Real Transcranial Magnetic Stimulation Research Articles

A pilot, randomized clinical trial: Left dorsolateral prefrontal cortex intermittent theta burst stimulation improves treatment outcomes in veterans with alcohol use disorder.

Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial to deliver intermittent theta burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) among US veterans with AUD. We hypothesized that 20 sessions of real TMS are tolerable and feasible. As a secondary line of inquiry, we hypothesized that, relative to sham TMS, individuals receiving real TMS would experience greater reductions in 6-month relapse rates, anhedonia, and alcohol cue-reactivity. Veterans (n = 17, one woman) were enrolled in a double-blind, sham-controlled trial (2-3 sessions/day; 7-10 days; 600 pulses/session; 20 sessions). Pre- and posttreatment assessments included responses to self-report questionnaires and functional magnetic resonance imaging measures of alcohol cue-reactivity. Alcohol consumption was assessed for 6 months. Linear mixed-effects models were constructed to predict posttreatment craving, mood, and cue-reactivity. Individuals who received active iTBS (n = 8) were less likely to relapse within 3 months after treatment than the sham-treated group (n = 9) (OR = 12.0). Greater reductions in anhedonia were observed following active iTBS (Cohen's d = -0.59), relative to sham (d = -0.25). Alcohol cue-reactivity was reduced following active iTBS and increased following sham within the left insula (d = -0.19 vs. 0.51), left thalamus (d = -0.28 vs. 0.77), right insula (d = 0.18 vs. 0.52), and right thalamus (d = -0.06 vs. 0.62). Relative to sham, we demonstrate that 20 sessions of real left DLPFC iTBS reduced the likelihood of relapse for at least 3 months. The potential utility of this approach is underscored by observed decreases in anhedonia and alcohol cue-reactivity-strong predictors of relapse among veterans. These initial data offer a valuable set of effect sizes to inform future clinical trials in this patient population.

Causal evidence for the role of the sensory visual cortex in visual short-term memory maintenance

The role of the sensory visual cortex during visual short-term memory (VSTM) remains controversial. This controversy is possibly due to methodological issues in previous attempts to investigate the effects of transcranial magnetic stimulation (TMS) on VSTM. The aim of this study was to use TMS, while covering previous methodological deficits. Sixty-four young adults were recruited to participate in two experiments (Experiment 1: n = 36; Experiment 2: n = 28) using a VSTM orientation change-detection task under TMS. Monocular vision was ensured using red-blue goggles combined with red-blue stimuli. Double-pulse TMS was delivered at different times (Experiment 1: 0, 200 or 1000 ms; Experiment 2: 200, 1000 ms) during a 2 s maintenance phase, on one side of the occipital hemisphere. In Experiment 2, a sham TMS condition was introduced. Decreased detection sensitivity (d') in the ipsilateral occipital hemisphere to visual hemifield, and in the real TMS (compared with sham TMS) condition indicated inhibitory TMS effects, and thus, a causal involvement of the sensory visual cortex during early (200 ms) and late (1000 ms) maintenance in VSTM. These findings are aligned with sensory recruitment, which proposes that both perceptual and memory processes rely upon the same neural substrates in the sensory visual cortex. The methods used in this study were preregistered and had received in-principle acceptance on 6 June 2022 (Stage 1 protocol can be found in: https://doi.org/10.17605/OSF.IO/EMPDT).

A Case Series of Intermittent Theta Burst Stimulation Treatment for Depressive Symptoms in Individuals with Autistic Spectrum Disorder: Real World TMS Study in the Tokyo Metropolitan Area.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. While the symptoms of ASD are present from early childhood, there has been an increase in the number of adults with ASD in recent years who visit healthcare professionals to seek the treatment of depression due to maladjustment resulting from the core symptoms and are eventually diagnosed with ASD. Currently, no treatment is available for the core symptoms of ASD, and pharmacotherapy and psychotherapy are often provided mainly for secondary disorders such as depression and anxiety. However, the effectiveness of these therapies is often limited in individuals with ASD compared to those with major depression. In this context, neuromodulation therapies such as transcranial magnetic stimulation (TMS) have gained increasing attention as potential treatments. In this case series, we retrospectively analyzed 18 cases with ASD from the TMS registry data who had failed to improve depressive symptoms with pharmacotherapy and were treated with intermittent theta burst stimulation (iTBS) therapy to the left dorsolateral prefrontal cortex (DLPFC). We also explored the relationship between treatment efficacy and clinical epidemiological profile. Our results indicated that, despite the limitations of an open-label preliminary case series, TMS therapy in the form of iTBS may have some beneficial therapeutic effects on depressive symptoms in individuals with ASD. The present findings warrant further validation through randomized, sham-controlled trials with larger sample sizes.

