Transcranial Magnetic Stimulation Of Motor Cortex Research Articles

Transcranial magnetic stimulation mapping of the motor cortex: comparison of five estimation algorithms.

There are currently five different kinds of transcranial magnetic stimulation (TMS) motor mapping algorithms available, from ordinary point-based algorithms to advanced field-based algorithms. However, there have been only a limited number of comparison studies conducted, and they have not yet examined all of the currently available algorithms. This deficiency impedes the judicious selection of algorithms for application in both clinical and basic neuroscience, and hinders the potential promotion of a potential superior algorithm. Considering the influence of algorithm complexity, further investigation is needed to examine the differences between fMRI peaks and TMS cortical hotspots that were identified previously. Twelve healthy participants underwent TMS motor mapping and a finger-tapping task during fMRI. The motor cortex TMS mapping results were estimated by five algorithms, and fMRI activation results were obtained. For each algorithm, the prediction error was defined as the distance between the measured scalp hotspot and optimized coil position, which was determined by the maximum electric field strength in the estimated motor cortex. Additionally, the study identified the minimum number of stimuli required for stable mapping. Finally, the location difference between the TMS mapping cortical hotspot and the fMRI activation peak was analyzed. The projection yielded the lowest prediction error (5.27 ± 4.24 mm) among the point-based algorithms and the association algorithm yielded the lowest (6.66 ± 3.48 mm) among field-based estimation algorithms. The projection algorithm required fewer stimuli, possibly resulting from its suitability for the grid-based mapping data collection method. The TMS cortical hotspots from all algorithms consistently deviated from the fMRI activation peak (20.52 ± 8.46 mm for five algorithms). The association algorithm might be a superior choice for clinical applications and basic neuroscience research, due to its lower prediction error and higher estimation sensitivity in the deep cortical structure, especially for the sulcus. It also has potential applicability in various other TMS domains, including language area mapping and more. Otherwise, our results provide further evidence that TMS motor mapping intrinsically differs from fMRI motor mapping.

Evoked EEG Responses to TMS Targeting Regions Outside the Primary Motor Cortex and Their Test–Retest Reliability

Transcranial magnetic stimulation (TMS)–evoked electroencephalography (EEG) potentials (TEPs) provide unique insights into cortical excitability and connectivity. However, confounding EEG signals from auditory and somatosensory co-stimulation complicate TEP interpretation. Our optimized sham procedure established with TMS of primary motor cortex (Gordon in JAMA 245:118708, 2021) differentiates direct cortical EEG responses to TMS from those caused by peripheral sensory inputs. Using this approach, this study aimed to investigate TEPs and their test–retest reliability when targeting regions outside the primary motor cortex, specifically the left angular gyrus, supplementary motor area, and medial prefrontal cortex. We conducted three identical TMS–EEG sessions one week apart involving 24 healthy participants. In each session, we targeted the three areas separately using a figure-of-eight TMS coil for active TMS, while a second coil away from the head produced auditory input for sham TMS. Masking noise and electric scalp stimulation were applied in both conditions to achieve matched EEG responses to peripheral sensory inputs. High test–retest reliability was observed in both conditions. However, reliability declined for the ‘cleaned’ TEPs, resulting from the subtraction of evoked EEG response to the sham TMS from those to the active, particularly for latencies > 100 ms following the TMS pulse. Significant EEG differences were found between active and sham TMS at latencies < 90 ms for all targeted areas, exhibiting distinct spatiotemporal characteristics specific to each target. In conclusion, our optimized sham procedure effectively reveals EEG responses to direct cortical activation by TMS in brain areas outside primary motor cortex. Moreover, we demonstrate the impact of peripheral sensory inputs on test–retest reliability of TMS-EEG responses.

