Transcranial Magnetic Stimulation Intensity Research Articles

Sex-related differences in corticospinal excitability outcomemeasures of the biceps brachii during a submaximal elbow flexor contraction.

The purpose of this study was to investigate the effects of sex, muscle thickness, and subcutaneous fat thickness (SFT) on corticospinal excitability outcome measures of the biceps brachii. Eighteen participants (10 males and 8 females) completed this study. Ultrasound was used to assess biceps brachii muscle thickness and the overlying SFT. Transcranial magnetic stimulation (TMS) was used to determine corticospinal excitability by inducing motor-evoked potentials (MEPs) at eight different TMS intensities from 90% to 160% of active motor threshold (AMT) from the biceps brachii during an isometric contraction of the elbow flexors at 10% of maximum voluntary contraction (MVC). Biceps brachii maximal compound muscle action potential (Mmax) was also recorded prior to and after TMS. Males had higher (p < 0.001) biceps brachii muscle thickness and lower SFT, produced higher levels of MVC force and had, on average, higher (p < 0.001) MEP amplitudes at lower (p < 0.05) percentages of maximal stimulator output than females during the 10% elbow flexion MVC. Multiple linear regression modeling revealed that sex was not associated with any of the neurophysiological parameters examined, while SFT showed a positive association with the stimulation intensity required at AMT (p = 0.035) and a negative association with biceps brachii pre-stimulus electromyography (EMG) activity (p = 0.021). Additionally, there was a small positive association between muscle thickness and biceps brachii pre-stimulus EMG activity (p = 0.049). Overall, this study suggests that some measures of corticospinal excitability may be different between the sexes and influenced by SFT and muscle thickness.

Corticospinal excitability at rest outside of a task does not differ from task intertrial intervals in healthy adults.

Human corticospinal excitability (CSE) modulates during movement, when muscles are active, but also at rest, when muscles are not active. These changes in resting motor system excitability can be transient or longer lasting. Evidence from transcranial magnetic stimulation (TMS) studies suggests even relatively short periods of motor learning on the order of minutes can have lasting effects on resting CSE. Whether individuals are able to return CSE to out-of-task resting levels during the intertrial intervals (ITI) of behavioral tasks that do not include an intended motor learning component is an important question. Here, in twenty-five healthy young adults, we used single-pulse TMS and electromyography (EMG) to measure motor evoked potentials (MEPs) during two different resting contexts: (1) prior to engaging in the response task during which participants were instructed only to rest (out-of-task), and (2) ITI of a choice-reaction time task (in-task). In both contexts, five TMS intensities were used to evaluate possible differences in recruitment of corticospinal (CS) output across a range of inputs. We hypothesized resting state CSE would be greater during ITI than out-of-task rest, reflected in larger MEP amplitudes. Contrary to our hypothesis, we observed no significant difference in MEP amplitudes between out-of-task rest and in-task ITI, and instead found evidence of equivalence, indicating that humans are able to return to a stable motor resting state within seconds after a response. These data support the interpretation that rest is a uniform motor state in the healthy nervous system. In the future, our data may be a useful reference for motor disorder populations with an impaired ability to return to rest.

Mapping the Cortical Representation of Paraspinal Muscles Using Transcranial Magnetic Stimulation Optimized in People With Chronic Back Pain.

