Dorsolateral Prefrontal Cortex rTMS Research Articles

Impact of high-frequency rTMS combined with pharmacotherapy on the left dorsolateral prefrontal cortex in treating major depressive disorder: A real-world study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) combined with pharmacotherapy is a promising treatment method for depression. However, its treatment mechanism needs further research. MethodsThis study recruited 38 healthy individuals (HC) and 52 patients with severe depression (MDD) and divided patients into two treatment groups: the rTMS combined antidepressant (rTMS+ADP) group and the single antidepressant (ADP) group. We used functional magnetic resonance imaging to calculate the fractional amplitude of low-frequency fluctuations (fALFF) in the left dorsolateral prefrontal cortex (DLPFC) to investigate the functional change after treatment. ResultThe fALFF in the left DLPFC was significantly lower in the MDD group than that in the HC group (p < 0.05). In addition, fALFF values of the left DLPFC negatively correlated with HAMD-24 scores (r = −0.294, p = 0.005). After treatment, both MDD groups showed a significant decrease in HAMD-24 scores, with a response rate of 88.89 % and a remission rate of 62.96 % in the rTMS+ADP group, compared to 64 % response and 56 % remission rates in the ADP group. The fALFF values in patients' left DLPFC significantly reduced in the rTMS+ADP group (p < 0.05), but not in the ADP group. LimitationsOur study only focused on the treatment effect in the left DLPFC, without exploring the other brain regions or networks. ConclusionsThis study emphasizes the significance of the left DLPFC in MDD treatment. However, combined left DLPFC rTMS with ADP causes deviation from the normal resting brain function of the left DLPFC, indicating that future research should explore targeted treatment methods to normalize the left DLPFC.

The Role of Repetitive Transcranial Magnetic Stimulation in Reduction of Opioid Craving; A Single Blinded Randomized Sham Controlled Clinical Trial

Abstract Background Opioid use disorder (OUD) poses a great concern due to problems associated with their abuse as well as fatal and non fatal overdose consequences. Craving has a complex relationship with opioid use and relapse. Developing new, effective treatments for substance use disorders (SUDs), including opioid use disorders is crucial. This study aimed to assess the effect of 18 sessions of high frequency (HF) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on opioid craving in early abstinence using brief substance craving scale (BSCS) for Tramadol and morphine and Heroin craving questionnaire (HCQ) for Heroin craving. Results There was a statistically significant reduction in craving scores in the group of OUD patients receiving real rTMS compared to those receiving sham rTMS for both BSCS( p value = 0.044) and HCQ (p value = 0.002). A statistically significant positive correlation was revealed between the number of hospital admissions and the mean scores of post rTMS HCQ scores (r = 0.05, p value = 0.040). Conclusion High frequency 10 Hz rTMS over the left DLPFC for 18 treatment sessions reduced craving OUD patients during early abstinence. These preliminary results suggest that 10 Hz rTMS of the left DLPFC may be used in treatment of OUD; so our study recommends that use of rTMS in reduction of opioid craving in early abstinence.

Transcranial Magnetic Stimulation–Induced Plasticity Improving Cognitive Control in Obsessive-Compulsive Disorder, Part I: Clinical and Neuroimaging Outcomes From a Randomized Trial

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for obsessive-compulsive disorder (OCD). The neurobiological mechanisms of rTMS in OCD have been incompletely characterized. We compared clinical outcomes and changes in task-based brain activation following 3 different rTMS protocols, all combined with exposure and response prevention. MethodsIn this 3-arm proof-of-concept randomized trial, 61 treatment-refractory adult patients with OCD received 16 sessions of rTMS immediately before exposure and response prevention over 8 weeks, with task-based functional magnetic resonance imaging scans and clinical assessments before and after treatment. Patients received high-frequency rTMS to the left dorsolateral prefrontal cortex (n = 19 [13 women/6 men]), high-frequency rTMS to the left pre-supplementary motor area (preSMA) (n = 23 [13 women/10 men]), or control rTMS to the vertex (n = 19 [13 women/6 men]). Changes in task-based functional magnetic resonance imaging activation before/after treatment were compared using both a Bayesian region of interest and a general linear model whole-brain approach. ResultsMean OCD symptom severity decreased significantly in all treatment groups (Δ = −10.836, p < .001, 95% CI −12.504 to −9.168), with no differences between groups. Response rate in the entire sample was 57.4%. The dorsolateral prefrontal cortex rTMS group showed decreased planning-related activation after treatment that was associated with greater symptom improvement. No group-level activation changes were observed for the preSMA and vertex rTMS groups. Participants in the preSMA group with greater symptom improvement showed decreased error-related activation, and symptom improvement in the vertex group was associated with increased inhibition-related activation. ConclusionsrTMS to preSMA and dorsolateral prefrontal cortex combined with exposure and response prevention led to activation decreases in targeted task networks in individuals showing greater symptom improvement, although we observed no differences in symptom reduction between groups.

