Sham Continuous Theta Burst Stimulation Research Articles

Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation (SHIFT): a preregistered randomized controlled trial

AbstractHypnotizability, one’s ability to experience cognitive, emotional, behavioral and physical changes in response to suggestions in the context of hypnosis, is a stable neurobehavioral trait associated with improved treatment outcomes from hypnosis-based therapy. Increasing hypnotizability in people who are low-to-medium hypnotizable individuals could improve both the efficacy and effectiveness of therapeutic hypnosis as a clinical intervention. Hypnotizability is associated with dorsolateral prefrontal cortex (DLPFC) functions and connectivity with the salience network, yet there is conflicting evidence as to whether unilateral inhibition of the DLPFC changes hypnotizability. We hypothesized that using personalized neuroimaging-guided targeting to non-invasively stimulate the left DLPFC with transcranial magnetic stimulation (TMS) would temporarily increase hypnotizability. In a preregistered, double-blinded, randomized controlled trial, we recruited a sample of 80 patients with fibromyalgia syndrome, a functional pain disorder for which hypnosis has been a demonstrated beneficial non-pharmacological treatment option. All participants were TMS-naive. Participants were randomly assigned to active or sham continuous theta-burst stimulation over a personalized neuroimaging-derived left-DLPFC target, a technique termed SHIFT (Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation). We tested our hypothesis using the hypnotic induction profile scores, a standardized measure of hypnotizability. Pre-to-post SHIFT change in the hypnotic induction profile scores was significantly greater in the active versus sham group after 92 s of stimulation (P = 0.046). Only the active SHIFT group showed a significant increase in hypnotizability following stimulation (active: P < 0.001; sham: P = 0.607). As such, modulation of trait hypnotizability is possible in humans using non-invasive neuromodulation. Our findings support a relationship between the inhibition of the left DLPFC and an increase in hypnotizability. Dose–response optimization of spaced SHIFT should be explored to understand the optimal dose–response relationship. ClinicalTrials.gov registration: NCT02969707.

Continuous Theta-Burst Stimulation of the Contralesional Primary Motor Cortex for Promotion of Upper Limb Recovery After Stroke: A Randomized Controlled Trial.

Despite improvements in acute stroke therapies and rehabilitation strategies, many stroke patients are left with long-term upper limb motor impairment. We assessed whether an inhibitory repetitive transcranial magnetic stimulation treatment paradigm started within 3 weeks after stroke onset promotes upper limb motor recovery. We performed a single-center randomized, sham-controlled clinical trial. Patients with ischemic stroke or intracerebral hemorrhage and unilateral upper limb motor impairment were randomized to 10 daily sessions of active or sham continuous theta-burst stimulation (cTBS) of the contralesional primary motor cortex combined with standard upper limb therapy, started within 3 weeks after stroke onset. The primary outcome was the change in the Action Research Arm Test score from baseline (pretreatment) at 3 months after stroke. Secondary outcomes included the score on the modified Rankin Scale at 3 months and the length of stay at the rehabilitation center. Statistical analyses were performed using mixed models for repeated measures. We enrolled 60 patients between April 2017 and February 2021, of whom 29 were randomized to active cTBS and 31 to sham cTBS. One patient randomized to active cTBS withdrew consent before the intervention and was excluded from the analyses. The mean difference in the change in Action Research Arm Test score from baseline at 3 months poststroke was 9.6 points ([95% CI, 1.2-17.9]; P=0.0244) in favor of active cTBS. Active cTBS was associated with better scores on the modified Rankin Scale at 3 months (OR, 0.2 [95% CI, 0.1-0.8]; P=0.0225) and with an 18 days shorter length of stay at the rehabilitation center than sham cTBS ([95% CI, 0.0-36.4]; P=0.0494). There were no serious adverse events. Ten daily sessions of cTBS of the contralesional primary motor cortex combined with upper limb training, started within 3 weeks after stroke onset, promote recovery of the upper limb, reduce disability and dependence and leads to earlier discharge from the rehabilitation center. URL: https://trialsearch.who.int/; Unique identifier: NTR6133.

Continuous theta burst stimulation dilates meningeal lymphatic vessels by up-regulating VEGF-C in meninges

BackgroundLymphatic vessels (LVs) of meninges and lymphatic drainage in the brain have been investigated previously. Here, we examined the role of continuous theta burst stimulation (CTBS) in the modulation of meningeal LVs. MethodsTo explore the effects of CTBS on meningeal LVs, the diameters of LVs were measured between a real CTBS group and sham CTBS group of wild-type male mice. Vascular endothelial growth factor-C (VEGF-C) expression was subsequently calculated in both groups to account for lymphatic changes after CTBS. Sunitinib was administered by 3-day oral gavage to inhibit the VEGF receptor (VEGFR), and the effects of CTBS were further examined in the following groups: vehicle with real CTBS, vehicle with sham CTBS, sunitinib treatment with real CTBS, and sunitinib treatment with sham CTBS. ResultsThe lymphatic vessels were augmented, and the level of VEGF-C in meninges increased after CTBS. CTBS dilated meningeal lymphatic vessels were impaired after the VEGF-C/VEGFR3 pathway was blocked. ConclusionsCTBS can dilate meningeal lymphatic vessels by up-regulating VEGF-C in meninges.

