Combined Transcranial Magnetic Stimulation Research Articles

Direct interrogation of cortical interneuron circuits in amyotrophic lateral sclerosis.

Cortical hyperexcitability is a key pathogenic feature of amyotrophic lateral sclerosis (ALS), believed to be mediated through complex interplay of cortical interneurons. To date, there has been no technological approach to facilitate the direct capture of cortical interneuron function. Through combination of transcranial magnetic stimulation (TMS) with advanced EEG, the present study examined GABA-ergic dysfunction in ALS, through recording focussed cortical output whilst applying TMS over the primary motor cortex contralateral to the site of symptom onset. Using both a single pulse and novel inhibitory paired-pulse paradigms, TMS-EEG studies were undertaken on 21 ALS patients and results compared to healthy controls. TMS responses captured by EEG form a discrete waveform known as the transcranial evoked potential (TEP), with positive (P) or upward deflections occurring at 30ms (P30), 60 ms (P60) and 190 ms (P190) after TMS stimulus. Negative (N) or downward deflections occur at 44 ms (N44), 100 ms (N100) and 280ms (N280) after T,MS stimulus. The single pulse TEPs recorded in ALS patients demonstrated novel differences suggestive of cortical GABA-ergic dysfunction. When compared to controls, the N100 component was significantly reduced (P<0.05) while the P190 component increased (P<0.05) in ALS patients. Additionally, the N44 component correlated with muscle weakness (r=-0.501, P<0.05). These finding were supported by reduced paired pulse inhibition of TEP components in ALS patients (P60, P<0.01; N100, P<0.005), consistent with dysfunction of cortical interneuronal GABAA-ergic circuits. Further, the reduction in SICI, as reflected by changes in paired-pulse inhibition of the N100 component, was associated with longer disease duration in ALS patients (r=-0.698, P<0.001). In conclusion, intensive and focussed interrogation of the motor cortex utilising novel TMS-EEG combined technologies has established localised dysfunction of GABA-ergic circuits, supporting the notion that cortical hyperexcitability is mediated by cortical disinhibition in ALS. Dysfunction of GABA-ergic circuits correlated with greater clinical disability and disease duration implying pathophysiological significance.

Involvement of muscarinic acetylcholine receptor-mediated cholinergic neurotransmission in TMS–EEG responses

The combination of transcranial magnetic stimulation and electroencephalography (TMS–EEG) is emerging as a valuable tool for investigating brain functions in health and disease. However, the detailed neural mechanisms underlying TMS–EEG responses, including TMS-evoked EEG potentials (TEPs) and TMS-induced EEG oscillations (TIOs), remain largely unknown. Combining TMS–EEG with pharmacological interventions provides a unique opportunity to elucidate the roles of specific receptor-mediated neurotransmissions in these responses. Here, we investigated the involvement of muscarinic acetylcholine receptor (mAChR)-mediated cholinergic neurotransmission in TMS–EEG responses by evaluating the effects of mAChR antagonists on TEPs and TIOs in twenty-four healthy participants using a randomized, placebo-controlled crossover design. TEPs and TIOs were measured before and after administering a single oral dose of scopolamine (a non-selective mAChR antagonist), biperiden (an M1 mAChR antagonist), or placebo, with TMS targeting the left medial prefrontal cortex (mPFC), angular gyrus (AG), and supplementary motor area (SMA). The results indicated that mAChR-mediated cholinergic neurotransmission played a role in TEPs, but not TIOs, in a target-specific manner. Specifically, scopolamine significantly increased the amplitude of a local TEP component between approximately 40 and 63 ms post-stimulus when TMS was applied to the SMA, but not the mPFC or AG. Biperiden produced a similar but less pronounced effect. Importantly, the effects of these mAChR antagonists on TEPs were independent of those on sensory-evoked EEG potentials caused by TMS-associated sensory stimulation. These findings expand our understanding of TMS–EEG physiology, providing insights for its application in physiological and clinical research.

