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1.

Background

Rapidly changing excitability states in an oscillating neuronal network can explain response variability to external stimulation, but if repetitive stimulation of always the same high- or low-excitability state results in long-term plasticity of opposite direction has never been explored in vivo.

Objective/hypothesis

Different phases of the endogenous sensorimotor μ-rhythm represent different states of corticospinal excitability, and repetitive transcranial magnetic stimulation (rTMS) of always the same high- vs. low-excitability state results in long-term plasticity of different direction.

Methods

State-dependent electroencephalography-triggered transcranial magnetic stimulation (EEG-TMS) was applied to target the EEG negative vs. positive peak of the sensorimotor μ-rhythm in healthy subjects using a millisecond resolution real-time digital signal processing system. Corticospinal excitability was indexed by motor evoked potential amplitude in a hand muscle.

Results

EEG negative vs. positive peak of the endogenous sensorimotor μ-rhythm represent high- vs. low-excitability states of corticospinal neurons. More importantly, otherwise identical rTMS (200 triple-pulses at 100 Hz burst frequency and ~1 Hz repetition rate), triggered consistently at this high-excitability vs. low-excitability state, leads to long-term potentiation (LTP)-like vs. no change in corticospinal excitability.

Conclusions

Findings raise the intriguing possibility that real-time information of instantaneous brain state can be utilized to control efficacy of plasticity induction in humans.  相似文献   

2.

Background

When single pulse transcranial magnetic stimulation (TMS) is applied over the primary motor cortex (M1) with sufficient intensity, it evokes muscular contractions (motor-evoked potentials, MEPs) and muscle twitches (TMS-evoked movements). Participants may also report various hand sensations related to TMS, but the perception elicited by TMS and its relationship to MEPs and evoked movements has not been systematically studied.

Objective

The main aim of this work is to evaluate participants' kinesthetic and somatosensory hand perceptions elicited by single-pulse TMS over M1-hand area at different intensities of stimulation and their relation with MEPs and TMS-evoked movements.

Methods

We compared the number of MEPs (measured by electromyography), TMS-evoked movements (measured by an accelerometer) and participants' hand perception (measured by verbal report) elicited by TMS at different intensity of stimulation. This way, we estimated the amplitude of MEPs and the acceleration of TMS-evoked movements sufficient to trigger TMS evoked hand perceptions.

Results

We found that TMS-evoked hand perceptions are induced at 105% of the individual resting motor threshold, a value significantly different from the threshold inducing MEPs (about 100%) and TMS-evoked movements (about 110%). Our data indicate that only MEPs with an amplitude higher than 0.62 mV and TMS-evoked movements with acceleration higher than 0.42 m/s2 were associated with hand perceptions at threshold.

Conclusions

Our data reveal the main features of TMS-evoked hand perception and show that in addition to MEPs and TMS-evoked movements, this is a separate discernible response associated to single-pulse TMS over M1.  相似文献   

3.

Background

Transcranial magnetic stimulation (TMS) is a non-invasive method to stimulate localized brain regions. Despite widespread use in motor cortex, TMS is seldom performed in sensory areas due to variable, qualitative metrics.

Objective

Assess the reliability and validity of tracing phosphenes, and to investigate the stimulation parameters necessary to elicit decreased visual cortex excitability with paired-pulse TMS at short inter-stimulus intervals.

Methods

Across two sessions, single and paired-pulse recruitment curves were derived by having participants outline elicited phosphenes and calculating resulting average phosphene sizes.

Results

Phosphene size scaled with stimulus intensity, similar to motor cortex. Paired-pulse recruitment curves demonstrated inhibition at lower conditioning stimulus intensities than observed in motor cortex. Reliability was high across sessions.

Conclusions

TMS-induced phosphenes are a valid and reliable tool for measuring cortical excitability and inhibition in early visual areas. Our results also provide appropriate stimulation parameters for measuring short-latency intracortical inhibition in visual cortex.  相似文献   

4.

