cTBS Protocols Research Articles

Transcranial Magnetic Stimulation of the Default Mode Network to Improve Sleep in Individuals With Insomnia Symptoms: Protocol for a Double-Blind Randomized Controlled Trial.

Cortical hyperarousal and ruminative thinking are common aspects of insomnia that have been linked with greater connectivity in the default mode network (DMN). Therefore, disrupting network activity within the DMN may reduce cortical and cognitive hyperarousal and facilitate better sleep. This trial aims to establish a novel, noninvasive method for treating insomnia through disruption of the DMN with repetitive transcranial magnetic stimulation, specifically with continuous theta burst stimulation (cTBS). This double-blind, pilot randomized controlled trial will assess the efficacy of repetitive transcranial magnetic stimulation as a novel, nonpharmacological approach to improve sleep through disruption of the DMN prior to sleep onset for individuals with insomnia. Primary outcome measures will include assessing changes in DMN functional connectivity before and after stimulation. A total of 20 participants between the ages of 18 to 50 years with reported sleep disturbances will be recruited as a part of the study. Participants will then conduct an in-person screening and follow-on enrollment visit. Eligible participants then conduct at-home actigraphic collection until their first in-residence overnight study visit. In a double-blind, counterbalanced, crossover study design, participants will receive a 40-second stimulation to the left inferior parietal lobule of the DMN during 2 separate overnight in-residence visits. Participants are randomized to the order in which they receive the active stimulation and sham stimulation. Study participants will undergo a prestimulation functional magnetic resonance imaging scan and a poststimulation functional magnetic resonance imaging scan prior to sleep for each overnight study visit. Sleep outcomes will be measured using clinical polysomnography. After their first in-residence study visit, participants conduct another at-home actigraphic collection before returning for their second in-residence overnight study visit. Our study was funded in September 2020 by the Department of Defense (W81XWH2010173). We completed the enrollment of our target study population in the October 2022 and are currently working on neuroimaging processing and analysis. We aim to publish the results of our study by 2024. Primary neuroimaging outcome measures will be tested using independent components analysis, seed-to-voxel analyses, and region of interest to region of interest analyses. A repeated measures analysis of covariance (ANCOVA) will be used to assess the effects of active and sham stimulation on sleep variables. Additionally, we will correlate changes in functional connectivity to polysomnography-graded sleep. The presently proposed cTBS protocol is aimed at establishing the initial research outcomes of the effects of a single burst of cTBS on disrupting the network connectivity of the DMN to improve sleep. If effective, future work could determine the most effective stimulation sites and administration schedules to optimize this potential intervention for sleep problems. ClinicalTrials.gov NCT04953559; https://clinicaltrials.gov/ct2/show/NCT04953559. DERR1-10.2196/51212.

Theta burst stimulation promotes nestin expression in experimental autoimmune encephalomyelitis

Background/Aim. Multiple sclerosis (MS) is an immune-mediated disease of the nervous system in which the myelin sheath is destroyed during the process of neurodegeneration. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS in which preservation of myelin and remyelination of axons can improve neuron survival. The aim of the study was to evaluate the activation capacity of neuronal tissue by autoimmune inflammation and treatment with intermittent (i) theta burst stimulation (TBS)- iTBS or continuous TBS (cTBS) based on the expression profiles of nestin in astrocytes, oligodendrocytes, and neurons. Methods. Two forms of TBS - iTBS and cTBS - were used to extend the period during which axons can be remyelinated. It was investigated how iTBS or cTBS protocols affect the expression profiles of nestin with glial fibrillary acidic protein, myelin basic protein (MBP), and neuronal nuclear protein in rat spinal cord. Changes at the molecular level were monitored using the immunofluorescence method. Results. The obtained results showed that both protocols (iTBS and cTBS) increased the expression of nestin and MBP and reduced astrogliosis in the spinal cord of EAE rats. Conclusion. The therapeutic potential of TBS in EAE contributes to the improvement of the intrinsic ability to recover from spinal cord injury.

