High-Frequency rTMS Combined with Task-Specific Hand Motor Training Modulates Corticospinal Plasticity in Motor Complete Spinal Cord Injury: A case report

Brihmat, Nabila; Bayram, Mehmed Bugrahan; Allexandre, Didier; Saleh, Soha; Yue, Guang H.; Guan, Xiaofei; Zhong, Jian; Forrest, Gail

doi:10.1109/embc48229.2022.9871134

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…Our results pave the way for future studies focusing on optimization of stimulation protocols to more effectively engage the cell-intrinsic axon growth/regeneration machinery. We have begun testing our HF-rTMS protocol on able-bodied individuals and patients with SCI ( 28 ). This study is ongoing.…”

Section: Discussionmentioning

confidence: 99%

“…HF-rTMS up-regulates energy metabolism and induces persistent phosphorylation of ribosomal protein S6 in deep layer cortical neurons (22,23). There is also an increasing body of evidence suggesting that rTMS applied over motor cortex may be beneficial for functional recovery in patients with SCI (24)(25)(26)(27)(28). Nevertheless, because we lack a basic understanding of the molecular and cellular mechanisms that underlie rTMS' beneficial effects, current rTMS applications still rely on trial and error.…”

Section: Introductionmentioning

confidence: 99%

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Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration

et al. 2023

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Facilitating axon regeneration in the injured central nervous system remains a challenging task. RAF-MAP2K signaling plays a key role in axon elongation during nervous system development. Here, we show that conditional expression of a constitutively kinase-activated BRAF in mature corticospinal neurons elicited the expression of a set of transcription factors previously implicated in the regeneration of zebrafish retinal ganglion cell axons and promoted regeneration and sprouting of corticospinal tract (CST) axons after spinal cord injury in mice. Newly sprouting axon collaterals formed synaptic connections with spinal interneurons, resulting in improved recovery of motor function. Noninvasive suprathreshold high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) activated the BRAF canonical downstream effectors MAP2K1/2 and modulated the expression of a set of regeneration-related transcription factors in a pattern consistent with that induced by BRAF activation. HF-rTMS enabled CST axon regeneration and sprouting, which was abolished in MAP2K1/2 conditional null mice. These data collectively demonstrate a central role of MAP2K signaling in augmenting the growth capacity of mature corticospinal neurons and suggest that HF-rTMS might have potential for treating spinal cord injury by modulating MAP2K signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration

et al. 2023

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Genetic or transcranial magnetic stimulation of B-RAF–MEK signaling promotes CST axon sprouting and functional regeneration

Boato

Guan

Zhu

et al. 2022

Preprint

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Facilitating axon regeneration in the injured central nervous system remains a challenging task. RAF - MEK signaling plays an important role in axon elongation during nervous system development. Here we show that activation of B-RAF in mature corticospinal neurons elicited the expression of a discrete set of transcription factors previously implicated in the regeneration of zebrafish optic nerve axons. Genetic activation of B-RAF - MEK signaling promoted robust regeneration and sprouting of corticospinal tract axons after injury. Newly sprouting axon collaterals formed synaptic connections with spinal interneurons, correlating with the recovery of skilled motor function. Seeking a non-invasive way to stimulate axon regeneration, we found that suprathreshold high-frequency repetitive transcranial magnetic stimulation activates the B-RAF canonical effectors MEK1/2 and requires MEK1/2 activity to promote corticospinal axon regeneration and sprouting after injury. These data demonstrate a central role of neuron-intrinsic RAF - MEK signaling in enhancing the growth capacity of mature corticospinal neurons and propose HF-rTMS as a potential therapy for spinal cord injury.

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Safety and effects of a therapeutic 15 Hz rTMS protocol administered at different suprathreshold intensities in able-bodied individuals

Brihmat

Allexandre

Bayram

et al. 2023

Journal of Neurophysiology

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Background and objectives: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the after-effects observed. Here, we examined if single sessions of a HF-rTMS protocol, administered at different suprathreshold SI, can be safely administered to able-bodied (AB) individuals. Methods: Six right-handed men were included in this pilot study. HF-rTMS was delivered over the left M1, in 10 trains of 75 biphasic stimuli at 15 Hz, at 105 to 120% of the individual resting motor threshold (RMT). Participants and EMG were monitored to control for signs of spread of excitation and brief EMG burst (BEB) post-stimulation. TMS side-effects questionnaires and the numeric rating scale (NRS) were administered during each session. Additionally, we assessed CSE and motor performance changes with measures of resting (rMEP) and active (aMEP) motor evoked potential and grip strength and the Box and Block test (BBT) scores, respectively. Results: Overall, the sessions were tolerated and feasible without any pain development. EMG analysis during HF-rTMS revealed increased BEB frequency with SI. Statistical models revealed an increase of CSE at rest (rMEP) but not during active muscle contraction (aMEP). No linear relationship was observed between HF-rTMS intensity and rMEP increase. No significant changes were highlighted for motor performance measures. Conclusion: Although feasible and tolerable by the AB tested, the results demonstrate that when administered at suprathreshold SI, 15 Hz-rTMS reveals signs of persistent excitation, suggesting that safety precautions and close monitoring of participants should be performed when testing such stimulation protocols.

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High-Frequency rTMS Combined with Task-Specific Hand Motor Training Modulates Corticospinal Plasticity in Motor Complete Spinal Cord Injury: A case report

Cited by 3 publications

References 19 publications

Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration

Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration

Genetic or transcranial magnetic stimulation of B-RAF–MEK signaling promotes CST axon sprouting and functional regeneration

Safety and effects of a therapeutic 15 Hz rTMS protocol administered at different suprathreshold intensities in able-bodied individuals

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