Efficient TMS-Based Motor Cortex Mapping Using Gaussian Process Active Learning.

Abstract: Background: Correlations of Transcranial magnetic stimulation (TMS) mapping of the cortical area and electromyography (EMG) + dynamometric testing may demonstrate active neuroplas-ticity events that are reliant on rehabilitation therapy (RT) compliance in adult postsurgical brachial plexus (BP) injuries. Material and Methods: On the right (dominant) arm of two patients with chronic operated BP lesions, we evaluated the progress of functional recovery. The trau-matic event was dated more than 10 years ago for both patients. The first patient (male, 50 years old) and the second one (female, 58 years old) had a history of several microsurgical neurotiza-tion and muscle transfer procedures, with less amelioration of the motor deficit, especially re-lated to elbow flexion (MRC 1/5 and 2/5, respectively). We followed up their evolution by EMG parameters, dynamometry, MRC scaling, and TMS. The motor region of the limb was mapped using TMS to assess the amplitudes of the motor evoked potentials (MEP), on a 4-axis protocol. The patients were assessed twice, with the second examination performed after RT had just fin-ished. TMS findings were compared with EMG and dynamometric results. Results: Higher MEP amplitudes were associated with improved MEP latency during stimulation of the left cerebral hemisphere's cortical area, as well as at the cervical level. EMG findings, both nerve conduction and needle EMG studies showed nonsignificant improvements, as well as muscle strength (as measured by the hydraulic dynamometer). The best results for the first patient showed an in-crease in MEP’s amplitude increase from 1.08 mV to 1.49 mV (in the hotspot), which correlated with measurable latencies, as compared to the first TMS (when no response was obtained at cer-vical stimulation). The second patient also had improvements in latencies: from 37.1 msec. to 36.3 msec. (cervical stimulation with recording at bicipital level) and from 39.2 msec. to 37.9 (cervical stimulation recording at the first interosseous), with a hotspot increase from 1.35 mV to 1.98 mV. The results demonstrate cortical region reactivity in regard to therapeutic techniques. Central modifications do not correlate with visible EMG and dynamometric improvements. Pa-tients with traumatic BP palsy may receive several microsurgical reconstructive procedures, nevertheless, the rehabilitation of the upper limb’s functionality may sometimes still be limited. This increases the risk of discontinuity of the neuromotor RT. We aim to prove that in spite of little correlations with clinical and EMG findings, mapping the cortical area using TMS provides proof of ongoing neuroplasticity phenomena, dependent on adherence to RT. Conclusion: The evidence of continued brain activity supports the requirement for long-term adherence to treatment guidelines and long-term study protocols.

What is the central question of this study? A transcranial magnetic stimulation (TMS)-induced twitch applied on isolated single breaths over the motor cortex somatotopic representation of the tongue briefly recruits submental muscles and improves airflow dynamics of flow-limited respiratory cycles without arousing sleep apnoea patients. However, the mechanical impact of the TMS-induced twitch applied during consecutive breathing cycles on airflow dynamics remains unknown. What is the main finding and what is its importance? Our results show that application of TMS with the stimulator output set at the sleep submental motor threshold intensity on consecutive respiratory cycles increases inspiratory flow and reduces the turbulent airflow component. These results indicate an improvement of airflow pattern after two single consecutive TMS-induced twitches without arousing sleep apnoea patients. Transcranial magnetic stimulation (TMS)-induced twitches applied on isolated breaths briefly recruit upper airway dilator muscles and improve airflow and inspiratory volume without arousing apnoeic patients from sleep, but the effects of applying such twitches consecutively on airflow dynamics is unknown. The objective of this study was to quantify the effects of five consecutive TMS-induced twitches applied on sleep-induced obstructive hypopnoeic breaths in 10 obstructive sleep apnoea patients. Submental muscle motor threshold (SUBMT) and motor-evoked potential were measured during wakefulness and sleep. The TMS-induced twitches were applied during stable non-rapid eye movement (NREM) sleep, at the beginning of inspiration of consecutive flow-limited respiratory cycles, with the stimulator output set at sleep SUBMT. Maximal inspiratory flow, inspiratory volume, inspiratory time, shifts of electroencephalogram frequency and pulse rate variability were assessed. During sleep, SUBMT increased (wakefulness, 25.3 ± 4.9%; NREM sleep, 27.0 ± 6.2%; P = 0.02). During each series of stimulations there was a rise in maximal inspiratory flow (from 306.7 ± 123.2 to 359.8 ± 154.1 ml s(-1); P = 0.0002) and in inspiratory volume (from 346.1 ± 128.1 to 414.9 ± 171.2 ml; P = 0.02) without differences in thoraco-abdominal efforts and inspiratory time. These responses were observed in the absence of arousals and ceased immediately after TMS interruption. Transcranial magnetic stimulation-induced cortical and/or autonomic arousal was observed in 30.2% of all series of stimulation. Consecutive twitch TMS of submental muscles may lead to arousals in a minority of patients but can be applied on consecutive respiratory cycles during sleep and can significantly improve maximal inspiratory flow and inspiratory volume of flow-limited cycles.

