Lower Resting Motor Threshold Research Articles

Paired-pulse navigated TMS is more effective than single-pulse navigated TMS for mapping upper extremity muscles in brain tumor patients

ObjectiveSingle-pulse navigated transcranial magnetic stimulation (sp-nTMS) is used for presurgical motor mapping in patients with motor-eloquent lesions. However, recently introduced paired-pulse nTMS (pp-nTMS) with biphasic pulses could improve motor mapping. MethodsThirty-four patients (mean age: 56.0 ± 12.7 years, 53.0% high-grade glioma) with motor-eloquent lesions underwent motor mapping of upper extremity representations and nTMS-based tractography of the corticospinal tract (CST) by both sp-nTMS and pp-nTMS with biphasic pulses for the tumor-affected hemisphere before resection. ResultsIn three patients (8.8%), conventional sp-nTMS did not provide motor-positive points, in contrast to pp-nTMS that was capable of generating motor maps in all patients. Good concordance between pp-nTMS and sp-nTMS in the spatial location of motor hotspots and center of gravity (CoG) as well as for CST tracking was observed, with pp-nTMS leading to similar motor map volumes (585.0 ± 667.8 vs. 586.8 ± 204.2 mm3, p = 0.9889) with considerably lower resting motor thresholds (35.0 ± 8.8 vs. 32.8 ± 7.6% of stimulator output, p = 0.0004). ConclusionsPp-nTMS with biphasic pulses may provide motor maps even in highly demanding cases with tumor-affected motor structures or edema, using lower stimulation intensity compared to sp-nTMS. SignificancePp-nTMS with biphasic pulses could replace standardly used sp-nTMS for motor mapping and may be safer due to lower stimulation intensity.

Longer cTMS pulse width switches 1 Hz inhibitory motor cortex rTMS aftereffects to excitation

The motor evoked responses (MEP) to antero-posterior transcranial magnetic stimulation (TMS) have higher motor thresholds and longer latencies in comparison to PA current direction stimulation. Discrepancies extend to the plastic after effects of rTMS. These effects might be due to stimulation of different population of neurones or different segments of the neuron, because of their variable membrane properties. Here we investigate the effect of different pulse widths and phase directions of AP TMS on latencies, thresholds and plastic aftereffects. Using a controllable pulse stimulator TMS (cTMS) on 10 subjects we compared thresholds and MEP AP latencies among TMS pulses with different pulse durations (40 μs, 80 μs and 120 μs) using 0.2 M ratio pulses, and compared the two different pulse directions (0.2, 0.6 and 1.0 M ratios) with 80 μs wide pulses. We then applied 900 pulses of the selected pulse shapes at 1 Hz. As previously published, narrower pulse shapes had longer latencies and higher resting motor thresholds (RMT) while wider pulse shapes showed shorter latencies and lower RMT. Shorter pulse widths rTMS produced inhibition while the wider pulse shape exhibited excitatory after-effects. Unidirectional rTMS pulses produced inhibition, while bidirectional pulses showed inhibition during the stimulation but facilitatory after-effects. We conclude that the neuronal response to rTMS can be tuned by manipulating pulse width and directionality; we gather it might be attributed to the variable membrane properties of different neuronal segments. Pulse width plays a distinctive role already in measuring MT. Here we show that pulse width affects plasticity probably by targeting different segments of neurones.

S151. Assessing lower limb cortical function with threshold tracking transcranial magnetic stimulation

Introduction Transcranial magnetic stimulation (TMS) is a useful, non-invasive tool that can explore the functional integrity of the primary motor cortex and corticomotor pathways. Although the application of TMS has rapidly increased in the last decade using upper limb muscle targets, there remains a relative paucity of lower limb studies. Additionally, the paired-pulse TMS paradigms that have been applied to explore lower limb cortical parameters have shown significant variability in motor evoked potential (MEP) amplitudes, questioning the reliability and clinical utility of this technique. Threshold tracking TMS (TT-TMS) was recently developed to overcome such methodological problems, but this protocol has been limited to upper limb studies. Importantly, the inherent differences in upper and lower limb normal cortical function and the differing pattern of disease in lower limb predominant neurological disorders highlights the need for a more robust understanding of lower limb corticomotoneuronal function. Thus, the aim of the present study was to employ TT-TMS to establish lower limb cortical parameters and to investigate side-to-side differences to determine laterality of normal cortical function. Methods Studies were performed in 40 healthy participants recording from the tibialis anterior muscle bilaterally. Three common coil choices (90 mm circular coil, 70 mm figure-8 coil, 110 mm double cone coil) were explored. Single-pulse TMS, paired-pulse TT-TMS and nerve conduction studies were performed. Results The double cone coil had the greatest efficacy, generating a significantly lower resting motor threshold than the circular (p = 0.04) or figure-8 (p = 0.01) coils. Paired-pulse TT-TMS generated an averaged short interval intracortical inhibition of 11.3 ± 1.2%, with an averaged intracortical facilitation of −8.5 ± 1.1%. Central motor conduction time (CMCT) was 8.9 ± 0. 6 ms.There were no differences between dominant and non-dominant sides for all single (RMT, MEP latency, MEP amplitude, MEP/CMAP ratio, CSP and CMCT) and paired-pulse TT-TMS parameters (peak SICI 1 ms, peak SICI 3 ms, averaged SICI and ICF). Similarly, peripheral measures of nerve function were not significantly different between the dominant and non-dominant hemispheres for all measures tested. Conclusion This study successfully assessed cortical excitability and corticospinal pathways from the lower limbs using TT-TMS, establishing normative data, symmetry of normal cortical function, and validating the double cone coil for future studies. These findings can now be applied to explore further aspects of lower limb physiology and used for the clinical interpretation of motor cortical dysfunction across a range of neurological diseases. Together with previously established upper limb TT-TMS, this study will now inevitably allow for a more comprehensive evaluation of normal neuronal processes and patterns of disease across a larger area of cortical representation.

