Intermittent Theta Burst Stimulation Research Articles

Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression.

To investigate the effect of 10Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) on suicidality in patients with treatment-resistant depression (TRD). We used data from a three-site randomized clinical trial comparing 10Hz rTMS and iTBS applied to the left dorsolateral prefrontal cortex (DLPFC) in patients with TRD. We compared the effect of 10Hz rTMS and iTBS on suicidality as measured by the suicide item of the Hamilton Depression Rating Scale 17-item (HDRS-17). Suicidality remitted in 71 (43.7%) participants randomized to 10Hz stimulation and 91 (49.1%) participants randomized to iTBS, without a significant difference between the proportions in the two groups (Χ2 =0.674, df=1, p=0.4117). There was a significant correlation between change in suicidality and change in depression severity for both modalities (10Hz, Pearson's r=0.564; iTBS, Pearson's r=0.502), with a significantly larger decrease in depression severity for those in whom suicidality remitted compared to those in whom it did not (t=10.912, df=276.8, p<0.001). Both 10Hz and iTBS rTMS were effective in reducing suicidality in TRD. Future trials of iTBS for depression should include discrete measures of suicidality.

Effect of Neuroanatomy on Intermittent Theta Burst Stimulation Motor Evoked Potentials

<h3>Research Objectives</h3> Previous work noted that there are significant variabilities in motor response to intermittent theta-burst stimulation (iTBS). It is possible this variability results from individual neuroanatomical differences. The current objective was to investigate the effect of individual neuroanatomy on first dorsal interosseous (FDI) and biceps brachii motor evoked potentials (MEPs) in response to iTBS. <h3>Design</h3> Cross-sectional study using a convenience sample. <h3>Setting</h3> Research laboratory. <h3>Participants</h3> Ten healthy individuals (7 females, 23.5 ± 5 years) participated in this study. Participants completed two iTBS sessions (one each targeting the FDI and biceps cortical hotspots) and an MRI on separate days. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> MEPs were calculated using data acquired with a Magstim Super Rapid2 Plus1 stimulator via a 70 mm double air film coil to the primary motor cortex and electromyography signals were measured from dominant FDI and biceps. Head models were generated from T1 & T2 weighted MRI. Diffusion tensor imaging was used to determine fiber tract geometry for FDI and biceps corticospinal tracts. We then established neuroanatomical parameters including: fiber tract surface area (FTSA), tract fiber count (TFC), and brain scalp distance (BSD). Cortical electric field strength (EFS) was calculated using simulated stimulation of head models and finite element analysis. <h3>Results</h3> For the FDI, there was no effect of iTBS (p = 0.223) but individual changes in corticomotor excitability scaled with stimulation type and resting motor potential (p < 0.001), EFS (p = 0.001), BSD (p = 0.004), and FTSA (p = 0.011). iTBS had a faciliatory response on the biceps and was dependent on FTSA (p < 0.001) and TFC (p < 0.001). <h3>Conclusions</h3> Our results show that MRI-based measures of neuroanatomy, specifically cortical architecture and tract anatomy, impact how the motor system responds to iTBS, subject to target-specific cortical control organization. MRI-based modeling of individual neuroanatomy may be a useful approach in selection of motor targets when designing iTBS-based therapies. <h3>Author(s) Disclosures</h3> None.

Intermittent theta burst stimulation improved visual-spatial working memory in treatment-resistant schizophrenia: A pilot study

BackgroundVisual-spatial working memory (vsWM) impairment in treatment-resistant schizophrenia (TRS) currently has no satisfactory treatment. Our study aimed to improve vsWM function in TRS through intermittent theta burst stimulation (iTBS) using neuronavigation equipment to target the left dorsolateral prefrontal cortex. MethodTRS patients (n = 59) were randomly allocated to receive iTBS (n = 33) or a sham treatment (n = 26) over 2 weeks. The participants including TRS patients and healthy controls (HCs) performed the vsWM n-back task, and TRS patients’ neuroimaging data were acquired before and after treatment. All patients also underwent a battery of symptom measures to assess the severity of illness. The main outcome measure was the accuracy (ACC) of n-back target responses, particularly 3-back ACC. ResultsThe iTBS group showed considerable improvement in n-back ACC compared to the sham group, especially 3-back ACC. After iTBS, performance on the n-back task was comparable to that of HCs. The interaction (group × time) results showed increased fractional amplitude of low frequency fluctuations (fALFF) in the right occipital areas and decreased fALFF in the right precuneus. However, there was a negative correlation between the 3-back ACC and improved clinical symptoms scores. Improvements in 3-back ACC were positively correlated with activity in the right visual cortex. ConclusionsOur study suggested that 2 weeks of iTBS intervention may be a novel, efficacious treatment for vsWM deficits in TRS, which can modulate the activity of local brain regions. iTBS can provide a solution for clinical treatment of TRS and may help patients approach normalcy.