TMS assessed cortical representation scales with stimulation intensity and muscle activation

Facilitation of ipsilateral motor pathways during recovery from hemiplegia in two adolescent patients

P 160. The “dormant potential” of the non-dominant hemisphere: In teremispheric a symmetry of cortial plasticity

Delivering transcranial magnetic brain stimulation over the motor cortex during motor imagination leads to enhanced motor output, which is selective for the muscles primarily involved in the imagined movement. This novel protocol may be useful to enhance function after damage to the motor system, such as after stroke. Several paired stimulation paradigms are known to induce plasticity in the motor cortex, reflected by changes in the motor evoked potential (MEP) following the paired stimulation. Motor imagery (MI) is capable of activating the motor system and affecting cortical excitability. We hypothesized that it might be possible to use MI in conjunction with transcranial magnetic stimulation (TMS) to induce plasticity in the human motor system. TMS was delivered to the motor cortex of healthy human subjects, and baseline MEPs recorded from forearm flexor, forearm extensor and intrinsic hand muscles. Subjects were then asked to imagine either wrist flexion or extension movements during TMS delivery (n=90 trials). Immediately after this intervention, MEP measurement was repeated. Control protocols tested the impact of imagination or TMS alone. Flexion imagination with TMS increased MEPs in flexors and an intrinsic hand muscle. Extensor imagination with TMS increased MEPs in extensor muscles only. The control paradigms did not produce significant changes. We conclude that delivering TMS during MI is capable of inducing plastic changes in the motor system. This new protocol may find utility to enhance functional rehabilitation after brain injury.

Background: An essential factor in the validity of motor evoked potential (MEP)s recorded by transcranial magnetic stimulation (TMS) over multiple times is their test-retest reliability which to a large extent depends on the accuracy and competence of the assessor (intra-rater reliability). However, intra-rater reliability is infrequently reported in TMS studies suggesting that this is rarely done. Objectives: This study was conducted to determine the intra-rater within and between-session reliability of a newly trained TMS assessor prior to a main TMS study and report on the methodology used to encourage similar practice. Methods: Fourteen (10 males, 4 females; mean age: 32 ± 5.8 years) participants took part in the study. Motor evoked potentials were elicited from a relaxed, right first dorsal interosseous (FDI) muscle three times (T1, T2 and T3) across two testing sessions at least 48 hours apart. During the first session, MEPs were recorded twice (T1 and T2) within an interval of 20 minutes to determine the within (intra) session reliability of the assessor. During the second session, a single measurement was carried out (T3) which was compared to T1 to determine the inter-session reliability. Results: Repeated measure analysis of variance (ANOVA) did not reveal significant difference in the amplitude of the MEPs obtained across the three time periods (P = 0.196) demonstrating agreement in the MEPs and hence the reliability of the assessor. Additionally, the intraclass correlation coefficient (ICC) between T1 and T2; and T1 and T3 were 0.952 (P < 0.001) and 0.833 (P = 0.001) respectively further indicating the within and between sessions reliability of the assessor. Conclusions: The agreement between the three measured MEPs amplitude and the significant ICC demonstrates the reliability of the assessor in this study to use TMS for research. We suggest that the intra-rater reliability of new TMS operators should be established using the methodology in this report prior to main TMS studies.