Developmental profile of motor cortex transcallosal inhibition in children and adolescents.

Transcallosal fibers facilitate interhemispheric networks involved in motor tasks. Despite their clinical relevance, interhemispheric motor control systems have not been completely defined in the developing brain. The objective of this study was to examine the developmental profile of transcallosal inhibition in healthy children and adolescents. Nineteen typically developing right-handed participants were recruited. Two transcranial magnetic stimulation (TMS) paradigms assessed transcallosal inhibition: ipsilateral silent periods (iSP) and paired-pulse interhemispheric inhibition (IHI). TMS was applied to the motor hotspot of the first dorsal interosseous muscle. Resting motor threshold (RMT), iSP latency, duration and suppression strength, and paired-pulse IHI were measured from both hemispheres. The Purdue Pegboard Test assessed unimanual motor function. Hemispheric differences were evident for RMT and iSP latency and suppression strength, where the left hemisphere had a lower RMT, prolonged latency, and greater suppression strength. iSP duration showed hemispheric symmetry. RMT and iSP latency decreased with age, whereas iSP suppression strength increased. Girls showed shorter iSP latency. Children typically displayed IHI, although hemispheric differences were observed. iSP suppression strength was uniquely associated with IHI within individuals. iSP duration correlated with motor performance. TMS can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, sex, and motor performance. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.NEW & NOTEWORTHY Here we demonstrate that transcranial magnetic stimulation can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, handedness, and motor performance. Interestingly, we also demonstrated sex effects, possibly related to the differing developmental profiles of boys and girls. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.

Single and paired pulse transcranial magnetic stimulation in drug naïve epilepsy

Transcranial magnetic stimulation (TMS) measures cortical excitability and is therefore potentially suitable as an additional tool for epilepsy diagnostics and therapy evaluation. In this review we discuss the application of TMS in epilepsy research and systematically analyze single and paired pulse TMS outcomes from 31 drug naïve patient studies. Despite a large variety in used TMS protocols, there was no relation between specific protocol aspects and the occurrence of significant results. Protocols were often not in accordance with latest guidelines and recommendations. Cortical excitability, as measured by TMS, was increased in drug naïve epilepsy patients, being most prominent for generalized epilepsy. Single pulse TMS indicated a trend towards a lower resting motor threshold (rMT) and a prolonged cortical silent period (CSP) for generalized epilepsy, while inconclusive results were found for focal epilepsy. The paired pulse TMS outcomes, short intracortical inhibition (SICI) and long intracortical inhibition (LICI), showed the most consistent significant increase in cortical excitability in generalized and focal epilepsy patients. Future epilepsy research should especially focus on the interstimulus intervals 2 and 5ms for SICI, and 250 and 300ms for LICI. Furthermore, combining TMS with electroencephalography (EEG) may contribute to analysis on an individual patient level.

Motor plasticity after extra-intracranial bypass surgery in occlusive cerebrovascular disease.

To explore plasticity in patients scheduled for extra-intracranial bypass surgery due to unilateral symptomatic occlusive cerebrovascular disease via navigated transcranial magnetic stimulation. In this observational study, patients were allocated to different substudies and examined before and 3 months after operation. (1) Corticospinal excitability was determined via identification of the resting motor threshold. (2) Intracortical inhibition and facilitation were tested by paired pulse transcranial magnetic stimulation. (3) Area of cortical representation of the first dorsal interosseous muscle was identified. (1) Resting motor thresholds were higher in the affected hemispheres with impaired cerebrovascular reserve capacity compared to the unaffected hemispheres (45.7% ± 2.2% compared to 39.2% ± 1.4%, n = 39, p < 0.05). Reduced excitability normalized 3 months after revascularization (51% ± 2.6% → 45% ± 1.9%, n = 21, p < 0.05). (2) In paired pulse paradigms, there was a motor disinhibition in the operated hemispheres. (3) There was a reduction of the cortical representation areas of the first dorsal interosseous muscle (2.3 ± 0.5 cm(2) → 0.9 ± 0.6 cm(2), n = 9, p < 0.05) after operation. Our data demonstrate a reversibly impaired motor cortical function in the chronically ischemic brain. In carefully selected patients, cerebral revascularization leads to improved motor output indicated by a lower resting motor threshold, intracortical disinhibition, and more focused motor cortical representation.