Continuous Theta-Burst Stimulation in a 9-year-old girl with a history of neurotoxicity after Acute Lymphoblastic Leukemia B

IntroductionTranscranial Magnetic Stimulation is a non invasive brain stimulation technique used for several neuropsychiatric conditions. The treatment of Acute Lymphoblastic Leukaemia (ALL) involves many cytotoxic drugs that inhibit the rapid growth of cancer cells, but also damage healthy cells, resulting in a wide range of adverse effects (Śliwa-Tytko et al., 2022). Studies have shown that approximately 10-30% of paediatric ALL patients suffer from psychiatric disorders. Therefore, new therapeutic tools are needed, and repetitive transcranial magnetic stimulation (rTMS) has demonstrated tolerability, effectiveness and safety in children (Allen et al., 2017).ObjectivesWe discuss the first case of a 9-year-old girl diagnosed with acute lymphoblastic leukaemia B in who underwent Continuous Theta-Burst StimulationMethodsCase Presentation. In this study, we describe a case of a 9-year-old girl diagnosed with acute lymphoblastic leukaemia B in November 2016 who completed treatment in July 2019. Since April 2018 she presented symptoms of intracranial hypertension and encephalopathy with behavioural alterations, attention deficit secondary to toxicity. Psychotic outbreaks after toxicity from different treatments was also present. Since starting pericyazine (July 2022) there has been a slight improvement, but her symptoms continue to have a severe impact in her daily functioning. Baseline developmental profile assessed with the Battelle Inventory was significantly below the expected level in all developmental areas except for gross motor skills. Treatment. The TMS intervention consisted of the application on right DLPFC (F4), inhibitory cTBS protocol (5Hz bursts and 3 pulses of 50 Hz each). The protocol consisted in delivering 2 sessions per day for 15 days (separated by 55 minutes), 4 minutes per session (3600 pulses/session), 30 sessions in total. An intensity of 100% of resting motor threshold (C4). TMS was performed with the Magventure Magpro X100 MagOption equipment, Cool DB-80 double cone coil. The Child Behaviour Checklist (CBCL) for parents was used to assess intervention effects.ResultsCBCL results reflect improvements in both internalising and externalising total scores after treatment. Specifically, the patient presents clinically significant decreases in several dimensions such as anxious/depressed symptoms, somatic complaints, and social problems. No adverse effects have been reported since the beginning of the intervention.ConclusionsInternalising and externalising behaviours severity were reduced after 30 TMS sessions. In accordance with the latest systematic reviews on the safety of TMS in the paediatric patient (Zewdie et al, 2020) we propose the development of paediatric guidelines to offer this technique to patients with a history of intolerability or poor drug response.Disclosure of InterestNone Declared

Continuous theta burst stimulation for drug-resistant epilepsy.

IntroductionRepetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.Materials and methodsWe performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.ResultsSeven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.ConclusionWe report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).

The role of the primary motor cortex in motor imagery: A theta burst stimulation study.

While mentally simulated actions activate similar neural structures to overt movement, the role of the primary motor cortex (PMC) in motor imagery remains disputed. The aim of the study was to use continuous theta burst stimulation (cTBS) to modulate corticospinal activity to investigate the putative role of the PMC in implicit motor imagery in young adults with typical and atypical motor ability. A randomized, double blind, sham‐controlled, crossover, offline cTBS protocol was applied to 35 young adults. During three separate sessions, adults with typical and low motor ability (developmental coordination disorder [DCD]), received active cTBS to the PMC and supplementary motor area (SMA), and sham stimulation to either the PMC or SMA. Following stimulation, participants completed measures of motor imagery (i.e., hand rotation task) and visual imagery (i.e., letter number rotation task). Although active cTBS significantly reduced corticospinal excitability in adults with typical motor ability, neither task performance was altered following active cTBS to the PMC or SMA, compared to performance after sham cTBS. These results did not differ across motor status (i.e., typical motor ability and DCD). These findings are not consistent with our hypothesis that the PMC (and SMA) is directly involved in motor imagery. Instead, previous motor cortical activation observed during motor imagery may be an epiphenomenon of other neurophysiological processes and/or activity within brain regions involved in motor imagery. This study highlights the need to consider multi‐session theta burst stimulation application and its neural effects when probing the putative role of motor cortices in motor imagery.

