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Background: Idiopathic normal pressure hydrocephalus (iNPH) is a multifactorial disease presenting with a classical symptom triad of cognitive decline, gait disturbance and urinary incontinence. The symptoms can be alleviated with shunt surgery but the etiology of the symptoms remains unclear. Navigated transcranial magnetic stimulation (nTMS) was applied to characterize corticospinal excitability and cortical motor function before and after shunt surgery in order to elucidate the pathophysiology of iNPH. We also aimed to determine, whether nTMS could be applied as a predictive tool in the pre-surgical work-up of iNPH., Methods: 24 patients with possible or probable iNPH were evaluated at baseline, after cerebrospinal fluid drainage test (TAP test) and three months after shunt surgery (follow-up). Symptom severity was evaluated on an iNPH scale and with clinical tests (walking test, Box & Block test, grooved pegboard). In the nTMS experiments, resting motor threshold (RMT), silent period (SP), input-output curve (IO-curve), repetition suppression (RS) and mapping of cortical representation areas of hand and foot muscles were assessed., Results: After shunt surgery, all patients showed improved performance in gait and upper limb function. The nTMS parameters showed an increase in the RMTs (hand and foot) and the maximum value of the IO-curve increased in subject with a good surgical outcome. The improvement in gait correlated with an increase in the maximum value of the IO-curve. SP, RS and mapping remained unchanged., Conclusion: The excitability of the motor cortex and the corticospinal tract increased in iNPH patients after shunt surgery. A favorable clinical outcome of shunt surgery is associated with a higher ability to re-form and maintain neuronal connectivity., (© 2022. The Author(s).)

Background: Motor mapping with navigated transcranial magnetic stimulation (nTMS) requires defining a "hotspot", a stimulation site consistently producing the highest-amplitude motor-evoked potentials (MEPs). The exact location of the hotspot is difficult to determine, and the spatial extent of high-amplitude MEPs usually remains undefined due to MEP variability and the spread of the TMS-induced electric field (E-field). Therefore, here we aim to define the hotspot as a sub-region of a motor map., New Method: We analyzed MEP amplitude distributions in motor mappings of 30 healthy subjects in two orthogonal directions on the motor cortex. Based on the widths of these distributions, the hotspot extent was estimated as an elliptic area. In addition, E-field distributions induced by motor map edge stimulations were simulated for ten subjects, and the E-field attenuation was analyzed to obtain another estimate for hotspot extent., Results: The median MEP-based hotspot area was 13 mm 2 (95% confidence interval (CI) = [10, 18] mm 2 ). The mean E-field-based hotspot area was 26 mm 2 (95% CI = [13, 38] mm 2 )., Comparison With Existing Methods: In contrast to the conventional hotspot, the new definition considers its spatial extent, indicating the most easily excited area where subsequent nTMS stimuli should be targeted for maximal response. The E-field-based hotspot provides an estimate for the extent of cortical structures where the E-field is close to its maximum., Conclusions: The nTMS hotspot should be considered as an area rather than a single qualitatively defined spot due to MEP variability and E-field spread., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with an unknown etiology. Disturbed corticospinal inhibition of the motor cortex has been reported in iNPH and can be evaluated in a noninvasive and painless manner using navigated transcranial magnetic stimulation (nTMS). This is the first study to characterize the immediate impact of cerebrospinal fluid (CSF) drainage on corticospinal excitability., Methods: Twenty patients with possible or probable iNPH (16 women and 4 men, mean age 74.4 years, range 67-84 years), presenting the classical symptom triad and radiological findings, were evaluated with motor function tests (10-m walk test, Grooved Pegboard and Box & Block test) and nTMS (silent period, SP, resting motor threshold, RMT and input-output curve, IO-curve). Evaluations were performed at baseline and repeated immediately after CSF drainage via lumbar puncture., Results: At baseline, iNPH patients presented shorter SPs (p < 0.001) and lower RMTs (p < 0.001) as compared to normative values. Positive correlation was detected between SP duration and Box & Block test (rho = 0.64, p = 0.002) in iNPH patients. CSF drainage led to an enhancement in gait velocity (p = 0.002) and a steeper IO-curve slope (p = 0.049)., Conclusions: Shorter SPs and lower RMTs in iNPH suggest impaired corticospinal inhibition and corticospinal hyperexcitability. The steeper IO-slope in patients who improve their gait velocity after CSF drainage may indicate a higher recovery potential. Corticospinal excitability correlated with the motor function of the upper limbs implying that the disturbance in motor performance in iNPH extends beyond the classically reported gait impairment.

