Transcranial Magnetic Stimulation Research Articles

Wireless neuromodulation at submillimeter precision via a microwave split-ring resonator.

A broad spectrum of electromagnetic waves has been explored for wireless neuromodulation. Transcranial magnetic stimulation, with long wavelengths, cannot provide submillimeter spatial resolution. Visible light, with its short wavelengths, suffers from strong scattering in the deep tissue. Microwaves have centimeter-scale penetration depth and have been shown to reversibly inhibit neuronal activity. Yet, microwaves alone do not provide sufficient spatial precision to modulate target neurons without affecting surrounding tissues. Here, we report a split-ring resonator (SRR) that generates an enhanced microwave field at its gap with submillimeter spatial precision. With the SRR, microwaves at dosages below the safe exposure limit are shown to inhibit the firing of neurons within 1 mm of the SRR gap site. The microwave SRR reduced seizure activity at a low dose in both in vitro and in vivo models of epilepsy. This microwave dosage is confirmed to be biosafe via histological and biochemical assessment of brain tissue.

Loss of the ipsilateral silent period in amyotrophic lateral sclerosis is associated with reduced white matter integrity in the motor section of the corpus callosum

ObjectiveInterhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates. MethodsThe demographic, clinical, and neuropsychological data of 127 ALS patients were analysed. Transcallosal inhibition was assessed with an ipsilateral silent period (iSP) protocol using transcranial magnetic stimulation. Patients were categorised based on an iSP response or its loss, and the groups were characterised by demographic, clinical, and neuropsychological variables. Diffusion-weighted images from a subset of 63 patients were analysed using tractography, and white matter (WM) structural integrity metrics were compared across groups. Results54 % of patients displayed iSP loss. The average free-water-corrected fractional anisotropy values within the callosal tract between the primary motor cortices were lower for patients with iSP loss compared to patients with an iSP response. There were no group differences based on other diffusivity metrics. The groups did not differ regarding any of the demographic, clinical, or neuropsychological variables. InterpretationWe found reduced WM integrity in the motor section of the corpus callosum that differentiated ALS patients with iSP loss from patients with an iSP response, but with a small effect size. Nevertheless, the underlying pathological substrate and potential genetic drivers for these structural and functional changes in a subset of ALS patients remain to be satisfactorily investigated.

Quelle réponse au trouble somatique fonctionnel : la filière ACSEPT

BackgroundFunctional somatic disorder (FSD) is a prevalent disorder that can be severely disabling for the patient and is associated with major health costs. There are few formalized care programs for these disorders in the country, and their management encounters various difficulties, both in the diagnosis and its announcement and the treatment. Cognitive-behavioural and emotional therapy (CBT) is the standard on psychiatry care, and its efficacy has been demonstrated through several randomised controlled studies on the intensity of physical and psychological symptoms. InterventionAt Lille's University Hospital Center, we have established the “ACSEPT” care pathway for TSF management which consists of a psychiatric consultation followed by an individual referral, including a treatment using repeated transcranial magnetic stimulation (rTMS) or the integration of a CBT-based psychoeducation group. This group had the particularity of caring for all patients presenting FSD regardless of the associated physical symptoms. Educating medical professionals and conducting FSD research were other goals of ACSEPT. Discussion/conclusionACSEPT allows an improvement in the care offered to these patients with a defined orientation and interdisciplinary, early, organized cares that are repeatable. Our goal is to study the effectiveness of these different interventions in subsequent studies, to continue the development of ACSEPT and to be able to distribute this intervention at the regional level to establish a clear care program allowing early management of these patients.

Neuromuscular electrical stimulation at submaximal intensity combined with motor imagery increases corticospinal excitability.