Corticospinal excitability is highest at the early rising phase of sensorimotor µ-rhythm

Alpha oscillations are thought to reflect alternating cortical states of excitation and inhibition. Studies of perceptual thresholds and evoked potentials have shown the scalp EEG negative phase of the oscillation to correspond to a short-lasting low-threshold and high-excitability state of underlying visual, somatosensory, and primary motor cortex. The negative peak of the oscillation is assumed to correspond to the state of highest excitability based on biophysical considerations and considerable effort has been made to improve the extraction of a predictive signal by individually optimizing EEG montages. Here, we investigate whether it is the negative peak of sensorimotor µ-rhythm that corresponds to the highest corticospinal excitability, and whether this is consistent between individuals.In 52 adult participants, a standard 5-channel surface Laplacian EEG montage was used to extract sensorimotor µ-rhythm during transcranial magnetic stimulation (TMS) of primary motor cortex. Post-hoc trials were sorted from 800 TMS-evoked motor potentials (MEPs) according to the pre-stimulus EEG (estimated instantaneous phase) and MEP amplitude (as an index of corticospinal excitability). Different preprocessing transformations designed to improve the accuracy by which µ-alpha phase predicts excitability were also tested.By fitting a sinusoid to the MEP amplitudes, sorted according to pre-stimulus EEG-phase, we found that excitability was highest during the early rising phase, at a significant delay with respect to the negative peak by on average 45° or 10 ms. The individual phase of highest excitability was consistent across study participants and unaffected by two different EEG-cleaning methods that utilize 64 channels to improve signal quality by compensating for individual noise level and channel covariance. Personalized transformations of the montage did not yield better prediction of excitability from µ-alpha phase.The relationship between instantaneous phase of a brain oscillation and fluctuating cortical excitability appears to be more complex than previously hypothesized. In TMS of motor cortex, a standard surface Laplacian 5-channel EEG montage is effective in extracting a predictive signal and the phase corresponding to the highest excitability appears to be consistent between individuals. This is an encouraging result with respect to the clinical potential of therapeutic personalized brain interventions in the motor system. However, it remains to be investigated, whether similar results can be obtained for other brain areas and brain oscillations targeted with EEG and TMS.

Resting-state functional connectivity predicts motor cortex stimulation-dependent pain relief in fibromyalgia syndrome patients

MRI-based resting-state functional connectivity (rsFC) has been shown to predict response to pharmacological and non-pharmacological treatments for chronic pain, but not yet for motor cortex transcranial magnetic stimulation (M1-rTMS). Twenty-seven fibromyalgia syndrome (FMS) patients participated in this double-blind, crossover, and sham-controlled study. Ten daily treatments of 10 Hz M1-rTMS were given over 2 weeks. Before treatment series, patients underwent resting-state fMRI and clinical pain evaluation. Significant pain reduction occurred following active, but not sham, M1-rTMS. The following rsFC patterns predicted reductions in clinical pain intensity after the active treatment: weaker rsFC of the default-mode network with the middle frontal gyrus (r = 0.76, p < 0.001), the executive control network with the rostro-medial prefrontal cortex (r = 0.80, p < 0.001), the thalamus with the middle frontal gyrus (r = 0.82, p < 0.001), and the pregenual anterior cingulate cortex with the inferior parietal lobule (r = 0.79, p < 0.001); and stronger rsFC of the anterior insula with the angular gyrus (r = − 0.81, p < 0.001). The above regions process the attentional and emotional aspects of pain intensity; serve as components of the resting-state networks; are modulated by rTMS; and are altered in FMS. Therefore, we suggest that in FMS, the weaker pre-existing interplay between pain-related brain regions and networks, the larger the pain relief resulting from M1-rTMS.

Repetitive transcranial magnetic stimulation of the primary motor cortex in stroke survivors-more than motor rehabilitation: A mini-review.

Stroke is a leading cause of morbidity and mortality among elderly populations worldwide. During the early phase of stroke, restoring blood circulation is of utmost importance to protect neurons from further injury. Once the initial condition is stabilized, various rehabilitation techniques can be applied to help stroke survivors gradually regain their affected functions. Among these techniques, transcranial magnetic stimulation (TMS) has emerged as a novel method to assess and modulate cortical excitability non-invasively and aid stroke survivors in the rehabilitation process. Different cortical regions have been targeted using TMS based on the underlying pathology and distorted function. Despite the lack of a standard operational procedure, repetitive TMS (rTMS) of the primary motor cortex (M1) is considered a promising intervention for post-stroke motor rehabilitation. However, apart from the motor response, mounting evidence suggests that M1 stimulation can be employed to treat other symptoms such as dysphagia, speech impairments, central post-stroke pain, depression, and cognitive dysfunction. In this mini-review, we summarize the therapeutic uses of rTMS stimulation over M1 in stroke survivors and discuss the potential mechanistic rationale behind it.

