Cortex Excitability Research Articles

Effects of Low-Frequency (0.5 Hz) and High-Frequency (10 Hz) Repetitive Transcranial Magnetic Stimulation on Neurological Function, Motor Function, and Excitability of Cortex in Ischemic Stroke Patients.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique. The purpose of our study is to explore the effects of low-frequency (0.5 Hz) and high-frequency (10 Hz) rTMS on neurological function, motor function, and excitability of cortex in Chinese ischemic stroke patients. A total of 240 ischemic stroke patients were collected. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), motor-evoked potential (MEP) cortical latency, central motor conduction time (CMCT), Fugel-Meyer assessment (FMA), Berg balance scale (BBS), and modified Barthel index (MBI) scores were recorded. After treatment, the NIHSS, mRS, MEP cortical latency, CMCT, FMA, BBS, and MBI scores of the high-frequency group and low-frequency group were significantly improved than the sham stimulation group, and the changes in the low-frequency group were more significant (adjusted P <0.05). Compared with the sham stimulation group, high-frequency stimulation reduced the NIHSS score by 9.5%, mRS score by 12.6%, MEP latency by 2.5%, and CMCT by 5.8%, and increased the upper limb FMA scale by 16.4%, lower limb FMA scale by 8.8%, BBS by 26.3%, and MBI by 9.3%, while low-frequency stimulation reduced the NIHSS score by 23.8%, mRS score by 25.3%, MEP Latency by 11.7%, and CMCT by 9.1%, and increased the upper limb FMA scale by 24.1%, lower limb FMA scale by 18.4%, BBS by 27.4%, and MBI by 23.7% in our cohort. Low-frequency rTMS is better than high-frequency rTMS stimulation in improving neurological function, motor function, and excitability of cortex in ischemic stroke.

Network alterations underlying anxiety symptoms in early multiple sclerosis

BackgroundAnxiety, often seen as comorbidity in multiple sclerosis (MS), is a frequent neuropsychiatric symptom and essentially affects the overall disease burden. Here, we aimed to decipher anxiety-related networks functionally connected to atrophied areas in patients suffering from MS.MethodsUsing 3-T MRI, anxiety-related atrophy maps were generated by correlating longitudinal cortical thinning with the severity of anxiety symptoms in MS patients. To determine brain regions functionally connected to these maps, we applied a technique termed “atrophy network mapping”. Thereby, the anxiety-related atrophy maps were projected onto a large normative connectome (n = 1000) performing seed‐based functional connectivity. Finally, an instructed threat paradigm was conducted with regard to neural excitability and effective connectivity, using transcranial magnetic stimulation combined with high-density electroencephalography.ResultsThinning of the left dorsal prefrontal cortex was the only region that was associated with higher anxiety levels. Atrophy network mapping identified functional involvement of bilateral prefrontal cortex as well as amygdala and hippocampus. Structural equation modeling confirmed that the volumes of these brain regions were significant determinants that influence anxiety symptoms in MS. We additionally identified reduced information flow between the prefrontal cortex and the amygdala at rest, and pathologically increased excitability in the prefrontal cortex in MS patients as compared to controls.ConclusionAnxiety-related prefrontal cortical atrophy in MS leads to a specific network alteration involving structures that resemble known neurobiological anxiety circuits. These findings elucidate the emergence of anxiety as part of the disease pathology and might ultimately enable targeted treatment approaches modulating brain networks in MS.

Effects of short-term upper limb immobilization on sensory information processing and corticospinal excitability.