Towards the definition of a standard in TMS-EEG data preprocessing

Combining Non-Invasive Brain Stimulation (NIBS) techniques with the recording of brain electrophysiological activity is an increasingly widespread approach in neuroscience. Particularly successful has been the simultaneous combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Unfortunately, the strong magnetic pulse required to effectively interact with brain activity inevitably induces artifacts in the concurrent EEG acquisition. Therefore, a careful but aggressive pre-processing is required to efficiently remove artifacts. Unfortunately, as already reported in the literature, different preprocessing approaches can introduce variability in the results. Here we aim at characterizing the three main TMS-EEG preprocessing pipelines currently available, namely ARTIST (Wu et al., 2018), TESA (Rogasch et al., 2017) and SOUND/SSP-SIR (Mutanen et al., 2018, 2016), providing an insight to researchers who need to choose between different approaches. Differently from previous works, we tested the pipelines using a synthetic TMS-EEG signal with a known ground-truth (the artifacts-free to-be-reconstructed signal). In this way, it was possible to assess the reliability of each pipeline precisely and quantitatively, providing a more robust reference for future research. In summary, we found that all pipelines performed well, but with differences in terms of the spatio-temporal precision of the ground-truth reconstruction. Crucially, the three pipelines impacted differently on the inter-trial variability, with ARTIST introducing inter-trial variability not already intrinsic to the ground-truth signal.

Effects of auricular vagus nerve stimulation and electrical earlobe stimulation on motor-evoked potential changes induced by paired associative stimulation.

Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS). PAS can induce long-term potentiation (LTP)-like plasticity in humans, manifested as motor-evoked potential (MEP) enhancement. We have developed a variant of PAS ("high-PAS"), which consists of high-frequency PNS and high-intensity TMS and targets spinal plasticity and promotes rehabilitation after spinal cord injury (SCI). Vagus nerve stimulation (VNS) promotes LTP-like plasticity and enhances recovery in SCI and stroke in humans and animals when combined with repetitive motor training. We combined high-PAS with simultaneous noninvasive transcutaneous auricular VNS (aVNS) to determine if aVNS enhances the extent of PAS-induced MEP amplitude increase. Sixteen healthy participants were stimulated for 20 min in four different sessions (PAS, PAS + aVNS, PAS + shamVNS, and aVNS) in a randomized single-blind setup. MEPs were measured before, immediately after, and at 30, 60, and 90 min post-stimulation. Stimulation protocols with PAS significantly potentiated MEPs (p= 0.005) when compared with aVNS (p= 0.642). Although not significant, MEP enhancement observed after PAS (43.5%) is further increased by aVNS (49.7%) and electrical earlobe stimulation (63.9%). Our aVNS setup failed to significantly enhance the effect of PAS, but sham VNS revealed a trend towards enhanced plasticity. Optimization of auricular VNS stimulation setup is required for possible tests of patients with SCI.

Intermittent theta burst stimulation of the left dorsolateral prefrontal cortex has no additional effect on the efficacy of virtual reality exposure therapy for acrophobia. A randomized double-blind placebo-controlled study

Anxiety disorders are among the most common mental disorders. Treatment guidelines recommend pharmacotherapy and cognitive behavioral therapy as standard treatment. Although cognitive behavioral therapy is an effective therapeutic approach, not all patients benefit sufficiently from it. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, have been investigated as promising adjuncts in the treatment of affective disorders. The aim of this study is to investigate whether a combination of intermittent theta burst stimulation (iTBS) and virtual reality exposure therapy leads to a significantly greater reduction in acrophobia than virtual reality exposure with sham stimulation. In this randomized double-blind placebo-controlled study, 43 participants with acrophobia received verum or sham iTBS over the left dorsolateral prefrontal cortex prior to two sessions of virtual reality exposure therapy. Stimulation of the left dorsolateral prefrontal cortex with iTBS was motivated by an experimental study showing a positive effect on extinction memory retention. Acrophobic symptoms were assessed using questionnaires and two behavioral approach tasks one week before, after treatment and six months after the second diagnostic session. The results showed that two sessions of virtual reality exposure therapy led to a significant reduction in acrophobic symptoms, with an overall remission rate of 79 %. However, there was no additional effect of iTBS of the left dorsolateral prefrontal cortex on the therapeutic effects. Further research is needed to determine how exactly a combination of transcranial magnetic stimulation and exposure therapy should be designed to enhance efficacy.

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans.

Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans

Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.

Influence of Large-Scale Brain State Dynamics on the Evoked Response to Brain Stimulation.