Motor functions are frequently impaired in Asperger syndrome (AS). In this study, we examined the motor cortex structure and function using navigated transcranial magnetic stimulation (nTMS) and voxel-based morphometry (VBM) and correlated the results with the box and block test (BBT) of manual dexterity and physical activity in eight boys with AS, aged 8-11 years, and their matched controls. With nTMS, we found less focused cortical representation areas of distinct hand muscles in AS. There was hemispheric asymmetry in the motor maps, silent period duration and active MEP latency in the AS group, but not in controls. Exploratory VBM analysis revealed less gray matter in the left postcentral gyrus, especially in the face area, and less white matter in the precentral area in AS as compared to controls. On the contrary, in the right leg area, subjects with AS displayed an increased density of gray matter. The structural findings of the left hemisphere correlated negatively with BBT score in controls, whereas the structure of the right hemisphere in the AS group correlated positively with motor function as assessed by BBT. These preliminary functional (neurophysiological and behavioral) findings are indicative of asymmetry, and co-existing structural alterations may reflect the motor impairments causing the deteriorations in manual dexterity and other motor functions commonly encountered in children with AS.

Navigated transcranial magnetic stimulation (nTMS) can be applied to locate cortical muscle representations. Usually, single TMS pulses are targeted to the motor cortex with the help of neuronavigation and by measuring motor evoked potential (MEP) amplitudes from the peripheral muscles. The efficacy of single-pulse TMS to induce MEPs has been shown to increase by applying facilitatory paired-pulse TMS (ppTMS). Therefore, the aim was to study whether the facilitatory ppTMS could enable more efficient motor mapping. Biphasic single-pulse TMS and ppTMS with inter-stimulus intervals (ISIs) of 1.4 and 2.8 ms were applied to measure resting motor thresholds (rMTs) as a percentage of the maximal stimulator output and to determine the cortical representation areas of the right first dorsal interosseous muscle in healthy volunteers. The areas, shapes, hotspots, and center of gravities (CoGs) of the representations were calculated. Biphasic ppTMS with ISI of 1.4 ms resulted in lower rMTs than those obtained with the other protocols (p = 0.001). With ISI of 2.8 ms, rMT was lower than with single-pulse TMS (p = 0.032). The ppTMS mapping was thus performed with lower intensity than when using single-pulse TMS. The areas, shapes, hotspots, and CoGs of the muscle representations were in agreement. Hence, biphasic ppTMS has potential in the mapping of cortical hand representations in healthy individuals as an alternative for single-pulses, but with lower stimulation intensity by utilizing cortical facilitatory mechanism. This could improve application of nTMS in subjects with low motor tract excitability.

Loud sounds have been demonstrated to increase motor cortex excitability when transcranial magnetic stimulation (TMS) is synchronized with auditory evoked N100 potential measured from electroencephalography (EEG). The N100 potential is generated by an afferent response to sound onset and feature analysis, and upon novel sound it is also related to the arousal reaction. The arousal reaction is known to originate from the ascending reticular activating system of the brain stem and to modulate neuronal activity throughout the central nervous system. In this study we investigated the difference in motor evoked potentials (MEPs) when deviant and novelty stimuli were randomly interspersed in a train of standard tones. Twelve healthy subjects participated in this study. Three types of sound stimuli were used: 1) standard stimuli (800 Hz), 2) deviant stimuli (560 Hz), and 3) novelty stimuli (12 different sounds). In each stimulus sequence 600 stimuli were given. Of these, 90 were deviant stimuli randomly placed between the standard stimuli. Each of 12 novel sounds was presented once in pseudorandomized order. TMS was randomly mixed with the sound stimuli so that it was either synchronized with the individual N100 or trailed the sound onset by 200 ms. All sounds elicited an increase in motor cortex excitability. The type of sound had no significant effect. We also demonstrated that TMS timed at 200-ms intervals caused a significant increment of MEPs. This contradicted our hypothesis that MEP amplitudes to TMS synchronized with N100 would be greater than those to TMS at 200 ms after a sound and remains unexplained. NEW & NOTEWORTHY We demonstrated modulation of motor cortical excitability with parallel auditory stimulus by combining navigated transcranial magnetic stimulation (TMS) with auditory stimuli. TMS was synchronized with auditory evoked potentials considered to be generated by the unconscious attention call process in the auditory system.

