Effects Of Transcranial Magnetic Stimulation Research Articles

Frequency-dependent effects of contralateral repetitive transcranial magnetic stimulation on penicillin-induced seizures

Transcranial magnetic stimulation (TMS) has been shown to modulate multiple brain functions, warranting further exploration in clinical applications. TMS treatment for epilepsy is particularly promising because of its anti-convulsive capabilities. However, TMS has been found to both inhibit and facilitate various experimental and clinical seizures, depending on the TMS parameters used. Repetitive TMS (rTMS) pulse frequency is recognized as one of the most influential parameters and thus was investigated in this study at 1, 5 and 10 Hz for its effects on a rat model of penicillin-induced seizures. High-dose penicillin-induced seizures were characterized by a combination of myoclonic and tonic–clonic (GTC) seizures. rTMS effects were analyzed with intracranial electroencephalographic (iEEG) data and video-captured behaviors. Animals treated with 1 and 5Hz consistently showed evidence of anti-convulsive properties in their iEEG-based seizure profiles when compared to sham rTMS treatment. In contrast, data from 10Hz rTMS suggested facilitative characteristics. Our results showed that 5 Hz rTMS consistently outperformed 1 Hz rTMS in seizure suppression. This re-emphasizes the importance in accurately characterizing TMS effects on seizure suppression due to the heterogeneous nature of seizures. Thus, finely tuned TMS treatment has great potential to become a powerful asset in combating epilepsy.

A Review of the Effects of Hypoxia, Sleep Deprivation and Transcranial Magnetic Stimulation on EEG Activity in Humans: Challenges for Drug Discovery for Alzheimer’s Disease

Different kinds of challenge can alter cognitive process and electroencephalographic (EEG) rhythms in humans. This can provide an alternative paradigms to evaluate treatment effects in drug discovery. Here, we report recent findings on the effects of challenges represented by sleep deprivation (SD), transient hypoxia, and transcranial magnetic stimulation (TMS) in healthy volunteers on cognitive processes and EEG rhythms to build a knowledge platform for novel research for drug discovery in AD Alzheimer's disease (AD). Sleep pressure enhanced frontal delta rhythms (< 4 Hz) during the night, while SD increased slow rhythms in the theta range (4-7 Hz), and reduced resting state alpha rhythms (8-12 Hz) after the following day. Furthermore, SD transiently affected cognitive performance. In contrast, transient experimental hypoxia induced abnormal posterior resting state delta and alpha rhythms in healthy volunteers that resemble the abnormal EEG rhythms typically recorded in AD patients. However, the relationship between the cognitive and EEG effects of such challenges is poorly understood. TMS reversibly interfered with higher brain functions during EEG recordings, but few studies have investigated the relationship between the cognitive and EEG effects of TMS. In conclusion, SD is the most mature challenge model for testing new drugs for AD. Future investigation is needed to better understand the opportunities offered by TMS and hypoxia challenges.

Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

The Future of Neuromodulation: Transcranial Magnetic Stimulation

This month’s issue of Psychiatric Annals, guest edited by Geoffrey Grammer, MD, and Tarique Perera, MD, features a very informative series of articles reviewing transcranial magnetic stimulation (TMS). It is a comprehensive review, beginning with an overview of neuromodulation by Brock and Demitrack and then a discussion of the science of TMS by Sauve and Crowther, followed by a review of TMS’ clinical efficacy in depression by Janicak and Carpenter. Grammer and his associates provide an interesting review of the role of TMS in other psychiatric disorders, followed by a current review of the effects of TMS in several neurological diseases by Shafi and his colleagues. The last article in this series by Hutton addresses the broader issue of the clinical application of TMS. This article addresses the vast difference in clinical practice that TMS presents—an office-based model of a procedure that is so different from the psychopharmacological and psychotherapeutic approaches that have been traditional in psychiatric practice. In this article, Hutton touches on the marketing, various models for receiving access to use this treatment, insurance coverage trends, and the evolving nature of this treatment as new technologies and techniques for its delivery are incorporated into practice. It appears that the efficacy of TMS is increasing as new technology and clinical techniques of administration are being developed. It also appears that the economic support by insurance companies is expanding as efficacy data improve. TMS is but one of a number of neuromodulation techniques being made available and being studied, as well as improved. Vagus nerve stimulation, deep brain stimulation, and newer forms of electroconvulsive therapy are being reported. However, TMS is the only treatment that has a potential to change the outpatient office-based treatment of psychiatric conditions. As efficacy improves with experience and further development and financial support improves through the extension of insurance coverage, based on improving efficacy, this technique could expand and broaden psychiatric practice. We should pay close attention to the evolution of this treatment—we might even incorporate it in the teaching of our psychiatric residents.