Understanding how spontaneous brain activity influences the response to neurostimulation is crucial for the development of neurotherapeutics and brain-computer interfaces. Localized brain activity is suggested to influence the response to neurostimulation, but whether fast-fluctuating (i.e., tens of milliseconds) large-scale brain dynamics also have any such influence is unknown. By stimulating the prefrontal cortex using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG), we examined how dynamic global brain state patterns, as defined by microstates, influence the magnitude of the evoked brain response. TMS applied during what resembled the canonical microstate C was found to induce a greater evoked response for up to 80 milliseconds compared to other microstates. This effect was found in a repeated experimental session, was absent during sham stimulation, and was replicated in an independent dataset. Ultimately, ongoing and fast-fluctuating global brain states, as probed by microstates, may be associated with intrinsic fluctuations in connectivity and excitation-inhibition balance and influence the neurostimulation outcome. We suggest that the fast-fluctuating global brain states be considered when developing any related paradigms.Significance Statement Previous findings suggested local spontaneous neural oscillations can influence neurophysiological response to stimuli. However, beyond the local oscillatory activity, the brain state is rapidly fluctuating on a millisecond time resolution on a global spatial scale. We investigated whether these rapid global fluctuations influenced the evoked response to brain stimulation. We used combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) to stimulate the prefrontal cortex while recording global brain states via EEG microstates. The evoked neurophysiological response was significantly larger when stimulation was applied after the occurrence of a specific global brain state (i.e., microstate C) linked to mind-wandering. The finding was selective to active stimulation, replicated for the same individuals in a repeated session, and replicated in an entirely independent dataset.

New functional dissociations between prefrontal and parietal cortex during task switching: A combined fMRI and TMS study

Preparatory control in task-switching has been suggested to rely upon a set of distributed regions within a frontoparietal network, with frontal and parietal cortical areas cooperating to implement switch-specific preparation processes. Although recent causal evidence using transcranial magnetic stimulation (TMS) have generally supported this model, alternative results from both functional neuroimaging and neurophysiological studies have questioned the switch-specific role of both frontal and parietal cortices. The aim of the present study was to clarify the involvement of prefrontal and parietal areas in preparatory cognitive control. With this purpose, an fMRI study was conducted to identify the brain areas activated during cue events in a task-switching paradigm, indicating whether to switch or to repeat among numerical tasks. Then, TMS was applied over the specific coordinates previously identified through fMRI, that is, the right inferior frontal gyrus (IFG) and right intraparietal sulcus (IPS). Results revealed that TMS over the right IFG disrupted performance in both switch and repeat trails in terms of delayed responses as compared to Sham condition. In contrast, TMS over the right IPS selectively interfered performance in switch trials. These findings support a multi-component model of executive control with the IFG being involved in more general switch-unspecific process such as the episodic retrieval of goals, and the IPS being related to the implementation of switch-specific preparation mechanisms for activating stimulus-response mappings. The results are discussed within the framework of contemporary hierarchical models of prefrontal cortex organization, suggesting that distinct prefrontal areas may carry out coordinated functions in preparatory control.

Combination of Transcranial Magnetic Stimulation and Ketamine in Treatment-Resistant Depression: A Systematic Review.

Treatment-resistant depression (TRD) is a significant challenge in psychiatric practice, affecting a substantial proportion of patients with major depressive disorder (MDD). Traditional treatment modalities often fall short, necessitating the exploration of alternative therapies. This literature review examines the combined use of Transcranial Magnetic Stimulation (TMS) and ketamine in treating TRD. The objectiveof this study is toevaluate the efficacy, safety, and potential synergies of combining TMS and ketamine in the treatment of TRD. A comprehensive literature search was conducted using PubMed and Google Scholar databases from 2014 to 2024. The search terms included combinations of "Transcranial Magnetic Stimulation," "Ketamine," "Depression," "Major Depressive Disorder," "Treatment-Resistant Depression," and "Combination." After screening for relevance and applying inclusion and exclusion criteria, six studies were selected for review, including three case reports, a retrospective study, a pilot study, and a review study. The selected studies demonstrated that the combination of TMS and ketamine resulted in substantial and sustained improvement in depressive symptoms for patients with TRD. Case reports and retrospective studies highlighted significant reductions in depression severity and improvements in psychosocial functioning. The combination therapy showed a higher efficacy compared to monotherapies of either TMS or ketamine alone. Notably, adverse effects were generally mild and transient, with no severe adverse events reported in most studies. In conclusion, the combination of TMS and ketamine presents a promising treatment modality for patients with TRD, offering significant improvements in depressive symptoms and better outcomes compared to traditional monotherapies. However, the heterogeneity in study designs and small sample sizes underline the need for larger, randomized controlled trials to establish standardized protocols and further validate these findings.

