites in individual patients. However, such approaches are expensive, time consuming and may not be feasible outside of specialized research centres, which complicates incorporation of transcranial direct current stimulation in day-to-day clinical practice. Stimulation of an ancillary system that is functionally connected to the residual language network, namely the primary motor system, would be more easily applicable, but effectiveness of such an approach has not been explored systematically. We conducted a randomized, parallel group, sham-controlled, double-blind clinical trial and 26 patients with chronic aphasia received a highly intensive naming therapy over 2 weeks (8 days, 2 × 1.5 h/day). Concurrently, anodal-transcranial direct current stimulation was administered to the left primary motor cortex twice daily at the beginning of each training session. Naming ability for trained items (n = 60 pictures that could not be named during repeated baseline assessments), transfer to untrained items (n = 284 pictures) and generalization to everyday communication were assessed immediately post-intervention and 6 months later. Naming ability for trained items was significantly improved immediately after the end of the intervention in both the anodal (Cohen's d = 3.67) and sham-transcranial direct current stimulation groups (d = 2.10), with a trend for larger gains in the anodal-transcranial direct current stimulation group (d = 0.71). Treatment effects for trained items were significantly better maintained in the anodal-transcranial direct current stimulation group 6 months later (d = 1.19). Transfer to untrained items was significantly larger in the anodal-transcranial direct current stimulation group after the training (d = 1.49) and during the 6 month follow-up assessment (d = 3.12). Transfer effects were only maintained in the anodal-transcranial direct current stimulation group. Functional communication was significantly more improved in the anodal-transcranial direct current stimulation group at both time points compared to patients treated with sham-transcranial direct current stimulation (d = 0.75-0.99). Our results provide the first evidence from a randomized, controlled trial that transcranial direct current stimulation can improve both function and activity-related outcomes in chronic aphasia, with medium to large effect sizes, and that these effects are maintained over extended periods of time. These effects were achieved with an easy-to-implement and thus clinical...

Anodal-tDCS exerts beneficial effects on cognition and brain functions in MCI, thereby providing a framework to test whether repeated stimulation sessions may yield sustained reversal of cognitive deficits.