P645: Case report: seizure induction by single-pulse transcranial magnetic stimulation after anodal transcranial direct current stimulation in a stroke patient

s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S225 Abstract P643 – Figure 1. Excitability modulation induced by paired pulses for the hand APB as a function of ISI for 4 capacitor combinations.P643 – Figure 1. Excitability modulation induced by paired pulses for the hand APB as a function of ISI for 4 capacitor combinations. Abstract P643 – Figure 2. Excitability modulation induced by paired pulses at ISIs of 200, 400 and 600 μs.P643 – Figure 2. Excitability modulation induced by paired pulses at ISIs of 200, 400 and 600 μs. different stimulation patterns in various channels. Multiple pulses operation with coils with various depth profiles can increase the focality of TMS effect in deep brain regions. P644 Anticipatory motor control is mediated via the left posterior parietal cortex (PPC) V. Krause, J. Weber, B. Pollok Heinrich-Heine-University, Institute of Clinical Neuroscience and Medical Psychology, Duesseldorf, Germany Question: Within the motor control network the posterior parietal cortex (PPC) has been related to anticipatory motor control while the primary motor cortex (M1) may be rather dedicated to movement execution. Assuming that cortical nodes within this network provide different contributions to motor control, the present study elucidates the specific relevance of left PPC for movement timing. Methods: Anodal vs. cathodal transcranial direct current stimulation (tDCS) was applied for 10 min over left PPC in right-handed subjects in separate sessions. Left M1 tDCS served as control condition. Anticipatory motor control was assessed by means of a synchronization task requiring subjects to synchronize their own finger taps with a regular auditory metronome. In addition, subjects performed a continuation task investigating interval reproduction and a simple auditory reaction task. Tasks were performed with the right and the left hand, respectively, prior to and immediately after tDCS. Results: Anodal left PPC tDCS decreased synchronization accuracy of either hand during the synchronization task. During continuation, cathodal left PPC tDCS increased the reproduced interval of the left hand but decreased the interval of the right hand. Reaction times were not significantly modulated by PPC stimulation. Left M1 tDCS was not efficient to significantly modulate performance in any of the tasks. Conclusions: The present data underline the superordinate role of left PPC for anticipatory motor control of either hand revealing a piece of evidence for left hemispheric PPC dominance. The observed effects cannot be explained by alterations of motor cortical excitability. P645 Case report: seizure induction by single-pulse transcranial magnetic stimulation after anodal transcranial direct current stimulation in a stroke patient S. Koganemaru1,2, A. Ikeda3, R. Takahashi3, H. Fukuyama1, T. Mima1 1Kyoto universtiy, Human Brain Research Center, Kyoto, Japan; 2Kyoto universtiy, Integrative Brain Science, Kyoto, Japan; 3Kyoto university, Neurology, Kyoto, Japan Transcranial direct current stimulation (tDCS) has been used as a safe therapeutic tool in neurological disorders, especially in stroke, because anodal stimulation given over the affected M1 area produces LTP-like effects on corticospinal excitability. Single-pulse transcranial magnetic stimulation (TMS) has been used as an evaluation tool of corticospinal excitability even in stroke, with a minimal risk of de novo seizure induction. Here, we report a 35 year-old male with postoperative subcortical hemorrhage in the left hemisphere, who developed a generalized convulsion starting from the affected upper limb after a single-pulse TMS subsequent to the anodal tDCS given over the ipsilesional M1 hand area for 10 minutes. He had no history of seizure or electroencephalogram (EEG) abnormality, and received several TMS tests without any side effects before tDCS intervention. EEG testing just after and 3 month after the event revealed no epileptiform discharges. He has been seizure-free at least for 3 months. The present case report raises the possibility that a single-pulse TMS after tDCS may be associated with a seizure risk in patients with brain lesion due to their accumulative excitatory effects. P646 Transcranial direct current stimulation (tDCS) in the treatment of adolescents with attention deficit hyperactivity disorder (ADHD) A. Sotnikova1, C. Soff1, K. Becker1, M. Siniatchkin2 1University of Marburg, Department of Child and Adolescents Psychiatry, Marburg, Germany; 2Goethe-University of Frankfurt, Department of Child and Adolescents Psychiatry, Frankfurt, Germany Question: The stimulation of the brain with weak direct current through the scalp (tDCS) is a safe, well tolerable and effective procedure which