Predicting Long-Term After-Effects of Theta-Burst Stimulation on Supplementary Motor Network Through One-Session Response.

To understand the neural mechanism of repetitive transcranial magnetic stimulation (rTMS), the after-effects following one session or multiple days of stimulation have been widely investigated. However, the relation between the short-term effect (STE) and long-term effect (LTE) of rTMS is largely unknown. This study aims to explore whether the after-effects of 5-day rTMS on supplementary motor area (SMA) network could be predicted by one-session response. A primary cohort of 38 healthy participants underwent five daily sessions of real or sham continuous theta-burst stimulation (cTBS) on the left SMA. Resting-state functional magnetic resonance imaging (fMRI) data were acquired at the first (before and after the first stimulation) and sixth experimental day. The SMA connectivity changes after the first cTBS and after 5 days of stimulation were defined as STE and LTE, respectively. Compared to the baseline, significant STE and LTE were found in the bilateral paracentral gyrus (ParaCG) after real stimulation, suggesting shared neural correlates of short- and long-term stimulations. Region-of-interest analysis indicated that the resting-state functional connectivity between SMA and ParaCG increased after real stimulation, while no significant change was found after sham stimulation. Leave-one-out cross-validation indicated that the LTE in ParaCG could be predicted by the STE after real but not sham stimulations. In an independent cohort, the after-effects of rTMS on ParaCG and short- to long-term prediction were reproduced at the region-of-interest level. These imaging evidences indicate that one-session rTMS can aid to predict the regions responsive to long-term stimulation and the individualized response degree.

The neurocognitive mechanisms underlying food cravings and snack food consumption. A combined continuous theta burst stimulation (cTBS) and EEG study

Regulation of food cravings is thought to be critical for modulating eating behavior, yet we do not fully understand the mechanisms by which cognitive control operates in the eating context. The current study combined rTMS and EEG paradigms to examine the causal role of the left dorsolateral prefrontal cortex (dlPFC) in modulating visceral and behavioral responses to high calorie foods, and the mediational mechanisms underlying this relation. 28 right-handed female participants received both active and sham continuous theta burst stimulation (cTBS; a rTMS variant used to decrease cortical activity) targeting the left dlPFC in a counterbalanced order. Prior to and following each stimulation session participants completed a flanker and food-cue presentation (high and low calorie food) task. Following cTBS participants had the opportunity to consume both high and low calorie foods during a taste test. Findings revealed a reliable effect of cTBS on food consumption, such that participants selectively ingested significantly more calories from appetitive calorie dense snack foods following active relative to sham cTBS; this effect did not translate to control (low calorie) food consumption. In addition, attenuation of dlPFC activity resulted in the significant increase in N2 amplitude and P3b latency to incongruent flanker trials, and the selective significant increase in the P3a amplitude to and P3a amplitude bias for high calorie food stimuli. Results from the parallel mediation analysis revealed that only the indirect effect of flanker task performance was significant; the indirect effects of stimulation induced changes in the P3 bias for high calorie foods, the urge to consume high calorie foods, and the general liking ratings for high calorie foods were not significant. These findings confirm the causal role of the left dlPFC in the modulation of calorie dense food consumption via inhibitory control capacity.

Effects of left dlPFC modulation on social cognitive processes following food sampling

BackgroundThe dorsolateral prefrontal cortex (dlPFC) plays a central role in the inhibition of eating, but also the modulation of conscious thought processes that might precede, accompany or follow initial food tasting. The latter might be particularly important to the extent that post-tasting cognitions may drive prolonged eating beyond the satiety point. However, we know very little about the effect of the dlPFC on conation following initial food sampling. This investigation compared the effects of dlPFC attenuation using repetitive transcranial magnetic stimulation (rTMS) on social cognition following (Study 1) and prior to (Study 2) a food consumption opportunity. MethodsIn Study 1, participants (N = 21; Mage = 21 years) were randomized to active or sham continuous theta-burst stimulation (cTBS; an inhibitory variant of rTMS) targeting the left dlPFC followed by an interference task. Participants subsequently completed measures of attitudes, norms and perceived control following a mock taste test. In Study 2, a second sample of right handed participants (N = 37; Mage = 21 years) were assigned to active or sham cTBS, followed by an interference task and two measures of attitudes (implicit and explicit), both assessed prior to the same taste test paradigm. ResultsIn Study 1, findings revealed a reliable effect of cTBS on post-tasting attitudes (t(1,19) = 3.055, p = .007; d = 1.34), such that attitudes towards calorie dense snack foods were significantly more positive following active stimulation than following sham stimulation. Similar effects were found for social norms (t(1,19) = 3.024, p = .007, d = 1.31) and perceived control (t(1,20) = 19.247, p < .001, d = 0.50). In Study 2, no effects of cTBS were observed on pre-consumption attitudes, despite reliable effects on interference scores and subsequent consumption. ConclusionsThe left dlPFC may selectively modulate facilitative social cognition following initial food sampling (but not pre-consumption).

