Neurophysiological markers of response to theta burst stimulation in youth depression.
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ABSTRACT: Background
Theta burst stimulation (TBS) has recently been proposed as a novel treatment for youth depression. However, the impact of TBS on the youth brain and neurophysiological predictors of response to TBS in this population have not been investigated.Methods
Cortical reactivity was assessed at baseline and following 2 weeks of bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment in 16 youth with depression (aged 16-24 years old). In 16 age-matched health youths, cortical reactivity was assessed twice, 2 weeks apart. Transcranial magnetic stimulation (TMS) combined with electroencephalography was used to assess TMS-evoked potentials in bilateral DLPFC, motor cortices, and intraparietal lobules (IPL). Resting-state functional magnetic resonance imaging (fMRI) data was also collected at baseline.Results
Left DLPFC pretreatment cortical reactivity, specifically the negativity at 45 ms (i.e., N45), which is related to GABAA neurotransmission, was associated with changes in depressive symptoms. Furthermore, TBS treatment was found to alter the N45 in the right IPL, a site distal to the treatment sites. The magnitude of the right IPL N45 modulation was correlated with the baseline fMRI connectivity between the right IPL and right DLPFC.Conclusions
TMS-probed cortical inhibition at the site of TBS application may have potential as a predictor of treatment response in youth depression. Furthermore, pre-treatment functional connectivity may predict the impact of TBS on the neurophysiology of regions distal to the stimulation site. Collectively, these results offer novel neurophysiological insights into the application of TBS for youth depression, which may facilitate its wider use in the youth population.
SUBMITTER: Dhami P
PROVIDER: S-EPMC8143862 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPrefrontal repetitive transcranial magnetic stimulation is an established add-on treatment for major depressive disorder and is increasingly feasible with protocols of short duration, such as intermittent theta burst stimulation (iTBS). The most common and limiting side effect is pain at the site of application. Our objective was to investigate how pain develops over time in patients with depression receiving iTBS compared to sham stimulation.MethodsThis is a subsample from a randomized clinical trial. Patients received daily sessions of 2400 pulses of dorsomedial prefrontal iTBS or sham stimulation with transcutaneous electric stimulation during 2 to 3 weeks. After unmasking of treatment allocation, patients receiving sham treatment were offered active iTBS in an open phase. Patients rated pain on a scale from 0 to 10 after the last train of stimulation on the first, fifth and final treatment day. A Mann-Whitney U-test was conducted to test for group differences and related-samples Friedman's tests to analyze changes in pain ratings over time.ResultsThe scalp pain in the group receiving iTBS was rated higher than sham treatment on the first (U = 263.5, p = 0.035) and fifth day (U = 271.0, p = 0.020) but not on the final day (U = 210.5, p = 0.121). The pain decreased mainly during the first 5 days of treatment (χ2 = 0.875, p = 0.040). In the open phase the pain decreased from the first day to the final day (χ2 = 1.194, p = 0.001).ConclusionsThe subjective pain perception of active dorsomedial iTBS was higher than sham treatment but decreased over time, indicating an analgesic effect, or habituation. The result from this study can be used to inform patients about what to expect regarding pain during an iTBS treatment course.Trial registrationClinicaltrials.gov, NCT02905604 . Registered 19 September 2016.
| S-EPMC7439669 | 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:Accelerated intermittent theta burst stimulation (aiTBS) is a noninvasive neurostimulation technique that shows promise for improving clinical outcome in patients suffering from treatment-resistant depression (TRD). Although it has been suggested that aiTBS may evoke beneficial neuroplasticity effects in neuronal circuits, the effects of aiTBS on brain networks have not been investigated until now. Fifty TRD patients were enrolled in a randomized double-blind sham-controlled crossover trial involving aiTBS, applied to the left dorsolateral prefrontal cortex. Diffusion-weighted MRI data were acquired at each of three time points (T1 at baseline; T2 after the first week of real/sham aiTBS stimulation; and T3 after the second week of treatment). Graph analysis was performed on the structural connectivity to examine treatment-related changes in the organization of brain networks. Changes in depression severity were assessed using the Hamilton Depression Rating Scale (HDRS). Baseline data were compared with 60 healthy controls. We observed a significant reduction in depression symptoms over time (p < 0.001). At T1, both TRD patients and controls exhibited a small-world topology in their white matter networks. More importantly, the TRD patients demonstrated a significantly shorter normalized path length (p AUC = 0.01), and decreased assortativity (p AUC = 0.035) of the structural networks, compared with the healthy control group. Within the TRD group, graph analysis revealed a less modular network configuration between T1 and T2 in the TRD group who received real aiTBS stimulation in the first week (p < 0.013). Finally, there were no significant correlations between changes on HDRS scores and reduced modularity. Application of aiTBS in TRD is characterized by reduced modularity, already evident 4 days after treatment. These findings support the potential clinical application of such noninvasive brain stimulation in TRD.