Several studies have reported the effects of short-term immobilization of the upper limb on the excitability of the primary motor cortex. In a report examining the effects of upper limb immobilization on somatosensory information processing using somatosensory-evoked potentials (SEPs), short-term upper limb immobilization reduced the amplitude and increased the latency of the P45 component recorded over the contralateral sensorimotor cortex of SEPs. However, the effects of upper limb immobilization on other regions involved in somatosensory information processing are unknown. Therefore, we investigated the effects of short-term right upper limb immobilization on sensory information processing, particularly in motor-related areas, by measuring the cortical components of SEPs. We also evaluated the excitability of the primary motor cortex and corticospinal tract as well as motor performance (visual simple reaction time and pinch force) related to these areas. All subjects were divided into two groups: the SEP group, in which the effects of upper limb immobilization on the excitability of somatosensory processing were investigated, and the transcranial magnetic stimulation (TMS) group, in which the effects of upper limb immobilization on the excitability of the corticospinal tract and primary motor cortex were investigated. Motor performance was evaluated in all subjects. We showed that 10-h right upper limb immobilization increased the cortical component of SEPs (N30) in the SEP group and decreased the excitability of the corticospinal tract, but not of the primary motor cortex, in the TMS group. The pinch force decreased after upper limb immobilization. However, the visual simple reaction time did not change between pre- and post-immobilization. The supplementary motor area and premotor cortex are believed to be the source of the N30. Therefore, these results suggest that upper limb immobilization affected somatosensory information processing in motor-related areas. Moreover, 10-h right upper limb immobilization reduced the excitability of corticospinal tracts but not that of the primary motor cortex, suggesting that circuits outside the M1, such as the intra- and inter-hemispheric inhibitory and facilitatory circuits rather than circuits within the M1, may be responsible for the reduced excitability of the central nervous system after restraint.

Decoding personalized motor cortical excitability states from human electroencephalography

Brain state-dependent transcranial magnetic stimulation (TMS) requires real-time identification of cortical excitability states. Current approaches deliver TMS during brain states that correlate with motor cortex (M1) excitability at the group level. Here, we hypothesized that machine learning classifiers could successfully discriminate between high and low M1 excitability states in individual participants using information obtained from low-density electroencephalography (EEG) signals. To test this, we analyzed a publicly available dataset that delivered 600 single TMS pulses to the right M1 during EEG and electromyography (EMG) recordings in 20 healthy adults. Multivariate pattern classification was used to discriminate between brain states during which TMS evoked small and large motor-evoked potentials (MEPs). Results show that personalized classifiers successfully discriminated between low and high M1 excitability states in 80% of tested participants. MEPs elicited during classifier-predicted high excitability states were significantly larger than those elicited during classifier-predicted low excitability states in 90% of tested participants. Personalized classifiers did not generalize across participants. Overall, results show that individual participants exhibit unique brain activity patterns which predict low and high M1 excitability states and that these patterns can be efficiently captured using low-density EEG signals. Our findings suggest that deploying individualized classifiers during brain state-dependent TMS may enable fully personalized neuromodulation in the future.

Altered Visual Cortical Excitability Is Associated With Psychopathological Symptoms in Major Depressive Disorder.

Previous studies suggest that in people with major depressive disorder (MDD), there exists a perturbation of the normal balance between the excitatory and inhibitory neurotransmitter systems in the visual cortex, indicating the possibility of altered visual cortical excitability. However, investigations into the neural activities of the visual cortex in MDD patients yielded inconsistent findings. The present study aimed to evaluate the visual cortical excitability utilizing a paired-pulse stimulation paradigm in patients with MDD and to access the paired-pulse behavior of recording visual evoked potentials (VEPs) as a marker of MDD. We analyzed the amplitudes of VEPs and paired-pulse suppression (PPS) at four different stimulus onset asynchronies (SOAs) spanning 93 ms to 133 ms. Further, the relationship between PPS and the symptom severity of depression was investigated using Spearman's correlation. We found that, whereas the first VEP amplitude remained unchanged, the second VEP amplitude was significantly higher in the MDD group compared to the healthy controls. As a result, the amplitude ratio (second VEP amplitude/first VEP amplitude) increased, indicating reduced PPS and thus increased excitability in the visual cortex. Moreover, we found the amplitude ratios had a significantly positive correlation with the symptom severity of depression in MDD, indicating a clinically useful biomarker for MDD. Our findings provide new insights into the changes in the excitation-inhibition balance of visual cortex in MDD, which could pave the way for specific clinical interventions.

