rTMS In Major Depressive Disorder Research Articles

Effects of Chronic Pain Diagnoses on the Antidepressant Efficacy of Transcranial Magnetic Stimulation.

Major depressive disorder (MDD) and chronic pain are highly comorbid and bidirectionally related. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex is effective in treating MDD, but additional research is needed to determine if chronic pain interferes with rTMS for MDD. Participants were 124 veterans ( Mage = 49.14, SD = 13.83) scheduled for 30 sessions of rTMS across 6 weeks. Depression severity was monitored weekly using the Patient Health Questionnaire-9 (PHQ-9). Having any pain diagnosis, low back pain, or headache/migraine were assessed by chart review. We fit latent basis models to estimate total change by pain diagnosis in depression scores and quadratic latent growth models to examine differences in growth rates. Then, we computed χ2 tests of group differences in response (PHQ-9 reduction ≥50%) and remission rates (final PHQ-9 < 5). A total of 92 participants (74%) had a documented pain diagnosis, 58 (47%) had low back pain, and 32 (26%) had headache/migraine. In growth models, depression scores initially decreased (linear slope estimate = -2.04, SE = 0.26, p < .0001), but the rate of decrease slowed over time (quadratic slope estimate = 0.18, SE = 0.04, p < .001). Overall change was not different as a function of any pain diagnosis ( p = .42), low back pain (p = .11 ), or headache/migraine ( p = .28). However, we found that low back pain was a negative predictor of response ( p = .032). These data support rTMS as a viable treatment option for comorbid populations. Although patients with comorbid chronic pain conditions are likely to receive benefit from rTMS for depression, adjunctive pain treatment may be indicated.

Motor cortex repetitive transcranial magnetic stimulation in major depressive disorder - A preliminary randomized controlled clinical trial

BackgroundRepetitive transcranial magnetic stimulation (rTMS) at left dorsolateral prefrontal cortex (lDLPFC) is commonly used in major depressive disorder (MDD), even though its therapeutic efficacy is limited. Given that many MDD patients show psychomotor retardation, we aim to examine whether the left motor cortex (lMC) as a novel rTMS target would provide effective and well-tolerated treatment as being comparable to lDLPFC-rTMS. MethodsIn this prospective double-blind randomized single-center study, 131 MDD patients were randomly assigned to the lDLPFC or lMC group and were treated with 10 Hz rTMS (90 % motor threshold) applied twice daily for 4000 pulses continuously over five days. The primary endpoint was the Hamilton Depression Scale (HAMD) total score change after treatment. ResultsAfter the five-day rTMS treatment, there was no significant difference in both HAMD reduction rate (lDLPFC 59.3 % ± 20.4 %, lMC 51.3 % ± 26.3 %, P = 0.10) and adverse effects (P = 0.79) between 48 (73.8 %) lMC subjects and 51 (77.3 %) lDLPFC subjects. Furthermore, the lMC study group showed stable HAMD scores at follow-up compared to their endpoint scores (P = 0.08). LimitationsSham-control group was not included and the sample size was small. Therefore, our results should be seen as exploratory and preliminary. ConclusionsThe preliminary good therapeutic response, comparability, and tolerability of lMC-rTMS suggest lMC a potential and more easily accessible rTMS target. Together, our findings raise the possibility of symptom-specific rTMS in motor cortex (psychomotor retardation) or lDLPFC (cognitive deficits). This warrants larger clinical trials of rTMS in MDD with symptom-specific stimulation targets.

Revisiting Hemispheric Asymmetry in Mood Regulation: Implications for rTMS for Major Depressive Disorder.

Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD.

