Excitability Of Cerebral Cortex Research Articles

Catamenial epilepsy

Epilepsy is a commonly encountered neurological condition characterised by recurrent episodes of unprovoked seizures. Epilepsy acts as a broad terminology that includes any abnormal mechanism in brain which cause an electrical short circuit or electrical storm that manifests as seizure1. Epilepsy affects both adults and children. Epileptic seizures can occur with wide variation in presentation and to provide effective appropriate treatment, systematic precise classification of epilepsy is mandatory. Seizures are mainly divided into partial and generalized seizures, but some are unclassified. The common definition of catamenial epilepsy is, “the seizure clusters occurring around menstrual cycle or an increased seizure frequency during certain phases of menstrual cycle”. Some female sex hormones and certain steroid gonadal hormones have neuroactive properties that can trigger seizures. Though there are many subtypes in catamenial epilepsy, neurosteroids have been found to influence the seizure clusters in women who have normal 28 day menstrual cycles who suffer during the perimenstrual period. It is thought that progesterone derived neurosteroids withdrawal causes enhanced stimulation or excitability of cerebral cortex which predispose to seizures. Varied concentrations of anticonvulsants during the different phases of menstrual cycle also because increased seizure susceptibility.

Progress on Low-frequency Repetitive Transcranial Magnetic Stimulation Based on Cerebral Cortex Excitability Control in the Treatment of Alzheimer's Disease

Low-frequency repetitive transcranial magnetic stimulation is a type of transcranial magnetic stimulation technology. Based on its high safety characteristics, researchers currently apply this technology to treat Alzheimer's disease and have achieved certain results. This paper summarizes low-frequency transcranial magnetic stimulation and its research progress in the treatment of Alzheimer's disease.

Motor neurorehabilitation in patients with epileptic seizures: limitations of methods with proven efficacy in stroke

Patients with epilepsy may require a neurorehabilitation aid particularly due to developing motor alterations related to stroke, sequelae of traumatic brain injury, multiple sclerosis and other brain damage. Modern neurorehabilitation approaches directly or indirectly affect neuroplastic processes altering cerebral cortex excitability, stimulate the afferentation systems, and result in fatigue and may act as factors provoking seizures or aggravated epilepsy. In addition, developing seizures may temporarily coincide but unrelated to the neurorehabilitation activities: e.g., while omitting antiepileptic drug administration, sleep deprivation or long-term stress occurring to patient etc. Here we present a review on recent studies aimed at investigating epilepsy triggers by aligning them with the factors of interventions used in motor rehabilitation. We also emphasize the safety data for routine use of the main neurorehabilitation methods as well as propose actions to reduce the risk of developing epileptic seizure.

Research Progress and Application Prospect of Nerve Rehabilitation by Transcranial Electrical and Magnetic Stimulation

Accidents or diseases may cause impairment or even loss of human motor function, among which stroke is a disease which is most likely to cause disability and seriously endangers social health. During recent years, as a new nerve regulation technology, non-invasive brain stimulation technology can achieve the application of nerve stimulation to the brain, induce and promote neuroplasticity and improve the excitability of cerebral cortex. Especially, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation(TMS) have shown high therapeutic potential in motor rehabilitation. This paper summarizes the mechanism and progress of the research and application of tDCS and TMS in the field of neurorehabilitation. Its technical challenges and future development trends are provided as well.

Promotion of Poststroke Motor-Function Recovery with Repetitive Transcranial Magnetic Stimulation by Regulating the Interhemispheric Imbalance.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain-stimulation technique that transiently modulates cerebral cortex excitability, achieving overall positive results in poststroke motor-function recovery. Excessive inhibition of the ipsilesional-affected hemisphere by the contralesional-unaffected hemisphere has seriously hindered poststroke motor-function recovery. Hence, intracortical disinhibition can be used as an approach to managing poststroke brain injury. This technique promotes neural plasticity for faster motor-function recovery. rTMS relieves unilateral inhibition of the brain function by regulatinga interhemispheric-imbalanced inhibition. This paper summarized 12 studies from 2016 to date, focusing on rTMS on motor function after acute and chronic stroke by regulating the interhemispheric imbalance of inhibitory inputs. Although rTMS studies have shown promising outcomes on recovery of motor functions in stroke patients, different intervention methods may lead to discrepancies in results. A uniform optimal stimulus model cannot routinely be used, mainly due to the stimulus schemes, stroke types and outcome-measuring differences among studies. Thus, the effect of rTMS on poststroke motor-function recovery should be investigated further to standardize the rTMS program for optimal poststroke motor-function recovery. More randomized, placebo-controlled clinical trials with standardized rTMS protocols are needed to ensure the effectiveness of the treatment.

