Effects Of Theta Burst Stimulation Research Articles

Theta burst stimulation for enhancing upper extremity motor functions after stroke: a systematic review of clinical and mechanistic evidence.

This systematic review aimed to evaluate the effects of different theta burst stimulation (TBS) protocols on improving upper extremity motor functions in patients with stroke, their associated modulators of efficacy, and the underlying neural mechanisms. We conducted a meta-analytic review of 29 controlled trials published from January 1, 2000, to August 29, 2023, which investigated the effects of TBS on upper extremity motor, neurophysiological, and neuroimaging outcomes in poststroke patients. TBS significantly improved upper extremity motor impairment (Hedge's g=0.646, p=0.003) and functional activity (Hedge's g=0.500, p<0.001) compared to controls. Meta-regression revealed a significant relationship between the percentage of patients with subcortical stroke and the effect sizes of motor impairment (p=0.015) and functional activity (p=0.018). Subgroup analysis revealed a significant difference in the improvement of upper extremity motor impairment between studies using 600-pulse and 1200-pulse TBS (p=0.002). Neurophysiological studies have consistently found that intermittent TBS increases ipsilesional corticomotor excitability. However, evidence to support the regional effects of continuous TBS, as well as the remote and network effects of TBS, is still mixed and relatively insufficient. In conclusion, TBS is effective in enhancing poststroke upper extremity motor function. Patients with preserved cortices may respond better to TBS. Novel TBS protocols with a higher dose may lead to superior efficacy compared with the conventional 600-pulse protocol. The mechanisms of poststroke recovery facilitated by TBS can be primarily attributed to the modulation of corticomotor excitability and is possibly caused by the recruitment of corticomotor networks connected to the ipsilesional motor cortex.

Efficacy of Theta Burst Stimulation in Bipolar Depression: A Systematic Review and Meta-analysis

Purpose: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative therapeutic modality for bipolar depression. Theta Burst Stimulation (TBS) a novel variant of rTMS is currently evolving as an effective and safe therapeutic tool in the management of bipolar depression, although it is still in the initial phase. In the present systematic review and meta-analysis, data from various studies investigating the effectiveness and tolerability of TBS in individuals with bipolar depression were synthesized. Data collection and analyses: Eight studies assessing the efficacy of TBS as a treatment for bipolar depression were included after a systematic search. The quality of the included studies was assessed using standard methods. Synthesized data included three uncontrolled clinical trials (non-randomized controlled trials [RCTs]; n = 48) and five RCTs ( n = 201). While four studies used intermittent TBS, two studies used continuous TBS and bilateral TBS, each. Data from the five RCTs meta-analyzed using the random effects model showed the pooled odds ratio and effect size for response in the active group compared to the sham group were 1.01 (95%CI: 0.56, 1.83) and 1.64 (95%CI: –0.46, 3.74), respectively. Although both models showed no/minimal heterogeneity or publication bias, they were not statistically significant. A supplementary trial sequential analysis confirmed the need for more studies and suggested that the total sample required for drawing meaningful inferences was 918 samples. Conclusion: The available evidence suggests that more studies are required to draw conclusive inferences for the efficacy of TBS in the therapeutic management of bipolar depression.

Predicting interindividual response to theta burst stimulation in the lower limb motor cortex using machine learning.

Using theta burst stimulation (TBS) to induce neural plasticity has played an important role in improving the treatment of neurological disorders. However, the variability of TBS-induced synaptic plasticity in the primary motor cortex prevents its clinical application. Thus, factors associated with this variability should be explored to enable the creation of a predictive model. Statistical approaches, such as regression analysis, have been used to predict the effects of TBS. Machine learning may potentially uncover previously unexplored predictive factors due to its increased capacity for capturing nonlinear changes. In this study, we used our prior dataset (Katagiri et al., 2020) to determine the factors that predict variability in TBS-induced synaptic plasticity in the lower limb motor cortex for both intermittent (iTBS) and continuous (cTBS) TBS using machine learning. Validation of the created model showed an area under the curve (AUC) of 0.85 and 0.69 and positive predictive values of 77.7 and 70.0% for iTBS and cTBS, respectively; the negative predictive value was 75.5% for both patterns. Additionally, the accuracy was 0.76 and 0.72, precision was 0.82 and 0.67, recall was 0.82 and 0.67, and F1 scores were 0.82 and 0.67 for iTBS and cTBS, respectively. The most important predictor of iTBS was the motor evoked potential amplitude, whereas it was the intracortical facilitation for cTBS. Our results provide additional insights into the prediction of the effects of TBS variability according to baseline neurophysiological factors.