Oscillatory brain network changes after transcranial magnetic stimulation treatment in patients with major depressive disorder

• Oscillatory network changes during rTMS in MDD were evaluated by clinical EEG. • Functional connectivity changes were observed in MDD after rTMS. • Improved theta-band functional connectivity was associated with improved cognition. : Repetitive transcranial magnetic stimulation (rTMS) has attracted attention for treating treatment-resistant major depressive disorder (MDD) because of its effectiveness and low invasiveness. Recent neuroimaging studies suggest that the effects of rTMS in MDD may be based on improvements in abnormal brain networks. However, oscillatory network changes after rTMS remain unclear. This study aimed to detect oscillatory electroencephalography (EEG) markers that reflect the therapeutic effects of rTMS. : We treated 15 treatment-resistant MDD patients with high-frequency (10 Hz) rTMS over the left prefrontal cortex for 6 weeks. The power spectral density at each electrode and the phase lag index between all electrode pairs were compared before and after rTMS using clinical EEG data. The relationships between EEG indices, depressive symptoms, and cognitive function were also examined. : Depressive symptoms were significantly improved after rTMS. Additionally, functional connectivity between the left frontal–temporal and occipital regions in the theta band and gamma power in the anterior–central area were increased in both hemispheres after rTMS. Increased functional connectivity in the theta band was correlated with improved cognitive function, while increased gamma power was correlated with worsened depressive symptoms. : The sample size was relatively small. : Our results demonstrated oscillatory changes in theta-band functional connectivity after rTMS in MDD patients. These findings, obtained using clinical EEG methods, provide evidence of the underlying neurophysiological effects of rTMS on MDD within the context of functional brain network changes, and may constitute a biomarker for evaluating MDD treatments.

Repetitive Transcranial Magnetic Stimulation for Comorbid Major Depressive Disorder and Alcohol Use Disorder.

Major depressive disorder (MDD) and alcohol use disorder (AUD) are leading causes of disability, and patients are frequently affected by both conditions. This comorbidity is known to confer worse outcomes and greater illness severity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation method that has demonstrated antidepressant effects. However, the study of rTMS for patients with MDD and commonly associated comorbidities, such as AUD, has been largely overlooked, despite significant overlap in clinical presentation and neurobiological mechanisms. This narrative review aims to highlight the interrelated aspects of the literature on rTMS for MDD and rTMS for AUD. First, we summarize the available evidence on the effectiveness of rTMS for each condition, both most studied through stimulation of the dorsolateral prefrontal cortex (DLPFC). Second, we describe common symptom constructs that can be modulated by rTMS, such as executive dysfunction, that are transdiagnostic across these disorders. Lastly, we describe promising approaches in the personalization and optimization of rTMS that may be applicable to both AUD and MDD. By bridging the gap between research efforts in MDD and AUD, rTMS is well positioned to be developed as a treatment for the many patients who have both conditions concurrently.

Early course PHQ-9 score reduction predicts outcomes in rTMS for Major Depressive Disorder

Early course PHQ-9 score reduction predicts outcomes in rTMS for Major Depressive Disorder

Indirect frontocingulate structural connectivity predicts clinical response to accelerated rTMS in major depressive disorder

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its clinical efficacy remains rather modest. One reason for this could be that the propagation of rTMS effects via structural connections from the stimulated area to deeper brain structures (such as the cingulate cortices) is suboptimal. We investigated whether structural connectivity — derived from diffusion MRI data — could serve as a biomarker to predict treatment response. We hypothesized that stronger structural connections between the patient-specific stimulation position in the left dorsolateral prefrontal cortex (dlPFC) and the cingulate cortices would predict better clinical outcomes. We applied accelerated intermittent theta burst stimulation (aiTBS) to the left dlPFC in 40 patients with MDD. We correlated baseline structural connectivity, quantified using various metrics (fractional anisotropy, mean diffusivity, tract density, tract volume and number of tracts), with changes in depression severity scores after aiTBS. Exploratory results (p < 0.05) showed that structural connectivity between the patient-specific stimulation site and the caudal and posterior parts of the cingulate cortex had predictive potential for clinical response to aiTBS. We used the diffusion tensor to perform tractography. A main limitation was that multiple fibre directions within voxels could not be resolved, which might have led to missing connections in some patients. Stronger structural frontocingular connections may be of essence to optimally benefit from left dlPFC rTMS treatment in MDD. Even though the results are promising, further investigation with larger numbers of patients, more advanced tractography algorithms and classic daily rTMS treatment paradigms is warranted. http://clinicaltrials.gov/show/NCT01832805

Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: An analysis from the randomised non-inferiority THREE-D trial

BackgroundAlthough repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), treatment selection is still mainly a process of trial-and-error. The present study aimed to identify clinical predictors of remission after a course of rTMS delivered to the left DLPFC to improve patient selection. MethodsData from a large randomised non-inferiority trial comparing standard 10 Hz and intermittent theta burst stimulation (iTBS) for the treatment of MDD were used for the exploratory analyses. Individual variables were assessed for their association with remission and then included in a logistic regression model to determine odds ratios (OR) and corresponding 95% confidence intervals. Model discrimination (internal validation) was carried out to assess model optimism using the c-index. ClinicalTrials.gov identifier: NCT01887782. Findings388 subjects were included in the analysis (199-iTBS and 189-10 Hz, respectively). Higher baseline severity of both depressive and anxiety symptoms were associated with a lower chance of achieving remission (OR=0.64, 95% CI 0.46–0.88; and 0.78, 95% CI 0·60–0.98, respectively). Current employment was a positive predictor for remission (OR=1.69, 95% CI 1.06–2.7), while greater number of treatment failures was associated with lower odds of achieving remission (OR=0.51, 95% CI 0.27–0.98). A non-linear effect of age and remission was observed. An analysis to allow an estimate of the probability of remission using all variables was assessed. The c-index for the fitted model was 0.687. InterpretationOur results suggest that measuring depression symptom severity, employment status, and refractoriness are important in prognosticating outcome to a course of rTMS in MDD. FundingCanadian Institutes of Health Research MOP-136801.

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.

Time to remission analysis for major depressive disorder after repetitive transcranial magnetic stimulation (rTMS)

We previously examined the efficacy of rTMS for major depressive disorder in an applied clinical practice. Clinical response was related to severity of depression as well as the rTMS instrument utilized suggesting a relationship to instrument or magnetic field parameters and individual factors. The effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder was further evaluated using Log-Rank statistics for time to remission outcomes. A follow-up retrospective medical records study was carried out on patients with major depressive disorder undergoing rTMS therapy at AwakeningsKC Clinical Neuroscience Institute (CNI), a suburban tertiary psychiatric clinic. Cox Proportional Hazard with Log-Rank statistics were applied and the time course to clinical remission was evaluated over a 6-week period with respect to age, gender, and depression severity. Clinical response was observed referencing two different rTMS instruments (MagVenture; NeuroStar). Time to remission studies of 247 case reports (N=98 males; N=149 females) showed consistently greater clinically defined remission rates after 6 weeks of rTMS treatment for patients using the MagVenture vs NeuroStar instrument. Patients previously admitted for inpatient psychiatric hospitalization exhibited higher response rates when treated with the MagVenture rTMS unit. Stepwise Cox Proportional Hazards Regression final model of time to remission included rTMS unit, inpatient psychiatric hospitalization and obese body habitus. Response to rTMS in applied clinical practice is related to severity of psychiatric illness and may require consideration of magnetic field parameters of the rTMS unit with respect to individual factors such as sex or body composition.