The role of prefrontal and parietal cortices in esthetic appreciation of representational and abstract art: A TMS study

To explain the biological foundations of art appreciation is to explain one of our species' distinctive traits. Previous neuroimaging and electrophysiological studies have pointed to the prefrontal and the parietal cortex as two critical regions mediating esthetic appreciation of visual art. In this study, we applied transcranial magnetic stimulation (TMS) over the left prefrontal cortex and the right posterior parietal cortex while participants were evaluating whether they liked, and by how much, a particular painting. By depolarizing cell membranes in the targeted regions, TMS transiently interferes with the activity of specific cortical areas, which allows clarifying their role in a given task. Our results show that both regions play a fundamental role in mediating esthetic appreciation. Critically though, the effects of TMS varied depending on the type of art considered (i.e. representational vs. abstract) and on participants' a-priori inclination toward one or the other.

Cerebellar vermis plays a causal role in visual motion discrimination

Cerebellar patients have been found to show deficits in visual motion discrimination, suggesting that the cerebellum may play a role in visual sensory processing beyond mediating motor control. Here we show that triple-pulse online transcranial magnetic stimulation (TMS) over cerebellar vermis but not over the cerebellar hemispheres significantly impaired motion discrimination. Critically, the interference caused by vermis TMS on motion discrimination did not depend on an indirect effect of TMS over nearby visual areas, as demonstrated by a control experiment in which TMS over V1 but not over cerebellar vermis significantly impaired orientation discrimination. These findings demonstrate the causal role of the cerebellar vermis in visual motion processing in neurologically normal participants.

Disruption of Locomotor Adaptation with Repetitive Transcranial Magnetic Stimulation Over the Motor Cortex

Locomotor patterns are adapted on a trial-and-error basis to account for predictable dynamics. Once a walking pattern is adapted, the new calibration is stored and must be actively de-adapted. Here, we tested the hypothesis that storage of newly acquired ankle adaptation in walking is dependent on corticospinal mechanisms. Subjects were exposed to an elastic force that resisted ankle dorsiflexion during treadmill walking. Ankle movement was adapted in <30 strides, leading to after-effects on removal of the force. We used a crossover design to study the effects of repetitive transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), compared with normal adaptation without TMS. In addition, we tested the effects of TMS over the primary sensory cortex (S1) and premotor cortex (PMC) during adaptation. We found that M1 TMS, but not S1 TMS and PMC TMS, reduced the size of ankle dorsiflexion after-effects. The results suggest that suprathreshold M1 TMS disrupted the initial processes underlying locomotor adaptation. These results are consistent with the hypothesis that corticospinal mechanisms underlie storage of ankle adaptation in walking.