There is sparse evidence in the literature that the combination of neuromuscular electrical stimulation (NMES) and motor imagery (MI) can increase corticospinal excitability more that the application of one or the other modality alone. However, the NMES intensity usually employed was below or at motor threshold, not allowing a proper activation of the whole neuromuscular system. This questions the effect of combined MI + NMES with higher intensities, closer to those used in clinical settings. The purpose here was to assess corticospinal excitability during either MI, NMES or a combination of both at different evoked forces. Seventeen healthy participants were enrolled in one session consisting of 6 conditions targeting flexor carpi radialis muscle (FCR): rest, MI, NMES at 5% and 20% of maximal voluntary contraction (MVC) and MI and NMES performed simultaneously (MI + NMES). During each condition, corticospinal excitability was assessed by evoking MEP of FCR by using transcranial magnetic stimulation. Maximal M-wave (Mmax) was measured by using the stimulation of the median nerve. MEPs during MI were greater as compared to rest (P = 0.005). MEPs during MI were significantly lower than during MI + NMES at 5% (P = 0.02) and 20% (P = 0.001). Then, MEPs during NMES 5% was significantly lower than during MI + NMES 20% (P < 0.005). The present study showed that MI + NMES increased corticospinal excitability more than MI alone. However, corticospinal excitability was not higher as the intensity increase during MI + NMES. Therefore, MI + NMES targeting FCR may not significantly increase the corticospinal excitability between different low-submaximal contractions intensities.

Inducing ipsilateral motor-evoked potentials in the biceps brachii muscle in healthy humans.

To assess reticulospinal tract excitability, high-intensity transcranial magnetic stimulation (TMS) has been used to elicit ipsilateral motor-evoked potentials (iMEPs). However, there is no consensus on robust and valid methods for use in human studies. The present study proposes a standardized method for eliciting and analysing iMEPs in the biceps brachii. Twenty-four healthy young adults participated in this study. Electromyography (EMG) electrodes recorded contralateral MEPs (cMEPs) from the right and iMEPs from the left biceps brachii. A dynamic preacher curl task was used with ~15% of the subject's one-repetition maximum load. The protocol included maximal compound action potential (M-max) determination of the right biceps brachii muscle, TMS hotspot determination, and four sets of five repetitions where 100% stimulator output was delivered at an elbow angle of 110° of flexion. We normalized cMEP amplitude by M-max (% M-max) and iMEP by cMEP amplitude ratio (ICAR). Clear iMEPs above background EMG were observed in 21 subjects (88%, ICAR = .31 ± .19). Good-to-excellent agreement (intraclass correlation coefficient [ICC] = .795-1.000) and low bias (.01-.08 mV and .60-1.11 ms) were demonstrated when comparing two different analysis methods (i.e. fixed time-window vs. manual onset detection) to determine the cMEP and iMEP amplitude and latency, respectively. Most subjects demonstrated clear iMEPs above background EMG triggered at a pre-determined joint angle during a light-load dynamic preacher curl exercise. Similar results were obtained when comparing a single-trial manual identification of iMEP and a semi-automated time-window data analysis approach.

TMS-induced phase resets depend on TMS intensity and EEG phase

Objective. The phase of the electroencephalographic (EEG) signal predicts performance in motor, somatosensory, and cognitive functions. Studies suggest that brain phase resets align neural oscillations with external stimuli, or couple oscillations across frequency bands and brain regions. Transcranial Magnetic Stimulation (TMS) can cause phase resets noninvasively in the cortex, thus providing the potential to control phase-sensitive cognitive functions. However, the relationship between TMS parameters and phase resetting is not fully understood. This is especially true of TMS intensity, which may be crucial to enabling precise control over the amount of phase resetting that is induced. Additionally, TMS phase resetting may interact with the instantaneous phase of the brain. Understanding these relationships is crucial to the development of more powerful and controllable stimulation protocols.Approach.To test these relationships, we conducted a TMS-EEG study. We applied single-pulse TMS at varying degrees of stimulation intensity to the motor area in an open loop. Offline, we used an autoregressive algorithm to estimate the phase of the intrinsicµ-Alpha rhythm of the motor cortex at the moment each TMS pulse was delivered.Main results. We identified post-stimulation epochs whereµ-Alpha phase resetting and N100 amplitude depend parametrically on TMS intensity and are significantversusperipheral auditory sham stimulation. We observedµ-Alpha phase inversion after stimulations near peaks but not troughs in the endogenousµ-Alpha rhythm.Significance. These data suggest that low-intensity TMS primarily resets existing oscillations, while at higher intensities TMS may activate previously silent neurons, but only when endogenous oscillations are near the peak phase. These data can guide future studies that seek to induce phase resetting, and point to a way to manipulate the phase resetting effect of TMS by varying only the timing of the pulse with respect to ongoing brain activity.