Prof K C Dube Poster Award

Background:Auditory verbal hallucinations (AVH) are one of the core features of schizophrenia. In approximately 25% of patients with schizophrenia, AVH are refractory to psychotropic drug treatment and can chronically persist. Superior temporal cortex is implicated in AVH. Continuous Theta Burst Stimulation (cTBS) can be one of the add on treatment for auditory hallucination in refractory cases. Accelerated cTBS protocols have the advantage of shorter application time and lower stimulation intensity. In addition use of robotized neuronavigation will improve the accuracy of coil placement and thus localization of the stimulation site.Aim:We aimed to evaluate the efficacy of accelerated cTBS over left superior temporal cortex (STC) in improvement of AVH in schizophrenia, using neuronavigation and robotic arm.Methods:40 patients of schizophrenia with AVH, were enrolled for this randomized, sham controlled, double-blind trial. Each participant in the active group received cTBS comprising of 900 pulses (bursts of 3 stimuli at 50 Hz repeated at 5 Hz frequency), twice a day for 5 days per week for 3 consecutive weeks. AVH were assessed with PSYRATS(AHRS), PANSS & CGI. Assessments were carried out at baseline,1st,3rd & 6th weeks.Results:The improvement in AVH in active group at 1st 3rd & 6th week was not statistically significant at 0.05 (p-value) as compared to sham group. Stimulation was well tolerated.Conclusion:Results suggest that accelerated robotized neuronavigated cTBS does not appear to have substantial potential in the treatment of auditory hallucinations and further research should investigate individualised MRI guided neuronavigation with higher sample size.

Plastic responsiveness of motor cortex to paired associative stimulation depends on cerebellar input

ObjectiveThe extent of plastic responses of motor cortex (M1) to paired associative stimulation (PAS) varies among healthy subjects. Continuous theta-burst stimulation (cTBS) of cerebellum enhances the mean PAS-induced plasticity in groups of healthy subjects. We tested whether the initial status of Responder or Non -Responder to PAS, influenced the effect of cerebellar stimulation on PAS-induced plasticity. MethodsWe assessed in 19 young healthy volunteers (8 Responders, 11 Non-Responders to PAS), how cTBS and iTBS (intermittent TBS) applied to the cerebellum before a PAS protocol influenced the plastic responsiveness of M1 to PAS. We tested whether the PAS-induced plastic effects could be depotentiated by a short cTBS protocol applied to M1 shortly after PAS and whether cerebellar stimulation influenced GABA-ergic intracortical inhibition and M1 plasticity in parallel. ResultsCerebellar cTBS restored the M1 response to PAS in Non-Responders while cerebellar iTBS turned the potentiating response to PAS to a depressive response in both groups. The depotentiation protocol abolished both responses. ConclusionNon-Responder status to PAS is a state of M1 amenable to bidirectional plastic modulation when primed by a change in cerebello-thalamic drive. SignificanceThe meaning of lack of responsiveness to certain protocols probing plasticity should be reconsidered.

Multiple Daily Rounds of Theta-Burst Stimulation for Tinnitus: Preliminary Results.

Background and Objectives: Tinnitus is a condition that negatively affects the quality of life and is difficult to treat. Theta burst stimulation (TBS), a new method of repetitive transcranial magnetic stimulation (rTMS), is a promising treatment approach because it shows stronger and more prolonged effects in a shorter time of stimulation than other rTMS protocols. However, the therapeutic effect of TBS for tinnitus was inconsistent. We hypothesized that more stimulation would be more effective. Therefore, this study aimed to explore the safety and effectiveness of multiple daily rounds of TBS over five consecutive days. Materials and Methods: The continuous TBS (cTBS) protocol is 300 pulses/day, but we applied 8 sessions of 300 pulses in a day (total 2400 pulses/day). A total of 15 patients with tinnitus were randomly assigned to treatment and sham groups. Outcome measurements were taken three times: before and after 5-day of stimulation; at a 1–3 month follow-up visit. Outcome measurements were the degree of annoyance due to ear fullness, duration of tinnitus, visual analog scales of tinnitus for annoyance, Tinnitus Handicap Inventory, pitch, loudness, minimum masking level, and residual inhibition. Results: Five-day cTBS was completed without adverse events. We did not find any significant therapeutic effect in the treatment group, but we needed to be cautious to interpret our result due to the small sample size. Conclusions: In conclusion, multiple rounds of cTBS in a day may be safe. Further research is needed in a larger sample size to determine the effectiveness and confirm the safety.