Unverricht-Lundborg disease (EPM1) is associated with progressive functional and anatomic changes in the thalamus and motor cortex. The neurophysiological mechanisms behind the impaired thalamocortical system were studied through short-term adaptation of the motor cortex to transcranial magnetic stimulation (TMS) via repetition suppression (RS) phenomenon. RS is considered to be related to neural processing of external stimuli. We hypothesized that this neural processing is progressively impaired in EPM1 from adolescence to adulthood. Eight adult patients with EPM1 (age: 40 ± 13 yr), six adolescent patients with EPM1 (age: 16 ± 1 yr), and ten adult controls (age: 35 ± 12 yr) were studied using navigated TMS and RS study protocol including trains of four repeated stimuli with intertrain interval of 20 s and interstimulus interval of 1 s. Changes in RS were investigated from adolescence to adulthood in EPM1 by comparing with adult controls. In controls, the RS was seen as 50-55% reduction in motor response amplitudes to TMS after the first stimulus. RS was mild or missing in EPM1. RS from first to second stimulus within the stimulus trains was significantly stronger in adolescent patients than in adult patients ( P = 0.046). Abnormal RS correlated with the myoclonus severity of the patients. In agreement with our hypothesis, neural processing of external stimuli is progressively impaired in EPM1 possibly due to anatomically impaired thalamocortical system or inhibitory tonus preventing sufficient adaptive reactiveness to stimuli. Our results suggest that RS abnormality might be used as a biomarker in the therapeutic trials for myoclonus. NEW & NOTEWORTHY Unverricht-Lundborg disease (EPM1) is associated with impaired thalamocortical function, which we studied in 8 adult and 6 adolescent patients and in 10 adult controls through repetition suppression (RS) of the motor cortex. We hypothesized that neural processing is progressively impaired in EPM1 from adolescence to adulthood. RS was normal in controls, whereas it was mild or missing in EPM1. Stronger RS was seen in adolescent patients than in adult patients correlating with the myoclonus severity.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Transcranial magnetic stimulation (TMS) induced I-wave behavior can be demonstrated at neuronal population level using paired-pulses and by observing short-interval cortical facilitation (SICF). Advancements in stimulator technology have made it possible to apply biphasic paired-pulses to induce SICF., Objective: Our aim was to characterize the SICF I-wave interaction by biphasic paired-pulses with the ultimate objective to enhance TMS effects via SICF in various TMS-applications., Methods: We used biphasic paired-pulses in 15 volunteers to characterize corticospinal SICF using various 1.2-8.0ms inter-stimulus intervals, and measuring SICF input-output response., Results: SICF interaction with the first I-wave (I1) was observed in the output responses (motor evoked potentials; MEPs) in all subjects. Most subjects (≥80%) also exhibited later SICF I-wave interaction. SICF at I1 was present at all applied intensities below 140% of resting motor threshold. At I2, we observed SICF only with intensities just above motor threshold., Conclusions: Biphasic paired-pulses can reliably induce SICF shown by the facilitatory I-wave interaction, and could therefore be applied with repetitive bursts to enhance responsiveness to TMS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Navigated transcranial magnetic stimulation (nTMS) can be applied to locate and outline cortical motor representations. This may be important, e.g., when planning neurosurgery or focused nTMS therapy, or when assessing plastic changes during neurorehabilitation. Conventionally, a cortical location is considered to belong to the motor cortex if the maximum electric field (E-field) targeted there evokes a motor-evoked potential in a muscle. However, the cortex is affected by a broad E-field distribution, which tends to broaden estimates of representation areas by stimulating also the neighboring areas in addition to the maximum E-field location. Our aim was to improve the estimation of nTMS-based motor maps by taking into account the E-field distribution of the stimulation pulse. The effect of the E-field distribution was considered by calculating the minimum-norm estimate (MNE) of the motor representation area. We tested the method on simulated data and then applied it to recordings from six healthy volunteers and one stroke patient. We compared the motor representation areas obtained with the MNE method and a previously introduced interpolation method. The MNE hotspots and centers of gravity were close to those obtained with the interpolation method. The areas of the maps, however, depend on the thresholds used for outlining the areas. The MNE method may improve the definition of cortical motor areas, but its accuracy should be validated by comparing the results with maps obtained with direct cortical stimulation of the cortex where the E-field distribution can be better focused.