The Effects of Motor Imagery Combined with Neuromuscular Electrical Stimulation on Using Transcranial Magnetic Stimulation in Stroke Patients

The purpose of this study was to investigate the effect of motor imagery combined with neuromuscular electrical stimulation (MI-NMES) on cerebral cortex excitability in stroke patients. We examined the effect of MINMES on cerebral cortex excitability using transcranial magnetic stimulation (TMS) of motor evoked potential (MEP) amplitude and latency, quantitative electroencephalography (QEEG) of δα ratio (DAR) and power ratio index (PRI) assessments. This study was to evaluate 30 stroke patients who were satisfied the selection criteria of the study. Experiments were divided into MI-NMES group, motor imagery (MI) group. This study showed that there was a significant difference for all evaluations within the MI-NMES group, with significant differences in MEP amplitude and latency, QEEG DAR, and PRI index values in the comparison that those of the MI group. MI-NMES is suggested to be an effective approach for cerebral cortex excitability in stroke patients.

The effect of combined transcranial direct current stimulation and peripheral nerve electrical stimulation on corticospinal excitability.

Transcranial direct current stimulation (tDCS) and peripheral nerve electrical stimulation (PES) can change corticospinal excitability. tDCS can be used to non-invasively modulate the cerebral cortex’s excitability by applying weak current to an electrode attached to the head, and the effect varies with the electrode’s polarity. Previous studies have reported the effect of combined tDCS and PES on corticospinal excitability; when compared to single stimulation, combined stimulation increases cortical excitability. In contrast, another study reported that the effect of tDCS is attenuated by PES; hence, there is no consensus opinion on the effect on combined stimulation. Therefore, this study aimed to clarify the effect of combined tDCS and PES on corticospinal excitability. In Experiment 1, the combined stimulation of anodal tDCS and PES (anodal tDCS + PES) was performed, and in Experiment 2, a combined stimulation with PES, after cathodal tDCS (PES after cathodal tDCS), was performed using a homeostatic metaplasticity theoretical model. In Experiment 1, anodal tDCS produced a significant increase from baseline in motor-evoked potential (MEP) amplitude 10 min after stimulation, but no significant changes in MEP amplitude were observed with PES or the anodal tDCS + PES condition. Experiment 2 showed a significant decrease in MEP amplitude immediately after cathodal tDCS, and a significant increase in MEP amplitude 15 min after PES, but no significant change in MEP amplitude was observed with sequential PES following cathodal tDCS. In conclusion, our data indicate that PES with anodal tDCS suppressed the effect of tDCS. Also, PES after cathodal tDCS did not induce homeostatic metaplasticity and increase corticospinal excitability.

Changes in recruitment of motor cortex excitation and inhibition in patients with drug-induced tardive syndromes

It has recently been suggested that drug-induced tardive syndromes (TS) might be due to maladaptive plasticity, which increases motor excitability in cerebral cortex and basal ganglia. In order to test this hypothesis, we performed the first measurements of cortical excitability in TS. Motor cortex excitability was examined using transcranial magnetic stimulation (TMS) in 22 TS patients and compared with that in 20 age and sex-matched healthy individuals. Resting and active motor threshold (RMT, AMT) and input-output curves (I/O curves) assessed corticospinal excitability. The duration of the contralateral silent period (cSP) at a range of stimulation intensities and ipsilateral silent period (iSP) were used as measures of inhibition. There were no significant differences in RMT and AMT between patients and controls, although the input-output curves were significantly steeper in patients. The cSP (at different stimulus intensities) and iSP were both longer in the patients compared to the control group. However, most of this difference could be accounted for by increased recruitment of motor evoked potentials (MEPs) in patients. TS is characterized by hyperexcitability of corticospinal output that might contribute to the lack of selectivity in muscle recruitment and contribute to excess involuntary movement. The findings are opposite to those in naturally-occurring hyperkinesia such as Sydenham's and Huntington's chorea, suggesting a fundamental difference in the pathophysiology.

