Sessions Of Theta Burst Stimulation Research Articles

Cerebellar transcranial magnetic stimulation in psychotic disorders: intermittent, continuous, and sham theta-burst stimulation on time perception and symptom severity.

The cerebellum contributes to the precise timing of non-motor and motor functions, and cerebellum abnormalities have been implicated in psychosis pathophysiology. In this study, we explored the effects of cerebellar theta burst stimulation (TBS), an efficient transcranial magnetic stimulation protocol, on temporal discrimination and self-reported mood and psychotic symptoms. We conducted a case-crossover study in which patients with psychosis (schizophrenias, schizoaffective disorders, or bipolar disorders with psychotic features) were assigned to three sessions of TBS to the cerebellar vermis: one session each of intermittent (iTBS), continuous (cTBS), and sham TBS. Of 28 enrolled patients, 26 underwent at least one TBS session, and 20 completed all three. Before and immediately following TBS, participants rated their mood and psychotic symptoms and performed a time interval discrimination task (IDT). We hypothesized that cerebellar iTBS and cTBS would modulate these measures in opposing directions, with iTBS being adaptive and cTBS maladaptive. Reaction time (RT) in the IDT decreased significantly after iTBS vs. Sham (LS-mean difference = -73.3, p = 0.0001, Cohen's d = 1.62), after iTBS vs. cTBS (LS-mean difference = -137.6, p < 0.0001, d = 2.03), and after Sham vs. cTBS (LS-mean difference = -64.4, p < 0.0001, d = 1.33). We found no effect on IDT accuracy. We did not observe any effects on symptom severity after correcting for multiple comparisons. We observed a frequency-dependent dissociation between the effects of iTBS vs. cTBS to the cerebellar midline on the reaction time of interval discrimination in patients with psychosis. iTBS showed improved (adaptive) while cTBS led to worsening (maladaptive) speed of response. These results demonstrate behavioral target engagement in a cognitive dimension of relevance to patients with psychosis and generate testable hypotheses about the potential therapeutic role of cerebellar iTBS in this clinical population. clinicaltrials.gov, identifier NCT02642029.

The use of theta burst stimulation in patients with schizophrenia - A systematic review.

Transcranial magnetic stimulation (TMS) can offer therapeutic benefits and provide value in neurophysiological research. One of the newer TMS paradigms is theta burst stimulation (TBS) which can be delivered in two patterns: continuous (cTBS - inducing LTD-like effects) and intermittent (iTBS - inducing LTP-like effects). This review paper aims to explore studies that have utilized TBS protocols over different areas of the cortex to study the neurophysiological functions and treatment of patients with schizophrenia. PubMed was searched using the following keywords "schizophrenia", "schizoaffective", or "psychosis", and "theta burst stimulation". Out of the 90 articles which were found, thirty met review inclusion criteria. The inclusion criteria included studying the reported effect (clinical, physiological, or both) of at least one session of TBS on human subjects, and abstracts (at minimum) must have been in English. The main target areas included prefrontal cortex (12 studies - 10 dorsolateral prefrontal cortex (DLPFC), 2 dorsomedial prefrontal cortex (DMPFC)) vermal cerebellum (5), and temporo-parietal cortex (8). Other target areas included inferior parietal lobe (2), and motor cortex (3). TBS neurophysiological effect was explored in 5 studies using functional magnetic resonance image (fMRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), electromyography (EMG) and positron emission topography (PET) scan. Overall, TBS can offer great therapeutic potential as it is well-tolerated, feasible, and has few, if any, adverse effects. TBS may be targeted to treat specific symptomatology, as an augmenting intervention to pharmacotherapy, or even improving patient's insight into their diagnosis.

Theta-burst stimulation as a therapeutic tool in neurological pathology: a systematic review.

TBS (theta-burst stimulation) is a novel therapeutic approach in a wide range of neurological diseases. The present systematic review aims to identify the various protocols used in the last years, to assess study quality and to offer a general overview of the current state of the literature. The systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-Analyses (PRISMA) guidelines. We applied the following inclusion criteria: (1) population over 18 years old with diagnosed neurological disorders, (2) patients treated with sessions of theta-burst stimulation, (3) randomized-controlled clinical trials, (4) articles in the English language, and (5) studies that report response and score reduction on a validated scale of the investigated disorder or remission rates. We included in the final analysis 56 randomized controlled trials focusing on different neurological pathologies (stroke, Parkinson`s disease, multiple sclerosis, tinnitus, dystonia, chronic pain, essential tremor and tic disorder), and we extracted data regarding study design, groups and comparators, sample sizes, type of coil, stimulation parameters (frequency, number of pulses, intensity, stimulation site etc.), number of sessions, follow-up, assessment through functional connectivity and neurological scales used. We observed a great interstudy heterogenicity that leads to a difficulty in drawing plain conclusions. TBS protocols have shown promising results in improving various symptoms in patients with neurological disorders, but larger and more coherent studies, using similar stimulation protocols and evaluation scales, are needed to establish guideline recommendations.