Treatment of Behavioral Addictions and Substance Use Disorders: a Focus on the Effects of Theta-Burst Stimulation Over the Pre-SMA

AbstractBehavioral addictions (BA) and substance use disorders (SUDs) share core features, including impaired control and craving, leading to significant personal and societal impacts. Previous research has identified the pre-supplementary motor area (pre-SMA) as a critical node in GD-related neurocircuitry, making it a potential target for interventions also in SUDs. Theta-burst stimulation (TBS) offers a non-invasive method to modulate pre-SMA activity. This study included 58 participants diagnosed with GD or SUDs. They underwent bilateral pre-SMA continuous TBS (cTBS) sessions targeting craving, impulsivity, and addiction severity. Standardized scales and questionnaires were employed to assess the outcomes. cTBS parameters included 20 daily sessions with 80% resting motor threshold (RMT). Both GD and SUD groups exhibited significant reductions in addiction severity and craving following cTBS. Impulsivity decreased significantly in SUD but not in GD. The study’s findings underscore the potential of pre-SMA TBS as an adjunctive treatment for GD and SUDs. The observed improvements in addiction severity and craving emphasize the shared neuronal mechanisms underlying these disorders. However, the nuanced differences, especially in impulsivity, indicate the need for further research to tailor interventions precisely.

Trait-dependent effects of theta burst stimulation after psychosocial stress: a sham-controlled study in healthy individuals

ObjectivePrevious studies suggest that theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising approach to modulate stress-reactive rumination and the associated psychophysiological stress response. Crucially, individuals showing higher levels of trait rumination might benefit more from prefrontal stimulation. MethodsIn this sham-controlled study, 127 healthy individuals, with varying ruminative tendencies, received a single-session of intermittent TBS (iTBS), continuous TBS (cTBS) or sham TBS (sTBS) over the left DLPFC before being confronted with a Trier Social Stress Test. ResultsResults showed significant TBS effects on salivary cortisol as a function of trait rumination. cTBS, as compared to sTBS and iTBS, resulted in an attenuated stress-induced cortisol response in high compared to low trait ruminators. Although independent of trait rumination levels, cTBS showed positive effects on stress-related changes in mood and, both cTBS and iTBS (versus sham) presented an enhanced heart rate recovery following the stressor. We found no evidence for (trait rumination-dependent) TBS effects on stress-reactive rumination, negative affect, subjective stress or heart rate variability. ConclusionscTBS shows beneficial effects on certain measures of stress, especially in high trait ruminators. SignificanceThese findings highlight the importance of accounting for individual differences when examining TBS effects.

Assessing the synergistic effectiveness of intermittent theta burst stimulation and the vestibular ocular reflex rehabilitation protocol in the treatment of Mal de Debarquement Syndrome: a randomised controlled trial

IntroductionMal de Debarquement Syndrome (MdDS) is a rare central vestibular disorder characterised by a constant sensation of motion (rocking, swaying, bobbing), which typically arises after motion experiences (e.g. sea, air, and road travel), though can be triggered by non-motion events. The current standard of care is non-specific medications and interventions that only result in mild-to-moderate improvements. The vestibular ocular reflex (VOR) rehabilitation protocol, a specialised form of rehabilitation, has shown promising results in reducing symptoms amongst people with MdDS. Accumulating evidence suggests that it may be possible to augment the effects of VOR rehabilitation via non-invasive brain stimulation protocols, such as theta burst stimulation (TBS).MethodsThe aim of this randomised controlled trial was to evaluate the effectiveness of intermittent TBS (iTBS) over the dorsolateral prefrontal cortex in enhancing the effectiveness of a subsequently delivered VOR rehabilitation protocol in people with MdDS. Participants were allocated randomly to receive either Sham (n = 10) or Active (n = 10) iTBS, followed by the VOR rehabilitation protocol. Subjective outcome measures (symptom ratings and mental health scores) were collected 1 week pre-treatment and for 16 weeks post-treatment. Posturography (objective outcome) was recorded each day of the treatment week.ResultsSignificant improvements in subjective and objective outcomes were reported across both treatment groups over time, but no between-group differences were observed.DiscussionThese findings support the effectiveness of the VOR rehabilitation protocol in reducing MdDS symptoms. Further research into iTBS is required to elucidate whether the treatment has a role in the management of MdDS. TRN: ACTRN12619001519145 (Date registered: 04 November 2019).