Repetitive transcranial magnetic stimulation as a therapy for post-stroke dysphagia: An overview of systematic reviews and meta-analysis

Objective Post-stroke dysphagia is a common swallowing disorder that occurs after a stroke, leading to an increased risk of aspiration pneumonia and malnutrition. There is a pressing need for effective and safe interventions for its rehabilitation. This review aims to answer two key scientific questions: (1) What is the efficacy of repetitive transcranial magnetic stimulation in the rehabilitation of post-stroke dysphagia? (2) Is repetitive transcranial magnetic stimulation a safe intervention for post-stroke dysphagia? Data Sources A comprehensive search was conducted across four electronic databases: PubMed, Cochrane Library, Web of Science, and Embase. The search aimed to identify relevant studies concerning our topic of interest and was completed on 28 May 2024. Review methods In accordance with the PRISMA checklist, a comprehensive search of four databases was conducted, which identified 13 relevant systematic reviews. The inclusion criteria were systematic reviews that evaluated the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. Exclusion criteria were reviews that did not focus on post-stroke dysphagia or did not evaluate repetitive transcranial magnetic stimulation as a therapeutic intervention. The quality, bias, reporting, and overall evidence quality of these reviews were assessed using validated tools, including the AMSTAR 2 tool for assessing the methodological quality of systematic reviews, the ROBIS tool for assessing the risk of bias, and the GRADE approach for evaluating the overall quality of evidence. This rigorous approach ensures that our review provides a comprehensive and reliable overview of the current state of knowledge on the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia. Results The sample sizes for the individual studies included in the systematic reviews/meta-analyses ranged from 66 to 555. The total number of participants across all studies included in the overall analyses was 752. The evidence was limited by the methodological flaws and heterogeneity of the systematic reviews. The quality of the evidence varied from high to low, with most outcomes having moderate quality. Future research should adopt more rigorous, standardized, and comprehensive designs to confirm the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. The main reason for downgrading the evidence quality was the small sample size and high heterogeneity of the primary studies. Conclusion This overview synthesized research on repetitive transcranial magnetic stimulation for dysphagia, aiming to inform clinical and policy decisions. However, the current evidence does not conclusively establish the safety and efficacy of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The studies reviewed varied in quality, and many were of poor quality. Therefore, while some studies suggest potential benefits of repetitive transcranial magnetic stimulation, these findings should be interpreted with caution. There is a pressing need for more rigorous, high-quality research to validate the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The implications of these findings for clinical practice and policy will be clearer once we have more robust, evidence-based recommendations.

TMS for the Prevention of Recurrence of Depression during Pregnancy and Post-Partum: A Case Series

Depression in pregnancy and the postpartum period is prevalent. Transcranial Magnetic Stimulation (TMS) has emerged as a promising alternative or adjunctive treatment in the second and third trimesters of pregnancy, especially for individuals with treatment resistant depression. However, the use of TMS to prevent relapse and recurrence of depression throughout all three trimesters of pregnancy and post-partum has not been studied. Here we present three pregnancy cases: (2 pregnancies in one patient with unipolar depression and 1 pregnancy in a patient with bipolar depression) where TMS had been used prior to treat depression successfully before pregnancy. TMS was subsequently administered safely adjunctive to medications on a maintenance (preservation) basis through all the three trimesters of pregnancy and for a full year or more post-partum.Patient outcome was monitored clinically and with psychometric measures throughout, with the frequency of TMS sessions adjusted in light of course, but typically at a frequency of 1-2 sessions per month. In each case there was no recurrence of a major depressive episode in pregnancy or post-partum despite a prior history of treatment resistance and multiple failed medication trials. The frequency of sessions required to maintain stability diminished over time as the total duration of treatment with TMS increased. Given the difficulty of managing and preventing depression relapse during pregnancy and the post-partum period and the lack of current research in this area, this case series suggests that maintenance TMS may be a promising option in this setting.