Motor cortex oscillates at its intrinsic post-movement beta rhythm following real (but not sham) single pulse, rhythmic and arrhythmic transcranial magnetic stimulation

We aimed to test the idea that rhythmic transcranial magnetic stimulation (TMS) entrains cortical oscillations. To do this, we examined oscillatory responses in the electroencephalogram (EEG) to TMS over primary motor cortex. In particular, we contrasted responses to real TMS with those to sham TMS in order to dissociate the contributions of direct (transcranial) activation and indirect activation (via auditory/sensory input) of the brain. We first showed that real single pulse TMS elicited a brief (∼200 ms) increase in sensorimotor beta power whose frequency closely matched that of each individual's post-movement beta rebound (PMBR, ∼18 Hz). Sham TMS triggered minimal oscillatory activity. Together this implies that real TMS interacts with endogenous oscillations via direct brain activation. We then showed that although trains of real rhythmic TMS delivered at each individuals PMBR frequency produced a brief increase in beta power at the same frequency, real arrhythmic TMS also elicited an equivalent increase in beta. The implication is that the oscillatory response is independent of the rhythm of stimulation. By contrast, sham stimulation elicited minimal activity in the beta band, and the responses to rhythmic and arrhythmic sham TMS were broadly similar, showing that sham rhythmic stimulation did not produce entrainment via sensory rhythms. Together, the data demonstrate that the beta oscillatory response of M1 to real TMS predominantly reflects direct activation of the underlying cortex. However, the data do not support the notion of rhythmic TMS enhancing oscillatory activity via entrainment-like mechanisms, at least within the constraints of the current experimental set-up.

Transcranial Magnetic Stimulation Over the Right Posterior Superior Temporal Sulcus Promotes the Feature Discrimination Processing.

Attention is the dynamic process of allocating limited resources to the information that is most relevant to our goals. Accumulating studies have demonstrated the crucial role of frontal and parietal areas in attention. However, the effect of posterior superior temporal sulcus (pSTS) in attention is still unclear. To address this question, in this study, we measured transcranial magnetic stimulation (TMS)-induced event-related potentials (ERPs) to determine the extent of involvement of the right pSTS in attentional processing. We hypothesized that TMS would enhance the activation of the right pSTS during feature discrimination processing. We recruited 21 healthy subjects who performed the dual-feature delayed matching task while undergoing single-pulse sham or real TMS to the right pSTS 300 ms before the second stimulus onset. The results showed that the response time was reduced by real TMS of the pSTS as compared to sham stimulation. N270 amplitude was reduced during conflict processing, and the time-varying network analysis revealed increased connectivity between the frontal lobe and temporo-parietal and occipital regions. Thus, single-pulse TMS of the right pSTS enhances feature discrimination processing and task performance by reducing N270 amplitude and increasing connections between the frontal pole and temporo-parietal and occipital regions. These findings provide evidence that the right pSTS facilitates feature discrimination by accelerating the formation of a dynamic network.

Adaptation of a semantic picture-word interference paradigm for future language mapping with transcranial magnetic stimulation: A behavioural study

Neuro-navigated transcranial magnetic stimulation (TMS) helps to identify language-related cortical regions prior to brain tumour surgery. We adapted a semantic picture-word interference (PWI) paradigm from psycholinguistics to high-resolution TMS language mapping which prospectively can be used to specifically address the level of semantic processing. In PWI, pictures are presented along with distractor words which facilitate or inhibit the lexical access to the picture name. These modulatory effects of distractors can be annihilated in language-sensitive areas by the inhibitory effects of TMS on language processing. The rationale here is to observe the distractor effect without active stimulation and then to observe presumably its elimination by interference of the TMS stimulation. The special requirements to use PWI in this setting are (1) identifying word material for accelerating reliably naming latencies, choosing (2) the ideal presentation modality, and (3) the appropriate timing of distractor presentation. These are then controlled in real TMS language mapping. To adapt a semantic PWI naming paradigm for TMS application we employed 30 object-pictures in spoken German language. Part-whole associative semantic related or unrelated distractors were presented in two experiments including 15 healthy volunteers each, once auditorily and once visually. Data analysis across the entire stimulus set revealed a trend for facilitation in the visual condition, whereas no effects were observed for auditory distractors. In a sub-set, we found a significant facilitation effect for visual semantic distractors. Thus, with this study we provide a well-controlled item set for future studies implementing effective TMS language mapping applying visual semantic PWI.