Chronic low back pain (CLBP) is a global burden with an unknown etiology. Reorganization of the cortical representation of paraspinal muscles in the primary motor cortex (M1) may be related to the pathology. Single-pulse transcranial magnetic stimulation (TMS), commonly used to map the functional organization of M1, is not potent enough to stimulate the cortical maps of paraspinal muscles in M1 in CLBP patients with reduced corticospinal excitability (CSE) with intensities even as high as maximum stimulator output (100% MSO). This makes TMS mapping impractical for these patients. The aim of this study was to increase the practicality of TMS mapping for people with CLBP. This study included eight men and ten women who had CLBP for over three months. A biphasic paired-pulse TMS paradigm, conjunct anticipatory postural adjustment (APA), and maximal voluntary activation of paraspinal muscles (MVC) were used to facilitate TMS mapping. TMS mapping was possible in all CLBP participants, with TMS intensities <50% of the MSO. Reorganization in terms of an anterior and lateral shift of the center of gravity (COG) of the cortical maps of paraspinal muscles was observed in all participants with CLBP, and a reduced number of discrete peaks was found in 33%. The facilitation of the CSE to paraspinal muscles makes TMS mapping more practical and tolerable in people with CLBP, lowering the risk of seizure and discomfort associated with high-intensity TMS pulses. Conventional transcranial magnetic stimulation (TMS) brain mapping is not optimal for patients with Chronic low back pain (CLBP).Paired-pulse TMS dramatically lessens the energy needed for brain mapping.Maximal voluntary contraction of back muscles facilitates TMS mapping.Anticipatory postural activity of back muscles enhances the efficacy of TMS mapping. Chronic low back pain (CLBP) is a social, emotional, and economic burden and the leading cause of disability worldwide. Yet the etiology of the CLBP is unknown. The persistence of aberrant or antalgic movement patterns observed in people with CLBP has been suggested as a possible cause of pain chronification by inducing continuous damage to sensitive structures of the lumbar spine. It is well known that the brain is in charge of the production and planning of movements, so it is likely that abnormal movement patterns also stem from the abnormalities in the brain. However, until recently, human knowledge about the structure and function of the brain has been very limited. The invention of noninvasive and painless brain imaging and stimulating techniques such as transcranial magnetic stimulation (TMS) during the last decades has augmented our knowledge about the structure and function of the brain. Modification in terms of shift, shrinkage, or expansion of areas of the brain devoted to movement control or sensation of the back muscles has been documented in CLBP via these techniques, which are argued to relate to pain chronification but need further clarification. Yet monitoring the course of CLBP via TMS, despite its many potentials, is challenging. This could be due to the reduced cortical drive to back muscles in CLBP patients and the small area devoted to control of back muscles in the brain in general that increases the brain threshold to TMS in people with CLBP. The aim of this study was to tailor an approach to make TMS more applicable for CLBP patients by reducing the threshold to TMS. This could be achieved by engaging back muscles in anticipatory postural activity in combination with maximal voluntary activation of these muscles, along with TMS paradigms that induce intracortical facilitation.

A dose-response characterization of transcranial magnetic stimulation intensity and evoked potential amplitude in the dorsolateral prefrontal cortex

By combining transcranial magnetic stimulation (TMS) with electroencephalography, human cortical circuits can be directly interrogated. The resulting electrical trace contains TMS-evoked potential (TEP) components, and it is not known whether the amplitudes of these components are stimulus intensity dependent. We examined this in the left dorsolateral prefrontal cortex in nineteen healthy adult participants and extracted TEP amplitudes for the N40, P60, N120, and P200 components at 110%, 120%, and 130% of resting motor threshold (RMT). To probe plasticity of putative stimulus intensity dose-response relationships, this was repeated after participants received intermittent theta burst stimulation (iTBS; 600 pulses, 80% RMT). The amplitude of the N120 and P200 components exhibited a stimulus intensity dose-response relationship, however the N40 and P60 components did not. After iTBS, the N40 and P60 components continued to exhibit a lack of stimulus intensity dose-dependency, and the P200 dose-response was unchanged. In the N120 component, however, we saw evidence of change within the stimulus intensity dose-dependent relationship characterized by a decrease in absolute peak amplitudes at lower stimulus intensities. These data suggest that TEP components have heterogeneous dose-response relationships, with implications for standardizing and harmonizing methods across experiments. Moreover, the selective modification of the N120 dose-response relationship may provide a novel marker for iTBS plasticity in health and disease.

The external evocation and movement-related modulation of motor cortex inhibition in children and adolescents with Tourette syndrome - a TMS/EEG study.

This study tested the reactivity of motor cortex inhibition to different intensities of external stimulation by transcranial magnetic stimulation (TMS) and its internal modulation during different motor states in children and adolescents with Tourette syndrome. TMS-evoked N100 served as an indirect measure of GABAB receptor function which is related to cortical inhibition. Combined TMS/EEG was used to analyze the TMS-evoked N100 component evoked by different stimulation intensities as well as during resting condition, movement preparation (contingent negative variation task) and movement execution. The study included 18 early adolescents with Tourette syndrome and 15 typically developing control subjects. TMS-evoked N100 showed a less steep increase with increasing TMS intensity in Tourette syndrome together with less modulation (disinhibition) over the primary motor cortex during the motor states movement preparation and movement execution. Children with Tourette syndrome showed equally high N100 amplitudes at 110% resting motor threshold (RMT) intensity during resting condition and a parallel decline of RMT and N100 amplitude with increasing age as control subjects. Our study yields preliminary evidence that modulation of motor cortical inhibitory circuits, during external direct stimulation by different TMS intensities and during volitional movement preparation and execution is different in children and adolescents with Tourette syndrome compared to controls. These results suggest that a reduced resting motor cortical inhibitory "reserve" could contribute to the production of unwanted movements. Our findings are compatible with increased regulation of motor cortex excitability by perception-action binding in Tourette syndrome instead of top-down / motor regulation and need to be replicated in further studies.

