TMS Treatment Research Articles

A multisite observational real-world study on the effectiveness of repetitive transcranial magnetic stimulation therapy for patients with treatment-resistant depression in Japan

The objective of this study was to reveal the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for Japanese patients with treatment-resistant depression (TRD) in clinical practice, based on real-world data from a nationwide multicenter observational study in Japan.Clinical data of patients with TRD treated with rTMS (NeuroStar TMS treatment system) under public insurance coverage were retrospectively collected from 21 institutes nationwide between June, 2019 and December, 2023. Depression severity was assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). Response and remission were defined as ≥50% reduction from baseline and ≤7 points on the HAMD-17, respectively. The primary outcome was the changes in the HAMD-17 score from baseline to the endpoint following rTMS. Data from 497 patients with TRD were candidates for this study. The HAMD-17 scores (mean (SD)) improved significantly from 18.9 (5.3) to 9.7 (6.6), respectively. The response and remission rates at the end of rTMS therapy as assessed by the HAMD-17 were 53.5% and 42.8%, respectively. The dropout rate due to adverse effects was 4.2%, and the treatment was generally well tolerated. No convulsive seizures or manic changes were observed. These results indicate that conventional rTMS is effective and safe in Japanese patients with TRD.

Effect of sleep quality on repetitive transcranial magnetic stimulation outcomes in depression.

While repetitive transcranial magnetic stimulation (rTMS) is effective for 50-60% of those treatment-resistant depression, it is critical to identify predictors of response for optimal patient selection to improve therapy. Insomnia is a known symptom of depression that is both correlated with depression severity and associated with poor antidepressant response. Therefore, understanding this relationship may open new opportunities for the optimization of rTMS treatment. We aimed to explore whether baseline sleep quality, specifically insomnia, is associated with rTMS outcomes in a naturalistic sample of 975 patients (age 18-90; 63.9% F) receiving a standard course of rTMS treatment from two outpatient TMS clinics located within psychiatric hospitals in the United States. One site additionally collected information on concurrent medication use on 350 patients; among these, we examined whether pharmacological treatment of insomnia affected TMS treatment response. Depression was measured using the 30-item Inventory of Depressive Symptomology Self Report (IDS-SR) in site one and an abbreviated 16-item Quick Inventory of Depressive Symptomology (QIDS) derived from the IDS-SR in site two. Sleep disturbances were measured using three insomnia-related questions. Multilevel logistic regression was used to determine whether baseline insomnia scores were associated with TMS treatment outcome. Upon dichotomous categorization of the sample by insomnia and sleep-medication use, depression and sleep scores were analyzed across time using mixed repeated measures ANOVA. We found that sleep quality improves after TMS (p<.001) and correlates with improvement in non-insomnia related depression symptoms (r= .318, p<.001). We found that among those who had significant insomnia at baseline, those not using sleep medications had significantly worse post-treatment IDS-SR scores compared to those using sleep medications (p=. 021) despite no difference in final insomnia score. Together, our results suggest that while baseline insomnia is not associated with TMS effectiveness, treating insomnia may affect the trajectory of TMS therapy. Future prospective studies are needed to examine the effect of insomnia treatment alongside TMS for depression.

Embryonic thermal manipulation and post-hatch dietary guanidinoacetic acid supplementation alleviated chronic heat stress impact on broiler chickens