Long-Term Motor Cortical Electrical Stimulation Ameliorates 6-Hydroxydopamine-Induced Motor Dysfunctions and Exerts Neuroprotective Effects in a Rat Model of Parkinson's Disease.

ObjectiveCortical electrical stimulation (CES) can modulate cortical excitability through a plasticity-like mechanism and is considered to have therapeutic potentials in Parkinson’s disease (PD). However, the precise therapeutic value of such approach for PD remains unclear. Accordingly, we adopted a PD rat model to determine the therapeutic effects of CES. The current study was thus designed to identify the therapeutic potential of CES in PD rats.MethodsA hemiparkinsonian rat model, in which lesions were induced using unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, was applied to identify the therapeutic effects of long-term (4-week) CES with intermittent theta-burst stimulation (iTBS) protocol (starting 24 h after PD lesion observation, 1 session/day, 5 days/week) on motor function and neuroprotection. After the CES intervention, detailed functional behavioral tests including gait analysis, akinesia, open-field locomotor activity, apomorphine-induced rotation as well as degeneration level of dopaminergic neurons were performed weekly up to postlesion week 4.ResultsAfter the CES treatment, we found that the 4-week CES intervention ameliorated the motor deficits in gait pattern, akinesia, locomotor activity, and apomorphine-induced rotation. Immunohistochemistry and tyrosine hydroxylase staining analysis demonstrated that the number of dopamine neurons was significantly greater in the CES intervention group than in the sham treatment group.ConclusionThis study suggests that early and long-term CES intervention could reduce the aggravation of motor dysfunction and exert neuroprotective effects in a rat model of PD. Further, this preclinical model of CES may increase the scope for the potential use of CES and serve as a link between animal and PD human studies to further identify the therapeutic mechanism of CES for PD or other neurological disorders.

Integration of Virtual Reality into Transcranial Magnetic Stimulation Improves Cognitive Function in Patients with Parkinson's Disease with Cognitive Impairment: A Proof-of-Concept Study.

Emerging evidence has indicated the positive effects of repetitive transcranial magnetic stimulation (rTMS) on patients with Parkinson's disease (PD) for the treatment of mild cognitive impairment (MCI). Investigating whether combining virtual reality (VR) training with rTMS can further enhance cognitive improvement induced by rTMS treatment. We randomly assigned 40 patients with PD and MCI into three groups, namely the rTMS-VR group (n = 13), rTMS group (n = 11), and sham rTMS group (n = 16). rTMS was administered as 10 consecutive sessions of intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex. In the rTMS-VR group, VR training was administered immediately after each rTMS session. Cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Montreal Cognitive Assessment (MoCA) at baseline, immediately after intervention, and at 3-month follow-up. Compared with the rTMS group, the rTMS-VR group exhibited significantly more improvements in total and delayed memory scores of the RBANS and the visuospatial/executive function score of the MoCA after intervention (p = 0.000∼0.046) and the delayed memory score of the RBANS at 3-month follow-up (p = 0.028). The integrated rTMS-VR protocol achieved a superior outcome in global cognitive function, more effectively enhancing working memory and visuospatial executive function than did the rTMS protocol alone. The combination of VR and rTMS can be an effective regimen for improving the cognitive function of patients with PD.

