Transcranial Magnetic Stimulation Responses Research Articles

Preoperative Cortical Mapping for Brain Tumor Surgery Using Navigated Transcranial Stimulation: Analysis of Accuracy

Transcranial magnetic stimulation (TMS) represents a distinctive technique for non-invasive brain stimulation. Recent advancements in image processing have enabled the enhancement of TMS by integrating magnetic resonance imaging (MRI) modalities with TMS via a neuronavigation system. The aim of this study is to assess the efficacy of navigated TMS for cortical mapping in comparison to surgical mapping using direct electrical stimulation (DES). This study involved 30 neurosurgical procedures for tumors located in or adjacent to the precentral gyrus. The DES points were compared with TMS responses based on the original distances of vectorial modules. There was a notable similarity in the points obtained from the two mapping methods. The distances between the geometric centers of TMS and DCS were 4.85 ± 1.89 mm. A strong correlation was identified between these vectorial points (r = 0.901, p < 0.001). The motor threshold in TMS was highest in the motor cortex adjacent to the tumor compared to the normal cortex (p < 0.001). Patients with deficits exhibited excellent accuracy in both methods. In view of this, TMS demonstrated reliable and precise application in brain mapping, which is a promising method for preoperative functional mapping in motor cortex tumor surgery.

Distinguishable neural circuit mechanisms associated with the clinical efficacy of rTMS in aMCI patients.

Repetitive transcranial magnetic stimulation is used in early-stage Alzheimer's disease to slow progression, but heterogeneity in response results in different treatment outcomes. The mechanisms underlying this heterogeneity are unclear. This study used resting-state neuroimaging to investigate the variability in episodic memory improvement from angular gyrus repetitive transcranial magnetic stimulation and tracked the neural circuits involved. Thirty-four amnestic mild cognitive impairment patients underwent angular gyrus repetitive transcranial magnetic stimulation (4weeks, 20Hz, 100% resting motor threshold) and were divided into high-response and low-response groups based on minimal clinically important differences in auditory verbal learning test scores. Baseline and pre/post-treatment neural circuit activities were compared. Results indicated that the orbital middle frontal gyrus in the orbitofrontal cortex network and the precuneus in the default mode network had higher local activity in the low-response group. After treatment, changes in local and remote connectivity within brain regions of the orbitofrontal cortex, default mode network, visual network, and sensorimotor network showed opposite trends and were related to treatment effects. This suggests that the activity states of brain regions within the orbitofrontal cortex and default mode network could serve as imaging markers for early cognitive compensation in amnestic mild cognitive impairment patients and predict the aftereffects of repetitive transcranial magnetic stimulation response.

A Review of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Combined with Medication and Psychotherapy for Depression.

After participating in this CME activity, the psychiatrist should be better able to:• Compare and contrast therapies used in combination with transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) for treating MDD. Noninvasive neuromodulation, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has emerged as a major area for treating major depressive disorder (MDD). This review has two primary aims: (1) to review the current literature on combining TMS and tDCS with other therapies, such as psychotherapy and psychopharmacological interventions, and (2) to discuss the efficacy, feasibility, limitations, and future directions of these combined treatments for MDD. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched three databases: PubMed, PsycInfo, and Cochrane Library. The last search date was December 5, 2023. The initial search revealed 2,519 records. After screening and full-text review, 58 studies (7 TMS plus psychotherapy, 32 TMS plus medication, 7 tDCS plus psychotherapy, 12 tDCS plus medication) were included. The current literature on tDCS and TMS paired with psychotherapy provides initial support for integrating mindfulness interventions with both TMS and tDCS. Adding TMS or tDCS to stable doses of ongoing medications can decrease MDD symptoms; however, benzodiazepines may interfere with TMS and tDCS response, and antipsychotics can interfere with TMS response. Pairing citalopram with TMS and sertraline with tDCS can lead to greater MDD symptom reduction compared to using these medications alone. Future studies need to enroll larger samples, include randomized controlled study designs, create more uniform protocols for combined treatment delivery, and explore mechanisms and predictors of change.