The increased in vivo firing of pyramidal cells but not interneurons in the anterior cingulate cortex after neuropathic pain

Chronic pain damages the balance between excitation and inhibition in the sensory cortex. It has been confirmed that the activity of cortical glutamatergic pyramidal cells increases after chronic pain. However, whether the activity of inhibitory interneurons synchronized changed remains obscure, especially in in vivo conditions. In the present study, we checked the firing rate of pyramidal cells and interneurons in the anterior cingulate cortex, a main cortical area for the regulation of nociceptive information in mice with spared nerve injury by using in vivo multi-channel recording system. We found that the firing rate of pyramidal cells but not interneurons increased in the ACC, which was further confirmed by the increased FOS expression in pyramidal cells but not interneurons, in mice with neuropathic pain. Selectively high frequency stimulation of the ACC nociceptive afferent fibers only potentiated the activity of pyramidal cells either. Our results thus suggest that the increased activity of pyramidal cells contributes to the damaged E/I balance in the ACC and is important for the pain hypersensitivity in mice with neuropathic pain.

Removal of Perineuronal Nets Leads to Altered Neuronal Excitability and Synaptic Transmission in Visual Cortex with Distinct Time Courses

Removal of Perineuronal Nets Leads to Altered Neuronal Excitability and Synaptic Transmission in Visual Cortex with Distinct Time Courses

Nicotine Exposure during Adolescence Leads to Changes of Synaptic Plasticity and Intrinsic Excitability of Mice Insular Pyramidal Cells at Later Life.

To find satisfactory treatment for nicotine addiction, synaptic and cellular mechanisms should be investigated comprehensively. Synaptic transmission, plasticity and intrinsic excitability in various brain regions are known to be altered by acute nicotine exposure. However, it has not been addressed whether and how nicotine exposure during adolescence alters these synaptic events and intrinsic excitability in the insular cortex in adulthood. To address this question, we performed whole-cell patch-clamp recordings to examine the effects of adolescent nicotine exposure on synaptic transmission, plasticity and intrinsic excitability in layer V pyramidal neurons (PNs) of the mice insular cortex five weeks after the treatment. We found that excitatory synaptic transmission and potentiation were enhanced in these neurons. Following adolescent nicotine exposure, insular layer V PNs displayed enhanced intrinsic excitability, which was reflected in changes in relationship between current strength and spike number, inter-spike interval, spike current threshold and refractory period. In addition, spike-timing precision evaluated by standard deviation of spike timing was decreased following nicotine exposure. Our data indicate that adolescent nicotine exposure enhances synaptic transmission, plasticity and intrinsic excitability in layer V PNs of the mice insular cortex at later life, which might contribute to severe nicotine dependence in adulthood.

Feasibility of combining noninvasive brain stimulation and personalized counseling to increase physical activity

Few older adults meet recommended physical activity guidelines. Behavioral interventions may be more effective when combined with other modalities to promote activity. Transcranial direct current stimulation (tDCS) designed to increase the excitability of the left dorsolateral prefrontal cortex (dlPFC) — a brain region subserving motivation and executive function — has the potential to augment behavioral interventions. We designed a randomized, double-blinded trial to examine the feasibility of combining personalized behavioral counseling and tDCS targeting the left dlPFC to improve physical activity and related outcomes in sedentary older adults living within the supportive housing. Participants wore a Fit-Bit throughout the study period. Baseline step counts were determined for two weeks, then participants completed four bi-weekly personalized counseling sessions over eight weeks. They were also randomized to receive 10 sessions of tDCS or sham stimulation over the two weeks after the baseline. Physical, cognitive, and patient-reported outcomes were assessed at baseline, after ten brain stimulation sessions, and after four behavioral sessions. 33 individuals were screened and 16 enrolled (age=80±7, 13 females). 13 participants completed the study, including 100% of study assessments, 99±5% of brain stimulation sessions, and 98±7% of behavioral sessions. Fit-Bit adherence rate was 93±13%. Daily step counts were 3197±1480 at baseline and 4722±2553 over the last two weeks of the intervention. While the study is ongoing and blinded, these preliminary results indicate that it is feasible to conduct a controlled study of tDCS combined with personalized behavioral counseling to increase physical activity in sedentary older adults living within supportive housing.

Electroacupuncture modulates cortical excitability in a manner dependent on the parameters used.