Effects of transcranial magnetic stimulation (TMS) current direction and pulse waveform on cortico-cortical connectivity: A registered report TMS-EEG study.

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) are a promising proxy for measuring effective connectivity, that is, the directed transmission of physiological signals along cortico-cortical tracts, and for developing connectivity-based biomarkers. A crucial point is how stimulation parameters may affect TEPs, as they may contribute to the general variability of findings across studies. Here, we manipulated two TMS parameters (i.e. current direction and pulse waveform) while measuring (a) an early TEP component reflecting contralateral inhibition of motor areas, namely, M1-P15, as an operative model of interhemispheric cortico-cortical connectivity, and (b) motor-evoked potentials (MEP) for the corticospinal pathway. Our results showed that these two TMS parameters are crucial to evoke the M1-P15, influencing its amplitude, latency, and replicability. Specifically, (a) M1-P15 amplitude was strongly affected by current direction in monophasic stimulation; (b) M1-P15 latency was significantly modulated by current direction for monophasic and biphasic pulses. The replicability of M1-P15 was substantial for the same stimulation condition. At the same time, it was poor when stimulation parameters were changed, suggesting that these factors must be controlled to obtain stable single-subject measures. Finally, MEP latency was modulated by current direction, whereas non-statistically significant changes were evident for amplitude. Overall, our study highlights the importance of TMS parameters for early TEP responses recording and suggests controlling their impact in developing connectivity biomarkers from TEPs. Moreover, these results point out that the excitability of the corticospinal tract, which is commonly used as a reference to set TMS intensity, may not correspond to the excitability of cortico-cortical pathways.

Effects of motor stimulation of the tibial nerve on corticospinal excitability of abductor hallucis and pelvic floor muscles.

Peripheral nerve stimulation can modulate the excitability of corticospinal pathways of muscles in the upper and lower limbs. Further, the pattern of peripheral nerve stimulation (continuous vs. intermittent) may be an important factor determining the modulation of this corticospinal excitability. The pelvic floor muscles (PFM) are crucial for maintaining urinary continence in humans, and share spinal segmental innervation with the tibial nerve. We explored the idea of whether the neuromodulatory effects of tibial nerve stimulation (TibNS) could induce effects on somatic pathways to the PFM. We evaluated the effects of two patterns of stimulation (intermittent vs. continuous) on corticospinal excitability of the PFM compared to its effect on the abductor hallucis (AH) muscle (which is directly innervated by the tibial nerve). We hypothesized that intermittent TibNS would increase, while continuous stimulation would decrease, the excitability of both AH and PFM. Twenty able-bodied adults (20-33 years of age) enrolled in this study. TibNS was delivered either intermittently (1 ms pulses delivered at 30Hz with an on:off duty cycle of 600:400 ms, for 60 min), or continuously (1 ms pulses delivered at 30Hz for 36 min) just above the motor threshold of the AH. We randomized the order of the stimulation pattern and tested them on separate days. We used surface electromyography (EMG) to record motor-evoked responses (MEP) in the PFM and AH following transcranial magnetic stimulation (TMS). We generated stimulus-response (SR) curves to quantify the changes in peak-to-peak MEP amplitude relative to TMS intensity to assess changes in corticospinal excitability pre- and post-stimulation. We found that TibNS increased corticospinal excitability only to AH, with no effects in PFM. There was no difference in responses to continuous vs. intermittent stimulation. Our results indicate a lack of effect of TibNS on descending somatic pathways to the PFM, but further investigation is required to explore other stimulation parameters and whether neuromodulatory effects may be spinal in origin.