The effect of high-frequency rTMS over left DLPFC and fluid abilities on goal neglect

Goal neglect refers to when an aspect of task instructions is not utilised due to increased competition between goal representations, an attentional limit theoretically linked to working memory. In an attempt to alleviate goal neglect and to investigate the association between dorsolateral prefrontal cortex (DLPFC)-supported working memory and goal neglect, we used high-frequency repetitive transcranial magnetic stimulation to the left DLPFC whilst participants completed the letter-monitoring task, a measure of goal neglect, and an N3-back task, a working memory task known to be affected by rTMS of the left DLPFC, following 20 min of active and sham stimulation (run on separate days). We found increased accuracy on the N3-back task in addition to decreased goal neglect in the active compared to sham condition when controlling for age and fluid abilities (as assessed by matrix reasoning performance). Furthermore, analysis showed that active stimulation improvements on both the N3-back and letter-monitoring tasks were greater for those with higher fluid abilities. These findings provide support for the link between the DLPFC-support working memory and goal neglect. Increased performance on the N3-back task also supports the literature reporting a link between left DLPFC and verbal working memory. Results are evaluated in the context of potential use to alleviate symptoms of disorders related to goal neglect.

Efficacy of non-invasive brain stimulation for disorders of consciousness: a systematic review and meta-analysis.

The aim of this study is to evaluate the efficacy of non-invasive brain stimulation (NIBS) in patients with disorders of consciousness (DoC) and compare differences in efficacy between different stimulation modalities. We searched the PubMed, Cochrane Library, Web of Science, and EMBASE databases for all studies published in English from inception to April 2023. Literature screening and quality assessment were performed independently by two investigators. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to evaluate the therapeutic effects of NIBS. The Cochrane Q test and I2 statistic were used to evaluate heterogeneity between studies. Subgroup analysis was performed to identify the source of heterogeneity, and differences in efficacy between different stimulation modalities were compared by Bayesian analysis. A total of 17 studies with 377 DoC patients were included. NIBS significantly improved the state of consciousness in DoC patients when compared to sham stimulation (WMD: 0.81; 95% CI: 0.46, 1.17; I2 = 78.2%, p = 0.000). When divided into subgroups according to stimulation modalities, the heterogeneity of each subgroup was significantly lower than before (I2: 0.00-30.4%, p >0.05); different stimulation modalities may be the main source of such heterogeneity. Bayesian analysis, based on different stimulation modalities, indicated that a patient's state of consciousness improved most significantly after repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Diagnosis-based subgroup analysis showed that NIBS significantly improved the state of consciousness in patients with a minimal consciousness state (WMD: 1.11; 95% CI: 0.37, 1.86) but not in patients with unresponsive wakefulness syndrome or a vegetative state (WMD: 0.31; 95% CI: -0.09, 0.71). Subgroup analysis based on observation time showed that single treatment did not improve the state of consciousness in DoC patients (WMD: 0.28; 95% CI: -0.27, 0.82) while multiple treatments could (WMD: 1.05; 95% CI: 0.49, 1.61). Furthermore, NIBS had long-term effects on DoC patients (WMD: 0.79; 95% CI: 0.08-1.49). Available evidence suggests that the use of NIBS on patients with DoC is more effective than sham stimulation, and that rTMS of the left DLPFC may be the most prominent stimulation modality.