Development and Validation of a Novel Calibration Methodology and Control Approach for Robot-Aided Transcranial Magnetic Stimulation (TMS).

This article presents the development and validation of a new robotic system for Transcranial Magnetic Stimulation (TMS), characterized by a new control approach, and an ad-hoc calibration methodology, specifically devised for the TMS application. The robotic TMS platform is composed of a 7 dof manipulator, controlled by an impedance control, and a camera-based neuronavigation system. The proposed calibration method was optimized on the workspace useful for the specific TMS application (spherical shell around the subject's head), and tested on three different hand-eye and robot-world calibration algorithms. The platform functionality was tested on six healthy subjects during a real TMS procedure, over the left primary motor cortex. employing our method significantly decreases ( ) the calibration error by 34% for the position and 19% for the orientation. The robotic TMS platform achieved greater orientation accuracy than the expert operators, significantly reducing orientation errors by 46% ( ). No significant differences were found in the position errors and in the amplitude of the motor evoked potentials (MEPs) between the robot-aided TMS and the expert operators. The proposed calibration represents a valid method to significantly reduce the calibration errors in robot-aided TMS applications. Results showed the efficacy of the proposed platform (including the control algorithm) in administering a real TMS procedure, achieving better coil positioning than expert operators, and similar results in terms of MEPs. This article spotlights how to improve the performance of a robotic TMS platform, providing a reproducible and low-cost alternative to the few devices commercially available.

Distilling the essence of TMS-evoked EEG potentials (TEPs): A call for securing mechanistic specificity and experimental rigor

Distilling the essence of TMS-evoked EEG potentials (TEPs): A call for securing mechanistic specificity and experimental rigor

Paired Associative Electroacupuncture and Transcranial Magnetic Stimulation in Humans.

Pairing transcutaneous electric nerve stimulation (TENS) and transcranial magnetic stimulation (TMS) with specific stimulus-intervals induces associative motor plasticity at the primary motor cortex (M1). Electroacupuncture (EA) is an established medical technique in the eastern countries. This study investigates whether EA paired with TMS induces distinct M1 motor plasticity. Fifteen healthy, right-handed subjects (aged 23.6 ± 2.0 years, eight women) were studied. Two-hundred and twenty-five pairs of TMS of the left M1 preceded by right EA at acupoint “Neiguan” [Pericardium 6 (PC6), located 2 decimeters proximal from the wrist wrinkle] were respectively applied with the interstimulus interval (ISI) of individual somatosensory evoked potential (SSEP) N20 latency plus 2 ms (N20+2) and minus 5 ms (N20-5) with at least 1-week interval. The paired stimulation was delivered at a rate of 0.25 Hz. Sham TMS with a sham coil was adopted to examine the low-frequency EA influence on M1 in eleven subjects. M1 excitability was assessed by motor-evoked potential (MEP) recruitment curve with five TMS intensity levels, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar inhibition (CBI) at the abductor pollicis brevis (APB) muscle of the right hand before and after the EA-M1 paired associative stimulation (PAS). In addition, median nerve SSEPs and H-reflex were respectively measured to monitor somatosensory and spinal excitability. The MEP showed significantly facilitated after the sham EA-M1 PAS while tested with 80% of the TMS intensity producing on average 1 mV amplitude (i.e., MEP1 mV) in the resting APB muscle. It was also facilitated while tested with 90% MEP1 mV irrespective of the stimulation conditions. The SSEP showed a higher amplitude from the real EA-M1 PAS compared to that from the sham EA-M1 PAS. No significant change was found on SICI, ICF, CBI and H-reflex. Findings suggest that repetitive low frequency EA paired with real TMS did not induce spike-timing dependent motor plasticity but EA paired with sham TMS induced specific M1 excitability change. Complex sensory afferents with dispersed time locked to the sensorimotor cortical area could hamper instead of enhancing the induction of the spike-timing dependent plasticity (STDP) in M1.

The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies

Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud “click” sound, the TMS-evoked EEG potentials (TEPs) reflect not only neural activity induced by transcranial neuronal excitation but also neural activity due to somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by realistic sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the design of TMS-EEG studies to enable a dissociation between truly transcranial and non-transcranial components of TEPs.