The Effect of Coil Orientation on the Stimulation of the Pre–Supplementary Motor Area: A Combined TMS and EEG Study

Studies using transcranial magnetic stimulation (TMS) have demonstrated the importance of direction and intensity of the applied current when the primary motor cortex (M1) is targeted. By varying these, it is possible to stimulate different subsets of neural elements, as demonstrated by modulation of motor evoked potentials (MEPs) and motor behaviour. The latter involves premotor areas as well, and among them, the presupplementary motor area (pre–SMA) has recently received significant attention in the study of motor inhibition. It is possible that, similar to M1, different neuronal populations can be activated by varying the direction and intensity of TMS; however, the absence of a direct electrophysiological outcome has limited this investigation. The problem can be solved by quantifying direct cortical responses by means of combined TMS and electroencephalography (TMS–EEG). We investigated the effect of variable coil orientations (0°, 90°, 180° and 270°) and stimulation intensities (100%, 120% and 140% of resting motor threshold) on local mean field potential (LMFP), transcranial evoked potential (TEP) peaks and TMS–related spectral perturbation (TRSP) from pre–SMA stimulation. As a result, early and late LMFP and peaks were larger, with the coil handle pointing posteriorly (0°) and laterally (90°). This was true also for TRSP in the β–γ range, but, surprisingly, θ–α TRSP was larger with the coil pointing at 180°. A 90° orientation activated the right M1, as shown by MEPs elicitation, thus limiting the spatial specificity of the stimulation. These results suggest that coil orientation and stimulation intensity are critical when stimulating the pre–SMA.

Quadriceps motor evoked torque is a reliable measure of corticospinal excitability in individuals with anterior cruciate ligament reconstruction

This study comprehensively evaluated the test–retest reliability of raw and normalized quadriceps motor evoked responses elicited by transcranial magnetic stimulation (TMS) in individuals with anterior cruciate ligament (ACL) reconstruction. Fifteen participants were tested on three different days that were separated at least by 24 h. Motor evoked responses were collected during a small background contraction on the reconstructed leg across a range of TMS intensities using torque (MEPTORQUE) and electromyographic (MEPEMG) responses. MEPTORQUE and MEPEMG were evaluated using different normalization procedures (raw, normalized to maximum voluntary isometric contraction [MVIC], peak MEP, and background contraction). MEPTORQUE was also normalized to the magnetically-evoked peripheral resting twitch torque. The area under the recruitment curve was computed for both raw and normalized MEPs. Intraclass correlation coefficients (ICCs) were determined to assess test–retest reliability. Results indicated that MEPTORQUE generally showed greater reliability than MEPEMG for all normalization procedures. Vastus medialis MEPEMG generally showed greater reliability than rectus femoris MEPEMG. Finally, both MEPTORQUE and MEPEMG exhibited good reliability, even when not normalized. These findings indicate that MEPTORQUE and MEPEMG offer reliable measures of corticospinal function and suggest that MEPTORQUE is a suitable alternative to MEPEMG for measuring quadriceps corticospinal excitability in individuals with ACL reconstruction.

Is it possible to compare inhibitory and excitatory intracortical circuits in face and hand primary motor cortex?

Face muscles are important in a variety of different functions, such as feeding, speech and communication of non‐verbal affective states, which require quite different patterns of activity from those of a typical hand muscle. We ask whether there are differences in their neurophysiological control that might reflect this. Fifteen healthy individuals were studied. Standard single‐ and paired‐pulse transcranial magnetic stimulation (TMS) methods were used to compare intracortical inhibitory (short interval intracortical inhibition (SICI); cortical silent period (CSP)) and excitatory circuitries (short interval intracortical facilitation (SICF)) in two typical muscles, the depressor anguli oris (DAO), a face muscle, and the first dorsal interosseous (FDI), a hand muscle. TMS threshold was higher in DAO than in FDI. Over a range of intensities, resting SICF was not different between DAO and FDI, while during muscle activation SICF was stronger in FDI than in DAO (P = 0.012). At rest, SICI was stronger in FDI than in DAO (P = 0.038) but during muscle contraction, SICI was weaker in FDI than in DAO (P = 0.034). We argue that although many of the difference in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting SICI in DAO, may reflect fundamental differences in the physiology of the two muscle groups. Key points Transcranial magnetic stimulation (TMS) single‐ and paired‐pulse protocols were used to investigate and compare the activity of facilitatory and inhibitory intracortical circuits in a face (depressor anguli oris; DAO) and hand (first dorsal interosseous; FDI) muscles. Several TMS intensities and interstimulus intervals were tested with the target muscles at rest and when voluntarily activated.At rest, intracortical inhibitory activity was stronger in FDI than in DAO. In contrast, during muscle contraction inhibitory activity was stronger in DAO than in FDI. As many previous reports have found, the motor evoked potential threshold was higher in DAO than in FDI.Although many of the differences in response to the TMS protocols could result from the difference in thresholds, some, such as the reduction of resting short interval intracortical inhibition in DAO, may reflect fundamental differences in the physiology of the two muscle groups.

Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

BackgroundA growing number of studies have suggested that transcranial magnetic stimulation (TMS) may represent a novel technique with both investigative and therapeutic potential for autism spectrum disorder (ASD). However, a full spectrum of the adverse effects (AEs) of TMS used in ASD has not been specifically and systematically evaluated.ObjectiveThis systematic review and meta-analysis was to assess the prevalence of AEs related to TMS in ASD and to further explore the potentially related factors on the AEs.MethodsA systematic literature research of articles published before 31 December 2020 was conducted in the databases of PubMed, Embase, Cochrane Library, Ovid, PsycINFO, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP, and WANFANG DATA. AEs reported in the studies were carefully examined and synthesized to understand the safety and tolerability of TMS among ASD. Then, subgroup and sensitivity analyses were performed to examine the potentially related factors on the AEs. PROSPERO registration number: CRD42021239827.ResultsEleven studies were included in the meta-analysis. The pooled prevalence with 95% confidence interval (CI) of AEs was calculated (overall AEs: 25%, 95% CI 18–33%; headache: 10%, 95% CI 3–19%; facial discomfort: 15%, 95% CI 4–29%; irritability 21%, 95% CI 8–37%; pain at the application site: 6%, 95% CI 0–19%; headedness or dizziness: 8%, 95% CI 0–23%). All reported AEs were mild and transient with relatively few serious AEs and can be resolved after having a rest or medication. In addition, the following variables showed no significant change in overall prevalence of AEs: the purpose of using TMS, mean age of participants, whether the stimulation site was dorsolateral pre-frontal cortex (DLPFC), intensity of TMS, and the number of stimulation sessions.ConclusionThe overall prevalence of reported AEs of TMS among ASD was 25%. No identified ASD-specific risk factors for TMS-induced AEs were found. Further studies are needed to clarify the variation in the prevalence.Systematic Review Registrationwww.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=239827, PROSPERO, identifier: CRD42021239827.

The effect of acute intermittent hypoxia on human limb motoneurone output.

What is the central question of this study? Does a single session of repeated bouts of acute intermittent hypoxic breathing enhance the motoneuronal output of the limb muscles of healthy able-bodied participants? What is the main finding and its importance? Compared to breathing room air, there were some increases in motoneuronal output following acute intermittent hypoxia, but the increases were variable across participants and in time after the intervention and depended on which neurophysiological measure was checked. Acute intermittent hypoxia (AIH) induces persistent increases in output from rat phrenic motoneurones. Studies in people with spinal cord injury (SCI) suggest that AIH improves limb performance, perhaps via postsynaptic changes at cortico-motoneuronal synapses. We assessed whether limb motoneurone output in response to reflex and descending synaptic activation is facilitated after one session of AIH in healthy able-bodied volunteers. Fourteen participants completed two experimental days, with either AIH or a sham intervention (randomised crossover design). We measured H-reflex recruitment curves and homosynaptic post-activation depression (HPAD) of the H-reflex in soleus, and motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS) and their recruitment curves in first dorsal interosseous. All measurements were performed at rest and occurred at baseline, 0, 20, 40 and 60min post-intervention. The intervention was 30min of either normoxia (sham, ≈0.21) or AIH (alternate 1-min hypoxia [ ≈0.09], 1-min normoxia). After AIH, the H-reflex recruitment curve shifted leftward. Lower stimulation intensities were needed to evoke 5%, 50% and 99% of the maximal H-reflex at 40 and 60min after AIH (P<0.04). The maximal H-reflex, recruitment slope and HPAD were unchanged after AIH. MEPs evoked by constant intensity TMS were larger 40min after AIH (P=0.027). There was no change in MEP recruitment or the maximal MEP. In conclusion, some measures of the evoked responses from limb motoneurones increased after a single AIH session, but only at discrete time points. It is unclear to what extent these changes alter functional performance.

