Excitability In Patients Research Articles

Comparison of the After-Effects of Transcranial Direct Current Stimulation Over the Motor Cortex in Patients With Stroke and Healthy Volunteers

ABSTRACTIt is known that weak transcranial direct current stimulation (tDCS) induces persistent excitability changes in the cerebral cortex. There are, however, few studies that compare the after-effects of anodal versus cathodal tDCS in patients with stroke. This study assessed the after-effects of tDCS over the motor cortex in patients with hemiparetic stroke and healthy volunteers. Seven stroke patients and nine healthy volunteers were recruited. Ten minutes of anodal and cathodal tDCS (1 mA) and sham stimulation were applied to the affected primary motor cortex (M1) on different days. In healthy subjects, tDCS was applied to the right M1. Before and after tDCS, motor-evoked potentials (MEPs) in the first dorsal interosseous (FDI) muscle and silent period were measured. Anodal tDCS increased the MEPs of the affected FDI in patients with stroke as well as in healthy subjects. Cathodal tDCS increased the MEPs of the affected FDI in patients with stroke. In healthy subjects, however, cathodal tDCS decreased the MEPs. We found no significant change in the duration of the silent period after anodal or cathodal tDCS. We found that both anodal and cathodal tDCS increased the affected M1 excitability in patients with stroke. It is thought that the after-effects of tDCS are different in patients with stroke compared with healthy subjects.

Visuomotor Gain Distortion Alters Online Motor Performance and Enhances Primary Motor Cortex Excitability in Patients With Stroke

Determine if ipsilesional primary motor cortex (M1) in stroke patients processes online visuomotor discordance in gain between finger movement and observed feedback in virtual reality (VR). Chronic stroke patients flexed (N= 7) or extended (N= 1) their finger with real-time feedback of a virtual hand presented in VR. Virtual finger excursion was scaled by applying a low-gain (G(0.25) ), high-gain (G(1.75) ), or veridical (G(1.00) ) scaling factor to real-time data streaming from a sensor glove. Effects of visuomotor discordance were assessed through analysis of movement kinematics (joint excursion, movement smoothness, and angular velocity) and amplitude of motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation applied to ipsilesional M1. Data were analyzed with a repeated-measures analysis of variance (significance set at 0.05). G(0.25) discordance (relative to veridical) leads to significantly larger joint excursion, online visuomotor correction evidenced by decreased trajectory smoothness, and significantly facilitated agonist MEPs. This effect could not be explained by potential differences in motor drive (background electromyographic) or by possible differences related to joint angle or angular velocity, as these variables remained invariant across conditions at the time of MEP assessment. M1 was not significantly facilitated in the G(1.75) condition. MEPs recorded in an adjacent muscle that was not involved in the task were unaffected by visual feedback in either discordance condition. These data suggest that the neuromodulatory effects of visuomotor discordance on M1 were relatively selective. Visuomotor discordance may be used to alter movement performance and augment M1 excitability in patients following stroke. Our data illustrate that visual feedback may be a robust way to selectively modulate M1 activity. These data may have important clinical implications for the development of future VR training protocols.

Blink reflex in patients with postparalytic facial syndrome and blepharospasm: Trigeminal and auditory stimulation

ObjectiveThe enhancement of blink reflex (BR) excitability was shown in patients with postparalytic facial syndrome (PFS) and essential blepharospasm (EB). We prospectively investigated patients with PFS and EB whether BR alterations demonstrated by trigeminal stimulation will similarly be observed upon auditory stimulation. MethodsFifteen patients with PFS, 15 patients with EB, and 30 healthy volunteers were involved. Electrically stimulated trigeminal BR and auditory BR were studied bilaterally. ResultsThe mean R2 amplitude and duration values were highest in EB patients, being significantly higher than PFS patients (p<0.05) and control group (p<0.01). The mean R2 duration in PFS patients were also significantly longer in compared to control group (p=0.025). EB patients showed a higher mean R (auditory) amplitude and duration than PFS patients (p<0.05) and controls (p<0.04). The mean R (auditory) duration was longer on symptomatic side of PFS patients in compared to controls (p=0.05). ConclusionsWe observed that there is an enhanced excitability of BR circuit in postparalytic facial syndrome and essential blepharospasm, which could be evoked by auditory stimulation in addition to trigeminal stimulation. SignificanceThe enhanced excitability in patients with EB and PFS probably originates from the final common pathway of BR circuit, namely facial motor or premotor neurons.