Effect of Lithium Preparations on Cerebral Electrophysiological Activity in Rats.

The study examined the effects of a novel neurotropic medication based on a lithium complex composed of lithium citrate, polymethylsiloxane, and aluminum oxide on electrophysiological parameters of the rat brain. In contrast to lithium carbonate (the reference drug), the novel preparation resulted in a wave-like dynamics of electrical activity in the visual cortex. Rhythmic photic stimulation of the rats treated with lithium carbonate resulted in appearance of the signs attesting to up-regulation of excitability of cerebral cortex in all examined ranges. In contrast, the complex lithium preparation diminished the delta power spectrum, which was the only affected frequency band. It is hypothesized that the complex lithium medication induces milder activation of the cerebral cortex in comparison with lithium carbonate. The novel medication composed of lithium citrate, aluminum oxide, and polymethylsiloxane, is characterized by greater efficacy and safety than the preparation based on inorganic lithium salt (lithium carbonate).

Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation.

Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40–80 Hz) oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude—the hallmark of a type II excitable medium—yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields.

Transcranial magnetic stimulation for monitoring the rehabilitation of upper-extremity function after stroke

Objective To evaluate the effect of the transcranial magnetic stimulation on upper-extremity function rehabilitation and changes in the excitability of cerebral cortex, and to evaluate from the viewpoint of electrophysiology the prognosis so as to guide the rehabilitation treatment of patients after stroke. Methods Forty-six patients in the early stage after a stroke were given TMS examinations of the ipsilateral brain region. Those with the motor evoked potentials (MEPs) amplitudes lower than 50 μV were classified into a motion-induced experimental negative group (the negative group), while those whose MEP amplitude reached 50 μV or more were classified as movement-induced positive (the positive group). Both groups were given the same treatment. Before and after 2, 4 and 8 weeks of treatment the Fugl-Meyer movement function rating scale was used to assess their bilateral upper limb movement function. TMS technology was used to detect any change in the resting motor threshold (RMT) and the amplitude (Amp) of MEPs in the motor cortex. The incubation period of the cortex (CL) and the central motor conduction time (CMCT) in the contralateral motor cerebral cortex were also observed. Results After 4 weeks of treatment, the average score of the positive group on Fugl-Meyer upper movement function rating scale reached (54.99±2.76), significantly higher than before treatment and significantly higher than the negative group's average (P 0.05). After the treatment the CL and CMCT had shortened significantly in the negative group compared to before the treatment (P 0.05). Conclusions The excitability of the contralateral motor cortex changes after a stroke. TMS can be used to characterize the MEP to monitor and predict recovery. This should help clinicians prepare more scientific rehabilitation plans. Key words: Transcranial magnetic stimulation; Stroke; Upper limb movement function; Cortical excitability

5 Hz Repetitive Transcranial Magnetic Stimulation with Maximum Voluntary Muscle Contraction Facilitates Cerebral Cortex Excitability of Normal Subjects.

Recently, high-frequency repetitive transcranial magnetic stimulation (rTMS) is reported to evaluating the corticospinal pathway and improving both cortical excitability and motor function significantly in subjects. According to some previous reports, the maximum voluntary muscle contraction (MVC) of target muscle can reinforce the influence by rTMS. The aim of this study was to confirm 5 Hz rTMS with MVC in healthy individuals is an effective method to facilitate motor neuron excitability and the efficiency can last at least 30 min post stimulation. To compare the motor evoked potentials (MEPs) elicited by 5Hz rTMS and 5Hz rTMS combined with MVC. In this randomized, controlled, assessor-blinded, crossover trial, 40 healthy right-handed subjects were divided into group A (n=20) and group B (n=20). All subjects received rTMS over the primary motor cortex area (M1) in the left hemisphere. The parameters of rTMS were 5 Hz, 90.of the resting motor threshold (RMT), for a total of 500 pulses in 100 trains (1-sec inter-stimulus and 8- sec inter-interval). Method 1: All subjects received rTMS over the hand area of left M1. Method 2: All subjects received rTMS at the same stimulated point, combined with maximum voluntary hand griping in each 10 trains. Test 1: group A underwent method 1, while group B underwent method 2. Test 2: A week later, group B underwent method 1, while group A underwent method 2. In each test, the MEP amplitude and latency was measured before (P-rTMS), 5 min after (Post 1) and 30 min after (Post 2) the rTMS intervention. MEP amplitude increased significantly from baseline at 5 minutes post intervention under both treatment regimes. However for both sequences, it decreased towards baseline under the rTMS intervention at 30 minutes post intervention but remained relatively high when rTMS was combined with MVC. MEP latency decreased significantly from baseline at 5 minutes post intervention under both treatment regimes. For both sequences, it then increased again towards baseline under both treatment regimes at 30 minutes post intervention. Although there was a trend for a less pronounced increase under the combined treatment, this effect was not significant. Both 5 Hz rTMS and 5 Hz rTMS combined with MVC facilitate motor cortical excitability, but the enhancement in rTMS with MVC is more pronounced and maintained longer than simple rTMS.