The study investigated the effects of embryonic thermal manipulation (TM) and post-hatch guanidinoacetic acid (GAA) supplementation on male broiler chickens exposed to chronic heat stress (HS). Ross 308 eggs (n = 710) were randomly assigned to control (37.8 °C, 56% RH) or TM (39.5 °C, 65% RH for 12 h/day from embryonic day 7–16) treatments. After hatching, chicks were further assigned to four dietary treatments (n = 12 birds/pen, 5 replicates/treatment): control, control with 1.2 g/kg GAA supplementation (CS), TM, and TM with 1.2 g/kg GAA supplementation (TMS). All birds were subjected to chronic HS (32–36 °C and 55% RH for 6 h/day) from day 28–42. Embryonic TM treatment decreased hatchability, hatching weight (HW), and facial temperature (FT). During the pre-HS period (days 1–28), no significant differences in feed conversion ratio (FCR) and mortality were observed, although the TM group exhibited the lowest body weight gain (BWG). Following HS exposure (days 29–42), the TMS group displayed significantly higher BWG than the control and CS groups. The TM and TMS groups also demonstrated significantly lower FCR and mortality rates during this period. Across the entire period (days 1–42), BWG was significantly higher in the TMS group compared to other groups. Furthermore, TM and TMS treatments were associated with lower mortality rates, improved FCR, better European Performance Efficiency Index (EPEI), and reduced abdominal fat deposition. The experimental treatments did not significantly affect intestinal morphology or most blood parameters, except triiodothyronine (T3), thyroxine (T4), and uric acid. Plasma concentrations of T3, T4, and uric acid were significantly lower in the TM and TMS groups compared to the control and CS treatments. The findings suggest that a combined strategy of embryonic TM and post-hatch dietary GAA supplementation may not only alleviate the detrimental effects of HS but also promote beneficial physiological responses in broiler chickens.

Sleep as a predictor of improved response to transcranial magnetic stimulation for depression (SPIRiTeD)

BackgroundTranscranial magnetic stimulation (TMS) is an evidence-based approach to treatment- resistant Major Depressive Disorder (TRD). Sleep dysfunction is associated with poor outcomes in TRD, however, the impacts of sleep dysfunction on TMS treatment has yet to be defined. This study examined the association between sleep dysfunction and improvement in depression symptoms with TMS treatment for TRD. MethodsA retrospective observational cohort study was conducted examining all Veterans receiving TMS treatments through the “VA TMS Clinical Pilot Program” over a three-year period. The Patient Health Questionnaire (PHQ-9) sleep item was utilized to assess sleep dysfunction. The association between sleep dysfunction improvements during TMS treatment with depression outcomes was analyzed. Results94.3 % (N = 778) of Veterans reported baseline sleep dysfunction. Chi-square analysis demonstrated higher rates of depression remission at the completion of TMS treatment for those with sleep improvement at weeks 1, 3 and 6 (all p < .001). ANOVA comparing sleep improvements and end of treatment PHQ-8 score (modified to remove sleep item) found a statistically significant difference in mean improvements of depression scores at all 3 time points. LimitationsLimitations include those that are inherent to retrospective studies, as well as limitations in using the PHQ-9 sleep item as the primary means to assess sleep dysfunction. ConclusionThis study reports on the largest sample size to date examining the relationship between sleep dysfunction and TMS treatment outcomes for MDD, and found that improvement in sleep dysfunction was associated with greater reductions in end of treatment depression symptoms including higher depression remission rates.

Determining the Number of Clusters in Clinical Response of TMS Treatment using Hyperdimensional Computing

Determining the Number of Clusters in Clinical Response of TMS Treatment using Hyperdimensional Computing

Altered blood parameters in “major depression” patients receiving repetitive transcranial magnetic stimulation (rTMS) therapy: a randomized case-control study

Major depressive disorder (MDD) is a debilitating illness that includes depressive mood. Repetitive Transcranial Magnetic Stimulation (rTMS) is a therapy method used in the treatment of MDD. The purpose of this study was to assess neurotrophic factors, and oxidative stress levels in MDD patients and evaluate the changes in these parameters as a result of rTMS therapy. Twenty-five patients with MDD and twenty-six healthy volunteers with the same demographic characteristics were included in the study. Brain-derived neurotrophic factors were measured photometrically with commercial kits. Oxidative stress parameters were measured by the photometric method. Oxidative stress index (OSI) and disulfide (DIS) levels were calculated with mathematical formulas. In this study, total antioxidant status (TAS), total thiol (TT), and native thiol (NT) antioxidant parameters and brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and allopregnanolone (ALLO) levels were reduced in pre-rTMS with regard to the healthy control group; TOS, OSI, DIS, and S100 calcium-binding protein B (S100B) levels were increased statistically significantly (p < 0.01). Moreover, owing to TMS treatment; TAS, TT, NT, BDNF, GDNF, and ALLO levels were increased compared to pre-rTMS, while DIS, TOS, OSI, and S100B levels were decreased significantly (p < 0.01). The rTMS treatment reduces oxidative stress and restores thiol-disulfide balance in MDD patients. Additionally, rTMS modulates neurotrophic factors and neuroactive steroids, suggesting its potential as an antidepressant therapy. The changes in the biomarkers evaluated may help determine a more specific approach to treating MDD with rTMS therapy.