µ-rhythm phase from somatosensory but not motor cortex correlates with corticospinal excitability in EEG-triggered TMS

BackgroundSensorimotor µ-rhythm phase is correlated with corticospinal excitability. Transcranial magnetic stimulation (TMS) of motor cortex results in larger motor evoked potentials (MEPs) during the negative peak of the EEG oscillation as extracted with a surface Laplacian. However, the anatomical source of the relevant oscillation is not clear and demonstration of the relationship is sensitive to the choice of EEG montage. Objective/hypothesisHere, we compared two EEG montages preferentially sensitive to oscillations originating from the crown of precentral gyrus (dorsal premotor cortex) vs. postcentral gyrus (secondary somatosensory cortex). We hypothesized that the EEG signal from precentral gyrus would correlate more strongly with MEP amplitude, given that the corticospinal neurons are located in the anterior wall of the sulcus and the corticospinal tract has input from premotor cortex. New methodReal-time EEG-triggered TMS of motor cortex was applied in 6 different conditions in randomly interleaved order, 3 phase conditions (positive peak, negative peak, random phase of the ongoing µ-oscillation), and each phase condition for 2 different EEG montages corresponding to oscillations preferentially originating in precentral gyrus (premotor cortex) vs. postcentral gyrus (somatosensory cortex), extracted using FCC3h vs. C3 centered EEG montages. ResultsThe negative vs. positive peak of sensorimotor µ-rhythm as extracted from the C3 montage (postcentral gyrus, somatosensory cortex) correlated with states of high vs. low corticospinal excitability (p < 0.001), replicating previous findings. However, no significant correlation was found for sensorimotor µ-rhythm as extracted from the neighboring FCC3 montage (precentral gyrus, premotor cortex). This implies that EEG-signals from the somatosensory cortex are better predictors of corticospinal excitability than EEG-signals from the motor areas. ConclusionsThe extraction of a brain oscillation whose phase corresponds to corticospinal excitability is highly sensitive to the selected EEG montage and the location of the EEG sensors on the scalp. Here, the cortical source of EEG oscillations predicting response amplitude does not correspond to the cortical target of the stimulation, indicating that even in this simple case, a specific neuronal pathway from somatosensory cortex to primary motor cortex is involved.

Task- and Intensity-Dependent Modulation of Arm-Trunk Neural Interactions in the Corticospinal Pathway in Humans.

Most human movements require coordinated activation of multiple muscles. Although many studies reported associations between arm, leg, and trunk muscles during functional tasks, their neural interaction mechanisms still remain unclear. Therefore, the aim of our study was to investigate arm-trunk or arm-leg neural interactions in the corticospinal tract during different arm muscle contractions. Specifically, we examined corticospinal excitability of the erector spinae (ES; trunk extensor), rectus abdominis (RA; trunk flexor), and tibialis anterior (TA; leg) muscles while participants exerted: (1) wrist flexion and (2) wrist extension isometric contraction at various contraction intensity levels ranging from rest to 50% of maximal voluntary contraction (MVC) effort. Corticospinal excitability was assessed using motor evoked potentials (MEPs) elicited through motor cortex transcranial magnetic stimulation (TMS). Results showed that ES MEPs were facilitated even at low contractions (>5% MVC) during wrist flexion and extension, while stronger contractions (>25% MVC) were required to facilitate RA MEPs. The extent of facilitation of ES MEPs depended on contraction intensity of wrist extension, but not flexion. Moreover, TA MEPs were facilitated at low contractions (>5% MVC) during wrist flexion and extension, but contraction intensity dependence was only shown during stronger wrist extension contractions (>25% MVC). In conclusion, trunk extensor corticospinal excitability seems to depend on the task and the intensity of arm contraction, while this is not true for trunk flexor and leg muscles. Our study therefore demonstrated task- and intensity-dependent neural interactions of arm-trunk connections, which may underlie anatomic and/or functional substrates of these muscle pairs.

Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation

TAK-653 is a novel α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-positive allosteric modulator being developed as a potential therapeutic for major depressive disorder (MDD). Currently, there are no translational biomarkers that evaluate physiological responses to the activation of glutamatergic brain circuits available. Here, we tested whether noninvasive neurostimulation, specifically single-pulse or paired-pulse motor cortex transcranial magnetic stimulation (spTMS and ppTMS, respectively), coupled with measures of evoked motor response captures the pharmacodynamic effects of TAK-653 in rats and healthy humans. In the rat study, five escalating TAK-653 doses (0.1–50 mg/kg) or vehicle were administered to 31 adult male rats, while measures of cortical excitability were obtained by spTMS coupled with mechanomyography. Twenty additional rats were used to measure brain and plasma TAK-653 concentrations. The human study was conducted in 24 healthy volunteers (23 males, 1 female) to assess the impact on cortical excitability of 0.5 and 6 mg TAK-653 compared with placebo, measured by spTMS and ppTMS coupled with electromyography in a double-blind crossover design. Plasma TAK-653 levels were also measured. TAK-653 increased both the mechanomyographic response to spTMS in rats and the amplitude of motor-evoked potentials in humans at doses yielding similar plasma concentrations. TAK-653 did not affect resting motor threshold or paired-pulse responses in humans. This is the first report of a translational functional biomarker for AMPA receptor potentiation and indicates that TMS may be a useful translational platform to assess the pharmacodynamic profile of glutamate receptor modulators.

Non-invasive brain stimulation as a tool to decrease chronic pain in current opiate users: A parametric evaluation of two promising cortical targets

BackgroundPoorly controlled chronic pain can lead to non-prescription use of opiates, which is a growing crisis in our communities. Transcranial magnetic stimulation (TMS) is a non-invasive therapeutic tool which has emerged as a potential treatment option for these patients. It is still unclear, however, if the dorsolateral prefrontal cortex (DLPFC) or the motor cortex (MC) is a more effective treatment location. The purpose of this study was to directly compare the effects of DLPFC versus MC TMS on pain severity and the urge to use opiates among chronic pain patients. MethodsTwenty-two individuals with chronic pain currently using prescription opiates were randomized to receive 10, 3000 pulse sessions of 10 Hz repetitive TMS (rTMS) to the left DLPFC (110% resting motor threshold) or left MC (90% resting motor threshold). Multivariate linear models were used to evaluate the effect of TMS on pain and opiate use, including items from the Brief Pain Inventory (BPI) as well as subjective ratings of pain, distress, and the urge for opiates. ResultsTwenty participants (91%) completed all 10 treatment sessions and follow up visits. There was a main effect of stimulation site (F7,210 = 3.742, p = 0.001), wherein MC stimulation decreased pain interference significantly more than DLPFC stimulation (F1,216 = 8.447, p = 0.004). While both sites had comparable effect sizes on stress, pain, and discomfort, MC stimulation had larger effects on pain interference (Cohen’s d: 0.7) and urge to use opiates (Cohen’s d: 0.5) than DLPFC stimulation. ConclusionThese data suggest that the MC may be a promising target for decreasing opiate dependence and pain interference among chronic pain patients.

Triad TMS of Human Motor Cortex

To study cortical excitability changes induced by external stimulation with a certain rhythm, we developed a new method using motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex. In this method, three conditioning TMS with the intensity below the motor threshold are given prior to the supra-threshold test stimulus with the four TMSs were separated by a certain interval (triad-conditioning stimulation: TCS). In healthy volunteers, MEP facilitation was elicited at an interval of 25ms, whereas TCSs with other intervals induced no facilitation. This frequency-dependent facilitation may reflect some intrinsic rhythm of M1 (25ms, i.e. 40Hz). In cortical myoclonus, the facilitation at 25ms was gone whereas facilitation was elicited by triad-conditioning stimulus at 40ms (25Hz), which is consistent with a previously reported abnormal beta rhythm in cortical myoclonus reported previously. Facilitation at 25ms was evoked in neither Parkinson's disease nor in amyotrophic lateral sclerosis. With TCS, we were able to investigate the intrinsic rhythmic activity of M1 and its changes in neurological disorders.

