Changes in somatosensory evoked responses by repetition of the median nerve stimulation

OBJECTIVE: We investigate the synaptic factor for the recovery function of evoked responses using a repetitive stimulation technique. METHODS: Somatosensory evoked cortical magnetic field (SEF) was recorded following stimulation of the median nerve using single to 6-train stimulation in 8 healthy subjects. The SEF responses after each stimulus in the train stimulation were extracted by subtraction of the waveforms. RESULTS: An attenuation of the SEF components was recognized after the second of the stimuli, but there was no significant attenuation with the third or later stimulations. The root mean square (RMS) of the 1M (peak latency at 20 ms after stimulation) and 4M (70 ms) components were smaller than that of the single stimulation during the train stimulation, while the 2M (30 ms) and 3M (45 ms) components were not attenuated, but the 3M was facilitated at the fourth to sixth stimulation. CONCLUSION: The synaptic factor was not responsible for the attenuation of the SEF components during repetitive stimulation in healthy subjects. The SEF change disclosed a functional difference among the SEF components during the train stimulation, especially among the later components.     

The timing of galvanic vestibular stimulation affects responses to platform translation

We compared the effects of galvanic vestibular stimulation applied at 0, 0.5, 1.5 and 2.5 s prior to a backward platform translation on postural responses. The effect of the galvanic stimulation was largest on the final equilibrium position of the center of pressure (CoP). The largest effects occurred for the 0.5 and 0-s pre-period, when the dynamic CoP pressure changes in response to both the galvanic stimulus and the platform translation coincided. The shift in the final equilibrium position was also larger than the sum of the shifts for the galvanic stimulus and the platform translation alone for the 0.5 and 0-s pre-periods. The initial rate of change of the CoP response to the platform translation was not significantly affected in any condition. Changes in the peak CoP position could be accounted for by local interaction of CoP velocity changes induced by the galvanic and translation responses alone, but the changes in final equilibrium position could only be accounted for by a change in global body orientation. These findings suggest that the contribution of vestibulospinal information is greatest during the dynamic phase of the postural response, and that the vestibular system contributes most to the later components of the postural response, particularly to the final equilibrium position. These findings suggest that a nonlinear interaction between the vestibular signal induced by the galvanic current and the sensory stimuli produced by the platform translation occurs when the two stimuli are presented within 1 s, during the dynamic phase of the postural response to the galvanic stimulus. When presented at greater separations in time, the stimuli appear to be treated as independent events, such that no interaction occurs.     

Intermittent theta burst stimulation over primary motor cortex enhances movement-related beta synchronisation

Objective

The objective of this study is to investigate how transcranial magnetic intermittent theta burst stimulation (iTBS) with a prolonged protocol affects human cortical excitability and movement-related oscillations.

Methods

Using motor-evoked potentials (MEPs) and movement-related magnetoencephalography (MEG), we assessed the changes of corticospinal excitability and cortical oscillations after iTBS with double the conventional stimulation time (1200 pulses, iTBS1200) over the primary motor cortex (M1) in 10 healthy subjects. Continuous TBS (cTBS1200) and sham stimulation served as controls.

Results

iTBS1200 facilitated MEPs evoked from the conditioned M1, while inhibiting MEPs from the contralateral M1 for 30 min. By contrast, cTBS1200 inhibited MEPs from the conditioned M1. Importantly, empirical mode decomposition-based MEG analysis showed that the amplitude of post-movement beta synchronisation (16–26 Hz) was significantly increased by iTBS1200 at the conditioned M1, but was suppressed at the nonconditioned M1. Alpha (8–13 Hz) and low gamma-ranged (35–45 Hz) rhythms were not notably affected. Movement kinetics remained consistent throughout.

Conclusions

TBS1200 modulated corticospinal excitability in parallel with the direction of conventional paradigms with modestly prolonged efficacy. Moreover, iTBS1200 increased post-movement beta synchronisation of the stimulated M1, and decreased that of the contralateral M1, probably through interhemispheric interaction.

Significance

Our results provide insight into the underlying mechanism of TBS and reinforce the connection between movement-related beta synchronisation and corticospinal output.     