Transformation but not generation of motor images is disrupted following stimulation over the left inferior parietal lobe

Motor imagery (MI) involves the generation, maintenance, and transformation of motor images; yet, the neural underpinnings of each stage are not well understood. Here, we investigated the role of the left inferior parietal lobe (IPL) in the stages of MI. Healthy participants (N=20) engaged in a MI task (making judgments about hands presented on a screen; hand laterality judgment task) over two days. Past literature demonstrates the mental rotation of hands in this task involves implicit MI (i.e., where MI occurs spontaneously in the absence of explicit instructions). During the task, active (Day A; 120% resting motor threshold) or sham (Day B; placebo) neuronavigated transcranial magnetic stimulation (TMS) was applied to the left IPL (location determined from past neuroimaging work) on 50% of trials at 250, 500, or 750ms post-stimulus onset, corresponding to different stages of MI. A/B days were randomized across participants. Linear mixed effects (LME) modelling conducted on reaction time and accuracy revealed that longer reaction times were observed when TMS was delivered at 750ms after trial onset, and more greatly for active vs. sham stimulation. This effect was exacerbated for palm- vs. back-view stimuli and for left vs. right hands. Accuracy overall was decreased for active vs. sham stimulation, and to a greater extent for palm- vs. back-view stimuli. Findings suggest that the left IPL is involved in image transformation. Overall this work informs on the neural underpinnings of the stages of MI.

Personalised transcranial magnetic stimulation for treatment-resistant depression, depression with comorbid anxiety and negative symptoms of schizophrenia: a narrative review.

Transcranial magnetic stimulation (TMS) is a promising intervention for treatment-resistant psychiatric disorders. However, conventional TMS typically utilises a one-size-fits-all approach when determining stimulation targets. Recent retrospective brain circuit-based analyses using lesion network mapping have suggested that a left dorsal lateral prefrontal cortex target has a higher efficacy for alleviating depression symptoms, a dorsomedial prefrontal cortex target is more effective for anxiety symptoms, and a rostromedial prefrontal cortex target is effective for schizophrenia-associated psychiatric symptoms. Nonetheless, symptom-specific brain circuit targeting has not been tested prospectively. We conducted a narrative review of selected literature to investigate individualised targeting for TMS and discuss potential future directions to elucidate the efficacy of this approach.

Modulation effects of repetitive transcranial magnetic stimulation on target and indirect target nodes in patients with major depressive disorder

Clinical studies intensively highlight two critical brain regions, i,e, dorsal lateral prefrontal cortex (DLPFC) (target node) and subgenual anterior cingulate cortex (sgACC) (indirect target node) for the treatment of neuroimaging-guided repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder (MDD). However, it remains unclear whether the clinical rTMS treatment could modulate the activity of the target and indirect target nodes in MDD patients. We aim to identify the rTMS-induced alteration of brain local and functional connectivity (FC) activities in the target and indirect target nodes. 38 patients with MDD were recruited for taking part in the 2-week rTMS treatment. We identified left DLPFC and right sgACC as the target and indirect target nodes for each participant, using the neuroimaging guided method, and further explored the rTMS-induced modulation on the brain functional activity of the two nodes. Ultimately, 28 patients were included in the analysis. We found that subjects had significant improvement in depressive symptoms, and their brain functional activities were reorganized. rTMS reduced the FC activity between the target and indirect target nodes, while the brain local activity in these nodes did not show rTMS-induced changes. The FC reduction was not associated with improvement in depressive symptoms. These results confirmed the clinical significance of the target node (DLPFC) and indirect target node (sgACC) in the rTMS treatment of MDD, and further shed light on the brain functional reorganization underpinning clinical practice of rTMS.

Precise Localization of the Central Left Frontal Cortex in Different Canine Skull Types: A Comparative Study of Frameless Neuronavigation and External Measurement Techniques

Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain modulation technique, has been explored as an additional treatment option for behaviorally disordered dogs. For optimal effectiveness of the rTMS treatment, accurate coil positioning to the stimulation target is pivotal. Frameless stereotactic neuronavigation for the localization of intracranial regions has been established as a reliable targeting method. However, given the varying skull shape and brain structures among dog breeds, divided into mesocephalic, brachycephalic, and dolichocephalic breeds, localizing the rTMS target area, the central left frontal cortex, can be challenging. Previous neuronavigation studies have only investigated its use in mesocephalic breeds of dogs. Because this neuronavigation is based on expensive high-tesla magnetic resonance imaging data, and anesthesia needed for immobilization, a cheaper and reliable localization alternative to broaden the rTMS use in the veterinary field is needed.The objective of this study was twofold. First, the study aimed to evaluate external localization of the central left frontal cortex within the three skull types (retrospective study 1). Then, this external localization method was compared to the conventional frameless neuronavigation technique to check the consistency, focusing on mesocephalic and dolichocephalic breeds (prospective study 2). Thirty-two brachycephalic, thirty-seven mesocephalic and thirty dolichocephalic dogs were included to evaluate the external localization of the central left frontal cortex by external measurement (retrospective study 1, data obtained from previously performed MRI scans). For the second objective, thirty-eight dogs (35 mesocephalic breeds and 3 dolichocephalic breeds) were recruited to compare the external measurement localization method and the localization by neuronavigation (prospective study 2, data extracted from study 1 and former rTMS studies). The first part of this study showed the central left frontal cortex was externally located approximately two-thirds of the total skull length (sagittal length) in meso- and dolichocephalic dogs, at the center of the skull length in brachycephalic dogs, and 0.65 to 0.70 cm to the left of the cerebral midline for all skull types (retrospective study 1). Using intraclass correlation coefficient (ICC) analysis, the second part of the study showed high consistency between these two methods, for the length of the skull (0.94), the relative position of the left frontal cortex (0.84), and the distance to the cerebral midline (0.69) in mesocephalic and dolichocephalic breeds (prospective study 2). Our findings suggest that the conventional frameless neuronavigation could be replaced by the external localization method in the mesocephalic and dolichocephalic dog breeds, and therefore ultimately reduce anesthesia time and financial burden when applying non-invasive brain modulation techniques like rTMS. More research needs to be conducted for brachycephalic dogs to validate this method in this specific population of dogs.

Investigating the synergistic neuromodulation effect of bilateral rTMS and VR brain-computer interfaces training in chronic stroke patients

Objective.Stroke is a major cause of adult disability worldwide, resulting in motor impairments. To regain motor function, patients undergo rehabilitation, typically involving repetitive movement training. For those who lack volitional movement, novel technology-based approaches have emerged that directly involve the central nervous system, through neuromodulation techniques such as transcranial magnetic stimulation (TMS), and closed-loop neurofeedback like brain-computer interfaces (BCIs). This, can be augmented through proprioceptive feedback delivered many times by embodied virtual reality (VR). Nonetheless, despite a growing body of research demonstrating the individual efficacy of each technique, there is limited information on their combined effects.Approach.In this study, we analyzed the Electroencephalographic (EEG) signals acquired from 10 patients with more than 4 months since stroke during a longitudinal intervention with repetitive TMS followed by VR-BCI training. From the EEG, the event related desynchronization (ERD) and individual alpha frequency (IAF) were extracted, evaluated over time and correlated with clinical outcome.Main results.Every patient's clinical outcome improved after treatment, and ERD magnitude increased during simultaneous rTMS and VR-BCI. Additionally, IAF values showed a significant correlation with clinical outcome, nonetheless, no relationship was found between differences in ERD pre- post- intervention with the clinical improvement.Significance.This study furnishes empirical evidence supporting the efficacy of the joint action of rTMS and VR-BCI in enhancing patient recovery. It also suggests a relationship between IAF and rehabilitation outcomes, that could potentially serve as a retrievable biomarker for stroke recovery.

Can Neuromodulation Improve Sleep and Psychiatric Symptoms?

In this review, we evaluate recent studies that employ neuromodulation, in the form of non-invasive brain stimulation, to improve sleep in both healthy participants, and patients with psychiatric disorders. We review studies using transcranial electrical stimulation, transcranial magnetic stimulation, and closed-loop auditory stimulation, and consider both subjective and objective measures of sleep improvement. Neuromodulation can alter neuronal activity underlying sleep. However, few studies utilizing neuromodulation report improvements in objective measures of sleep. Enhancements in subjective measures of sleep quality are replicable, however, many studies conducted in this field suffer from methodological limitations, and the placebo effect is robust. Currently, evidence that neuromodulation can effectively enhance sleep is lacking. For the field to advance, methodological issues must be resolved, and the full range of objective measures of sleep architecture, alongside subjective measures of sleep quality, must be reported. Additionally, validation of effective modulation of neuronal activity should be done with neuroimaging.