Unilateral movement preparation causes task-specific modulation of TMS responses in the passive, opposite limb.

Activity in the primary motor cortices of both hemispheres increases during unilateral movement preparation, but the functional role of ipsilateral motor cortex activity is unknown. Ipsilateral motor cortical activity could represent subliminal 'motor planning' for the passive limb. Alternatively, it could represent the state of the active limb, to support coordination between the limbs should a bimanual movement be required. Here we assessed how preparation of forces toward different directions, with the left wrist, alters evoked responses to transcranial magnetic stimulation of left motor cortex. Preparation of a unilateral movement caused excitability increases in ipsilateral motor cortex that reflected forces produced with the active limb in an intrinsic (body-centred), rather than an extrinsic (world-centred), coordinate system. These results suggest that ipsilateral motor cortical activity prior to unilateral action reflects the state of the active limb, rather than subliminal motor planning for the passive limb. Corticospinal excitability is modulated for muscles on both sides of the body during unilateral movement preparation. For the effector, there is a progressive increase in excitability, and a shift in direction of muscle twitches evoked by transcranial magnetic stimulation (TMS) toward the impending movement. By contrast, the directional characteristics of excitability changes in the opposite (passive) limb have not been fully characterized. Here we assessed how preparation of voluntary forces towards four spatially distinct visual targets with the left wrist alters muscle twitches and motor-evoked potentials (MEPs) elicited by TMS of left motor cortex. MEPs were facilitated significantly more in muscles homologous to agonist rather than antagonist muscles in the active limb, from 120ms prior to voluntary EMG onset. Thus, unilateral motor preparation has a directionally specific influence on pathways projecting to the opposite limb that corresponds to the active muscles rather than the direction of movement in space. The directions of TMS-evoked twitches also deviated toward the impending force direction of the active limb, according to muscle-based coordinates, following the onset of voluntary EMG. The data indicate that preparation of a unilateral movement increases task-dependent excitability in ipsilateral motor cortex, or its downstream projections, that reflects the forces applied by the active limb in an intrinsic (body-centred), rather than an extrinsic (world-centred), coordinate system. The results suggest that ipsilateral motor cortical activity prior to unilateral action reflects the state of the active limb, rather than subliminal motor planning for the passive limb.

Cortical Excitability and Interhemispheric Connectivity in Early Relapsing-Remitting Multiple Sclerosis Studied With TMS-EEG.

Evoked potentials (EPs) are well established in clinical practice for diagnosis and prognosis in multiple sclerosis (MS). However, their value is limited to the assessment of their respective functional systems. Here, we used transcranial magnetic stimulation (TMS) coupled with electroencephalography (TMS-EEG) to investigate cortical excitability and spatiotemporal dynamics of TMS-evoked neural activity in MS patients. Thirteen patients with early relapsing–remitting MS (RRMS) with a median Expanded Disability Status Scale (EDSS) of 1.0 (range 0–2.5) and 16 age- and gender-matched healthy controls received single-pulse TMS of left and right primary motor cortex (L-M1 and R-M1), respectively. Resting motor threshold for L-M1 and R-M1 was increased in MS patients. Latencies and amplitudes of N45, P70, N100, P180, and N280 TMS-evoked EEG potentials (TEPs) were not different between groups, except a significantly increased amplitude of the N280 TEP in the MS group, both for L-M1 and R-M1 stimulation. Interhemispheric signal propagation (ISP), estimated from the area under the curve of TEPs in the non-stimulated vs. stimulated M1, also did not differ between groups. In summary, findings show that ISP and TEPs were preserved in early-stage RRMS, except for an exaggerated N280 amplitude. Our findings indicate that TMS-EEG is feasible in testing excitability and connectivity in cortical neural networks in MS patients, complementary to conventional EPs. However, relevance and pathophysiological correlates of the enhanced N280 will need further study.