Background

Paired associative stimulation (PAS), with stimulus interval of 21.5 or 25?ms, using transcranial magnetic stimulation in the posterior-anterior (PA) current direction, produces a long-term-potentiation-like effect. Stimulation with PA directed current generates both early and late indirect (I)-waves while that in anterior-posterior (AP) current predominantly elicits late I-waves. Short interval intracortical inhibition (SICI) inhibits late I-waves but not early I-waves.

Objective

To investigate how cortical inhibition modulates the effects of PAS.

Methods

PAS at stimulus interval of 21.5?ms conditioned by SICI (SICI-PAS) was compared to PAS alone with both PA and AP directed currents.

Results

PAS with both current directions increased cortical excitability. SICI-PAS increased cortical excitability in the PA but not the AP current direction.

Conclusions

Both early and late I-waves circuits can mediate cortical PAS plasticity under different conditions. Plasticity induction with the late but not the early I-wave circuits is blocked by SICI.  相似文献   

5.

Background

Transcranial static magnetic field stimulation (tSMS) was recently added to the family of inhibitory non-invasive brain stimulation techniques. However, the application of tSMS for 10–20?min over the motor cortex (M1) induces only short-lasting effects that revert within few minutes.

Objective

We examined whether increasing the duration of tSMS to 30?min leads to long-lasting changes in cortical excitability, which is critical for translating tSMS toward clinical applications.

Methods

The study comprised 5 experiments in 45 healthy subjects. We assessed the impact of 30-min-tSMS over M1 on corticospinal excitability, as measured by the amplitude of motor evoked potentials (MEPs) and resting motor thresholds (RMTs) to single-pulse transcranial magnetic stimulation (TMS) (experiments 1–2). We then assessed the impact of 30-min-tSMS on intracortical excitability, as measured by short-interval intracortical facilitation (SICF) and short-interval intracortical inhibition (SICI) using paired-pulse TMS protocols (experiments 2–4). We finally assessed the impact of 10-min-tSMS on SICF and SICI (experiment 5).

Results

30-min-tSMS decreased MEP amplitude compared to sham for at least 30?min after the end of the stimulation. This long-lasting effect was associated with increased SICF and reduced SICI. 10-min-tSMS –previously reported to induce a short-lasting decrease in MEP amplitude– produced the opposite changes in intracortical excitability, decreasing SICF while increasing SICI.

Conclusions

These results suggest a dissociation of intracortical changes in the consolidation from short-lasting to long-lasting decrease of corticospinal excitability induced by tSMS. The long-lasting effects of 30-min-tSMS open the way to the translation of this simple, portable and low-cost technique toward clinical trials.  相似文献   

6.

Background

Responses to continuous theta burst stimulation (cTBS) applied to the human primary motor cortex are highly variable between individuals. However, little is known about how to improve the after-effects of cTBS by adjusting the protocol characteristics.

Objective

We examined whether current directions adopted in the measurement of cortical motor excitability indexed as motor evoked potentials (MEPs) affect the responses to cTBS. We also tested whether the stimulus intensity of cTBS influences the after-effects.

Methods

Thirty-one healthy volunteers participated. The after-effects of cTBS with the conventional intensity of 80% of individual active motor threshold (AMT) (cTBS80%) were tested by measuring MEP amplitudes induced by not only posterior-anterior (PA) but also anterior-posterior (AP) and biphasic (PA-AP) currents. We also investigated cTBS with 65% AMT (cTBS65%) and 100% AMT (cTBS100%) in subjects who showed depression of MEP amplitudes after cTBS80%, as well as cTBS65% in subjects in whom facilitation of MEPs was induced by cTBS80%.

Results

Current directions in MEP measurement had no influence on the cTBS responses. In subjects whose MEPs were depressed by cTBS80%, cTBS100% partly induced MEP facilitation, while cTBS65% abolished the after-effects. In subjects who showed MEP facilitation by cTBS80%, cTBS65% partly induced MEP depression.

Conclusions

Stimulus intensity of cTBS influenced the responses to cTBS, and lowering stimulus intensity induced the expected after-effects of cTBS in some subjects.  相似文献   

7.

Background

Alpha (8–14?Hz) oscillatory power is linked to cortical excitability and corresponding modulations of sensory evoked potentials and perceptual detection performance. In somatosensory cortex (S1), negative linear and inverted U-shape relationships exist, whereas its effect on the primary motor cortex (M1) is hardly known.