TMS intensity and focality correlation with coil orientation at three non-motor regions

Objective. The aim of this study is to define the best coil orientations for transcranial magnetic stimulation (TMS) for three clinically relevant brain areas: pre-supplementary motor area (pre-SMA), inferior frontal gyrus (IFG), and posterior parietal cortex (PPC), by means of simulations in 12 realistic head models of the electric field (E-field). Methods. We computed the E-field generated by TMS in our three volumes of interest (VOI) that were delineated based on published atlases. We then analysed the maximum intensity and spatial focality for the normal and absolute components of the E-field considering different percentile thresholds. Lastly, we correlated these results with the different anatomical properties of our VOIs. Results. Overall, the spatial focality of the E-field for the three VOIs varied depending on the orientation of the coil. Further analysis showed that differences in individual brain anatomy were related to the amount of focality achieved. In general, a larger percentage of sulcus resulted in better spatial focality. Additionally, a higher normal E-field intensity was achieved when the coil axis was placed perpendicular to the predominant orientations of the gyri of each VOI. A positive correlation between spatial focality and E-field intensity was found for PPC and IFG but not for pre-SMA. Conclusions. For a rough approximation, better coil orientations can be based on the individual’s specific brain morphology at the VOI. Moreover, TMS computational models should be employed to obtain better coil orientations in non-motor regions of interest. Significance. Finding better coil orientations in non-motor regions is a challenge in TMS and seeks to reduce interindividual variability. Our individualized TMS simulation pipeline leads to fewer inter-individual variability in the focality, likely enhancing the efficacy of the stimulation and reducing the risk of stimulating adjacent, non-targeted areas.

Threshold Tracked Short-Interval Intracortical Inhibition More Closely Predicts the Cortical Response to Transcranial Magnetic Stimulation

ObjectivesShort-interval intracortical inhibition (SICI) is a paired-pulse transcranial magnetic stimulation (TMS) technique that is commonly used to quantify intracortical inhibitory tone in the primary motor cortex. Whereas conventional measures of SICI (C-SICI) quantify inhibition by the amplitude of the motor evoked potential (MEP), alternative measures involving threshold tracked SICI (TT-SICI) instead record the TMS intensity required to maintain a consistent MEP amplitude. Although both C-SICI and TT-SICI are thought to reflect inhibition mediated by γ-aminobutyric acid type A (GABAA) receptors, recent evidence suggests that the mechanisms involved with each measure may not be equivalent. This study aimed to use combined TMS-electroencephalography (TMS-EEG) to investigate the cortical mechanisms contributing to C-SICI and TT-SICI. Materials and MethodsIn 20 young adults (30.6 ± 8.1 years), C-SICI and TT-SICI were recorded with multiple conditioning intensities, using both posterior-to-anterior (PA) and anterior-to-posterior (AP) induced currents, and this was compared with the TMS-evoked EEG potential (TEP). ResultsWe found no relationship between the magnitude of C-SICI and TT-SICI within each current direction. However, there was a positive relationship between the slope (derived from multiple conditioning intensities) of inhibition recorded with C-SICI and TT-SICI, but only with a PA current. Furthermore, irrespective of conditioning intensity or current direction, measures of C-SICI were unrelated to TEP amplitude. In contrast, TT-SICI was predicted by the P30 generated with AP stimulation. ConclusionsOur findings further demonstrate that C-SICI and TT-SICI likely reflect different facets of GABAA-mediated processes, with inhibition produced by TT-SICI appearing to align more closely with TMS-EEG measures of cortical excitability.

Modification in Pittsburgh Sleep Quality Index after low intensity transcranial magnetic stimulation in patients with fibromyalgia

Fibromyalgia is a disease of unknown origin in which sleep involvement is very prevalent, and one of the main symptoms, even as prevalent as pain. In fact, one condition has been linked to the other, and the two may feedback on each other. We investigated what happens if by applying low-field magnetic stimulation in patients with fibromyalgia, it could improve sleep variables, and if this would be related to an improvement in the pain of the patients. We compared the results of a group of female patients with fibromyalgia, who underwent treatment for 6 weeks, with another group of patients with similar characteristics, who were not treated. The results were also compared with a group of healthy women, who served as a second control group. The Pittsburgh sleep scale was used as a sleep scale and a global clinical scale was used to assess general state. A significant improvement was observed in the different items of the sleep scale applied, from the four weeks of treatment, being even more evident at the end of treatment at six weeks. A total of 82% of patients improved at the end of treatment. There was a correlation of this improvement with the overall pain situation of the patients. In addition, there was a trend towards equal sleep outcomes between treated patients and healthy subjects. Treatment with low intensity magnetic stimulation could improve the sleep of fibromyalgia patients, as well as their overall clinical situation, and both processes could be interrelated.

