Clinical and electrophysiological impact of repetitive low-frequency transcranial magnetic stimulation on the sensory–motor network in patients with restless legs syndrome

Abstract

Background:Based on the hyperexcitability and disinhibition observed in patients with restless legs syndrome (RLS) following transcranial magnetic stimulation (TMS), we conducted a study with low-frequency repetitive TMS (rTMS) over the primary motor (M1) and somatosensory cortical areas (S1) in patients with RLS.Methods:A total of 13 right-handed patients and 10 age-matched controls were studied using clinical scales and TMS. Measurements included resting motor threshold (rMT), motor-evoked potentials (MEPs), cortical silent period (CSP), and central motor conduction time (CMCT). A single evening session of rTMS (1 Hz, 20 trains, 50 stimuli each) was administered over the left M1, left S1, and sham stimulation over M1 in a random order. Clinical and TMS measures were repeated after each stimulation modality.Results:Baseline CSP was shorter in patients than in controls and remained shorter in patients for both motor and somatosensory stimulation. The patients reported a subjective improvement of both initiating and maintaining sleep the night after the rTMS over S1. Patients exhibited a decrease in rMT after rTMS of S1 only, although the effect was smaller than in controls. MEP latency and CMCT changed only in controls after stimulation. Sham stimulation was without effect on the observed variables.Conclusions:rTMS on S1-M1 connectivity alleviated the sensory–motor complaints of RLS patients. The TMS indexes of excitation and inhibition indicate an intracortical and corticospinal imbalance, mainly involving gamma-aminobutyric acid (GABA)ergic and glutamatergic circuitries, as well as an impairment of the short-term mechanisms of cortical plasticity. The rTMS-induced activation of the dorsal striatum with the consequent increase of dopamine release may have contributed to the clinical and neurophysiological outcome.

High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: a pilot double-blind, randomized controlled study in Veterans with schizophrenia

“…Preclinical studies have shown that rTMS causes complex biochemical effects and neurotropic effects by reducing inflammation and oxidative stress 33,34 . For example, studies have revealed that rTMS increases the release of dopamine in certain brain pathways 35 , which is consistent with the hypoactive dopaminergic hypothesis in cognitive deficits of patients with SCZ 36 .…”

Symptom‐related changes in current perception threshold of restless legs syndrome

“…Our finding has been recently confirmed through neuromodulation experiments. Inhibitory repetitive transcranial magnetic stimulation applied to the sensory‐motor cortical areas was able to alleviate sensory symptoms (Lanza et al., ) and modulate the short‐term mechanisms of plasticity (Lanza et al., ).…”

The Effect of sequential bilateral low‐frequency rTMS over dorsolateral prefrontal cortex on serum level of BDNF and GABA in patients with primary insomnia

“…Recently, neuroimaging has also suggested that insomnia patients have higher excitability in the bilateral dorsolateral prefrontal cortex (DLPFC) compared with healthy individuals (Nofzinger, ). Moreover, TMS measures showed cortical hyperexcitability in the restless legs syndrome, chronic insomnia, and sleep deprived healthy individuals, but cortical hypoexcitability in the obstructive sleep apnea syndrome (Lanza et al, ; Lanza, Cantone, et al, ; Lanza, Lanuzza, et al, ; Lin et al, ; Nardone et al, ; Salas et al, ). Combined with the inhibitory effect on cortical excitability by low‐frequency stimulation, we speculated that sequential bilateral low‐frequency magnetic stimulation over DLPFC may have a significant therapeutic effect on PI.…”