F193. What remains as transcranial cortical response after accounting for the contribution of somatosensory and auditory evoked responses?

Focal transcranial magnetic stimulation (TMS) induces somatosensory input due to excitation of peripheral trigeminal nerve branches as well as auditory input caused by the loud click produced during stimulus discharge. In a recent study, we have demonstrated that these peripheral sources of cortical activation make a strong contribution to the transcranial evoked potentials (TEPs) that can be recorded with EEG at the scalp. Here we investigated the components of the TEP after removal of multisensory contributions. In 10 healthy young volunteers, we applied single-pulse neuronavigated TMS using two coil orientations (perpendicular and parallel to the target gyrus) and two positions (superior frontal gyrus and superior parietal lobule) and recorded the TEPs. We also recorded the evoked EEG response in a sham condition during which the TMS click was given simultaneously with bipolar electrical skin stimulation at the site corresponding to the centre of the coil during real TMS. We applied a fitting procedure to the sham and real-TMS conditions to exclude the signal related to somatosensory and auditory processing from the transcranially evoked TMS response. Some of the standard peaks commonly reported in the TMS/EEG literature were reduced or modified, suggesting that they were also caused by multisensory peripheral stimulation. For example, this was the case for the negative deflection that appears at around 100 ms after single-pulse TMS. We also identified TEP components which were not changed after accounting for somatosensory and auditory EEG response. This uncovered TEP signal was sensitive to the direction of the coil orientation, showing statistical difference in time intervals that were not present in the original TEP. This study confirms the need to exclude the somatosensory and auditory confounds in order to have a deeper insight into the TMS/EEG results. The appropriate approach is to include a sham procedure that controls for the contribution of peripheral sensory stimulation to the TEPs. Our novel procedure renders it possible to study the brain response to direct magnetic stimulation of the cortex also in time intervals affected or covered by unwanted sensory inputs.

Sub-threshold transcranial magnetic stimulation applied after the go-signal facilitates reaction time under control but not startle conditions.

The presentation of a startling acoustic stimulus (SAS) in a simple reaction time (RT) task significantly reduces RT due to the involuntary early initiation of a prepared movement; however, the underlying neural mechanism remains unclear. It has been proposed that a SAS triggers a cortically stored motor program by involuntarily increasing initiation-related activation. Sub-threshold transcranial magnetic stimulation (TMS) can be used to investigate cortical processes, as it increases cortical excitability for 6-30ms and significantly reduces RT. The purpose of the present experiments was to determine whether the application of sub-threshold TMS over motor cortex in close temporal proximity to a SAS would facilitate startle RT in the same manner as control RT, providing evidence for cortical involvement in startle-related RTs. Participants completed a simple RT task requiring targeted wrist extension in response to an auditory go-signal, which was randomly replaced by a SAS on 25% of trials. On a subset of trials, sub-threshold TMS was applied 30ms following the go-signal in control trials or at -15, 0, +15 or +30ms with respect to the SAS in startle trials. In all three experiments, sham and real TMS significantly reduced RT in control trials, with real TMS having a larger effect, but there was no effect of either real or sham TMS on startle-related RT. These results suggest that there may be limited cortical involvement in the initiation of movements in response to a SAS. As an alternative, startle may produce the fastest possible RTs, with little room for additional facilitation.

P301 Contribution of somatosensory and auditory processing to the TMS evoked cortical response: A sham TMS-EEG study

Objectives Transcranial Magnetic Stimulation (TMS) is capable to non-invasively stimulate the human cortex. Electroencephalography (EEG) can record the cortical response evoked by TMS (TEPs), which are a summation of the brain responses to the TMS-induced electric field in the cortex, and to the multisensory peripheral stimulation derived from the TMS coil discharge. This multisensory stimulation is composed by a somatosensory component relative to the activation of trigeminal nerve fibers and by an auditory component due to the loud click of the coil. Here, we aim to describe the contribution of somatosensory and auditory processing to the TEPs by comparing a somatosensory-auditory sham condition with real TMS. Methods In 18 healthy individuals, TMS was delivered with a figure-of-eight coil over two target sites (parietal and frontal) using two coil orientations. On the same target sites, a sham condition was applied by delivering a cutaneous electrical stimulation concurrently with the TMS click. The EEG was recorded with a 61-channel TMS-compatible system. Results The potentials evoked by real TMS and by somatosensory-auditory sham TMS were highly similar in terms of shape and spatial distribution, particularly at later latencies, 70–200 ms, after stimulus administration. Conclusion The present results challenge a straight-forward interpretation of TEPs as an index of cortical connectivity of the focally stimulated brain region, because of the strong contribution of TMS-induced somatosensory and auditory stimulation. This work has been funded by the Novo Nordisk Foundation Interdisciplinary Synergy Program 2014 [“Biophysically adjusted state-informed cortex stimulation (BASICS); Grant No. NNF14OC0011413 ].