Objective

We used real-time EEG-triggered transcranial magnetic stimulation (TMS) of M1 to characterize the relationship between spontaneous sensorimotor mu-alpha power fluctuations at rest and corticospinal excitability.

Methods

In 16 subjects, mu-alpha power was continuously monitored over the left sensorimotor cortex, and each 10%-percentile bin of the individual mu-alpha power distribution was repeatedly targeted in pseudorandomized order by single-pulse TMS of left M1, measuring motor evoked potentials (MEP) in the contralateral hand.

Results

We found a weak positive relationship between mu-alpha power and MEP amplitude.

Conclusion

Sensorimotor mu-alpha power may reflect a net facilitation or disinhibition of M1, possibly resulting from mu-alpha based suppression of excitatory and inhibitory input from S1.  相似文献   

8.

Background

Pairing cortical and peripheral input during motor imagery (MI)-related sensorimotor desynchronization (ERD) modulates corticospinal excitability at the cortical representation (hotspot) of the imagined movement.

Objective

To determine the effects of this associative stimulation protocol on the cortical motor map beyond the hotspot.

Methods

In healthy subjects, peripheral stimulation through passive hand opening by a robotic orthosis and single-pulse transcranial magnetic stimulation to the respective cortical motor representation were applied in a brain-machine interface environment. State-dependency was investigated by concurrent, delayed or non-specific stimulation with respect to ERD in the beta-band (16–22?Hz) during MI of finger extension.

Results

Concurrent stimulation led to increased excitability of an extended motor map. Delayed and non-specific stimulation led to heterogeneous changes, i.e., opposite patterns of increased excitability in either the center or the periphery of the motor map.

Conclusion

These results could be instrumental in closed-loop, state-dependent stimulation in the context of neurorehabilitation.  相似文献   

9.

Background

Recent studies have shown that neurophysiological outcomes of transcranial direct current stimulation (TDCS) are influenced by current flow in brain regions between the electrodes, and in particular the orientation of current flow relative to the cortical surface.

Objective

We asked whether the directional effects of TDCS on physiological measures in the motor system would also be observed on motor behaviours.

Methods

We applied TDCS during the practice of a ballistic movement task to test whether it affected learning or the retention of learning 48?h later. TDCS electrodes were oriented perpendicular to the central sulcus and two current orientations were used (posterior-anterior, TDCSPA; and anterior-posterior, TDCSAP). Transcranial magnetic stimulation (TMS) was used to assess whether changes in corticospinal excitability reflected any behavioural changes.

Results

Directional TDCSAP impaired the retention of learning on the ballistic movement task compared to TDCSPA and a sham condition. Although TDCSPA had no effect on learning or retention, it blocked the typical increase in corticospinal excitability after a period of motor practice.

Conclusions

Our results extend on previous reports of TDCS producing directionally specific changes in neurophysiological outcomes by showing that current direction through a cortical target also impacts upon behavioural outcomes. In addition, changes in corticospinal excitability after a period of motor practice are not causally linked to behavioural learning.  相似文献   

10.

Background

Cortical dysfunctioning significantly contributes to the pathogenesis of motor symptoms in Parkinson's disease (PD).

Objective

We aimed at testing whether an acute levodopa administration has measurable and specific cortical effects possibly related to striatal dopaminergic deficit.

Methods

In thirteen PD patients, we measured the electroencephalographic responses to transcranial magnetic stimulation (TMS/EEG) of the supplementary motor area and superior parietal lobule (n?=?8) before and after an acute intake of levodopa. We also performed a single-photon emission computed tomography and [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane to identify the more affected and the less affected brain side in each patient, according to the dopaminergic innervation loss of the putamen. Cortical excitability changes before and after an acute intake of levodopa were computed and compared between the more and the less affected brain side at the single-patient as well as at the group level.

Results

We found that levodopa intake induces a significant increase (P?<?0.01) of cortical excitability nearby the supplementary motor area in the more affected brain side, greater (P?<?0.025) than in the less affected brain side. Notably, cortical excitability changes nearby the superior parietal lobule were not statistically significant.

