A. Chervyakov

Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

Increased motor cortex excitability during motor imagery in brain-computer interface trained subjects

Background: Motor imagery (MI) is the mental performance of movement without muscle activity. It is generally accepted that MI and motor performance have similar physiological mechanisms. Purpose: To investigate the activity and excitability of cortical motor areas during MI in subjects who were previously trained with an MI-based brain-computer interface (BCI). Subjects and Methods: Eleven healthy volunteers without neurological impairments (mean age, 36 years; range: 24–68 years) were either trained with an MI-based BCI (BCI-trained, n = 5) or received no BCI training (n = 6, controls). Subjects imagined grasping in a blocked paradigm task with alternating rest and task periods. For evaluating the activity and excitability of cortical motor areas we used functional MRI and navigated transcranial magnetic stimulation (nTMS). Results: fMRI revealed activation in Brodmann areas 3 and 6, the cerebellum, and the thalamus during MI in all subjects. The primary motor cortex was activated only in BCI-trained subjects. The associative zones of activation were larger in non-trained subjects. During MI, motor evoked potentials recorded from two of the three targeted muscles were significantly higher only in BCI-trained subjects. The motor threshold decreased (median = 17%) during MI, which was also observed only in BCI-trained subjects. Conclusion: Previous BCI training increased motor cortex excitability during MI. These data may help to improve BCI applications, including rehabilitation of patients with cerebral palsy.

D-amino acids in normal ageing and pathogenesis of neurodegenerative diseases

We review the potential role of D-amino acids (D-AAs) in the functioning of the human CNS. About 50 years ago, scientists believed that D-AAs do not exist in living organisms. Studies in the last decades have shown that D-AAs are widely present in the tissues of higher organisms, including humans. D-serine plays an important role in neuroplasticity, memory, and learning; D-aspartate is involved in developmental and endocrine functions. The main pathways for the appearance and metabolism of D-AAs have been described. The pathogenicity of D-AAs is associated with excess activation of NMDA receptors and incorporation into normal protein molecules (conformational changes), which results in functional inactivation of the protein or its toxicity, and an increase in the concentration of reactive oxygen species (oxidative stress) during disintegration of D-AAs by D-AA oxidase (DAAO). The level of D-AAs in biological fluids, the activity of enzymes, and mutations in genes that encode these enzymes may be used as a diagnostic marker in some diseases. We believe that it is possible to develop methods that will alter the intake of D-AAs, their synthesis, and degradation and to use D-AAs as modulators of receptors, which may be useful for the development of new therapeutic strategies. Finally, the use of exogenous D-AAs (unbound or as a component of proteins) may also provide new therapeutic possibilities because they have specific and highly effective actions.

Navigated transcranial magnetic stimulation in amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is a set of disorders associated with preferential degeneration of both upper and lower motor neurons. Navigated transcranial magnetic stimulation (nTMS) is a tool used to perform noninvasive functional brain mapping. We aimed to assess function of upper motor neurons in ALS. Methods: nTMS was performed on 30 patients with ALS (mean age 54.4 ± 12.1 years) and 24 healthy volunteers (mean age 32.7 ± 13.3 years). Results: The resting motor threshold (MT) was significantly higher in ALS patients compared with controls (P < 0.001). The mean map areas were smaller in patients with ALS than in healthy individuals, although some patients with short disease duration had extended maps. Conclusions: Motor area maps serve as markers of upper motor neuron damage in ALS. Further research may elucidate the pathogenic mechanisms of the neurodegenerative process and aid in development of diagnostic and prognostic markers. Muscle Nerve 51: 125–131, 2015

New approaches in the study of the neuroplasticity process in patients with central nervous system lesions