The role of repetitive transcranial magnetic stimulation in reduction of opioid craving: a single-blinded randomized sham-controlled clinical trial

BackgroundOpioid use disorder (OUD) poses a great concern due to problems associated with their abuse as well as fatal and non-fatal overdose consequences. Craving has a complex relationship with opioid use and relapse. Developing new, effective treatments for substance use disorders (SUDs), including opioid use disorders is crucial. This study aimed to assess the effect of 18 sessions of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on opioid craving in 26 OUD male patients compared to sham rTMS in 26 OUD patients, during early abstinence, with craving assessment using brief substance craving scale (BSCS) for tramadol and morphine and heroin craving questionnaire (HCQ) for heroin craving.ResultsThere was a statistically significant reduction in craving scores in the group of OUD patients receiving real rTMS compared to those receiving sham rTMS for both BSCS (p value = 0.044) and HCQ (p value=0.002). A statistically significant positive correlation was revealed between the number of hospital admissions and the mean scores of post-rTMS HCQ scores (r=0.05, p value= 0.040).ConclusionsA high frequency of 10-Hz rTMS over the left DLPFC for 18 treatment sessions reduced craving OUD patients during early abstinence. These preliminary results suggest that 10-Hz rTMS of the left DLPFC may be used in the treatment of OUD, so our study recommends that the use of rTMS in the reduction of opioid craving in early abstinence.Trial registrationUnique identification number PACTR202206487514449 in the Pan African Clinical Trial Registry retrospectively (www.pactr.org) registered on 10 June 2022.

Repetitive transcranial magnetic stimulation: Course and early prediction of response in depression

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, yet few studies have mapped the trajectories of symptom change over treatment. Tracking clinical response during early treatment may be helpful to predict outcome, particularly non-response. MethodsWe used naturalistic data (N = 117) to examine changes in the Daily Symptom Index (DI-5) scores of adult patients with unipolar or bipolar depression who underwent ≥16 treatment sessions of left dorsolateral prefrontal cortex rTMS at a private psychiatric facility in Western Australia, between 2016 and 2019. ResultsTwo response trajectories were charted: non-response (N = 71, 61%) and response (N = 46, 39%). Both trajectories diverged at 99% confidence interval at session 10, which was used as the point to predict treatment response at session 20. The response group showed a reduction of 4.21 in the mean DI-5 score from baseline at session 10. On this basis, a 4-point reduction in the DI-5 score at session 10 was defined as predictor of responder status at session 20. If the improvement is < 4 points at session 10, the probability of non-response at session 20 is 75%. If the improvement is ≥ 4 points, the probability of response at session 20 is 66%. LimitationsThe DI-5 scores were not examined beyond 20 treatment sessions, which may have shown delayed responders in the non-response group. ConclusionsIn this study of depression response trajectories with rTMS treatment, prediction of response at session 20 can be made at session 10 of treatment. Further research is required to generalise the current findings.

Comparative efficacy of high-frequency repetitive transcranial magnetic stimulation to left dorsolateral prefrontal cortex as an augmentation strategy versus pharmacological augmentation in non-psychotic, unipolar, treatment-resistant depression: A randomized controlled trial.

Depression causes significant morbidity, disability and mortality, along with socioeconomic losses. Patients with depression who don't remit even with the second trial of anti-depressants need optimization, combination or augmentation strategies. Pharmacological strategies sometimes have unacceptable adverse effects. The aim of this study is to compare the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to left dorsolateral prefrontal cortex (DLPFC) with that of pharmacological augmentation strategies in unipolar non-psychotic treatment-resistant depression. This is a randomized controlled trial. Cases of unipolar, non-psychotic, treatment-resistant depression between ages 20 and 60 years were taken. The study period was from November 2016 to May 2018. Cases diagnosed as per ICD-10 criteria by a qualified psychiatrist. Cases of treatment-resistant depression (100) were divided into two arms by using a random number generator: rTMS arm and treatment as usual (TAU) arm. HF-rTMS to left DLPFC (rTMS group) and pharmacological augmentation with lithium, serotonin-dopamine antagonist, buspirone or thyroxine. In the rTMS arm, 44 patients and in TAU arm 41 completed the study. After 4 weeks of treatment augmentation, rTMS and TAU groups showed response rates of 52% and 46%, respectively. The difference between the two groups in terms of number of responders at the end of 4 weeks is not statistically significant. Additionally, factors associated with good response to rTMS were absence of a family history of psychiatric illness, no concomitant psychoactive substance use, being first episode of depression and mild-moderate severity of illness. The study did not find rTMS augmentation to be significantly better than standard pharmacological augmentation therapies.

