A systematic review of the efficacy of intermittent theta burst stimulation (iTBS) on cognitive enhancement

Intermittent theta-burst stimulation (iTBS) has been used to focally regulate excitability of neural cortex over the past decade – however there is little consensus on the generalizability of effects reported in individual studies. Many studies use small sample sizes (n < 30), and there is a considerable amount of methodological heterogeneity in application of the stimulation itself. This systematic meta-analysis aims to consolidate the extant literature and determine if up-regulatory theta-burst stimulation reliably enhances cognition through measurable behavior. Results show that iTBS – when compared to suitable control conditions — may enhance cognition when outlier studies are removed, and there is a significant amount of heterogeneity across studies. Significant contributors to between-study heterogeneity include location of stimulation and method of navigation to the stimulation site. Surprisingly, the type of cognitive domain investigated was not a significant contributor of heterogeneity. The findings of this meta-analysis demonstrate that standardization of iTBS is urgent and necessary to determine if neuroenhancement of particular cognitive faculties are reliable and robust, and measurable through observable behavior.

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Efficacy and tolerability of theta-burst stimulation for major depression: A systematic review and meta-analysis

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2020.110168 ◽

2021 ◽

Vol 106 ◽

pp. 110168

Author(s):

Hsuan-Te Chu ◽

Chih-Ming Cheng ◽

Chih-Sung Liang ◽

Wen-Han Chang ◽

Chi-Hung Juan ◽

...

Keyword(s):

Systematic Review ◽

Major Depression ◽

Meta Analysis ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Theta Burst

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Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis

BMJ ◽

10.1136/bmj.l1079 ◽

2019 ◽

pp. l1079 ◽

Cited By ~ 36

Author(s):

Julian Mutz ◽

Vijeinika Vipulananthan ◽

Ben Carter ◽

René Hurlemann ◽

Cynthia H Y Fu ◽

...

Keyword(s):

Brain Stimulation ◽

Meta Analysis ◽

High Dose ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Major Depressive ◽

Magnetic Seizure Therapy ◽

Major Depressive Episodes ◽

Depressive Episodes ◽

Theta Burst

AbstractObjectiveTo estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults.DesignSystematic review with pairwise and network meta-analysis.Data sourcesElectronic search of Embase, PubMed/Medline, and PsycINFO up to 8 May 2018, supplemented by manual searches of bibliographies of several reviews (published between 2009 and 2018) and included trials.Eligibility criteria for selecting studiesClinical trials with random allocation to electroconvulsive therapy (ECT), transcranial magnetic stimulation (repetitive (rTMS), accelerated, priming, deep, and synchronised), theta burst stimulation, magnetic seizure therapy, transcranial direct current stimulation (tDCS), or sham therapy.Main outcome measuresPrimary outcomes were response (efficacy) and all cause discontinuation (discontinuation of treatment for any reason) (acceptability), presented as odds ratios with 95% confidence intervals. Remission and continuous depression severity scores after treatment were also examined.Results113 trials (262 treatment arms) that randomised 6750 patients (mean age 47.9 years; 59% women) with major depressive disorder or bipolar depression met the inclusion criteria. The most studied treatment comparisons were high frequency left rTMS and tDCS versus sham therapy, whereas recent treatments remain understudied. The quality of the evidence was typically of low or unclear risk of bias (94 out of 113 trials, 83%) and the precision of summary estimates for treatment effect varied considerably. In network meta-analysis, 10 out of 18 treatment strategies were associated with higher response compared with sham therapy: bitemporal ECT (summary odds ratio 8.91, 95% confidence interval 2.57 to 30.91), high dose right unilateral ECT (7.27, 1.90 to 27.78), priming transcranial magnetic stimulation (6.02, 2.21 to 16.38), magnetic seizure therapy (5.55, 1.06 to 28.99), bilateral rTMS (4.92, 2.93 to 8.25), bilateral theta burst stimulation (4.44, 1.47 to 13.41), low frequency right rTMS (3.65, 2.13 to 6.24), intermittent theta burst stimulation (3.20, 1.45 to 7.08), high frequency left rTMS (3.17, 2.29 to 4.37), and tDCS (2.65, 1.55 to 4.55). Network meta-analytic estimates of active interventions contrasted with another active treatment indicated that bitemporal ECT and high dose right unilateral ECT were associated with increased response. All treatment strategies were at least as acceptable as sham therapy.ConclusionsThese findings provide evidence for the consideration of non-surgical brain stimulation techniques as alternative or add-on treatments for adults with major depressive episodes. These findings also highlight important research priorities in the specialty of brain stimulation, such as the need for further well designed randomised controlled trials comparing novel treatments, and sham controlled trials investigating magnetic seizure therapy.