Methods that, on the one hand, can ensure patient’s mobility and, on the other hand, activate afferent inputs are the main in the rehabilitation treatment. Recent studies have shown that plasticity is the structural basis of recovery after central nervous system lesions. Reorganization of cortical areas, increase in the efficiency of the functioning of preserved structures; and active use of alternative ascending pathways, e.g., intensification of afferent input, constitute the anatomical basis of plasticity. However, sensory correction methods, without accounting of functional condition of patients, may lead to the formation of pathological symptoms: spasticity, hyperreflexia, etc. So, the main aim is to study adequate management of the neuroplasticity process. This problem cannot be solved without modern methods of neuroimaging and brain mapping. The new approach for the study of cortical mechanisms of neuroplasticity, responsible for locomotion, was developed in the present study. This approach is an integrated use of functional magnetic resonance imaging (fMRI) and navigation transcranial magnetic stimulation (nTMS). It has been shown that vast fMRI activation area in the first and second sensorimotor areas emerges with a passive sensorimotor paradigm usage that imitates backing load during walking. The Korvit mechanical stimulator of backing zones of footsteps is used to create this paradigm. The nTMS examination used after fMRI helps to localize motor representation of muscles which control locomotion more accurately. We assume that the new approach can be used for studying the neuroplasticity process and assessing neuroplasticity changes when taking rehabilitation measures to restore and correct the walking process.

Specific activation of brain cortical areas in response to stimulation of the support receptors in healthy subjects and patients with focal lesions of the CNS

The space medicine data on the nature of motor disorders suggest an important role of the support inputs in the control of mammalian tonic and postural systems. Progress in functional magnetic resonance tomography (fMRT) makes it possible to perform in vivo analysis of various brain areas during stimulation of the support afferentation. Under these conditions, specific activation of the brain cortical areas was studied in 19 healthy subjects (with the mean age of 38 ± 15.13 years) and 23 patients (with the mean age of 53 ± 9.07 years) with focal CNS lesions (cortical-subcortical ischemic stroke). During scanning of subjects, the support areas of the soles of the feet were stimulated using a block design to simulate slow walking. In healthy subjects, significant activation was recorded (p < 0.05 at the cluster level) in the primary somatosensory cortex, premotor and dorsolateral prefrontal cortex, and insular lobe. In patients that had had a stroke, activation of the locomotion-controlling supraspinal systems clearly depended on the stage of the disease. In patients with a cortical-subcortical stroke, the pattern of contralateral activation of the sensorimotor locomotion predominated during motility rehabilitation.

Variability of Neuronal Responses: Types and Functional Significance in Neuroplasticity and Neural Darwinism

HIGHLIGHTS We suggest classifying variability of neuronal responses as follows: false (associated with a lack of knowledge about the influential factors), “genuine harmful” (noise), “genuine neutral” (synonyms, repeats), and “genuine useful” (the basis of neuroplasticity and learning). The genuine neutral variability is considered in terms of the phenomenon of degeneracy. Of particular importance is the genuine useful variability that is considered as a potential basis for neuroplasticity and learning. This type of variability is considered in terms of the neural Darwinism theory. In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection.

Electroencephalographic Characteristics of the Déjà Vu Phenomenon

Déjà vu (DV) – is an aberration of mental activity associated with the perception of surrounding reality with the impression that unknown objects, new contexts, and people seen for the first time are for some moments perceived as familiar. The aim of the present work was to study the EEG characteristics of the DV phenomenon in epilepsy. A total of 166 subjects took part in the study; subjects were 25.17 ± 9.19 years old and 63.2% were women. The déjà vu phenomenon was compared in groups of healthy subjects (139 subjects) and epilepsy patients (27 cases). Patients were interviewed regarding the characteristics of DV and underwent prolonged (12–16 h) ambulatory EEG monitoring. On the EEG, the phenomenon of DV was characterized by onset with multispike activity in the right temporal leads and, in some cases, ended with slow-wave θ–δ activity in the right hemisphere.

VALUE OF THE PHENOMENON OF DEJA VU IN HEALTHY EXAMINEES

The purpose of the investigation was to study the clinical value of the deja vu phenomenon in healthy examinees as it may occur in healthy individuals, on the one hand, and is a symptom of a number of psychoneurological diseases, on the other. One hundred and twenty-nine subjects, mean age 25,2±4,4 years, were examined. All the examinees were questioned by the original questionnaire developed by the authors, which was to reveal the characteristics of the phenomenon, and the Cambridge depersonalization questionnaire; standard electroencephalography was also performed. The deja vu phenomenon was detected in 97% of the respondents. In healthy individuals, the phenomenon was most common at the age of 21-25 years; 52,2% experienced deja vu several times a year; 64,5% of the respondents reported the 10-sec state; 85% did not associate the occurrence of the phenomenon with any provoking factor; 66% perceived deja vu with a positive emotional tinge, and only 4% of the respondents were afraid of the onset of this phenomenon. These criteria may be used to rule out pathological deja vu

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

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 transcrani‐ al 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.