Motor threshold predicts working memory performance in healthy humans.

Cognitive functions, such as working memory, depend on neuronal excitability in a distributed network of cortical regions. It is not known, however, if interindividual differences in cortical excitability are related to differences in working memory performance. In the present transcranial magnetic stimulation study, which included 188 healthy young subjects, we show that participants with lower resting motor threshold, which is related to higher corticospinal excitability, had increased 2-back working memory performance. The findings may help to better understand the link between cortical excitability and cognitive functions and may also have important clinical implications with regard to conditions of altered cortical excitability.

Transcranial magnetic stimulation with a half-sine wave pulse elicits direction-specific effects in human motor cortex

BackgroundTranscranial magnetic stimulation (TMS) commonly uses so-called monophasic pulses where the initial rapidly changing current flow is followed by a critically dampened return current. It has been shown that a monophasic TMS pulse preferentially excites different cortical circuits in the human motor hand area (M1-HAND), if the induced tissue current has a posterior-to-anterior (PA) or anterior-to-posterior (AP) direction. Here we tested whether similar direction-specific effects could be elicited in M1-HAND using TMS pulses with a half-sine wave configuration.ResultsIn 10 young participants, we applied half-sine pulses to the right M1-HAND which elicited PA or AP currents with respect to the orientation of the central sulcus.Measurements of the motor evoked potential (MEP) revealed that PA half-sine stimulation resulted in lower resting motor threshold (RMT) than AP stimulation. When stimulus intensity (SI) was gradually increased as percentage of maximal stimulator output, the stimulus–response curve (SRC) of MEP amplitude showed a leftward shift for PA as opposed to AP half-sine stimulation. Further, MEP latencies were approximately 1 ms shorter for PA relative to AP half-sine stimulation across the entire SI range tested. When adjusting SI to the respective RMT of PA and AP stimulation, the direction-specific differences in MEP latencies persisted, while the gain function of MEP amplitudes was comparable for PA and AP stimulation.ConclusionsUsing half-sine pulse configuration, single-pulse TMS elicits consistent direction-specific effects in M1-HAND that are similar to TMS with monophasic pulses. The longer MEP latency for AP half-sine stimulation suggests that PA and AP half-sine stimulation preferentially activates different sets of cortical neurons that are involved in the generation of different corticospinal descending volleys.

The number of full-sine cycles per pulse influences the efficacy of multicycle transcranial magnetic stimulation

Previous studies have shown that the efficacy of transcranial magnetic stimulation (TMS) to excite corticospinal neurons depends on pulse waveform. In this study, we examined whether the effectiveness of polyphasic TMS can be increased by using a pulse profile that consists of multiple sine cycles. In eight subjects, single-pulse TMS was applied to the left primary motor hand area through a round coil attached to a stimulator device that generated polyphasic pulses consisting of one to six full-sine cycles with a cycle length of 86 μs. In different blocks, we varied the number of sine cycles per pulse and recorded the motor-evoked potential (MEP) from the right first dorsal interosseus muscle. For each stimulus type, we determined resting motor threshold (RMT), stimulus-response curve (SRC), and mean MEP amplitude evoked at maximal stimulator output to assess the efficacy of stimulation. Multicycle pulses were more effective than a single full-sine cycle in exciting corticospinal neurons. TMS with multicycle pulses resulted in lower RMT, larger MEP amplitudes at maximal stimulator output and a steeper slope of the SRC relative to a TMS pulse consisting of a single-sine cycle. The increase in efficacy was already evident when two full-sine cycles were used and did not increase further by adding more cycles to the TMS pulse. Increasing the number of full-sine cycles per pulse can improve the efficacy of TMS to excite corticospinal neurons, but there is no simple linear relationship between the number of cycles and TMS efficacy.

Automatic analysis of single motor unit potentials for the diagnosis of central motor disorders

Previous studies have shown that the efficacy of transcranial magnetic stimulation (TMS) to excite corticospinal neurons depends on pulse waveform.In this study, we examined whether the effectiveness of polyphasic TMS can be increased by using a pulse profile that consists of multiple sine cycles.In eight subjects, single-pulse TMS was applied to the left primary motor hand area through a round coil attached to a stimulator device that generated polyphasic pulses consisting of one to six full-sine cycles with a cycle length of 86 μs. In different blocks, we varied the number of sine cycles per pulse and recorded the motor-evoked potential (MEP) from the right first dorsal interosseus muscle. For each stimulus type, we determined resting motor threshold (RMT), stimulus-response curve (SRC), and mean MEP amplitude evoked at maximal stimulator output to assess the efficacy of stimulation.Multicycle pulses were more effective than a single full-sine cycle in exciting corticospinal neurons. TMS with multicycle pulses resulted in lower RMT, larger MEP amplitudes at maximal stimulator output and a steeper slope of the SRC relative to a TMS pulse consisting of a single-sine cycle. The increase in efficacy was already evident when two full-sine cycles were used and did not increase further by adding more cycles to the TMS pulse.Increasing the number of full-sine cycles per pulse can improve the efficacy of TMS to excite corticospinal neurons, but there is no simple linear relationship between the number of cycles and TMS efficacy.