Conclusions

These results strengthen the idea that dysfunction of specific cortico-subcortical circuits may contribute to pathophysiology of PD symptoms. Most important, they support the use of navigated TMS/EEG as a non-invasive tool to better understand the pathophysiology of PD.  相似文献   

11.

Background

the influence of pulse width, pulse waveform and current direction on transcranial magnetic stimulation (TMS) outcomes is of critical importance. However, their effects have only been investigated indirectly with motor-evoked potentials (MEP). By combining TMS and EEG it is possible to examine how these factors affect evoked activity from the cortex and compare that with the effects on MEP.

Objective

we used a new controllable TMS device (cTMS) to vary systematically pulse width, pulse waveform and current direction and explore their effects on global and local TMS-evoked EEG response.

Methods

In 19 healthy volunteers we measured (1) resting motor threshold (RMT) as an estimate of corticospinal excitability; (2) global mean field power (GMFP) as an estimate of global cortical excitability; and (3) local mean field power (LMFP) as an estimate of local cortical excitability.

Results

RMT was lower with monophasic posterior-to-anterior (PA) pulses that have a longer pulse width (p?<?0.001). After adjusting for the individual motor threshold of each pulse type we found that (a) GMFP was higher with monophasic pulses (p?<?0.001); (b) LMFP was higher with longer pulse width (p?=?0.015); (c) early TEP polarity was modulated depending on the current direction (p?=?0.01).

Conclusions

Despite normalizing stimulus intensity to RMT, we found that local and global responses to TMS vary depending on pulse parameters. Since EEG responses can vary independently of the MEP, titrating parameters of TMS in relation to MEP threshold is not a useful way of ensuring that a constant set of neurons is activated within a cortical area.  相似文献   

12.

Background

Transcranial magnetic stimulation (TMS) induced I-wave behavior can be demonstrated at neuronal population level using paired-pulses and by observing short-interval cortical facilitation (SICF). Advancements in stimulator technology have made it possible to apply biphasic paired-pulses to induce SICF.

Objective

Our aim was to characterize the SICF I-wave interaction by biphasic paired-pulses with the ultimate objective to enhance TMS effects via SICF in various TMS-applications.

Methods

We used biphasic paired-pulses in 15 volunteers to characterize corticospinal SICF using various 1.2–8.0ms inter-stimulus intervals, and measuring SICF input-output response.

Results

SICF interaction with the first I-wave (I1) was observed in the output responses (motor evoked potentials; MEPs) in all subjects. Most subjects (≥80%) also exhibited later SICF I-wave interaction. SICF at I1 was present at all applied intensities below 140% of resting motor threshold. At I2, we observed SICF only with intensities just above motor threshold.

Conclusions

Biphasic paired-pulses can reliably induce SICF shown by the facilitatory I-wave interaction, and could therefore be applied with repetitive bursts to enhance responsiveness to TMS.  相似文献   

13.

Background

Biphasic pulses produced by most commercially available TMS machines have a cosine waveform, which makes it difficult to study the interaction between the two phases of stimulation.

Objective

We used a controllable pulse TMS (cTMS) device delivering quasi-rectangular pulse outputs to investigate whether monophasic are more effective than biphasic pulses.

Methods

Temporally symmetric (“biphasic”) or highly asymmetric (“monophasic”) charge-balanced biphasic stimuli were used to target the hand area of motor cortex in the anterior-posterior (AP) or posterior-anterior (PA) initial current direction.

Results

We observed the lowest motor thresholds and shortest motor evoked potential (MEP) latencies with initial PA pulses, and highest thresholds and longest latencies with AP pulses. Increasing pulse symmetry tended to increase threshold with a PA direction whereas it lowered thresholds and shortened latencies with an AP direction. Furthermore, it steepened the MEP input-output curve with both directions.

