Table 2.
Studies of Concurrent Direct Cortical Stimulation and Physical Rehabilitation for Functional Recovery in Stroke
| Study | Phase | Purpose | Electrode Type | Frequency Current Duration |
Behavioral Results | Reorganization Results |
|---|---|---|---|---|---|---|
| Plautz et al (2003) | Primate | Feasibility and safety | Subdural (circular 1.5 mm2) | 50 Hz 50% MT 1 s |
Improved distal forelimb function | Expansion of distal forelimb representation in peri-infarct M1 |
| Kleim et al (2003) | Rodent | Compare different polarities | Subdural electrodes (0.4 mm2) | 50 Hz 50% MT 1 s |
Higher reach accuracy in monopolar cathodal group | Increased functional peri-infarct cortex |
| Teskey et al (2003) | Rodent | Compare different frequencies | Subdural (0.4×3 mm2) | 0, 25, 50, 100, 250 Hz 50% MT 3 s |
Frequency ≥50 Hz showed increased accuracy | Frequency ≥50 Hz showed increased polysynaptic potentiation |
| Adkins-Muir and Jones (2003) | Rodent | Compare different frequencies | Subdural (1×3 mm2) | 0, 50, 250 Hz 50–70% MT 3 s |
50-Hz group improved most in accuracy | 50 Hz group— increased MAP-2 reactivity in the perilesional cortex |
| Adkins et al (2006) | Rodent | Compare polarities and try epidural method of electrode implantation | Epidural (0.4×2 mm2) | 0, 100 Hz 50% MT 3 s |
Reaching performance better in stimulated groups | Neuronal density increased in perilesional cortex in cathodal 100-Hz group |
| Adkins et al (2008) | Animal | Variation of Cortical stimulation effects based on impairment level | Epidural monopolar | 100 Hz 40–50% MT |
Reaching improved in moderately impaired rats, not in severely impaired rats | Moderately impaired rats showed increase in the efficacious synapses |
| Brown et al (2003) | Human-single case | Explore combined treatment in humans | Epidural | 50 Hz 4.5 mA 100 s |
Improvement on pincer movement, UEFM, and SIS | Not explored |
| Brown et al (2006) | Human-Phase I (8 patients) | Safety | Epidural (3×3 array of 2-mm electrodes) | 50 Hz 50% MT or 6.5 mA 3 s |
Improvement on UEFM and SIS—2 patients withdrawn | Not explored |
| Phase II (Huang et al, 2008; Levy et al, 2008) | Human (24 patients) | Efficacy and safety | Epidural (2×3 array of 3-mm electrodes) | 50 and 101 Hz 50% MT or 6.5 mA 3-s pulse trains |
Combined group showed greater improvement on UEFM and AMAT | Not explored |
| Phase III clinical trial | Humans (146 patients) | Effectiveness and safety | Epidural (2×3 array of 3-mm electrodes) | 50 Hz 50% MT or 6.5 mA 250-µs pulse duration |
Combined group not better than control group on UEFM and AMAT | Not explored |
SIS indicates Stroke Impact Scale; AMAT, Arm Motor Ability Test; MT, motor threshold; MAP, microtubule-associated protein.