**1. Introduction**

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons. Despite the significant advance in molecular biology and genetics over the past years, many aspects of etiology and pathogenesis of ALS remain unstudied; neither biomarkers of the disease nor effective treatment methods have been designed [1].

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A significant advance in understanding the pathophysiological mechanisms of the develop‐ ment of the neurodegenerative process of ALS has been made over the past years after novel neurophysiological and neuroimaging techniques were introduced into the research and clinical practice [2–4]. Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation method that is used to evaluate the functional status of the upper motor neuron in ALS patients. It has been shown in the recent studies that different TMS parameters are altered in ALS patients [4]. TMS is currently viewed as a valuable research and diagnostic tool in ALS.

Development of hyperexcitability of the primary motor cortex and the entire motor system is a well-studied phenomenon in ALS. Motor cortex hyperexcitability can be determined using TMS as reduced resting motor threshold and increased motor evoked potential (MEP) amplitude, decreased silent period, reduced effectiveness of short-interval intracortical inhibition (SICI), and increased intracortical facilitation (ICF) (see review [4]). Most authors attribute motor cortex hyperexcitability in ALS patients to enhanced glutamatergic neuro‐ transmission in the neocortex and reduced gamma-aminobutyric acid (GABA)ergic inhibitory neurotransmission, thus suggesting that hyperexcitability provokes degeneration of motor neurons [5–7]. However, no direct evidence has been obtained yet that would unambiguously demonstrate the relationship between motor cortex hyperexcitability in ALS patients and its degeneration. There is an alternative opinion that hyperexcitability can potentially be related to neuroplasticity processes taking place in the motor cortex and compensation for the lost function.

We would like to discuss the potential relationship of motor cortex hyperexcitability with motor neuron degeneration and neuroplasticity in ALS patients, as well as the possible methods to solve this problem using modern neurophysiological and neuroimaging methods.
