Cortical Excitability In Healthy Subjects Research Articles

The effect of stimulation frequency on transcranial evoked potentials.

IntroductionTranscranial magnetic stimulation-evoked electroencephalography potentials (TEPs) have been used to study motor cortical excitability in healthy subjects and several neurological conditions. However, optimal recording parameters for TEPs are still debated. Stimulation rates could affect TEP amplitude due to plasticity effects, thus confounding the assessment of cortical excitability. We tested whether short interpulse intervals (IPIs) affect TEP amplitude.MethodsWe investigated possible changes in TEP amplitude and global mean field amplitude (GMFA) obtained with stimulation of the primary motor cortex at IPIs of 1.1–1.4 s in a group of healthy subjects.ResultsWe found no differences in TEP amplitude or GMFA between the first, second and last third of trials.DiscussionShort IPIs do not affect TEP size and can be used without the risk of confounding effects due to short-term plasticity.

Changes in motor cortical excitability in schizophrenia following transcranial direct current stimulation

Schizophrenia is a disorder associated with cortical inhibition deficits. Transcranial direct current stimulation (tDCS) induces changes in cortical excitability in healthy subjects and individuals with neuropsychiatric disorders depending on the stimulation parameters. Our aim was to investigate whether a previously published tDCS protocol associated with symptomatic improvement in schizophrenia would induce changes in motor cortical excitability, assessed by transcranial magnetic stimulation paradigms, i.e., short-interval intracortical inhibition (SICI) and intra-cortical facilitation (ICF). We assessed cortical excitability measurements in 48 subjects with schizophrenia before and after a single session of active tDCS (20 min, 2 mA, anode over left dorsolateral prefrontal cortex, cathode over left temporoparietal cortex) or sham. Those who received active tDCS had a significant increase of SICI in the left motor cortex compared to those who received sham stimulation (Cohen's d = 0.54, p = .019). No changes were observed for ICF. In addition, lower SICI was associated with higher age (β = −0.448, p < .01). Increase in intracortical inhibition may indicate a mechanism of action of tDCS in this population. Future studies should investigate whether this finding is a biomarker of treatment response for schizophrenia.

Simultaneous stimulation using rTMS and tDCS produces the most effective modulation of motor cortical excitability in healthy subjects: A pilot study

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) can be used to modulate the excitability of the cortex, but instances of the two technologies being used to stimulate two positions of the human brain simultaneously are rare. As an initial investigation into the efficacy, feasibility and safety of such an approach, we compared the effects of simultaneously applying rTMS and cathodal tDCS with that of four other stimulation regimens (cathodal tDCS alone, rTMS alone, rTMS after cathodal tDCS, and sham stimulation) on a single population of subjects consisting of five healthy volunteers. Additionally, we also conducted SimNibs simulations of the electric field patterns that combined rTMS and cathodal tDCS would produce in cerebral cortices of the subjects.Compared with baseline levels, motor evoked potentials (MEPs; used here as a surrogate measure of cortical excitability) were significantly increased with all four ‘real’ stimulation methods (p < 0.05). Compared with sham measurements, significant increases in MEPs were also observed with rTMS alone (p = 0.0021), rTMS after tDCS (p = 0.0004), simultaneous rTMS and tDCS (p < 0.0001), but not with tDCS alone (p = 0.4182). We also determined that simultaneous rTMS and cathodal tDCS induced a significant increase in MEPs compared with the baseline or sham at all-time points, and resulted in the largest significant increase in MEPs. Our simulations show that applying cathodal tDCS at the standard stimulation position would cause only a 5.8% increase in the strength of the electric field produced by rTMS when the two techniques are used in conjunction. Our findings in this study indicate that combining rTMS with cathodal tDCS is not only safe, but highly-effective as well.

Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson\u2019s disease

Transcranial static magnetic field stimulation (tSMS) is a recent low-cost non-invasive brain stimulation technique that decreases cortical excitability in healthy subjects. The objective of the present study was to test the ability of tSMS to modulate cortical excitability in patients with Parkinson’s disease. We performed a randomized double-blind sham-controlled cross-over study to assess cortical excitability before and immediately after tSMS (or sham) applied for 10 min to the more affected motor cortex of patients with Parkinson’s disease. Cortical excitability was quantified by the amplitude of motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). tSMS significantly decreased MEP amplitudes in patients OFF medication (after overnight withdrawal of dopaminergic drugs), but not ON medication (after an acute dose of levodopa). The between-patients variability of tSMS-induced changes was significantly greater ON medication. The variability ON medication could be partly explained by disease progression, i.e. the more advanced the patient, the more likely it was to observe a switch from inhibitory tSMS plasticity OFF medication to paradoxical facilitatory plasticity ON medication. These results suggest that tSMS induces dopamine-dependent changes of cortical excitability in patients with Parkinson’s disease.

