Neural effects of continuous theta-burst stimulation in macaque parietal neurons.
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SUBMITTER: Romero MC
PROVIDER: S-EPMC9470151 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
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Neural effects of continuous theta-burst stimulation in macaque parietal neurons.
Romero Maria C MC Merken Lara L Janssen Peter P Davare Marco M
eLife 20220913
Theta-burst transcranial magnetic stimulation (TBS) has become a standard non-invasive technique to induce offline changes in cortical excitability in human volunteers. Yet, TBS suffers from a high variability across subjects. A better knowledge about how TBS affects neural activity in vivo could uncover its mechanisms of action and ultimately allow its mainstream use in basic science and clinical applications. To address this issue, we applied continuous TBS (cTBS, 300 pulses) in awake behaving ...[more]
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Project description:ObjectivesThe utility of continuous theta-burst stimulation (cTBS) as index of cortical plasticity is limited by inadequate characterization of its test-retest reliability. We thus evaluated the reliability of cTBS aftereffects, and explored the roles of age and common single-nucleotide polymorphisms in the brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) genes.MethodsTwenty-eight healthy adults (age range 21-65) underwent two identical cTBS sessions (median interval = 9.5 days) targeting the motor cortex. Intraclass correlation coefficients (ICCs) of the log-transformed, baseline-corrected amplitude of motor evoked potentials (ΔMEP) at 5-60 min post-cTBS (T5-T60) were calculated. Adjusted effect sizes for cTBS aftereffects were then calculated by taking into account the reliability of each cTBS measure.ResultsΔMEP at T50 was the most-reliable cTBS measure in the whole sample (ICC = 0.53). Area under-the-curve (AUC) of ΔMEPs was most reliable when calculated over the full 60 min post-cTBS (ICC = 0.40). cTBS measures were substantially more reliable in younger participants (< 35 years) and in those with BDNF Val66Val and APOE ε4- genotypes.ConclusioncTBS aftereffects are most reliable when assessed 50 min post-cTBS, or when cumulative ΔMEP measures are calculated over 30-60 min post-cTBS. Reliability of cTBS aftereffects is influenced by age, and BDNF and APOE polymorphisms. Reliability coefficients are used to adjust effect-size calculations for interpretation and planning of cTBS studies.
| S-EPMC6533847 | biostudies-literature
Project description:Non-invasive brain stimulation is a useful tool to probe brain function and provide therapeutic treatments in disease. When applied to the right posterior parietal cortex (PPC) of healthy participants, it is possible to temporarily shift spatial attention and mimic symptoms of spatial neglect. However, the field of brain stimulation is plagued by issues of high response variability. The aim of this study was to investigate baseline functional connectivity as a predictor of response to an inhibitory brain stimulation paradigm applied to the right PPC. In fourteen healthy adults (9 female, aged 24.8 ± 4.0 years) we applied continuous theta burst stimulation (cTBS) to suppress activity in the right PPC. Resting state functional connectivity was quantified by recording electroencephalography and assessing phase consistency. Spatial attention was assessed before and after cTBS with the Landmark Task. Finally, known determinants of response to brain stimulation were controlled for to enable robust investigation of the influence of resting state connectivity on cTBS response. We observed significant inter-individual variability in the behavioral response to cTBS with 53.8% of participants demonstrating the expected rightward shift in spatial attention. Baseline high beta connectivity between the right PPC, dorsomedial pre-motor region and left temporal-parietal region was strongly associated with cTBS response (R 2 = 0.51). Regression analysis combining known cTBS determinants (age, sex, motor threshold, physical activity, stress) found connectivity between the right PPC and left temporal-parietal region was the only significant variable (p = 0.011). These results suggest baseline resting state functional connectivity is a strong predictor of a shift in spatial attention following cTBS. Findings from this study help further understand the mechanism by which cTBS modifies cortical function and could be used to improve the reliability of brain stimulation protocols.
| S-EPMC8455944 | biostudies-literature
Project description:IntroductionRepetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.Materials and methodsWe performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.ResultsSeven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.ConclusionWe report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).