Repetition suppression (RS) is evident as a weakened response to repeated stimuli after the initial response. RS has been demonstrated in motor-evoked potentials (MEPs) induced with transcranial magnetic stimulation (TMS). Here, we investigated the effect of inter-train interval (ITI) on the induction of RS of MEPs with the attempt to optimize the investigative protocols. Trains of TMS pulses, targeted to the primary motor cortex by neuronavigation, were applied at a stimulation intensity of 120% of the resting motor threshold. The stimulus trains included either four or twenty pulses with an inter-stimulus interval (ISI) of 1 s. The ITI was here defined as the interval between the last pulse in a train and the first pulse in the next train; the ITIs used here were 1, 3, 4, 6, 7, 12, and 17 s. RS was observed with all ITIs except with the ITI of 1 s, in which the ITI was equal to ISI. RS was more pronounced with longer ITIs. Shorter ITIs may not allow sufficient time for a return to baseline. RS may reflect a startle-like response to the first pulse of a train followed by habituation. Longer ITIs may allow more recovery time and in turn demonstrate greater RS. Our results indicate that RS can be studied with confidence at relatively short ITIs of 6 s and above.

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., (© 2017 Wiley Periodicals, Inc.)

Background: Although the relationship between neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) has been widely studied in motor mapping, it is unknown how the motor response type or the choice of motor task affect this relationship., New Method: Centers of gravity (CoGs) and response maxima were measured with blood-oxygen-level dependent (BOLD) and arterial spin labeling (ASL) fMRI during motor tasks against nTMS CoGs and response maxima, which were mapped with motor evoked potentials (MEPs) and silent periods (SPs)., Results: No differences in motor representations (CoGs and response maxima) were observed in lateral-medial direction (p=0.265). fMRI methods localized the motor representation more posterior than nTMS (p<0.001). This was not affected by the BOLD fMRI motor task (p>0.999) nor nTMS response type (p>0.999). ASL fMRI maxima did not differ from the nTMS nor BOLD fMRI CoGs (p≥0.070), but the ASL CoG was deeper in comparison to other methods (p≤0.042). The BOLD fMRI motor task did not influence the depth of the motor representation (p≥0.745). The median Euclidean distances between the nTMS and fMRI motor representations varied between 7.7mm and 14.5mm and did not differ between the methods (F≤1.23, p≥0.318)., Comparison With Existing Methods: The relationship between fMRI and nTMS mapped excitatory (MEP) and inhibitory (SP) responses, and whether the choice of motor task affects this relationship, have not been studied before., Conclusions: The congruence between fMRI and nTMS is good. The choice of nTMS motor response type nor BOLD fMRI motor task had no effect on this relationship., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To assess the inter-hemispheric differences in neuronal function and structure of the motor cortex in a small group of chronic stroke patients having suffered a restricted ischemic lesion affecting hand motor representation. GABAergic intracortical inhibition, known to be affected by stroke lesion, was also investigated., Methods: Eight patients exhibiting little or no motor impairment were studied using transcranial magnetic stimulation (TMS) and diffusion weighted imaging (DWI) >15months from diagnosis. Resting motor threshold (MT) for 50μV and 2mV motor evoked potentials, and short-interval intracortical inhibition (SICI) were measured from hand muscles. Apparent diffusion coefficients (ADCs) were analyzed from the DWI for the primary motor cortex (M1), the supplementary motor area (SMA) and thalamus for reflecting changes in neuronal organization., Results: The MTs did not differ between the affected (AH) and unaffected hemisphere (UH) in 50μV responses, while the MTs for 2mV responses were higher (p=0.018) in AH. SICI was weakened in AH (p=0.008). ADCs were higher in the affected M1 compared to the unaffected M1 (p=0.018) while there were no inter-hemispheric differences in SMA or thalamus., Conclusions: Inter-hemispheric asymmetry and neuronal organization demonstrated abnormalities in the M1. However, no confident inference can be made whether the observed alterations in neurophysiological and imaging measures have causal role for motor rehabilitation in these patients., Significance: Neurophysiological changes persist and are detectable using TMS years after stroke even though clinical symptoms have normalized., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Navigated transcranial magnetic stimulation (nTMS) is becoming a popular tool in pre-operative mapping of functional motor areas. The stimulation intensities used in the mapping are commonly suprathreshold intensities with respect to the patient's resting motor threshold (rMT). There is no consensus on which suprathreshold intensity should be used nor on the optimal criteria for selecting the appropriate stimulation intensity (SI). In this study, the left motor cortices of 12 right-handed volunteers (8 males, age 24-61 years) were mapped using motor evoked potentials with an SI of 110 and 120 % of rMT and with an upper threshold (UT) estimated by the Mills-Nithi algorithm. The UT was significantly lower than 120 % of rMT (p < 0.001), while no significant difference was observed between UT and 110 % of rMT (p = 0.112). The representation sizes followed a similar trend, i.e. areas computed based on UT (5.9 cm(2)) and 110 % of rMT (5.0 cm(2)) being smaller than that of 120 % of rMT (8.8 cm(2)) (p ≤ 0.001). There was no difference in representation sizes between 110 % of rMT and UT. The variance in representation size was found to be significantly lower with UT compared to 120 % of rMT (p = 0.048, uncorrected), while there was no difference between 110 % of rMT and UT or 120 % of rMT. Indications of lowest inter-individual variation in representation size were observed with UT; this is possibly due to the fact that it takes into account the individual input-output characteristics of the motor cortex. Therefore, the UT seems to be a good option for SI in motor mapping applications to outline functional motor areas with nTMS and it could potentially reduce the inter-individual variation caused by the selection of SI in motor mapping in pre-surgical applications and radiosurgery planning.

Background: Transcranial magnetic stimulation (TMS) can evaluate cortical excitability and integrity of motor pathways via TMS-induced responses. The responses are affected by the orientation of the stimulated neurons with respect to the direction of the TMS-induced electric field. Therefore, besides being a functional imaging tool, TMS may potentially assess the local structural properties. Yet, TMS has not been used for this purpose., New Method: A novel principle to evaluate the relation between function and structure of the motor cortex is presented. This functional anisotropy is evaluated by an anisotropy index (AI), based on motor evoked potential amplitudes induced with different TMS coil orientations, i.e. different electric field directions at a cortical target. To compare the AI with anatomical anisotropy in an explorative manner, diffusion tensor imaging-derived fractional anisotropy (FA) was estimated at different depths near the stimulation site., Results: AI correlated inversely with cortical excitability through the TMS-induced electric field at motor threshold level. Further, there was a trend of negative correlation between AI and FA., Comparison With Existing Methods: None of the existing methods alone can detect the relationship between direct motor cortex activation and local neuronal structure., Conclusions: The AI appears to provide information on the functional neuronal anisotropy of the motor cortex by coupling neurophysiology and neuroanatomy within the stimulated cortical region. The AI could prove useful in the evaluation of neurological disorders and traumas involving concurrent structural and functional changes in the motor cortex. Further studies on patients are needed to confirm the usability of AI., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Transcranial magnetic stimulation (TMS) can be used for evaluating the function of motor pathways. According to the principles of electromagnetism and electrophysiology, TMS activates those neurons that are suitably oriented with respect to the TMS-induced electric field. We hypothesized that TMS could potentially be able to evaluate the neuronal structure, although until now, this putative application has not been exploited. We have developed a TMS-based method to evaluate the function and structure of the motor cortex concurrently in a quantitative manner. This method produced a measure, the anisotropy index (AI), which is based on the motor-evoked potentials induced at different coil orientations. The AI was demonstrated to exhibit an association with both motor cortex excitability and neuronal structure. In the present study, we evaluated the repeatability (intrasession and intersession) of AI in three consecutive measurements. In addition, we studied the repeatability of the optimal coil angle in inducing motor-evoked potentials. Two of the measurements were conducted on the same stimulation target and the third on a remapped target. The coefficient of repeatability of the AI was 0.022 for intrasession and 0.040 for intersession assessments. For the optimal stimulation angle, the coefficients of repeatability were 3.7° and 5.1°, respectively. Both the AI and the optimal stimulation angle demonstrated good repeatability (Cronbach's α>0.760). In conclusion, the results indicate that the AI can provide a reliable estimation of local functional anisotropy changes under conditions affecting the cortex, such as during stroke or focal dysplasia.