P122 Contribution of integrated somatosensory and auditory inputs to the cortical response evoked by transcranial magnetic stimulation: A sham TMS-EEG study

Transcranial Magnetic Stimulation (TMS) can effectively stimulate non-invasively the human cortex. The TMS-evoked cortical response can be recorded with electroencephalography (EEG). However, TMS also stimulates our senses by stimulating peripheral trigeminal nerve fibers and creating a loud click. This implies that the TMS-evoked EEG response not only reflects neural activity induced by transcranial excitations of neurons but also neural activity due to somatosensory and auditory stimulation. To characterize the contribution of multisensory peripheral stimulation to TMS-evoked cortical potentials (TEPs), we recorded the evoked EEG response caused by a somato-auditory sham condition which mimicked real TMS. In 20 healthy individuals, TMS was delivered with a figure-of-eight coil over two target sites (posterior parietal cortex and superior frontal gyrus) using two different coil orientations, perpendicular or parallel to sulcus orientation. The sham condition comprised of simultaneous somatosensory and auditory stimulation over the same hotspots as for real TMS. Somatosensory stimulation was achieved via cutaneous electrical stimulation of the scalp, while the TMS coil was used for auditory stimulation ensuring no electric field was induced in the brain by physically separating the coil from the scalp. EEG was acquired with a 61-channel TMS-compatible EEG system. While the early cortical potentials evoked by real or sham TMS differed, TEPs were closely matched in terms of shape and spatial distribution for late components of the evoked EEG responses 70–200 ms after the TMS pulse (see Fig. 1 Download : Download high-res image (666KB) Download : Download full-size image ). This was also the case for the N100 which has been commonly attributed to TMS-induced cortical inhibition. The resemblance of the EEG responses evoked by real and sham TMS challenges the notion that TEPs are mainly reflecting transcranial excitation of cortical neurons. This work has been funded by the Novo Nordisk Foundation Interdisciplinary Synergy Program 2014 [“Biophysically adjusted state-informed cortex stimulation (BASICS); Grant No. NNF14OC0011413].

Transcranial Magnetic Stimulation of Human Adult Stem Cells in the Mammalian Brain.

Introduction: The burden of stroke on the community is growing, and therefore, so is the need for a therapy to overcome the disability following stroke. Cellular-based therapies are being actively investigated at a pre-clinical and clinical level. Studies have reported the beneficial effects of exogenous stem cell implantation, however, these benefits are also associated with limited survival of implanted stem cells. This exploratory study investigated the use of transcranial magnetic stimulation (TMS) as a complementary therapy to increase stem cell survival following implantation of human dental pulp stem cells (DPSC) in the rodent cortex.Methods: Sprague-Dawley rats were anesthetized and injected with 6 × 105 DPSC or control media via an intracranial injection, and then received real TMS (TMS0.2 Hz) or sham TMS (TMSsham) every 2nd day beginning on day 3 post DPSC injection for 2 weeks. Brain sections were analyzed for the survival, migration and differentiation characteristics of the implanted cells.Results: In animals treated with DPSC and TMS0.2 Hz there were significantly less implanted DPSC and those that survived remained in the original cerebral hemisphere compared to animals that received TMSsham. The surviving implanted DPSC in TMS0.2 Hz were also found to express the apoptotic marker Caspase-3.Conclusions: We suggest that TMS at this intensity may cause an increase in glutamate levels, which promotes an unfavorable environment for stem cell implantation, proliferation and differentiation. It should be noted that only one paradigm of TMS was tested as this was conducted as a exploratory study, and further TMS paradigms should be investigated in the future.

Direct Causal Networks for the Study of Transcranial Magnetic Stimulation Effects on Focal Epileptiform Discharges.