The effect of EEG microstate on the characteristics of TMS-EEG

ObjectiveDifferences in neural states at the time of transcranial magnetic stimulation (TMS) can lead to variations in the effectiveness of TMS stimulation. Strategies that aim to lock neural activity states and improve the precision of stimulation timing in TMS optimization should gradually receive attention. One feasible approach is to utilize microstate locking for TMS stimulation, and understanding the impact of microstates at the time of stimulation on TMS response forms the foundation of this approach. ApproachTMS-EEG data were extracted from 21 healthy subjects through experiments. Based on the different microstates at the time of stimulation, the trials were classified into four datasets. TMS-evoked potential (TEP), topographical distribution, and natural frequency, were computed for each dataset to explore the differences in TMS-EEG characteristics across different microstates. Main resultsThe N100 component of microstate C group (−2.376 μV) was significantly higher (p = 0.003) than of microstate D group (−1.739 μV), and the P180 component of microstate D group (2.482 μV) was significantly higher (p = 0.024) than of microstate B group (1.766 μV) and slightly higher (p = 0.058) than of microstate C group (1.863 μV) by calculating the ROI. The topographical distribution of TEP components during microstate C and microstate D still retained the template characteristics of the microstate at the time of stimulation, and the natural frequencies did not differ among the four classical microstates. SignificanceThis study showed the potential for future closed-loop TMS based on microstates and would guiding the development of microstate-based closed-loop TMS techniques.

The effect of functional magnetic resonance imaging connectivity on resting motor threshold transcranial magnetic stimulation in schizophrenia participants

Schizophrenia is a neurological disorder known to influence the motor region. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique being investigated as a treatment for schizophrenia. Resting motor threshold (RMT) is the dosage parameter for TMS treatment protocols and is known to vary between participants with limited understanding of the drivers of this variance. Previous investigations have used functional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and individual level neuroanatomy to explain RMT variability. Our previous investigation showed neuroanatomy influences RMT in both schizophrenia and healthy populations and this relationship was weakened by the presence of schizophrenia. In this study, 54 participants with schizophrenia-diagnosed, who were antipsychotic naive and 43 non-impaired controls underwent single pulse TMS, structural magnetic resonance imaging, and fMRI. An independent component analysis (ICA) was used to process fMRI data into 25 distinct channels where correlations were derived between channels. Linear and multiple regression models were used to evaluate first, the influence of these channel interactions on RMT followed by their influence when individual level neuroanatomy was also considered. We found that between-channel functional connectivity was altered in individuals with schizophrenia and that fMRI can contribute to prediction of RMT, but differently in both cohorts and to a lesser degree than individual level neuroanatomical measures. This suggests that functional connectivity influences TMS response and fMRI might help in dosage calculations of clinical TMS protocols.

Investigation of EEG Neurophysiological Relationship to TMS Response in Mild Traumatic Brain Injury Patients

Transcranial magnetic stimulation (TMS) is utilized as a treatment method for a variety of neurological and psychiatric disorders. The standard dose parameter for administration of TMS is known as the resting motor threshold (RMT). Between individuals, the RMT has traditionally been thought to reflect differences in neuroanatomy; however, the functional state of the brain has also been shown to have an influence on this value. In this study, 19 mild traumatic brain injury participants (mTBI) resting state electroencephalographs (EEG) were obtained before undergoing TMS treatment. Various time frequency and power spectra values were derived from this EEG data to examine the relationship between RMT and neurophysiology. These EEG connectivity metrics were then used to establish relationships with RMT alone and accounting for differences in individual neuroanatomy. We found that the incorporation of EEG functional connectivity improved multiple regression model predictions of inter-participant RMT variability than neuroanatomy alone. Future investigations into the evaluation of EEG in predicting RMT variability should include a larger participant population with a healthy control.

Understanding corticomotor mechanisms for activation of non-target muscles during unilateral isometric contractions of leg muscles after stroke

Purpose Muscle activation often occurs in muscles ipsilateral to a voluntarily activated muscle and to a greater extent after stroke. In this study, we measured muscle activation in non-target, ipsilateral leg muscles and used transcranial magnetic stimulation (TMS) to provide insight into whether corticomotor pathways contribute to involuntary activation. Materials and methods Individuals with stroke performed unilateral isometric ankle dorsiflexion, ankle plantarflexion, knee extension, and knee flexion. To quantify involuntary muscle activation in non-target muscles, muscle activation was measured during contractions from the ipsilateral tibialis anterior (TA), medial gastrocnemius (MG), rectus femoris (RF), and biceps femoris (BF) and normalized to resting muscle activity. To provide insight into mechanisms of involuntary non-target muscle activation, TMS was applied to the contralateral hemisphere, and motor evoked potentials (MEPs) were recorded. Results We found significant muscle activation in nearly every non-target muscle during isometric unilateral contractions. MEPs were frequently observed in non-target muscles, but greater non-target MEP amplitude was not associated with greater non-target muscle activation. Conclusions Our results suggest that non-target muscle activation occurs frequently in individuals with chronic stroke. The lack of association between non-target TMS responses and non-target muscle activation suggests that non-target muscle activation may have a subcortical or spinal origin. Non-target muscle activation has important clinical implications because it may impair torque production, out-of-synergy movement, and muscle activation timing.

