Table 1.

Animal Studies of Direct Cortical Stimulation (CS) Combined with Rehabilitation Training (RT) for Upper Extremity Motor Recovery

Study	Animal model	Cortical Stimulation Parameters	Rehabilitation Training	Behavioral Outcomes	Neuroanatomical/Neurophysiological Outcomes
Kleim et al., 2003	Rodent Compared monopolar cathodal, bipolar cathodal, monopolar anodal, and no CS	Subdural 50Hz 1 sec pulse	Single pellet reaching task 20minutes/day for 10 days	Both monopolar and bipolar CS enhanced motor recover – monopolar stimulation more effective	Both monopolar and bipolar CS increased area of cortex from which microstimulation movements could be evoked
Teskey et al., 2003	Rodent Compared frequencies (0, 25, 50, 100, 250, and 500 Hz)	Subdural 0,25,50, 100, 250, 500 Hz 3 sec pulse 50% MT	Pasta Matrix Task 20 minutes/day for 10 days	CS with frequencies between 50 and 250 Hz more effective Returned to preinfarct training levels for reaching success.	Enhanced evoked potentials and lowering of the MT (25Hz and above) Larger polysynaptic potentiation between 50 and 500 Hz.
Adkins- Muir & Jones, 2003	Rodent Compared frequencies (50Hz, 250 Hz, and no CS)	Subdural 50Hz, 250 Hz no CS 3 sec pulse 50–70% MT	Montoya staircase – retrieved food pellets placed at variable distances on a “staircase” 20 minutes/day for 10 days	No sig. difference in reaching between 250 Hz and no CS. 50 Hz group had significantly greater rate of improvement in reaching	50 Hz significant increase in surface density of dendritic processes in perilesion cortex compared to other two groups
Plautz et al., 2003 Plautz & Nudo (2005)	Nonhuman Primate Assessed feasibility of CS/RT in primates	Subdural 50 Hz 50% MT 1 sec continuous stimulation – unlimited duration pulse train Monopolar Modified stimulus parameters – monopolar cathodal 100 μsec duration 100 Hz 50% MT	Unimanual pellet retrieval task requiring skilled use of hand – progressed through training stages in which gradual decrease in the diameter of the wells required increasing finger dexterity. Two 35 minute sessions per day for 30 days. CS initiated 5 minutes before RT.	Sig improvement in motor performance (success, speed, efficiency) of pellet retrieval which persisted for at least 4 months. Substantial but incomplete resolution of chronic motor performance deficits. Peak recovery level (% recovery to preinfarct level) was 88% for CS/RT and 43% for RT alone	Large scale emergence of new hand representations in peri-infarct motor cortex, notably in cortical tissue underlying the electrode
Adkins et al., 2006	Rodent Compared anodal versus cathodal stimulation	Epidural 100Hz monopolar stimulation 50% MT	Single pellet retrieval task 60 trials per day or 15 minutes whichever occurred first for 18 days	Demonstrated efficacy of epidural CS/RT Both anodal and cathodal CS enhanced reaching performance compared to no CS group	Cathodal CS/RT group showed increased neuronal density in perilesion cortex
Adkins et al., 2008	Rodent Compared effect of CS/RT on rats with moderate versus severe retrieval deficits	Epidural 100Hz monopolar cathodal stimulation 40–50% MT	Single pellet retrieval task 60 trials per day or 15 minutes whichever occurred first for 18 days	CS/RT enhanced recovery of reaching success in the moderately but not severely impaired subgroups.	Both CS/RT groups had increased density of axodendritic synapses compared to no CS and there was a positive correlation between post rehab reaching success and synaptic density.
Boychuk et al., 2011	Rodent Compared focal versus distributed CS	Epidural monopolar 1-second, 50- Hz cathodal pulse 50% motor threshold	Single pellet skilled reaching task 15 minutes/day for 12 consecutive days	Only the distributed CS/RT enhanced motor performance with RT.	Both the focal and distributed CS/RT promoted motor map reorganization

CS = cortical stimulation; RT = rehabilitation training; MT = motor threshold