Effects of Repetitive Transcranial Magnetic Stimulation on Gait and Postural Control Ability of Patients with Executive Dysfunction after Stroke.

Objective: To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on the gait and postural control ability of patients with executive dysfunction (ED) after stroke. Methods: A total of 18 patients with ED after stroke were randomly assigned into two groups, including an experimental group and a sham group. Patients in both groups received routine rehabilitation therapy, and patients in the experimental group underwent rTMS on the left dorsolateral prefrontal cortex (DLPFC) for 2 weeks (5 HZ, 80%MT, 1200 pulses). In the sham group, patients experienced sham stimulation treatment, in which the coil was placed vertically with the head. Before and after treatment, patients in both groups were subjected to Montreal cognitive assessment (MoCA) scoring, Fugl–Meyer assessment of lower extremity (L-FMA), Stroop color-word test (SCWT), gait analysis, foot plantar pressure test, 10-m walking test (10MWT), Berg balance scale (BBS), and timed up and go test (TUGT). In the SCWT, it was attempted to record the time of each card (SCWT-T), the correct number (SCWT-C), Stroop interference effect-time (SIE-T), and SIE correct count (SIE-C). The TUGT was categorized into four stages: getting up (GT), walking straight (WT), turning around (TT), and sitting down (ST), in which the total time of TUGT was calculated. Results: After two weeks of treatment, the evaluation indexes were improved in the two groups, some of which were statistically significant. In the experimental group, SCWT-T, SIE-T, SIE-C, GT, WT, TT, ST, and TUGT were significantly improved after treatment (p < 0.05). SCWT-C, L-FMA score, 10MWT, GT, WT, stride length, step width, foot plantar pressure, pressure center curve, and activities of daily living were not statistically different from those before treatment (p > 0.05). After treatment, SCWT-T, SIE-C, SIE-T, BBS score, TT, and ST in the experimental group were significantly shorter than those before treatment, with statistical differences (p < 0.05). Compared with the sham group, SCWT-C, L-FMA score, 10MWT, GT, WT, TUGT, stride length, step width, foot plantar pressure, pressure center curve, and motor skills were not significantly improved (p > 0.05). Conclusion: It was revealed that post-stroke rTMS treatment of patients with ED could improve executive function, improve postural control function, and reduce the risk of falling. In addition, rTMS of DLPFC could be a therapeutic target for improving postural control ability and reducing the risk of falling.

Cardiovascular biomarkers of response to accelerated low frequency repetitive transcranial magnetic stimulation in major depression

Background and objectiveRepetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for major depressive disorder (MDD). rTMS is in need of a reliable biomarker of treatment response. High frequency (HF) dorsolateral prefrontal cortex (DLPFC) rTMS has been reported to induce significant changes in the cardiac activity of MDD patients. Low frequency DLPFC rTMS has many advantages over HF-DLPFC rTMS and thus this study aims to further investigate the effect of low frequency 1 Hz right hemisphere (R)-DLPFC rTMS on the cardiac activity of MDD patients, as well as the potential of using electrocardiogram (ECG) parameters as biomarkers of treatment outcome. MethodsBaseline ECG sessions were performed for 19 MDD patients. All patients then underwent 40 sessions of accelerated 1 Hz R-DLPFC rTMS one week after the baseline session. ResultsHeart rate (HR) significantly decreased from the resting period to the first and third minute of the 1 Hz R-DLPFC rTMS period. Resting HR was found to have a significant negative association with treatment outcome. Prior to Bonferroni correction, HR during stimulation and the degree of rTMS-induced HR reduction were significantly negatively associated with treatment outcome. No significant changes were observed for the heart rate variability (HRV) parameters. LimitationsSample size (n = 19); the use of electroencephalography equipment for ECG; lack of respiration monitoring; relatively short recording duration for HRV parameters. ConclusionThis novel study provides further preliminary evidence that ECG may be utilized as a biomarker of rTMS treatment response in MDD. Trial registrationClinicalTrials.gov Identifier: NCT04376697.