Connectivity-Guided Theta Burst Transcranial Magnetic Stimulation Versus Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Moderate to Severe Depression: Magnetic Resonance Imaging Protocol and SARS-CoV-2–Induced Changes for a Randomized Double-blind Controlled Trial

BackgroundDepression is a substantial health and economic burden. In approximately one-third of patients, depression is resistant to first-line treatment; therefore, it is essential to find alternative treatments. Transcranial magnetic stimulation (TMS) is a neuromodulatory treatment involving the application of magnetic pulses to the brain that is approved in the United Kingdom and the United States in treatment-resistant depression. This trial aims to compare the clinical effectiveness, cost-effectiveness, and mechanism of action of standard treatment repetitive TMS (rTMS) targeted at the F3 electroencephalogram site with a newer treatment—a type of TMS called theta burst stimulation (TBS) targeted based on measures of functional brain connectivity. This protocol outlines brain imaging acquisition and analysis for the Brain Imaging Guided Transcranial Magnetic Stimulation in Depression (BRIGhTMIND) study trial that is used to create personalized TMS targets and answer the proposed mechanistic hypotheses.ObjectiveThe aims of the imaging arm of the BRIGhTMIND study are to identify functional and neurochemical brain signatures indexing the treatment mechanisms of rTMS and connectivity-guided intermittent theta burst TMS and to identify imaging-based markers predicting response to treatment.MethodsThe study is a randomized double-blind controlled trial with 1:1 allocation to either 20 sessions of TBS or standard rTMS. Multimodal magnetic resonance imaging (MRI) is acquired for each participant at baseline (before TMS treatment) with T1-weighted and task-free functional MRI during rest used to estimate TMS targets. For participants enrolled in the mechanistic substudy, additional diffusion-weighted sequences are acquired at baseline and at posttreatment follow-up 16 weeks after treatment randomization. Core data sets of T1-weighted and task-free functional MRI during rest are acquired for all participants and are used to estimate TMS targets. Additional sequences of arterial spin labeling, magnetic resonance spectroscopy, and diffusion-weighted images are acquired depending on the recruitment site for mechanistic evaluation. Standard rTMS treatment is targeted at the F3 electrode site over the left dorsolateral prefrontal cortex, whereas TBS treatment is guided using the coordinate of peak effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. Both treatment targets benefit from the level of MRI guidance, but only TBS is provided with precision targeting based on functional brain connectivity.ResultsRecruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023.ConclusionsThis trial will determine the impact of precision MRI guidance on rTMS treatment and assess the neural mechanisms underlying this treatment in treatment-resistant depressed patients.Trial RegistrationISRCTN Registry ISRCTN19674644; https://www.isrctn.com/ISRCTN19674644International Registered Report Identifier (IRRID)DERR1-10.2196/31925

Continuous and intermittent theta burst stimulation to the visual cortex do not alter GABA and glutamate concentrations measured by magnetic resonance spectroscopy.

BackgroundTheta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), uses repeated high‐frequency bursts to non‐invasively modulate neural processes in the brain. An intermittent TBS (iTBS) protocol is generally considered “excitatory,” while continuous TBS (cTBS) is considered “inhibitory.” However, the majority of work that has led to these effects being associated with the respective protocols has been done in the motor cortex, and it is well established that TMS can have variable effects across the brain.Objectives and methodWe investigated the effects of iTBS and cTBS to the primary visual cortex (V1) on composite levels of gamma‐aminobutyric acid + co‐edited macromolecules (GABA+) and glutamate + glutamine (Glx) since these are key inhibitory and excitatory neurotransmitters, respectively. Participants received a single session of cTBS, iTBS, or sham TBS to V1. GABA+ and Glx were quantified in vivo at the stimulation site using spectral‐edited proton magnetic resonance spectroscopy (1H‐MRS) at 3T. Baseline pre‐TBS GABA+ and Glx levels were compared to immediate post‐TBS and 1 h post‐TBS levels.ResultsThere were no significant changes in GABA+ or Glx following either of the TBS conditions. Visual cortical excitability, measured using phosphene thresholds, remained unchanged following both cTBS and iTBS conditions. There was no relationship between excitability thresholds and GABA+ or Glx levels. However, TBS did alter the relationship between GABA+ and Glx for up to 1 h following stimulation.ConclusionsThese findings demonstrate that a single session of TBS to the visual cortex can be used without significant effects on the tonic levels of these key neurotransmitters; and add to our understanding that TBS has differential effects at visual, motor, and frontal cortices.

