帕金森病患者运动皮质兴奋性的经颅磁刺激研究

目的:本研究拟应用低频重复性经颅磁刺激(rTMS)分别刺激帕金森病(PD)患者M1手代表区(M1Hand)及运动前区(PMC),探讨不同干预手段对运动皮质兴奋性的影响,以及M1与PMC间的联系。方法:对18名确诊PD患者先后进行4种不同干预,即口服美多芭、低频rTMS刺激M1Hand(0.5Hz,100%静息阈值,共1600次脉冲)、低频rTMS刺激PMC(0.5Hz,100%静息阈值,共1600次脉冲)以及假刺激。于每次干预前后各进行临床评价并测定运动诱发电位(MEP)相关指标。结果:①口服美多芭后UPDRSⅢ(P=0.001)以及其中有关僵直(P=0.001)、运动迟缓(P<0.001)的评分均较服药前显著改善。三种不同磁刺激干预产生结果不同,M1Hand组UPDRSⅢ减低(P=0.015),僵直(P=0.010)、运动迟缓(P=0.004)亦有所改善;PMC组UPDRSⅢ较干预前减低(P=0.046),僵直评分亦减低,但无显著性意义(P=0.163);②口服美多芭1h后MEP120减低(P=0.002),CSP延长(P=0.006);M1Hand组MEP120无著变,而CSP延长(P=0.015);PMC组MEP120减低(P=0.004),而CSP无著变;假刺激组则均无显著性改变。结论:低频rTMS对不同脑区产生的效应不同:刺激M1可使CSP延长;而刺激PMC可使MEP波幅减低。     

Corticospinal excitability during motor imagery is diminished by continuous repetition-induced fatigue

Application of continuous repetition of motor imagery can improve the performance of exercise tasks. However, there is a lack of more detailed neurophysiological evidence to support the formulation of clear standards for interventions using motor imagery. Moreover, identification of motor imagery intervention time is necessary because it exhibits possible central fatigue. Therefore, the purpose of this study was to elucidate the development of fatigue during continuous repetition of motor imagery through objective and subjective evaluation. The study involved two experiments. In experiment 1, 14 healthy young volunteers were required to imagine grasping and lifting a 1.5-L plastic bottle using the whole hand. Each participant performed the motor imagery task 100 times under each condition with 48 hours interval between two conditions: 500 mL or 1500 mL of water in the bottle during the demonstration phase. Mental fatigue and a decrease in pinch power appeared under the 1500-mL condition. There were changes in concentration ability or corticospinal excitability, as assessed by motor evoked potentials, between each set with continuous repetition of motor imagery also under the 1500-mL condition. Therefore, in experiment 2, 12 healthy volunteers were required to perform the motor imagery task 200 times under the 1500-mL condition. Both concentration ability and corticospinal excitability decreased. This is the first study to show that continuous repetition of motor imagery can decrease corticospinal excitability in addition to producing mental fatigue. This study was approved by the Institutional Ethics Committee at the Nagasaki University Graduate School of Biomedical and Health Sciences(approval No. 18121302) on January 30, 2019.     

Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study

We studied the excitability of the motor cortex in patients with migraine without aura (MWOA) (n = 20) and with chronic migraine (CM) (n = 20) using transcranial magnetic stimulation (TMS). By using a 90-mm circular coil placed over the vertex and recording of the first dorsal interosseous muscle, we measured thresholds, latencies and amplitudes of motor evoked potentials and duration of cortical silent periods in patient groups and in controls (n = 20). No differences were found between groups for threshold, latency and amplitude values. However, the duration of the cortical silent period was longer in CM patients, being significantly different from both controls and MWOA. We suggest that either this difference in cortical excitability may develop during transformation from MWOA to CM or different pathophysiological mechanisms may play a role in these two headache syndromes. Received: 28 December 2001, Received in revised form: 19 March 2002, Accepted: 21 March 2002     