| S-EPMC9433314 | biostudies-literature
Project description:The current study used a high frequency TMS protocol known as continuous theta burst stimulation (cTBS) to test a model of hand choice that relies on competing interactions between the hemispheres of the posterior parietal cortex. Based on the assumption that cTBS reduces cortical excitability, the model predicts a significant decrease in the likelihood of selecting the hand contralateral to stimulation. An established behavioural paradigm was used to estimate hand choice in each individual, and these measures were compared across three stimulation conditions: cTBS to the left posterior parietal cortex, cTBS to the right posterior parietal cortex, or sham cTBS. Our results provide no supporting evidence for the interhemispheric competition model. We find no effects of cTBS on hand choice, independent of whether the left or right posterior parietal cortex was stimulated. Our results are nonetheless of value as a point of comparison against prior brain stimulation findings that, in contrast, provide evidence for a causal role for the posterior parietal cortex in hand choice.
| S-EPMC9560494 | biostudies-literature
Project description:ObjectivesApraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation.Materials and methodsNineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model.ResultsPairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 - 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI -0.20 - 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI -0.49 - 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R.ConclusionOne single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia.
| S-EPMC9800932 | biostudies-literature
Project description:Transcranial magnetic stimulation (TMS) treats neuropsychiatric disorders, but effects of stimulation are highly state-dependent and in most therapeutic applications, mental state is not controlled. This exploratory proposal will test the broad hypothesis that when TMS, specifically intermittent theta burst stimulation (iTBS), is applied during a controlled mental state, network changes will be facilitated, compared to stimulation when mental state is uncontrolled. We will focus on the dorsolateral prefrontal cortex (dlPFC) and the associated fronto-parietal network (FPN), which subserves cognitive control, an important neural and behavioral target of therapeutic TMS. After a baseline functional magnetic resonance imaging (fMRI) session, iTBS will be administered to 40 healthy subjects in three sessions over three days in a within-subjects, cross-over design: (1) dlPFC stimulation by iTBS alone, (2) dlPFC stimulation by iTBS while simultaneously performing a cognitive task, and (3) vertex (control) iTBS stimulation. Immediately after each iTBS session, we will measure blood oxygenation level-dependent (BOLD) activation during a cognitive control task ("n-back" task) and during the resting state, using BOLD connectivity and arterial spin labeling (ASL). We will test hypotheses that persisting neural changes and performance enhancement induced by iTBS to the dlPFC, compared to iTBS to the vertex, will affect the FPN, and these effects will be modulated by whether or not subjects receive iTBS when they are engaged in a cognitive control task. Demonstrating this interaction between iTBS and mental state will lay critical groundwork for future studies to show how controlling mental state during TMS can improve therapeutic effects. Clinicaltrials.gov NCT04010461.
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Project description:Following parietal damage most patients with visual neglect bisect horizontal lines significantly away from the true centre. Neurologically intact individuals also misbisect lines; a phenomenon referred to as 'pseudoneglect'. In this study we examined the relationship between neglect and pseudoneglect by testing how patterns of pre-existing visuospatial asymmetry predict asymmetry caused by parietal interference. Twenty-four participants completed line bisection and Landmark tasks before receiving continuous theta burst stimulation to the left or right angular gyrus. Results showed that a pre-existing pattern of left pseudoneglect (i.e. right bias), but not right pseudoneglect, predicts left neglect-like behaviour during line bisection following right parietal cTBS. This correlation is consistent with the view that neglect and pseudoneglect arise via a common or linked neural mechanism.