Investigating the effects of Theta Burst Stimulation (TBS) on experimentally-induced hamstring pain

Background: Maximising recovery and facilitating return to sport following a hamstring injury are key considerations for athletes and rehabilitation providers. Interventions that can accelerate pain resolution following a hamstring injury may allow earlier exposure to hamstring rehabilitation and accelerate return to sport. Recently, non-invasive stimulation of the primary motor cortex (M1) has been shown to expedite recovery following acute musculoskeletal pain. However, previous research has involved prolonged stimulation sessions that require multiple days of treatment, which may not be feasible for many athletes. Theta burst stimulation (TBS) is a novel paradigm that has been shown to produce comparable effects to other brain stimulation modalities in a fraction of the time. Accordingly, this study aimed to investigate the effect of theta burst stimulation (TBS) on the recovery of pain severity and sensitivity following experimentally-induced hamstring pain. Methods: Twenty pain-free people participated in this randomised controlled trial. All participants attended two sessions (Day 0 and 2). On Day 0, participants performed an eccentric exercise protocol (resisted unilateral knee flexion, 10 x 10 repetitions) to induce delayed onset muscle soreness. On Day 2, participants received 4 blocks of either active or sham TBS (approximately 3 minutes each) over M1 contralateral to the painful leg. Pain severity (visual analogue scale) and sensitivity (pressure pain thresholds [PPTs]) over the painful site were assessed before and after the TBS intervention. Pain severity was assessed during functional tasks including walking up and down stairs, forward bending with extended knees, and removing shoes using the contralateral foot. Results: The eccentric protocol induced comparable pain in both groups across all functional tasks (mean pain intensity of 4.5 for both groups when walking upstairs).There was a significant increase in PPTs amongst the active TBS group when compared to sham (p = 0.03). No differences were observed between groups following TBS in pain severity during any of the functional tasks (p > 0.05 for all). Discussion: A single session of TBS reduced pain sensitivity (an increase in PPTs) associated with experimentally-induced hamstring pain but did not reduce pain severity during functional tasks. This treatment may assist in expediting the resolution of peripheral sensitisation observed following an acute hamstring injury, an effect that could translate to earlier engagement with rehabilitation. Further exploration of the effects of TBS on acute clinical hamstring injury, and whether improvements in pain sensitivity translate into shorter recovery time, is warranted. Conflict of interest statement: My co-authors and I acknowledge that we have no conflict of interest of relevance to the submission of this abstract.

Theta-Burst Stimulation Is Able to Impact Cognitive Processing: A P300 and Neuropsychological Test Study

Introduction: Theta-burst stimulation (TBS) is a safe non-invasive neurostimulation technique used to improve cognitive and neuropsychiatric impairments. Combined outcome evaluation using event-related potentials (ERPs) and neuropsychological tests may allow a more thorough assessment of TBS treatment efficacy; however, some mixed results have been found, and their use remains scarce. Our main objective was to evaluate whether a session of TBS to the left dorsolateral prefrontal cortex (DLPFC) can impact upon the performance of both neuropsychological and neurophysiological tests. Methods: This double-blind sham-controlled study involved 28 healthy adults, between 18 and 30 years. Volunteers were randomly allocated to receive excitatory (intermittent [iTBS]), inhibitory (continuous TBS [cTBS]) or sham stimulation on the left DLPFC. Subjects were evaluated using ERPs (auditory oddball paradigm P300) and neuropsychological tests (Trail making test [TMT] and Stroop test of words and colours [STWC]), using a pre-post stimulation protocol. Results: Inhibitory stimulation led to significantly delayed P300 peak latencies (p < 0.001), with no consistent change in N2P3 amplitudes. cTBS also significantly influenced the expected group performance in Stroop C and Stroop interference (p = 0.025) compared to the iTBS and sham groups. No significant results were found in TMT tests after TBS. Conclusion: Our results suggest that P300 and specific Stroop colour and words test parameters can be similarly influenced by the same TBS protocol. This emphasizes the importance of mixed evaluation using neuropsychological and neurophysiological resources in research associated with the use of transcranial magnetic stimulation and cognition.

Impaired motor cortical plasticity associated with cannabis use disorder in young adults.