Corticomotor plasticity as a predictor of response to high frequency transcranial magnetic stimulation treatment for major depressive disorder

BackgroundMany patients with treatment-resistant depression (TRD) respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This study aimed to investigate whether modulation of corticomotor excitability by rTMS predicts response to rTMS treatment for TRD in 10 Hz and intermittent theta-burst stimulation (iTBS) protocols. MethodsThirteen TRD patients underwent two evaluations of corticomotor plasticity—assessed as the post-rTMS (10 Hz, iTBS) percent change (%∆) in motor evoked potential (MEP) amplitude elicited by single-pulse TMS. Following corticomotor plasticity evaluations, patients subsequently underwent a standard 6-week course of 10 Hz rTMS (4 s train, 26 s inter-train interval, 3000 total pulses, 120% of motor threshold) to the left dorsolateral prefrontal cortex. Treatment efficacy was assessed by the Beck Depression Inventory II (BDI-II) and Hamilton Depression Rating Scale (HAM-D). The change in MEPs was compared between 10 Hz and iTBS conditions and related to the change in BDI-II and HAM-D scores. ResultsAnalyses of variance revealed that across all time-points, higher post-10 Hz MEP change was a significant predictor of greater improvement on the BDI-II (p < 0.001) and HAM-D (p = 0.022). This relationship was not observed with iTBS (p-values≥0.100). Post-hoc tests revealed the MEP change 20 min post-10 Hz was the strongest predictor of BDI-II improvement. LimitationsCortical excitability was measured from the motor cortex, rather than the dorsolateral prefrontal cortex, where treatment is applied. The 10 Hz and iTBS protocols were performed at different intensities consistent with common practice. ConclusionsModulation of corticomotor excitability by 10 Hz can predict response to rTMS treatment with 10 Hz rTMS.

Heart Rate Variability Features as Predictors of Intermittent Theta-Burst Stimulation Response in Posttraumatic Stress Disorder

BackgroundPosttraumatic stress disorder (PTSD) is associated with autonomic dysfunction as indicated by deficits in the sympathetic and parasympathetic nervous systems. These abnormalities are expressed as elevated heart rate and reduced heart rate variability (HRV), respectively. Intermittent theta-burst stimulation (iTBS), a form of transcranial magnetic stimulation, has demonstrated effectiveness in PTSD. Nevertheless, it remains unclear whether HRV may be an iTBS biomarker for PTSD and whether iTBS impacts autonomic activity. Materials and MethodsFifty veterans with PTSD participated in a randomized controlled trial, receiving ten daily sessions of sham-controlled iTBS (right dorsolateral prefrontal cortex, 1800 pulses/day, 80% active motor threshold, 9.5 min). With a usable dataset (N = 47), HRV parameters were assessed as predictors of clinical response immediately after stimulation. iTBS effects on autonomic response (mean RR interval, root mean square of successive differences [RMSSD], total power [TP], and low-frequency/high-frequency [LF/HF] ratio) were evaluated using an ultra-short approach. ResultsTP and RMSSD were significant predictors of acute clinical response to iTBS. Individuals with higher TP had better response to iTBS with improved symptoms on the Clinician-Administered PTSD Scale (rs = −0.58, p = 0.004), and higher functionality on the Social and Occupational Function Scale (rs = 0.43, p = 0.04). Similarly, higher RMSSD was associated with superior outcomes (rs = −0.44, p = 0.04). No other significant changes in HRV metrics were observed (p ≥ 0.05). ConclusionsOur findings indicate that autonomic activity is a potential low-cost and technically simple predictive biomarker of iTBS response in PTSD. Less autonomic dysfunction was associated with superior clinical improvements with iTBS. Future studies might consider HRV acquisition during iTBS, as well as prospective testing of these findings in patients with elevated hyperarousal.

Large-scale structural network change correlates with clinical response to rTMS in depression.

Response to repetitive transcranial magnetic stimulation (rTMS) among individuals with major depressive disorder (MDD) varies widely. The neural mechanisms underlying rTMS are thought to involve changes in large-scale networks. Whether structural network integrity and plasticity are associated with response to rTMS therapy is unclear. Structural MRIs were acquired from a series of 70 adult healthy controls and 268 persons with MDD who participated in two arms of a large randomized, non-inferiority trial, THREE-D, comparing intermittent theta-burst stimulation to high-frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). Patients were grouped according to percentage improvement on the 17-item Hamilton Depression Rating Score at treatment completion. For the entire sample and then for each treatment arm, multivariate analyses were used to characterize structural covariance networks (SCN) from cortical gray matter thickness, volume, and surface area maps from T1-weighted MRI. The association between SCNs and clinical improvement was assessed. For both study arms, cortical thickness and volume SCNs distinguished healthy controls from MDD (p = 0.005); however, post-hoc analyses did not reveal a significant association between pre-treatment SCN expression and clinical improvement. We also isolated an anticorrelated SCN between the left DLPFC rTMS target site and the subgenual anterior cingulate cortex across cortical measures (p = 0.0004). Post-treatment change in cortical thickness SCN architecture was associated with clinical improvement in treatment responders (p = 0.001), but not in non-responders. Structural network changes may underpin clinical response to rTMS, and SCNs are useful for understanding the pathophysiology of depression and neural mechanisms of plasticity and response to circuit-based treatments.