The effect of electrical stimulation on impairment of the painful post-stroke shoulder

Background: Transcutaneous electrical nerve stimulation (TENS) and transcutaneous neuromuscular electrical stimulation (t-NMES) are commonly used therapies in the treatment of chronic hemiplegic shoulder pain. These treatments are often utilized during physical or occupational therapy sessions, yet research into the acute analgesic effects of TENS and t-NMES on hemiplegic shoulder pain and use during therapy is limited.

Objective: To compare the acute effects of transcutaneous electrical nerve stimulation (TENS), transcutaneous neuromuscular electrical stimulation (t-NMES), and no stimulation on pain-free passive range of motion of the shoulder in subjects with hemiplegic shoulder pain.

Methods: Prospective cohort study of 10 subjects randomly treated with t-NMES, TENS, and one non-stimulation experimental condition. Pain-free passive external rotation and abduction range of motion of the affected shoulder were measured during stimulation.

Results: There was not a significant within-subject difference in pain-free range of motion for external rotation or abduction. Subject to subject differences explained the majority of the variability in pain-free range of motion.

Conclusion: This pilot study is the first to measure pain-free passive range of motion during electrical stimulation. Our findings demonstrate the lack of an acute effect of TENS and t-NMES on pain reduction.     

A MEG study of sleep

A 64-channel, whole cortex magnetoencephalographic system was employed to obtain sleep data from three healthy subjects. Based upon visual inspection of the signals and the corresponding power spectra, we were able to discern a number of features characterizing the evolution of sleep. These included: (1) the transition from records dominated by the alpha rhythm to records in which alpha is attenuated and slower waves increase; (2) the appearance of sleep spindles, particularly in the parietal channels; and, perhaps most interesting, (3) a slow wave phase whose multichannel spectral signature is a broad rounded maximum in the frequency region around 0.5 Hz. Topographical features of the sleep record were also studied. In two of our subjects, rough lateral symmetry was apparent. As their sleep deepened, the distribution of signal power over the head changed such that the maximum moved in the forward and lateral directions, with parietal and temporal signals strengthening relative to the occipital. The records of the third subject showed a tendency toward right dominance, while topographic changes with sleep depth were minimal. Only one of the subjects was able to sustain the deep, slow-wave stage. Here, characteristic multi-detector outbursts appeared, lasting between 150 and 500 ms. During these intervals, widespread topographic patterns were sustained over the head (often with striking dipolar or quadrupolar forms), while crude source modeling yielded two persisting dipoles, laterally paired. Thus, these outbursts seem to represent large-scale, quasi-static configurations of brain activity perhaps related to the K-complexes, which occur earlier in sleep. Finally, we compare our results with those of previous investigators, including work on human electroencephalographic data and research reported by Steriade et al. from animal studies.     

Reducing aggressive responses to social exclusion using transcranial direct current stimulation

A vast body of research showed that social exclusion can trigger aggression. However, the neural mechanisms involved in regulating aggressive responses to social exclusion are still largely unknown. Transcranial direct current stimulation (tDCS) modulates the excitability of a target region. Building on studies suggesting that activity in the right ventrolateral pre-frontal cortex (rVLPFC) might aid the regulation or inhibition of social exclusion-related distress, we hypothesized that non-invasive brain polarization through tDCS over the rVLPFC would reduce behavioral aggression following social exclusion. Participants were socially excluded or included while they received tDCS or sham stimulation to the rVLPFC. Next, they received an opportunity to aggress. Excluded participants demonstrated cognitive awareness of their inclusionary status, yet tDCS (but not sham stimulation) reduced their behavioral aggression. Excluded participants who received tDCS stimulation were no more aggressive than included participants. tDCS stimulation did not influence socially included participants’ aggression. Our findings provide the first causal test for the role of rVLPFC in modulating aggressive responses to social exclusion. Our findings suggest that modulating activity in a brain area (i.e. the rVLPFC) implicated in self-control and emotion regulation can break the link between social exclusion and aggression.     