FEATURES ANALYSIS AND SYSTEM IDENTIFICATION OF MECHANOMYOGRAPHY AND ELECTROMYOGRAPHY UNDER TRANSCRANIAL MAGNETIC STIMULATION

Transcranial magnetic stimulation (TMS) is an electrophysiological technique that uses alternating magnetic fields to deliver electric current and stimulate the cerebral cortex. When TMS is used for the evaluation of brain diseases, it is necessary to detect the contraction of the corresponding muscles in the cerebral cortex stimulated by TMS, and the muscle activity referred to as motor evoked potential (MEP). This study simultaneously recorded the mechanomyography (MMG) and electromyography (EMG) from the right abductor pollicis brevis muscle during TMS with different intensities in order to observe whether the MEP parameters from MMG signals showed similar trait of EMG recordings. Moreover, the subspace method (N4SID) and transfer function were used to identify the TMS–MMG system. In this system, the input was a pulse signal of TMS, and the output was the MMG signal detected from the target muscle. The TMS–MMG system was identified as a fourth-order model. This study also analyzed the internal features of the system and demonstrated that the poles of healthy subjects were distributed in a range, and the gain increased with the increase of the TMS intensity. It was found that MMG signals can be used as diagnostic indicators of TMS, and the TMS–MMG model can be used to further explore the details of how TMS generates responses measured with MMG.

High Frequency and Low Intensity Transcranial Magnetic Stimulation for Smoking Cessation.

Introduction Tobacco consumption is one of the main causes of mortality in the world. Because of its effect on health, smoking cessation should be prioritized as an important health intervention; however, current interventions have shown low success rates as only 31% of the cases can stop smoking. In this paper, an intervention with high frequency and low intensity transcranial magnetic stimulation (HFLI TMS) was applied to determine if this type of neuromodulation could have an effect in decreasing tobacco addiction. Methods Retrospective data from ten ambulatory smoker patients that underwent 24 sessions of HFLI TMS over 8 weeks were retrieved and are here presented. Results Exhaled CO concentrations were statistically significantly different from baseline at the weeks 3, 5, 6, and 8. After the 24 sessions, all patients stopped smoking; this was confirmed directly by exhaled carbon monoxide and the smoking diary. Three months after intervention, eight out of ten subjects continued without smoking. No severe adverse effects were reported by participants. Conclusions Overall, employing HFLI TMS appears to have acceptable result; however, further evidence is needed to determine with more certainty its therapeutic effect and adverse effects for addiction intervention.

Establishing the Minimum Intensity of Transcranial Magnetic Stimulation Superconditioning Pulses to Effect Inhibition and Facilitation of Motor Evoked Potentials.

Previously, we showed that a three-pulse train of weak transcranial magnetic stimulation (TMS) pulses-a superconditioning (SC) train-when followed by a stronger TMS pulse could enhance the inhibition or facilitation of the resultant motor evoked potential (MEP) compared with that seen with traditional dual-pulse inputs. The purpose of the present study was to establish the relative minimum intensity of SC pulses needed to influence MEP output and whether this differed for upper- versus lower-limb muscles. We examined 33 older adult subjects, targeting abductor pollicis brevis and tibialis anterior muscles. Older subjects were included in the anticipation of using findings from this study to guide further studies in persons with amyotrophic lateral sclerosis. Three-pulse trains of SC inputs of different intensities were delivered either 1 millisecond before (for inhibition) or 10 millisecond before (for facilitation) a stronger TMS test pulse. Motor evoked potential magnitudes for SC +test sets were normalized to test input responses and were compared within and between subjects. For inhibition, the minimum intensity of SC pulses needed to influence the follow-on MEP was found to be 60% of the target muscle's resting three-pulse MEP threshold for most abductor pollicis brevis and tibialis anterior muscles (2-millisecond interpulse intervals). For facilitation, somewhat higher intensities (70%) were typically needed to cause facilitation. Both values of SC pulses for inhibition/facilitation are considerably lower than the intensity of the conditioning pulse-often reported as 80% of the single-pulse threshold-typically used in dual-pulse TMS paradigms. This approach may allow testing of upper motor neuron function using weaker stimulus pulse intensities than are typically employed, improving testing compliance in persons whose thresholds are elevated because of injury or disease.