Preliminary evidence of prolonged timing effects of theta-burst stimulation in the reading system.

Theta-burst stimulation (TBS) is a repetitive transcranial magnetic stimulation technique that can be used to upregulate or downregulate different brain regions. However, the timing of its effects and the differing effects of continuous TBS (cTBS) versus intermittent TBS (iTBS) in the reading system have not been explored. This study assessed how stimulation type and post-stimulation timing affected change in performance during a phonological discrimination and sight word recognition task after stimulation of supramarginal gyrus (SMG). Fourteen right-handed young adults (age 18-27 years; 44% male) were block-randomized to receive either iTBS or cTBS to the supramarginal gyrus. Participants then performed a pseudoword discrimination task and an orthographic awareness task (behavioral control) at four different time points and change in reaction time compared to baseline was measured from each time point. There was no effect of stimulation type on change in reaction time [t(16) = -0.2, p = 0.9], suggesting that both types of TBS caused similar effects. Percent change in reaction time decreased over time in the pseudoword task [t(50) = -5.9, p < 0.001], indicating faster pseudoword processing speed with better performance 60-70 min after stimulation. In contrast, no change was demonstrated over time for the behavioral control task [t(43) = -0.6, p = 0.6], suggesting that the change over time seen in the test condition was not a learning effect. These findings provide insight into the effects of TBS on the reading system and can guide future study designs.

Effects of theta burst stimulation on the coherence of local field potential during working memory task in rats

Theta burst stimulation (TBS), a highly efficient repetitive transcranial magnetic stimulation (rTMS) paradigm, has been widely used to modulate the working memory (WM) ability in experimental and clinical study. However, the underly neuroelectrophysiological mechanism remains unclear. The aim of this study was to compare the effect of iTBS, cTBS and rTMS on WM and explore the neural oscillatory communication changes in PFC involved in spatial WM task. 18 rats were treated by iTBS, cTBS and rTMS respectively (n = 6 each), while the rats in control group (n = 6) received no stimulation. T-maze WM task was used to assess the rats’ performance of WM after stimulation. Local field potentials (LFPs) were recorded from a microelectrode array implanted in the medial prefrontal cortex (mPFC) while the rats were performing the WM task. Functional connectivity (FC) strength was assessed by LFP–LFP coherence calculations. The results showed that the rats from the rTMS group and iTBS group are able to reach criteria in less time than the control group's duration of the T-maze task. The power and the coherence value of rTMS and iTBS groups show a significant increase in the theta-band and gamma-band activity, wheras there are no significant differences of the energy and the coherence value between the cTBS group and the control group in theta-band. Furthermore, significantly positive correlations were observed between changes of memory performance during the WM task and the changes of the coherence value of the LFPs. In conclusion, these results indicate that rTMS and iTBS may improve the ability of WM by modulating the neural activity and connectivity in PFC.

Continuous and intermittent theta burst stimulation of primary visual cortex do not modulate resting state functional connectivity: A sham-controlled multi-echo fMRI study.

Theta burst stimulation (TBS) is a type of rTMS protocol which has the advantage of a shorter delivery time over traditional rTMS.When applied to motor cortex, intermittent TBS (iTBS) has been shown to yield excitatory aftereffects, whereas continuous TBS (cTBS) may lead to inhibitory aftereffects, both lasting from minutes to hours. The majority of TBS research has targeted motor, frontal, and parietal regions, and to date very few studies have examined its efficacy at visual areas. We designed a sham-controlled study to investigate the immediate poststimulation and short-term (1 h post-stimulation) effects of iTBS and cTBS to V1. Using multiecho functional magnetic resonance imaging, we measured the direct and indirect effects of TBS by comparing resting state functional connectivity (FC) before and after stimulation in whole brain networks, and seeds from V1 (stimulation site) and neighboring occipital and parietal visual networks. In addition, we also measured pre- and post-TBS phosphene thresholds (PTs) to examine the modulatory effects of TBS on cortical excitability. We found no changes in FC for iTBS, cTBS or sham stimulation conditions from baseline to poststimulation timepoints. Additionally, cTBS and iTBS had no effect on visual cortical excitability. Our results indicate that unlike our previous low frequency rTMS to V1 study, which resulted in widespread FC changes up to at least 1 h after stimulation, TBS to V1 does not affect FC.Contrary to the studies showing comparable TBS and rTMS aftereffects in motor and frontal regions,our findings suggest that a single session of cTBS or iTBS to V1 at 80% PT using a standard protocol of 600 pulses may not be effective in targeting FC, especially in clinical settings where therapy for pathological networks is the goal.