Epilepsy: Ever-changing states of cortical excitability

It has been proposed that the underlying epileptic process is mediated by changes in both excitatory and inhibitory circuits leading to the formation of hyper-excitable seizure networks. In this review we aim to shed light on the many physiological factors that modulate excitability within these networks. These factors have been discussed extensively in many reviews each as a separate entity and cannot be extensively covered in a single manuscript. Thus for the purpose of this work in which we aim to bring those factors together to explain how they interact with epilepsy, we only provide brief descriptions. We present reported evidence supporting the existence of the epileptic brain in several states; interictal, peri-ictal and ictal, each with distinct excitability features. We then provide an overview of how many physiological factors influence the excitatory/inhibitory balance within the interictal state, where the networks are presumed to be functioning normally. We conclude that these changes result in constantly changing states of cortical excitability in patients with epilepsy.

FOSMN syndrome

To better define the pathophysiologic mechanisms underlying the development of the novel facial-onset sensory and motor neuronopathy (FOSMN) syndrome and, in particular, to determine whether neurodegenerative processes, mediated by excitotoxicity, or autoimmune mechanisms contribute to the development of FOSMN syndrome. Clinical, laboratory, neurophysiologic, and pathologic assessments were undertaken for 5 patients with FOSMN syndrome (3 male and 2 female), the largest cohort of FOSMN syndrome reported to date. In addition to conventional neurophysiologic studies, novel threshold tracking transcranial magnetic stimulation (TMS) techniques were undertaken to assess for the presence of cortical excitability. Clinically, all patients exhibited the typical FOSMN syndrome phenotype, heralded by facial-onset sensory deficits with subsequent development of motor deficits evolving in a rostral-caudal direction. Pathologic studies, including an autopsy, disclosed widespread degeneration of sensory and motor neurons with no evidence of inflammation, amyloid deposition, or intraneuronal inclusions, such as TDP-43, Bunina bodies, or ubiquitin inclusions. Conventional neurophysiologic studies revealed abnormalities of blink reflexes, along with features of motor and sensory neuronopathy. Threshold tracking TMS disclosed normal cortical excitability in patients with FOSMN syndrome, with preserved short-interval intracortical inhibition, resting motor threshold, motor evoked potential amplitude, and cortical silent period duration. Patients with FOSMN syndrome failed to respond to immunomodulatory approaches. Findings from the present study suggest that FOSMN syndrome is a primary neurodegenerative disorder of sensory and motor neurons, with distinct pathophysiologic mechanisms.

Patients in a vegetative state following traumatic brain injury display a reduced intracortical modulation

ObjectivePatients in coma who fail to wake develop a condition known as a vegetative state (VS). While we know that some cortical activities exist in patients in VS, it remains unclear whether interneuronal modulation can be abnormal in the cerebral cortex of these patients. The aim of the study was to evaluate the inhibitory and excitatory interneuronal circuits in patients in VS following a traumatic brain injury. MethodsCortical excitability was studied in 5 VS patients and in 10 healthy subjects using paired pulses transcranial magnetic stimulation (TMS). Resting motor threshold and intracortical inhibition and facilitation at short intervals (2 and 10ms, respectively) were evaluated. Two patients were studied again after their level of consciousness transitioned into a minimally conscious state (MCS). ResultsBoth intracortical inhibition and facilitation were significantly reduced in patients compared to healthy subjects (p<0.05). In addition, these results did not significantly change in the 2 patients who evolved into a MCS. ConclusionsThis is the first report showing an abnormal cortical excitability in patients in VS. SignificanceOur findings suggest a pathophysiological base for future work aiming to restore the lack of interneuronal transmission in patients in VS.