Comparative Study of a Continuous Train of Theta-Burst Stimulation for a Duration of 20 s (cTBS 300) versus a Duration of 40 s (cTBS 600) in a Pre-Stimulation Relaxed Condition in Healthy Volunteers.

As variable after effects have been observed following phasic muscle contraction prior to continuous theta-burst stimulation (cTBS), we here investigated two cTBS protocols (cTBS300 and cTBS600) in 20 healthy participants employing a pre-relaxed muscle condition including visual feedback on idle peripheral surface EMG activity. Furthermore, we assessed corticospinal excitability measures also from a pre-relaxed state to better understand the potential impact of these proposed contributors to TBS. Motor-evoked potential (MEP) magnitude changes were assessed for 30 min. The linear model computed across both experimental paradigms (cTBS300 and cTBS600) revealed a main effect of TIME COURSE (p = 0.044). Separate exploratory analysis for cTBS300 revealed a main effect of TIME COURSE (p = 0.031), which did not maintain significance after Greenhouse–Geisser correction (p = 0.073). For cTBS600, no main effects were observed. An exploratory analysis revealed a correlation between relative SICF at 2.0 ms (p = 0.006) and after effects (relative mean change) of cTBS600, which did not survive correction for multiple testing. Our findings thereby do not support the hypothesis of a specific excitability modulating effect of cTBS applied to the human motor-cortex in setups with pre-relaxed muscle conditions.

Resting-state functional connectivity in the attention networks is not altered by offline theta-burst stimulation of the posterior parietal cortex or the temporo-parietal junction as compared to a vertex control site

Disruption of resting-state functional connectivity (RSFC) between core regions of the dorsal attention network (DAN), including the bilateral superior parietal lobule (SPL), and structural damage of the right-lateralized ventral attention network (VAN), including the temporo-parietal junction (TPJ), have been described as neural basis for hemispatial neglect.Pursuing a virtual lesion model, we aimed to perturbate the attention networks of 22 healthy subjects by applying continuous theta burst stimulation (cTBS) to the right SPL or TPJ. We first created network masks of the DAN and VAN based on RSFC analyses from a RS-fMRI baseline session and determined the SPL and TPJ stimulation site within the respective mask. We then performed RS-fMRI immediately after cTBS of the SPL, TPJ (active sites) or vertex (control site). RSFC between SPL/TPJ and whole brain as well as between predefined regions of interest (ROI) in the attention networks was analyzed in a within-subject design.Contrary to our hypothesis, seed-based RSFC did not differ between the four experimental conditions. The individual change in ROI-to-ROI RSFC from baseline to post-stimulation did also not differ between active (SPL, TPJ) and control (vertex) cTBS.In our study, a single session offline cTBS over the right SPL or TPJ could not alter RSFC in the attention networks as compared to a control stimulation, maybe because effects wore off too early. Future studies should consider a modified cTBS protocol, concurrent TMS-fMRI or transcranial direct current stimulation.

Impaired LTD-like motor cortical plasticity in female patients with major depression disorder

BackgroundsLong-term depression (LTD) is a form of physiologic plasticity that is important for reversal learning and may be linked to major depression. Few studies have examined LTP-like plasticity in patients with depression. It is unclear if continuous theta burst stimulation (cTBS) induced LTD is altered in depression patients. MethodsHere we recruited 29 healthy control subjects and 31 female patients with depression. We performed cTBS protocol on left motor cortex and employed motor evoked potentials (MEPs) response to measure LTD-like plasticity. Peripheral molecules were measured for correlation analyses to cortical plasticity. ResultsOur results revealed persistent LTD-like plasticity deficits in female patients with depression. LTD-like plasticity was impaired in patients with depression despite the fact that peripheral concentrations of BDNF were comparable to that of healthy subjects. Conclusions: Our findings provide evidence for impaired LTD-like plasticity in patients with depression which may be an important mechanism linked to the pathophysiology and treatment of this disorder.