Maladaptive cortical plasticity has been described in individuals with heroin and methamphetamine addiction and may mediate other substance abuse disorders. It is unknown whether cannabis dependence in humans alters the capacity for induction of cortical plasticity. The aim of this study was to non-invasively investigate cortical plasticity with transcranial magnetic stimulation in young adults who meet DSM-5 criteria for cannabis use disorder (CUD). Thirty men (ages 20- 30) who used cannabis daily over the previous 6 months (15 diagnosed of CUD) and 15 demographically matched non-users were enrolled in this study. All participants underwent two sessions of theta burst stimulation (TBS) in which either continuous TBS (cTBS; 600 pulses, 80% active motor threshold) or intermittent TBS (iTBS; 2-s train of cTBS repeated every 10 s for a total of 190 s, 600 pulses) was applied over the primary motor cortex. The effects of these protocols were assessed by analysing the contralateral motor evoked potentials (MEPs). The relationships between cortical plasticity and problematic cannabis use, degree of dependence, and nicotine addiction were also investigated. Significant MEP inhibition after cTBS was observed in both cannabis users without CUD and non-users, while this inhibition was not seen in cannabis users with CUD. Strikingly, less motor cortical plasticity was observed in subjects with severe problematic cannabis use. No significant differences between users and non-users were found in the iTBS-induced cortical plasticity measures. Our study provides the first evidence of maladaptive cortical plasticity associated with cannabis use disorder and problematic cannabis use in humans.

Feasibility and clinical effects of theta burst stimulation in youth with major depressive disorders: An open-label trial

BackgroundConventional treatments for youth depression, such as antidepressants, have modest efficacy, side effects, and ongoing controversies regarding safety. Repetitive transcranial magnetic stimulation (rTMS), specifically theta burst stimulation (TBS), applied to the dorsolateral prefrontal cortex (DLPFC) has demonstrated efficacy for the treatment of depression in adults. However, the feasibility and clinical response to TBS for youth depression has yet to be explored. MethodsTwenty participants between the ages of 16 to 24 years old with MDD were recruited. The intervention consisted of 10 treatment sessions over the course of two weeks, in which participants received intermittent TBS and continuous TBS stimulation to the left and right DLPFC, respectively. Change in the Hamilton Rating Scale for Depression (HRSD-17) score was the primary outcome. Clinical assessments occurred at baseline, after the fifth treatment session, and within a week after treatment completion. ResultsOf the twenty participants, eighteen received all TBS sessions, and seventeen completed all clinical assessments. There was a significant reduction in depressive symptoms following treatment completion (p < 0.001). Four of the twenty patients had more than 50% reduction in their depressive symptoms, two of whom achieved remission. All participants received and tolerated at least six daily TBS treatments with no major adverse events. LimitationsStudy was an uncontrolled, open-label design. ConclusionTen sessions of TBS was feasible, well tolerated, and appeared to have clinical effects for the treatment of depressed youth. Future sham-controlled randomized trials are warranted to validate these findings in a larger cohort of youth depression.

Cumulative effect of 5 daily sessions of theta burst stimulation on corticospinal excitability in amyotrophic lateral sclerosis

Excitotoxicity plays an important role in the pathogenesis of the preferential motor neuron death observed in amyotrophic lateral sclerosis (ALS). Continuous theta burst stimulation (cTBS) by transcranial magnetic stimulation has an inhibitory effect on corticospinal excitability (CSE). We characterized the neurophysiological changes induced by cTBS in ALS. The patients received 5 daily sessions of cTBS. CSE was assessed at baseline and after each session of cTBS. The amplitude of a single pulse motor evoked potential was significantly decreased (34%) over the days. The amplitude returned to baseline a week after the last session. The resting motor threshold increased significantly, whereas intracortical inhibition and facilitation did not change over the sessions. Daily cTBS has a cumulative depressing effect on CSE in patients with ALS. These results suggest that modulation of CSE in ALS is possible, but repetitive sessions are needed to maintain the effect.

Safety and tolerability of theta‐burst transcranial magnetic stimulation in children

Theta-burst stimulation (TBS) is a lower intensity, high-frequency repetitive transcranial magnetic stimulation technique developed recently for quantifying and modulating cerebral cortical function. Nearly all published studies have involved adults. The aim of this study was to obtain safety data as a basis for evaluating potential risks versus benefits of TBS research in children. Forty participants under 18 years: 16 with Tourette syndrome (five females, 11 males; mean age 12y, SD 2y 10mo) and 24 typically developing children (12 females, 12 males; mean age 12y 11mo, SD 2y 10mo) underwent intermittent or continuous TBS over the left motor cortex. Open questions, a structured 16-question review of systems, and visual analog mood scale (VAMS) were administered before and after TBS. A Wilcoxon signed-rank sum test was used to analyze differences in VAMS scores before and after TBS. There were no serious adverse events. Five of the 40 children reported mild, self-limited adverse events: a subjective sensation of finger twitching (n=1), neck stiffness (n=1), and mild headache (n=3). The total adverse event rate was 11.6%. There was no significant change in VAMS score in either group after one session of TBS. A single session of TBS in children appears to be safe and well tolerated.