P 26. Ipsilateral silent period in multiple sclerosis and healthy controls depends on stimulus intensity

Background. In patients with multiple sclerosis (MS) lesions of the corpus callosum can be found even at early disease stages. With transcranial magnetic stimulation (TMS) the transcallosal interhemispheric inhibition can be investigated using the ipsilateral silent period (ISP). Various studies revealed differences in the duration of ISP in MS-patients compared to healthy controls (HC), both as increased (Schmierer et al. 2002) or decreased (Lenzy et al., 2007), presumably because of methodological differences in stimulus intensities. Therefore this study aimed to investigate the influence of stimulus intensities on the ISP in MS compared to HC.Methods: 20 MS (13 females, age: 44.6 ± 10.6) and 15 HC (9 females, age: 41.4 ± 10.0) matched by age and sex received a structural cranial MRI to perform MR-navigated TMS of the motor cortex. In total 40 TMS pulses were applied and durations of ISP were estimated in each participant. To examine to which extent the intensity of the TMS pulses modulate the duration, measurements were repeated at four stimulus intensities (state 1 to 4, 10 stimuli per state) calculated by the individuals resting motor threshold (RMT; 1.2 RMT/1.5 RMT/1.75 RMT/2 RMT). Results. rmANOVA revealed an effect for ISP-duration (RMT intensities; p < 0.05) but no significant group effect (MS, HC; n.s.). Post hoc analyses for RMT showed significant increase in duration between 1.2 and 1.5 RMT (p < 0.05). Conclusion. Our data provide evidence that the intensity of TMS may have an impact on the resulting duration of ISP in both MS and HC, which might explain the somewhat contradictory results in the literature so far. Future studies in patient cohorts should use different stimulus intensities in ISP. References Schmierer et al., 2002. Neurology 59: 1218-24. Lenzy et al., 2007. Hum Brain Mapp 28: 636-44.

P 60. Influence of TMS intensity on the ipsilateral silent period - comparison of RMT-adjusted and maximum stimulator output intensities

Introduction. Transcranial magnetic stimulation (TMS) induced ipsilateral silent periods (iSP) provide information on interhemispheric inhibitory drive, but varying methodological approaches in equipment, measurement, and data analysis hamper the comparability and overall reproducibility. Even though it is generally agreed that only pulses above resting motor threshold (RMT) result in reliable occurrence of iSPs, studies differ on intensity conditions, either using fixed % maximum stimulator outputs (MSO) or individualized intensities based on RMT 1,2 . Our aim was to demonstrate the intensity-dependent changes of iSP parameters and to analyse which intensity configuration, either plotted by RMT or MSO values, predict the effect with a better fit. Method. We investigated 20 (9 F) right-handed healthy adults between 24y and 67y (M = 38.55, SD = 12.11) using navigated TMS. 50% maximal voluntary contraction of the left first dorsal interosseous muscle was performed during stimulation with intensities of 120%, 150%, 175%, and 200% RMT on the dominant motor hand area. A regression analysis was performed with RMT-adjusted states and their respective percentage of MSO as independent variable each for iSP onset, duration, and depth. Results. Overall, we found 54 iSPs across all states. In 12 cases, highest RMT states could not be reached due to stimulator output limits, in 14 recordings iSPs were missing. Neither MSO nor RMT intensity correlated with iSP onset. Duration increase was significantly associated with RMT intensity ( p = .013, r = .33), but not with MSO values ( p = .17, r = .16). Contrary, depth increase was significantly associated with MSO intensity ( p = .049, r = .26), with a trend for the RMT model ( p = .096, r = .22). Discussion. We here demonstrate an intensity-dependent increase in iSP duration and depth, but not onset. Additionally, we did not find a clear difference between the RMT or the MSO approach for the correlation of stimulus intensity to iSP depth or duration. Contrary to previous findings 1,3 , no evidence of a ceiling effect emerged from our data. Our data suggest that each aspect of the iSP has a different association with increasing TMS intensities. Considering the lacking power for analysis of iSP depth and diverging results further investigation with larger samples is needed to compare the effects of fixed MSO versus RMT-adjusted stimulation increase on iSP measurements. 1: Chen et al., 2003. J. Neurophysiol. 89, 1256–1264. 2: Davidson, T., 2016. In: Tremblay, F. (Ed.), Doctor of Philosophy in Human Kinetics. University of Ottawa. 3: Meyer et al. 1995. Brain 118, 429–440.