Central fatigue as revealed by postexercise decrement of motor evoked potentials

We have previously shown that the amplitudes of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The responsible mechanism is apparently decreased efficiency in the generation of the descending volleys in the motor cortex. We also noted a progressive decrement inamplitude from the first to the fourth MEP. To further clarify the mechanism of this phenomenon, 5 subjects were studied with TMS deliveredat the rates of 0.1, 0.15, 0.3, 1, 3, and 6 Hz. The effect was best demonstrated at 0.3 Hz, and occurred after both isometric and isotonic exercise. Three of the subjects also had 0.3-Hz percutaneous electrical stimulation of the brainstem, and a decrement in MEP amplitude did not occur. Further, the delivery of TMS during muscle contraction after muscle fatigue failed to produce a decrement. The results are similar to those found at the neuromuscular junction in myasthenia gravis and are consistent with a reduced safety factor of cortical synaptic transmission in central nervous system fatigue. © 1994 John Wiley & Sons, Inc.     

Autonomic function in patients with chronic fatigue syndrome

Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in 37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be lower in CFS patients (28.4±10.5 beats) than in healthy controls (32.2±9.5) (p=0.11). The maximal increase in HR during standing up was not significantly different between the CFS group (37.6±8.9 beats) and the control group (40.2±8.9 beats). There were no significant differences between both groups with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva maneuver. The HR response to MA was significantly less in the CFS group (22.6±9.9) than in the control group (29.5±16.7) (p<0.05), suggesting impaired cardiac sympathetic responsiveness to mental stress. The lower HR responses could not be explained by the level of concentration in the CFS group. During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group, but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant differences between CFS patients with and without symptoms of autonomic dysfunction regarding the hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are no gross alterations in cardiovascular autonomic function in patients with CFS.     

Corticospinal excitability during walking in humans with absent and partial body weight support

Objective

To establish changes in corticospinal excitability with absent and partial body weight support (BWS), and determine test–retest reliability of motor evoked potentials (MEPs) recordings during stepping in healthy humans.

Methods

The tibialis anterior (TA) and soleus MEPs during stepping at 0 and at 25 BWS were recorded in two experimental sessions in the same subjects. Transcranial magnetic stimulation was delivered randomly across the step cycle at 1.2 × TA MEP resting threshold. The non-stimulated associated electromyogram (EMG) was subtracted from the TA and soleus MEPs at identical time windows and bins of the step cycle, and the resultant values were normalized to the maximal homologous EMG activity during stepping. The relationship between MEPs and background EMG activity was determined for each BWS level and session tested.

Results

The TA MEPs were facilitated at heel contact, progressively decreased during the stance phase, and facilitated throughout the swing phase of the step cycle. In contrast, the soleus MEPs were progressively increased at early-stance, depressed at the stance-to-swing transition, and remained depressed throughout the swing phase. The TA and soleus MEPs were modulated in a similar pattern across sessions at 0 and at 25 BWS, and were linearly related to the associated background EMG activity.

Conclusions

These results provide evidence that reduced body weight loading does not alter the strength of corticospinal excitability, and that MEPs can be reliably recorded at different sessions during stepping in healthy humans.

Significance

A rehabilitation strategy to restore gait in neurological disorders utilizes BWS during stepping on a motorized treadmill. Based on our findings, the strength of corticospinal drive will not be affected negatively during stepping under conditions of partial body loading.     

Differences between patients with chronic fatigue syndrome and with chronic fatigue at an infectious disease clinic in Stockholm,Sweden

Background data were collected from patients presenting with fatigue at the clinic of infectious diseases at Huddinge University Hospital, Stockholm. The main purpose was to look for differences as to demographic and functional status for patients fulfilling criteria for chronic fatigue syndrome (CFS) and chronic fatigue (CF). A cross-sectional questionnaire survey was performed using a variety of instruments. A thorough medical investigation was performed. No difference was found as to social situation, occupation and illness attributions for patients in the two categories. Patients with CFS reported in general a higher degree of 'sickness' with more self-reported somatic symptoms, more self-reported functional impairment and more absence from work. A higher degree of psychiatric comorbidity was observed in CF than in CFS patients. A majority of CFS patients (80%) had an acute infectious onset compared to 43% in the CF group. Presently used criteria might, according to findings presented here, define two different patient categories in a population characterized by severe, prolonged fatigue. Because CFS patients (compared to patients with CF) have more somatic symptoms, more often report an infectious, sudden onset and have less psychiatric comorbidity, and CF patients seem to have more of an emotional, burn-out-like component one could speculate about the existence of different pathogenetic backgrounds behind the two diagnoses.     