There is evidence that electroacupuncture (EA) acts through the modulation of brain activity, but little is known about its influence on corticospinal excitability of the primary motor cortex (M1). To investigate the influence of EA parameters on the excitability of M1 in healthy individuals. A parallel, double blind, randomized controlled trial in healthy subjects, evaluating the influence of an EA intervention on M1 excitability. Participants had a needle inserted at LI4 in the dominant hand and received electrical stimulation of different frequencies (10 or 100 Hz) and amplitude (sensory or motor threshold) for 20 min. In the control group, only a brief (30 s) electrical stimulation was applied. Single and paired pulse transcranial magnetic stimulation coupled with electromyography was applied before and immediately after the EA intervention. Resting motor threshold, motor evoked potential, short intracortical inhibition and intracortical facilitation were measured. EA increased corticospinal excitability of M1 compared to the control group only when administered with a frequency of 100 Hz at the sensory threshold (p < 0.05). There were no significant changes in the other measures. The results suggest that EA with an intensity level at the sensorial threshold and 100 Hz frequency increases the corticospinal excitability of M1. This effect may be associated with a decrease in the activity of inhibitory intracortical mechanisms. U1111-1173-1946 (Registro Brasileiro de Ensaios Clínicos; http://www.ensaiosclinicos.gov.br/).

Deficits in central auditory processing among migraine patients

BackgroundMigraine is a neurological disease associated with abnormal excitability in visual, somatosensory, and motor cortex. This study aimed to verify and compare auditory processing performance in migraine patients with and without dizziness and healthy controls.ResultsSixty subjects were divided into 3 groups: control group, twenty normal healthy subjects, and study group I (twenty subjects diagnosed with migraine) and study group II (twenty subjects diagnosed with vestibular migraine). They were evaluated using the Central Auditory Processing Questionnaire for adults, tympanometry, pure tone audiometry, Psychophysical Central Auditory Tests, including Arabic Speech Intelligibility in Noise Test for adults, Arabic Dichotic Digit Test [version II], Gap in Noise Test, Duration Pattern Test, and Arabic Memory Tests. No significant difference was found between the two study groups I and II, but the significant difference was found between the study groups and the control group in all central auditory test results. Statistically significant difference was found between the control group and study groups I and II regarding all memory tests. The highest percentage of abnormality was present in temporal resolution and selective auditory attention in both study groups. There was no significant statistical correlation between the number of attacks/month and central auditory test results. There was no significant statistical correlation between the frequency of attacks in VM patients and central auditory test results.ConclusionsPatients with migraine and vestibular migraine had an inferior performance in all psychophysical central auditory tests when compared with control. Also, there was no significant difference between the 2 study groups regarding central auditory test results which may support that both migraine with and without dizziness have the same pathophysiology.

Using Neurofeedback to Restore Inter-Hemispheric Imbalance: A Study Protocol for Adults With Dyslexia

Neurofunctional models of developmental dyslexia (DD) point out disruption of the left-lateralized reading network. In individuals with DD, the left temporo-parietal (TP) regions are underactivated during reading tasks and a dysfunctional activation of the contralateral regions is reported. After a successful reading intervention, left TP lateralization was found to be increased in children with DD. Previous studies measured the effect of modulating the excitability of the left TP cortex using non-invasive brain stimulation (NIBS) in individuals with reading difficulties, showing significant reading improvements. NIBS exclusion criteria and safety guidelines may limit its application in settings without medical supervision and in younger populations. Neurofeedback (NF) training could be an alternative intervention method for modulating the inter-hemispheric balance of the temporal–parietal regions in DD. To date, the effect of NF on reading has been scarcely investigated. Few protocols increasing beta activity in underactivated areas showed improved reading outcomes. However, none of the previous studies designed the NF intervention based on a neurofunctional model of DD. We aim to propose a study protocol for testing the efficacy of a NF training specifically designed for inducing a functional hemispheric imbalance of the tempo-parietal regions in adults with DD. A randomized clinical trial aimed at comparing two experimental conditions is described: (a) Enhancing left beta/theta power ratio NF training in combination with reducing right beta/theta power ratio NF training and (b) sham NF training.Clinical Trial Registration: www.ClinicalTrials.gov, identifier [NCT04989088].

Anxiolytic effect of GABAergic neurons in the anterior cingulate cortex in a rat model of chronic inflammatory pain

Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABAAR agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABAAR antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety.

