Motor Cortex Hyperexcitability, Neuroplasticity, and Degeneration in Amyotrophic Lateral Sclerosis

Abstract

Neuronal hyperexcitability is a well-known phenomenon in amyotrophic lateral sclerosis and other neurodegenerative diseases. The use of transcranial magnetic stimulation in clinical and research practice has recently made it possible to detect motor cortex hyperexcitability under clinical conditions. Despite numerous studies, the mechanisms and sequelae of the development of hyperexcitability still have not been completely elucidated. In this chapter, we discuss the possibilities for detecting motor cortex hyperexcitability in patients with amyotrophic lateral sclerosis using transcranial magnetic stimulation. The potential relationship between hyperexcitability and neuronal degeneration or neuroplasticity processes is discussed using the data obtained by navigated transcranial magnetic stimulation and neuroimaging data, as well as the data of experimental studies.

Motor Neuron Susceptibility in ALS/FTD

“…Increasing evidence suggests that ALS begins in the cortical regions of the brain, which is referred to as the “dying-forward hypothesis.” Features of cortical hyperexcitability – heralded by reduction in short interval intracortical inhibition – have been detected during the early phases of ALS in transcranial magnetic stimulation studies (Thomsen et al, 2014; Menon et al, 2015). This can precede the clinical onset of bulbar/spinal motor dysfunction by ∼3–6 months (Vucic et al, 2008; Bakulin et al, 2016). The dying forward hypothesis is consistent with Charcot, who first postulated that ALS begins in the cortex (Charcot, 1874).…”

Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

“…In particular, the excitotoxicity hypothesis, which proposes that neurodegeneration in ALS is associated with selective neuronal deaths that occur as a result of overstimulation of the glutamate receptors in the brain (Bakulin, Chervyakov, Suponeva, Zakharova, & Piradov, 2016;Van Den Bosch, Van Damme, Bogaert, & Robberecht, 2006), has promoted the development of riluzole, the only drug licensed for treating ALS. Of note, however, several hypotheses have been proposed regarding the mechanisms underlying the neurodegeneration in ALS.…”

“…Notably, however, there also existed some fMRI studies showing increased FC or activation of the primary motor cortex in patients with ALSMenke et al, 2016). The mixed picture of FC decrease and increase in the primary motor cortex of ALS may reflect a dynamic pathological process mediated by the development of cortical hyperexcitability(Bakulin et al, 2016). Indeed, cortical hyperexcitability is not a static phenomenon but rather shows a pattern of spatiotemporal progression, and may play different roles at different stages of ALS(Bae, Simon, Menon, Vucic, & Kiernan, 2013).…”

“…Of note, however, several hypotheses have been proposed regarding the mechanisms underlying the neurodegeneration in ALS. In particular, the excitotoxicity hypothesis, which proposes that neurodegeneration in ALS is associated with selective neuronal deaths that occur as a result of overstimulation of the glutamate receptors in the brain (Bakulin, Chervyakov, Suponeva, Zakharova, & Piradov, 2016;Van Den Bosch, Van Damme, Bogaert, & Robberecht, 2006), has promoted the development of riluzole, the only drug licensed for treating ALS. Unfortunately, riluzole could only prolong survival by 2-3 months and provide no cure for ALS (Bensimon, Lacomblez, Meininger, & Group, 1994;Miller, Mitchell, Lyon, & Moore, 2007).…”

Using Cutaneous Receptor Vibration to Uncover the Effect of Transcranial Magnetic Stimulation (TMS) on Motor Cortical Excitability

“…Our findings underline the importance of further investigating the activation of somatosensory afferents with the vibration of hand digits for motor cortical plasticity in neurological patients [ 24 , 49 , 64 , 65 ]. Recent TMS studies demonstrated increased motor cortex excitability in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases [ 66 , 67 ]. Further neurophysiological TMS studies are needed to investigate the neurophysiological background of hand digit vibration and other peripheral inputs (muscle vibration, percutaneous electrical stimulation of nerves and fingers) to reinforce possible implications of our findings in neurorehabilitation of neurological patients.…”