BackgroundIntronic pentanucleotide insertion in the sterile alpha motif domain‐containing 12 gene was recently identified as the genetic cause of familial cortical myoclonic tremor with epilepsy type 1.ObjectivesWe thereafter conducted a multimodal MRI research to further understand familial cortical myoclonic tremor with epilepsy type 1.MethodsWe enrolled 31 patients carrying heterozygous pathogenic intronic pentanucleotide insertion in the sterile alpha motif domain‐containing 12 gene and 31 age‐ and sex‐matched healthy controls. We compared multimodal MRI metrics, including voxel‐based morphometry, fractional anisotropy of diffuse tensor imaging, frequency‐dependent percent amplitude fluctuation, and seed‐based functional connectivity of resting‐state functional MRI.ResultsSignificant decreased gray matter volume was found in the cerebellum. Percent amplitude fluctuation analysis showed significant interaction effect of “Frequency by Group” in three regions, including the vermis VIII, left cerebellar lobule VIII, and left precentral gyrus. Specifically, the lowest‐frequency band exhibited significant increased percent amplitude fluctuation in patients in the two cerebellar subregions, whereas the highest‐frequency band exhibited decreased percent amplitude fluctuation in the precentral gyrus in patients. Discriminative analysis by support vector machine showed a mean accuracy of 82% (P = 1.0–5). An increased functional connectivity between vermis VIII and the left precentral gyrus was found in patients with familial cortical myoclonic tremor with epilepsy type 1. A positive correlation between the percent amplitude fluctuation in the left cerebellar lobule VIII and duration of cortical tremor was also found.ConclusionThe cerebellum showed both structural and functional damages. The distinct change of spontaneous brain activity, that is, increased ultra‐low‐frequency amplitude in the cerebellum and the decreased higher‐frequency amplitude in the motor cortex, might be a pathophysiological feature of familial cortical myoclonic tremor with epilepsy type 1. © 2020 International Parkinson and Movement Disorder Society

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Previous resting state functional magnetic resonance imaging (RS-fMRI) studies suggested that repetitive transcranial magnetic stimulation (rTMS) can modulate local activity in distant areas via functional connectivity (FC). A brain region has more than one connection with the superficial cortical areas. The current study proposed a multi-target focused rTMS protocol for indirectly stimulating a deep region, and to investigate 1) whether FC strength between stimulation targets (right middle frontal gyrus [rMFG] and right inferior parietal lobule [rIPL]) and effective region (dorsal anterior cingulate cortex [dACC]) can predict local activity changes of dACC and 2) whether multiple stimulation targets can focus on the dACC via FC. A total of 24 healthy participants received rTMS with two stimulation targets, both showing strong FC with the dACC. There were four rTMS conditions (>1 week apart, 10 Hz, 1800 pulses for each): rMFG-target, rIPL-target, Double-targets (900 pulses for each target), and Sham. The results failed to validate the multi-target focused rTMS hypothesis. But rMFG-target significantly decreased the local activity in the dACC. In addition, stronger dACC-rMFG FC was associated with a greater local activity change in the dACC. Future studies should use stronger FC to focus stimulation effects on the deep region.

Repetitive transcranial magnetic stimulation (rTMS) has been used in the clinical treatment of Parkinson's disease (PD). Most of rTMS studies on PD used high‐frequency stimulation; however, excessive nonvoluntary movement may represent abnormally cortical excitability, which is likely to be suppressed by low‐frequency rTMS. Decreased neural activity in the basal ganglia on functional magnetic resonance imaging (fMRI) is a characteristic of PD. In the present study, we found that low‐frequency (1 Hz) rTMS targeting individual finger‐tapping activation elevated the amplitude of local neural activity (percentage amplitude fluctuation, PerAF) in the putamen as well as the functional connectivity (FC) of the stimulation target and basal ganglia in healthy participants. These results provide evidence for our hypothesis that low‐frequency rTMS over the individual task activation site can modulate deep brain functions, and that FC might serve as a bridge transmitting the impact of rTMS to the deep brain regions. It suggested that a precisely localized individual task activation site can act as a target for low‐frequency rTMS when it is used as a therapeutic tool for PD.