Paradoxical Alteration in Cortical Excitability Following 10 Hz rTMS in Patients with Untreated Obstructive Sleep Apnea Syndrome (OSAS) (P05.007)

Objective: To investigate changes in cortical excitability in patients with obstructive sleep apnea syndrome (OSAS) undergoing 10Hz repetitive transcranial magnetic stimulation (rTMS) during wakefulness. Background OSAS is a syndrome characterized by repetitive upper airway collapse or narrowing during sleep with sequelae include adverse cardiovascular and metabolic outcomes, decline in quality of life, and neurocognitive impairment. Although altered cortical excitability in OSAS is well documented, the effect of rTMS on the excitability changes in OSAS patients has not previously been studied. This is important as rTMS can potentially be used as an adjunct therapy in OSAS. Design/Methods: We recruited 13 untreated severe OSAS (10 males, mean apnea-hypopnea index=54.6±13.01h) patients and 12 age-matched healthy volunteers. The TMS parameters measured were resting motor threshold (RMT), motor evoked potential (MEP) amplitude, central motor conduction time (CMCT), cortical silent period (CSP) and short-interval intracortical inhibition (SICI). These parameters were measured in the morning more than 2h after arising. After the baseline TMS studies, the patients and healthy volunteers were subjected to 10 Hz rTMS over left dorsolateral prefrontal cortex. The TMS parameters (RMT, MEP, CMCT, CSP and SICI) were repeated thereafter. Results: OSAS patients had a significantly higher RMT and a longer CSP duration (t-test, p 0.05). The rTMS showed an prolongation of CSP in OSAS subjects (ANOVA, p Conclusions: This TMS-based study suggests that untreated severe OSAS patients have imbalanced cortical excitabilities that enhanced inhibition or decreased brain excitability when awake during the day. The paradoxical response of rTMS in OSAS patients highlights the complex interplay of excitatory and inhibitory cortical circuits in OSAS. This intriguing result needs further replication. Disclosure: Dr. Das has nothing to disclose. Dr. Vijayakumari has nothing to disclose. Dr. Radhakrishnan has nothing to disclose.

Corticospinal excitability in patients with anoxic, traumatic, and non-traumatic diffuse brain injury

BackgroundTranscranial magnetic stimulation (TMS) have been frequently used to explore changes in motor cortex excitability in stroke and traumatic brain injury, while the extent of motor cortex reorganization in patients with diffuse non-traumatic brain injury remains largely unknown. Objective/HypothesisIt was hypothesized that the motor cortex excitability would be decreased and would correlate to the severity of brain injury and level of functioning in patients with anoxic, traumatic, and non-traumatic diffuse brain injury. MethodsTMS was applied to primary motor cortices of 19 patients with brain injury (5 traumatic and 14 non-traumatic causes; on average four months after insult), and 9 healthy controls. The test parameters included resting motor threshold (RMT), short intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI). Excitability parameters were correlated to the severity of brain injury measured with Glasgow Coma Scale and the level of functioning assessed using the Ranchos Los Amigos Levels of Cognitive Functioning Assessment Scale and Functional Independence Measure. ResultsThe patient group revealed a significantly decreased SICI and SAI compared to healthy controls with the amount of SICI correlated significantly to the severity of brain injury. Other electrophysiological parameters did not differ between the groups and did not exhibit any significant relationship with clinical functional scores. ConclusionsThe present study demonstrated the impairment of the cortical inhibitory circuits in patients with brain injury of traumatic and non-traumatic aetiology. Moreover, the significant correlation was found between the amount of SICI and the severity of brain injury.

Short latency afferent inhibition associated with cortical compression and memory impairment in patients with chronic subdural hematoma

ObjectiveTo evaluate the cortical excitability in patients with mild cortical compression. MethodsThe present study used short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI) to evaluate motor cortex excitability in 16 chronic subdural hematoma (CSDH) patients with memory impairment and compared the data with those of 16 healthy controls. ResultsSAI was reduced in patients compared with controls (99±14 vs. 47±11% of the test size; p<0.0001, unpaired t-test). CSDH patients tended to have a high resting motor threshold and less pronounced SICI and ICF than controls, but these differences were not significant. Treatment of hematoma improved memory impairment and SAI in CSDH patients with wide individual variations that ranged from an increase of 74% to 17% of test size. ConclusionThese findings suggest that measuring SAI may provide a means of probing the integrity of cortical cholinergic networks in a compressed human brain.