The comfort level in breast cancer patients’ based on patients’ characteristics during the COVID-19 pandemic

Background: Comfort level in breast cancer patients is one of the most critical factors influencing patient’s treatment commitment. The COVID-19 pandemic has affected various sectors, especially health status.&#x0D; Objectives: This study aims to describe patients' comfort levels during the COVID-19 pandemic and to investigate the relationship between patients’ characteristics and comfort levels.&#x0D; Methods: This study involved 108 respondents using a consecutive sampling technique at one time (cross-sectional). The research instrument was Comfort Assessment Breast Cancer Instrument (CABCI). The data were analyzed using Chi-Square.&#x0D; Results: The results showed that the comfort level in this study is categorized as comfortable. The best comfort aspect is the environmental aspect and the least is the physical aspect. In addition, there are two variables related to comfort, treatment (p = 0.007; α = 0.05) and treatment room (p = 0.000; α = 0.05). The best comfort level was found in chemotherapy treatment and outpatient rooms. Patients feel comfortable with a neat, clean, conducive hospital environment and the implementation of health protocols. These aspects could effectively prevent the spread of COVID-19.&#x0D; Conclusions: The results of this study recommend nursing services to optimize all aspects of comfort, which could still be improved. Interventions that maintain or improve comfort will optimize patients’ health conditions.

Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation

Psychomotor slowing is a frequent symptom of psychosis, impairing gross and fine motor behavior. It is associated with poor outcomes and functioning, and no treatment is available. To investigate whether 15 sessions of inhibitory repetitive transcranial magnetic stimulation (rTMS) may reduce psychomotor slowing. This was a 4-arm, double-blind, randomized, sham-controlled trial at a university hospital in Switzerland. Enrollment took place from March 2019 to August 2022. Adults aged 18 to 60 years with schizophrenia spectrum disorders and severe psychomotor slowing were eligible. All patients continued existing medications, including antipsychotics and benzodiazepines. Those with substance misuse (other than nicotine), conditions associated with impaired or aberrant movement, convulsions, history of hearing problems, other conditions typically excluded from magnetic resonance imaging or TMS, any TMS treatment in the past 3 months, or those who were pregnant or breastfeeding were excluded. Of 615 patients screened for eligibility, 103 were randomized and 88 received at least 1 session of rTMS: 22 were assigned to 1-Hz rTMS, 22 to iTBS, 22 to sham, and 22 to the waiting group. Follow-up was conducted at 6 weeks and 24 weeks following the week 3 assessments including clinical, functional, and motor measures. Fifteen sessions of rTMS in 3 weeks over the supplementary motor area: 1-Hz rTMS, iTBS, sham, or no treatment (waiting). After 3 weeks, the waiting group received 15 sessions of 1-Hz rTMS over the supplementary motor area. The main outcome was the proportion of responders at week 3 in the Salpêtrière Retardation Rating Scale (SRRS) defined as a 30% or greater reduction from baseline (last-observation-carried-forward). The SRRS has 15 items and a maximum total score of 60. Of the 88 participants analyzed, 45 were men and 43 were women. The mean (SD) age was 36.3 (12.4) years and the mean (SD) SRRS score was 24.0 (5.9). A total of 69 participants completed the study. At week 3, response rates differed between groups: 15 of 22 (68%) in the 1-Hz rTMS group, 8 of 22 (36%) in the iTBS group, 7 of 22 (32%) in the sham group, and 4 of 22 (18%) in the waiting group (χ23 = 12.1; P = .007). The 1-Hz rTMS group had more responders than sham (odds ratio [OR], 0.13; 95% CI, 0.02-0.65; P = .03), iTBS (OR, 0.12; 95% CI, 0.02-0.61; P = .02), and waiting (OR, 0.04; 95% CI, 0.01-0.22; P = .003). In the waiting group, 10 of 16 participants (63%) responded after receiving 15 sessions of 1-Hz rTMS. No serious adverse events occurred. In this study, inhibitory add-on rTMS safely alleviated psychomotor slowing in psychosis compared with iTBS, sham, and no treatment. The treatment was also effective with delayed onset. Future studies need to explore the neural changes associated with supplementary motor area rTMS in psychosis. ClinicalTrials.gov Identifier: NCT03921450.