Effect of opposing needling on motor cortex excitability in healthy participants and in patients with post-stroke hemiplegia: study protocol for a single-blind, randomised controlled trial

BackgroundOpposing needling has an obvious curative effect in the treatment of post-stroke hemiplegia; however, the mechanism of the opposing needling in the treatment of post-stroke hemiplegia is still not clear. The purpose of this study is to investigate the effect of opposing needling on the excitability of primary motor cortex (M1) of healthy participants and patients with post-stroke hemiplegia, which may provide insight into the mechanisms of opposing needling in treating post-stroke hemiplegia.MethodsThis will be a single-blind, randomised, sham-controlled trial in which 80 healthy participants and 40 patients with post-stroke hemiplegia will be recruited. Healthy participants will be randomised 1:1:1:1 to the 2-Hz, 50-Hz, 100-Hz, and sham electroacupuncture groups. Patients with post-stroke hemiplegia will be randomised 1:1 to the opposing needling or conventional treatment groups. The M1 will be located in all groups by using neuroimaging-based navigation. The stimulator coil of transcranial magnetic stimulation (TMS) will be moved over the left and right M1 in order to identify the TMS hotspot, followed by a recording of resting motor thresholds (RMTs) and motor-evoked potentials (MEPs) of the thenar muscles induced by TMS before and after the intervention. The primary outcome measure will be the percent change in the RMTs of the thenar muscles at baseline and after the intervention. The secondary outcome measures will be the amplitude (μV) and latency (ms) of the MEPs of the thenar muscles at baseline and after the intervention.DiscussionThe aim of this trial is to explore the effect of opposing needling on the excitability of M1 of healthy participants and patients with post-stroke hemiplegia.Trial registrationChinese Clinical Trial Registry ChiCTR1900028138. Registered on 13 December 2019.

Intraoperative seizures occurrence in cortical mapping of eloquent areas

The effect of structural epilepsy on the frequency of intraoperative convulsive seizures is assessed when mapping functionally significant areas of the cerebral cortex during resection of intracerebral neoplasms. The work is based on the analysis of the results of intraoperative neurophysiological studies at the Polenov Neurosurgical Institute. For the period 20192020 87 intraoperative mappings of eloquent cortex were carried out during resections of intracerebral neoplasms: 79 mappings of the motor cortex and 16 mappings of auditory-speech areas during operations with awakening. When mapping the motor zones of the cortex, the frequency of seizures was 5.1%, while mapping the auditory-speech zones with awakening 18.75%. The division of cases of intraoperative convulsive seizures into two groups: seizures arising from motor mapping and seizures associated with the mapping of auditory zones reflects differences in factors that affect the excitability of the cerebral cortex. In motor mapping, stimulation occurs against the background of general anesthesia, unlike waking operations. The intensity of stimulation in auditory mapping is higher than in motor mapping in motor mapping. Formally, the current used in motor mapping is significantly higher than in mapping auditory zones. In general, with the development of intraoperative convulsive seizures, the current intensity of cortical stimulation does not exceed the average values required to stimulate functionally significant cortical zones. The presence of epileptic syndrome in patients with intracerebral tumors cannot be considered as a predictor of intraoperative seizure development when performing motor mapping under general anesthesia as well as during surgery with awakening for mapping of motor or auditory verbal zones.

Transcutaneous spinal direct current stimulation shows no effect on paired stimulation suppression of the somatosensory cortex

Transcutaneous spinal direct current stimulation (tsDCS) is a safe and convenient method of neuromodulation. It has been proven to alter sensory processing at cervicomedullary level by amplitude changes of the P30 response of tibial nerve somatosensory evoked potentials (TN SEPs). With knowledge that tsDCS affects cortical circuits, we hypothesized that tsDCS may also affect intracortical excitability of the somatosensory cortex assessed by paired stimulation suppression (PSS). Fourteen healthy men were included in this prospective, single-blinded, placebo-controlled crossover study. Single (SS) and paired stimulation (PS) TN SEPs were recorded over the scalp before, immediately as well as 30 and 60 min after applying 15 min of tsDCS over the twelfth thoracic vertebra. Each volunteer underwent three independent and randomized sessions of either cathodal, anodal or sham stimulation. tsDCS showed no effect on peak-to-peak amplitudes or latencies of cortical P40-N50 response after SS. Furthermore, tsDCS failed to induce significant changes on amplitude ratios of PSS, thus showing no impact on intracortical excitability of the somatosensory cortex in healthy subjects. Further research is required to reveal the different mechanisms and to strengthen clinical use of this promising technique.

