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Repetitive transcranial magnetic stimulation improves Parkinson's freezing of gait via normalizing brain connectivity.

ABSTRACT: Robust, effective treatments for Parkinson's freezing of gait remain elusive. Our previous study revealed beneficial effects of high-frequency rTMS over the supplementary motor area. The present study aims to explore the neural mechanisms of rTMS treatments utilizing novel exploratory multivariate approaches. We first conducted a resting-state functional MRI study with a group of 40 Parkinson's disease patients with freezing of gait, 31 without freezing of gait, and 30 normal controls. A subset of 30 patients with freezing of gait (verum group: N?=?20; sham group: N?=?10) who participated the aforementioned rTMS study underwent another scan after the treatments. Using the baseline scans, the imaging biomarkers for freezing of gait and Parkinson's disease were developed by contrasting the connectivity profiles of patients with freezing of gait to those without freezing of gait and normal controls, respectively. These two biomarkers were then interrogated to assess the rTMS effects on connectivity patterns. Results showed that the freezing of gait biomarker was negatively correlated with Freezing of Gait Questionnaire score (r?=?-0.6723, p?

SUBMITTER: Mi TM

PROVIDER: S-EPMC7368045 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Repetitive transcranial magnetic stimulation improves Parkinson's freezing of gait via normalizing brain connectivity.

Mi Tao-Mian TM Garg Saurabh S Ba Fang F Liu Ai-Ping AP Liang Pei-Peng PP Gao Lin-Lin LL Jia Qian Q Xu Er-He EH Li Kun-Cheng KC Chan Piu P McKeown Martin J MJ

NPJ Parkinson's disease 20200717

Robust, effective treatments for Parkinson's freezing of gait remain elusive. Our previous study revealed beneficial effects of high-frequency rTMS over the supplementary motor area. The present study aims to explore the neural mechanisms of rTMS treatments utilizing novel exploratory multivariate approaches. We first conducted a resting-state functional MRI study with a group of 40 Parkinson's disease patients with freezing of gait, 31 without freezing of gait, and 30 normal controls. A subset ...[more]

PMID: 32699818

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Project description:A core feature of drug-resistant epilepsy is hyperexcitability in the motor cortex, and low-frequency repetitive transcranial magnetic stimulation (rTMS) is a suitable treatment for seizures. However, the antiepileptic effect causing network reorganization has rarely been studied. Here, we assessed the impact of rTMS on functional network connectivity (FNC) in resting functional networks (RSNs) and their relation to treatment response. Fourteen patients with medically intractable epilepsy received inhibitive rTMS with a figure-of-eight coil over the vertex for 10 days spread across two weeks. We designed a 6-week follow-up phase divided into four time points to investigate FNC and rTMS-induced timing-dependent plasticity, such as seizure frequency and abnormal interictal discharges on electroencephalography (EEG). For psychiatric comorbidities, the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A) were applied to measure depression and anxiety before and after rTMS. FNC was also compared to that of a cohort of 17 healthy control subjects. The after-effects of rTMS included all subjects that achieved the significant decrease rate of more than 50% in interictal epileptiform discharges and seizure frequency, 12 (14) patients with the reduction rate above 50% compared to the baseline, as well as emotional improvements in depression and anxiety (p < 0.05). In the analysis of RSNs, we found a higher synchronization between the sensorimotor network (SMN) and posterior default-mode network (pDMN) in epileptic patients than in healthy controls. In contrast to pre-rTMS, the results demonstrated a weaker FNC between the anterior DMN (aDMN) and SMN after rTMS, while the FNC between the aDMN and dorsal attention network (DAN) was greater (p < 0.05, FDR corrected). Importantly, the depressive score was anticorrelated with the FNC of the aDMN-SMN (r = -0.67, p = 0.0022), which was markedly different in the good and bad response groups treated with rTMS (p = 0.0115). Based on the vertex suppression by rTMS, it is possible to achieve temporary clinical efficacy by modulating network reorganization in the DMN and SMN for patients with refractory epilepsy.

Project description:Repetitive transcranial magnetic stimulation (rTMS) is a popular noninvasive technique for modulating motor cortical plasticity and has therapeutic potential for the treatment of Parkinson's disease (PD). However, the therapeutic benefits and related mechanisms of rTMS in PD are still uncertain. Accordingly, preclinical animal research is helpful for enabling translational research to explore an effective therapeutic strategy and for better understanding the underlying mechanisms. Therefore, the current study was designed to identify the therapeutic effects of rTMS on hemiparkinsonian rats. A hemiparkinsonian rat model, induced by unilateral injection of 6-hydroxydopamine (6-OHDA), was applied to evaluate the therapeutic potential of rTMS in motor functions and neuroprotective effect of dopaminergic neurons. Following early and long-term rTMS intervention with an intermittent theta burst stimulation (iTBS) paradigm (starting 24 h post-6-OHDA lesion, 1 session/day, 7 days/week, for a total of 4 weeks) in awake hemiparkinsonian rats, the effects of rTMS on the performance in detailed functional behavioral tests, including video-based gait analysis, the bar test for akinesia, apomorphine-induced rotational analysis, and tests of the degeneration level of dopaminergic neurons, were identified. We found that four weeks of rTMS intervention significantly reduced the aggravation of PD-related symptoms post-6-OHDA lesion. Immunohistochemically, the results showed that tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta (SNpc) and fibers in the striatum were significantly preserved in the rTMS treatment group. These findings suggest that early and long-term rTMS with the iTBS paradigm exerts neuroprotective effects and mitigates motor impairments in a hemiparkinsonian rat model. These results further highlight the potential therapeutic effects of rTMS and confirm that long-term rTMS treatment might have clinical relevance and usefulness as an additional treatment approach in individuals with PD.

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Repetitive transcranial magnetic stimulation improves Parkinson's freezing of gait via normalizing brain connectivity.

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Repetitive transcranial magnetic stimulation improves Parkinson's freezing of gait via normalizing brain connectivity.

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