Effects of bilateral sequential theta-burst stimulation on 5-HT1A receptors in the dorsolateral prefrontal cortex in treatment-resistant depression: a proof-of-concept trial

Theta-burst stimulation (TBS) represents a brain stimulation technique effective for treatment-resistant depression (TRD) as underlined by meta-analyses. While the methodology undergoes constant refinement, bilateral stimulation of the dorsolateral prefrontal cortex (DLPFC) appears promising to restore left DLPFC hypoactivity and right hyperactivity found in depression. The post-synaptic inhibitory serotonin-1A (5-HT1A) receptor, also occurring in the DLPFC, might be involved in this mechanism of action. To test this hypothesis, we performed PET-imaging using the tracer [carbonyl-11C]WAY-100635 including arterial blood sampling before and after a three-week treatment with TBS in 11 TRD patients compared to sham stimulation (n = 8 and n = 3, respectively). Treatment groups were randomly assigned, and TBS protocol consisted of excitatory intermittent TBS to the left and inhibitory continuous TBS to the right DLPFC. A linear mixed model including group, hemisphere, time, and Hamilton Rating Scale for Depression (HAMD) score revealed a 3-way interaction effect of group, time, and HAMD on specific distribution volume (VS) of 5-HT1A receptor. While post-hoc comparisons showed no significant changes of 5-HT1A receptor VS in either group, higher 5-HT1A receptor VS after treatment correlated with greater difference in HAMD (r = −0.62). The results of this proof-of-concept trial hint towards potential effects of TBS on the distribution of the 5-HT1A receptor. Due to the small sample size, all results must, however, be regarded with caution.

Effects of bilateral sequential theta-burst stimulation on functional connectivity in treatment-resistant depression: First results

BackgroundPrevious studies suggest that transcranial magnetic stimulation exerts antidepressant effects by altering functional connectivity (FC). However, knowledge about this mechanism is still limited. Here, we aimed to investigate the effect of bilateral sequential theta-burst stimulation (TBS) on FC in treatment-resistant depression (TRD) in a sham-controlled longitudinal study. MethodsTRD patients (n = 20) underwent a three-week treatment of intermittent TBS of the left and continuous TBS of the right dorsolateral prefrontal cortex (DLPFC). Upon this trial's premature termination, 15 patients had received active TBS and five patients sham stimulation. Resting-state functional magnetic resonance imaging was performed at baseline and after treatment. FC (left and right DLPFC) was estimated for each participant, followed by group statistics (t-tests). Furthermore, depression scores were analyzed (linear mixed models analysis) and tested for correlation with FC. ResultsBoth groups exhibited reductions of depression scores, however, there was no significant main effect of group, or group and time. Anticorrelations between DLPFC and the subgenual cingulate cortex (sgACC) were observed for baseline FC, corresponding to changes in depression severity. Treatment did not significantly change DLPFC-sgACC connectivity, but significantly reduced FC between the left stimulation target and bilateral anterior insula. ConclusionsOur data is compatible with previous reports on the relevance of anticorrelation between DLPFC and sgACC for treatment success. Furthermore, FC changes between left DLPFC and bilateral anterior insula highlight the effect of TBS on the salience network. LimitationsDue to the limited sample size, results should be interpreted with caution and are of exploratory nature.

The Effect of Theta Burst Stimulation Over the Primary Motor Cortex on Experimental Hamstring Pain: A Randomized, Controlled Study