Cortical Inhibition and Plasticity in Major Depressive Disorder.

BackgroundMajor depressive disorder (MDD) is a severe psychiatric disorder that is associated with various cognitive impairments, including learning and memory deficits. As synaptic plasticity is considered an important mechanism underlying learning and memory, deficits in cortical plasticity might play a role in the pathophysiology of patients with MDD. We used Transcranial Magnetic Stimulation (TMS) to assess inhibitory neurotransmission and cortical plasticity in the motor cortex of MDD patients and controls.MethodsWe measured the cortical silent period (CSP) and short interval cortical inhibition (SICI), as well as intermittent theta-burst stimulation (iTBS), in 9 drug-free MDD inpatients and 18 controls.ResultsThe overall response to the CSP, SICI, and iTBS paradigms was not significantly different between the patient and control groups. iTBS induction resulted in significant potentiation after 20 mins in the control group (t(17) = −2.8, p = 0.01), whereas no potentiation was observed in patients.ConclusionsPotentiation of MEP amplitudes was not observed within the MDD group. No evidence was found for medium-to-large effect size differences in CSP and SICI measures in severely depressed drug-free patients, suggesting that reduced cortical inhibition is unlikely to be a robust correlate of the pathophysiological mechanism in MDD. However, these findings should be interpreted with caution due to the high inter-subject variability and the small sample size.SignificanceThese findings advance our understanding of neurophysiological functioning in drug-free severely depressed inpatients.

Is the vertex a good control stimulation site? Theta burst stimulation in healthy controls.

The vertex has been used as a suitable control stimulation site in repetitive transcranial magnetic stimulation studies. The objectives of this study are (1) to assess cognitive performance (CP) after theta burst stimulation (TBS); (2) to evaluate whether clinically relevant cortical areas might be reached by vertex stimulation and how that might influence CP. Twenty young healthy subjects performed a cognitive task prior to and immediately after intermittent TBS (iTBS) and continuous TBS (cTBS) of two active cortical stimulation sites and the vertex. We used the Wilcoxon signed-rank test to compare the pre- and post-stimulation reaction times (RTs) and a mixed ANOVA analysis to evaluate the effect of the stimulation on changes in RTs. A three-dimensional finite-element model (FEM) was used to calculate the vertex TBS-induced electrical field (E-field) in the adjacent regions of interest (ROIs). Correlation analyses were performed between E-fields in the ROIs and cognitive outcomes. We found a significant effect only of the stimulation time factor (F (1,12) = 65.37, p < 0.001) on RT shortening, with no superiority of the active site stimulation compared to the vertex stimulation. In 73.5% of vertex TBS sessions, a significant E-field was induced in at least one ROI. We found a negative association between the magnitude of the iTBS-induced E-fields and RT changes (R = - 0.54, p = 0.04). TBS protocols may lead to changes in CP when applied over the craniometrically targeted vertex. We therefore suggest not using a conventional approach as a vertex targeting method.

Motor cortex plasticity response to acute cardiorespiratory exercise and intermittent theta-burst stimulation is attenuated in premanifest and early Huntington\u2019s disease

Huntington’s disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest and 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD.

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN)

BackgroundSchizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham. MethodsThe study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. Assuming an effect size of 0.64 to be detected with a power of 80%, the calculated sample size is 90 patients. Primary outcome will be the difference in the Scale for the Assessment of Negative Symptoms (SANS) score between each active arm and the sham arm at end of treatment.In addition, the trial investigates effects on depressive symptoms, cognitive performance and cigarette smoking. Recording magnetic resonance imaging (MRI) and electroencephalography (EEG) data will serve to assess whether treatment success can be predicted by neural markers and is related to specific neurobiological changes. DiscussionThis is a clinical trial directly comparing 10 Hz-rTMS and iTBS in a sham-controlled manner in treating negative symptoms of schizophrenia. If successful, this would present an interesting treatment option for a chronic and severe condition that can be applied at most psychiatric hospitals and only takes up a few minutes per day. Trial registration numberThis trial has been registered at clinicaltrials.gov, Identifier: NCT04318977. Data disseminationResults from the trial shall be published in peer-reviewed journals and presented at meetings and conferences.