Corticomotor excitability and perception of effort during sustained exercise in the chronic fatigue syndrome.

OBJECTIVE: We have investigated the possibility of a central basis for the complaints of fatigue and poor exercise tolerance in subjects with chronic fatigue syndrome (CFS). METHODS: Transcranial magnetic stimulation of the motor cortex was used to measure sequential changes in motor evoked potential (MEP) amplitude, post-excitatory silent period (SP) duration and twitch force of the biceps brachii muscle during a 20% maximum isometric elbow flexor contraction maintained to the point of exhaustion. Ten patients with post-infectious CFS and 10 age- and sex-matched control subjects were studied. Results were analysed using non-parametric repeated measures analysis of variance (Friedman's test) and Mann-Whitney U-tests for intra- and inter-group comparisons respectively. RESULTS: Mean endurance time for the CFS group was lower (13.1+/-3.2 min, mean +/- SEM) than controls (18.6+/-2.6 min, P < 0.05) and CFS subjects reported higher ratings of perceived exertion. During the exercise period MEP amplitude and SP duration increased in both groups but to a lesser extent in CFS subjects. Interpolated twitch force amplitude also increased during exercise, being more pronounced in CFS subjects. CONCLUSION: The findings are in keeping with an exercise-related diminution in central motor drive in association with an increased perception of effort in CFS.     

Focal enhancement of motor cortex excitability during motor imagery: a transcranial magnetic stimulation study

OBJECTIVES: In order to learn more about the physiology of the motor cortex during motor imagery, we evaluated the changes in excitability of two different hand muscle representations in the primary motor cortex (M1) of both hemispheres during two imagery conditions. MATERIALS AND METHODS: We applied focal transcranial magnetic stimulation (TMS) over each M1, recording motor evoked potentials (MEPs) from the contralateral abductor pollicis brevis (APB) and first dorsal interosseus (FDI) muscles during rest, imagery of contralateral thumb abduction (C-APB), and imagery of ipsilateral thumb abduction (I-APB). We obtained measures of motor threshold (MT), MEP recruitment curve (MEP-rc) and F waves. RESULTS: Motor imagery compared with rest significantly decreased the MT and increased MEPs amplitude at stimulation intensities clearly above MT in condition C-APB, but not in condition I-APB. These effects were not significantly different between right and left hemisphere. MEPs simultaneously recorded from the FDI, which was not involved in the task, did not show facilitatory effects. There were no significant changes in F wave amplitude during motor imagery compared with rest. CONCLUSIONS: Imagery of unilateral simple movements is associated with increased excitability only of a highly specific representation in the contralateral M1 and does not differ between hemispheres.     

Kick with the finger: symbolic actions shape motor cortex excitability

A large body of research indicates that observing actions made by others is associated with corresponding motor facilitation of the observer's corticospinal system. However, it is still controversial whether this matching mechanism strictly reflects the kinematics of the observed action or its meaning. To test this issue, motor evoked potentials induced by single‐pulse transcranial magnetic stimulation were recorded from hand and leg muscles while participants observed a symbolic action carried out with the index finger, but classically performed with the leg (i.e., a soccer penalty kick). A control condition in which participants observed a similar (but not symbolic) hand movement was also included. Results showed that motor facilitation occurs both in the observer's hand (first dorsal interosseous) and leg (quadriceps femoris) muscles. The present study provides evidence that both the kinematics and the symbolic value of an observed action are able to modulate motor cortex excitability. The human motor system is thus not only involved in mirroring observed actions but is also finely tuned to their symbolic value.     