Impact of magnetostimulation on nerve and muscle electrical excitability in patients with increased muscle tone

Abstract Introduction Increased muscle tension and the shortening of the trapezius muscle are the two most characteristic symptoms of the static–dynamic balance disorder in the muscular system. An abnormal muscle tone is a local reaction, which is located in the immediate vicinity of the disorder, or it may be a generalized reaction of the body associated with the additional psychic burden on the patient. Magnetostimulation, along with magnetotherapy, due to their physical and biophysical mechanisms of interaction are the basic kinds of weak magnetic fields used in the treatment of individuals with increased muscle tone – increased stabilization of the membrane polarization in nerve and muscle cells reduces increased muscle tension and pain. Aim The aim of this study was to assess the effect of magnetostimulation on changes in the excitability of nerves and muscles after a single and repeated exposure to a magnetic field. Materials and methods The study group comprised 34 patients divided into two subgroups: group I – 22 patients who were treated with magnetostimulation, and group II (control) – 12 subjects exposed to the so-called sham field. All patients underwent nerve and muscle excitability examinations (rheobase and chronaxie calculation), and the severity of spasticity was evaluated in each case according to the Ashworth scale. Results and discussion In patients with increased muscle tone with magnetostimulation treatment reduction of nerve–muscle excitability in the rheobase and chronaxie study has been shown. Changes in rheobase and chronaxie took on different values. Conclusions Magnetostimulation contributes significantly to reducing the excitability of nerves and muscles in patients with increased muscle tone. Magnetostimulation exhibits the greatest therapeutic efficacy after the first application of the magnetic field. A magnetic field providing magnetic stimulation can be used as an adjuvant therapy in patients with increased muscle tone.

Electrical probing of cortical excitability in patients with epilepsy

Standard methods for seizure prediction involve passive monitoring of intracranial electroencephalography (iEEG) in order to track the ‘state’ of the brain. This paper introduces a new method for measuring cortical excitability using an electrical probing stimulus. Electrical probing enables feature extraction in a more robust and controlled manner compared to passively tracking features of iEEG signals. The probing stimuli consist of 100 bi-phasic pulses, delivered every 10min. Features representing neural excitability are estimated from the iEEG responses to the stimuli. These features include the amplitude of the electrically evoked potential, the mean phase variance (univariate), and the phase-locking value (bivariate). In one patient, it is shown how the features vary over time in relation to the sleep–wake cycle and an epileptic seizure. For a second patient, it is demonstrated how the features vary with the rate of interictal discharges. In addition, the spatial pattern of increases and decreases in phase synchrony is explored when comparing periods of low and high interictal discharge rates, or sleep and awake states. The results demonstrate a proof-of-principle for the method to be applied in a seizure anticipation framework. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.

Characterization of a novel, dominant negative KCNJ2 mutation associated with Andersen-Tawil syndrome

Andersen-Tawil syndrome is characterized by periodic paralysis, ventricular ectopy, and dysmorphic features. Approximately 60% of patients exhibit loss-of-function mutations in KCNJ2, which encodes the inwardly rectifying K+ channel pore forming subunit Kir2.1. Here, we report the identification of a novel KCNJ2 mutation (G211T), resulting in the amino acid substitution D71Y, in a patient presenting with signs and symptoms of Andersen-Tawil syndrome. The functional properties of the mutant subunit were characterized using voltage-clamp experiments on transiently transfected HEK-293 cells and neonatal mouse ventricular myocytes. Whole-cell current recordings of transfected HEK-293 cells demonstrated that the mutant protein Kir2.1-D71Y fails to form functional ion channels when expressed alone, but co-assembles with wild-type Kir2.1 subunits and suppresses wild-type subunit function. Further analysis revealed that current suppression requires at least two mutant subunits per channel. The D71Y mutation does not measurably affect the membrane trafficking of either the mutant or the wild-type subunit or alter the kinetic properties of the currents. Additional experiments revealed that expression of the mutant subunit suppresses native IK1 in neonatal mouse ventricular myocytes. Simulations predict that the D71Y mutation in human ventricular myocytes will result in a mild prolongation of the action potential and potentially increase cell excitability. These experiments indicate that the Kir2.1-D71Y mutant protein functions as a dominant negative subunit resulting in reduced inwardly rectifying K+ current amplitudes and altered cellular excitability in patients with Andersen-Tawil syndrome.