Dose-response of intermittent theta burst stimulation of the prefrontal cortex: A TMS-EEG study

ObjectiveUsing concurrent transcranial magnetic stimulation (TMS) and electroencephalography (TMS-EEG), this study aims to compare the effect of three intermittent theta-burst stimulation (iTBS) doses on cortical activity in the left dorsolateral prefrontal (DLPFC) cortex. MethodsFourteen neurotypical participants took part in the following three experimental conditions: 600, 1200 and 1800 pulses. TMS-EEG recordings were conducted on the left DLPFC pre/post iTBS, including single-pulse TMS and short- and long-interval intracortical inhibition (SICI, LICI). TMS-evoked potentials (TEP) and event-related spectral perturbation (ERSP) were quantified. Linear mixed models were used to assess the effect of iTBS on brain activity. ResultsThe effects of iTBS on DLPFC activity did not significantly differ between the three doses. Specifically, regardless of dose, iTBS modulated the amplitude of most TEP components (P30, N45, P60, P200), reduced SICI and LICI ratios of P30 and P200, and decreased ERSP power of theta oscillations. ConclusionsIn neurotypical individuals, doubling or tripling the number of iTBS pulses does not result in stronger potentiation of prefrontal activity. However, all iTBS conditions induced significant modulations of DLPFC activity. SignificanceReplicating the study in clinical populations could help define optimal parameters for clinical applications.

Peripheral magnetic theta burst stimulation to muscles can effectively reduce spasticity: a randomized controlled trial

BackgroundSpasticity is a common complication of many neurological diseases and despite contributing much disability; the available therapeutic options are limited. Peripheral magnetic stimulation is one promising option. In this study, we investigated whether peripheral intermittent theta burst stimulation (piTBS) will reduce spasticity when applied directly on spastic muscles.MethodsIn this sham-controlled study, eight successive sessions of piTBS were applied directly to spastic muscles with supra threshold intensity. Assessment was done by modified Ashworth scale (mAS) and estimated Botulinum toxin dose (eBTD) at baseline and after the 8th session in both active and sham groups.ResultsA total of 120 spastic muscles of 36 patients were included in the analysis. Significant reduction of mAS and eBTD was found in the active compared to sham group (p < 0.001). The difference in mAS was also significant when tested in upper limb and lower limb subgroups. The degree of reduction in mAS was positively correlated with the baseline scores in the active group.ConclusionpiTBS could be a promising method to reduce spasticity and eBTD. It consumes less time than standard high frequency protocols without compromising treatment efficacy.Trial registration: Clinical trial registry number: PACTR202009622405087. Retrospectively Registered 14th September, 2020.

Facilitatory Effect of Intermittent Repetitive Transcranial Magnetic Stimulation on Perceptual Distortion of the Face

Orofacial pain patients often report that the painful facial area is “swollen” without clinical signs - known as perceptual distortion (PD). The neuromodulatory effect of facilitatory repetitive transcranial magnetic stimulation (rTMS) on PD in healthy individuals was investigated, to provide further support that the primary somatosensory cortex (SI) is involved in facial PD. Participants were allocated to active (n = 26) or sham (n = 26) rTMS group in this case-control study. PD was induced experimentally by injecting local anesthesia (LA) in the right infraorbital region. PD was measured at baseline, 6 min after LA, immediately, 20 and 40 min after rTMS. Intermittent theta-burst stimulation (iTBS) as active rTMS and sham rTMS was applied to the face representation area of SI at 10 min after LA. The magnitude of PD was compared between the groups. The magnitude of PD significantly increased immediately after iTBS compared with sham rTMS (P = .009). The PD was significantly higher immediately after iTBS compared to 6 min after LA (P = .004) in the active rTMS group, but not in the sham rTMS group (P = .054). iTBS applied to a somatotopic-relevant cortical region appears to facilitate facial PD further supporting the involvement of SI in the processing of one´s own face and PD. PerspectiveThis study provides information on neural substrate responsible for processing of perceptual distortion of the face which is speculated to contribute to the chronification of orofacial pain. The findings of this study may aid in mechanism-based management of the condition in orofacial pain disorders and possibly other chronic pain states.

Theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for poststroke dysphagia: A randomized, double-blind, controlled trial.

Background:Repetitive transcranial magnetic stimulation (rTMS) of high-frequency (10 Hz) on suprahyoid motor cortex has been an evidence-based treatment for poststroke dysphagia. Intermittent theta burst stimulation (iTBS) can be performed in 3 minutes compared with 20 ± 5 minutes for 10 Hz rTMS. This study aimed to ensure the clinical efficacy, safety, and tolerability of iTBS compared with 10 Hz rTMS for patients with poststroke dysphagia.Method:In this randomized, double-blind, single-center, controlled trial, 47 participants were randomly assigned to iTBS (n = 24) and rTMS (n = 23) group. Each participant received iTBS or rTMS daily at suprahyoid motor cortex of affected hemisphere for 10 consecutive days. The outcomes were assessed at baseline, immediately, and 2 weeks after intervention, including water-swallowing test, standardized swallowing assessment, Mann assessment of swallowing ability, Murray Secretion Scale, Yale Pharyngeal Residue Severity Rating Scale, Penetration-Aspiration Scale, and motor evoked potential (MEP) of bilateral suprahyoid muscle.Results:There were no significant differences between groups. There was a significant improvement on all rating scales and MEP after rTMS and iTBS. No significant differences on water-swallowing test, Mann assessment of swallowing ability, standardized swallowing assessment, Murray Secretion Scale scores, and MEP were observed between groups. In particular, there was significant differences on Penetration-Aspiration Scale scores (viscous liquid: mean difference = 1.016; 95% CI: 0.32–1.71; effect size: 0.360; P = .005) and the residue rate of pyriform fossa (viscous liquid: mean difference = 0.732; 95% CI: 0.18–1.28; effect size: 0.248; P = .010) in between-group. Comparing the differences over the changes of all rating scales, only the residue rate of epiglottis valley between groups was found to be significantly different (dilute liquid: mean difference = –0.567; 95% CI: –0.98 to –0.15; P = .009). There was no severe adverse effect and high dropout rates in both groups.Conclusion:The clinical efficacy, safety, and tolerability of iTBS showed non-inferior to 10 Hz rTMS for patients with poststroke dysphagia. The present study can be used to improve the clinicians’ knowledge and clinical decision skills on iTBS and rTMS for poststroke dysphagia.

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.

Low-Frequency vs. Theta Burst Transcranial Magnetic Stimulation for the Treatment of Chronic Non-fluent Aphasia in Stroke: A Proof-of-Concept Study.

BackgroundAlthough low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise in the treatment of poststroke aphasia, the efficacy of high-frequency rTMS (HF-rTMS) has yet to be determined.PurposeWe investigated the efficacy of intermittent theta burst stimulation (iTBS) in ameliorating chronic non-fluent aphasia and compared it with that of LF-rTMS.MethodsWe randomly assigned patients with poststroke non-fluent aphasia to an ipsilesional iTBS (n = 29), contralesional 1-Hz rTMS (n = 27), or sham (n = 29) group. Each group received the rTMS protocol executed in 10 daily sessions over 2 weeks. We evaluated language function before and after the intervention by using the Concise Chinese Aphasia Test (CCAT).ResultsCompared with the sham group, the iTBS group exhibited significant improvements in conversation, description, and expression scores (P = 0.0004–0.031), which characterize verbal production, as well as in auditory comprehension, reading comprehension, and matching scores (P < 0.01), which characterize language perception. The 1-Hz group exhibited superior improvements in expression, reading comprehension, and imitation writing scores compared with the sham group (P < 0.05). The iTBS group had significantly superior results in CCAT total score, matching and auditory comprehension (P < 0.05) relative to the 1-Hz group.ConclusionOur study findings contribute to a growing body of evidence that ipsilesional iTBS enhances the language recovery of patients with non-fluent aphasia after a chronic stroke. Auditory comprehension was more preferentially enhanced by iTBS compared with the 1-Hz protocol. Our findings highlight the importance of ipsilesional modulation through excitatory rTMS for the recovery of non-fluent aphasia in patients with chronic stroke.Clinical Trial Registration:[www.ClinicalTrials.gov], identifier [NCT03059225].