Central fatigue and motor cortical excitability during repeated shortening and lengthening actions

A decline in voluntary muscle activation and adaptations in motor cortical excitability contribute to the progressive decline in voluntary force during sustained isometric contractions. However, the neuronal control of muscle activation differs between isometric and dynamic contractions. This study was designed to investigate voluntary activation, motor cortex excitability, and intracortical inhibition during fatiguing concentric and eccentric actions. Eight subjects performed 143 torque motor-controlled, repeated shortening and lengthening actions of the elbow flexor muscles. Transcranial magnetic stimulation (TMS) was applied three times every 20 cycles. Magnetic evoked motor potentials (MEP), duration of the silent period (SP), and the torque increase due to TMS were analyzed. TMS resulted in a small torque increase in unfatigued actions. With repeated actions, voluntary torque dropped rapidly and the amplitude of the TMS-induced twitches increased, especially during repeated lengthening actions. MEP area of biceps brachii and brachioradialis muscles increased during repeated actions to a similar extent during lengthening and shortening fatigue. The duration of biceps and brachioradialis SP did not change with fatigue. Thus, voluntary activation became suboptimal during fatiguing dynamic actions and motor cortex excitability increased without any changes in intracortical inhibition. The apparent dissociation of voluntary activation and motor cortex excitability suggests that the central fatigue observed, especially during lengthening actions, did not result from changes in motor cortex excitability.     

Motor cortical excitability in patients with poststroke epilepsy

PURPOSE: To gain insight into the mechanisms underlying poststroke epilepsy (PSE), we evaluated motor cortical function in chronic stroke patients with (N = 18) and without (N = 18) PSE. METHODS: We measured resting motor threshold (RMT), motor evoked potential (MEP) amplitudes, cortical silent period (CSP), intracortical inhibition (ICI), influenced by GABAergic neurotransmission, and intracortical facilitation (ICF), influenced by glutamatergic activity, to transcranial magnetic stimulation. RESULTS: We found (1) larger MEP amplitudes and ICF, in the affected than unaffected hemispheres of patients in the PSE group but not in patients without epilepsy, and (2) comparably higher RMT and longer CSP in the absence of differences in ICI, H-reflexes or F-waves in the affected and unaffected hemispheres of both PSE and non-PSE patients. CONCLUSIONS: Enhanced cortical excitability in the affected hemisphere, possibly related to increased glutamatergic activity, could be one of the mechanisms contributing to the development of poststroke epilepsy.     

Relative increase in choline in the occipital cortex in chronic fatigue syndrome

OBJECTIVE: To test the hypothesis that chronic fatigue syndrome (CFS) is associated with altered cerebral metabolites in the frontal and occipital cortices. METHOD: Cerebral proton magnetic resonance spectroscopy (1H MRS) was carried out in eight CFS patients and eight age- and sex-matched healthy control subjects. Spectra were obtained from 20 x 20 x 20 mm3 voxels in the dominant motor and occipital cortices using a point-resolved spectroscopy pulse sequence. RESULTS: The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008). No other metabolite ratios were significantly different between the two groups in either the frontal or occipital cortex. In addition, there was a loss of the normal spatial variation of Cho in CFS. CONCLUSION: Our results suggest that there may be an abnormality of phospholipid metabolism in the brain in CFS.     

Pathogenesis and management of delayed orthostatic hypotention in patients with chronic fatigue syndrome

The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the parthogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustainedrelease formulation for 8 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p=0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.     

tDCS changes in motor excitability are specific to orientation of current flow

Background

Measurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the folded cortex results in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS.

Long‐term progressive motor skill training enhances corticospinal excitability for the ipsilateral hemisphere and motor performance of the untrained hand