P037 Transcranial static magnetic field stimulation-induced modulation of motor cortex excitability in Parkinson’s disease

Question tSMS is a new non-pharmacological, low-cost, non-invasive brain stimulation (NIBS) technique that decreases cortical excitability in healthy subjects. The effects of tSMS in Parkinson’s disease remain unknown. We designed this study to test the ability of transcranial static magnetic field stimulation (tSMS) to modulate motor cortex excitability in patients with Parkinson’s disease. Methods We performed a randomized double-blind sham-controlled cross-over study to assess cortical excitability before and immediately after tSMS (or sham) applied for 10 min to the motor cortex of patients with Parkinson’s disease. Motor cortex excitability was quantified by the amplitude of motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). In a separated single-blind experimental session we evaluated the effects of tSMS on SICI and SICF. Patients were studied both after overnight withdrawal of dopaminergic therapy (OFF) medication and after an acute dose of levodopa (ON). Results tSMS significantly decreased MEP amplitudes compared to sham in patients OFF medication, but not ON medication. Furthermore, tSMS induced an increase in SICI and a reduction in SICF only in OFF condition. Conclusions These results suggest a dopamine dependency of tSMS-induced cortical changes and encourage the application of tSMS for future clinical trials in patients with Parkinson’s disease.

P148 Dose–effect of transcranial static magnetic field stimulation on excitatory and inhibitory intracortical circuits

Question Transcranial static magnetic field stimulation (tSMS) is a new low-cost, non-invasive brain stimulation (NIBS) technique. When tSMS is applied for 10–15 min over the motor cortex, it leads to a short-lasting decrease of cortical excitability in healthy subjects, as measured by a decreased amplitude of motor-evoked potentials (MEPs), associated with an increase of short-latency intracortical inhibition (SICI). Here we aimed to test the effects of a longer application of tSMS (30 min) on excitatory and inhibitory intracortical circuits. Methods We performed 3 randomized double-blind sham-controlled experiments in a total of 31 right-handed healthy subjects. In experiment 1 we assessed MEP amplitudes before and after tSMS (or sham) applied for 30 min to the non-dominant motor cortex. In experiment 2 we tested the effects of 30 min of tSMS on SICI and I wave interaction. In experiment 3 we evaluated the effects of 10 min of tSMS on SICI and on the first peak of I wave interaction (short-latency intracortical facilitation, SICF). Results Prolonged application of tSMS (30 min) significantly decreased MEP amplitudes compared to sham till 30 min after the end of tSMS and, surprisingly, reduced SICI while increasing SICF. By applying tSMS for only 10 min, we found a significant and short-lasting increase of SICI with reduction of SICF. Conclusions We found that a prolonged application of tSMS leads to a long-lasting reduction in motor cortex excitability, similar to those typically induced by continuous theta-burst stimulation (cTBS) and cathodal transcranial direct current stimulation (tDCS). Moreover, SICI and SICF could be modulated in a bidirectional way by tSMS, depending on the application time, revealing a dose–effect of tSMS on excitatory and inhibitory intracortical circuits.

P700: Trigeminal nerve stimulation does not affect cortical excitability in healthy subjects

P700: Trigeminal nerve stimulation does not affect cortical excitability in healthy subjects