Combination of transcranial magnetic stimulation with guided imagery for treating OCD in an adolescent girl.

Combination of transcranial magnetic stimulation with guided imagery for treating OCD in an adolescent girl.

A simulation study: comparing independent component analysis and signal-space projection - source-informed reconstruction for rejecting muscle artifacts evoked by transcranial magnetic stimulation.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows researchers to explore cortico-cortical connections. To study effective connections, the first few tens of milliseconds of the TMS-evoked potentials are the most critical. Yet, TMS-evoked artifacts complicate the interpretation of early-latency data. Data-processing strategies like independent component analysis (ICA) and the combined signal-space projection-source-informed reconstruction approach (SSP-SIR) are designed to mitigate artifacts, but their objective assessment is challenging because the true neuronal EEG responses under large-amplitude artifacts are generally unknown. Through simulations, we quantified how the spatiotemporal properties of the artifacts affect the cleaning performances of ICA and SSP-SIR. We simulated TMS-induced muscle artifacts and superposed them on pre-processed TMS-EEG data, serving as the ground truth. The simulated muscle artifacts were varied both in terms of their topography and temporal profiles. The signals were then cleaned using ICA and SSP-SIR, and subsequent comparisons were made with the ground truth data. ICA performed better when the artifact time courses were highly variable across the trials, whereas the effectiveness of SSP-SIR depended on the congruence between the artifact and neuronal topographies, with the performance of SSP-SIR being better when difference between topographies was larger. Overall, SSP-SIR performed better than ICA across the tested conditions. Based on these simulations, SSP-SIR appears to be more effective in suppressing TMS-evoked muscle artifacts. These artifacts are shown to be highly time-locked to the TMS pulse and manifest in topographies that differ substantially from the patterns of neuronal potentials. Selecting between ICA and SSP-SIR should be guided by the characteristics of the artifacts. SSP-SIR might be better equipped for suppressing time-locked artifacts, provided that their topographies are sufficiently different from the neuronal potential patterns of interest, and that the SSP-SIR algorithm can successfully find those artifact topographies from the high-pass-filtered data. ICA remains a powerful tool for rejecting artifacts that are not strongly time locked to the TMS pulse.

Breakdown of effective information flow in disorders of consciousness: Insights from TMS-EEG

BackgroundThe complexity of the neurophysiological mechanisms underlying human consciousness is widely acknowledged, with information processing and flow originating in cortex conceived as a core mechanism of consciousness emergence. Combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is considered as a promising technique to understand the effective information flow associated with consciousness. ObjectivesTo investigate information flow with TMS-EEG and its relationship to different consciousness states. MethodsWe applied an effective information flow analysis by combining time-varying multivariate adaptive autoregressive model and adaptive directed transfer function on TMS-EEG data of frontal, motor and parietal cortex in patients with disorder of consciousness (DOC), including 14 vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients, 21 minimally conscious state (MCS) patients, and 22 healthy subjects. ResultsTMS in DOC patients, particularly VS/UWS, induced a significantly weaker effective information flow compared to healthy subjects. The bidirectional directed information flow was lost in DOC patients with TMS of frontal, motor and parietal cortex. The interactive ROI rate of the information flow network induced by TMS of frontal and parietal cortex was significantly lower in VS/UWS than in MCS. The interactive ROI rate correlated with DOC clinical scales. ConclusionsTMS-EEG revealed a physiologically relevant correlation between TMS-induced information flow and levels of consciousness. This suggests that breakdown of effective cortical information flow serves as a viable marker of human consciousness. SignificanceFindings offer a unique perspective on the relevance of information flow in DOC, thus providing a novel way of understanding the physiological basis of human consciousness.