Inter-session repeatability of cortical excitability measurements in patients with epilepsy

Previous studies have evaluated the inter-session variability of motor thresholds (MT), short intracortical inhibition and intracortical facilitation using paired pulse transcranial magnetic stimulation (TMS) in normal individuals. Here we evaluate the reproducibility of a range of measures of cortical excitability in patients with epilepsy. Twenty-four drug naïve patients with newly diagnosed epilepsy (13 idiopathic generalised epilepsy [IGE], 11 focal epilepsy) and seventeen non-epilepsy controls were studied. Motor threshold (MT) at rest and recovery curves constructed using paired pulse stimulation at short (2-15 ms) and long (50-400 ms) interstimulus intervals (ISIs) were analysed on two separate occasions, 4-20 weeks apart. The Lin's concordance correlation coefficient test was used to measure agreement between the two sessions. Significant levels of agreement between the two sessions were observed at MT and all the ISIs measured. This was highest in non-epilepsy controls. Cortical excitability measures are repeatable over time in both patients with epilepsy and healthy controls. Increased motor cortex excitability is a stable feature in epilepsy without significant inter-session variability.

Effects of anodal tDCS on lumbar propriospinal system in healthy subjects

ObjectiveIt has recently been shown that transcranial direct current stimulation (tDCS) (1) can modify lumbar spinal network excitability and (2) decreases cervical propriospinal system excitability. Thus the purpose of this series of experiments was to determine if anodal tDCS applied over the leg motor cortex area induces changes in lumbar propriospinal system excitability. To that end, the effects of anodal tDCS and sham tDCS on group I and group II propriospinal facilitation of quadriceps motoneurones were studied in healthy subjects. MethodsCommon peroneal nerve group I and group II quadriceps H-reflex facilitation was assessed in 15 healthy subjects in two randomised conditions: anodal tDCS condition and sham tDCS condition. Recordings were performed before, during and after the end of the cortical stimulation. ResultsCompared to sham, anodal tDCS decreases significantly CPN-induced group I and II quadriceps H-reflex facilitation during and also after the end of the cortical stimulation. ConclusionsAnodal tDCS induces (1) modulation of lumbar propriospinal system excitability (2) post-effects on spinal network. SignificanceThese results open a new vista to regulate propriospinal lumbar system excitability in patients and suggest that anodal tDCS would be interesting for neuro-rehabilitation of patients with central nervous system lesions.

Corticospinal excitability in patients with secondary dystonia due to focal lesions of the basal ganglia and thalamus

ObjectiveTo investigate the possible correlations between clinico-radiological features and pathophysiological mechanisms in patients with dystonia secondary to focal brain lesions. MethodsSingle and paired-pulse transcranial magnetic stimulation was used to assess corticospinal excitability in 10 patients (4 females; mean age 61) and a group of normal controls. Active threshold, latency and amplitude of motor evoked potentials (MEPs), silent period (SP) duration and short-interval intracortical inhibition (SICI) were evaluated. ResultsPatients with lesions involving the putamen and caudate presented with dystonic postures at rest. TMS assessment in these subjects showed increased MEP amplitude on the affected side and a bilateral decrease of SP duration and SICI. When the lesion spared the putamen and caudate, mainly involving the thalamus, the clinical picture was dominated by slow repetitive involuntary movements and tremor. In the affected side of these subjects the MEP amplitude was reduced and the MEP threshold was increased. ConclusionsWhen putamen and caudate were lesioned, the patients presented with dystonic postures at rest; furthermore the patients showed changes of corticospinal excitability in comparison to both healthy subjects and other dystonic patients. SignificanceThere are correlations between type of dystonia, site of the lesion and neurophysiological findings.