It is well established that unilateral motor practice can lead to increased performance in the opposite non‐trained hand. Here, we test the hypothesis that progressively increasing task difficulty during long‐term skill training with the dominant right hand increase performance and corticomotor excitability of the left non‐trained hand. Subjects practiced a visuomotor tracking task engaging right digit V for 6 weeks with either progressively increasing task difficulty (PT) or no progression (NPT). Corticospinal excitability (CSE) was evaluated from the resting motor threshold (rMT) and recruitment curve parameters following application of transcranial magnetic stimulation (TMS) to the ipsilateral primary motor cortex (iM1) hotspot of the left abductor digiti minimi muscle (ADM). PT led to significant improvements in left‐hand motor performance immediately after 6 weeks of training (63 ± 18%, P < 0.001) and 8 days later (76 ± 14%, P < 0.001). In addition, PT led to better task performance compared to NPT (19 ± 15%, P = 0.024 and 27 ± 15%, P = 0.016). Following the initial training session, CSE increased across all subjects. After 6 weeks of training and 8 days later, only PT was accompanied by increased CSE demonstrated by a left and upwards shift in the recruitment curves, e.g. indicated by increased MEP_max (P = 0.012). Eight days after training similar effects were observed, but 14 months later motor performance and CSE were similar between groups. We suggest that progressively adjusting demands for timing and accuracy to individual proficiency promotes motor skill learning and drives the iM1‐CSE resulting in enhanced performance of the non‐trained hand. The results underline the importance of increasing task difficulty progressively and individually in skill learning and rehabilitation training.     

Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion

The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than 21.30 hours, reflective of delayed circadian rhythmicity. The patients took 5 mg of melatonin orally, 5 h before DLMO during 3 months. Their responses to the checklist individual strength (CIS), a reliable questionnaire measuring the severity of personally experienced fatigue, were assessed twice with a 6-week interval immediately before the treatment and once after 3 months treatment. In the pre-treatment period the fatigue sub-score improved significantly. After treatment, the total CIS score and the sub-scores for fatigue, concentration, motivation and activity improved significantly. The sub-score fatigue normalized in two of the 29 patients in the pre-treatment period and in eight of 27 patients during treatment. This change was significant. In the patients with DLMO later than 22.00 hours (n=21) the total CIS score and the sub-scores for fatigue, concentration and activity improved significantly more than in the patients (n=8) with DLMO earlier than 22.00 hours. Melatonin may be an effective treatment for patients with CFS and late DLMO, especially in those with DLMO later than 22.00 hours.     

Comparison of heart rate variability in patients with chronic fatigue syndrome and controls

Recent studies have reported a close association between chronic fatigue syndrome and neurally mediated hypotension. We hypothesized that this association may result from an abnormality in autonomic function among patients with chronic fatigue syndrome, which may be detectable using an analysis of heart rate variability. We prospectively studied 19 patients who fulfilled the Centers for Disease Control criteria for chronic fatigue syndrome and 11 controls. Each subject underwent a two-stage tilt-table test while wearing a Holter monitor. Heart rate variability was assessed in the supine baseline position and during upright tilt using frequency domain parameters. In the baseline supine position, high frequency (HF) power, low frequency (LF) power, and the ratio of low frequency power to high frequency power (LF/HF ratio) were similar. In both patient groups, upright tilt resulted in a similar decrease in HF power, increase in LF power, and increase in the LF/HF ratio. In conclusion, autonomic function, as assessed using an analysis of heart rate variability, does not differ in the baseline supine state, nor in response to upright tilt among patients with chronic fatigue syndrome and healthy controls.     

Motor cortical excitability and plasticity in patients with neurofibromatosis type 1

ObjectiveNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that is associated with cognitive disabilities. Based on studies involving animals, the hypothesized cause of these disabilities results from increased activity of inhibitory interneurons that decreases synaptic plasticity. We obtained transcranial magnetic stimulation (TMS)-based measures of cortical inhibition, excitability and plasticity in individuals with NF1.MethodsWe included 32 NF1 adults and 32 neurotypical controls. Cortical inhibition was measured with short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Excitability and plasticity were studied with intermittent theta burst stimulation (iTBS).ResultsThe SICI and CSP response did not differ between NF1 adults and controls. The response upon iTBS induction was significantly increased in controls (70%) and in NF1 adults (83%). This potentiation lasted longer in controls than in individuals with NF1. Overall, the TMS response was significantly lower in NF1 patients (F(1, 41) = 7.552, p = 0.009).ConclusionsIndividuals with NF1 may have reduced excitability and plasticity, as indicated by their lower TMS response and attenuation of the initial potentiated response upon iTBS induction. However, our findings did not provide evidence for increased inhibition in NF1 patients.SignificanceThese findings have potential utility as neurophysiological outcome measures for intervention studies to treat cognitive deficits associated with NF1.