Characterizing and predicting cortical evoked responses to direct electrical stimulation of the human brain

BackgroundDirect electrical stimulation of the human brain has been used to successfully treat several neurological disorders, but the precise effects of stimulation on neural activity are poorly understood. Characterizing the neural response to stimulation, however, could allow clinicians and researchers to more accurately predict neural responses, which could in turn lead to more effective stimulation for treatment and to fundamental knowledge regarding neural function.ObjectiveHere we use a linear systems approach in order to characterize the response to electrical stimulation across cortical locations and then to predict the responses to novel inputs.MethodsWe use intracranial electrodes to directly stimulate the human brain with single pulses of stimulation using amplitudes drawn from a random distribution. Based on the evoked responses, we generate a simple model capturing the characteristic response to stimulation at each cortical site.ResultsWe find that the variable dynamics of the evoked response across cortical locations can be captured using the same simple architecture, a linear time-invariant system that operates separately on positive and negative input pulses of stimulation. We demonstrate that characterizing the response to stimulation using this simple and tractable model of evoked responses enables us to predict the responses to subsequent stimulation with single pulses with novel amplitudes, and the compound response to stimulation with multiple pulses.ConclusionOur data suggest that characterizing the response to stimulation in an approximately linear manner can provide a powerful and principled approach for predicting the response to direct electrical stimulation.     

Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters

BackgroundElectrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses.ObjectiveTo better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated.MethodsWe measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites).ResultsIncreasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation.ConclusionThese results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.     

Different short-term modulation of cortical motor output to distal and proximal upper-limb muscles during painful sensory nerve stimulation

The pattern of upper-limb muscle activation following painful stimulation has not been clarified in detail. We investigated the short-term inhibitory and excitatory effects of painful electrical digital stimulation on the motoneuron pools of distal and proximal upper-limb muscles. Transcranial magnetic stimulation (TMS) was used as test stimulus, and painful digital nerve stimulation as conditioning stimulus for motor evoked potential (MEP) recordings over the abductor digiti minimi (ADM), abductor pollicis brevis (APB), biceps brachii (BB), and deltoid muscles. Inhibition of the conditioned MEP response was most prominent in the distal muscles, whereas BB and deltoid muscles were only weakly inhibited. The mean MEP response over APB decreased with painful cutaneous stimuli, showing maximum inhibition (by 82%) at interstimulus intervals (ISIs) of 50 ms. Inhibition in the ADM was maximal (49%) but less pronounced at an ISI of 40 ms. The BB and deltoid muscles showed inhibition by 25% and 29%, respectively. Significant facilitation was present in BB and deltoid muscles by 43% and 41% at an ISI of 100 ms, but not in the smaller hand muscles. The observed pattern of upper-limb muscle activation corresponds to the protective withdrawal reflex and the neuronal basis of the observed short-term modulation of motor activity is compatible with a spinal or brainstem pathway.     

Steady-state auditory evoked fields reflect long-term effects of repetitive transcranial magnetic stimulation in tinnitus

ObjectivesEvidence of plastic changes in tinnitus has been demonstrated in functional brain imaging. Although repetitive transcranial magnetic stimulation (rTMS) has been shown to decrease steady-state auditory evoked fields (SSAEFs) in tinnitus, the long-term consequence remained unknown. In addition, association between plastic changes as reflected by hemispheric asymmetry and tinnitus handicap inventory (THI) before and after rTMS have not been addressed.MethodsTwelve tinnitus patients received rTMS and 12 received sham stimulation. Another 12 healthy participants served as the normal hearing controls. Patients responded to the THI before the 1st session and at one month after the final session of rTMS/sham stimulation. Changes in brain activity were assessed by measuring SSAEFs.ResultsSSAEFs remained decreased one month after rTMS compared to before treatment, along with a significant reduction in THI score. There was no significant effect between the index of hemispheric asymmetry and THI score.ConclusionsThe current study objectively demonstrated the long-term effects of rTMS on tinnitus using SSAEFs. A longitudinal study to develop an index using SSAEFs to assess the subjective severity of tinnitus is warranted.SignificanceThis study suggests the possible use of SSAEFs to assess the long-term effects of rTMS on tinnitus.     