Objective: We evaluated the induction of corticospinal silent period (SP) using transcranial magnetic stimulation (TMS) at stimulation intensities normalized to resting motor threshold (rMT) or silent period thresholds (SPTs). The aim was to reduce the characteristic inter-individual variation in SP measurements in healthy population to improve the sensitivity of such measurements., Methods: The cortical representation area of the right hand musculature of 12 healthy subjects was stimulated with navigated TMS with varying stimulating intensities. Subsequently, the individual SPTs for eliciting SPs of 20, 30, and 50ms in duration were determined from the input-output characteristics., Results: While SPT for 20 and 50ms SPs differed from rMT, the SPT for 30ms was similar to rMT. Nevertheless, the inter-individual variation in SP duration was reduced significantly at 120% of SPT30 when compared with SP durations obtained at 120% of rMT., Conclusions: Inter-individual variation in the SP duration decreases when applying TMS at stimulation intensities normalized to the individual SPTs instead to the rMT. This makes the SP duration more specific to inhibition and less affected by changes in cortical excitability., Significance: Use of individual SPTs may improve the sensitivity of the SP measures in studies with inter-individual design., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Cortical silent period (cSP) is a short interruption in electromyography (EMG) during active muscle contraction induced with transcranial magnetic stimulation (TMS). The cSP is a measure of cortical inhibition and is believed to represent inhibitory interneuron effects on excited motor cortical areas. Several pathological conditions and pharmacological manipulations induce changes to cSP duration indicating alterations in intracortical inhibition. At present, it is common to manually analyse the cSP duration from measured EMG. However, to avoid inter-examiner effects on cSP interpretation and detection, as well as to allow for quick measurement online, automated routine would be preferable. In this study, we evaluate the feasibility of a straight-forward cSP detection routine based on analysing the rectified first derivative of the EMG signal following TMS. Previously measured cSPs of 54 healthy subjects were reanalysed manually by two of the authors and using the automated routine. Furthermore, we recruited one subject for whom the cSPs were induced with several stimulation intensities, and those cSPs were analysed manually by two of the authors as well as using the automated routine. We found that cSPs were detected correctly by the automated cSP detection routine, and agreement with manually analysed subject-specific mean cSPs was excellent (ICC=0.992, p<0.001). The inter-examiner variability was similar to the variability between manual and automated analysis. Hence, we believe the introduced cSP detection routine would be feasible for online cSP detection, in such a way that is presently used to detect the motor evoked potentials., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Repetitive transcranial magnetic stimulation (rTMS) targeted to primary motor cortex (M1) has been proven effective in treating therapy-resistant chronic neuropathic pain (Lefaucheur et al, 2014). However, the mechanisms of action of rTMS are so far unknown, though probably at least partly shared with epidural motor cortex stimulation (MCS). TMS can be used to assess the excitability of the cortex (resting motor threshold, rMT) and corticospinal inhibition (silent period duration). Previously, defective inhibition has been described in chronic neuropathic pain (Lefaucheur et al, 2006). As well, neuroplastic changes have been observed in sensory-motor areas (Krause et al, 2006). Objectives: We hypothesized that there are changes in the excitability or motor map configuration in chronic pain. In addition, we studied whether these changes normalize after two 5-days rTMS treatment sessions separated by 6 weeks. Therapy was targeted to the somatotopic facial primary motor cortex using neuronavigated TMS. Patients and Methods: Six patients with severe unilateral, chronic atypical facial pain were enrolled in the study. High-frequency rTMS (randomized to 10 Hz or 20 Hz, 2400 or 3600 pulses per session, 