The Efficacy of Electroconvulsive Therapy in Major Depressive Disorder Relapsed or Unresponsive to Transcranial Magnetic Stimulation in Pregnancy: Three Case Studies

About 5-10% of women experience depression during pregnancy. The potentially adverse effects of pharmacological treatment (e.g. teratogenicity, toxicity, foetal developmental abnormalities and withdrawal symptoms) on both the mother and the foetus mean that psychopharmacological treatments have limited application for pregnant women. In these cases treatment needs to be tailored to the individual patient and non-pharmacological options may be appropriate. Transcranial Magnetic Stimulation (TMS) and Electroconvulsive treatment (ECT) may be viable alternatives for these patients. We report on three patients in their first trimester of pregnancy suffering from major depressive disorder (MDD). All three were initially treated with TMS and psychotherapy because of the reduced risk of side effects. Two patients failed to respond adequately to treatment and were switched to ECT. The third patient displayed an adequate response to TMS but failed to maintain the improvement. This patient had to receive ECT in the post-partum period due to on-going depressive symptoms. Subsequently this patient responded adequately to ECT. Further studies of novel, non-pharmacological treatment methods for MDD during pregnancy (such as TMS and ECT) and detailed investigations of the factors associated with treatment responses in such patients are needed. Our cases demonstrate the need to evaluate the effectiveness of TMS in larger samples of pregnant patients diagnosed with MDD.

The effects of lateral prefrontal transcranial magnetic stimulation on item memory encoding

Previous neuroimaging research has established that the left ventrolateral prefrontal cortex (VLPFC) is involved in long-term memory (LTM) encoding for individual items. Dorsolateral prefrontal cortex (DLPFC) is implicated less frequently, and one theory that has gained support to explain this discrepancy is that DLPFC is involved in forming item-item relational but not item LTM. Given that neuroimaging results are correlational, complimentary methods such as repetitive transcranial magnetic stimulation (TMS) have been used to test causal hypotheses generated from imaging data. Most TMS studies of LTM encoding have found that disruption of lateral PFC activity impairs subsequent memory. However these studies have lacked methods to precisely localize and directly compare TMS effects from frontal subregions implicated by the neuroimaging literature. Here, we target specific subregions of lateral PFC with TMS to test the prediction from the item/relational framework that temporary disruption of VLPFC during encoding will impair subsequent memory whereas TMS to DLPFC during item encoding will not. Frontal TMS was administered prior to a LTM encoding task in which participants were presented with a list of individual nouns and asked to judge whether each noun was concrete or abstract. After a 40min delay period, item recognition memory was tested. Results indicate that VLPFC and DLPFC TMS have differential effects on subsequent item memory. VLPFC TMS reliably disrupted subsequent item memory whereas DLPFC TMS led to numerical enhancement in item memory, relative to TMS to a control region.

Motor cortical processing is causally involved in object recognition

BackgroundMotor activity during vicarious experience of actions is a widely reported and studied phenomenon, and motor system activity also accompanies observation of graspable objects in the absence of any actions. Such motor activity is thought to reflect simulation of the observed action, or preparation to interact with the object, respectively.ResultsHere, in an initial exploratory study, we ask whether motor activity during observation of object directed actions is involved in processes related to recognition of the object after initial exposure. Single pulse Transcranial Magnetic Stimulation (TMS) was applied over the thumb representation of the motor cortex, or over the vertex, during observation of a model thumb typing on a cell-phone, and performance on a phone recognition task at the end of the trial was assessed. Disrupting motor processing over the thumb representation 100 ms after the onset of the typing video impaired the ability to recognize the phone in the recognition test, whereas there was no such effect for TMS applied over the vertex and no TMS trials. Furthermore, this effect only manifested for videos observed from the first person perspective. In an additional control condition, there was no evidence for any effects of TMS to the thumb representation or vertex when observing and recognizing non-action related shape stimuli.ConclusionOverall, these data provide evidence that motor cortical processing during observation of object-directed actions from a first person perspective is causally linked to the formation of enduring representations of objects-of-action.