Maturation of somatosensory cortical processing from birth to adulthood revealed by magnetoencephalography

ObjectiveTo evaluate the maturation of tactile processing by recording somatosensory evoked magnetic fields (SEFs) from healthy human subjects.MethodsSEFs to tactile stimulation of the left index finger were measured from the contralateral somatosensory cortex with magnetoencephalography (MEG) in five age groups: newborns, 6- and 12–18-month-olds, 1.6–6-year-olds, and adults. The waveforms of the measured signals and equivalent current dipoles (ECDs) were analyzed in awake and sleep states in order to separate the effects of age and vigilance state on SEFs.ResultsThere was an orderly, systematic change in the measured and ECD source waveforms of the initial cortical responses with age. The broad U-shaped response in newborns (M60) shifted to a W-shaped response with emergence of a notch by 6 months of age. The adult-type response with M30 and M50 components was present by 2 years. The ECDs of M60 and M30 were oriented anteriorly and that of M50 posteriorly. These maturational changes were independent of vigilance state.ConclusionsThe most significant maturation of short latency cortical responses to tactile stimulation takes place during the first 2 years of life.SignificanceThe maturational changes of somatosensory processing can noninvasively be evaluated with MEG already in infancy.     

Anticipatory cortical responses during the expectancy of a predictable painful stimulation. A high-resolution electroencephalography study

In the present study, high‐resolution electroencephalography techniques modelled the spatiotemporal pattern of human anticipatory cortical responses preceding expected galvanic painful stimuli (non‐painful stimuli as a control). Do these responses reflect the activation of associative other than somatosensory systems? Anticipatory processes were probed by alpha oscillations (6–12 Hz) for the evaluation of thalamocortical channels and by negative event‐related potentials for the evaluation of cortical excitability. Compared with the control condition, a progressive reduction of the alpha power was recognized over the primary somatosensory cortex from 2 s before the painful stimulation. In contrast, the anticipatory event‐related potentials were negligible during the expectancy period. The results on the alpha power suggest that the expectancy of the painful stimulation specifically facilitated the somatosensory thalamocortical channel. Remarkably, the associative frontal‐parietal areas were not involved, possibly due to the predictable and repetitive features of the painful stimulus. The present results also suggest that negative event‐related potentials are modest preceding warned stimuli (even if painful) with a simple information content.     

The pain suppressive effect of vibratory stimulation and transcutaneous electrical nerve stimulation (TENS) as compared to aspirin

The pain reducing effect of vibratory stimulation and transcutaneous electrical nerve stimulation (TENS) as compared to aspirin and placebo was studied in 60 patients suffering myofascial or musculoskeletal pain. Vibratory stimulation at 20 Hz, 100 Hz and 200 Hz and two modes of TENS were used for peripheral stimulation. In 48 patients these modes of stimulation produced pain reduction. Out of these patients 29 rated vibratory stimulation or TENS as more effective than aspirin while 9 patients rated aspirin as more effective. Ten patients rated the pain suppressive effect of vibratory stimulation andTENS as being equal to that of aspirin. Six of the patients who experienced pain reduction with peripheral stimulation reported an effect only for one particular type of peripheral stimulation. The present results provide evidence that vibratory stimulation and TENS are as efficient and in some patients more efficient pain suppressive measures as compared to aspirin. It is suggested on the basis of these findings that vibratory stimulation and TENS merit consideration in the choice of treatment of myofascial or musculoskeletal pain.     

脑磁图在运动区脑膜瘤手术中的应用研究

目的 探讨脑磁图（MEG）在手术治疗皮质运动区脑膜瘤中的应用价值。方法 选择21例脑皮质运动区或其附近脑膜瘤患者，常规行影像学和MEG检查，配合神经导航系统行肿瘤显微手术切除。结果 肿瘤切除按Simpson分级，Ⅰ级10例，Ⅱ9例，Ⅳ级2例。术后神经功能障碍完全恢复正常17例，明显好转3例，加重1例。结论 MEG是无创性功能区定位、确定病变与皮质运动区位置关系的重要方法，对皮质功能区病变的手术方案制定和功能区脑组织的保护具有重要的指导价值。     

Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex

IntroductionThere is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects.ObjectiveThe aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity.MethodsAn 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated.ResultstbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence.ConclusionThe findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.     

Effects of interstimulus interval on cortical responses to painful laser stimulation.