Possible replacement of augmenting medication in treatment-resistant depression by transcranial magnetic stimulation

Abstract Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. As the left prefrontal cortex activity is linked to depression, rTMS induces blood flow in the left dorsolateral prefrontal cortex. We used rTMS in a middle-aged male patient with depression who had discontinued psychostimulant medication over a 12-month period. He had been consistently taking dextroamphetamine-amphetamine extended release 30 mg once daily prior to the onset of rTMS treatment. The patient achieved depression remission through 39 sessions of high-frequency left dorsolateral prefrontal cortex rTMS treatments. We assessed disease progression using the Quick Inventory of Depressive Symptomatology, and we measured blood pressure before each session of rTMS. After tapering the dextroamphetamine-amphetamine extended release from 30 mg to 10 mg, the patient's score on the Quick Inventory of Depressive Symptomatology increased slightly to 7 and then dropped to 0. The results indicate that interval rTMS can lower blood pressure and may be an alternative to adjunctive psychostimulants.

Acceptability, safety and tolerability of antidepressant repetitive transcranial magnetic stimulation for adolescents: A mixed-methods investigation

ObjectiveMajor depressive disorder (MDD) is relatively common in adolescence, with far-reaching impacts. Current treatments frequently fail to alleviate depression severity for a substantial portion of adolescents. Repetitive transcranial magnetic stimulation (rTMS) may assist with this unmet clinical need. However, little is known about adverse events (AEs) experienced by adolescents receiving rTMS, subjective treatment experiences of adolescents and their parents, or treatment acceptability. MethodsFourteen adolescents (16.5 years ± 1.2; 71.4% female) with MDD received 20 sessions of either high-frequency (10 Hz; n = 7) left dorsolateral prefrontal cortex (DLPFC) or low-frequency (1 Hz; n = 7) right DLPFC rTMS. AEs were monitored at baseline and at weekly intervals via New York State Psychiatric Institute Side Effects Form for Children and Adolescents. Eight adolescents and nine parents participated in interviews regarding subjective treatment experience, analysed via content analysis. ResultsDrowsiness and lethargy were common AEs, reported by 92.3% of participants in week one. Number of AEs decreased throughout treatment course (after 5 treatments: M = 11.23, SD = 5.00; after 20 treatments: M = 8.92, SD = 5.95). Thirty-five AEs emerged during treatment, most commonly transient dizziness. Frequency, severity, and number of AEs reported were equivalent between treatment groups. Treatment adherence and satisfaction were high. Qualitative findings identified three themes relating to rTMS experience: Preparation and connection; Physical experience of treatment; and Perceived role of treatment. LimitationsSample size was small, therefore findings are preliminary. ConclusionsrTMS was an acceptable treatment for adolescent MDD, from both adolescents' and parents' perspectives, and was safe and well-tolerated, as AE frequency and type did not differ from rTMS treatment courses in adults.

Increased Prefrontal Activation During Verbal Fluency Task After Repetitive Transcranial Magnetic Stimulation Treatment in Depression: A Functional Near-Infrared Spectroscopy Study.

BackgroundPrevious studies have shown the clinical effect of 2 Hz repetitive transcranial magnetic stimulation (rTMS) for depression; however, its underlying neural mechanisms are poorly understood. The aim of this study was to examine the effects of rTMS on the activity of the prefrontal cortex in patients with depression, using functional near-infrared spectroscopy (fNIRS).MethodsForty patients with major depressive disorder (MDD) and 40 healthy controls were enrolled in this study. Patients underwent 4 weeks of 2 Hz TMS delivered to the right dorsolateral prefrontal cortex (DLPFC). fNIRS was used to measure the changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex during a verbal fluency task (VFT) in depressed patients before and after rTMS treatment. The severity of depression was assessed using the Hamilton Rating Scale for Depression-24 item (HAMD-24).ResultsPrior to rTMS, depressed patients exhibited significantly smaller [oxy-Hb] values in the bilateral prefrontal cortex during the VFT compared with the healthy controls. After 4 weeks of 2 Hz right DLPFC rTMS treatment, increased [oxy-Hb] values in the bilateral frontopolar prefrontal cortex (FPPFC), ventrolateral prefrontal cortex (VLPFC) and left DLPFC during the VFT were observed in depressed patients. The increased [oxy-Hb] values from baseline to post-treatment in the right VLPFC in depressed patients were positively related to the reduction of HAMD score following rTMS.ConclusionThese findings suggest that the function of the prefrontal cortex in depressed patients was impaired and could be recovered by 2 Hz rTMS. The fNIRS-measured prefrontal activation during a cognitive task is a potential biomarker for monitoring depressed patients’ treatment response to rTMS.