Effects of Cerebellar Theta Burst Stimulation on Contralateral Motor Cortex Excitability in Patients with Alzheimer's Disease.

Although the cerebellum is not among the most renowned brain structures affected in Alzheimer`s disease (AD), recent evidence suggest that it undergoes degenerative changes during the course of the disease. A main neurophysiological feature of AD patients is the remarkable impairment of long term potentiation (LTP)-like cortical plasticity assessed in the primary motor cortex (M1) using theta burst stimulation (TBS) protocols. In healthy conditions, continuous (cTBS) and intermittent TBS (iTBS) of the cerebellum induce respectively long term depression (LTD)-like and LTP-like after effects in the contralateral M1. Here we aimed at examining the effects of cerebellar TBS on contralateral M1 excitability in a sample of 15 AD patients and 12 healthy age matched controls (HS). Motor evoked potentials (MEPs) were obtained in the contralateral M1 before and after cerebellar cTBS and iTBS protocols. As compared to HS, AD patients showed an impairment of LTP-like cortical plasticity mechanisms following cerebellar iTBS. No difference was observed for the cTBS protocol, in which both populations exhibited the expected LTD-like after effect. This study shows that mechanisms of cerebellar-cortical plasticity are impaired in AD. Given its role in high order cognitive functions, new potential therapeutic strategies could be built up in the future to modulate neural activity in the cerebellum in AD.

Theta burst stimulation in neglect after stroke: functional outcome and response variability origins.

Spatial neglect is a strong and negative predictor of general functional outcome after stroke, and its therapy remains a challenge. Whereas inhibitory non-invasive brain stimulation over the contralesional, intact hemisphere has generally been shown to ameliorate neglect on a group level, a conspicuous variability of the effects at the individual level is typically observed. We aimed to assess the characteristics and determinants of the effects of inhibitory non-invasive brain stimulation in neglect, identifying which patients would respond to this therapeutic approach and which not. To this end, we prospectively included 60 patients with a subacute right-hemispheric stroke. In 30 patients with spatial neglect, continuous theta burst stimulation (cTBS) was applied over the left posterior parietal cortex in a randomized clinical trial, either in eight or 16 trains, or as sham stimulation. Thirty patients without neglect served as a control group. Neglect severity was measured with a neuropsychological test battery and the Catherine Bergego Scale, at admission to and at discharge from inpatient neurorehabilitation, as well as at 3 months follow-up. General functional outcome was assessed by means of the Functional Independence Measure and the Lucerne ICF-based Multidisciplinary Observation Scale. The impact of clinical and demographic factors was evaluated, and the influence of lesion location and extension was assessed by means of voxel-based lesion-symptom mapping. On a group level, both cTBS protocols (i.e. eight and 16 trains) significantly reduced neglect severity in both the Catherine Bergego Scale and the neuropsychological tests, at discharge and 3 months later. Furthermore, cTBS significantly improved general functional outcome. On an individual level, hierarchical cluster and voxel-based lesion-symptom mapping analyses revealed that the variability in the responses to cTBS is determined by the integrity of interhemispheric connections within the corpus callosum, in particular parieto-parietal connections. In cTBS responders, in whom neglect and general functional outcome were significantly improved, the corpus callosum was intact, whereas this was not the case in cTBS non-responders. Moreover, analyses based on the proportional recovery rule and the Maugeri predictive stroke recovery model showed that the recovery of neglect and of the activities of daily living was accelerated only in cTBS responders. Furthermore, the level of activities of daily living recovery of these neglect patients was brought close to the one of right-hemispheric control patients without neglect. Hence, in neglect patients with intact interhemispheric connectivity, cTBS over the contralesional posterior parietal cortex significantly improves and accelerates neglect recovery and, associated with it, general functional outcome.