Comparing the efficacies of transcranial magnetic stimulation treatments using different targeting methods in major depressive disorder: protocol for a network meta-analysis

IntroductionTranscranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (lDLPFC) has been widely used as a treatment for major depressive disorder (MDD) in the past two decades. Different methods...

Growing placebo response in TMS treatment for depression: a meta-analysis of 27-year randomized sham-controlled trials

Growing placebo response in TMS treatment for depression: a meta-analysis of 27-year randomized sham-controlled trials

Accelerated intermittent theta-burst stimulation for the treatment of adolescent depression: A case series

BackgroundIntermittent theta burst stimulation (iTBS) is a safe and effective form of repetitive transcranial magnetic stimulation (rTMS) for depression in adults. Accelerated protocols involving multiple sessions per day, have become popular possibly attributed to their potential for rapid antidepressant effects. Previous literature has shown iTBS to be safe for adolescents with depressive symptoms, however, outcomes from accelerated iTBS protocols in this population have not been thoroughly described. MethodsThis case series describes six adolescent patients who received outpatient accelerated iTBS treatment for depression symptoms. Self-reported depression severity was assessed using the Patient Health Questionnaire-9 (PHQ-9) scale at baseline, and various follow-up time points including immediate, one-week, and one-month post-treatment. Individual accelerated iTBS protocols varied with regard to specific brain targets and TMS treatment parameters. ResultsFollowing treatment, three of six patients achieved remission (PHQ-9 score < 5), two responded (≥ 50% reduction in PHQ-9 scores), and one had no response. All patients tolerated treatment well without significant adverse events. LimitationsPHQ-9 scores were not available at all post-treatment timepoints for all patients. Additionally, primary diagnoses, clinical comorbidities, and treatment parameters differed between patients, which may have impacted treatment outcomes. ConclusionIn six adolescents, accelerated iTBS was well-tolerated and in most cases, was followed by rapid antidepressant effects. These findings support the safe, clinical use of accelerated iTBS in adolescents with depression and warrant future prospective clinical trials to optimize treatment parameters and confirm efficacy.

EEG Individual Alpha Frequencies May Predict Clinical Outcome in TMS Treatment

EEG Individual Alpha Frequencies May Predict Clinical Outcome in TMS Treatment

Sleep Dysfunction as a Predictor of Improvement in Depressive Symptoms with TMS Treatment

Sleep Dysfunction as a Predictor of Improvement in Depressive Symptoms with TMS Treatment

Is Bilateral TMS Treatment with Left iTBS as effective as Bilateral TMS Treatment with Left 10 Hz?

Is Bilateral TMS Treatment with Left iTBS as effective as Bilateral TMS Treatment with Left 10 Hz?

Network effects of Stanford Neuromodulation Therapy (SNT) in treatment-resistant major depressive disorder: a randomized, controlled trial

Here, we investigated the brain functional connectivity (FC) changes following a novel accelerated theta burst stimulation protocol known as Stanford Neuromodulation Therapy (SNT) which demonstrated significant antidepressant efficacy in treatment-resistant depression (TRD). In a sample of 24 patients (12 active and 12 sham), active stimulation was associated with significant pre- and post-treatment modulation of three FC pairs, involving the default mode network (DMN), amygdala, salience network (SN) and striatum. The most robust finding was the SNT effect on amygdala-DMN FC (group*time interaction F(1,22) = 14.89, p < 0.001). This FC change correlated with improvement in depressive symptoms (rho (Spearman) = −0.45, df = 22, p = 0.026). The post-treatment FC pattern showed a change in the direction of the healthy control group and was sustained at the one-month follow-up. These results are consistent with amygdala-DMN connectivity dysfunction as an underlying mechanism of TRD and bring us closer to the goal of developing imaging biomarkers for TMS treatment optimization.Trial registration: ClinicalTrials.gov NCT03068715

Transcranial and Transcutaneous Stimulation for Pain: What Have We Learned From the COVID-19 Pandemic Shutdown?

