Continuous Theta Burst Stimulation Research Articles

Personalised functional imaging-guided multitarget continuous theta burst stimulation for post-stroke aphasia: study protocol for a randomised controlled trial

IntroductionContinuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of post-stroke aphasia (PSA) patients shows promising results in...

Intermittent theta-burst stimulation to the right dorsolateral prefrontal cortex may increase potentiated startle in healthy individuals.

Repetitive transcranial magnetic stimulation (rTMS) treatment protocols targeting the right dlPFC have been effective in reducing anxiety symptoms comorbid with depression. However, the mechanism behind these effects is unclear. Further, it is unclear whether these results generalize to non-depressed individuals. We conducted a series of studies aimed at understanding the link between anxiety potentiated startle and the right dlPFC, following a previous study suggesting that continuous theta burst stimulation (cTBS) to the right dlPFC can make people more anxious. Based on these results we hypothesized that intermittent TBS (iTBS), which is thought to have opposing effects on plasticity, may reduce anxiety when targeted at the same right dlPFC region. In this double-blinded, cross-over design, 28 healthy subjects underwent 12 study visits over a 4-week period. During each of their 2 stimulation weeks, they received four 600 pulse iTBS sessions (2/day), with a post-stimulation testing session occurring 24 h following the final iTBS session. One week they received active stimulation, one week they received sham. Stimulation weeks were separated by a 1-week washout period and the order of active/sham delivery was counterbalanced across subjects. During the testing session, we induced anxiety using the threat of unpredictable shock and measured anxiety potentiated startle. Contrary to our initial hypothesis, subjects showed increased startle reactivity following active compared to sham stimulation. These results replicate work from our two previous trials suggesting that TMS to the right dlPFC increases anxiety potentiated startle, independent of both the pattern of stimulation and the timing of the post stimulation measure. Although these results confirm a mechanistic link between right dlPFC excitability and startle, capitalizing upon this link for the benefit of patients will require future exploration.

Pilot study with randomised control of dual site theta burst transcranial magnetic stimulation (TMS) for methamphetamine use disorder: a protocol for the TARTAN study

BackgroundTranscranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting.MethodsThirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition).DiscussionThis study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks).Trial registrationAustralia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

Continuous Theta-Burst Stimulation on the Left Posterior Inferior Frontal Gyrus Perturbs Complex Syntactic Processing Stability in Mandarin Chinese

Abstract The structure of human language is inherently hierarchical. The left posterior inferior frontal gyrus (LpIFG) is proposed to be a core region for constructing syntactic hierarchies. However, it remains unclear whether LpIFG plays a causal role in syntactic processing in Mandarin Chinese and whether its contribution depends on syntactic complexity, working memory, or both. We addressed these questions by applying inhibitory continuous theta-burst stimulation (cTBS) over LpIFG. Thirty-two participants processed sentences containing embedded relative clauses (i.e., complex syntactic processing), syntactically simpler coordinated sentences (i.e., simple syntactic processing), and non-hierarchical word lists (i.e., word list processing) after receiving real or sham cTBS. We found that cTBS significantly increased the coefficient of variation, a representative index of processing stability, in complex syntactic processing (esp., when subject relative clause was embedded) but not in the other two conditions. No significant changes in d′ and reaction time were detected in these conditions. The findings suggest that (a) inhibitory effect of cTBS on the LpIFG might be prominent in perturbing the complex syntactic processing stability but subtle in altering the processing quality; and (b) the causal role of the LpIFG seems to be specific for syntactic processing rather than working memory capacity, further evidencing their separability in LpIFG. Collectively, these results support the notion of the LpIFG as a core region for complex syntactic processing across languages.

A 10-day theta burst stimulation intervention facilitates the clinical rehabilitation of patients following an isolated limb fracture: A longitudinal SHAM-controlled pilot study.

We investigated if theta burst stimulation (TBS) could enhance recovery by reducing key symptoms when implemented acutely post-fracture in participants with an isolated upper limb fracture (IULF). This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous TBS protocol. Two main groups were included: I) participants with IULF receiving active TBS; and II) patients with IULF receiving SHAM/placebo. Another group (III) of healthy individuals were the reference group. Disability and pain intensity were collected through questionnaires (DASH & NRA) at three timepoints (baseline; 72 h post-intervention & 3 months post-injury). Group III completed the baseline assessment. 79 participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between Intervention and Time approached significance (F = 2.33; p = 0.11), whereas it was significant for pain (F = 3.42; p = 0.04). At 3 months post-injury, the ACTIVE group reported reduced disability (F = 4.71; p = 0.04) and pain (F = 5.84; p = 0.02) at three months post-injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls. In IULF patients, a 10-day TBS intervention implemented acutely post-trauma had beneficial effects on symptoms of functional recovery and pain at 3 months post-trauma.

Switching off: disruptive TMS reveals distinct contributions of the posterior middle temporal gyrus and angular gyrus to bilingual speech production.