Theta burst stimulation (TBS) over the primary motor cortex (M1) is an emerging technique that may have utility in the treatment of musculoskeletal pain. However, previous work exploring the analgesic effects of noninvasive brain stimulation has been limited largely to the arm or hand, despite 80% of acute musculoskeletal injuries occurring in the lower limb. This is a pertinent point, given the functional and neurophysiological differences between upper and lower limb musculature, as well as evidence suggesting that reorganization of corticomotor pathways is region-specific. This study investigated the effect of excitatory TBS on pain, function, and corticomotor organization during experimentally induced lower limb pain. Twenty-eight healthy participants attended 2 experimental sessions. On Day 0, participants completed 10 sets of 10 maximal eccentric contractions of the right hamstring muscles to induce delayed onset muscle soreness. Four consecutive blocks of either active or sham TBS were delivered on Day 2. Measures of mechanical sensitivity, pain (muscle soreness, pain intensity, pain area) function (single-leg hop distance, maximum voluntary isometric contraction, lower extremity functional scale), and corticomotor organization were recorded before and after TBS on Day 2. Pain and function were also assessed daily from Days 2 to 10. Active TBS reduced mechanical sensitivity compared to sham stimulation (P = .01). Corticomotor organization did not differ between groups, suggesting that improvements in mechanical sensitivity were not mediated by changes in M1. Subjective reports of pain intensity and function did not change following active TBS, contrasting previous reports in studies of the upper limb. PerspectiveM1 TBS reduces mechanical sensitivity associated with experimentally induced hamstring pain. Though further work is needed, these findings may hold important implications for those seeking to expedite recovery or reduce muscle sensitivity following hamstring injury.

Neuromodulatory effects of theta burst stimulation to the prefrontal cortex

Theta burst stimulation (TBS) is a new form of repetitive transcranial magnetic stimulation (TMS) capable of non-invasively modulating cortical excitability. In recent years TBS has been increasingly used as a neuroscientific investigative tool and therapeutic intervention for psychiatric disorders, in which the dorsolateral prefrontal cortex (DLPFC) is often the primary target. However, the neuromodulatory effects of TBS on prefrontal regions remain unclear. Here we share EEG and ECG recordings and structural MRI scans, including high-resolution DTI, from twenty-four healthy participants who received intermittent TBS (two sessions), continuous TBS (two sessions), and sham stimulation (one session) applied to the left DLPFC using a single-blinded crossover design. Each session includes eyes-open resting-state EEG and single-pulse TMS-EEG obtained before TBS and 2−, 15−, and 30-minutes post-stimulation. This dataset enables foundational basic science investigations into the neuromodulatory effects of TBS on the DLPFC.

24.2 Effects of Theta Burst Stimulation on Symptoms and the Brain in Youth with ASD: A Randomized Sham-Controlled Trial

Early data suggest that theta burst stimulation (TBS), a modified form of repetitive transcranial magnetic stimulation (rTMS) with shorter stimulation duration and lower pulses and intensity, might be promising to improve symptoms in children with ASD. But the feasibility of TBS in children with ASD in a rigorous design is unknown. The current presentation will: 1) present published findings from an RCT reporting on the feasibility, tolerability, and preliminary efficacy of an intermittent TBS (excitatory) to the posterior superior temporal sulcus (pSTS) in children with ASD; 2) present results from the same trial with pre/post-MRI to track stimulation-induced brain change; and 3) present the protocol and preliminary results from an ongoing RCT using continuous TBS (inhibitory) to the left dorsolateral prefrontal cortex (DLPFC) in children with ASD.

Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression

Treatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in TRD. Theta burst stimulation (TBS), a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right continuous TBS for only 4 minutes. To establish the effectiveness and tolerability of TBS compared with standard rTMS in older adults with TRD. In this randomized noninferiority trial with open treatment and blinded assessors, recruitment occurred between December 2016 and March 2020. The trial was conducted at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada and included outpatients 60 years and older with a diagnosis of depression, moderate severity, and nonresponse to 1 or more antidepressant trial of adequate dosage and duration or intolerance of 2 or more trials. Participants were randomized to receive a course of 4 to 6 weeks of either bilateral standard rTMS or TBS. The primary outcome measure was change in Montgomery-Åsberg Depression Rating Scale; secondary outcome measures included the 17-item Hamilton Rating Scale for Depression, Quick Inventory of Depressive Symptomatology (16-item) (self-report), and dropout rates. A noninferiority margin of 2.75 points was used for the primary outcome. All participants who attained the primary completion point of 4 weeks were analyzed. A total of 87 participants (mean [SD] age, 67.1 [6.7] years; 47 [54.0%] female) were randomized to standard bilateral rTMS and 85 (mean [SD] age, 66.3 [5.3] years; 45 [52.9%] female) to TBS, of whom 85 (98%) and 79 (93%) were assessed for the primary outcome, respectively, whereas tolerability was assessed in all randomized participants. In the rTMS group, 4 (4.6%) were American Indian, reported other, or preferred not to answer; 5 (5.8%) were Asian; and 78 (89.7%) were White. In the TBS group, 6 (7.1%) were Asian, 2 (2.4%) were Black or reported other, and 77 (90.3%) were White. Mean (SD) Montgomery-Åsberg Depression Rating Scale total scores improved from 25.6 (4.0) to 17.3 (8.9) for rTMS and 25.7 (4.7) to 15.8 (9.1) for TBS (adjusted difference, 1.55; lower 95% CI -0.67), establishing noninferiority for TBS. The all-cause dropout rates were relatively similar between groups (rTMS: 2 of 87 [2.3%]; TBS: 6 of 85 [7.1%]; P = .14; χ2 = 2.2). In older adults with TRD, bilateral TBS compared with standard bilateral rTMS achieved noninferior reduction in depression symptoms. Both treatments had low and similar dropout rates. Using TBS rather than rTMS could increase access to treatment several-fold for older adults with TRD. ClinicalTrials.gov Identifier: NCT02998580.