Parallel modulation of intracortical excitability of somatosensory and visual cortex by the gonadal hormones estradiol and progesterone

The levels of the gonadal hormones estradiol and progesterone vary throughout the menstrual cycle thereby affecting cognition, emotion, mood, and social behaviour. However, how these hormones modulate the balance of neural excitation and inhibition, which crucially regulate processing and plasticity, is not fully understood. We here used paired-pulse stimulation to investigate in healthy humans the action of low and high estradiol and progesterone on intracortical inhibition in somatosensory (SI) and visual cortex (V1). We found that paired-pulse suppression in both SI and VI depended on estradiol. During high estradiol levels, paired-pulse suppression was significantly reduced. No comparable effects were found for progesterone, presumably due to a confounding effect of estradiol. Also, no hormone level-depending effects were observed for single-pulse evoked SEPs (somatosensory evoked potentials) and VEPs (visual evoked potentials) indicating a specific hormonal action on intracortical processing. The results demonstrate that estradiol globally modulates the balance of excitation and inhibition of SI and VI cortex.

Effects of repetitive transcranial magnetic stimulation combined with transcranial direct current stimulation on motor function and cortex excitability in subacute stroke patients: A randomized controlled trial

Objective: To explore effects of repetitive transcranial magnetic stimulation (rTMS) combined with transcranial direct current stimulation (tDCS) on motor function and cortex excitability in subacute stroke patients. Design: Randomized controlled trial. Setting: Inpatient hospitals. Subjects: Sixty-five participants were randomly assigned to four groups: sham, 1Hz rTMS, cathodic tDCS combined with 1Hz rTMS (tDCS-/rTMS-) and anodic tDCS combined with 1Hz rTMS (tDCS+/rTMS-). Interventions: Four interventions were used, including sham, 1Hz rTMS, and cathodal or anodal tDCS, followed by 1Hz rTMS over contralesional motor cortex, which continued for four weeks. Main measures: Outcome measures were motor function and cortical excitability, evaluated by Fugl-Meyer Assessment, National Institutes of Health Stroke Scale and Barthel Index, resting Motion Threshold, Motor Evoked Potentials and Central Motor Conduction Time, assessed at baseline, four weeks and eight weeks. Results: At four weeks after interventions, Fugl-Meyer Assessment lower limb change score in tDCS+/rTMS- group was significantly larger than other three groups (P < 0.001). There were significant differences in bilateral Motor Evoked Potentials changes between tDCS+/rTMS- group and sham group (P < 0.05). At eight weeks, compared to other groups, National Institutes of Health Stroke Scale (P = 0.003), Barthel Index (P = 0.002), FMA lower limb score (P < 0.001), and bilateral resting Motion Threshold, Motor Evoked Potentials (P < 0.05) showed significant changes in tDCS+/rTMS- group. Furthermore, Fugl-Meyer Assessment lower limb change score was associated with increased ipsilesional Motor Evoked Potentials (r = 0.703 P < 0.001) in tDCS+/rTMS- group. Conclusion: 1Hz rTMS combined with anode tDCS stimulation protocol could be a preferable rehabilitative strategy for motor recovery in subacute stroke patients.

Cortical inexcitability defines an adverse clinical profile in amyotrophic lateral sclerosis.

Background and purposeIn amyotrophic lateral sclerosis, studies using threshold‐tracking transcranial magnetic stimulation (TMS) have identified corticomotoneuronal dysfunction as a key pathogenic mechanism. Some patients, however, display no motor response at maximal TMS intensities, termed here an ‘inexcitable’ motor cortex. The extent to which this cortical difference impacts clinical outcomes remains unclear. The aim of this study was to determine the clinical profile of patients with inexcitability to TMS.MethodsMotor cortex excitability was evaluated using TMS. Patients in whom a motor evoked potential could not be recorded in one or more limbs at maximal TMS intensities were classified as four‐limb or partially inexcitable. Demographic information, clinical variables and survival data were analysed.ResultsFrom 133 patients, 40 were identified with inexcitability. Patients with four‐limb inexcitability were younger (P = 0.03) and had lower‐limb disease onset (64%), greater functional disability (P < 0.001) and faster disease progression (P = 0.02), particularly if inexcitability developed within 1 year of symptoms (P < 0.01). Patients with partial inexcitability had higher resting motor thresholds compared to the excitable cohort (P < 0.01), but averaged short‐interval intracortical inhibition was similar (P = 0.5). Mean survival was reduced if inexcitability involved all limbs within 12 months of symptom onset (P = 0.04).ConclusionAmyotrophic lateral sclerosis patients with inexcitability of all four limbs to TMS have a distinct clinical profile of younger age and lower‐limb onset. Importantly, these patients display a more malignant disease trajectory, with faster progression, greater functional disability and reduced survival when occurring in early disease. This measure may provide an important prognostic marker in amyotrophic lateral sclerosis.