Shourei Prize 2. Utility of TMS for neuroscience of speech

Transcranial magnetic stimulation (TMS) has widely been accepted as a useful method of non-invasive brain stimulation in neuroscience. Compared with neuroimaging and intraoperative mapping, the number of speech experiments using TMS has, however, still been small. Here, an introduction to recent TMS studies that explored speech perception and imitation is presented. Single-pulse TMS of the primary motor cortex (M1) showed a speech specific and topographically specific increase of excitability in the M1 lip area during speech perception. This may be explainable by the motor theory of speech perception and reflect the function of mirror neurons. The updated speech model is constituted of dual speech processing streams ; dorsal and ventral streams. A paired-coil stimulation demonstrates an increase in the effective connectivity from brain regions in the dorsal stream to the M1 lip area. Application of repetitive TMS (rTMS) to parts of the dorsal stream can modulate performance of phonological recognition, whereas semantic perception is altered by rTMS over the ventral pathway. Speech imitation combined with facilitatory rTMS over the left posterior inferior frontal gyrus can enhance accuracy of imitation performance. In summary, TMS is an innovative tool to understand the brain network of speech processing on perception and imitation.

Association of the N100 TMS-evoked potential with attentional processes: A motor cortex TMS–EEG study

The most thoroughly studied transcranial magnetic stimulation (TMS)-evoked electroencephalogram (EEG) potential (TEP), N100, is often defined as a measure of cortical inhibition.We explored the association of the N100 amplitude with attention in 51 young healthy adults. Navigated TMS with simultaneous EEG registering was applied over the left primary motor cortex at the intensity of 110% of the resting motor threshold. Attention was assessed with the Paced Auditory Serial Addition Test (PASAT).We found a negative Pearson correlation (p = .023, r = −0.317) between the left centroparietal N100 amplitude and the PASAT score. Of the participants, the 17 with the highest PASAT scores and 17 with the lowes scores were selected for further analysis, in which a significant between-group difference in the left centroparietal N100 was found (p = .017). The topographic specificity of this finding was further confirmed with linear mixed model (LMM) analysis, in which significant differences were detected in the N100 amplitude; most prominently in the left centroparietal region (p = .001). A smaller N100 amplitude was associated with better performance in the attention task.Our findings suggest that the GABA-B-ergic TEP N100 is associated with attentional processes and thus represents cortical inhibition beyond motor inhibition.

Primary Motor Cortex Excitability in Karate Athletes: A Transcranial Magnetic Stimulation Study.

Purpose: The mechanisms involved in the coordination of muscle activity are not completely known: to investigate adaptive changes in human motor cortex Transcranial magnetic stimulation (TMS) was often used. The sport models are frequently used to study how the training may affect the corticospinal system excitability: Karate represents a valuable sport model for this kind of investigations for its high levels of coordination required to athletes. This study was aimed at examining possible changes in the resting motor threshold (rMT) and in the corticospinal response in karate athletes, and at determining whether athletes are characterized by a specific value of rMT.Methods: We recruited 25 right-handed young karate athletes and 25 matched non-athletes. TMS was applied to primary motor cortex (M1). Motor evoked potential (MEP) were recorded by two electrodes placed above the first dorsal interosseous (FDI) muscle. We considered MEP latencies and amplitudes at rMT, 110% of rMT, and 120% of rMT.Results: The two groups were similar for age (p > 0.05), height (p > 0.05) and body mass (p > 0.05). The TMS had a 70-mm figure-of-eight coil and a maximum output of 2.2 T, placed over the left motor cortex. During the stimulation, a mechanical arm kept the coil tangential to the scalp, with the handle at 45° respect to the midline. The SofTaxic navigator system (E.M.S. Italy, www.emsmedical.net) was used in order to correctly identifying and repeating the stimulation for every subject. Compared to non-athletes, athletes showed a lower resting motor threshold (p < 0.001). Furthermore, athletes had a lower MEP latency (p < 0.001) and a higher MEP amplitude (p < 0.001) compared to non-athletes. Moreover, a ROC curve for rMT was found significant (area: 0.907; sensitivity 84%, specificity 76%).Conclusions: As the main finding, the present study showed significant differences in cortical excitability between athletes and non-athletes. The training can improve cortical excitability inducing athletes' modifications, as demonstrated in rMT and MEP values. These finding support the hypothesis that the sport practice determines specific brain organizations in relationship with the sport challenges.

