Modulation of movement-related intracortical inhibition (SICI) in acute stroke predicts motor recovery after one year

Introduction: It has been proposed that changes of intracortical inhibition (ICI) contribute to reorganization of motor circuits following stroke. However, it is not known how movement-related ICI changes in the early days after stroke and whether early modifications of ICI contribute to long-term motor recovery.

Methods: Using transcranial magnetic stimulation, we investigated GABAergic short-interval ICI (SICI) in the ipsilesional primary motor cortex (M1) of patients with acute subcortical stroke (n=11; 63.2±3.0 years) and in the left hemisphere of right-handed healthy control subjects (n=9; 65.2±1.4). SICI was obtained in a simple reaction time (RT) paradigm at four different time points during preparation of a movement with the affected hand (t1: 20%, t2: 50%, t3: 80%, t4: 95% of individual RT). Modulation of SICI (SICImod) was calculated as the ratio of t4/t1. To test the hypothesis whether changes in SICImod early after stroke predicted motor recovery the Nine Hole Peg Test (NHPT), speed (FTs) and accuracy (FTa) of unimanual finger tapping as well as grip strength (GS), for which M1 is particularly essential, were evaluated. Physiological and behavioural measurements were evaluated at 3–5 days, 6 weeks, 3 months and 1 year after stroke. Motor recovery was defined as the difference of values at 1 year compared to 3 days after stroke in each test.

Results: In the healthy control subjects we observed a continuous decrease of SICI during movement preparation with high SICImod values. During the 1st week and 6 weeks after stroke SICImod was comparable to healthy control subjects, but some of the patients already demonstrated a decrease of SICI mod during the first week. At 3 months the complete stroke group consistently showed less SICImod than healthy subjects (p=0.002). At 1 year after stroke, SICImod returned to normal in most of the subjects. Multiple regression analysis demonstrated that SICImod in the acute stage (first week), but none of any later measurements predicted the recovery in GS (F=31.26, p<0.001) and FTs (F=15.29, p=0.008) one year after stroke. Patients that had less SICImod in the acute stage proved to develop greater motor functional gains. Partial correlation analyses including initial degree of motor function as a control variable confirmed multiple regression results (GS: Pearson's r=–0.9, p=0.004; FTs: Pearson's r=–0.7, p=0.06) and stress the association of acute SICImod with motor recovery. However, persistent loss of SICImod in the chronic stage was associated with less FTa (Pearson's r=–0.6, p=0.03) and slower performance in the NHPT (Pearson's r=–0.8, p=0.007).

Conclusions: Our study lends evidence to the assumption that reorganization of SICI in acute stroke patients might be one essential factor for motor recovery. Our results also demonstrated that persistent loss of SICImod may have a detrimental effect on motor function in the chronic phase. Hence, any therapeutic intervention targeting movement-related SICI in the stroke hemisphere needs to be transient and precisely timed.