P 22. Transcranial direct current stimulation (tDCS) and peripheral lymphocytes

Introduction Non-invasive brain stimulation techniques modulate cortical excitability in healthy subjects and in patients. Electric fields can induce directional cell migration (i.e. electrotaxis) of epithelial cells, endothelial cells, fibroblasts, and neutrophils. Human lymphocytes respond in vitro to electric fields migrating toward the cathode. Whereas repetitive transcranial magnetic stimulation (rTMS) increases peripheral lymphocytes number, no data are available about transcranial direct current stimulation (tDCS).The possible effect of tDCS on lymphocytes has potential implication on its safety. Objective The aim of the present study is to investigate the effect of tDCS on peripheral lymphocytes in humans. Materials and Methods Eight healthy right-handed subjects (six women and two men aged 23–39; mean+SD: 29.6±5,64) participated in the study. Subjects underwent anodal and sham tDCS in a cross over design. Anodal tDCS was performed with the active electrode (anode) placed over the left temporal lobe (T3) and the reference (cathode) over the right arm (current intensity at 2mA, 20min, electrode size of 35cm 2 ). Peripheral blood samples for immunological testing were collected at baseline (T0) and one (T1) and four hours (T2) after tDCS offset and monoclonal antibodies identified the following lymphocyte subsets: T-lymphocytes (CD3+, CD4+3+, CD8+3+ and CD3+DR+), B-lymphocytes (CD20+), IL-2 receptor (CD25+) and natural killer cells (CD56+16+3−). Monocytes were also tested (CD14+, CD14+DR+). Results Baseline values were comparable between sham and active tDCS. While T-lymphocytes and B-lymphocytes significantly increased after stimulation offset (factor time point: total lymphocytes, p : 0.035; CD3+, p : 0.010, CD4+3+, p : 0.012; CD20, p : p : 0.042, total monocytes, p : 0.004; CD14+, p : 0.005; CD14+DR+, p : 0.003) in both stimulation conditions without significant differences. Discussion In the present study the extra-cephalic reference anodal tDCS on dominant hemisphere did not affect the number of circulating lymphocytes and monocytes. Changes in lymphocytes number both in anodal and sham stimulation could depend onlymphocytes circadian rhythm.These results could have important implications for anodal tDCS clinical use and safety especially in immunodepressed and stroke patients. Infact, cerebrovascular lesions in the dominant hemisphere are associated to decreased total blood lymphocytes countand greater morbidity.In conclusion, unlike TMS, anodal tDCS does not influence peripheral lymphocytes thus further supporting the systemic safety of this technique.

IS 15. Flashes of insight: Non-conventional NIBS reveals novel ways to stimulate the brain

Modulating, disrupting or otherwise interfering with the activity of the cerebral cortex by non-invasive, external stimulation methods not only offers the possibility of clinical intervention in neurological and psychiatric diseases, but provides us with a powerful research tool for understanding the workings of the intact human brain. In the past years new non-conventional, non-invasive brain stimulation (NIBS) techniques have been developed. Application of near-infrared light to the scalp has recently been introduced in order to treat neurological conditions such as stroke and the treatment of traumatic brain disorders ( Hashmi et al., 2010 ). Another very simple method, the application of static magnetic fields (tSMS) through the scalp by using small cylindrical magnets, has been shown to induce robust effects on levels of cortical excitability in healthy subjects ( Oliviero et al., 2011 ). Nevertheless, a deeper knowledge of the mechanisms of how these methods work on a neuronal level, is required. In our laboratory we have demonstrated that applying near-infrared light at a wavelength of 810 nm for 10 min to the primary motor cortex (M1), results in cortical excitability changes, assessed by means of motor-evoked potentials (MEP). MEP amplitudes showed a 20–40% decrease compared to sham stimulation, for up to 1 h post-stimulation. Furthermore, it was observed that the stimulation modified the long intracortical inhibition. Similarly, with the application of tSMS to the M1, an inhibition could be observed. On the functional level it has been demonstrated that both of these methods can modify implicit motor learning. These non-conventional NIBS techniques may thus be opening new research domains for influencing brain activity and to treat neurological and psychiatric disorders in a non-invasive way.

Increased cortical excitability after selective REM sleep deprivation in healthy humans: A transcranial magnetic stimulation study

REM sleep has antiepileptogenic properties whereas, its loss is known to have a proconvulsive role. However, the mechanisms underlying the proepileptogenic effects of REM sleep deprivation are yet not fully understood. The aim of our study was to evaluate the effects of selective REM sleep deprivation (SRD) on cortical excitability in healthy subjects by means of transcranial magnetic stimulation (TMS). Ten normal subjects underwent three TMS sessions: (1) in baseline condition (BL), (2) after SRD by awakening them at each REM sleep onset and (3) after non-rapid eye movement sleep awakenings (NREM-A) as control for potential non-specific effects of interruptions. The TMS investigation included two protocols: (a) the evaluation of motor evoked potentials (MEPs) and silent period (SP) parameters, recorded in response to single pulse magnetic stimulation; (b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1-10 ms. After SRD the principal finding observed using single pulse TMS was a significant reduction in the duration of SP whereas, a reduction of intracortical inhibition was found, using the paired-pulse TMS. TMS parameters did not show significant changes after NREM-A with respect to BL. SRD may influence cortical excitability with a reduction of inhibitory intracortical mechanisms, thus supporting the proconvulsant role of REM loss.