Both 50 and 30 Hz continuous theta burst transcranial magnetic stimulation depresses the cerebellum

The cerebellum is implicated in the pathophysiology of numerous movement disorders, which makes it an attractive target for noninvasive neurostimulation. Continuous theta burst stimulation (cTBS) can induce long lasting plastic changes in human brain; however, the efficacy of different simulation protocols has not been investigated at the cerebellum. Here, we compare a traditional 50-Hz and a modified 30-Hz cTBS protocols at modulating cerebellar activity in healthy subjects. Seventeen healthy adults participated in two testing sessions where they received either 50-Hz (cTBS50) or 30-Hz (cTBS30) cerebellar cTBS. Cerebellar brain inhibition (CBI), a measure of cerebello-thalamocortical pathway strength, and motor evoked potentials (MEP) were measured in the dominant first dorsal interosseous muscle before and after (up to ~ 40min) cerebellar cTBS. Both cTBS protocols induced cerebellar depression, indicated by significant reductions in CBI (P < 0.001). No differences were found between protocols (cTBS50 and cTBS30) at any time point (P = 0.983). MEP amplitudes were not significantly different following either cTBS protocol (P = 0.130). The findings show cerebellar excitability to be equally depressed by 50-Hz and 30-Hz cTBS in heathy adults and support future work to explore the efficacy of different cerebellar cTBS protocols in movement disorder patients where cerebellar depression could provide therapeutic benefits.

Intra- and Inter-Regional Priming of Ipsilateral Human Primary Motor Cortex With Continuous Theta Burst Stimulation Does Not Induce Consistent Neuroplastic Effects.

Human responses to non-invasive brain stimulation (NIBS) techniques can be highly variable. Recently, priming protocols involving a conditioning round of NIBS applied to a target brain region prior to the application of a test protocol have shown promise in inducing more reliable effects. We investigated whether intra- or inter-regional priming of the left primary motor cortex (M1) using continuous theta burst stimulation (cTBS) can induce consistent, and reliable modulation of corticospinal excitability. Twenty healthy adults (six males) underwent four cTBS protocols. For intra-regional priming, cTBS was applied twice to the left M1 (M1-M1). For inter-regional M1 priming, cTBS was applied to the ipsilateral (left) dorsal premotor cortex (dPMC-M1), and ipsilateral (left) dorsolateral prefrontal cortex (DLPFC-M1). In the control condition, sham stimulation was applied to left M1, followed by active cTBS also applied to the left M1 (sham-M1). Each round of cTBS was separated by 10 min. Neuroplastic responses were indexed using motor evoked potentials (MEPs) elicited from the left M1 hand region, and measured from the contralateral first dorsal interosseous (right hand). MEP measurements were taken before the first round of cTBS priming, then immediately, 10, 20 and 30 min after the second test round of cTBS. The primary two-way repeated measures ANOVA revealed no significant differences in MEP responses across each condition (no main effects or interaction). Intra- and inter-regional priming of the left M1 using cTBS does not induce consistent neuroplastic effects. Further work is required to identify factors which contribute to such variability in human responses to NIBS.

P225 Effect of 30, 50 and 100 Hz tetha burst stimulation on healthy individuals

Objective Continuous tetha burst stimulation (cTBS) protocol mainly consists of 3 stimulus bursts repeating every 200 ms at 50 Hz and It has been interpreted that cTBS had inhibitory effects on human motor cortex. On the other hand, there are some reports that 50 Hz cTBS had variability within and between subjects on cortical excitability. In addition, little was known about the effect of different cTBS modalities. The objective of this study is to investigate the effects of 50 Hz, 30 Hz and 100 Hz cTBS on motor cortical excitability healthy subjects. Method Resting motor treshold (rMT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and motor evoked potential (MEP) amplitude were studied in 30 healthy subjects. Conditioning stimuli was 80% of rMT and test stimuli was 120% of rMT during SICI and ICF studies. rMT, MEP, SICI and ICF tests were repeated at just after and 30 min later than first 30, 50 and 100 Hz cTBS studies. Results In consistent with the current literature 50 Hz cTBS has inhibitory effects on MEP responses. 30 Hz cTBS has more greater inhibition than 50 Hz cTBS. On the other hand 100 Hz cTBS has facilitatory effects on cortical excitability. Discussion The effects of cTBS on motor cortical excitability depend on the studied paradigm. These results should be considered for selection of the research protocols or therapeutic application of cTBS.