The role of the left temporoparietal cortex in speech production has been extensively studied during native language processing, proving crucial in controlled lexico-semantic retrieval under varying cognitive demands. Yet, its role in bilinguals, fluent in both native and second languages, remains poorly understood. Here, we employed continuous theta burst stimulation to disrupt neural activity in the left posterior middle-temporal gyrus (pMTG) and angular gyrus (AG) while Italian-Friulian bilinguals performed a cued picture-naming task. The task involved between-language (naming objects in Italian or Friulian) and within-language blocks (naming objects ["knife"] or associated actions ["cut"] in a single language) in which participants could either maintain (non-switch) or change (switch) instructions based on cues. During within-language blocks, cTBS over the pMTG entailed faster naming for high-demanding switch trials, while cTBS to the AG elicited slower latencies in low-demanding non-switch trials. No cTBS effects were observed in the between-language block. Our findings suggest a causal involvement of the left pMTG and AG in lexico-semantic processing across languages, with distinct contributions to controlled vs. "automatic" retrieval, respectively. However, they do not support the existence of shared control mechanisms within and between language(s) production. Altogether, these results inform neurobiological models of semantic control in bilinguals.

7. Continuous Theta Burst Stimulation of Ventrolateral Prefrontal Cortex and Associated Reductions in Hypomanic Symptoms

7. Continuous Theta Burst Stimulation of Ventrolateral Prefrontal Cortex and Associated Reductions in Hypomanic Symptoms

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.

0435 Continuous Theta-burst Stimulation Lowers the Impact of Anxiety on Sleep Duration in Individuals with Insomnia

0435 Continuous Theta-burst Stimulation Lowers the Impact of Anxiety on Sleep Duration in Individuals with Insomnia

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.

Causally Probing the Role of the Hippocampus in Fear Discrimination: A Precision Functional Mapping–Guided, Transcranial Magnetic Stimulation Study in Participants With Posttraumatic Stress Symptoms

BackgroundFear overgeneralization is a promising pathogenic mechanism of clinical anxiety. A dominant model posits that hippocampal pattern separation failures drive overgeneralization. Hippocampal network–targeted transcranial magnetic stimulation (HNT-TMS) has been shown to strengthen hippocampal-dependent learning/memory processes. However, no study has examined whether HNT-TMS can alter fear learning/memory. MethodsContinuous theta burst stimulation was delivered to individualized left posterior parietal stimulation sites derived via seed-based connectivity, precision functional mapping, and electric field modeling methods. A vertex control site was also stimulated in a within-participant, randomized controlled design. Continuous theta burst stimulation was delivered prior to 2 visual discrimination tasks (1 fear based, 1 neutral). Multilevel models were used to model and test data. Participants were undergraduates with posttraumatic stress symptoms (final n = 25). ResultsMain analyses did not indicate that HNT-TMS strengthened discrimination. However, multilevel interaction analyses revealed that HNT-TMS strengthened fear discrimination in participants with lower fear sensitization (indexed by responses to a control stimulus with no similarity to the conditioned fear cue) across multiple indices (anxiety ratings: β = 0.10, 95% CI, 0.04 to 0.17, p = .001; risk ratings: β = 0.07, 95% CI, 0.00 to 0.13, p = .037). ConclusionsOvergeneralization is an associative process that reflects deficient discrimination of the fear cue from similar cues. In contrast, sensitization reflects nonassociative responding unrelated to fear cue similarity. Our results suggest that HNT-TMS may selectively sharpen fear discrimination when associative response patterns, which putatively implicate the hippocampus, are more strongly engaged.

Age-related changes in responsiveness to non-invasive brain stimulation neuroplasticity paradigms: A systematic review with meta-analysis

ObjectivesWe aimed to summarise and critically appraise the available evidence for the effect of age on responsiveness to non-invasive brain stimulation (NBS) paradigms delivered to the primary motor cortex. MethodsFour databases (Medline, Embase, PsycINFO and Scopus) were searched from inception to February 7, 2023. Studies investigating age group comparisons and associations between age and neuroplasticity induction from NBS paradigms were included. Only studies delivering neuroplasticity paradigms to the primary motor cortex and responses measured via motor-evoked potentials (MEPs) in healthy adults were considered. Results39 studies, encompassing 40 experiments and eight NBS paradigms were included: paired associative stimulation (PAS; n = 12), repetitive transcranial magnetic stimulation (rTMS; n = 2), intermittent theta burst stimulation (iTBS; n = 8), continuous theta burst stimulation (cTBS; n = 7), transcranial direct and alternating current stimulation ((tDCS; n = 7; tACS; n = 2)), quadripulse stimulation (QPS; n = 1) and i-wave periodic transcranial magnetic stimulation (iTMS; n = 1). Pooled findings from PAS paradigms suggested older adults have reduced post-paradigm responses, although there was considerable heterogeneity. Mixed results were observed across all other NBS paradigms and post-paradigm timepoints. Conclusions/significanceWhilst age-dependent reduction in corticospinal excitability is possible, there is extensive inter- and intra-individual variability both within and between studies, making it difficult to draw meaningful conclusions from pooled analyses.