| S-EPMC3688802 | biostudies-literature
Project description:Continuous theta-burst stimulation (cTBS) induces long-lasting inhibitory effects on cortical excitability. Although cTBS has been reported to modulate neural oscillations and functional connectivity, it is still unclear how cTBS affects brain dynamics that could be captured by the resting-sate EEG microstate sequences. This study aims to investigate how cTBS over the left motor cortex affects brain dynamics. We applied 40 s-long cTBS over the left motor cortex of 28 healthy participants. Before and in multi-sessions up to 90 min after cTBS, their performance in a Nine-Hole Peg Test (NHPT), that measures the hand dexterity, and resting state EEG were recorded. Resting-sate EEG data were clustered into four microstates (namely A, B, C, and D) using k-means clustering algorithms. cTBS-induced changes in NHPT performance, microstate dynamics and functional connectivity networks were comprehensively assessed. As compared with baseline, the completion time of NHPT became shorter immediately after cTBS, suggesting cTBS-induced motor function improvement. After cTBS, the topography of microstate B revealed a greater change compared with other three topographies. Importantly, cTBS-induced decrease in completion time of NHPT correlated with cTBS-induced decrease of the mean occurrence of microstate B. Functional connectivity analysis further revealed that cTBS led to an increase of the node efficiency at C4 electrode in microstate B. These results indicated the specific modulation of cTBS over the motor cortex on the dynamics of microstate B. This work provided the evidence of the association between B and motor function, and it also implies the modulation of cTBS over the motor network.Supplementary informationThe online version contains supplementary material available at 10.1007/s11571-021-09726-6.
| S-EPMC9120322 | biostudies-literature
Project description:OBJECTIVE:We used complete-linkage cluster analysis to identify healthy subpopulations with distinct responses to continuous theta-burst stimulation (cTBS). METHODS:21 healthy adults (age±SD, 36.9±15.2years) underwent cTBS of left motor cortex. Natural log-transformed motor evoked potentials (LnMEPs) at 5-50min post-cTBS (T5-T50) were calculated. RESULTS:Two clusters were found; Group 1 (n=12) that showed significant MEP facilitation at T15, T20, and T50 (p's<0.006), and Group 2 (n=9) that showed significant suppression at T5-T15 (p's<0.022). LnMEPs at T10 and T40 were best predictors of, and together accounted for 80% of, cluster assignment. In an exploratory analysis, we examined the roles of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) polymorphisms in the cTBS response. Val66Met participants showed greater facilitation at T10 than Val66Val participants (p=0.025). BDNF and cTBS intensity predicted 59% of interindividual variability in LnMEP at T10. APOE did not significantly affect LnMEPs at any time point (p's>0.32). CONCLUSIONS:Data-driven cluster analysis can identify healthy subpopulations with distinct cTBS responses. T10 and T40 LnMEPs were best predictors of cluster assignment. T10 LnMEP was influenced by BDNF polymorphism and cTBS intensity. SIGNIFICANCE:Healthy adults can be sorted into subpopulations with distinct cTBS responses that are influenced by genetics.
| S-EPMC5675807 | biostudies-literature
Project description:Objective. Heterogeneous clinical responses to treatment with non-invasive brain stimulation are commonly observed, making it necessary to determine personally optimized stimulation parameters. We investigated neuroimaging markers of effective brain targets of treatment with continuous theta burst stimulation (cTBS) in mal de débarquement syndrome (MdDS), a balance disorder of persistent oscillating vertigo previously shown to exhibit abnormal intrinsic functional connectivity.Approach.Twenty-four right-handed, cTBS-naive individuals with MdDS received single administrations of cTBS over one of three stimulation targets in randomized order. The optimal target was determined based on the assessment of acute changes after the administration of cTBS over each target. Repetitive cTBS sessions were delivered on three consecutive days with the optimal target chosen by the participant. Electroencephalography (EEG) was recorded at single-administration test sessions of cTBS. Simultaneous EEG and functional MRI data were acquired at baseline and after completion of 10-12 sessions. Network connectivity changes after single and repetitive stimulations of cTBS were analyzed.Main results.Using electrophysiological source imaging and a data-driven method, we identified network-level connectivity changes in EEG that correlated with symptom responses after completion of multiple sessions of cTBS. We further determined that connectivity changes demonstrated by EEG during test sessions of single administrations of cTBS were signatures that could predict optimal targets.Significance.Our findings demonstrate the effect of cTBS on resting state brain networks and suggest an imaging-based, closed-loop stimulation paradigm that can identify optimal targets during short-term test sessions of stimulation.ClinicalTrials.gov Identifier:NCT02470377.
| S-EPMC8801344 | biostudies-literature