Time to remission analysis for major depressive disorder after repetitive transcranial magnetic stimulation (rTMS)

We previously examined the efficacy of rTMS for major depressive disorder in an applied clinical practice. Clinical response was related to severity of depression as well as the rTMS instrument utilized suggesting a relationship to instrument or magnetic field parameters and individual factors. The effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder was further evaluated using Log-Rank statistics for time to remission outcomes. A follow-up retrospective medical records study was carried out on patients with major depressive disorder undergoing rTMS therapy at AwakeningsKC Clinical Neuroscience Institute (CNI), a suburban tertiary psychiatric clinic. Cox Proportional Hazard with Log-Rank statistics were applied and the time course to clinical remission was evaluated over a 6-week period with respect to age, gender, and depression severity. Clinical response was observed referencing two different rTMS instruments (MagVenture; NeuroStar). Time to remission studies of 247 case reports (N=98 males; N=149 females) showed consistently greater clinically defined remission rates after 6 weeks of rTMS treatment for patients using the MagVenture vs NeuroStar instrument. Patients previously admitted for inpatient psychiatric hospitalization exhibited higher response rates when treated with the MagVenture rTMS unit. Stepwise Cox Proportional Hazards Regression final model of time to remission included rTMS unit, inpatient psychiatric hospitalization and obese body habitus. Response to rTMS in applied clinical practice is related to severity of psychiatric illness and may require consideration of magnetic field parameters of the rTMS unit with respect to individual factors such as sex or body composition.

Moving away from depression: Physical activity changes in patients undergoing r-TMS for major depressive disorder

BackgroundPhysical activity (PA) may predict or mark successful treatment from major depressive disorder after repeated-transcranial magnetic stimulation (r-TMS). ObjectivesTo explore if r-TMS treatment responders were more physically active than non-responders at baseline, and to determine if treatment responders increased PA compared to non-responders post-treatment. MethodsThirty subjects were included in the study. PA was measured through Actical accelerometers. Baseline PA levels were compared through separate independent t-tests, whereas post-treatment changes were compared through separate ANCOVAs. ResultsThere were no differences in PA at baseline between groups. Controlling for baseline PA levels, ANCOVAs identified a non-significant treatment effect between moderate-to-vigorous physical activity levels post-treatment between groups [p = 0.276, η2 = 0.044]. A significant treatment effect was found between groups for light physical activity favouring responders [p = 0.009, η2 = 0.226]. ConclusionResponders’ LPA significantly increased in comparison to non-responders receiving r-TMS for major depressive disorder.

Completeness of Descriptions of Repetitive Transcranial Magnetic Stimulation Intervention

Repetitive transcranial magnetic stimulation (rTMS) is an innovative therapeutic option in major depressive disorder (MDD). A complete description of the procedure in reports of randomized controlled trials (RCTs) is a prerequisite for implementation of rTMS in clinical practice. The aim of this study was to evaluate the completeness of descriptions of the intervention in RCTs assessing rTMS in MDD. We performed a systematic review of RCTs evaluating rTMS in MDD and published until August 2016. We searched PubMed, the Cochrane library, and PsycINFO to identify eligible trials. The completeness of the intervention description was evaluated by the use of an adapted-to-rTMS version of the Template for Intervention Description and Replication (TIDieR) checklist. We defined core items that are the most essential to be reported. Missing information was then sought from additional sources and by e-mailing authors. We identified 98 trials reporting 134 interventions. None of the interventions were completely described in the full text of the articles, even after searching additional sources. After contacting the authors, 14 (10.4%) of 134 interventions were completely described. The core items were completely described in 74 (55.2%) of 134 interventions after contacting the authors. We found that rTMS interventions delivered in RCTs are incompletely reported, which prevents their adequate implementation in clinical practice and accurate interpretation of their efficacy. We encourage authors, editors, and reviewers to use the existing reporting guidelines and specifically the TIDieR checklist when describing the intervention. We provide an adapted-to-rTMS TIDieR checklist that could help in the reporting of future trials.