The Impact of Theta-Burst Stimulation on Cortical GABA and Glutamate in Treatment-Resistant Depression: A Surface-Based MRSI Analysis Approach.

Background: Theta burst stimulation (TBS) belongs to one of the biological antidepressant treatment options. When applied bilaterally, excitatory intermittent TBS (iTBS) is commonly targeted to the left and inhibitory continuous TBS (cTBS) to the right dorsolateral prefrontal cortex. TBS was shown to influence neurotransmitter systems, while iTBS is thought to interfere with glutamatergic circuits and cTBS to mediate GABAergic neurotransmission.Objectives: We aimed to expand insights into the therapeutic effects of TBS on the GABAergic and glutamatergic system utilizing 3D-multivoxel magnetic resonance spectroscopy imaging (MRSI) in combination with a novel surface-based MRSI analysis approach to investigate changes of cortical neurotransmitter levels in patients with treatment-resistant depression (TRD).Methods: Twelve TRD patients (five females, mean age ± SD = 35 ± 11 years) completed paired MRSI measurements, using a GABA-edited 3D-multivoxel MEGA-LASER sequence, before and after 3 weeks of bilateral TBS treatment. Changes in cortical distributions of GABA+/tNAA (GABA+macromolecules relative to total N-acetylaspartate) and Glx/tNAA (Glx = mixed signal of glutamate and glutamine), were investigated in a surface-based region-of-interest (ROI) analysis approach.Results: ANCOVAs revealed a significant increase in Glx/tNAA ratios in the left caudal middle frontal area (pcorr. = 0.046, F = 13.292), an area targeted by iTBS treatment. Whereas, contralateral treatment with cTBS evoked no alterations in glutamate or GABA concentrations.Conclusion: This study demonstrates surface-based adaptions in the stimulation area to the glutamate metabolism after excitatory iTBS but not after cTBS, using a novel surface-based analysis of 3D-MRSI data. The reported impact of facilitatory iTBS on glutamatergic neurotransmission provides further insight into the neurobiological effects of TBS in TRD.

Reliability of transcranial magnetic stimulation evoked potentials to detect the effects of theta-burst stimulation of the prefrontal cortex

BackgroundTranscranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) is a novel method for assessing cortical properties outside the motor region. Theta burst stimulation (TBS), a form of repetitive TMS, can non-invasively modulate cortical excitability and has been increasingly used to treat psychiatric disorders by targetting the dorsolateral prefrontal cortex (DLPFC). The TMS-evoked potentials (TEPs) and local mean field power (LMFP) analyses have been used to evaluate local cortical excitability changes after TBS. However, it remains unclear whether TEPs can detect the neuromodulatory effects of TBS. ObjectivesTo confirm the reliability of TEP components and LMFP within and between sessions and to measure changes in neural excitability induced by intermittent (iTBS) and continuous TBS (cTBS) applied to the left DLPFC. MethodsTest-retest reliability of TEPs/LMFP and TBS-induced changes in cortical excitability were assessed in twenty-four healthy participants by stimulating the DLPFC in five separate sessions, once with sham and twice with iTBS and cTBS. EEG responses were recorded of 100 single TMS pulses before and after TBS, and the reproducibility measures were quantified with the concordance correlation coefficient (CCC). ResultsThe N100 and P200 components presented substantial reliability within the baseline block (CCCs>0.8) and moderate concordance between sessions (CCCmax> 0.6). Both N40 and P60 TEP amplitudes showed little concordance between sessions. Similar results were achieved using LMFP responses. Changes in TEP amplitudes after iTBS were marginally reliable for N100 (CCCmax = 0.52), P200 (CCCmax = 0.47) and P60 (CCCmax = 0.40), presenting only fair levels of concordance at specific time points. LMFP changes showed poor reproducibility after iTBS and cTBS. ConclusionsThe present findings show that only the N100 and P200 components had good concordance between sessions. The reliability of earlier TEP components and LMF responses may have been affected by a sub-optimal removal of TMS-related artefacts. The poor reliability in detecting changes in neural excitability induced by TBS indicates that TEPs/LMFP do not provide a precise estimate of the changes in excitability in the DLPFC or, alternatively, that TBS did not induce consistent changes in neural excitability.