P 191. Modulation of the functional connectivity between the cerebellum and the cortico-striatal loops

Question Artificial modulation of the cerebellar output with repetitive transcranial magnetic stimulation could directly influence the plastic response of the motor cortex that depends on the peripheral input ( Popa et al., 2012 ). Here we investigate the change of the resting-state functional connectivity between the cerebellum, the basal ganglia, the thalamus, and the cortical motor areas before and after the inhibitory rTMS or sham stimulation of the right cerebellar hemisphere. Methods The resting state fMRI of seventeen right-handed healthy subjects (age 26.6 ± 9 years, range: 18–53) was acquired twice at three time points around two types of intervention. The intervention types were either real or sham continuous theta-burst stimulation (cTBS; Huang et al., 2005 ) of the right cerebellar hemisphere, delivered in two different days. The scanning time-points for each day were: baseline, before the intervention, and at 10 min and 60 min after the end of the intervention. The stimulation was aimed at the VIII lobule of the right cerebellar hemisphere ( Popa et al., 2010 ) and delivered at 90% of the active motor threshold. The MRI data was preprocessed with SPM5 ( SPM5, xxxx ) and time series of the signal in selected regions of interest were extracted. The regions of interest were selected in FSLview ( FSLview, xxxx ) as 4 mm-radius spheres around specific coordinates previously defined for circuits involved in motor-skill learning, which are both distinct and connected ( Doyon et al., 2009 ): the cerebello-thalamo-cortical (CTC) loop and the striatio-thalamo-cortical (STC) loop. The integration within a circuit was defined as Ix = −1/2 ln∣Rx∣ and between circuits as Ix/y = 1/2 ln(∣Rx∣. ∣Ry∣/∣Rxy∣), where Rx is the correlation matrix of network X and ∣·∣ stands for the determinant function ( Merrelec et al., 2008 ). The integration was computed for each subject, each stimulation type, each time-point, and every combination of regions/circuits. Results We have found that despite the lack of effect on the integration of the whole motor network, there were significant changes within and between sub-networks: an increase in integration from baseline to10 min after the intervention between the left cortico-cerebellar and the left and right cortico-striatal loops, as well as within the cerebello-thalamo-striatal loops bilaterally. All parameters returned to baseline levels at 60 min after the intervention. Conclusions This demonstrates that inhibitory cerebellar stimulation is actively influencing the connectivity within the motor loops, involving both cortical and subcortical structures. It suggests that the stimulation of one area can potentially change the flow of information throughout the brain, and that the inhibition of cerebellar cortex in particular can enhance the strength of the communication between the cortical motor areas and the basal ganglia.

Modulation of the Disturbed Motor Network in Dystonia by Multisession Suppression of Premotor Cortex

Daily sessions of therapeutic transcranial brain stimulation are thought to prolong or amplify the effect of a single intervention. Here we show in patients with focal hand dystonia that additional, new effects build up progressively over time, making it difficult to predict the effect of long term interventions from shorter treatment sessions. In a sham-controlled study, real or sham continuous theta burst stimulation (cTBS) was given once daily for five consecutive days to dorsolateral premotor cortex (PMd). Five days of real, but not sham, premotor cTBS improved intracortical inhibition in primary motor cortex (M1) to a similar extent on day 1 and day 5. However 5 days of cTBS were required to restore the abnormal PMd-M1 interactions observed on day 1. Similarly, excessive M1 plasticity seen at baseline was also significantly reduced by five days of real premotor cTBS. There was only a marginal benefit on writing. The results show that additional, new effects, at sites distant from the point of stimulation, build up progressively over time, making it difficult to predict the effect of long term interventions from shorter treatment sessions. The results indicate that it may take many days of therapeutic intervention to rebalance activity in a complex network.

Theta burst stimulation over the primary motor cortex does not induce cortical plasticity in Parkinson’s disease

The purpose of this study was to investigate whether a period of continuous theta burst stimulation (cTBS) induces cortical plasticity and thus improves bradykinesia of the upper limb in Parkinson's disease. In eight patients with Parkinson's disease (two females; mean age: 68.5 ± 5 years; disease duration: 4 ± 3 years) electrophysiological (motor evoked potentials, contralateral and ipsilateral silent period) and behavioural (Purdue pegboard test, UPDRS motor subscore) parameters were evaluated before (baseline condition) and after a 40-s period of (1) real or (2) sham continuous theta burst stimulation over the primary motor cortex contralateral to the more affected body side off dopaminergic drugs. Compared to baseline, cTBS did change neither measures of cortical excitability nor behavioural measures. cTBS over the primary motor cortex does not impact on cortical excitability or motor function of the upper limb in Parkinson's disease. We interpret these data to reflect impaired cortical plasticity in Parkinson's disease. This study is an important contribution to the knowledge about impaired plasticity in Parkinson's disease.