1 Hz rTMS of the right orbitofrontal cortex for major depression: Safety, tolerability and clinical outcomes

Conventional rTMS in major depressive disorder (MDD) targets the dorsolateral prefrontal cortex (DLPFC). However, many patients do not respond to DLPFC-rTMS. Recent evidence suggests that the right lateral orbitofrontal cortex (OFC) plays a key role in ‘non-reward’ functions and shows hyperconnectivity in MDD. OFC-rTMS has been used successfully in obsessive-compulsive disorder, and achieved remission in an MDD case nonresponsive to DLPFC- and DMPFC-rTMS. Here, we assess the safety and tolerability of right OFC-rTMS, and examine the effectiveness of inhibitory right OFC-rTMS in MDD, particularly among patients with previous nonresponse to DMPFC-rTMS. We performed a chart review to retrieve data on clinical characteristics, stimulation parameters, adverse events, and clinical symptom outcomes for a series of 42 patients with medication-resistant and/or DMPFC-rTMS-nonresponsive MDD, who underwent 20–30 sessions of 1Hz right OFC-rTMS at a single Canadian clinic from 2015 to 2017. Over 882 sessions of treatment, there were no seizures, visual/ocular complications, or other serious or treatment-limiting adverse events. Pain ratings averaged 6–7/10 (10=maximum tolerable); no patient discontinued treatment prematurely due to pain. 15/42 patients (35.7%) achieved response (≥50% symptom reduction) and 10/42 (23.8%) achieved remission. Among the 30/42 patients who were previous nonresponders to DMPFC-rTMS, 9/30 (30.0%) achieved response and 7/30 (23.8%) achieved remission. Response distribution was sharply bimodal. 1Hz right OFC-rTMS appears safe and tolerable, and may achieve remission in MDD patients even when conventional rTMS has failed. Sham-controlled follow-up studies may be warranted.

A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials

BackgroundAlthough several studies indicate that placebo response is large to antidepressant pharmacotherapy in major depressive disorder (MDD), no updated meta-analysis has quantified the magnitude of the placebo (sham) response to repetitive transcranial magnetic stimulation (rTMS) in MDD yet. ObjectiveTo conduct a systematic review and meta-analysis on this issue in randomized controlled trials (RCTs) involving participants with MDD; and to explore potential moderators. MethodologyPubMed/MEDLINE, Embase, PsycINFO, and Web of Science electronic databases were searched from inception up to March 15, 2017 for RCTs that investigated the efficacy of any rTMS modality compared to sham intervention in participants with acute depressive episodes. Cochrane Risk of Bias Tool was used to estimate risks. We estimated the placebo effect size (Hedges's g, random-effects model) response using placebo groups baseline and endpoint depressive symptom scores. Meta-regressions have been employed to explore potential moderators of response. ResultsSixty-one studies met eligibility criteria (N=1328; mean age, 47years; 57% females). Placebo response was large (g=0.8, 95% CI=0.65–0.95, p<0.01) regardless of the modality of intervention. Placebo response was directly associated with publication year and depression improvement of the active group, and inversely associated with higher levels of treatment-resistant depression. Other moderators, including gender, age, and stimulator type, were not associated with the outcome. Overall, 24.6%, 67.2%, and 8.2% of studies had an overall low, unclear, and high bias risk, respectively. ConclusionPlacebo response in rTMS depression trials was large and associated with depression improvement of the active treatment group. Such result suggests that excluding placebo responders with a run-in phase may not confer advantage since response to ‘active’ rTMS may decrease as well. Moreover, placebo response may be a component of therapeutic response to rTMS in MDD. In addition, placebo response increase over time could indicate improvement in rTMS trial designs, including better sham rTMS methods.

P274 Neuro-Cardiac-Guided TMS (NCG TMS): A new and cost-effective method for accurately localizing the DLPFC in the treatment of depression

