Table 40.1.
Summary of previous studies investigating the effectiveness of inhibitory rTMS or tDCS over primary motor cortex of unaffected hemisphere on motor behavior
| Technique | Reference | Area of stimulation | No. of patients, mean age, lesion location, and time since stroke | Study design | Control condition | Stimulation parameters | Main results |
|---|---|---|---|---|---|---|---|
| rTMS, low frequency | Mansur et al., 2005 | Hand area of M1 and dorsal PMC, unaffected hemisphere | 10 adults, 54 years, 10 subcortical, <12 months | Single-blind, crossover, sham- controlled | Real TMS, sham TMS (sham coil), real TMS over PMC | 1 Hz, 100% rMT, 10 min | Decrease in simple and choice RTs and improved performance of Purdue Pegboard Test with affected hand after real rTMS |
| rTMS, low frequency | Takeuchi et al., 2005 | Hand area of M1, unaffected hemisphere | 20 adults, 59 years, 20 subcortical, 6–60 months | Double-blind, randomized, sham- controlled | 20 patients, 10 real TMS, 10 sham TMS (perpendicular to the scalp ) | 1 Hz, 90% rMT, 25 min | Real rTMS reduced MEP amplitude in contralesional M1 and abnormal transcallosal inhibition. Moreover rTMS induced improvement in pinch acceleration |
| rTMS, low frequency | Fregni et al., 2006 | Hand area of M1, unaffected hemisphere | 15 adults, 56 years, 2 cortical, 13 subcortical, 1–11 years | Single-blind, longitudinal, randomized, sham- controlled, Phase II | 15 patients, 10 real TMS, 5 patients sham TMS (sham coil) | 1 Hz, 100% MT, 20 min, repeated daily over 5 days | Real TMS resulted in improvement of motor function performance (Jebsen–Taylor Hand Function Test, simple and choice RTs, Purdue Pegboard Test) in affected hand that lasted for 2 weeks. Corticospinal excitability decreased in stimulated unaffected hemisphere and increased in affected hemisphere |
| rTMS, low frequency | Boggio et al., 2006 | Hand area of M1, unaffected hemisphere | 1 adult, 74-year- old woman, subcortical, 23–107 months | Double-blind, crossover, single-case study | Real TMS, sham TMS (sham coil) over M1 | 1 Hz, 100% rMT, 20 min | rTMS improved motor function (thumb and finger movements) |
| rTMS, low frequency | Liepert et al., 2007 | Hand area of M1, unaffected hemisphere | 12 adults, 64 years, 12 subcortical, <14 days | Double-blind, crossover, sham- controlled | Real TMS, sham TMS (sham coil) | 1 Hz, 90% rMT, 20 min | Real rTMS improved Nine Hole Peg Test results but not grip strength in affected hand |
| rTMS, low frequency | Dafotakis et al., 2008 | Hand area of M1, unaffected hemisphere | 12 adults, 45 years, 12 subcortical, 1–15 months | Double-blind, crossover, sham- controlled | Real TMS, sham TMS over vertex | 1 Hz, 100% rMT, 10 min | Real rTMS improved efficiency and timing of grasping and lifting with affected hand |
| rTMS, low frequency | Nowak et al., 2008 | Hand area of M1, unaffected hemisphere | 15 adults, 46 years, 15 subcortical, 1–4 months | Double-blind, crossover, sham- controlled | Real TMS, sham TMS over vertex | 1 Hz, 100 rMT, 10 min | Real rTMS improved kinematics of finger and grasp movements in affected hand and reduced overactivity in contralesional M1 and nonprimary motor areas. Overactivity of contralesional dorsal PMC, contralesional parietal operculum, and ipsilesional mesial frontal cortex at baseline predicted improvement of movement |
| rTMS, low frequency | Kirton et al., 2008 | Hand area of M1, unaffected hemisphere | 10 children, 14 years, 10 subcortical, 3–13 years | Single-blind, longitudinal, randomized, sham controlled | 10 patients, 5 real TMS, 5 sham TMS (perpendicular to scalp) | 1 Hz, 100% rMT, 20 min repeated daily for 8 days | Real rTMS improved grip strength and Melbourne assessment of upper extremity function |
| rTMS, low frequency | Takeuchi et al., 2008 | Hand area of M1, unaffected hemisphere | 20 adults, 62 years, 20 subcortical, 7–121 months | Double-blind, randomized, sham- controlled | 20 patients, 10 real TMS, 10 sham TMS (perpendicular to scalp) | 1 Hz, 90% rMT, 25 min +motor training | Real rTMS induced an increase in excitability in affected hemisphere and improvement in acceleration of affected hand. Improvements in motor function lasted for 1 week |
| rTMS, priming stimulation | Carey et al., 2008 | Hand area of M1, unaffected hemisphere | 10 adults, 66 years, 8 cortical, 2 subcortical, 16–192 months | No sham rTMS, sham- controlled | 10 patients real TMS | 10 min of 6 Hz (600 pulses), 90% rMT. Immediately after, 10 min of 1 Hz (600 pulses), 90% rMT | Safety of treatment. No seizures and impairment in National Institutes of Health Stroke Scale, Wechsler Adult Intelligence Scale (3rd edition), Hopkins Verbal Learning Test–Revised, Beck Depression Inventory (2nd edition) |