| S-EPMC6372023 | biostudies-literature
Project description: Not available
| S-EPMC7906022 | 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:IntroductionRepetitive transcranial magnetic stimulation (TMS) is increasingly used to treat neurocognitive symptoms in mood disorders. Intermittent theta burst stimulation (iTBS) is a brief version of TMS that may preferentially target cognitive functions. This study evaluated whether iTBS leads to cognitive improvements and associated increased hippocampal volumes in bipolar depression.MethodsIn a two-site double-blind randomised sham controlled trial (NCT02749006), 16 patients received active iTBS to the Left Dorsolateral Prefrontal Cortex (DLPF) and 15 patients received sham stimulation across four weeks. A composite neuropsychological score and declarative memory scores served as the cognitive outcomes. Hippocampal volumes were derived from T1 weighted MRI scans using the longitudinal ComBat method to harmonise data across sites.ResultsNo significant improvements were observed in any cognitive variables in the active relative to the sham group; however, there was a trend for increased left hippocampal volume in the former. Left hippocampal volume increases were associated with improvements in nonverbal memory in the active group.ConclusionsAlthough cognitive improvements were not associated with iTBS, the finding that hippocampal volume increases were associated with memory improvement suggests there may be some level of prefrontal-temporal neuroplasticity that could support cognitive change in future studies of iTBS in bipolar disorder.
| S-EPMC10026761 | biostudies-literature
Project description:OBJECTIVE:Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder associated with disruption in social and occupational function. Transcranial magnetic stimulation (TMS) represents a novel approach to PTSD, and intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression. The authors conducted a sham-controlled study of iTBS for PTSD. METHODS:Fifty veterans with PTSD received 10 days of sham-controlled iTBS (1,800 pulses/day), followed by 10 unblinded sessions. Primary outcome measures included acceptability (retention rates), changes in PTSD symptoms (clinician- and self-rated), quality of life, social and occupational function, and depression, obtained at the end of 2 weeks; analysis of variance was used to compare active with sham stimulation. Secondary outcomes were evaluated 1 month after treatment, using mixed-model analyses. Resting-state functional MRI was acquired at pretreatment baseline on an eligible subset of participants (N=26) to identify response predictors. RESULTS:Retention was high, side effects were consistent with standard TMS, and blinding was successful. At 2 weeks, active iTBS was significantly associated with improved social and occupational function (Cohen's d=0.39); depression was improved with iTBS compared with the sham treatment (d=-0.45), but the difference fell short of significance, and moderate nonsignificant effect sizes were observed on self-reported PTSD symptoms (d=-0.34). One-month outcomes, which incorporated data from the unblinded phase of the study, indicated superiority of active iTBS on clinician- and self-rated PTSD symptoms (d=-0.74 and -0.63, respectively), depression (d=-0.47), and social and occupational function (d=0.93) (all significant). Neuroimaging indicated that clinical improvement was significantly predicted by stronger (greater positive) connectivity within the default mode network and by anticorrelated (greater negative) cross-network connectivity. CONCLUSIONS:iTBS appears to be a promising new treatment for PTSD. Most clinical improvements from stimulation occurred early, which suggests a need for further investigation of optimal iTBS time course and duration. Consistent with previous neuroimaging studies of TMS, default mode network connectivity played an important role in response prediction.
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Project description:Introduction:Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. Methods:We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). Results:Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. Conclusion:Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.
| S-EPMC7006239 | biostudies-literature
Project description:BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment for depression that is increasingly implemented in healthcare systems across the world. A new form of rTMS called intermittent theta burst stimulation (iTBS) can be delivered in 3 min and has demonstrated comparable effectiveness to the conventional 37.5 min 10Hz rTMS protocol in patients with depression.ObjectivesTo compare the direct treatment costs per course and per remission for iTBS compared to 10Hz rTMS treatment in depression.MethodsWe conducted a cost analysis from a healthcare system perspective using patient-level data from a large randomized non-inferiority trial (THREE-D). Depressed adults 18 to 65 received either 10Hz rTMS or iTBS treatment. Treatment costs were calculated using direct healthcare costs associated with equipment, coils, physician assessments and technician time over the course of treatment. Cost per remission was estimated using the proportion of patients achieving remission following treatment. Deterministic sensitivity analyses and non-parametric bootstrapping was used to estimate uncertainty.ResultsFrom a healthcare system perspective, the average cost per patient was USD$1,108 (SD 166) for a course of iTBS and $1,844 (SD 304) for 10Hz rTMS, with an incremental net savings of $735 (95% CI 688 to 783). The average cost per remission was $3,695 (SD 552) for iTBS and $6,146 (SD 1,015) for 10Hz rTMS, with an average incremental net savings of $2,451 (95% CI 2,293 to 2,610).ConclusionsThe shorter session durations and treatment capacity increase associated with 3 min iTBS translate into significant cost-savings per patient and per remission when compared to 10Hz rTMS.
| S-EPMC6742475 | biostudies-literature
Project description:To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD).Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS.In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures.We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation.iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD.This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.
| S-EPMC3053339 | biostudies-literature