Hakuei Fujiyama

Abstract
Resting tremor—involuntary and rhythmic shaking that usually occurs in the limbs—is the most common presenting motor symptom in Parkinson’s disease (PD). Tremor is not associated with the severity of dopamine depletion in the basal ganglia, and dopaminergic medication, which is used primarily to target dopamine depletion in the basal ganglia, has limited efficacy in reducing tremor. This suggests that other brain regions might underpin tremor in PD. Intracortical inhibition within the primary motor cortex (M1) has been implicated in tremor: intracortical inhibition in M1 is lower in PD than controls, higher motor cortex GABA is associated with lower tremor severity in PD, and pharmacological increases in GABA activity reduce tremor severity in PD. A combined intermittent theta-burst stimulation (iTBS)—gamma transcranial alternating current stimulation (tACS) protocol has been shown to increase short-interval intracortical inhibition (SICI) in PD. Therefore, in the current study, we examined M1 excitability, SICI, and resting tremor before and after real and sham iTBS-tACS. In a within-subjects design, we tested 19 participants (13 male; mean age 66 years) with idiopathic, tremor-dominant PD OFF medication. M1 excitability increased after real but not sham iTBS-tACS. There was no change in SICI after either real or sham iTBS-tACS. Resting tremor in the extensor carpi radialis showed a trend to increase after sham but not real iTBS, indicating that real iTBS-tACS might have prevented resumption of tremor activity in PD participants OFF medication. These findings provide preliminary evidence that iTBS-tACS induced long-term potentiation-like plasticity in M1 in tremor-dominant PD, which could influence tremor severity. However, further research is needed to examine the time-course of iTBS-tACS-induced changes in M1 excitability and tremor severity. If iTBS-tACS can reduce tremor, it could offer an alternative, or supplementary, treatment to levodopa medication for people with tremor-dominant PD.

Research Category and Technology and Methods
Clinical Research: 10. Transcranial Magnetic Stimulation (TMS)

The role of the dorsolateral prefrontal cortex (DLPFC) in the regulation of bimanual coordination appears to become crucial with aging. Age-related changes in the involvement of the DLPFC in bimanual coordination were studied by using disruptive repetitive TMS (rTMS), inducing a transient lesion in this brain structure. Neurophysiological as well as behavioral effects of suppressing DLPFC during the preparation and execution of a bimanual task were studied in 41 healthy adults (young and old). Specifically, we combined short-train rTMS with single pulse TMS to examine the effect of DLPFC suppression on the interhemispheric projection to the contralateral primary motor cortex (M1) during motor preparation. Findings revealed that compromised interhemispheric DLPFC-M1 disinhibition during motor preparation in older adults resulted in less accurate bimanual performance. The altered DLPFC-M1 interaction in older adults appeared to result from a decline in local inhibitory mechanisms in the DLPFC. In addition, the induction of DLPFC suppression affected task accuracy, but not movement stability in both age groups. Taken together, these results suggest that DLPFC acts as a key regulator in the control of bimanual movement coordination.