The effect of transcutaneous vagus nerve stimulation on cortical excitability.

There is great interest about the therapeutic potentialities of transcutaneous vagus nerve stimulation (tVNS) applied to neuropsychiatric disorders. However, the mechanisms of action of tVNS and its impact on cortical excitability are unclear. To this regard, transcranial magnetic stimulation (TMS) can be useful because it is able of evaluating non-invasively excitatory and inhibitory circuitry of the human cortex. Aim of the present study is to investigate the effects of tVNS on cerebral cortex excitability in healthy volunteers by means of TMS. Ten healthy subjects participated in this randomized placebo-controlled double-blind study. Real tVNS was administered at left external acoustic meatus, while sham stimulation was performed at left ear lobe, both of them for 60min. We evaluated motor thresholds, motor evoked potential amplitude, recruitment curves, and short-interval intracortical inhibition (SICI) in right and left motor cortex. Such parameters were evaluated before and 60min after the exposure to tVNS, for both the real and the sham stimulation. Cardiovascular parameters were monitored during the stimulation. A generalized linear model for repeated measures was implemented to assess the effect of time and stimulation type on cardiovascular and neurophysiological variables. SICI, a double-pulse TMS paradigm informative of GABA-A activity, was significantly increased in right motor cortex after real tVNS. Other neurophysiological parameters, as well as cardiovascular variables, remained unchanged. Our findings confirm that tVNS is a safe and effective way to stimulate vagus nerve and provide innovative data about the possible mechanisms of action that supports the potential therapeutic application of this technique.

P241: Change of cerebral cortex excitability after electromyogram triggered electrical stimulation combined with mirror visual feedback in healthy elderly subjects

P241: Change of cerebral cortex excitability after electromyogram triggered electrical stimulation combined with mirror visual feedback in healthy elderly subjects

Minocycline exerts acute inhibitory effects on cerebral cortex excitability in humans

Minocycline has efficacy to alleviate seizure activity in animal models of epilepsy. Among other mechanisms it has been postulated that minocycline can inhibit microglial activation and develop beneficial effects by decreasing glutamate excitotoxicity. To explore acute effects of minocycline on human motor cortex excitability we used single- and paired-pulse transcranial magnetic stimulation in 12 healthy subjects 4h after a single oral dose of 200mg minocycline or placebo was administered in a randomised, double-blind, placebo-controlled crossover design. Mean cortical silent period, an inhibitory parameter of predominantly intracortical origin, was prolonged after minocycline compared to placebo, while other TMS parameters of cortical excitability remained unchanged. The results demonstrate that a particular parameter of cortical inhibition is rapidly increased after a single oral dose of minocycline in humans.

Movement, Confusion, and Orienting in Frontal Cortices

In this issue, two studies, by Ehrlich etal. and Hill etal., address the role of the frontal motor cortices in behavior of the rat and suggest a potential role for this structure in high-level control of diverse behaviors. Hill etal. show that motor cortical neurons predict whisker movements even without sensory feedback and that their activity reflects efferent control. Surprisingly, Ehrlich etal. report the participation of this same cortical region in the preparation and execution of orienting behaviors.