Concurrent modulation of the brain-heart pathway: Unveiling potential antagonisms through transcranial magnetic stimulation and transcutaneous auricular vagus nerve stimulation integration

Concurrent modulation of the brain-heart pathway: Unveiling potential antagonisms through transcranial magnetic stimulation and transcutaneous auricular vagus nerve stimulation integration

Parent perceptions of various treatment approaches for PANS and PANDAS

Pediatric autoimmune neuropsychiatric disorder (PANDAS) is characterized by sudden, dramatic onset obsessive-compulsive disorder (OCD) following a Group A Streptococcus infection. Pediatric acute neuropsychiatric syndrome (PANS) refers to sudden, dramatic onset OCD and/or restricted eating triggered by infections and other inflammatory reactions. A variety of treatments have been utilized for PANS/PANDAS; however, there is no “gold standard” intervention protocol. Parental expectations of a given treatment have been found to improve a child's overall treatment experience; however, parent attitudes towards PANS/PANDAS treatments are unknown, which was the purpose of this study. An online survey was distributed to 208 parents of children with self-reported PANS/PANDAS. Treatments were grouped together within overarching categories (i.e., psychotherapy, psychiatric/psychotropic, inflammation/infection mitigation, supplements, lifestyle changes, and surgery). Categorically, parents rated inflammation/infection mitigation interventions and lifestyle changes as most appropriate, and psychiatric/psychotropic interventions as least appropriate. At the individual level, treatments including antibiotics, non-steroidal anti-inflammatory drugs, intravenous immunoglobulin, and family counseling received ratings between “appropriate” and “extremely appropriate” Alternatively, treatments including deep brain stimulation, transcranial magnetic stimulation, antidepressant medications, and exposure and response prevention received ratings between “inappropriate” and “extremely inappropriate.” Study limitations include a lack of gender and race representation in our sample. Findings indicate a need for dissemination of current, relevant research to the parent population as well as further examination of the parent experience throughout onset, diagnosis, and treatment.

Improvements in Sleep Quality in Patients With Major Depressive and Generalized Anxiety Disorders Treated With Individualized, Parcel-Guided Transcranial Magnetic Stimulation.

Poor quality sleep has often been cited as a cause of lowered quality of life in patients with affective disorders such as major depressive disorder (MDD) and generalized anxiety disorder (GAD). As sleep and affective disorders are affected by multi-network interactions, we hypothesize that the modulation of the central executive network (CEN), salience, and default mode networks (DMNs) through individualized repetitive transcranial magnetic stimulation (rTMS) may improve sleep and quality of life. A retrospective analysis from 2020 to 2023 was conducted in patients with affective disorders at Cingulum Health. Multiple targets were selected based on anomalies detected from individual, functional connectivity networks from a machine-learning connectivity software. rTMS was conducted with accelerated continuous or intermittent theta burst stimulation (TBS) based on the anomaly detected. Pittsburgh Sleep Quality Index (PSQI), EuroQol (EQ5D), Beck's Depression Inventory (BDI), and the General Anxiety Disorder-7 (GAD-7) questionnaires were administered prior to, after, and at follow-up of rTMS. Twenty-seven patients were identified, and the most common diagnoses were MDD (41%) or MDD with GAD (41%). All patients had at least one rTMS target in the CEN. The most common target (19 patients) was L8Av in the dorsolateral prefrontal cortex (dlPFC). Patients experienced significant improvements in sleep, quality of life, depressive, and anxiety symptoms after rTMS and during follow-up. Improvements in sleep correlated with quality of life at follow-up. This study suggests that personalized, parcel-guided rTMS is safe and may provide sustained improvements in sleep, quality of life, and affective symptoms for patients with affective disorders.