Inter-individual variation in reciprocal Ia inhibition is dependent on the descending volleys delivered from corticospinal neurons to Ia interneurons

IntroductionWe investigated the extent to which the corticospinal inputs delivered to Ia inhibitory interneurons influence the strength of disynaptic reciprocal Ia inhibition. MethodsSeventeen healthy subjects participated in this study. The degree of reciprocal Ia inhibition was determined via short-latency (condition-test interval: 1–3ms) suppression of Sol H-reflex by conditioning stimulation of common peroneal nerve. The effect of corticospinal descending inputs on Ia inhibitory interneurons was assessed by evaluating the conditioning effect of transcranial magnetic stimulation (TMS) on the Sol H-reflex. Then, we determined the relationship between the degree of reciprocal Ia inhibition and the conditioning effect of TMS on the Sol H-reflex. ResultWe found that the degree of reciprocal Ia inhibition and the extent of change in the amplitude of the TMS-conditioned H-reflex, which was measured from short latency facilitation to inhibition, displayed a strong correlation (r=0.76, p<0.01) in the resting conditions. ConclusionThe extent of reciprocal Ia inhibition is affected by the corticospinal descending inputs delivered to Ia inhibitory interneurons, which might explain the inter-individual variations in reciprocal Ia inhibition.

Trait-like Differences in Underlying Oscillatory State Predict Individual Differences in the TMS-evoked Response

BackgroundCombined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) can provide insights into how differing cognitive contexts produce different brain states, through TMS-based measures of effective connectivity. For instance, in a recent study, the amplitude of the TMS-evoked response (TMS-ER) derived during the delay-period of a spatial short-term memory (STM) task had a larger amplitude, and greater spread to distal cortical areas, than the TMS-ER from a fixation condition (Johnson et al. J Neurophysiol, 2012). This indicated that the brain's electrical response to TMS is influenced by the cognitive context (STM or fixation) at the time of stimulation. This study also showed significant individual differences in the shape of the TMS-ER. Further, delay-period spectrograms revealed patterns of activity, the sustained pattern of delay-period activity (SPDPA), which were different across individuals. Objective/hypothesisThe present study addressed whether individual differences in the SPDPA predict spectral properties of the TMS-ER. We predicted that significant relationships would exist in task-relevant areas, such as the prefrontal cortex in the case of STM. MethodsThe TMS-ER was derived using TMS-EEG and source-localization methods. ResultsThe SPDPA varied significantly across subjects, and these differences predicted individual differences in several frequency-dependent parameters of the TMS-ER that were specific to task-relevant areas, including prefrontal cortex for STM. Furthermore, a follow-up test–retest study revealed that the SPDPA was stable over sessions. ConclusionsThese observations offer a window into how individual differences in the effects of TMS are related to trait-like individual differences in physiological profile.

Cortical brain states and corticospinal synchronization influence TMS-evoked motor potentials

Transcranial magnetic stimulation (TMS) influences cortical processes. Recent findings indicate, however, that, in turn, the efficacy of TMS depends on the state of ongoing cortical oscillations. Whereas power and phase of electromyographic (EMG) activity recorded from the hand muscles as well as neural synchrony between cortex and hand muscles are known to influence the effect of TMS, to date, no study has shown an influence of the phase of cortical oscillations during wakefulness. We applied single-pulse TMS over the motor cortex and recorded motor-evoked potentials along with the electroencephalogram (EEG) and EMG. We correlated phase and power of ongoing EEG and EMG signals with the motor-evoked potential (MEP) amplitude. We also investigated the functional connectivity between cortical and hand muscle activity (corticomuscular coherence) with the MEP amplitude. EEG and EMG power and phase in a frequency band around 18 Hz correlated with the MEP amplitude. High beta-band (∼34 Hz) corticomuscular coherence exhibited a positive linear relationship with the MEP amplitude, indicating that strong synchrony between cortex and hand muscles at the moment when TMS is applied entails large MEPs. Improving upon previous studies, we demonstrate a clear dependence of TMS-induced motor effects on the state of ongoing EEG phase and power fluctuations. We conclude that not only the sampling of incoming information but also the susceptibility of cortical communication flow depends cyclically on neural phase.