BACKGROUND: Transcranial magnetic stimulation (TMS) and transcutaneous magnetic stimulation (tMS) offer a novel noninvasive treatment option for chronic pain. While the recent COVID-19 pandemic caused by the SARS-CoV-2 virus resulted in a temporary interruption of the treatments for patients, it provided an excellent opportunity to assess the long-term sustainability of the treatment, and the feasibility of resuming the treatments after a brief period of interruption as no such data are available in current literature. METHODS: First, a list of patients whose pain/headache conditions have been stably controlled with either treatment for at least 6 months prior to the 3-month pandemic-related shutdown was generated. Those who returned for treatments after the shutdown were identified and their underlying pain diagnoses, pre- and posttreatment Mechanical Visual Analog Scale (M-VAS) pain scores, 3-item Pain, Enjoyment, and General Activity (PEG-3), and Patient Health Questionnaire-9 scores were assessed in 3 phases: Phase I (P1) consisted of a 6-month pre-COVID-19 period in which pain conditions were stably managed with either treatment modality; Phase II (P2) consisted of the first treatment visit period immediately after COVID-19 shutdown; and Phase III (P3) consisted of a 3-4 month post-COVID-19 shutdown period patients received up to 3 sessions of either treatment modality after the P2 treatment. RESULTS: For pre- and posttreatment M-VAS pain scores, mixed-effect analyses for both treatment groups demonstrated significant (P &lt; 0.01) time interactions across all phases. For pretreatment M-VAS pain scores, TMS (n = 27) between-phase analyses indicated a significant (F = 13.572, P = 0.002) increase from 37.7 ± 27.6 at P1 to 49.6 ± 25.9 at P2, which then decreased significantly (F = 12.752, P = 0.001) back to an average score of 37.1 ± 24.7 at P3. Similarly, tMS (n = 25) between-phase analyses indicated the mean pretreatment pain score (mean ± standard deviation [SD]) increased significantly (F = 13.383, P = 0.003) from 34.9 ± 25.1 at P1 to 56.3 ± 27.0 at P2, which then decreased significantly (F = 5.464, P = 0.027) back to an average score of 41.9 ± 26.4 at P3. For posttreatment pain scores, the TMS group between-phase analysis indicated the mean posttreatment pain score (mean ± SD) increased significantly (F = 14.206, P = 0.002) from 25.6 ± 22.9 at P1 to 36.2 ± 23.4 at P2, which then significantly decreased (F = 16.063, P &lt; 0.001) back to an average score of 23.2 ± 21.3 at P3. The tMS group between-phase analysis indicates a significant (F = 8.324, P = 0.012) interaction between P1 and P2 only with the mean posttreatment pain score (mean ± SD) increased from 24.9 ± 25.7 at P1 to 36.9 ± 26.7 at P2. The combined PEG-3 score between-phase analyses demonstrated similar significant (P &lt; 0.001) changes across the phases in both treatment groups. CONCLUSIONS: Both TMS and tMS treatment interruptions resulted in an increase of pain/headache severity and interference of quality of life and functions. However, the pain/headache symptoms, patients’ quality of life, or function can quickly be improved once the maintenance treatments were restarted. KEY WORDS: Pain, headache, transcranial magnetic stimulation (TMS), transcutaneous magnetic stimulation (tMS), COVID_19 pandemic

0416 Preliminary Study of the Effects of Continuous Theta Burst Stimulation of the Default Mode Network on Subjective Sleepiness