Conclusions

“Biphasic” TMS pulses can be viewed as two monophasic pulses of opposite directions, each stimulating a different set of interneurons with different thresholds (PA?<?AP). At threshold, the reverse phase of an initially PA pulse increases threshold compared with “monophasic” stimulation. At higher intensities, the reverse phase begins to activate AP-sensitive neurones and increase the effectiveness of stimulation above that of a “monophasic” PA pulse. “Biphasic” stimulation with initially AP pulses is dominated at threshold by activation produced by the lower threshold reverse (PA) phase.

Significance

The effects of biphasic stimulation are best understood as the summed output of two independent sets of directionally selective neural populations.  相似文献   

14.

Background

Facilitating neural activity using non-invasive brain stimulation may improve extinction-based treatments for posttraumatic stress disorder (PTSD).

Objective/hypothesis

Here, we examined the feasibility of simultaneous transcranial direct current stimulation (tDCS) application during virtual reality (VR) to reduce psychophysiological arousal and symptoms in Veterans with PTSD.

Methods

Twelve Veterans with PTSD received six combat-related VR exposure sessions during sham-controlled tDCS targeting ventromedial prefrontal cortex. Primary outcome measures were changes in skin conductance-based arousal and self-reported PTSD symptom severity.

Results

tDCS + VR components were combined without technical difficulty. We observed a significant interaction between reduction in arousal across sessions and tDCS group (p = .03), indicating that the decrease in physiological arousal was greater in the tDCS + VR versus sham group. We additionally observed a clinically meaningful reduction in PTSD symptom severity.

Conclusions

This study demonstrates feasibility of applying tDCS during VR. Preliminary data suggest a reduction in psychophysiological arousal and PTSD symptomatology, supporting future studies.  相似文献   

15.

Background

Alzheimer's disease (AD) is characterized by a primary impairment of long-term declarative memory caused by deposition of misfolded protein aggregates. Experimental studies showed that AD neuropathological alterations impair synaptic plasticity and memory performance. Transcranial Magnetic Stimulation protocols have been recently introduced to investigate altered mechanisms of cortical plasticity in AD patients.

Aim

To investigate relationship between Long-Term Potentiation (LTP)-like cortical plasticity and patients’ neuropsychological performance.

Methods

We applied intermittent theta burst stimulation and extensive neuropshycological battery in 75 newly diagnosed AD patients.

Results

We found that LTP-like cortical plasticity impairment is selectively associated to a less efficient verbal memory (r?=?0.45; p?=?0.002), but not to other cognitive functions, independently from biomarkers and other demographic and clinical factors.

Conclusion

These findings suggest that LTP-like cortical plasticity may represent a neurophysiological surrogate of memory in AD patients by evaluating the weight of pathological changes responsible for cognitive dysfunction.  相似文献   

16.

Background

The ability to stop a suboptimal response is integral to decision making and is commonly impaired across psychiatric disorders. Cortical paired associative stimulation (cPAS) is a form of transcranial magnetic stimulation in which paired pulses can induce plasticity at cortical synapses. Here we used cPAS protocols to target cortico-cortical and cortico-subcortical networks by using different intervals between the paired pulses in an attempt to modify response inhibition.

Methods

A total of 25 healthy volunteers underwent four cPAS sessions in random order 1 week apart: right inferior frontal cortex (IFC) stimulation preceding right presupplementary motor area (pre-SMA) stimulation by 10 or 4 ms and pre-SMA stimulation preceding IFC stimulation by 10 or 4 ms. Subjects were tested on the stop signal task along with the delay discounting task as control at baseline (randomized across sessions and cPAS protocol) and after each cPAS session.

Results

The stop signal reaction time showed a main effect of cPAS condition when controlling for age (F3,57 = 4.05, p = .01). Younger subjects had greater impairments in response inhibition when the pre-SMA pulse preceded the IFC pulse by 10 ms. In older individuals, response inhibition improved when the IFC pulse preceded the pre-SMA pulse by 4 ms. There were no effects on delay discounting.

Conclusions

cPAS modified response inhibition through age-dependent long-term potentiation and depression-like plasticity mechanisms via putative cortico-cortical and cortico-subcortical networks. We show for the first time the capacity for cPAS to modify a cognitive process highly relevant to psychiatric disorders.  相似文献   

17.

