tFUS Stimulation on the Ischemic Stroke Rat Model Contralesional Motor Cortex Modulates Interhemispheric Balance

Abstract

Purpose Ischemic stroke is known to cause interhemispheric imbalances including abnormal hyperexcitability in the contralesional cortex. We aimed to investigate the effects of suppressive transcranial focused ultrasound (tFUS) applied to the contralesional motor cortex in an ischemic stroke rat model to reorganize interhemispheric balance.

Materials & Methods 90-min middle cerebral artery occlusion (MCAO) was performed in the right hemisphere of male SpragueDawley rats, followed by reperfusion to establish an ischemic stroke model. To perform tFUS sessions, a pair of EEG screw electrodes were implanted on the skull bilaterally over the left/right somatosensory cortical areas, and a custom-built tFUS transducer operating at a fundamental frequency of 300 kHz was placed over the left motor cortical area (M1). On post-MCAO days 0 and 3, tFUS sonication was delivered to the contralesional M1 at 2.53 W/cm2 Isppa for 20 minutes, with a suppressive pulsing scheme at 5% duty cycle and 40 Hz pulse repetition frequency. EEG was acquired during the tFUS session, along with 5-minute EEG recording before and after.

Results Following tFUS sessions, the ipsilesional EEG delta power showed a trend towards an increase on post-MCAO day 3 compared to day 0, indicating a re-organization of interhemispheric balance. In the sham control MCAOgroup (i.e., stroke rats without sonication), the ipsilesional EEG delta power did not increase on post-MCAO day 3. The MCAO rats that underwent tFUS sessions travelled a longer distance during Y-maze behavioral tests compared to the sham animals. Histological analysis showed no tissue damage was observed in sonicated brain regions.

Conclusion This study demonstrated that contralesional M1 stimulation with suppressive tFUS modulated interhemispheric balance by enhancing the relative power of ipsilesional delta oscillations. The results suggest the potential efficacy of low-intensity tFUS-mediated suppression of abnormal hyperexcitability in the contralesional M1 to recover interhemispheric balance and facilitate post-stroke rehabilitation.