Left 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.

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.

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.

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.

Effect of repetitive transcranial magnetic stimulation on depression and cognition in individuals with traumatic brain injury: a systematic review and meta-analysis

Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved therapy in major depressive disorder. However, its treatment efficacy on depression after traumatic brain injury (TBI) remains inconclusive. We conducted a meta-analysis to assess the effectiveness of executing rTMS over dorsolateral prefrontal cortex (DLPFC) on depression, cognitive impairment and post-concussion syndrome in individuals with traumatic brain injury. This study contained seven randomized controlled trials that published before April 5, 2020 in PubMed, Embase, Scopus, Cochrane, and Web of Science databases. The rTMS had significant anti-depressant effect (SMD = 1.03, p = 0.02), but the effects dissipated at 1-month follow-up (SMD = 0.39, p = 0.62). In the subgroup analysis, only applying rTMS to left DLPFC area of post-TBI patients showed significant anti-depressant effect (SMD = 0.98, p = 0.04). Moreover, current data observed that rTMS on post-TBI patients possessed substantial improvement in visuospatial memory (SMD = 0.39, p < 0.0001), but wasn’t in processing speed (SMD = − 0.18, p = 0.32) and selective attention (SMD = 0.21, p = 0.31). In addition, the effect of rTMS is not superior to sham on postconcussion syndrome. In conclusion, the short-term antidepressant effect of left DLPFC rTMS in patients with TBI was significant. However, the effectiveness of rTMS on cognition and postconcussion syndrome in patients with post-TBI depression was limited.

Modification of rectal function and emotion by repetitive transcranial magnetic stimulation in humans

Gut microbiota may affect function of the dorsolateral prefrontal cortex (DLPFC). However, there have been a few studies on modification of brain-gut interactions with repetitive transcranial magnetic stimulation (rTMS) to the DLPFC. We hypothesized that stimulation of the right or left DPFC by rTMS modifies the brain-gut interactions in humans. Subjects were 25 healthy males. Viscerosensory evoked potential (VEP) with sham (0 mA) or actual (30 mA) electrical stimulation (ES) of the rectum was taken after sham, low frequency rTMS at 0.1 Hz, and high frequency rTMS at 10 Hz to the right or left DLPFC. Rectal tone was measured with a rectal barostat. Visceral perception and emotion were analyzed using ordinates scale, rectal barostat, and viscerosensory evoked potential. Low frequency rTMS to the right DLPFC significantly reduced the visceral sensation and emotion composite score evoked by ES at 30 mA (p < 0.05). Plasma ACTH was significantly increased by high frequency rTMS to the right or left DLPFC (p < 0.05). Rectal fine contractions were significantly induced by low frequency rTMS to the right or left DLPFC and high frequency rTMS to the right DLPFC (p < 0.05). These results suggest that stimulation of the right or left DPFC by rTMS modifies the brain-gut interactions in humans.

Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning

BackgroundFunctional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate (sgACC) may serve as a biomarker for transcranial magnetic stimulation (rTMS) treatment response. The first aim was to establish whether this finding is veridical or artifactually induced by the pre-processing method. Furthermore, alternative biomarkers were identified and the clinical utility for personalized medicine was examined. MethodsResting-state fMRI data were collected in medication-refractory depressed patients (n = 70, 16 males) before undergoing neuronavigated left DLPFC rTMS. Seed-based analyses were performed with and without global signal regression pre-processing to identify biomarkers of short-term and long-term treatment response. Receiver Operating Characteristic curve and supervised machine learning analyses were applied to assess the clinical utility of these biomarkers for the classification of categorical rTMS response. ResultsRegardless of the pre-processing method, DLPFC-sgACC connectivity was not associated with treatment outcome. Instead, poorer connectivity between the sgACC and three clusters (peak locations: frontal pole, superior parietal lobule, occipital cortex) and DLPFC-central opercular cortex were observed in long-term nonresponders. The identified connections could serve as acceptable to excellent markers. Combining the features using supervised machine learning reached accuracy rates of 95.35% (CI=82.94–100.00) and 88.89% (CI=63.96–100.00) in the cross-validation and test dataset, respectively. LimitationsThe sample size was moderate, and features for machine learning were based on group differences. ConclusionsLong-term nonresponders showed greater disrupted connectivity in regions involving the central executive network. Our findings may aid the development of personalized medicine for medication-refractory depression.

