***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background . No rehabilitation intervention has effectively improved functional use of the arm and h and in patients with severe upper limb paresis after stroke . Pilot studies suggest the potential for transcranial direct current stimulation and bilateral robotic training to enhance gains . Objective . In a double-blind , r and omized trial the combination of these interventions was tested . Methods . This study r and omized 96 patients with an ischemic supratentorial lesion of 3 to 8 weeks ’ duration with severe impairment of motor control with a Fugl-Meyer score ( FMS ) for the upper limb < 18 into 3 groups . For 6 weeks , group A received anodal stimulation of the lesioned hemisphere , group B received cathodal stimulation of the nonlesioned side for 20 minutes at 2.0 mA , and group C received sham stimulation . The electrodes were placed over the h and area and above the contralateral orbit . Contemporaneously , the subjects practice d 400 repetitions each of 2 different bilateral movements on a robotic assistive device . Results . The groups were matched at onset . The FMS improved in all patients at 6 weeks ( P < .001 ) . No between-group differences were found ; initial versus finish FMS scores were 7.8 ± 3.8 versus 19.1 ± 14.4 in group A , 7.9 ± 3.4 versus 18.8 ± 10.5 in group B , and 8.2 ± 4.4 versus 19.2 ± 15.0 in group C. No significant changes between groups were present at 3 months . Conclusions . Neither anodal nor cathodal transcranial direct current stimulation enhanced the effect of bilateral arm training in this exploratory trial of patients with cortical involvement and severe weakness . Unilateral h and training and upregulation of the nonlesioned hemisphere might also be tried in this population 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 r and omized 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 r and omly 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 ) assessment s were outcome measures while functional imaging parameters were used to identify neural correlates of motor improvement . Results : The improvement of motor function was significantly greater in the real stimulation group ( 20.7 % in Fugl-Meyer and 19.1 % in Wolf Motor Function Test scores ) when compared to the sham group ( 3.2 % in Fugl-Meyer and 6.0 % in Wolf Motor Function Test scores ) . The effects outlasted the stimulation by at least 1 week . In the real-stimulation group , stronger activation of intact ipsilesional motor regions during paced movements of the affected limb were found postintervention whereas no significant activation changes were seen in the control group . Conclusions : The combination of bihemispheric tDCS and peripheral sensorimotor activities improved motor functions in chronic stroke patients that outlasted the intervention period . This novel approach may potentiate cerebral adaptive processes that facilitate motor recovery after stroke . Classification of evidence : This study provides Class I evidence that for adult patients with ischemic stroke treated at least 5 months after their first and only stroke , bihemispheric tDCS and simultaneous physical/occupational therapy given over 5 consecutive sessions significantly improves motor function as measured by the Upper Extremity Fugl-Meyer assessment ( raw change treated 6.1 ± 3.4 , sham 1.2 ± 1.0 ) Transcranial direct current stimulation ( tDCS ) can up- and down-regulate cortical excitability depending on current direction , however our abilities to measure brain-tissue effects of the stimulation and its after-effects have been limited so far . We used regional cerebral blood flow ( rCBF ) , a surrogate measure of brain activity , to examine regional brain-tissue and brain-network effects during and after tDCS . We varied the polarity ( anodal and cathodal ) as well as the current strength ( 0.8 to 2.0mA ) of the stimulation .  Fourteen healthy subjects were r and omized into receiving either anodal or cathodal stimulation ( two subjects received both , one week apart ) while undergoing Arterial Spin Labeling ( ASL ) in the MRI scanner with an alternating off-on sampling paradigm . The stimulating , MRI-compatible electrode was placed over the right motor region and the reference electrode over the contralateral supra-orbital region . SPM5 was used to process and extract the rCBF data using a 10 mm spherical volume of interest ( VOI ) placed in the motor cortex directly underneath the stimulating scalp electrode . Anodal stimulation induced a large increase ( 17.1 % ) in rCBF during stimulation , which returned to baseline after the current was turned off , but exhibited an increase in rCBF again in the post-stimulation period . Cathodal stimulation induced a smaller increase ( 5.6 % ) during stimulation , a significant decrease compared to baseline ( -6.5 % ) after cessation , and a continued decrease in the post-stimulation period . These changes in rCBF were all significant when compared to the pre-stimulation baseline or to a control region . Furthermore , for anodal stimulation , there was a significant correlation between current strength and the increase in rCBF in the on-period relative to the pre-stimulation baseline . The differential rCBF after-effects of anodal ( increase in resting state rCBF ) and cathodal ( decrease in resting state rCBF ) tDCS support findings of behavioral and cognitive after-effects after cathodal and anodal tDCS . We also show that tDCS not only modulates activity in the brain region directly underlying the stimulating electrode but also in a network of brain regions that are functionally related to the stimulated area . Our results indicate that ASL may be an excellent tool to investigate the effects of tDCS and its stimulation parameters on brain activity OBJECTIVES 1 ) To investigate the feasibility of combining transcranial direct current stimulation ( tDCS ) to the lower extremity ( LE ) motor cortex with novel locomotor training to facilitate gait in subjects with chronic stroke and low ambulatory status , and 2 ) to obtain insight from study subjects and their caregivers to inform future trial design . METHODS Double-blind , r and omized controlled study with additional qualitative exploratory descriptive design . One-month follow-up.10 subjects with stroke were recruited and r and omized to active tDCS or sham tDCS for 12 sessions . Both groups participated in identical locomotor training with a robotic gait orthosis ( RGO ) following each tDCS session . RGO training protocol was design ed to harness cortical neuroplasticity . Data analysis included assessment of functional and participation outcome measures and qualitative thematic analysis . RESULTS Eight subjects completed the study . Both groups demonstrated trends toward improvement , but the active tDCS group showed greater improvement than the sham group . Qualitative analyses indicated beneficial effects of this combined intervention . CONCLUSIONS It is feasible to combine tDCS targeting the LE motor cortex with our novel locomotor training . It appears that tDCS has the potential to enhance the effectiveness of gait training in chronic stroke . Insights from participants provide additional guidance in design ing future trials Weak transcranial direct current stimulation ( tDCS ) induces persisting excitability changes in the human motor cortex . These plastic excitability changes are selectively controlled by the polarity , duration and current strength of stimulation . To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity , we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine ( CBZ ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan ( DMO ) . Monitored by transcranial magnetic stimulation ( TMS ) , motor cortical excitability changes of up to 40 % were achieved in the drug-free condition . Increase of cortical excitability could be selected by anodal stimulation , and decrease by cathodal stimulation . Both types of excitability change lasted several minutes after cessation of current stimulation . DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation , strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity . In contrast , CBZ selectively eliminated anodal effects . Since CBZ stabilizes the membrane potential voltage-dependently , the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials . Similar to the induction of established types of short- or long-term neuroplasticity , a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS . On the basis of these results , we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects , leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation Transcranial direct current stimulation ( tDCS ) over the primary motor cortex ( M1 ) has been shown to induce changes in motor performance and learning . Recent studies indicate that tDCS is capable of modulating widespread neural network properties within the brain . However the temporal evolution of online- and after-effects of tDCS on functional connectivity ( FC ) within and across the stimulated motor cortices ( M1 ) still remain elusive . In the present study , two different tDCS setups were investigated : ( i ) unilateral M1 tDCS ( anode over right M1 , cathode over the contralateral supraorbital region ) and ( ii ) bilateral M1 tDCS ( anode over right M1 , cathode over left M1 ) . In a r and omized single-blinded cross-over design , 12 healthy subjects underwent functional magnetic resonance imaging at rest before , during and after 20 min of either bi- , unilateral , or sham M1 tDCS . Seed-based FC analysis was used to investigate tDCS-induced changes across and within M1 . We found that bilateral M1 tDCS induced ( a ) a decrease in interhemispheric FC during stimulation and ( b ) an increase in intracortical FC within right M1 after termination of the intervention . While unilateral M1 tDCS also result ed in similar effects during stimulation , no such changes could be observed after termination of tDCS . Our results provide evidence that depending on the electrode montage , tDCS acts upon a modulation of either intracortical and /or interhemispheric processing of M1 OBJECTIVE To investigate the efficacy and effects of transcranial direct current stimulation ( tDCS ) on motor imagery brain-computer interface ( MI-BCI ) with robotic feedback for stroke rehabilitation . DESIGN A sham-controlled , r and omized controlled trial . SETTING Patients recruited through a hospital stroke rehabilitation program . PARTICIPANTS Subjects ( N=19 ) who incurred a stroke 0.8 to 4.3 years prior , with moderate to severe upper extremity functional impairment , and passed BCI screening . INTERVENTIONS Ten sessions of 20 minutes of tDCS or sham before 1 hour of MI-BCI with robotic feedback upper limb stroke rehabilitation for 2 weeks . Each rehabilitation session comprised 8 minutes of evaluation and 1 hour of therapy . MAIN OUTCOME MEASURES Upper extremity Fugl-Meyer Motor Assessment ( FMMA ) scores measured end-intervention at week 2 and follow-up at week 4 , online BCI accuracies from the evaluation part , and laterality coefficients of the electroencephalogram ( EEG ) from the therapy part of the 10 rehabilitation sessions . RESULTS FMMA score improved in both groups at week 4 , but no intergroup differences were found at any time points . Online accuracies of the evaluation part from the tDCS group were significantly higher than those from the sham group . The EEG laterality coefficients from the therapy part of the tDCS group were significantly higher than those of the sham group . CONCLUSIONS The results suggest a role for tDCS in facilitating motor imagery in stroke Transcranial direct current stimulation ( tDCS ) of the primary motor h and area ( M1 ) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans . In 16 healthy volunteers , O positron emission tomography ( PET ) of regional cerebral blood flow ( rCBF ) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS ( + /-1 mA ) . Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex . Eight subjects received anodal or cathodal tDCS  of the left M1 , respectively . When compared to sham tDCS , anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas . These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning . Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1 , right frontal pole , right primary sensorimotor cortex and posterior brain regions ir 
    Output:
    
4 moderator variable analyses revealed beneficial effects of tDCS on long-term motor learning : ( 1 ) stimulation protocol s : anodal on the ipsilesional hemisphere , cathodal on the contralesional hemisphere , or bilateral ; ( 2 ) recovery stage : subacute or chronic stroke ; ( 3 ) stimulation timing : tDCS before or during motor practise ; and ( 4 ) task-specific training or conventional rehabilitation protocol s. This robust meta- analysis identified novel long-term motor learning effects with tDCS and motor practise post-stroke