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1.  Predicting behavioural response to TDCS in chronic motor stroke☆ 
Neuroimage  2014;85(Pt 3):924-933.
Transcranial direct current stimulation (TDCS) of primary motor cortex (M1) can transiently improve paretic hand function in chronic stroke. However, responses are variable so there is incentive to try to improve efficacy and or to predict response in individual patients. Both excitatory (Anodal) stimulation of ipsilesional M1 and inhibitory (Cathodal) stimulation of contralesional M1 can speed simple reaction time. Here we tested whether combining these two effects simultaneously, by using a bilateral M1–M1 electrode montage, would improve efficacy. We tested the physiological efficacy of Bilateral, Anodal or Cathodal TDCS in changing motor evoked potentials (MEPs) in the healthy brain and their behavioural efficacy in changing reaction times with the paretic hand in chronic stroke. In addition, we aimed to identify clinical or neurochemical predictors of patients' behavioural response to TDCS. There were three main findings: 1) unlike Anodal and Cathodal TDCS, Bilateral M1–M1 TDCS (1 mA, 20 min) had no significant effect on MEPs in the healthy brain or on reaction time with the paretic hand in chronic stroke patients; 2) GABA levels in ipsilesional M1 predicted patients' behavioural gains from Anodal TDCS; and 3) although patients were in the chronic phase, time since stroke (and its combination with Fugl–Meyer score) was a positive predictor of behavioural gain from Cathodal TDCS. These findings indicate the superiority of Anodal or Cathodal over Bilateral TDCS in changing motor cortico-spinal excitability in the healthy brain and in speeding reaction time in chronic stroke. The identified clinical and neurochemical markers of behavioural response should help to inform the optimization of TDCS delivery and to predict patient outcome variability in future TDCS intervention studies in chronic motor stroke.
Highlights
•Ipsilesional M1 GABA levels predict motor gains from Anodal TDCS in chronic stroke.•Time since stroke and Fugl–Meyer score jointly predict response to Cathodal TDCS.•Bilateral motor cortex TDCS did not reliably change motor evoked potentials.•Bilateral motor cortex TDCS did not reliably change manual reaction time.
doi:10.1016/j.neuroimage.2013.05.096
PMCID: PMC3899017  PMID: 23727528
Motor stroke; Plasticity; TDCS; Brain stimulation; Magnetic resonance spectroscopy; GABA
2.  Relationships between functional and structural corticospinal tract integrity and walking post stroke 
Clinical Neurophysiology  2012;123(12):2422-2428.
Highlights
► We investigated the relationship between walking impairment after stroke and integrity of the corticospinal tract (CST). ► We used transcranial magnetic stimulation and diffusion tensor imaging to assess CST integrity. ► We demonstrate that patients with more ipsilateral connectivity between the unlesioned M1 and the affected leg had more structural damage to their CST.
Objective
Studies on upper limb recovery following stroke have highlighted the importance of the structural and functional integrity of the corticospinal tract (CST) in determining clinical outcomes. However, such relationships have not been fully explored for the lower limb. We aimed to test whether variation in walking impairment was associated with variation in the structural or functional integrity of the CST.
Methods
Transcranial magnetic stimulation was used to stimulate each motor cortex while EMG recordings were taken from the vastus lateralis (VL) bilaterally; these EMG measures were used to calculate both ipsilateral and contralateral recruitment curves for each lower limb. The slope of these recruitment curves was used to examine the strength of functional connectivity from the motor cortex in each hemisphere to the lower limbs in chronic stroke patients and to calculate a ratio between ipsilateral and contralateral outputs referred to as the functional connectivity ratio (FCR). The structural integrity of the CST was assessed using diffusion tensor MRI to measure the asymmetry in fractional anisotropy (FA) of the internal capsule. Lower limb impairment and walking speed were also measured.
Results
The FCR for the paretic leg correlated with walking impairment, such that greater relative ipsilateral connectivity was associated with slower walking speeds. Asymmetrical FA values, reflecting reduced structural integrity of the lesioned CST, were associated with greater walking impairment. FCR and FA asymmetry were strongly positively correlated with each other.
Conclusions
Patients with relatively greater ipsilateral connectivity between the contralesional motor cortex and the paretic lower limb were more behaviorally impaired and had more structural damage to their ipsilesional hemisphere CST.
Significance
Measures of structural and functional damage may be useful in the selection of therapeutic strategies, allowing for more tailored and potentially more beneficial treatments.
doi:10.1016/j.clinph.2012.04.026
PMCID: PMC3778984  PMID: 22717679
CST, corticospinal tract; DTI, diffusion tensor imaging; FA, fractional anisotropy; FCR, functional connectivity ratio; M1, primary motor cortex; TMS, transcranial magnetic stimulation; VL, vastus lateralis; Stroke; Locomotion; Motor recovery; TMS; DTI
3.  Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke 
Brain  2011;135(1):276-284.
Transcranial direct current stimulation, a form of non-invasive brain stimulation, is showing increasing promise as an adjunct therapy in rehabilitation following stroke. However, although significant behavioural improvements have been reported in proof-of-principle studies, the underlying mechanisms are poorly understood. The rationale for transcranial direct current stimulation as therapy for stroke is that therapeutic stimulation paradigms increase activity in ipsilesional motor cortical areas, but this has not previously been directly tested for conventional electrode placements. This study was performed to test directly whether increases in ipsilesional cortical activation with transcranial direct current stimulation are associated with behavioural improvements in chronic stroke patients. Patients at least 6 months post-first stroke participated in a behavioural experiment (n = 13) or a functional magnetic resonance imaging experiment (n = 11), each investigating the effects of three stimulation conditions in separate sessions: anodal stimulation to the ipsilesional hemisphere; cathodal stimulation to the contralesional hemisphere; and sham stimulation. Anodal (facilitatory) stimulation to the ipsilesional hemisphere led to significant improvements (5–10%) in response times with the affected hand in both experiments. This improvement was associated with an increase in movement-related cortical activity in the stimulated primary motor cortex and functionally interconnected regions. Cathodal (inhibitory) stimulation to the contralesional hemisphere led to a functional improvement only when compared with sham stimulation. We show for the first time that the significant behavioural improvements produced by anodal stimulation to the ipsilesional hemisphere are associated with a functionally relevant increase in activity within the ipsilesional primary motor cortex in patients with a wide range of disabilities following stroke.
doi:10.1093/brain/awr313
PMCID: PMC3267983  PMID: 22155982
transcranial direct current stimulation; stroke rehabilitation; motor system

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