Three novel methods for determining motor threshold with transcranial magnetic stimulation outperform conventional procedures.

Objective. Thresholding of neural responses is central to many applications of transcranial magnetic stimulation (TMS), but the stochastic aspect of neuronal activity and motor evoked potentials (MEPs) challenges thresholding techniques. We analyzed existing methods for obtaining TMS motor threshold and their variations, introduced new methods from other fields, and compared their accuracy and speed.Approach. In addition to existing relative-frequency methods, such as the five-out-of-ten method, we examined adaptive methods based on a probabilistic motor threshold model using maximum-likelihood (ML) or maximuma-posteriori(MAP) estimation. To improve the performance of these adaptive estimation methods, we explored variations in the estimation procedure and inclusion of population-level prior information. We adapted a Bayesian estimation method which iteratively incorporated information of the TMS responses into the probability density function. A family of non-parametric stochastic root-finding methods with different convergence criteria and stepping rules were explored as well. The performance of the thresholding methods was evaluated with an independent stochastic MEP model.Main Results. The conventional relative-frequency methods required a large number of stimuli, were inherently biased on the population level, and had wide error distributions for individual subjects. The parametric estimation methods obtained the thresholds much faster and their accuracy depended on the estimation method, with performance significantly improved when population-level prior information was included. Stochastic root-finding methods were comparable to adaptive estimation methods but were much simpler to implement and did not rely on a potentially inaccurate underlying estimation model.Significance. Two-parameter MAP estimation, Bayesian estimation, and stochastic root-finding methods have better error convergence compared to conventional single-parameter ML estimation, and all these methods require significantly fewer TMS pulses for accurate estimation than conventional relative-frequency methods. Stochastic root-finding appears particularly attractive due to the low computational requirements, simplicity of the algorithmic implementation, and independence from potential model flaws in the parametric estimators.

Identifying predictive biomarkers for repetitive transcranial magnetic stimulation response in depression patients with explainability

Repetitive Transcranial Magnetic Stimulation (rTMS) is an evidence-based treatment for depression. However, the patterns of response to this treatment modality are inconsistent. Whilst many people see a significant reduction in the severity of their depression following rTMS treatment, some patients do not. To support and improve patient outcomes, recent work is exploring the possibility of using Machine Learning to predict rTMS treatment outcomes. Our proposed model is the first to combine functional magnetic resonance imaging (fMRI) connectivity with deep learning techniques to predict treatment outcomes before treatment starts. Furthermore, with the use of Explainable AI (XAI) techniques, we identify potential biomarkers that may discriminate between rTMS responders and non-responders. Our experiments utilize 200 runs of repeated bootstrap sampling on two rTMS datasets. We compare performances between our proposed feedforward deep neural network against existing methods, and compare the average accuracy, balanced accuracy and F1-score on a held-out test set. The results of these experiments show that our model outperforms existing methods with an average accuracy of 0.9423, balanced accuracy of 0.9423, and F1-score of 0.9461 in a sample of 61 patients. We found that functional connectivity measures between the Subgenual Anterior Cingulate Cortex and Centeral Opercular Cortex are a key determinant of rTMS treatment response. This knowledge provides psychiatrists with further information to explore the potential mechanisms of responses to rTMS treatment. Our developed prototype is ready to be deployed across large datasets in multiple centres and different countries.

