Transcranial static magnetic field stimulation can modify disease progression in amyotrophic lateral sclerosis

Lazzaro, Vincenzo Di; Musumeci, Gabriella; Boscarino, Marilisa; Liso, Alfredo De; Motolese, Francesco; Pino, Giovanni Di; Capone, Fioravante; Ranieri, Federico

doi:10.1016/j.brs.2020.11.003

Cited by 13 publications

(6 citation statements)

References 10 publications

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“…This inhibitory modulation of SMA opens new possibilities for therapeutic applications, especially for neurological and psychiatric disorders that compromise the control of movements. In line with this, a few investigations already described promising findings using M1-tSMS in patients with amyotrophic lateral sclerosis 9 , levodopa-induced dyskinesias 10 , and stroke 11 . While the therapeutic potential of SMA-tSMS has yet to be explored, other inhibitory non-invasive neuromodulatory techniques such as repetitive TMS or transcranial direct current stimulation applied to SMA have already shown beneficial effects in different pathologies especially when administered for multiple sessions 17 , 27 , 28 .…”

Section: Discussionsupporting

confidence: 55%

“…Since the first study that proposed this method 1 , several others 2 – 8 confirmed that tSMS can produce a decrease of corticospinal excitability when applied over the primary motor cortex (M1). In parallel, promising clinical applications that apply tSMS over M1 are emerging for amyotrophic lateral sclerosis 9 , Parkinson's disease 10 , and stroke 11 . Importantly, the portable and user-friendly nature of tSMS makes it appealing for home-based treatments.…”

Section: Introductionmentioning

confidence: 99%

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Transcranial static magnetic field stimulation of the supplementary motor area decreases corticospinal excitability in the motor cortex: a pilot study

Pagge,

Caballero-Insaurriaga,

Oliviero

et al. 2024

Sci Rep

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Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation technique that is portable and easy to use. Long-term, home-based treatments with tSMS of the supplementary motor area (SMA) are promising for movement disorders and other brain diseases. The aim of the present work was to investigate the potential of SMA-tSMS for reducing corticospinal excitability. We completed an open pilot study in which twenty right-handed healthy subjects (8 females; age: 31.3 ± 5.4 years) completed two 30-min sessions (at least one week apart) of SMA-tSMS. We assessed corticospinal excitability by applying transcranial magnetic stimulation (TMS) over the primary motor cortex, recording 30 motor evoked potentials (MEPs) from either the left or right first dorsal interosseous (FDI, ‘hotspot’ muscle) and extensor carpi radialis (ECR, ‘offspot’ muscle) in each session before and after (up to 30 min) tSMS. We observed moderate-to-extreme level of Bayesian evidence for a reduction of MEP amplitude after 30 min of tSMS over SMA compared to baseline. Thus, tSMS applied over SMA may reduce corticospinal excitability. These findings, if confirmed with double-blind, placebo-controlled experiments, support the potential of targeting the SMA for neuromodulating a large motor network in future therapeutic applications of tSMS.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Transcranial static magnetic field stimulation of the supplementary motor area decreases corticospinal excitability in the motor cortex: a pilot study

Pagge,

Caballero-Insaurriaga,

Oliviero

et al. 2024

Sci Rep

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“…Transcranial static magnetic field stimulation (tSMS) is possibly the simplest NIBS technique currently available ( 24 , 25 ), which makes it particularly attractive for delivering long-term treatments at home ( 26 , 27 ). Previous studies showed that tSMS can reduce cortical excitability ( 24 , 28 – 35 ) and modulate local as well as distant cortical activity ( 36 – 39 ), but the effects of tSMS over subcortical structures remain unexplored.…”

mentioning

confidence: 99%

Noninvasive modulation of human corticostriatal activity

Caballero‐Insaurriaga

Pineda-Pardo

Obeso

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging measure demonstrating a change in corticostriatal activity is currently lacking. Here, we combine transcranial static magnetic field stimulation (tSMS) with resting-state functional MRI (fMRI). We first present and validate the ISAAC analysis, a well-principled framework that disambiguates functional connectivity between regions from local activity within regions. All measures of the framework suggested that the region along the medial cortex displaying greater functional connectivity with the striatum is the supplementary motor area (SMA), where we applied tSMS. We then use a data-driven version of the framework to show that tSMS of the SMA modulates the local activity in the SMA proper, in the adjacent sensorimotor cortex, and in the motor striatum. We finally use a model-driven version of the framework to clarify that the tSMS-induced modulation of striatal activity can be primarily explained by a change in the shared activity between the modulated motor cortical areas and the motor striatum. These results suggest that corticostriatal activity can be targeted, monitored, and modulated noninvasively in humans.

