Objective:
To determine the mechanisms on cognitive improvement with repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex(L-DLPFC) in subacute stroke patients.
Methods
Twenty-eight first-ever stroke patients with cognitive impairment were recruited. All subjects were randomly assigned to real or sham stimulation group and completed 10 sessions of rTMS for 2 weeks. 10Hz of navigation rTMS were applied (5sec stimulation and 25sec resting, total 1500 pulses) on the L-DLPFC at 80% of resting motor threshold (rMT). At the time of baseline, 1 month and 3 months after stroke onset, all subjects received the Korean-mini mental state examination(K-MMSE), Korean-Montreal Cognitive Assessment(K-MOCA), Upper Fugl-Meyer Assessment(U-FMA), Korean-Modified Bathel Index(K-MBI), European Quality of life 5 Dimension(EQ-5D), Korean-Geriatric Depression Scale(K-GDS). In addition, the Continuous performance test(CPT), Vascular cognitive impairment harmonization standards (VCIHS), motor evoked potentials (MEP), event-related potentials (ERPs), resting state functional magnetic resonance imaging (RS fMRI) and diffusion tensor imaging (DTI) were completed at baseline and 3 months after stroke onset.
Results
After the intervention period, the real stimulation group improved significantly in the K-MMSE, K-MOCA, K-MBI and K-GDS compared with sham stimulation group. And these effects lasted after three months in MOCA. There was no significant timexgroup effect among the U-FMA, EQ-5D, and CPT. Among the VCIHS parameters, Z- scores of executive and memory function showed higher delta value between baseline and 3months timepoints in rTMS group. The MEP showed higher TIME x GROUP interaction in the intracortical inhibition value on right hand. It suggests that there is beneficial effect on premotor cortical excitability of rTMS. The change of P300 amplitude on F3 and C3 was more increased in real stimulation group significantly only in the auditry Oddball paradigm. The RS fMRI analysis results showed more increased functional connectivity of Cingulate Gyrus, Supramarginal Gyrus, Cerebelum Crus2, Precentral gyrus, Middle temporal gyrus and Inferial temporal gyrus after stimulation compare with the sham group. Brain activation in the cingulum showed a tendency that after 3 months, fractional anisotropy (FA) and fiber number (FN) in real group were larger than sham group, however there was no significant effect. The relationship between the change of K-MOCA and fractional anisotropy of the cingulum was found positive correlation in all subjects.
Conclusion:
These results suggest that high frequency rTMS on the L-DLPFC improves cognitive function and functional network activity in subacute stroke. The rTMS seems to be a recommendable treatment in stroke patients with cognitive impairment.
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