Probing the inhibitory motor circuits in adductor laryngeal dystonia during a dystonia-unrelated task

BackgroundThe pathophysiology of adductor laryngeal dystonia (AdLD) remains unknown; however, there is growing evidence that dystonia is associated with disruptions in the inhibitory regulation of sensorimotor cortical areas. Using functional MRI (fMRI) and transcranial magnetic stimulation (TMS) complementarily, we previously demonstrated an overly activated laryngeal motor cortex and revealed correlations between blood-oxygen-level dependent (BOLD) activation and intracortical inhibition in a phonation (dystonia-related) task in adductor laryngeal dystonia (AdLD). ObjectiveHere, we aimed to characterize the brain-based findings in the primary motor cortex (M1) during a dystonia-unrelated (finger tapping) task in AdLD and controls (CTL). MethodsWe examined the between-group differences in task-dependent BOLD activation and intracortical inhibition, measured by the TMS-evoked cortical silent period (cSP), in the M1. The correlations between fMRI and TMS responses were assessed. ResultsThere is more broadly dispersed BOLD activation, not confined to the hand motor cortex, and reduced intracortical inhibition in AdLD compared to CTL. Further, there are more positive correlations between cSP and BOLD activation in a task unrelated to dystonic symptoms in AdLD compared with CTL. This is in contrast to our previous work that demonstrated fewer positive correlations in AdLD during a dystonic phonation task. ConclusionsIn unaffected musculature activation, there is dispersed BOLD activation that is correlated with intracortical inhibition suggesting a possible compensatory strategy in the non-dystonic muscles.

Modulation of dorsal premotor cortex differentially influences I-wave excitability in primary motor cortex of young and older adults.

Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I-wave excitability in M1 of young and older adults. Twenty-two young (mean±SD, 22.9±2.9years) and 20 older (66.6±4.2years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor-evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior-anterior (PA) and anterior-posterior (AP) current single-pulse TMS to assess corticospinal excitability (PA1mV ; AP1mV ; PA0.5mV , early; AP0.5mV , late), and paired-pulse TMS short intracortical facilitation for I-wave excitability (PA SICF, early; AP SICF, late). Although PMd iTBS potentiated PA1mV and AP1mV MEPs in both age groups (both P<0.05), the time course of this effect was delayed for AP1mV in older adults (P=0.001). Furthermore, while AP0.5mV , PA SICF and AP SICF were potentiated in both groups (all P<0.05), potentiation of PA0.5mV was only apparent in young adults (P<0.0001). While PMd influences early and late I-wave excitability in young adults, direct PMd modulation of the early circuits is specifically reduced in older adults. KEY POINTS: Interneuronal circuits responsible for late I-waves within primary motor cortex (M1) mediate projections from dorsal premotor cortex (PMd), but this communication probably changes with advancing age. We investigated the effects of intermittent theta burst stimulation (iTBS) to PMd on transcranial magnetic stimulation (TMS) measures of M1 excitability in young and older adults. We found that PMd iTBS facilitated M1 excitability assessed with posterior-anterior (PA, early I-waves) and anterior-posterior (AP, late I-waves) current TMS in young adults, with a stronger effect for AP TMS. M1 excitability assessed with AP TMS also increased in older adults following PMd iTBS, but there was no facilitation for PA TMS responses. We conclude that changes in M1 excitability following PMd iTBS are specifically reduced for the early I-waves in older adults, which could be a potential target for interventions that enhance cortical excitability in older adults.

Pairing Transcranial Magnetic Stimulation and Loud Sounds Produces Plastic Changes in Motor Output.

Most current methods for neuromodulation target the cortex. Approaches for inducing plasticity in subcortical motor pathways, such as the reticulospinal tract, could help to boost recovery after damage (e.g., stroke). In this study, we paired loud acoustic stimulation (LAS) with transcranial magnetic stimulation (TMS) over the motor cortex in male and female healthy humans. LAS activates the reticular formation; TMS activates descending systems, including corticoreticular fibers. Two hundred paired stimuli were used, with 50 ms interstimulus interval at which LAS suppresses TMS responses. Before and after stimulus pairing, responses in the contralateral biceps muscle to TMS alone were measured. Ten, 20, and 30 min after stimulus pairing ended, TMS responses were enhanced, indicating the induction of LTP. No long-term changes were seen in control experiments which used 200 unpaired TMS or LAS, indicating the importance of associative stimulation. Following paired stimulation, no changes were seen in responses to direct corticospinal stimulation at the level of the medulla, or in the extent of reaction time shortening by a loud sound (StartReact effect), suggesting that plasticity did not occur in corticospinal or reticulospinal synapses. Direct measurements in female monkeys undergoing a similar paired protocol revealed no enhancement of corticospinal volleys after paired stimulation, suggesting no changes occurred in intracortical connections. The most likely substrate for the plastic changes, consistent with all our measurements, is an increase in the efficacy of corticoreticular connections. This new protocol may find utility, as it seems to target different motor circuits compared with other available paradigms.SIGNIFICANCE STATEMENT Induction of plasticity by neurostimulation protocols may be promising to enhance functional recovery after damage such as following stroke, but current protocols mainly target cortical circuits. In this study, we developed a novel paradigm which may generate long-term changes in connections between cortex and brainstem. This could provide an additional tool to modulate and improve recovery.