A comprehensive characterization of cognitive performance, clinical symptoms, and cortical activity following mild traumatic brain injury (mTBI)

Objective The objective of this study was to investigate clinical symptoms, cognitive performance and cortical activity following mild traumatic brain injury (mTBI). Methods We recruited 30 individuals in the sub-acute phase post mTBI and 28 healthy controls with no history of head injury and compared these groups on clinical, cognitive and cortical activity measures. Measures of cortical activity included; resting state electroencephalography (EEG), task related EEG and combined transcranial magnetic stimulation with electroencephalography (TMS-EEG). Primary analyses investigated clinical, cognitive and cortical activity differences between groups. Exploratory analyses investigated the relationships between these measures. Results At 4 weeks’ post injury, mTBI participants exhibited significantly greater post concussive and clinical symptoms compared to controls; as well as reduced cognitive performance on verbal learning and working memory measures. mTBI participants demonstrated alterations in cortical activity while at rest and in response to stimulation with TMS. Conclusions The present study comprehensively characterized the multidimensional effect of mTBI in the sub-acute phase post injury, showing a broad range of differences compared to non-mTBI participants. Further research is needed to explore the relationship between these pathophysiologies and clinical/cognitive symptoms in mTBI.

Exploring the potential of combining transcranial magnetic stimulation and electroencephalography to investigate mild cognitive impairment and Alzheimer's disease: a systematic review.

Transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are non-invasive techniques used for neuromodulation and recording brain electrical activity, respectively. The integration of TMS-EEG has emerged as a valuable tool for investigating the complex mechanisms involved in age-related disorders, such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). By systematically synthesizing TMS-EEG studies, this review aims to shed light on the neurophysiological mechanisms underlying MCI and AD, while also exploring the practical applications of TMS-EEG in clinical settings. PubMed, ScienceDirect, and PsychInfo were selected as the databases for this review. The 22 eligible studies included a total of 592 individuals with MCI or AD as well as 301 cognitively normal adults. TMS-EEG assessments unveiled specific patterns of corticospinal excitability, plasticity, and brain connectivity that distinguished individuals on the AD spectrum from cognitively normal older adults. Moreover, the TMS-induced EEG features were observed to be correlated with cognitive performance and the presence of AD pathological biomarkers. The comprehensive examination of the existing studies demonstrates that the combination of TMS and EEG has yielded valuable insights into the neurophysiology of MCI and AD. This integration shows great potential for early detection, monitoring disease progression, and anticipating response to treatment. Future research is of paramount importance to delve into the potential utilization of TMS-EEG for treatment optimization in individuals with MCI and AD.

Feasibility of a randomized, sham-controlled pilot study for accelerated rTMS-treatment of the cerebellum plus physiotherapy in CANVAS patients.

Cerebellar ataxia, neuropathy and bilateral vestibular areflexia (CANVAS) is a rare neurodegenerative disease affecting the cerebellum, the peripheral nervous system and the vestibular system. Due to the lack of approved drugs, therapy comprises physiotherapy and speech therapy. Transcranial magnetic stimulation is a promising non-invasive therapeutic option to complement classical symptomatic therapies. To test feasibility of the combination of transcranial magnetic stimulation using an accelerated protocol and standard symptomatic therapy in patients with CANVAS. Eight patients with genetically confirmed CANVAS were assigned to either verum or sham cerebellar transcranial magnetic stimulation using an accelerated protocol. Treatment duration was limited to 5 days. Additionally, patients in both groups received symptomatic therapy (speech and physiotherapy) for the duration of the study. All patients completed the stimulation protocol. Adverse events were rare. Ataxia severity improved in the verum group only. The combination of transcranial magnetic stimulation and classic symptomatic therapy is feasible in a neuro-rehabilitation setting and potentially ameliorates ataxia severity.

A three-dimensional adaptive rational interpolation algorithm for removing TMS-EEG pulse artifacts

Objective. Transcranial magnetic stimulation in combination with electroencephalography (TMS-EEG) has been widely used to study the reactivity and connectivity of brain regions. In order to efficiently and fast solve the pulse artifacts problem caused by TMS electromagnetic pulses, a three-dimensional adaptive rational quadratic Hermite interpolation algorithm is proposed. Approach. Firstly, a three-dimensional signal matrix is obtained by a signal recombination algorithm, where the removed window is automatically obtained by a derivative threshold. Secondly, the adaptive rational quartic Hermite interpolation algorithm is used to interpolate the removed window. Finally, the performance of the algorithm is verified using simulated and public database data. Main results. The simulation results show that the proposed algorithm improves the SNR by 23.88%–47.60%, reduces the RMSE by 46.52%–81.11%, reduces the average MAE by 47.83%–58.33%, and reduces the time consumption of the proposed algorithm by 45.90% compared with the piecewise cubic Hermite interpolation algorithm. Significance. Therefore, TMS-EEG pulse artifacts can be removed effectively and quickly with the proposed algorithm.

