Remote changes in cortical excitability after stroke

Changes in the cerebral metabolism and the excitability of brain areas remote from an ischaemic brain lesion have been reported in animals and humans and implicated as a mechanism relevant to functional recovery. The aim of the present study was to determine whether changes in the inhibitory and excitatory activity in motor cortex of the non-affected hemisphere are present in stroke patients, and whether these changes are related to the extent of the patients' recovery of function. Transcranial magnetic stimulation (TMS) was used to study the first dorsal interosseus muscle (FDI) of the non-affected hand in 13 patients with good recovery of hand function after stroke, and was compared with left hemispheric stimulation in 13 healthy age-matched volunteers. In the first experiment, paired-pulse TMS with the conditioning stimulus (CS) set at 80% of the subject's motor threshold (MT) and interstimulus intervals (ISIs) of 2, 3, 10 and 15 ms was used. In the second experiment, different intensities of CS were used to study its inhibitory effect on a succeeding suprathreshold test stimulus at an ISI that was kept constant at 2 ms. In a third experiment, the rise in motor evoked potential (MEP) amplitudes with increasing stimulus intensities was measured. In two additional control experiments, the effect of left versus right hemispheric stimulation in normal volunteers and good versus poor recovery of hand function in patients after stroke on the excitability of inhibitory and excitatory activity was studied. MT, mean test MEP and recruitment curves were similar in patients and healthy volunteers. In those patients with good recovery, paired-pulse excitability was increased at ISIs of 2 and 3 ms, similar to healthy volunteers at ISIs of 10 and 15 ms. When tested with different CS intensities at an ISI of 2 ms, inhibitory activity was similar in patients and healthy subjects at small CS intensities, but faded rapidly at higher CS intensities in patients. In contrast, in patients with poor recovery, this increase in cortical excitability at higher CS intensities was not seen. The similarity of MT, mean test MEP and recruitment curves in patients and healthy volunteers indicates that the overall cortico-motoneuronal excitability has not changed in patients. The similarity of the inhibitory effect at low CS intensities in the patients with good recovery and healthy subjects, and the steeper increase of conditioned MEP amplitude at higher CS intensities in the recovering patients suggest that in the patients' contralesional motor cortex the balance of excitatory and inhibitory activity was shifted towards an increase of excitatory activity in the neuronal circuits tested at ISIs of 2 and 3 ms. This shares similarities to mechanisms implicated as relevant for reorganizational processes after experimental brain injury and may be relevant for functional recovery after stroke. The absence of changes in cortical excitability in patients with poor recovery supports the relevance of our findings for recovery.