Motor overflow in the lower limb after stroke: Insights into mechanisms.

Motor overflow (involuntary muscle activation) is common after stroke, particularly in the non-paretic upper limb. Two potential cortical mechanisms are as follows: (1) The contralesional hemisphere controls both limbs, and (2) inhibition from the ipsilesional to the contralesional hemisphere is diminished. Few studies have differentiated between these hypotheses or investigated motor overflow in the lower limb after stroke. To investigate these potential mechanisms, individuals with chronic stroke performed unilateral isometric and dynamic dorsiflexion. Motor overflow was quantified in the contralateral, resting (non-target) ankle. Transcranial magnetic stimulation (TMS) was applied, and responses were measured in both legs. Relations between motor overflow, excitability of ipsilateral motor pathways, and interhemispheric inhibition were assessed. Non-target muscle activity (motor overflow) was greater during isometric and dynamic conditions than rest in both legs (p≤0.001) and was higher in the non-paretic than the paretic leg (p= 0.03). Some participants (25%) had motor overflow >4SD above the group mean in the non-paretic leg. Greater motor overflow in the non-paretic leg was associated with lesser inhibition from the ipsilesional to the contralesional hemisphere (p= 0.04). In both legs, non-target TMS responses were greater during the isometric and dynamic than the rest condition (p≤0.01) but not when normalized to background muscle activity. Overall, motor overflow occurred in both legs after stroke, suggesting a common bilateral mechanism. Our correlational results suggest that alterations in interhemispheric inhibition may contribute to motor overflow. Furthermore, the lack of differences in non-target motor evoked potentials MEPs between rest, isometric, and dynamic conditions suggests that subcortical and/or spinal pathways may contribute to motor overflow.

The Efficacy and Safety of Transcranial Magnetic Stimulation in Treatment-Resistant Bipolar Depression.

The aim of the current study is to investigate the efficacy and safety of Transcranial magnetic stimulation (TMS) treatment, a non-invasive brain stimulation technique, on depressive symptoms in treatment-resistant bipolar depression (TRBD). The study included 29 patients between the ages of 18-65, with bipolar disorder depressive episode according to DSM-5 and with the decision of non-response to treatment according to the Canadian Mood and Anxiety Treatment Network (CANMAT). Patients were divided into two groups double-blind-randomly, 20 sessions of TMS and 20 sessions of sham TMS were applied crossover. Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Young Mania Rating Scale (YMRS) and TMS Side Effect Questionnaire were applied to the patients before the treatment, at the 2nd week which is the crossover phase, and at the end of the treatment at 4th week. In both groups, the severity of depression was decreased significantly according to HAM-D and BDI scores after the procedure. As well as active stimulation, some positive placebo effects were observed with sham stimulation. But the decreases seen in HAM-D and BDI scores and response to the treatment were higher during the weeks when the groups received active stimulation (respectively p=0.000, p=0.001, p=0.005). At the end of the study, according to HAM-D, 55.7% of the patients showed response to the treatment, 24.13% partial response. According to BDI, 41.37% of the patients showed response to the treatment, and 31.03% partial response. No associations were found between TMS response and sociodemographic - clinical features, or type of the disease (p>0.05). During the study, no serious adverse effects such as seizures or manic / hypomanic switches were observed. The results of our study showed that TMS treatment is an effective and safe treatment for patients with treatment-resistant bipolar depression.