Evaluation of the effects of rTMS on self-reported quality of life and disability in treatment-resistant depression: A THREE-D study

IntroductionAlthough the antidepressant efficacy of rTMS is well documented, patient reported outcomes (PROs) with rTMS are poorly characterized. The aim of the current study is to assess short and long-term changes in self-reported quality of life and disability following a 6-week course of rTMS. MethodsWe performed a secondary analysis of data from the multi-centre THREE-D trial of 10 Hz high-frequency (HF) rTMS (n = 192) vs. intermittent theta-burst stimulation (iTBS) (n = 193) of the left dorsolateral prefrontal cortex (DLPFC). We assessed changes in the Quality of Life Enjoyment and Satisfaction Questionnaire and Sheehan Disability Scale pre-treatment, at 1-week post-rTMS treatment (Acute Follow-up), and at 12-weeks post-treatment (Long-Term Follow-Up). ResultsPROs significantly improved with rTMS. There were no differences in PROs between iTBS and HF left DLPFC rTMS at either the Acute or Long-Term Follow-Up. The magnitude of the change in effect sizes seen for the PROs were significantly greater in those who achieved greater resolution their depressive symptoms, with remitters demonstrating very large effect size improvements in PROs compared to small-to-medium effect sizes in non-remitters. ConclusionsThis study is the largest in the literature exploring at the effect of rTMS on PROs. rTMS yielded acute and sustained improvements in PROs. The improvements in PROs were strongly associated with the degree of resolution of depressive symptoms. The magnitude of the change in remitters was comparable to those reported with ECT. The goal of a course of rTMS should be for full remission of depressive symptoms in order to achieve optimal functional outcomes.

Brain oscillation-synchronized stimulation of the left dorsolateral prefrontal cortex in depression using real-time EEG-triggered TMS

BackgroundRepetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an effective treatment for major depressive disorder (MDD), but response rates are low and effect sizes small. Synchronizing TMS pulses with instantaneous brain oscillations can reduce variability and increase efficacy of TMS-induced plasticity. ObjectiveTo study whether brain oscillation-synchronized rTMS is feasible, safe and has neuromodulatory effects when targeting the DLPFC of patients with MDD. MethodsUsing real-time EEG-triggered TMS we conducted a pseudo-randomized controlled single-session crossover trial of brain oscillation-synchronized rTMS of left DLPFC in 17 adult patients with antidepressant-resistant MDD. Stimulation conditions in separate sessions were: (1) rTMS triggered at the negative EEG peak of instantaneous alpha oscillations (alpha-synchronized rTMS), (2) a variation of intermittent theta-burst stimulation (modified iTBS), and (3) a random alpha phase control condition. ResultsTriggering TMS at the negative peak of instantaneous alpha oscillations by real-time analysis of the electrode F5 EEG signal was successful in 15 subjects. Two subjects reported mild transient discomfort at the site of stimulation during stimulation; no serious adverse events were reported. Alpha-synchronized rTMS, but not modified iTBS or the random alpha phase control condition, reduced resting-state alpha activity in left DLPFC and increased TMS-induced beta oscillations over frontocentral channels. ConclusionsAlpha-synchronized rTMS of left DLPFC is feasible, safe and has specific single-session neuromodulatory effects in patients with antidepressant-resistant MDD. Future studies need to further elucidate the mechanisms, optimize the parameters and investigate the therapeutic potential and efficacy of brain oscillation-synchronized rTMS in MDD.

Trajectories of Response to Dorsolateral Prefrontal rTMS in Major Depression: A THREE-D Study.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics. This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score ≥18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics. Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory. Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.

High frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex modulates sensorimotor cortex function in the transition to sustained muscle pain

Based on reciprocal connections between the dorsolateral prefrontal cortex (DLPFC) and basal-ganglia regions associated with sensorimotor cortical excitability, it was hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC would modulate sensorimotor cortical excitability induced by muscle pain. Muscle pain was provoked by injections of nerve growth factor (end of Day-0 and Day-2) into the right extensor carpi radialis brevis (ECRB) muscle in two groups of 15 healthy participants receiving 5 daily sessions (Day-0 to Day-4) of active or sham rTMS. Muscle pain scores and pressure pain thresholds (PPTs) were collected (Day-0, Day-3, Day-5). Assessment of motor cortical excitability using TMS (mapping cortical ECRB muscle representation) and somatosensory evoked potentials (SEPs) from electrical stimulation of the right radial nerve were recorded at Day-0 and Day-5. At Day-0 versus Day-5, the sham compared to active group showed: Higher muscle pain scores and reduced PPTs (P < 0.04); decreased frontal N30 SEP (P < 0.01); increased TMS map volume (P < 0.03). These results indicate that muscle pain exerts modulatory effects on the sensorimotor cortical excitability and left DLPFC rTMS has analgesic effects and modulates pain-induced sensorimotor cortical adaptations. These findings suggest an important role of prefrontal to basal-ganglia function in sensorimotor cortical excitability and pain processing.

Left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation reduces the development of long-term muscle pain.

The left dorsolateral prefrontal cortex (DLPFC) is involved in the experience and modulation of pain, and may be an important node linking pain and cognition. Repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC can reduce chronic and experimental pain. However, whether left DLPFC rTMS can influence the development of chronic pain is unknown. Using repeated intramuscular injection of nerve growth factor to induce the development of sustained muscle pain (lasting weeks), 30 healthy individuals were randomized to receive 5 consecutive daily treatments of active or sham left DLPFC rTMS, starting before the first nerve growth factor injection on day 0. Muscle soreness and pain severity were collected daily for 14 days and disability on every alternate day. Before the first and 1 day after the last rTMS session, anxiety, depression, affect, pain catastrophizing, and cognitive performance on the attention network test were assessed. Left DLPFC rTMS treatment compared with sham was associated with reduced muscle soreness, pain intensity, and painful area (P < 0.05), and a similar trend was observed for disability. These effects were most evident during the days rTMS was applied lasting up to 3 days after intervention. Depression, anxiety, pain catastrophizing, and affect were unchanged. There was a trend toward improved cognitive function with rTMS compared with sham (P = 0.057). These data indicate that repeated left DLPFC rTMS reduces the pain severity in a model of prolonged muscle pain. The findings may have implications for the development of sustained pain in clinical populations.

Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms

Persistent mild traumatic brain injury related headache (MTBI-HA) represents a neuropathic pain state. This study tested the hypothesis that repetitive transcranial magnetic stimulation (rTMS) at the left prefrontal cortex can alleviate MTBI-HA and associated neuropsychological dysfunctions. Veterans with MTBI-HA were randomized to receive four sessions of either real (REAL group) or sham (SHAM group) high frequency rTMS delivered at 10 Hz, 80% of resting motor threshold and 2000 pulses per session at >24 and <72 hours apart. Pre-treatment, post-treatment 1-week and 4-week headache and neuropsychological assessments were conducted. Twenty nine out of forty-four consented subjects completed the study. A two-factor (visit × treatment) repeated measures ANOVA showed a significant (p = 0.002, F = 11.63, df = 1) interaction for the average daily persistent headache intensity with the REAL group exhibiting a significant (p < 0.0001) average reduction (±SD) of 25.3 ± 16.8% and 23.0 ± 17.7% reduction in their numerical rating scale at the one-week and four-week post-treatment assessments in comparison to <1 ± 11.7% and 2.3 ± 14.5% reduction found in the SHAM group. In addition, a significant (p < 0.01) 50% and 57% reduction was found in the prevalence of persistent headache in the REAL group at the one-week and four-week assessments in comparison to 7% and 20% reduction found in the SHAM group. Furthermore, the REAL group demonstrated a significant (p = 0.033) improvement (from 22.3 ± 6.4 at pre-treatment to 19.0 ± 5.0 at post-treatment one-week) in the Hamilton Rating Scale for Depression score, while the SHAM group's score remained largely unchanged (from 25.33 ± 8.43 to 24.64 ± 5.03) in the same time frame. This trend of improvement, although not statistically significant, continues to the post-treatment four-week assessment. A short-course rTMS at the left DLPFC can alleviate MTBI-HA symptoms and provide a transient mood enhancing benefit. Further studies are required to establish a clinical protocol balancing both treatment efficacy and patient compliance.

