Cerebellar ataxia is the predominant motor feature of multiple system atrophy cerebellar subtype (MSA-C). Although repetitive transcranial magnetic stimulation (TMS) of the cerebellum is growingly applied in MSA, the mechanism is unknown. We examined dynamic connectivity changes of 20 patients with MSA and 25 healthy controls using TMS combined with electroencephalography. Observations that significantly decreased dynamic cerebello-frontal connectivity in patients have inspired attempts to modulate cerebellar connectivity in order to benefit MSA. We further explore the therapeutic potential of a 10-day treatment of cerebellar intermittent theta burst stimulation (iTBS) in MSA by a randomized, double-blind, sham-controlled trial. The functional reorganization of cerebellar networks was investigated after the end of treatment in active and sham groups. The severity of the symptoms was evaluated using the Scale for Assessment and Rating of Ataxia scores. Patients treated with active stimulation showed an improvement of cerebello-frontal connectivity and balance functions, as revealed by a significant decrease in the ataxia scores (P < 0.01). Importantly, the neural activity of frontal connectivity from 80 to 100 ms after a single TMS was significantly related to the severity of the disease. Our study provides new proof that cerebellar iTBS improves motor imbalance in MSA by acting on cerebello-cortical plasticity.

The interaction between dorsal and ventral attention networks (VANs) is mediated by the middle frontal gyrus (MFG), which is functionally connected to both networks. However, the direct role of the MFG in selective and sustained attention remains controversial. In the current study, we used transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to probe the connectivity dynamic changes of MFG-associated regions during different attention modes. The participants underwent visual, selective, and sustained attention tasks to observe TMS-induced network changes. Twenty healthy participants received single-pulse TMS over the left or right MFG during tasks, while synchronous EEG data was acquired. Behavioral results were recorded and time-varying brain network analyses were performed. We found that the MFG is involved in attention processing and that sustained attention was preferentially controlled by the right MFG. Moreover, compared with the right hemisphere, the left hemisphere was associated with selective attention tasks. Visual and selective attention tasks induced MFG-related changes in network nodes were within the left hemisphere; however, sustained attention induced changes in network nodes were in the bilateral posterior MFG. Our findings indicated that the MFG plays a crucial role in regulating attention networks. In particular, TMS-induced MFG alterations influenced key nodes of the time-varying brain network, leading to the reorganization of brain network modules.

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Previous studies have indicated that the adenosine triphosphate-sensitive homomeric P2X7 receptor (P2X7R) plays an important role and exhibits therapeutic potential in a number of brain disorders, including temporal lobe epilepsy (TLE). The aim of the present study was to assess the expression of P2X7R, glutamate (GLU) and glial fibrillary acidic protein (GFAP) in the temporal neocortex and hippocampus of rats with lithium-pilocarpine-induced epilepsy as well as in patients with intractable TLE. The results demonstrated that the levels of P2X7R, GLU and GFAP were significantly upregulated in rats with spontaneous recurrent seizures, whereas they were reduced in rats that were treated with brilliant blue G (BBG), a P2X7R antagonist. To the best of our knowledge, the present study is also the first to demonstrate that P2X7R expression was elevated in patients with intractable TLE. These findings suggest that P2X7R plays a key role in the development of TLE and that BBG treatment may be a promising therapeutic strategy for TLE.