Question The efficacy of rTMS in the treatment of major depressive disorder (MDD) has been well established in recent years in multi-center RCT’s as well as meta-analyses. Most studies to date have employed the ‘5-cm’ rule for targeting stimulation of the Dorsolateral Prefrontal Cortex (DLPFC). New variations and improvements of this targeting technique include a ‘6-cm’ rule, the Beam-F3 method, and neuronavigated rTMS. Furthermore, it has been proposed that the efficacy of rTMS in MDD is more related to stimulating the area that is functionally connected to the subgenual anterior cingulate cortex (sgACC) rather then to specific cortical areas (Fox et al., 2012). Therefore, we set-out to develop and test a new method that employs knowledge about the functional role of the sgACC to establish in real time if the right cortical area is targeted. Method Several studies have shown that areas in the ventromedial prefrontal cortex (VMPFC; including the subgenual and rostral ACC) are involved in processing of emotional information as well as the regulation of heart rate in response to emotional stimuli. Therefore, based on the notion that rTMS aims to transsynaptically stimulate the sgACC, we used electrocardiogram (ECG) R-peak triggered single pulse TMS to various frontal locations to establish the location that most consistently resulted in a lengthening of the R-R latency (reflective of a heart rate deceleration). This method of Neuro-Cardiac-Guided TMS or NCG TMS thus could be the equivalent of what the Motor Threshold is for the motor system, but then for the DLPFC with heart rate as an output. Results First preliminary results using a burst of 10 Hz TMS stimulation demonstrated that in a subject with a relatively large head circumference, no response was found at the ‘5 cm’ site (corresponding to FC4 in this subject), whereas the F4 location did result in a consistent heart rate deceleration. More data are currently being collected using a single pulse R-peak triggered approach and data will be presented. Conclusions In the treatment of MDD, Neuro-Cardiac-Guided TMS has the potential to become the equivalent of the ‘motor threshold’ for the DLPFC, and thereby would be a cost-effective and easy to use method for localizing the right stimulation target in the treatment of MDD, and also serve as a real-time control of adequate coil contact in patients undergoing rTMS treatment.

Neural Network Based Response Prediction of rTMS in Major Depressive Disorder Using QEEG Cordance.

ObjectiveThe combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN).MethodsThe artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation.ResultsThe ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively.ConclusionPotential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values.

Resting-State Cortico-Thalamic-Striatal Connectivity Predicts Response to Dorsomedial Prefrontal rTMS in Major Depressive Disorder

Despite its high toll on society, there has been little recent improvement in treatment efficacy for major depressive disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting-state functional connectivity predicted response to treatment with repetitive transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty-five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting-state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal, and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased subgenual cingulate cortex-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work.

1565 – Safety, efficacy, and tolerability of intermittent theta-burst rtms of the dorsomedial prefrontal cortex for refractory major depression

rTMS is an emerging treatment for major depressive disorder (MDD) refractory to medications and psychotherapy. The conventional target for rTMS in MDD is the dorsolateral prefrontal cortex (DLPFC). However, convergent evidence from lesion, stimulation, and neuroimaging studies suggests that the dorsomedial prefrontal cortex (DMPFC) may play a more central role in emotion regulation. We have recently demonstrated robust and potentially superior antidepressant properties for excitatory rTMS of the DMPFC. However, one of the enduring limitations of rTMS is the long duration of each treatment session under conventional protocols, which require ~40 minutes per day over 20-30 sessions for maximum efficacy using conventional 10 Hz stimulation. More recent studies have suggested that theta-burst stimulation (TBS) protocols can achieve stronger and more durable effects in markedly less time. Intermittent theta-burst stimulation (iTBS) generates robust and long-lasting excitatory effects with 600 pulses over ~3 min. Pilot studies have previously reported antidepressant effects with TBS over the DLPFC. However, TBS over the DMPFC has not previously been studied. Here we report robust antidepressant effects for a 7 min course of iTBS, administered bilaterally over the DMPFC with MRI-guidance at 120% resting motor threshold, over 20-30 sessions, in an open-label series of 40 patients with refractory MDD. Safety, efficacy, and tolerability are comparable to a 10 Hz rTMS protocol requiring 30-40 min of treatment. iTBS of the DMPFC may effectively reduce the duration (and cost) of rTMS >4-fold, thus increasing patient capacity per clinic and improving the overall accessibility of rTMS in refractory MDD.