| rTMS, priming stimulation | Carey et al., 2010 | Hand area of M1, unaffected hemisphere | 2 adults, with middle cerebral artery stroke, 71-year-old male, 52-year-old female, >10 years | Longitudinal, no sham rTMS, sham- controlled | 2 patients real TMS | 10 min of 6 Hz (600 pulses), 90% rMT. Immediately after, 10 min of 1 Hz (600 pulses), 90% rMT, 5 sessions | fMRI showed that intervention disrupted cortical activation at contralesional M1. Behavioral results (Box and Block Test, Motor Activity Log) were mixed |
| rTMS, priming stimulation | Kakuda et al., 2011 | Hand area of M1, unaffected hemisphere | 11 adults, 61 years, 11 subcortical, average 70.2 months | Longitudinal, no sham rTMS, sham- controlled | 5 patients real TMS | 10 min of 6 Hz (600 pulses), 90% rMT. Immediately after, 20 min of 1 Hz (600 pulses), 90% rMT+OT, 15-day protocol, 22 sessions | rTMS improved Fugl–Meyer score and shortened log performance time of Wolf Motor Function Test |
| rTMS, low frequency | Kakuda et al., 2010a | Hand area of M1, unaffected hemisphere | 5 adults, 66.8 years, 5 subcortical, 14.6 months | Longitudinal, no sham rTMS, sham- controlled | 5 patients real TMS | 1 Hz (20 min, 90% rMT)+OT, 10 sessions over 6 consecutive days | Improvements in scores of Fugl– Meyer Assessment, Wolf Motor Function Test, and Ten-Second Test. No deterioration of improved upper limb function observed at 4 weeks after treatment |
| rTMS, low frequency | Kakuda et al., 2010b | Hand area of M1, unaffected hemisphere | 15 adults, 55 years, 15 subcortical, 57±55 months | Longitudinal | Real TMS | 1 Hz, 1200 pulses, 90% MT, 22 sessions in 2-week period combined with OT | Fugl–Meyer Assessment score increased in all 15 patients. Shortening of performance time on Wolf Motor Function Test noted in 12 patients. Modified Ashworth Scale score for some flexor muscles decreased in 12 patients |
| rTMS, low frequency | Grefkes et al., 2010 | Hand area of M1, unaffected hemisphere | 11 adults, 46 years, 11 subcortical, 1–3 months | Single-blind, crossover, sham- controlled | Real TMS, sham TMS over vertex | 1 Hz, 100% rMT, 10 min | Real rTMS improved motor performance of paretic hand. Connectivity analysis (Dynamic Causal Modeling) revealed that behavioral improvements were significantly correlated with a reduction of negative influences originating from contralesional M1 during paretic hand movements. Concurrently, endogenous coupling between ipsilesional SMA and M1 was significantly enhanced only after rTMS |
| rTMS, low frequency | Conforto et al., 2012 | Hand area of M1, unaffected hemisphere | 30 adults, 55.75 years, 14 corticosub- cortical, 16 subcortical, average 27.65 days | Double-blind, randomized, longitudinal, sham- controlled | 30 patients, 15 real TMS, 15 sham TMS (perpendicular to vertex) | 1 Hz, 90% rMT, 25 min, 10 sessions | Real rTMS improved performance in Jebsen–Taylor Test (1 month after treatment) and pinch force |
| rTMS, low frequency | Kakuda et al., 2011 | Hand area of M1, unaffected hemisphere | 204 adults, 58.4 years, 107 intracerebral hemorrhage, 27 cerebral cortical infarction, 70 lacunar infarction, 5.0±4.5 years | Multi-center, longitudinal, no sham rTMS, sham- controlled | 204 patients real TMS | 1 Hz, 90% rMT, 20 min, 120-min intensive OT daily, 22 sessions during 15-day hospitali-zation | Fugl–Meyer Assessment score and Wolf Motor Function Test log performance time decreased significantly at discharge. Changes seen persistently up to 4 weeks after discharge in 79 patients |
| rTMS, low frequency | Avenanti et al., 2012 | Hand area of M1, unaffected hemisphere | 30 adults, 60.9 years, 29 subcortical, 1 cortical, average 31 months | Double-blind, randomized, parallel, factorial design, longitudinal, sham- controlled, Phase II | 30 patients, 8 real TMS+PT, 8 PT+real TMS, 7 sham TMS+PT, 7PT+sham TMS | 1 Hz, 90% rMT, 25 min, 45 min physical training daily, 10 sessions | Behavioral improvement (Jebsen– Taylor Hand Function Test, Nine- Hole Peg Test) and reduction of interhemispheric inhibition found after real rTMS, with the group receiving real TMS+PT showing robust and stable improvements, and the other group (PT+real TMS) showing a slight improvement decline over time |
| tDCS, cathodal | Nair et al., 2011 | Hand area of M1, unaffected hemisphere | 14 adults, 58.5 years, 9 cortical and 5 subcortical, average 30.5 months | Double-blind, randomized, longitudinal, sham- controlled | 14 patients, 7 cathodal tDCS, 7 sham tDCS | 60 min of OT and 30 min of tDCS (1 mA) each day for 5 days in a row | Cathodal tDCS+OT results in more improvement in range-of-motion in multiple joints of paretic upper extremity and in upper extremity Fugl–Meyer score than sham tDCS+OT |
fMRI, functional magnetic resonance imaging; M1, primary motor cortex; MEP, motor evoked potential; OT, occupational therapy; PMC, premotor cortex; PT, physical training; rMT, resting motor threshold; RT, reaction time; rTMS, repetitive transcranial magnetic stimulation; SMA, supplementary motor area; tDCS, transcranial direct current stimulation.