Hybrid Transcranial Magnetic Stimulation and Deep Brain Stimulation in the Presence of an Implantable Pulse Generator

Transcranial Magnetic Stimulation (TMS) has been shown to improve speech impairment in Parkinson’s Disease (PD) patients. Most PD patients undergo Deep Brain Stimulation (DBS) implantation to improve their motor function prior to the development of speech impairment. Therefore the potential for TMS treatment must take into account the DBS probes’ high conductivity, potentially causing excess stimulation. Prior research regarding this phenomenon is highly conflicting and needs investigation. This study reports electromagnetic interference using a highly accurate finite element analysis approach to determine the electric field distribution in patients with DBS probes undergoing TMS therapy. Additionally, we tested various coil orientations and coil models to fully examine the extent that TMS affects DBS. We considered accurate DBS geometry by creating high-resolution models of Medtronic 3389 DBS, including an Implantable Pulse Generator (IPG) and multiple loops at the exit point of the cranium, which previous studies lack. By studying the induced current in the DBS leads, we determined that the combination of TMS and DBS varies in safety relative to its coil orientation and coil type. Specifically, the quadruple butterfly coil (QBC) targeted at the lateral motor cortex did not induce unsafe levels of currents in the DBS leads even at 100% of the maximum stimulator output.

Improved language function for post-stroke aphasia in the long term following repeated repetitive transcranial magnetic stimulation and intensive speech-language-hearing therapy: a case report

BackgroundThere have been no papers reporting improvement in language function and changes in cerebral blood flow following repeated use of repetitive transcranial magnetic stimulation in combination with intensive speech-language-hearing therapy. This case report concerns the efficacy of repeated use of repetitive transcranial magnetic stimulation and intensive speech-language-hearing therapy for a certain patient suffering from aphasia following stroke, plus the findings of the cerebral blood flow measurements.Case presentationThe patient was a 71-year-old right-handed Japanese male who developed fluent aphasia following a left middle cerebral artery stroke. He underwent repetitive transcranial magnetic stimulation and intensive speech-language-hearing therapy five times in total. The repetitive transcranial magnetic stimulation was applied to right inferior frontal gyrus at the frequency of 1 Hz plus 2 hours per day of intensive speech-language-hearing therapy. The patient’s language function was evaluated in the short term and long term. Cerebral blood flow was measured with single photon emission computed tomography scan. As a result, in the short term, the patient’s language function improved especially during the initial hospitalization. In the long term, it improved gradually and stabilized.Cerebral blood flow was increased in the right hemisphere.ConclusionsThe findings of the study indicate that the repeated use of repetitive transcranial magnetic stimulation and intensive speech-language-hearing therapy may be effective in improving and preserving language function and increasing cerebral blood flow for aphasia following stroke.

Machine Learning-Based Classification to Disentangle EEG Responses to TMS and Auditory Input.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) offers an unparalleled opportunity to study cortical physiology by characterizing brain electrical responses to external perturbation, called transcranial-evoked potentials (TEPs). Although these reflect cortical post-synaptic potentials, they can be contaminated by auditory evoked potentials (AEPs) due to the TMS click, which partly show a similar spatial and temporal scalp distribution. Therefore, TEPs and AEPs can be difficult to disentangle by common statistical methods, especially in conditions of suboptimal AEP suppression. In this work, we explored the ability of machine learning algorithms to distinguish TEPs recorded with masking of the TMS click, AEPs and non-masked TEPs in a sample of healthy subjects. Overall, our classifier provided reliable results at the single-subject level, even for signals where differences were not shown in previous works. Classification accuracy (CA) was lower at the group level, when different subjects were used for training and test phases, and when three stimulation conditions instead of two were compared. Lastly, CA was higher when average, rather than single-trial TEPs, were used. In conclusion, this proof-of-concept study proposes machine learning as a promising tool to separate pure TEPs from those contaminated by sensory input.