P160 Enhanced biasing effect of prior knowledge on perceptual decision processes following continuous theta burst stimulation of motor cortex

Introduction Separate interneuron circuits in human motor cortex (M1) have been suggested to subserve different forms of motor behaviour, but it is not clear what role they play in other aspects such as decision-to-action processes. Objectives We tested whether two distinct interneuron networks in M1 play different roles in perceptual decision-making. Materials & methods 10 participants completed 3 blocks of a decision making task in each of 2 measurement sessions. Participants responded to a left/right visual imperative cue with left/right hand key presses. A random dot kinetogram (RDK) with 2 levels of coherent motion (low, high) preceded the visual cue. In 80% of trials the motion direction of the dots was congruent with that of the imperative cue, and thus could be used to prepare a response in advance. Accuracy and reaction time (RT) associated with correct responses in congruent trials were measured. A controllable pulse parameter transcranial magnetic stimulation (cTMS; Rogue Resolutions Ltd.) device was used to target distinct interneuron circuits in M1 by changing the coil orientation (posterior-anterior, PA; anterior-posterior, AP) and pulse width (45–75 μ s). A continuous theta burst stimulation (cTBS) protocol was applied with AP45 or PA75 pulses, in separate sessions, to the left M1 following the first block of the decision-making task. Results Accuracy of responses was typically ⩾95%, therefore we focus on RTs. As expected, RTs were faster with high versus low RDK coherence (Fig. 1A–D). There was no effect of pulse type on RTs, but ANOVA revealed an interaction of hand, block and coherence (P = 0.029). Calculating the percentage change in RT from low to high coherence trials (Fig. 1E and F) revealed an improvement in RTs for right, but not left, hand responses in high, but not low, coherence trials immediately after cTBS. Conclusion Irrespective of the pulse type, and thus M1 interneuron circuits targeted, cTBS over left M1 enhanced the bias effect for corresponding right hand responses, but only following high coherence RDK. cTBS may have altered the integration in M1 of the sensory evidence from the bias and imperative cue, giving more weight to the bias which normally has a relatively minor influence. Download : Download high-res image (772KB) Download : Download full-size image

Dynamic aftereffects in supplementary motor network following inhibitory transcranial magnetic stimulation protocols

The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols [1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS)] on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or “protocol” main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies.

Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively.

Investigations of motor-cortex cortical plasticity following facilitatory and inhibitory transcranial theta-burst stimulation in schizophrenia: A proof-of-concept study

Impaired neural plasticity has been proposed as an important pathophysiological feature underlying the neurobiology and symptomatology of schizophrenia. In this proof-of-concept study, we aimed to explore cortical plasticity in schizophrenia patients with two different transcranial theta-burst (TBS) paradigms. TBS induces Ca2+-dependent long-term-potentiation (LTP)-like and long-term-depression (LTP)-like plasticity in the human motor cortex. A total of 10 schizophrenia patients and 10 healthy controls were included in this study. Cortical excitability was investigated using transcranial magnetic stimulation in each study participant before and after TBS applied to the left primary motor-cortex on two different days. cTBS600 was used to induce LTD-like and cTBS300 was used to induce LTP-like plasticity in the absence of any prior motor-cortex activation. Repeated measures ANOVAs showed a significant interaction between the timecourse, the study group and the stimulation paradigm (cTBS600 vs. cTBS300) for the left, but not for the right hemisphere. Healthy controls showed an MEP amplitude decrease at a trend level following cTBS600 and a numeric, but not significant, increase in MEP amplitudes following cTBS300. Schizophrenia patients did not show an MEP amplitude decrease following cTBS600, but surprisingly a significant MEP decrease following cTBS300. The proportion of subjects showing the expected changes in motor-cortex excitability following both cTBS paradigms was higher in healthy controls. These preliminary results indicate differences in cortical plasticity following two different cTBS protocols in schizophrenia patients compared to healthy controls. However, the incomplete plasticity response in the healthy controls and the proof-of-concept nature of this study need to be considered as important limitations.