Development of cortical motor circuits between childhood and adulthood: A navigated TMS-HdEEG study.

Motor functions improve during childhood and adolescence, but little is still known about the development of cortical motor circuits during early life. To elucidate the neurophysiological hallmarks of motor cortex development, we investigated the differences in motor cortical excitability and connectivity between healthy children, adolescents, and adults by means of navigated suprathreshold motor cortex transcranial magnetic stimulation (TMS) combined with high-density electroencephalography (EEG). We demonstrated that with development, the excitability of the motor system increases, the TMS-evoked EEG waveform increases in complexity, the magnitude of induced activation decreases, and signal spreading increases. Furthermore, the phase of the oscillatory response to TMS becomes less consistent with age. These changes parallel an improvement in manual dexterity and may reflect developmental changes in functional connectivity. Hum Brain Mapp 38:2599-2615, 2017. © 2017 Wiley Periodicals, Inc.

Transcranial magnetic stimulation as a treatment for functional (psychogenic) upper limb weakness

ObjectiveThere has been a recent resurgence of interest in physical treatments for functional motor disorders (FMD) including Transcranial Magnetic Stimulation (TMS). This pilot study aimed to test the effectiveness of a single session of motor cortex TMS as a treatment for functional upper limb weakness. MethodsTen subjects with a diagnosis of functional upper limb weakness were randomised to immediate (n=7) or delayed (3months) (n=3) TMS treatment. Median age was 35 (range 23–52) and median symptom duration was 2.3years (range 5months – 20years). 46–70 single pulses were applied to the motor cortex at 120–150% motor threshold. We used a verbal protocol designed to standardized the effects of suggestion. Primary outcome measures were self-reported symptom severity, grip strength and tapping frequency immediately after treatment, and symptom severity and disability (SF-12 and Modified Rankin Scale (MRS)) after 3months. ResultsThere was a small significant reduction in symptom severity immediately after treatment, but no improvement in grip strength or tapping frequency and no change in symptom severity, SF-12 or MRS 3months after treatment. Small numbers precluded comparison of immediate treatment with delayed treatment. Four of eight subjects responding to three-month follow-up reported late-onset adverse effects. ConclusionThis pilot study suggests limited benefits for TMS as a one-off non-neuromodulatory treatment for stable chronic outpatients. TMS may still have a role alongside more intensive multidisciplinary therapy input, or in patients with severe deficits where the possibility of normal movement can be hard to demonstrate. Trial registrationNCT02102906

Transcranial Magnetic Stimulation of the Prefrontal Cortex in Awake Nonhuman Primates Evokes a Polysynaptic Neck Muscle Response That Reflects Oculomotor Activity at the Time of Stimulation

Transcranial magnetic stimulation (TMS) has emerged as an important technique in cognitive neuroscience, permitting causal inferences about the contribution of a given brain area to behavior. Despite widespread use, exactly how TMS influences neural activity throughout an interconnected network, and how such influences ultimately change behavior, remain unclear. The oculomotor system of nonhuman primates (NHPs) offers a potential animal model to bridge this gap. Here, based on results suggesting that neck muscle activity provides a sensitive indicator of oculomotor activation, we show that single pulses of TMS over the frontal eye fields (FEFs) in awake NHPs evoked rapid (within ∼25 ms) and fairly consistent (∼50-75% of all trials) expression of a contralateral head-turning synergy. This neck muscle response resembled that evoked by subsaccadic electrical microstimulation of the FEF. Systematic variation in TMS location revealed that this response could also be evoked from the dorsolateral prefrontal cortex (dlPFC). Combining TMS with an oculomotor task revealed state dependency, with TMS evoking larger neck muscle responses when the stimulated area was actively engaged. Together, these results advance the suitability of the NHP oculomotor system as an animal model for TMS. The polysynaptic neck muscle response evoked by TMS of the prefrontal cortex is a quantifiable trial-by-trial reflection of oculomotor activation, comparable to the monosynaptic motor-evoked potential evoked by TMS of primary motor cortex. Our results also speak to a role for both the FEF and dlPFC in head orienting, presumably via subcortical connections with the superior colliculus.