Transient neural oscillations reveal new biomarkers for therapeutic transcranial magnetic stimulation for comorbid MDD and PTSD

Abstract Repetitive transcranial magnetic stimulation (TMS) is a therapy for major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). TMS effectiveness varies across patients and optimal protocols are unknown. Electroencephalography (EEG) examines brain dynamics associated with TMS often in highly averaged data (Zandvakili et al, 2019). In non-averaged signals, EEG oscillations may emerge as high power transients, coined “events” (Jones, 2016; Shin et al, 2017). We applied methods to analyze event features to describe biomarkers of TMS and their relationship to clinical outcomes. We collected resting 8-channel EEG before and after therapeutic TMS for 23 patients with comorbid MDD and PTSD targeting the left dorsolateral prefrontal cortex. Using our open-source toolbox (https://github.com/jonescompneurolab/SpectralEvents), we tested if resting state oscillations can be quantified as events in non-averaged data using 2-second windows. We assessed if event characteristics – event rate, power, duration, frequency span – changed after TMS or correlated with symptom improvement. Averaged omnibus power spectral density revealed peaks in frequency bands including delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz). Transient high-power events emerged from non-averaged data. Overall, frontal delta/theta and alpha event number and medial delta/theta event duration decreased after TMS (all p < 0.05). Pretreatment event characteristics correlated with subsequent clinical response. Frontal delta/theta event frequency span negatively correlated with MDD & PTSD improvement; medial alpha event power and duration positively correlated with MDD improvement, whereas medial alpha event rate and duration positively correlated with PTSD improvement; and frontal beta duration negatively correlated with PTSD improvement (all r2 > 0.15). Novel methods to characterize spectral events in non-averaged signals identified periods of high power activity in resting EEG data and revealed changes in event features potentially predictive of TMS response. EEG-recorded events ultimately may provide new biomarkers of response and a better mechanistic understanding of TMS. Keywords: Transcranial magnetic stimulation, Resting state EEG, Major depressive disorder, Post-traumatic stress disorder

Standing Neurophysiological Assessment of Lower Extremity Muscles Post-Stroke.

Transcranial magnetic stimulation (TMS) is a common tool used to measure the behavior of motor circuits in healthy and neurologically impaired populations. TMS is used extensively to study motor control and the response to neurorehabilitation of the upper extremities. However, TMS has been less utilized in the study of lower extremity postural and walking-specific motor control. The limited use and the additional methodological challenges of lower extremity TMS assessments have contributed to the lack of consistency in lower extremity TMS procedures within the literature. Inspired by the decreased ability to record lower extremity TMS motor evoked potentials (MEP), this methodological report details steps to enable post-stroke TMS assessments in a standing posture. The standing posture allows for the activation of the neuromuscular system, reflecting a state more akin to the system's state during postural and walking tasks. Using dual-top force plates, we instructed participants to equally distribute their weight between their paretic and non-paretic legs. Visual feedback of the participants' weight distribution was provided. Using image guidance software, we delivered single TMS pulses via a double-cone coil to the participants' lesioned and non-lesioned hemispheres and measured the corticomotor response of the paretic and non-paretic tibialis anterior and soleus muscles. Performing assessments in the standing position increased the TMS response rate and allowed for the use of the lower stimulation intensities compared to the standard sitting/resting position. Utilization of this TMS protocol can provide a common approach to assess the lower extremity corticomotor response post-stroke when the neurorehabilitation of postural and gait impairments are of interest.

Brain-Derived Neurotrophic Factor Polymorphism Influences Response to Single-Pulse Transcranial Magnetic Stimulation at Rest

The ability of noninvasive brain stimulation to modulate corticospinal excitability and plasticity is influenced by genetic predilections such as the coding for brain-derived neurotrophic factor (BDNF). Otherwise healthy individuals presenting with BDNF Val66Met (Val/Met) polymorphism are less susceptible to changes in excitability in response to repetitive transcranial magnetic stimulation (TMS) and paired associative stimulation paradigms, reflecting reduced neuroplasticity, compared to Val homozygotes (Val/Val). In the current study, we investigated whether BDNF polymorphism influences "baseline" excitability under TMS conditions that are not repetitive or plasticity-inducing. Cross-sectional BDNF levels could predict TMS response more generally because of the ongoing plasticity processes. Forty-five healthy individuals (23 females; age: 25.3 ± 7.0 years) participated in the study, comprising two groups. Motor evoked potentials (MEP) were collected using single-pulse TMS paradigms at fixed stimulation intensities at 110% of the resting motor threshold in one group, and individually-derived intensities based on MEP sizes of 1 mV in the second group. Functional variant Val66Met (rs6265) was genotyped from saliva samples by a technician blinded to the identity of DNA samples. Twenty-seven participants (60.0%) were identified with Val/Val, sixteen (35.5%) with Val/Met genotype, and two with Met/Met genotype. MEP amplitudes were significantly diminished in the Val/Met than Val/Val individuals. These results held independent of the single-pulse TMS paradigm of choice (p = 0.017110% group; p = 0.035 1 mV group), age, and scalp-to-coil distances. The findings should be further substantiated in larger-scale studies. If validated, intrinsic differences by BDNF polymorphism status could index response to TMS prior to implementing plasticity-inducing protocols.