Circadian Modulation of GABA-Mediated Cortical Inhibition

Circadian rhythms exert powerful influence on various aspects of human physiology and behavior. Here, we tested changes of human cerebral cortex excitability over the course of the day with transcranial magnetic stimulation (TMS). At different times of the day, intracortical and corticospinal excitability of the primary motor cortex (M1) was evaluated in 15 healthy subjects by TMS of left M1. While motor thresholds, short-interval intracortical inhibition and facilitation and input/output curves remained unchanged, we found that a specific form of γ-aminobutyric acid (GABA)-mediated intracortical inhibition, revealed by long-interval intracortical inhibition and cortical silent periods, progressively decreased during the course of the day. Additional experiments demonstrated that morning inhibition persisted irrespective of previous sleep or sleep deprivation. Corticotropin-releasing hormone (CRH) infusions in the evening lead to morning cortisol levels but did not restore levels of morning inhibition, whereas suppression of endogenous CRH release by repeated oral dexamethasone intake over 24 h prevented morning inhibition. The findings suggest a specific modulation of GABAergic motor cortex inhibition within the circadian cycle, possibly linked to the CRH system, and may indicate a neurobiological basis for variable neuroplasticity over the course of the day.

Headache, epilepsy and photosensitivity: how are they connected?

Although headache and epilepsy have often been associated, the precise electroclinical and pathophysiological interaction between these disorders and in particular its relations with photosensitivity is as yet to be fully understood in adults or children. The association between headache and epilepsy commonly occurs in all types of epilepsy and not only in occipital epilepsy. Generally, peri-ictal headache is often neglected, regardless of its severity, because patients are more concerned about their seizures. Altered cerebral cortex excitability may be the link between these two conditions and photosensitivity shows this. The physician should bear this association in mind when dealing with epileptic and migraine patients so as to be able to offer such patients an accurate diagnosis and appropriate treatment; this should be borne in mind when declaring epileptic patients ‘seizure free’. To date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may, on occasion, be the sole ictal epileptic manifestation. Lastly, studies designed to investigate the triggering role of photosensitivity in both headache and epilepsy are warranted.

Modulating cortical excitability in acute stroke: A repetitive TMS study

ObjectiveChanges in cerebral cortex excitability have been demonstrated after a stroke and are considered relevant for recovery. Repetitive transcranial magnetic stimulation (rTMS) of the brain can modulate cerebral cortex excitability and, when rTMS is given as theta burst stimulation (TBS), LTP- or LTD-like changes can be induced. The aim of present study was to evaluate the effects of TBS on cortical excitability in acute stroke. MethodsIn 12 acute stroke patients, we explored the effects of facilitatory TBS of the affected hemisphere and of inhibitory TBS of the unaffected hemisphere on cortical excitability to single-pulse transcranial magnetic stimulation (TMS) on both sides. The effects produced by TBS in patients were compared with those observed in a control group of age-matched healthy individuals. ResultsIn patients, both the facilitatory TBS of the affected motor cortex and the inhibitory TBS of the unaffected motor cortex produced a significant increase of the amplitude of MEPs evoked by stimulation of the affected hemisphere. The effects observed in patients were comparable to those observed in controls. ConclusionsFacilitatory TBS over the stroke hemisphere and inhibitory TBS over the intact hemisphere in acute phase enhance the excitability of the lesioned motor cortex. SignificanceTBS might be useful to promote cortical plasticity in stroke patients.

Repetitive transcranial magnetic stimulation and chronic tinnitus

Conclusion: There is a good theoretical basis and early research evidence suggesting that transcranial magnetic stimulation (TMS) may have treatment potential in tinnitus. Further studies with larger sample sizes and additional assessment of neurobiological effects are necessary. Objectives: Tinnitus is a common and often severely disabling disorder for which there is no satisfactory treatment. TMS is a new, non-invasive method of modifying the excitability of the cerebral cortex, which has proven effective in auditory hallucinations and other disorders. Some early studies have been published in which TMS has been used in the treatment of tinnitus. The objective of this paper is to examine the literature and consider the potential for TMS as a therapy in tinnitus. Methods: A thorough search of the tinnitus and TMS literature was conducted, and all available relevant material was examined. Results: Tinnitus is common, with a prevalence of 8.2% in subjects aged 50 years and over, and may be associated with great distress (tinnitus sufferers). There are no effective treatments. Tinnitus is frequently associated with deafness, and may be the result of a pathological plasticity process. Neuroimaging studies demonstrate increased activity within the central auditory system. TMS is a non-invasive method of modulating excitability in cerebral cortex. It uses electromagnetic principles and has been successfully employed in the treatment of other conditions associated with increased activity of the cerebral cortex. Meanwhile, a growing number of studies suggest that repetitive TMS may be effective in the treatment of chronic tinnitus.