Cerebellar Continuous Theta Burst Stimulation for Aphasia Rehabilitation: Study Protocol for a Randomized Controlled Trial.

BackgroundLanguage recovery is limited in moderate to severe post-stroke aphasia patients. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising tool in improving language dysfunctions caused by post-stroke aphasia, but the treatment outcome is as yet mixed. Considerable evidence has demonstrated the essential involvement of the cerebellum in a variety of language functions, suggesting that it may be a potential stimulation target of TMS for the treatment of post-stroke aphasia. Theta burst stimulation (TBS) is a specific pattern of rTMS with shorter stimulation times and better therapeutic effects. The effect of continuous TBS (cTBS) on the cerebellum in patients with aphasia with chronic stroke needs further exploration.MethodsIn this randomized, sham-controlled clinical trial, patients (n = 40) with chronic post-stroke aphasia received 10 sessions of real cTBS (n = 20) or sham cTBS (n = 20) over the right cerebellar Crus I+ a 30-min speech-language therapy. The Western Aphasia Battery (WAB) serves as the primary measure of the treatment outcome. The secondary outcome measures include the Boston Diagnostic Aphasia Examination, Boston Naming Test and speech acoustic parameters. Resting-state fMRI data were also obtained to examine treatment-induced changes in functional connectivity of the cerebro-cerebellar network. These outcome measures are assessed before, immediately after, and 12 weeks after cerebellar cTBS intervention.DiscussionThis protocol holds promise that cerebellar cTBS is a potential strategy to improve language functions in chronic post-stroke aphasia. The resting-state fMRI may explore the neural mechanism underlying the aphasia rehabilitation with cerebellar cTBS.

P.054 Effects of cerebellar Theta Burst Stimulation (TBS) on working memory

Background: Recent evidence suggests that the cerebellum is involved in cognitive functions. Theta burst stimulation (TBS), a modality of transcranial magnetic stimulation (TMS), on the cerebellum can change its contribution to working memory. Therefore, we hypothesize that excitatory intermittent TBS (iTBS) on the cerebellum would improve performance on working memory tasks, whereas inhibitory continuous TBS (cTBS) would disrupt it. Methods: As this is an ongoing study, nine participants (6 women) took part in this study so far. TBS was applied on the cerebellum bilaterally. All subjects received iTBS, cTBS, and sham iTBS in three sessions in random order. After TBS in each session, participants performed three types of working memory tasks: letter 2-back, digit span forward (DSF), and digit span backward (DSB). Results: The preliminary results suggest that participants performed better in the sham condition in the letter 2-back and the DSB tasks compared to the iTBS and cTBS conditions, but the results did not reach statistical significance due to the small sample size. Conclusions: The preliminary results show that the cerebellar contribution to working memory may be disrupted by TBS. As we gain more statistical power by recruiting more participants, we hope to further demonstrate the effects of cerebellar TBS on working memory.

Reliability of theta burst stimulation as a neuromodulation tool.

Theta burst stimulation (TBS), a specific version of transcranial magnetic stimulation (TMS), is known to induce long-term plasticity of the brain with a short-term administration. Although many studies and treatments have increasingly used TBS as a neuromodulation tool, its reliability is still in question. This article reviews a study by Boucher et al. (Boucher PO, Ozdemir RA, Momi D, Burke MJ, Jannati A, Fried PJ, Pascual-Leone A, Shafi MM, Santarnecchi E. Sci Rep 11: 21170, 2021) that found minimal reliability of TBS by examining different TBS protocols (intermittent/continuous/sham) and considers possible alternative explanations for the variability of TBS effects.