INFLUENCE OF OTOTOXIC PHARMACEUTICALS ON BIOELECTRIC RESPONSES IN CEREBRAL CORTEX AND COCHLEA

The article describes the results of the experiment aimed to find out the nature of changes in the excitability of the auditory cortex during prolonged taking of antibiotics, aminoglycosides, diuretics and salicylates. Methodology. The series of experiments was carried out on cats of both sexes weighing 3-3.5 kg, in natural behaviour. Rectangular threshold (1.5-3 V) and supra-threshold (5-7 V) electrical impulses lasting 0.1 ms were applied to the TCR fibres, using single and paired (interstimular intervals of 20-500ms) stimulation of the TCR fibres. As a source of irritating impulses, a multi-channel stimulator "SEN-3201" of the company "Nikon-Kohden" (Japan) was used. For each skeletal interval was carried out on 10 repetitions. The SOFTWARE was registered using the average Det-1100 average from Nikon-Kohden (Japan). The resulting visual control was performed from the screen of the "Disa-Indicator" oscilloscope (Denmark). The maximum level of the intensity value reached 110 dB. Sound signals were transmitted through special high-frequency phones (or speakers) of the GD-4 type, which were in a free state, at a distance of 10 cm from the ear of the test ear. All the studied pharmaceuticals (furosemide, streptomycin, gentamicin, kanamycin, monomycin, tobramycin and amikacin) except acetylsalicylic acid, which was injected intraperitoneally, were administered to cats intramuscularly 2 times a day at intervals of 10-12 hours. Bioelectric reactions of the cortex and cochlea were recorded daily 2-3 hours after the next administration of drugs. Streptomycin, kanamycin and monomycin were used at a dose of 40 mg / kg, which causes inhibition of the cochlea's MIC response (MOI) and auditory nerve PD only with long-term use. Gentamicin, tobramycin and amikacin were administered in a lower (15 mg/kg) dose. Results. Furosemide reduced by 50% the value of the microphone potential recorded during sound stimulation with a frequency of 10 kHz after 4 days, with a frequency of 1 kHz-5 days, with a frequency of 0.5 kHz-6 days from the beginning of use. The most sensitive to furosemide were auditory nerve PD, which occurred during sound stimulation at a frequency of 10 kHz (T50 – 5 days), and less – at a frequency of 0.5 kHz (T50 – 7 days). The cancellation of furosemide was accompanied by the restoration of the value of these bioelectric reactions to the initial level in 5 days. Thus, the data obtained indicate the possibility of a reversible depressing effect of furosemide on the responses of the CGM and the cochlea that occur on sound stimulation. All the studied antibiotics-aminoglycosides had the ability to reduce the value of the testing primary response when paired electrical stimulation of TCR fibres. These changes were observed 2-3 days after the start of the use of antibiotics. Initial changes in the value of MP and PD of the auditory nerve occurred after 12-24 times of drug administration. In this case, a decrease in these potentials by 20-25% was noted. Further use of antibiotics led to an increase in changes in responses registered in the cochlea, with the greatest sensitivity to the effects of drugs were reactions to high-frequency sound stimuli. When analyzing the ability of the studied tools to disrupt the activity of the peripheral fragment of the auditory analyzer, a pattern similar to that for the cerebral cortex was found. Withdrawal of drugs at the stage of initial changes in potentials registered in the cochlea is not accompanied by their recovery for a long (6 weeks) period after stopping the administration of antibiotics. Conclusions. Different rates of formation of damage to interneuronal transmissions were found during long-term use of different antibiotics.