P 5. Motor cortical excitability in psychiatric disorders probed by transcranial magnetic stimulation: A systematic review

Introduction Since many years, transcranial magnetic stimulation (TMS) has been used to probe cortical physiology in awake humans. In particular, single-and paired-pulse TMS-protocols applied to the human motor cortex allowed the exploration of various intracortical inhibitory and facilitatory networks. In psychiatry, TMS offers the possibility to access motor-cortical excitability and to link the findings to possible neurotransmitter alterations with regard to the investigated disorder. However, little is known about general patterns of cortical excitability across psychiatric disorders. Objectives We aimed to review the evidence for impaired cortical excitability in psychiatric disorders using TMS. Methods A systematically literature research for this review was conducted via the internet database PubMed (1985–2012) using predefined search-algorithms. This search offered 684 publications in total. After screening of the abstracts and careful review of the content by two independent researchers with regard to the objectives of this review, a number of 82 publications was considered to be suitable. Results Most studies (n = 20) investigated the effects of TMS in patients with schizophrenia. Remarkably, all major psychiatric disorders were investigated by TMS: dementia (n = 19), attention deficit hyperactivity disorder (n = 13), Tourette syndrome (n = 6), cocaine dependence (n = 5), depression (n = 4), alcohol dependence (n = 3), cannabis-dependence (n = 3), nicotine dependence (n = 2), obsessive compulsive disorder (n = 2), borderline personality disorder (n = 1), bipolar disorder (n = 1), posttraumatic stress disorder (n = 1), altered personality traits (n = 1) and subjects at risk to develop psychosis (n = 1). In general, psychiatric illness can be linked to reduced cortical inhibition and in parts to enhanced cortical facilitation, resulting in a motor-cortex hyperexcitability. Detailed descriptions and exceptions will be presented and discussed at the conference. Conclusion Our results show that motor-cortex TMS is currently not suitable as a general diagnostic tool for psychiatric disorders. The disease state, different phenotypes of the same diseases and the influence of neuroactive medication can be discussed as major confounding factors. While it seems to be possible to hypothetically transmit results from motor-cortex TMS to other cortical and subcortical structures, further investigations are needed to understand the meaning of alterations in motor-cortex excitability in psychiatric disorders.

P 52. Corticospinal activity during the preparation of bimanual and unimanual movements: Investigating the neural mechanisms of bimanual coupling

Previous research has demonstrated that the movements produced by each hand are correlated and have a tendency to converge during bimanual actions, a phenomenon referred to as bimanual coupling. Bimanual coupling appears to depend on excitatory and inhibitory transcallosal circuits although it is not presently clear specifically which circuits contribute to this effect or the stage of motor preparation or execution at which they act. The current study aimed to determine whether corticospinal excitability (CSE) is suppressed during the preparation of unimanual forces and simultaneous bimanual forces where the hands produce unequal forces, compared to the production of forces of equal magnitude with each hand. Single-pulse transcranial magnetic stimulation (TMS) was used to measure CSE during the preparation of bimanual and unimanual pinch forces that were synchronized with an auditory tone. Bimanual coupling was observed across all bimanual conditions and was stronger in equal-force conditions than unequal-force conditions. TMS of either motor cortex significantly expedited forces onsets for both hands, with left motor cortex (M1) TMS producing a greater effect than right M1 TMS. Significantly greater CSE was observed when the primary motor cortex contralateral to the hand preparing a force was stimulated. However, no differences in corticospinal excitability were observed between unimanual and bimanual force conditions or between different bimanual conditions. The present study did not find any support for the hypothesis that suppression of force coupling to produce strictly unimanual forces or bimanual forces of unequal magnitude results in corticospinal inhibition. These results suggest that the inhibition of CSE during the production of unequal bimanual forces does not occur until motor execution [2] . The bimanual coupling dependent modulation of CSE during motor preparation may be confined to specific movement parameters such as movement direction [1] . The strong effect of left M1 TMS on force onset times suggests a role of the left M1 in the control of motor timings.