Prestimulus cortical EEG oscillations can predict the excitability of the primary motor cortex

Transcranial magnetic stimulation (TMS) can induce motor evoked potentials (MEPs). In TMS applications, near-threshold stimulation intensities (SIs) are often used for characterizing corticospinal excitability using MEPs. We aimed to characterize the individual near-threshold recruitment of MEPs and to test the assumptions related to selection of the suprathreshold SI. We utilized MEP data from a right-hand muscle induced at variable SIs. The single-pulse TMS (spTMS) data from previous studies (27 healthy volunteers), as well as data from new measurements (10 healthy volunteers) that included also MEPs modulated by paired-pulse TMS (ppTMS), were included. The probability of MEP (pMEP) was represented with individually fitted cumulative distribution function (CDF) with two parameters: resting motor threshold (rMT) and spread relative to rMT. MEPs were recorded with 110% and 120% of rMT as well as with Mills-Nithi upper threshold (UT). The individual near-threshold characteristics varied with CDF parameters: the rMT and the relative spread (median: 0.052). The rMT was lower with ppTMS than with spTMS (p < 0.001), while the relative spread remained similar (p = 0.812). At suprathreshold SIs, the probability of MEP was similar between UT and 110% of rMT (pMEP > 0.88), and higher for 120% of rMT (pMEP > 0.98). The individual near-threshold characteristics determine how probably MEPs are produced at common suprathreshold SIs. At the population level, the used SIs UT and 110% of rMT produced MEPs at similar probability. The individual variability in the relative spread parameter was large; therefore, the method of determining the proper suprathreshold SI for TMS applications is of crucial importance.

Introduction: It has been shown from invasive epidural recordings that in transcranial magnetic stimulation (TMS) a current in the brain flowing from a posterior to an anterior (p.a.) direction mainly evokes I1, I2 and I3 waves whereas a current flowing from an anterior to a posterior direction mainly evokes I3 waves. This leads to the hypotheses that in p.a. current direction the motor threshold (MT) is lower, motor evoked potentials (MEPs) are higher and latency is shorter than in a.p. direction. The aim of this study was to re-evaluate the inconsistent results in literature by means of a stimulation technique that enabled us to change the current direction without turning the coil. Methods: We investigated n=23 healthy subjects (female: n=12; mean age: 26.2±1.9 years). We recorded the MT, MEP amplitude to target 400µV (SI400µV), MT adapted IO curves and maximum stimulator output (MSO) adapted IO curves in a.p. and p.a. current direction (monophasic waveform) with the P-Stim 160 stimulator (Mag and More, Germany). Results: MT was significantly lower (p=0.003), MEP amplitudes (SI400µV) were significantly higher (p<0.001) and latencies significantly shorter (p<0.001) in p.a. current direction. RmANOVA revealed a significant influence of current direction in MSO adapted IO curves on both, MEP amplitude and latency. We observed a significant influence of current direction on latencies in MT adapted recording of IO-curves but not on MEP amplitudes. Discussion: Our results consistently demonstrate for the first time a significant influence of current direction on MT, MEP amplitude and latency at fixed stimulus intensities as well as in IO curves due to the hypotheses generated from the specific I-wave pattern. The high consistency of the results when changing the current direction without altering coil position offers the opportunity of I wave specific evaluation and stimulation in TMS.

Transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1), elicits motor-evoked potentials (MEPs) in contralateral limb muscles which are valuable indicators of corticospinal excitability (CSE) at the time of stimulation. So far, most studies have used single-coil TMS over one M1, yielding MEPs in muscles of a single limb—usually the hand. However, tracking CSE in the two hands simultaneously would be useful in many contexts. We recently showed that, in the resting state, double-coil stimulation of the two M1 with a 1 ms inter-pulse interval (double-coil1 ms TMS) elicits MEPs in both hands that are comparable to MEPs obtained using single-coil TMS. To further evaluate this new technique, we considered the MEPs elicited by double-coil1 ms TMS in an instructed-delay choice reaction time task where a prepared response has to be withheld until an imperative signal is displayed. Single-coil TMS studies have repetitively shown that in this type of task, the motor system is transiently inhibited during the delay period, as evident from the broad suppression of MEP amplitudes. Here, we aimed at investigating whether a comparable inhibitory effect can be observed with MEPs elicited using double-coil1 ms TMS. To do so, we compared the amplitude as well as the coefficient of variation (CV) of MEPs produced by double-coil1 ms or single-coil TMS during action preparation. We observed that MEPs were suppressed (smaller amplitude) and often less variable (smaller CV) during the delay period compared to baseline. Importantly, these effects were equivalent whether single-coil or double-coil1 ms TMS was used. This suggests that double-coil1 ms TMS is a reliable tool to assess CSE, not only when subjects are at rest, but also when they are involved in a task, opening new research horizons for scientists interested in the corticospinal correlates of human behavior.