Transcranial direct current stimulation does not modulate motor cortex excitability in patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive disease caused by the degeneration of upper and lower motor neurons. The etiology of ALS is unclear, but there is evidence that loss of cortical inhibition could be related to motor neuron degeneration. We sought to determine whether cathodal transcranial direct current stimulation (tDCS) can reduce cortical excitability in patients with ALS. Three sessions of cathodal tDCS, lasting 7, 11, or 15 minutes, were performed in 10 patients and 10 healthy controls. Corticospinal excitability was measured before and after the tDCS. Cathodal tDCS induced a consistent decrease in corticospinal excitability in healthy controls, but not in ALS patients. The failure of tDCS to produce an excitability shift in the patients supports the potential diagnostic value of tDCS as a marker of upper motor neuron involvement. However, variation in corticospinal excitability measurements both inter- and intraindividually will limit its usefulness.

P2.12 Mobile phone emissions modulate brain excitability in patients affected by focal epilepsy

P2.12 Mobile phone emissions modulate brain excitability in patients affected by focal epilepsy

Novel etiopathophysiological aspects of thyrotoxic periodic paralysis

Thyrotoxicosis can lead to thyrotoxic periodic paralysis (TPP), an endocrine channelopathy, and is the most common cause of acquired periodic paralysis. Typically, paralytic attacks cease when hyperthyroidism is abolished, and recur if hyperthyroidism returns. TPP is often underdiagnosed, as it has diverse periodicity, duration and intensity. The age at which patients develop TPP closely follows the age at which thyrotoxicosis occurs. All ethnicities can be affected, but TPP is most prevalent in people of Asian and, secondly, Latin American descent. TPP is characterized by hypokalemia, suppressed TSH levels and increased levels of thyroid hormones. Nonselective β adrenergic blockers, such as propranolol, are an efficient adjuvant to antithyroid drugs to prevent paralysis; however, an early and definitive treatment should always be pursued. Evidence indicates that TPP results from the combination of genetic susceptibility, thyrotoxicosis and environmental factors (such as a high-carbohydrate diet). We believe that excess T(3) modifies the insulin sensitivity of skeletal muscle and pancreatic β cells and thus alters potassium homeostasis, but only leads to a depolarization-induced acute loss of muscle excitability in patients with inherited ion channel mutations. An integrated etiopathophysiological model is proposed based on molecular findings and knowledge gained from long-term follow-up of patients with TPP.

A distinctive pattern of cortical excitability in patients with the syndrome of dystonia and cerebellar ataxia

Objective The syndrome of dystonia and cerebellar ataxia (DYTCA) is a recently described condition where cervical dystonia and mild cerebellar ataxia are the major clinical features. Here we attempted to explore the pathophysiology of this condition by comparing measurements of cortical excitability between patients with DYTCA, typical primary dystonia and healthy controls. Methods Motor threshold, active MEP recruitment and CSP duration were measured and the excitability of the intracortical inhibitory and excitatory circuits was assessed at rest using a paired pulse protocol. Results We identified a distinctive pattern of cortical excitability in DYTCA patients different from that found in primary dystonia, namely hyperexcitable short-interval intracortical inhibition. Conclusion DYTCA patients have a noticeably dissimilar excitability profile from patients with primary dystonia. Significance A tendency for increased SICI has been previously described in cerebellar syndromes and the altered excitability profile seen in these patients is therefore possibly a consequence of the cerebellar dysfunction in DYTCA. A direct link between reduced intracortical inhibition and dystonia has recently been questioned and our results additionally suggest that reduced motor cortex inhibition is not a prerequisite for dystonia to occur.

P14-14 Enhanced subcortical excitability in patients with migraine revealed by high-frequency oscillations

P14-14 Enhanced subcortical excitability in patients with migraine revealed by high-frequency oscillations