A Retrospective Naturalistic Study Comparing the Efficacy of Ketamine and Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression.

Depression is a common mental disorder that affects many people worldwide, while a significant proportion of patients remain non-responsive to antidepressant medications. Alternative treatment options such as ketamine therapy and repetitive transcranial magnetic stimulation (rTMS) therapy are offered nowadays. This study aims to describe and compare the acute antidepressive efficacy of both, intramuscular ketamine and rTMS in depression patients seeking help in a naturalistic clinical mental health setting. The clinical records of 24 patients with treatment resistant depression were collected from the clinical base of a real life clinic. Twelve patients were treated with intramuscular ketamine, twice weekly for 8 sessions, and twelve patients were treated with 30 sessions of left dorsolateral prefrontal cortex – intermittent theta-burst stimulation (DLPFC-iTBS). Using three clinical assessments (HDRS, HAM-A, BDI-II), our data reveal that both therapies led to significant improvement in symptoms from pre- to post- treatment, as well as that the two experimental groups did not differ significantly with respect to pre- to post- depressive and anxiety symptoms, indicating that the effect of both experimental groups in our sample was equally effective. Furthermore, our results showed high remission and response rates in both groups, with no statistical differences between the patients of ketamine group and rTMS group in remission and response rates. We show a significant pre- to post- treatment reduction in depressive and anxiety symptoms, with no significant differences between the two experimental groups, indicating that the effect of both therapies was equally effective in our limited sample.

Prehabilitation and rehabilitation using data-driven, parcel-guided transcranial magnetic stimulation treatment for brain tumor surgery

Improved knowledge of the neuroplastic potential of the brain connectome has facilitated the advancement of neuromodulatory treatments for brain tumor patients especially in the perioperative period. More recently, the idea of inducing neuroplastic changes before surgery as “prehabilitation” has been suggested in low-grade gliomas with favorable data. However, it is uncertain the degree to which this treatment with transcranial magnetic stimulation (TMS) would benefit patients with high-grade gliomas, especially with additional rehabilitation after surgery and targets defined by personalized connectomic data. The current report details a case of a patient with recurrent glioblastoma in the right motor area 2 years after previous total resection. Given the desire for a more aggressive recurrent surgery in a highly functional area, the authors decided to proceed with “prehabilitation” by stimulating the surrounding motor cortices around the lesion to turn down the motor cortex connectivity before the recurrent surgery and then completing “rehabilitation” after the surgery. Structural-functional connectomic analyses were completed using Infinitome software based on an individualized patient brain atlas using machine-learning based parcellations. Repetitive TMS was employed, specifically using continuous and intermittent theta burst stimulation protocols. Prehabilitation consisted of using continuous theta burst stimulation at the estimated surgical entry point parcel and intermittent theta burst stimulation at adjacent parcellations for a total of 10 days with 5 sessions per day per target leading up until the surgery. A gross-total resection was obtained, but the patient woke up with left-sided hemiparesis. Resting-state functional magnetic resonance imaging derived connectivity demonstrated a case of a primarily pure cingulate-motor resection causing hemiplegia with an intact corticospinal tract and supplementary motor area. Functional connectivity outliers in cingulate-motor parcels were identified and compared with connectivity matrices from a healthy control atlas. Anomalies, parcels defined as functioning significantly outside a normal range, were chosen as rehabilitation TMS targets to be similarly treated for a total of 10 days with 5 sessions per day per target approximately two weeks after surgery. By using continuous theta burst stimulation on hyperconnected parcels and intermittent theta burst stimulation on hypoconnected parcels, the patient demonstrated significant motor improvement with only 4+/5 strength in the left arm 1 month after surgery. This report demonstrates for the first time the feasibility of using TMS treatment for glioblastoma surgery near “eloquent” cortices as a means of prehabilitation before surgery and rehabilitation after surgery. This parcel-guided approach for TMS treatment based on the cortical site of entry and individualized connectivity analyses allowed for maximal tumor resection and minimal long-term neurologic deficits.