Short laser pulses applied to the skin are used increasingly in both clinical and basic assessment of nociceptive brain mechanisms. The authors aimed to characterize further the cortical responses to noxious laser stimuli and to define the interstimulus interval (ISI) for the optimum signal-to-noise ratio during a fixed measurement time. Three hundred six-channel whole-scalp magnetoencephalographic (MEG) and midline EEG signals were recorded from nine healthy adults during painful thulium laser stimulation. The stimuli were delivered on the dorsum of the left hand at ISIs of 0.5, 1, 2, 4, 8, and 16 seconds. The MEG responses peaked at 160 to 195 msec around the contralateral primary somatosensory (SI) cortex, at 150 to 190 msec in the contralateral secondary somatosensory (SII) cortex, and at 160 to 205 msec in the ipsilateral SII cortex. The simultaneously measured electrical vertex potentials peaked at 190 to 230 msec and 310 to 330 msec (N200-P300). All these responses showed rather similar refractory times: The amplitudes increased strongly from 0.5 to 4-second ISIs and thereafter saturated at ISIs of 8 to 16 seconds. On the basis of the time constants of the recovery cycles, the optimum ISI for obtaining the best signal-to-noise ratio for laser-evoked MEG and EEG responses during a fixed measurement interval is 4 to 5 seconds.     

Intense and sustained pain reduces cortical responses to auditory stimuli: Implications for the interpretation of the effects of heterotopic noxious conditioning stimulation in humans

Phasic pain stimuli are inhibited when they are applied concomitantly with a conditioning tonic stimulus at another body location (heterotopic noxious conditioning stimulation, HNCS). While the effects of HNCS are thought to rely on a spino‐bulbo‐spinal mechanism in animals (termed diffuse noxious inhibitory controls, DNIC), the underlying neurophysiology in humans may involve other pathways. In this study, we investigated the role of concomitant supraspinal mechanisms during HNCS by presenting auditory stimuli during a conditioning tonic painful stimulus (the cold pressor test, CPT). Considering that auditory stimuli are not conveyed through the spinal cord, any changes in brain responses to auditory stimuli during HNCS can be ascribed entirely to supraspinal mechanisms. Electroencephalography (EEG) was recorded during HNCS, and auditory stimuli were administered in three blocks, before, during and after HNCS. Nociceptive withdrawal reflexes (NWRs) were recorded at the same time points to investigate spinal processing. Our results showed that AEPs were significantly reduced during HNCS. Moreover, the amplitude of the NWR was significantly diminished during HNCS in most participants. Given that spinal and supraspinal mechanisms operate concomitantly during HNCS, the possibility of isolating their individual contributions in humans is questionable. We conclude that the net effects of HCNS are not independent from attentional/cognitive influences.     

Voluntary contraction and responses to submaximal cervical nerve root stimulation

Voluntary contraction of hand muscles increases compound muscle action potential (CMAP) amplitudes evoked by submaximal electrical percutaneous cervical stimulation (EPCS). This has been reported to be due to an intraspinal, presynaptic mechanism. We studied the effects of voluntary contraction on hypothenar CMAP amplitudes in 5 volunteers following electrical peripheral nerve stimulation at the wrist, EPCS, magnetic stimulation at the neck and the effects of a conditioning subthreshold cortical magnetic stimulus on CMAPs evoked by EPCS at rest. CMAP amplitudes increased with voluntary contraction of the target muscle, regardless of type or location of stimulus (P < 0.001). No increase in CMAP amplitude occurred when a conditioning transcranial stimulus was employed with EPCS (P = 0.35). Our findings indicate a peripheral rather than central mechanism underlies this effect of voluntary contraction. It is probably related to the recruitment order of motor axons, comparing voluntary activation with electrical or magnetic stimulation. © 1994 John Wiley & Sons, Inc.     

Decremental motor responses to repetitive nerve stimulation in ALS

Repetitive nerve stimulation (RNS) of the trapezius muscle at slow rates was performed on 192 patients with amyotrophic lateral sclerosis (ALS). Fifty-six patients (29%) showed classical neuromuscular decrement of 10–43% (mean 16.8%) while 44 patients (23%) had a borderline decrement of 5–9%. The trapezius was significantly more sensitive in revealing the defect than the distal hypothenar muscles. In 30 patients followed serially, the decremental response remained constant or increased with time. However, 25% of patients continued to show no decrement in spite of progression of disease. No statistical correlation was found between decrement and clinical severity, disease staging, or disease progression. The finding that at least 50% of ALS patients show some degree of decrement on RNS of the trapezius muscle suggests that functional alterations of the neuromuscular junction accompany this disease. © 1994 John Wiley & Sons, Inc.