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“…The application of rTMS protocols is limited by the necessity of being administered within the hospital, while tDCS could be implemented for home self-administration. The administration at the patient's site of a new NIBS technique, transcranial static magnetic field stimulation (194,195), has been recently proposed in ALS (196) and is currently being tested in a randomized controlled trial (ClinicalTrials.gov ID: NCT04393467). Alternatively, implanted devices could warrant prolonged daily stimulation, but their interaction with intracortical circuits is still largely unexplored.…”

Section: Discussion and Perspectivementioning

confidence: 99%

Brain Stimulation as a Therapeutic Tool in Amyotrophic Lateral Sclerosis: Current Status and Interaction With Mechanisms of Altered Cortical Excitability

et al. 2021

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In the last 20 years, several modalities of neuromodulation, mainly based on non-invasive brain stimulation (NIBS) techniques, have been tested as a non-pharmacological therapeutic approach to slow disease progression in amyotrophic lateral sclerosis (ALS). In both sporadic and familial ALS cases, neurophysiological studies point to motor cortical hyperexcitability as a possible priming factor in neurodegeneration, likely related to dysfunction of both excitatory and inhibitory mechanisms. A trans-synaptic anterograde mechanism of excitotoxicity is thus postulated, causing upper and lower motor neuron degeneration. Specifically, motor neuron hyperexcitability and hyperactivity are attributed to intrinsic cell abnormalities related to altered ion homeostasis and to impaired glutamate and gamma aminobutyric acid gamma-aminobutyric acid (GABA) signaling. Several neuropathological mechanisms support excitatory and synaptic dysfunction in ALS; additionally, hyperexcitability seems to drive DNA-binding protein 43-kDA (TDP-43) pathology, through the upregulation of unusual isoforms directly contributing to ASL pathophysiology. Corticospinal excitability can be suppressed or enhanced using NIBS techniques, namely, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as well as invasive brain and spinal stimulation. Experimental evidence supports the hypothesis that the after-effects of NIBS are mediated by long-term potentiation (LTP)-/long-term depression (LTD)-like mechanisms of modulation of synaptic activity, with different biological and physiological mechanisms underlying the effects of tDCS and rTMS and, possibly, of different rTMS protocols. This potential has led to several small trials testing different stimulation interventions to antagonize excitotoxicity in ALS. Overall, these studies suggest a possible efficacy of neuromodulation in determining a slight reduction of disease progression, related to the type, duration, and frequency of treatment, but current evidence remains preliminary. Main limitations are the small number and heterogeneity of recruited patients, the limited “dosage” of brain stimulation that can be delivered in the hospital setting, the lack of a sufficient knowledge on the excitatory and inhibitory mechanisms targeted by specific stimulation interventions, and the persistent uncertainty on the key pathophysiological processes leading to motor neuron loss. The present review article provides an update on the state of the art of neuromodulation in ALS and a critical appraisal of the rationale for the application/optimization of brain stimulation interventions, in the light of their interaction with ALS pathophysiological mechanisms.

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Transcranial static magnetic field stimulation can modify disease progression in amyotrophic lateral sclerosis

Cited by 13 publications

References 10 publications

Transcranial static magnetic field stimulation of the supplementary motor area decreases corticospinal excitability in the motor cortex: a pilot study

Transcranial static magnetic field stimulation of the supplementary motor area decreases corticospinal excitability in the motor cortex: a pilot study

Noninvasive modulation of human corticostriatal activity

Brain Stimulation as a Therapeutic Tool in Amyotrophic Lateral Sclerosis: Current Status and Interaction With Mechanisms of Altered Cortical Excitability

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