Transcranial magnetic stimulation (TMS) can have inhibitory effects on epileptiform discharges (EDs) of patients with focal seizures. However, the brain connectivity before, during and after EDs, with or without the administration of TMS, has not been extensively explored. To investigate the brain network of effective connectivity during ED with and without TMS in patients with focal seizures. For the effective connectivity a direct causality measure is applied termed partial mutual information from mixed embedding (PMIME). TMS-EEG data from two patients with focal seizures were analyzed. Each EEG record contained a number of EDs in the majority of which TMS was administered over the epileptic focus. As a control condition, sham stimulation over the epileptogenic zone or real TMS at a distance from the epileptic focus was also performed. The change in brain connectivity structure was investigated from the causal networks formed at each sliding window. The PMIME could detect distinct changes in the network structure before, within, and after ED. The administration of real TMS over the epileptic focus, in contrast to sham stimulation, terminated the ED prematurely in a node-specific manner and regained the network structure as if it would have terminated spontaneously.

No Change in Neuropsychological Functioning After Receiving Repetitive Transcranial Magnetic Stimulation Treatment for Major Depression

Early studies of transcranial magnetic stimulation (TMS) have shown no adverse effects on neuropsychological function. However, further research using higher TMS intensities as well as a greater number of TMS pulses and with larger sample sizes is needed. We studied 68 patients with major depressive disorder who were randomized to receive either 15 sessions of sham or real TMS at 110% of the estimated prefrontal cortex threshold to the left dorsolateral prefrontal cortex. Each session consisted of 32 5-second trains of 10-Hz repetitive TMS at 110% adjusted motor threshold. A total of 24,000 pulses were given. Neuropsychological function was assessed before and immediately after TMS treatment with a battery of 8 tests. Using a higher TMS intensity as well as a greater number of pulses and having a larger sample size compared with most previous studies, this study found no negative neuropsychological effects of TMS. Changes in neuropsychological function were unrelated to changes in depression.

Ten years of inhibition revisited.

Ten years of inhibition revisited.

Time- and task-dependent non-neural effects of real and sham TMS.

Transcranial magnetic stimulation (TMS) is widely used in experimental brain research to manipulate brain activity in humans. Next to the intended neural effects, every TMS pulse produces a distinct clicking sound and sensation on the head which can also influence task performance. This necessitates careful consideration of control conditions in order to ensure that behavioral effects of interest can be attributed to the neural consequences of TMS and not to non-neural effects of a TMS pulse. Surprisingly, even though these non-neural effects of TMS are largely unknown, they are often assumed to be unspecific, i.e. not dependent on TMS parameters. This assumption is inherent to many control strategies in TMS research but has recently been challenged on empirical grounds. Here, we further develop the empirical basis of control strategies in TMS research. We investigated the time-dependence and task-dependence of the non-neural effects of TMS and compared real and sham TMS over vertex. Critically, we show that non-neural TMS effects depend on a complex interplay of these factors. Although TMS had no direct neural effects, both pre- and post-stimulus TMS time windows modulated task performance on both a sensory detection task and a cognitive angle judgment task. For the most part, these effects were quantitatively similar across tasks but effect sizes were clearly different. Moreover, the effects of real and sham TMS were almost identical with interesting exceptions that shed light on the relative contribution of auditory and somato-sensory aspects of a TMS pulse. Knowledge of such effects is of critical importance for the interpretation of TMS experiments and helps deciding what constitutes an appropriate control condition. Our results broaden the empirical basis of control strategies in TMS research and point at potential pitfalls that should be avoided.

S14-3. Development of a neurorehabilitation technique for elder persons using transcranial magnetic stimulation with maximum voluntary muscle contraction

To evaluate effects of transcranial magnetic stimulation (TMS) with maximum voluntary muscle contraction (MVC) for serial 4 days to facilitate motor neuron function in elder persons, motor evoked potentials (MEPs) and maximum pinching muscle force were recorded sequentially. Four MEPs in the first digital interossei (FDI) muscle elicited by TMS during pinching a strain-gauge transducer with MVC for 2 s were recorded before and at each 15 min interval until 1 h after starting a session (test condition). In a control condition, sham TMS was employed except that real TMS was delivered to record MEPs before and 1 h after the onset of a session. As a result, MEP amplitudes or areas and pinching muscle force were significantly increased by TMS with MVC. Pinching muscle force tended to be significantly larger before starting the sessions from the day 2 to the day 4 in the test condition compared with the control condition. Changes of MEP sizes did not significantly differ between the groups. We think that TMS with MVC for serial days has a potential to facilitate motor function in elder persons. However, we need further studies about the effect of TMS with MVC.