Background

Temporal lobe epilepsy is most prevalent among focal epilepsies, and nearly one-third of patients are refractory to pharmacological intervention. Persistent cognitive and neurobehavioral comorbidities also occur due to the recurrent nature of seizures and medication-related side effects.

Hypothesis

Electrical neuromodulation is an effective strategy to reduce seizures both in animal models and clinically, but its efficacy to modulate cognition remains unclear. We hypothesized that theta frequency stimulation of the medial septum would increase septohippocampal oscillations, increase seizure threshold, and improve spatial learning in a rat model of pilocarpine-induced epilepsy.

Methods

Sham and pilocarpine rats were implanted with electrodes in the medial septum, hippocampus and prefrontal cortex. EEG was assessed days prior to and following stimulation. Sham and pilocarpine-treated rats received either no stimulation, continuous (throughout each behavior), or pre-task (one minute prior to each behavior) 7.7?Hz septal stimulation during the Barnes maze spatial navigation test and also during assessment of flurothyl-induced seizures.

Results

Both continuous and pre-task stimulation prevented epilepsy-associated reductions in theta oscillations over time. Additionally, both stimulation paradigms significantly improved spatial navigation in the Barnes maze, reducing latency and improving search strategy. Moreover, stimulation led to significant increases in seizure threshold in pilocarpine-treated rats. There was no evidence of cognitive enhancement or increased seizure threshold in stimulated sham rats.

Conclusion

These findings have profound implications as theta stimulation of the septum represents a single frequency and target that has the potential to both improve cognition and reduce seizures for patients with refractory epilepsy.  相似文献   

18.
19.

Background

Brain stimulation interventions are increasingly used to reduce craving and consumption in individuals with drug addiction or excessive eating behavior. However, the efficacy of these novel treatments and whether effect sizes are affected by the length of the intervention has not been comprehensively evaluated.

Objective

A meta-analytical approach was employed to evaluate the effectiveness of non-invasive excitatory brain stimulation [transcranial Direct Current Stimulation (tDCS) and high-frequency repetitive Transcranial Magnetic Stimulation (rTMS)] targeted at dorsolateral prefrontal cortex (dlPFC) for reducing craving and consumption levels in drug and eating addiction, including both single- and multi-session protocols.

Methods

After a comprehensive literature search, 48 peer-reviewed studies (1095 participants in total) were included in the current meta-analysis. We computed Hedge's g as a conservative measure for evaluating effect sizes.

Results

Random effects analyses revealed a small effect of neuromodulation interventions on craving and a medium effect on consumption, favoring active over sham stimulation. These effects did not differ across the different populations investigated (alcohol, nicotine, illicit drugs, eating addictions) or by the used technique (rTMS/tDCS, left/right hemisphere). Multi-session protocols showed a larger effect size for reducing craving and consumption than single-session protocols, with a positive linear association between the number of sessions or administered pulses and craving reduction, indicating a dose-response effect.

Conclusions

Our results provide compelling evidence that novel non-invasive brain stimulation targeted at dlPFC reduces craving and consumption levels (providing the first meta-analytical evidence for the latter effect in drug addiction), with larger effects in multi-session as compared to single-session interventions.  相似文献   

20.

Background

Repetitive convergent inputs to a single post-synaptic neuron can induce long-term potentiation (LTP) or depression (LTD) of synaptic activity in a spike timing-dependent manner.

Objective

Here we set a protocol of visual paired associative stimulation (vPAS) of the primary visual cortex (V1) in humans to induce persistent changes in the excitatory properties of V1 with a spike timing rule.

Methods

We provided convergent inputs to V1 by coupling transcranial magnetic stimulation (TMS) pulses of the occipital cortex with peripheral visual inputs, at four interstimulus intervals of ?50/-25/+25/+50 ms relative to the visual evoked potential (VEP) P1 latency. We analysed VEP amplitude and delayed habituation before and up to 10 min after each vPAS protocol.

Results

VEP amplitude was reduced after vPAS+25. Delayed VEP habituation was increased after vPAS-25 while it was reduced after vPAS+25.

Conclusions

We provide evidence that associative bidirectional synaptic plasticity is a feature not only of the sensorimotor but also of the human visual system.  相似文献   

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