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.

Acute muscle pain alters corticomotor output of the affected muscle stronger than a synergistic, ipsilateral muscle

ObjectivesTo explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on motor function and cortical excitability in stroke patients with different motor evoked potential (MEP) status.MethodsA total of 80 stroke patients were enrolled in this randomized controlled trial and divided into two groups according to MEP status (− or +) of lesioned hemisphere. Then, each group was randomly assigned to receive either active or sham LF-rTMS. In addition to conventional rehabilitation, all participants received 20 sessions of rTMS at 1 Hz frequency through the active or the sham coil over 4 weeks. Fugl-Meyer Assessment (FMA), National Institutes of Health Stroke Scale (NIHSS), Shoulder Abduction Finger Extension (SAFE) and Barthel Index (BI), bilateral resting motor threshold (rMT), amplitude of Motor evoked potential (MEP) and Central Motor Conduction Time (CMCT), and Interhemispheric asymmetry (IHA) were blindly assessed at baseline, 4 weeks and 8 weeks after treatment, respectively.ResultsAt 4 weeks after intervention, FMA and NIHSS changed scores in 1 Hz MEP(+) group were significantly higher than those in the other three groups (p < 0.001). After receiving 1 Hz rTMS, stroke patients with MEP(+) showed significant changes in their bilateral cortical excitability (p < 0.05). At 8 weeks after intervention, 1 Hz MEP(+) group experienced higher changes in NIHSS, FMA, SAFE, and BI scores than other groups (p < 0.001). Furthermore, 1 Hz rTMS intervention could decrease unaffected cortical excitability and enhance affected cortical excitability of stroke patients with MEP(+) (p < 0.05). The correlation analysis revealed that FMA motor change score was associated with decreased unaffected MEP amplitude (r = −0.401, p = 0.010) and decreased affected rMT (r = −0.584, p < 0.001) from baseline, which was only observed in the MEP(+) group.ConclusionThe effects of LF-rTMS on motor recovery and cortical excitability were more effective in stroke patients with MEP than those with no MEP.

Motor evoked potentials (MEPs) induced through transcranial magnetic stimulation (TMS) are susceptible to several sources of variability including gender, hand dominance, and upper extremity length. Conflicting evidence on the relationship between MEPs and subject characteristics has been reported. The purposes of this study were to determine if MEPs are different between genders and between right- and left-hand dominant subjects, and to determine if MEPs are correlated with upper extremity length. Using a case-control design, we recorded MEPs from 45 healthy subjects (age 21.6 ± 2.0 years; 24 females, 21 males) with a MagStim200 stimulating coil positioned over the primary motor cortex. Evoked responses were recorded by surface EMG electrodes from the abductor pollicis brevis, abductor digiti minimi and first dorsal interosseous muscles contralateral to the site of TMS. Evoked responses were analyzed to determine motor thresholds, latencies and amplitudes. Central motor conduction time (CMCT) was estimated from MEP, M response, and F wave latencies. Gender and hand dominance did not significantly influence thresholds, MEP amplitudes, or CMCT (P > .05). MEP latencies were moderately correlated with upper extremity length (R = .62 right median, R = .50 left median, R = .45 right ulnar, R = .51 left ulnar MEP latency, P < .01). An ANCOVA using upper extremity length as the covariate demonstrated no significant differences between genders (Wilk's λ = .89, F = 2.45, P = .10). After adjusting MEP latencies to upper limb length, no significant differences were observed between dominant and non-dominant limbs (F = .002, P = .97 median, and F = .03, P = .56 ulnar) nor between genders (F = 2.7, P = .11 median; F = .05, P = .82 ulnar). Variability in MEP latencies between genders was due to differences in upper extremity length. Adjusting MEP latencies to upper limb length is recommended for more accurate comparison and meaningful interpretation between subjects. Hand dominance and gender do not significantly influence motor thresholds, MEP amplitude, or CMCT.