Left dorsolateral prefrontal cortex rTMS in alleviating MTBI related headaches and depressive symptoms

Left dorsolateral prefrontal cortex rTMS in alleviating MTBI related headaches and depressive symptoms

Network-wise cerebral blood flow redistribution after 20 Hz rTMS on left dorso-lateral prefrontal cortex

The repetitive application of transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) has been consistently shown to be beneficial for treating various neuropsychiatric or neuropsychological disorders, but its neural mechanisms still remain unclear. The purpose of this study was to measure the effects of high-frequency left DLPFC rTMS using cerebral blood flow (CBF) collected from 40 young healthy subjects before and after applying 20 Hz left DLPFC rTMS or SHAM stimulations. Relative CBF (rCBF) changes before and after 20 Hz rTMS or SHAM were assessed with paired-t test. The results show that 20 Hz DLPFC rTMS induced CBF redistribution in the default mode network, including increased rCBF in left medial temporal cortex (MTC)/hippocampus, but reduced rCBF in precuneus and cerebellum. Meanwhile, SHAM stimulation didn’t produce any rCBF changes. After controlling SHAM effects, only the rCBF increase in MTC/hippocampus remained. Those data suggest that the beneficial effects of high-frequency rTMS may be through a within-network rCBF redistribution.

Rostral anterior cingulate cortex is a structural correlate of repetitive TMS treatment response in depression

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an effective treatment for medication-refractory major depression, yet the mechanisms of action for this intervention are poorly understood. Here we investigate cerebral cortex thickness as a possible biomarker of rTMS treatment response. MethodsLongitudinal change in cortical thickness is evaluated relative to clinical outcomes across 48 participants in 2 cohorts undergoing left dorsolateral prefrontal cortex rTMS as a treatment for depression. ResultsOur results reveal changes in thickness in a region of the left rostral anterior cingulate cortex that correlate with clinical response, with this region becoming thicker in patients who respond favorably to rTMS and thinner in patients with a less favorable response. Moreover, the baseline cortical thickness in this region correlates with rTMS treatment response – those patients with thinner cortex before treatment tended to have the most clinical improvement. ConclusionsThis study is the first analysis of longitudinal cortical thickness change with rTMS as a treatment for depression with similar results across two cohorts. These results support further investigation into the use of structural MRI as a possible biomarker of rTMS treatment response.

Increased Low-Frequency Resting-State Brain Activity by High-Frequency Repetitive TMS on the Left Dorsolateral Prefrontal Cortex.

Beneficial effects of repetitive transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) have been consistently shown for treating various neuropsychiatrical or neuropsychological disorders, but relatively little is known about its neural mechanisms. Here we conducted a randomized, double-blind, SHAM-controlled study to assess the effects of high-frequency left DLPFC rTMS on resting-state activity. Thirty-eight young healthy subjects received two sessions of either real rTMS (N = 18, 90% motor-threshold; left DLPFC at 20 Hz) or SHAM TMS (N = 20) and functional magnetic resonance imaging scan during rest in 2 days separated by 48 h. Resting-state bran activity was measured with the fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC). Increased fALFF was found in rostral anterior cingulate cortex (rACC) after 20 Hz rTMS, while no changes were observed after SHAM stimulation. Using the suprathreshold rACC cluster as the seed, increased FC was found in left temporal cortex (stimulation vs. group interaction). These data suggest that high-frequency rTMS on left DLPFC enhances low-frequency resting-state brain activity in the target site and remote sites as reflected by fALFF and FC.