90% of the rMT) was targeted to functional motor representation area of the lower face (mentalis or orbicularis oris muscle). The optimal stimulation site for face and hand was assessed and rMTs determined on both hemispheres. Silent period duration was measured on the hand muscle. Motor areas corresponding to the painful side were mapped using 105% of the rMT. The area and the center-of-gravity (CoG) of the map were determined. Results: rTMS sessions did not significantly change the rMTs of either hand or face on either hemisphere. However, there was a trend of interhemispheric difference decrease in rMT of the face after rTMS (p = 0.229, paired t-test). There was no difference in the sizes of the representation areas though they were individually slightly altered in shape. The CoGs moved laterally in all patients and posteriorly in all but one patient (non-significant). There was a trend of increase in the duration of the silent period (p = 0.060, paired t-test). Conclusion: No statistically significant changes were observed in the excitability, though corticospinal inhibition seemed to normalize after rTMS treatments. These preliminary results suggest that rTMS induces slight changes in the motor map plasticity measurable 4-10 days after last rTMS treatment session. These may have potential implications in better tailoring of rTMS treatment for chronic pain and for efficient placing of the MCS electrode. [ABSTRACT FROM AUTHOR]

Introduction The reactivity to transcranial magnetic stimulation (TMS) changes with development. For example, motor cortex TMS-evoked EEG response decreases significantly with age. Structurally, the grey matter of the motor cortex reaches maturity by the age of 10 years, whereas the maturation of superficial white matter continues until early adulthood. The relationship between these concurrent structural and functional changes remains unclear. Methods We studied 10 healthy children (mean age 10.5), 10 adolescents (mean age 16.0 years) and 7 adults (mean age 26.5 years). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were defined from diffusion weighted MRI data obtained from the left hand knob area on motor cortex. Cortical thickness (grey matter, GM) of the same area was assessed from T1-weighted MRI. TMS was focused on the left hand knob with a stimulation intensity of 110% of the resting motor threshold. EEG was recorded with a 60-channel TMS-compatible amplifier. The total EEG activity was assessed using the global mean field power (GMFP) calculated across all electrodes and the local activation as a local mean field power (LMFP left ) computed across the electrodes surrounding the left hand knob. GMFP and LMFP left areas in the 15–500 ms post stimulus interval were used for statistical analyses. Between-group differences in TMS-EEG, GM and DTI metrics were analyzed with one-way ANOVA, and Pearson’s correlation was used to analyze correlations between functional and structural data. Results GMFP area ( F  = 12.65, p  < 0.001) as well as LMFP left ( F  = 20.19, p  < 0.001) differed between the groups, the values being largest in children and smallest in adults, as expected. AD decreased significantly with age ( F  = 7.30, p  < 0.01), while FA and MD showed trend of age dependent changes ( p  = 0.05–0.07). However, GM at the left hand knob did not differ between the age groups ( p  > 0.8). GMFP and LMFP left showed a significant correlation with MD ( r  = 0.421, p  < 0.05 for the GMFP and r  = 0.591, p  < 0.01 for LMFP left ) and AD ( r  = 0.555, p  < 0.01 for GMFP and r  = 0.595, p  < 0.01 for the LMFP left ) values. GM correlated significantly with RD ( r  = 0.443, p  < 0.05) and MD ( r  = 0.411, p  < 0.05) but not with GMFP or LMFP left . Conclusion Previously, it has been suggested that smaller EEG responses in adults compared with those in children may be associated with GM loss in the pre- and peripubescent period. In this study, a developmental decline of TMS evoked global and local EEG responses correlated with the maturation of local short-range microstructural changes revealed by DTI rather than GM in the motor cortex. These results indicate that the development profile of TMS-evoked EEG activity may associate with maturation of the microstructure of underlying short range white matter connections. [ABSTRACT FROM AUTHOR]