Abstract Introduction Repetitive transcranial Magnetic Stimulation (rTMS) is a noninvasive intervention commonly used to treat clinical depression by modulating brain activity in specific regions. We investigated rTMS of the default mode network (DMN) as a potential treatment for insomnia. The DMN is associated with internally focused cognition and rumination. Therefore, we expected that modulation of this network would improve sleep. As reported elsewhere, this trial showed that active cTBS to the DMN improved polysomnographically (PSG) measured sleep. Here, we hypothesized that participants who were treated with active continuous theta burst stimulation (cTBS) rTMS over the DMN versus sham cTBS would report reduced subjective sleepiness following post-treatment sleep. Methods Twenty adults with clinical insomnia completed this study (Mage=26.90, SD=6.56). Participants completed two overnight visits; one where they received active cTBS treatment and one where they received sham TMS treatment. We analyzed the Karolinska Sleepiness Scale (KSS), which was administered six times throughout each visit. KSS 1-3 were administered prior to treatment and KSS 4-6 were post TMS treatment. We used a repeated measures ANOVA to analyze effects of TMS on reported daytime sleepiness. Results There was no main effect of condition on sleepiness score F(1,18 )=1.165, p=0.295, ηp 2=0.061. There was a significant interaction effect of condition and pre/post intervention on reported subjective sleepiness F(1,18)=3.079, p=0.013, ηp 2 = 0.146, although follow-up analyses did not reveal significant differences. Nonetheless, there was a continuous negative trend toward reduced sleepiness for post TMS administration after overnight sleep in active cTBS (M = 4.8, SD = 1.96) compared to the sham cTBS session (M = 5.2, SD = 1.91) (p = 0.366). Conclusion As reported elsewhere, this trial of a single administration of cTBS showed improved PSG sleep. Here we saw that there was no significant change in subjective sleepiness following a night of sleep with or without the trial of cTBS, but there was a nonsignificant trend toward declining sleepiness for the active cTBS group relative to the sham condition. This preliminary study is encouraging and suggests that further research into this approach is warranted. Support (if any) W81XWH2010173

372. Early Symptom Improvement as a Predictor for TMS Treatment Outcomes in Post-Traumatic Stress Disorder

372. Early Symptom Improvement as a Predictor for TMS Treatment Outcomes in Post-Traumatic Stress Disorder

Pinpointing the precise stimulation targets for brain rehabilitation in early-stage Parkinson’s disease

BackgroundTranscranial magnetic stimulation (TMS) is increasingly used as a promising non-pharmacological treatment for Parkinson’s disease (PD). Scalp-to-cortex distance (SCD), as a key technical parameter of TMS, plays a critical role in determining the locations of treatment targets and corresponding dosage. Due to the discrepancies in TMS protocols, the optimal targets and head models have yet to be established in PD patients.ObjectiveTo investigate the SCDs of the most popular used targets in left dorsolateral prefrontal cortex (DLPFC) and quantify its impact on the TMS-induced electric fields (E-fields) in early-stage PD patients.MethodsStructural magnetic resonance imaging scans from PD patients (n = 47) and normal controls (n = 36) were drawn from the NEUROCON and Tao Wu datasets. SCD of left DLPFC was measured by Euclidean Distance in TMS Navigation system. The intensity and focality of SCD-dependent E-fields were examined and quantified using Finite Element Method.ResultsEarly-stage PD patients showed an increased SCDs, higher variances in the SCDs and SCD-dependent E-fields across the seven targets of left DLPFC than normal controls. The stimulation targets located on gyral crown had more focal and homogeneous E-fields. The SCD of left DLPFC had a better performance in differentiating early-stage PD patients than global cognition and other brain measures.ConclusionSCD and SCD-dependent E-fields could determine the optimal TMS treatment targets and may also be used as a novel marker to differentiate early-stage PD patients. Our findings have important implications for developing optimal TMS protocols and personalized dosimetry in real-world clinical practice.

Individualizing TMS treatment targets for PTSD using neuroimaging: Preliminary findings from an ongoing clinical trial

Individualizing TMS treatment targets for PTSD using neuroimaging: Preliminary findings from an ongoing clinical trial