Mechanisms and pathways underlying the therapeutic effect of transcranial magnetic stimulation

It has been almost 40 years since Barker, Jalinous, and Freeston designed and used the first device of transcranial magnetic stimulation (TMS). From then until now, this technique has evolved vertiginously, appearing a lot of new protocols and device modifications, which associated with new technologies complement and enhance the versatility of this technique. TMS has demonstrated to be a safe technology and become a key tool in the study of the complex brain processes. Despite this, it is as a therapeutic tool where this technique has caused a revolution. In this regard, this type of non-invasive brain stimulation has been proven useful in a variety of neurodegenerative and psychiatric disorders due to its biochemical, molecular, and cellular effects, with depression being the paradigm of the therapeutic effectiveness of this technique. This review focuses on a detailed vision of how this type of radiation modifies different biochemical and cellular processes that induce the mechanisms and pathways underlying the therapeutic effects of TMS.

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.

P 222. Studying the dynamics of the TMS-EEG signal

Introduction Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has proven to be a useful tool when probing the effective connectivity. However, the TMS-evoked responses seem to vary significantly from trial to another. This is partially due to the constantly changing underlying brain state, which is likely to affect the evoked response. Thus, it is important to understand the relationship between the current brain state dynamics and the evoked TMS-EEG responses. This work concentrates on the non-linear dynamic behaviour of EEG signal before and after TMS stimuli. Objectives Our objective is to study the effects of TMS on the dynamics of the brain state as well as the effects of the current brain state dynamics on the TMS-evoked responses. Materials and methods In the analysis, 16 different TMS-EEG data sets, where the stimuli had been delivered on the left primary motor cortex with 100% motor threshold intensity. The Nexstim eXimia magnetic stimulator and TMS-compatible EEG system were used to collect the data. It is known that the trajectory of a system in the state space can reveal some vital properties of the underlying dynamics. In this work, we studied the projection of the state-space trajectory onto the EEG signal space using 16 EEG channels confining the stimulation area. The data analysis consisted of computation of three commonly known non-linear measures for trial-level data: quantitative recurrence analysis, Lyapunov stability, and correlation dimension. In short, the recurrence analysis measures the distances between the state vectors defining the state of the system as a function of time. Lyapunov stability is used to describe the chaotic properties of the system, whereas correlation dimension measures the complexity of the underlying system. In the figure one can see a schematic picture of the hypothesis behind the present work. The post-synaptic currents (A) define accurately the electric state of the brain. The brain state advances spontaneously in the state space (red line). However, TMS might shift the system rapidly to a certain subset and also affect the later motion of the trajectory (green line). We can observe the projection of the trajectory on the EEG signal space (dotted lines) spanned by channels ch i and ch j . Results The mean distance between the state vectors right before and right after the stimulus was greater than the mean distance separating state vectors during spontaneous activity. Furthermore, the results indicated that the state vector was moving faster during approximately 300-ms long period after the stimulus than during spontaneous activity. The results also showed some evidence that the correlation dimension might decrease as an effect of TMS. With the present data available the Lyapunov-stability analysis did not show clear results. Conclusion The results indicate that the “artificial” activity created by TMS is propagating faster in the system than the spontaneous activity. This might be due to higher local free energy close to the stimulation site, which the system tries to minimize as fast as possible. Furthermore, it seems that TMS actually does shift the brain state to a slightly different subset in the brain state space.

P 206. Monitoring short term effects of repetitive transcranial magnetic stimulation (TMS) by TMS-evoked potentials in children

Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children. TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available. In a single-blind sham-controlled study, 25 school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition. TMS-evoked N100 amplitude decr eased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation. The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition.

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.

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.