Assessment of the Efficacy of Intensive Continuous Theta Burst Stimulation over Supplementary Motor Area in Psychogenic Non-Epileptic Seizure: A Randomized Sham-Controlled Pilot Trial

Objectives: There is a need for novel treatment strategies for psychogenic non-epileptic seizures (PNES). Thus, we aimed to evaluate the effectiveness of continuous theta burst stimulation (cTBS) over supplementary motor area (SMA) in PNES using a randomized, sham-controlled design.Material and Methods: About 20 right-handed patients aged between 18 to 59 years were randomly allocated into active and sham groups to receive cTBS sessions (2 sessions /day, half an hour apart, 1200 pulses per day, at 80% MT) for 5 days in a week over SMA. PNES patients were evaluated on the psychogenic non-epileptic seizure scale (PNSS), dissociative experiences scale (DES-II), hospital anxiety depression scale (HADS), WHOQOL-BREF, and clinical global impression-severity (CGI-S) at baseline, after 10th rTMS session, and2-weeks post cTBS.Results: Our study fails to show a significant effect on between group* time interaction in the frequency of PNES attacks (F = 0.011; p = 0.998), total-PSS (F = 0.429; p = 0.654), DES-II (F = 1.865; p = 0.169), CGI-S (F = 0.239; p = 0.789)in an intention to treat protocol across 3 weeks. Minimal side effects were reported and no patient discontinued the trial citing side effects.Conclusion: We conclude that intensive SMA, cTBS in PNES is well tolerated with non-inferior clinical benefits when compared to placebo

Accelerated Continuous Theta Burst Stimulation in the Treatment of Trichotillomania: A Comprehensive Case Study From Acute Intervention to Maintenance Phase.

Accelerated Continuous Theta Burst Stimulation in the Treatment of Trichotillomania: A Comprehensive Case Study From Acute Intervention to Maintenance Phase.

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.

Parietal theta burst TMS does not modulate bistable perception.

The role of the parietal cortex in perceptual awareness and in resolving perceptual ambiguity is unsettled. Early influential transcranial magnetic stimulation studies have revealed differences in conscious perception following parietal stimulation, fuelling the notion that parietal cortex causally contributes to resolving perceptual ambiguity. However, central to this conclusion is the reliability of the method employed. Several prior studies have revealed opposing effects, such as shortening, lengthening, or no effect on multistable perceptual transitions following parietal stimulation. Here we addressed the reliability of continuous theta-burst stimulation (cTBS) on parietal cortex on the perception of bistable stimuli. We conducted three cTBS experiments that were matched to prior experiments in terms of stimuli, stimulation protocol, and target site, and used a higher number of participants. None of our cTBS experiments replicated prior cTBS results. The only experiment using individual functional localizers led to weak effects, while the two others led to null results. Individual variability of motor cortex cTBS did not predict parietal cTBS effects. In view of recent reports of highly variable cTBS effects over motor cortex, our results suggest that cTBS is particularly unreliable in modulating bistable perception when applied over parietal cortex.

Lack of effects of eight-week left dorsolateral prefrontal theta burst stimulation on white matter macro/microstructure and connection in autism.

Whether brain stimulation could modulate brain structure in autism remains unknown. This study explored the impact of continuous theta burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (DLPFC) on white matter macro/microstructure in intellectually able children and emerging adults with autism. Sixty autistic participants were randomized (30 active) and received active or sham cTBS for eight weeks twice per week, 16 total sessions using a double-blind (participant-, rater-, analyst-blinded) design. All participants received high-angular resolution diffusion MR imaging at baseline and week 8. Twenty-eight participants in the active group and twenty-seven in the sham group with good imaging quality entered the final analysis. With longitudinal fixel-based analysis and network-based statistics, we found no significant difference between the active and sham groups in changes of white matter macro/microstructure and connections following cTBS. In addition, we found no association between baseline white matter macro/microstructure and autistic symptom changes from baseline to week 8 in the active group. In conclusion, we did not find a significant impact of left DLPFC cTBS on white matter macro/microstructure and connections in children and emerging adults with autism. These findings need to be interpreted in the context that the current intellectually able cohort in a single university hospital site limits the generalizability. Future studies are required to investigate if higher stimulation intensities and/or doses, other personal factors, or rTMS parameters might confer significant brain structural changes visible on MRI in ASD.

Causal role of the frontal eye field in attention-induced ocular dominance plasticity.

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the 'dichoptic-backward-movie' adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.

Causal role of the frontal eye field in attention-induced ocular dominance plasticity

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the ‘dichoptic-backward-movie’ adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.