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

Medicina ◽

10.3390/medicina57080743 ◽

2021 ◽

Vol 57 (8) ◽

pp. 743

Author(s):

Seok-Min Hong ◽

Sung-Kyun Kim ◽

Moo-Young Seo ◽

Suk-Yun Kang

Keyword(s):

Sample Size ◽

Therapeutic Effect ◽

Repetitive Transcranial Magnetic Stimulation ◽

Small Sample Size ◽

Small Sample ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Outcome Measurements ◽

Visual Analog Scales ◽

Theta Burst

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.

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Theta-Burst Stimulation for Cognitive Enhancement in Parkinson's Disease With Mild Cognitive Impairment: A Randomized, Double-Blind, Sham-Controlled Trial

Frontiers in Neurology ◽

10.3389/fneur.2020.584374 ◽

2020 ◽

Vol 11 ◽

Author(s):

Stefan Lang ◽

Liu Shi Gan ◽

Eun Jin Yoon ◽

Alexandru Hanganu ◽

Mekale Kibreab ◽

...

Keyword(s):

Executive Function ◽

Dorsolateral Prefrontal Cortex ◽

Controlled Trial ◽

Cognitive Domain ◽

Theta Burst Stimulation ◽

Burst Stimulation ◽

Double Blind ◽

Dorsolateral Prefrontal ◽

Z Scores ◽

Theta Burst

Background: Mild cognitive impairment is a common non-motor symptom of Parkinson's disease (PD-MCI) and has minimal treatment options.Objective: In this double-blind, randomized, sham-controlled trial, we assessed the effect of repeated sessions of intermittent theta-burst stimulation over the left dorsolateral prefrontal cortex on cognition and brain connectivity in subjects with PD-MCI.Methods: Forty-one subjects were randomized to receive real (n = 21) or sham stimulation (n = 20). All subjects underwent neuropsychological assessments before, 1 day, and 1 month after stimulation. Subjects also underwent resting-state functional magnetic resonance imaging before and 48 h after stimulation. The primary outcome was the change in the cognitive domain (executive function, attention, memory, language, and visuospatial abilities) z-scores across time.Results: There was an insignificant effect on cognitive domain z-scores across time when comparing real with sham stimulation and correcting for multiple comparisons across cognitive domains (p > 0.05 Bonferroni correction). However, the real stimulation group demonstrated a trend toward improved executive functioning scores at the 1-month follow-up compared with sham (p < 0.05 uncorrected). After real stimulation, the connectivity of the stimulation site showed decreased connectivity to the left caudate head. There was no change in connectivity within or between the stimulation network (a network of cortical regions connected to the stimulation site) and the striatal network. However, higher baseline connectivity between the stimulation network and the striatal network was associated with improved executive function scores at 1 month.Conclusions: These results suggest that intermittent theta-burst stimulation over the dorsolateral prefrontal cortex in subjects with PD-MCI has minimal effect on cognition compared with sham, although there were trends toward improved executive function. This intervention may be more effective in subjects with higher baseline connectivity between the stimulation network and the striatal network. This trial supports further investigation focusing on executive function and incorporating connectivity-based targeting.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03243214.

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