Resting EEG theta connectivity and alpha power to predict repetitive transcranial magnetic stimulation response in depression: A non-replication from the ICON-DB consortium

ObjectiveOur previous research showed high predictive accuracy at differentiating responders from non-responders to repetitive transcranial magnetic stimulation (rTMS) for depression using resting electroencephalography (EEG) and clinical data from baseline and one-week following treatment onset using a machine learning algorithm. In particular, theta (4–8 Hz) connectivity and alpha power (8–13 Hz) significantly differed between responders and non-responders. Independent replication is a necessary step before the application of potential predictors in clinical practice. This study attempted to replicate the results in an independent dataset. MethodsWe submitted baseline resting EEG data from an independent sample of participants who underwent rTMS treatment for depression (N = 193, 128 responders) (Krepel et al., 2018) to the same between group comparisons as our previous research (Bailey et al., 2019). ResultsOur previous results were not replicated, with no difference between responders and non-responders in theta connectivity (p = 0.250, Cohen’s d = 0.1786) nor alpha power (p = 0.357, ηp2 = 0.005). ConclusionsThese results suggest that baseline resting EEG theta connectivity or alpha power are unlikely to be generalisable predictors of response to rTMS treatment for depression. SignificanceThese results highlight the importance of independent replication, data sharing and using large datasets in the prediction of response research.

Transcranial Magnetic Stimulation-Induced Motor Cortex Activity Influences Visual Awareness Judgments.

The influence of non-visual information on visual awareness judgments has recently gained substantial interest. Using single-pulse transcranial magnetic stimulation (TMS), we investigate the potential contribution of evidence from the motor system to judgment of visual awareness. We hypothesized that TMS-induced activity in the primary motor cortex (M1) would increase reported visual awareness as compared to the control condition. Additionally, we investigated whether TMS-induced motor-evoked potential (MEP) could measure accumulated evidence for stimulus perception. Following stimulus presentation and TMS, participants first rated their visual awareness verbally using the Perceptual Awareness Scale (PAS), after which they responded manually to a Gabor orientation identification task. Delivering TMS to M1 resulted in higher average awareness ratings as compared to the control condition, in both correct and incorrect identification task response trials, when the hand with which participants responded was contralateral to the stimulated hemisphere (TMS-response-congruent trials). This effect was accompanied by longer PAS response times (RTs), irrespective of the congruence between TMS and identification response. Moreover, longer identification RTs were observed in TMS-response-congruent trials in the M1 condition as compared to the control condition. Additionally, the amplitudes of MEPs were related to the awareness ratings when response congruence was taken into account. We argue that MEP can serve as an indirect measure of evidence accumulated for stimulus perception and that longer PAS RTs and higher amplitudes of MEPs in the M1 condition reflect integration of additional evidence with visual awareness judgment. In conclusion, we advocate that motor activity influences perceptual awareness judgments.

Motor cortical excitability and plasticity in patients with neurofibromatosis type 1

ObjectiveNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that is associated with cognitive disabilities. Based on studies involving animals, the hypothesized cause of these disabilities results from increased activity of inhibitory interneurons that decreases synaptic plasticity. We obtained transcranial magnetic stimulation (TMS)-based measures of cortical inhibition, excitability and plasticity in individuals with NF1. MethodsWe included 32 NF1 adults and 32 neurotypical controls. Cortical inhibition was measured with short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Excitability and plasticity were studied with intermittent theta burst stimulation (iTBS). ResultsThe SICI and CSP response did not differ between NF1 adults and controls. The response upon iTBS induction was significantly increased in controls (70%) and in NF1 adults (83%). This potentiation lasted longer in controls than in individuals with NF1. Overall, the TMS response was significantly lower in NF1 patients (F(1, 41) = 7.552, p = 0.009). ConclusionsIndividuals with NF1 may have reduced excitability and plasticity, as indicated by their lower TMS response and attenuation of the initial potentiated response upon iTBS induction. However, our findings did not provide evidence for increased inhibition in NF1 patients. SignificanceThese findings have potential utility as neurophysiological outcome measures for intervention studies to treat cognitive deficits associated with NF1.