Effects of 10 Hz and 20 Hz transcranial alternating current stimulation (tACS) on motor functions and motor cortical excitability

Synchronized oscillatory activity at alpha (8–12Hz) and beta (13–30Hz) frequencies plays a key role in motor control. Nevertheless, its exact functional significance has yet to be solved. Transcranial alternating current stimulation (tACS) allows the frequency-specific modulation of ongoing oscillatory activity. The goal of the present study was to investigate the effect of 10 and 20Hz tACS over left primary motor cortex (M1) on motor functions and cortical excitability in healthy subjects. To this end, tACS was applied for 10min. Sham stimulation served as control condition. Movement speed and accuracy of the right hand were assessed in 15 right-handed subjects before and after (0, 30 and 60min) tACS of M1. Cortical silent period (CSP) and motor evoked potentials (MEPs) were determined as measures of M1 excitability. While 10Hz tACS particularly increased movement variability, especially in tasks requiring internal pacing, 20Hz tACS resulted in movement slowing. Behavioural effects occurred in distinct time windows. While 10Hz effects developed over 30min after stimulation, 20Hz tACS effects were found immediately after stimulation. Following 10Hz tACS these effects were significantly correlated with CSP duration, indicating interference with inhibitory pathways. The present findings suggest differential effects of stimulation frequency on motor behaviour and M1 excitability.

Mobile Phone Emissions Modulate Brain Excitability in Patients with Focal Epilepsy

BackgroundElectromagnetic fields (EMFs) emitted by mobile phones had been shown to increase cortical excitability in healthy subjects following 45 min of continuous exposure on the ipsilateral hemisphere. ObjectiveUsing Transcranial Magnetic Stimulation (TMS), the current study assessed the effects of acute exposure to mobile phone EMFs on the cortical excitability in patients with focal epilepsy. MethodsTen patients with cryptogenic focal epilepsy originating outside the primary motor area (M1) were studied. Paired-pulse TMS were applied to the M1 of both the hemisphere ipsilateral (IH) and contralateral (CH) to the epileptic focus before and immediately after real/sham exposure to the GSM-EMFs (45 min). The TMS study was carried out in all subjects in three different experimental sessions (IH and CH exposure, sham), 1 week apart, according to a crossover, double-blind and counter-balanced paradigm. ResultsThe present study clearly demonstrated that an acute and relatively prolonged exposure to GSM-EMFs modulates cortical excitability in patients affected by focal epilepsy; however, in contrast to healthy subjects, these effects were evident only after EMFs exposure over the hemisphere contralateral to the epileptic focus (CH). They were characterized by a significant cortical excitability increase in the exposed hemisphere paired with slight excitability decrease in the other one (IH). Both sham and real EMFs exposure of the IH did not affect brain excitability. ConclusionPresent results suggest a significant interaction between the brain excitability changes induced by EMFs and the epileptic focus, which eliminated the excitability enhancing effects of EMFs evident only in the CH.

Cortical excitability changes following grasping exercise augmented with electrical stimulation

Rehabilitation with augmented electrical stimulation can enhance functional recovery after stroke, and cortical plasticity may play a role in this process. The purpose of this study was to compare the effects of three training paradigms on cortical excitability in healthy subjects. Cortical excitability was evaluated by analysing the input-output relationship between transcranial magnetic stimulation intensity and motor evoked potentials (MEPs) from the flexor muscles of the fingers. The study was performed with 25 healthy volunteers who underwent 20-min simulated therapy sessions of: (1) functional electrical stimulation (FES) of the finger flexors and extensors, (2) voluntary movement (VOL) with sensory stimulation, and (3) therapeutic FES (TFES) where the electrical stimulation augmented voluntary activation. TFES training produced a significant increase in MEP magnitude throughout the stimulation range, suggesting an increase in cortical excitability. In contrast, neither the FES nor voluntary movement alone had such an effect. These results suggest that the combination of voluntary effort and FES has greater potential to induce plasticity in the motor cortex and that TFES might be a more effective approach in rehabilitation after stroke than FES or repetitive voluntary training alone.

Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation

Objective To investigate the effect of high frequency rTMS (25 Hz at 90–100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects. Methods Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facilitation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers. Results Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30 min) and had returned to normal by 2 h. There were no significant effects on SICI/ICF. Conclusion Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects. Significance This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity.

Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects

Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). Ten healthy volunteers received a 20-sec train of 5-Hz rTMS given at an intensity of individual active motor threshold to the left primary motor hand area. This interventional protocol was preconditioned by 10 min of anodal, cathodal, or sham tDCS. We used single-pulse TMS to assess corticospinal excitability at rest before, between, and after the two interventions. The 5-Hz rTMS given after sham tDCS failed to produce any after-effect, whereas 5-Hz rTMS led to a marked shift in corticospinal excitability when given after effective tDCS. The direction of rTMS-induced plasticity critically depended on the polarity of tDCS conditioning. Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.