Effects of cervical transcutaneous spinal direct current stimulation on spinal excitability

ObjectiveTo investigate the effects of transcutaneous spinal direct current stimulation (tsDCS) on spinal cord excitability using neurophysiological methods. MethodsSpinal cord motoneuron excitability was assessed using various neurophysiological techniques in a sham-controlled randomized experiment, which involved delivering 2 mA tsDCS and testing four different montages. Transcranial magnetic stimulation (TMS), F-waves to supramaximal ulnar nerve stimulation and somatosensory evoked potentials to upper limb nerves stimulation were measured in the participants with the electrode configuration that yielded the greatest effect, for a total of about 18 min. 18 young volunteers were recruited. ResultsAmong the tested ones, the most promising tsDCS montage was the one with the anode placed on the 7th cervical spinous process and the cathode on the glottis. With this configuration, a significant enhancement of motor responses in the hand muscles to TMS of the contralateral hand motor area was observed during tsDCS (p<0.00001), reaching a plateau after 6 min. This facilitation rapidly declined within a few minutes after the tsDCS was stopped. ConclusionResults of the different techniques suggest a possible contribution to facilitatory neuromodulation of the motoneurons at the cervical spine level. SignificanceThe occurrence of enhanced excitability after tsDCS suggests potential application in individuals with partial corticospinal fiber impairment affecting hand motor function.

Abnormal individualized functional connectivity: A potential stimulation target for pediatric tourette syndrome

ObjectiveIn order to examine whether individualized peak functional connectivity could potentially serve as a target for repetitive transcranial magnetic stimulation (rTMS) therapy, we investigated the location of peak functional connectivity (FC) between the cortical motor area and the key brain region, the globus pallidus internus (GPi), in Tourette syndrome, and explored the relationship between the severity of the disease and these aberrant functional connections. MethodsThe study involved a cohort of 103 children diagnosed with Tourette syndrome and 66 age-matched typically developing children. The GPi was served as the seed, and the study compared individualized peak FC strength in the supplementary motor area (SMA) and premotor area between the two groups. Spatial distribution of peak FC in the motor area and GPi-based voxel-wise FC were also analyzed. ResultsChildren with Tourette syndrome exhibited lower peak FC in the left SMA when using left GPi as the seed. This reduction in peak FC demonstrated a significant and negative correlation with the Yale Global Tic Severity Scale scores. ConclusionsSMA-GPi FC is one of the key pathological circuit in Tourette syndrome. SignificanceThe individual peak FC location in the left SMA potentially serve as stimulation targets for rTMS treatment of TS.

Neural Circuitry and Therapeutic Targeting of Depressive Symptoms in Schizophrenia Spectrum Disorders.

Conceptual similarities between depressive and negative symptoms complicate biomarker and intervention development. This study employed a data-driven approach to delineate the neural circuitry underlying depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). Data from three studies were analyzed (157 participants with SSDs) to assess brain-behavior relationships: two neuroimaging studies and a randomized trial of repetitive transcranial magnetic stimulation (rTMS). Partial least squares correlation (PLSC) was used to investigate associations between resting-state functional connectivity and depressive and negative symptoms. Secondary analyses of rTMS trial data (active, N=37; sham, N=33) were used to assess relationships between PLSC-derived symptom profiles and treatment outcomes. PLSC identified three latent variables (LVs) relating functional brain circuitry with symptom profiles. LV1 related a general depressive symptom factor with positive associations between and within the default mode network (DMN), the frontoparietal network (FPN), and the cingulo-opercular network (CON). LV2 related negative symptoms (no depressive symptoms) via negative associations, especially between the FPN and the CON, but also between the DMN and the FPN and the CON. LV3 related a guilt and early wakening depression factor via negative rather than positive associations with the DMN, FPN, and CON. The secondary visual network had a positive association with general depressive symptoms and negative associations with guilt and negative symptoms. Active (but not sham) rTMS applied bilaterally to the dorsolateral prefrontal cortex (DLPFC) reduced general depressive but not guilt-related or negative symptoms. The results clearly differentiate the neural circuitry underlying depressive and negative symptoms, and segregated across the two-factor structure of depression in SSDs. These findings support divergent neurobiological pathways of depressive symptoms and negative symptoms in people with SSDs. As treatment options are currently limited, bilateral rTMS to the DLPFC is worth exploring further for general depressive symptoms in people with SSDs.