Effects of repeated transcranial magnetic stimulation in the dorsolateral prefrontal cortex versus motor cortex in patients with neuropathic pain after spinal cord injury: a study protocol

IntroductionNeuropathic pain is one of the common complications of spinal cord injuries (SCI), which will slow down the recovery process and result in lower quality of life. Previous studies have...

Treatment of anxiety symptoms in patients receiving rTMS for treatment resistant depression

This retrospective analysis examined the effects of left-sided dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on comorbid anxiety symptoms patients with treatment resistant depression (TRD). Response rates, remission rates, reliable change index (RCI), and clinically significant change (CSC) were assessed using the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety subscale at over an average of 32.9 treatments ( SD ​= ​9.2). Fifty-seven TRD patients showed statistically and clinically significant improvement in all anxiety measurements with left DLPFC rTMS. This retrospective study had no sham control and allowed for medication changes during the rTMS treatment course. Left DLPFC rTMS may be an important tool in reducing anxiety in TRD patients, improving overall treatment resistant symptoms and suicide risk. • Anxious depression is associated with more suicide risk and treatment resistance. • Transcranial Magnetic Stimulation (TMS) may be a treatment option. • TMS improved anxiety in patients with treatment resistant depression and anxiety.

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.

Repetitive Transcranial Magnetic Stimulation for Tobacco Treatment in Cancer Patients: A Preliminary Report of a One-Week Treatment.

Background Smoking cessation represents a significant opportunity to improve cancer survival rates, reduces the risk of cancer treatment complications, and improves quality of life. However, about half of cancer patients who smoke continue to smoke despite the availability of several treatments. Previous studies demonstrate that repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) decreases cue craving, reduces cigarette consumption, and increases the quit rate in tobacco use disorder. We investigated whether 5 sessions of rTMS can be safely and efficaciously used for smoking cessation in cancer patients. Methods We enrolled 11 treatment-seeking smokers with cancer (>5 cigarettes per day) in a randomized, double-blind, sham-controlled proof-of-concept study. Participants received 5 daily sessions of active 10 Hz rTMS of the left DLPFC (3000 pulses per session) or sham rTMS and were followed up for 1 month via phone assessments. Main outcomes included reductions in the number of smoked-cigarettes per day (primary) and craving (secondary). Adverse effects were reported daily by participants. Results Seven of 11 participants completed 5 sessions of rTMS over one week. Compared to sham treatment (n = 4), the active rTMS (n = 3) exhibited modest effects overtime on smoking (Cohen's f2 effect size of 0.16) and large effects on cue craving (Cohen′s f2 = 0.40). No serious side effects related to rTMS were reported in the treatment. Conclusions Five sessions of daily rTMS over the left DLPFC might benefit cancer patients who smoke cigarettes. However, further evidence is needed to determine with more certainty its therapeutic effect and adverse effects for cancer patients who smoke cigarettes.

Right orbitofrontal TMS as a fallback after unsuccessful DLPFC rTMS?

Abstract Repetitive transcranial magnetic stimulation (rTMS) as a treatment in major depressive disorder (MDD) conventionally targets the dorsolateral prefrontal cortex (DLPFC). It is deemed clinically effective, yet there is still at least 44% of MDD patients not achieving remission. 1 Hz right orbitofrontal cortex (OFC) stimulation was developed as a relatively new target for rTMS treatment, based on, and adding to the theory of its role in ”non-reward” signaling in MDD. A first study shows a response rate of 30% (at least 50% reduction of MDD symptoms) in those not responding to dorsomedial prefrontal cortex targeted rTMS in an earlier stage (Feffer et al., 2018). Implementing this experimental protocol, we offered 1 Hz OFC TMS to 16 patients with MDD in two outpatient clinics in the Netherlands. Their complete rTMS treatment consisted of 75 sessions on average, of which 30 sessions were OFC targeted. The average moment of switch to OFC TMS was after 44 sessions of DLPFC stimulation. The average age was 53.5 years (SD = 13.0) and 54% are female. Collected data includes clinical history, medication, stimulation parameters, and illness severity over the course of treatment, based on a self-rated symptom scale and clinical evaluation. Through these and other additional data, we will investigate response and remission in this sample and predictive factors of treatment success, developing stratification methods based on baseline EEG and psychological factors. Given clinically observed behavior in OFC TMS responders, we hypothesize that patients can be stratified to OFC TMS in an earlier stage, hopefully aiding to battle depression treatment resistance. Feffer, K., Fettes, P., Giacobbe. P., Daskalakis, Z.J., Blumberger, D.M., Downar, J., 2018. 1 Hz rTMS of the right orbito frontal cortex for major depression: Safety, tolerability and clinical outcomes. European Neuropsychopharmacology, 28, 109-117. https://doi.org/10.1016/j.euroneuro.2017.11.011 Keywords: OFC TMS, Depression, Treatment stratification, rTMS

Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Executive Function and Its Neural Mechanism: An Event-Related Potential Study.

Objective: Executive function refers to the conscious control of thinking and behavior in psychological process. Executive dysfunction widely exists in a variety of neuropsychiatric diseases, and is closely related to the decline of daily living ability and function. This study intends to explore the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on executive function and its neural mechanism by using event-related potential (ERP), so as to provide basis for further study on the relationship between cerebral cortex and executive function.Methods: Task switching paradigm was used to study the cognitive flexibility in executive function. Thirty-one healthy subjects were randomly assigned to receive rTMS stimulations (1 Hz rTMS or sham rTMS) to the left dorsolateral prefrontal cortex (DLPFC) twice. The switching task and the electroencephalography EEG recordings were performed before (pre-rTMS/pre-sham rTMS) and immediately after the end of the rTMS application (post-rTMS/post-sham rTMS).Results: The analysis of RTs showed that the main effects of switching and time were statistically significant. Further analysis revealed that the RT of rTMS stimulation was longer than sham rTMS at post-stimulation. ERP analysis showed that there was a significant switching effect in frontal and central scalp location, and the P2 amplitude in switch trials was greater than that in non-switch trials. At post-stimulation, the N2 amplitude of rTMS is more negative than that of sham rTMS at non-switch trials, whereas no such difference was found at switch trials. The P3 amplitude and LPC amplitude are significantly reduced by rTMS at post-stimulation.Conclusion: Low-frequency rTMS of the left DLPFC can cause decline of cognitive flexibility in executive function, resulting in the change of N2 amplitude and the decrease of P3 and LPC components during task switching, which is of positive significance for the evaluation and treatment of executive function.

Efficacy and Safety Evaluation of High-Frequency Repetitive Transcranial Magnetic Stimulation on Negative Symptoms of Schizophrenia

There are currently no approved treatments for working memory deficits in schizophrenia spectrum disorders (SSDs). The objective of the present study was to assess whether repetitive transcranial magnetic stimulation (rTMS) to the bilateral dorsolateral prefrontal cortex (DLPFC) in people with SSDs 1) improves working memory deficits and 2) changes brain structure.We conducted a double-blind, parallel, randomized, sham-controlled study at the Centre for Addiction and Mental Health in Toronto, Canada. We randomized 83 participants with SSDs to receive either active 20 Hz rTMS applied to the bilateral DLPFC or sham rTMS for 4 weeks. The participants also completed pre/posttreatment magnetic resonance imaging. Clinical and cognitive assessments were performed at baseline, treatment end, and 1 month later. The primary outcome was change in verbal n-back working memory performance accuracy (d-prime). The secondary outcome measures were change in DLPFC thickness and fractional anisotropy of white matter tracts connecting to the DLPFC. Prespecified exploratory outcome measures were changes in general cognition; positive, negative, and depressive symptoms.Compared with sham treatment, active rTMS did not lead to significant change in working memory performance; it was associated with an increase in right DLPFC thickness but not fractional anisotropy. Prespecified exploratory analysis showed a significant decrease in depressive symptoms in the active group; the decrease in depressive symptoms was correlated with an increase in right DLPFC thickness.Although rTMS applied to the bilateral DLPFC was not efficacious in treating working memory deficits in SSDs, it did increase right DLPFC thickness and decrease depressive symptoms. These findings deserve further study given the lack of efficacy of antidepressant medications in SSDs.