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Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder.

ABSTRACT: Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression.Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10?Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6-8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5?cm rule and Beam F3 methods.Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5?cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment.Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

SUBMITTER: Wall CA

PROVIDER: S-EPMC5035831 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder.

Wall Christopher A CA Croarkin Paul E PE Maroney-Smith Mandie J MJ Haugen Laura M LM Baruth Joshua M JM Frye Mark A MA Sampson Shirlene M SM Port John D JD

Journal of child and adolescent psychopharmacology 20160205 7

<h4>Objective</h4>Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression.<h4>Methods</h ...[more]

PMID: 26849202

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Project description:ObjectiveA minimally conscious state (MCS) is characterized by discernible behavioral evidence of consciousness that cannot be reproduced consistently. This condition is highly challenging to treat. Recent studies have demonstrated the potential therapeutic effect of non-invasive brain stimulation in patients with MCS. In one patient in an MCS, we delivered simultaneous transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) based on an individual brain network analysis and evaluated the therapeutic effect.MethodsThe directional transfer function (DTF) was calculated based on electroencephalograph (EEG) analysis. Global brain connectivity was calculated based on functional magnetic resonance imaging (fMRI) analysis. By referring to the EEG and fMRI results, we identified inferior parietal lobes (IPLs) as targets. In the 2-week treatment period, 14 sessions were applied to the identified bilateral parietal regions. Simultaneous 1.5-mA anodal tDCS and 5-Hz rTMS were delivered for 20 min per hemisphere in each session. Clinical evaluation scores were recorded weekly throughout the treatment. A second patient given the routine treatment was evaluated as a control.ResultsThe clinical scores of patient 1 with MCS improved after 2 weeks of stimulation treatment, and the effect lasted for up to 1 month. EEG analysis showed a significant increase (p < 0.001) in the DTF value in the gamma band in a bilateral set of posterior regions, and fMRI showed a trend toward normalized activity in the IPLs. The clinical scores of patient 2 with coma did not improve much after 2 weeks of routine treatment. The EEG analysis showed a significant increase (p = 0.021) in the DTF value in the gamma band in a bilateral set of posterior regions.ConclusionThe application of EEG and fMRI to characterize the functional connectivity features of the network in an MCS patient provided a reasonable and accurate stimulation target and verified the changes in functional connectivity resulting from stimulation.

Project description:BackgroundEmotional blunting is a symptom that has always been present in depressed patients. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective supplementary therapy for treating depression. However, the effectiveness and brain imaging processes of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) in the treatment of depression with emotional blunting have not been observed in randomized controlled trials.MethodsThis study is a randomized, controlled, double-blind, and single-center clinical trial in which 80 eligible depressed patients with emotional blunting will be randomly assigned to two groups: a functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) group and a control group. Individuals in the fMRI-rTMS group (n = 40) will receive high-frequency rTMS (10 Hz, 120% MT). The main target of stimulation will be the area most relevant to the functional connectivity of the right medial prefrontal cortex (mPFC) and amygdala. The control group (n = 40) will receive sham stimulation, with a coil flipped to 90 degrees relative to the vertical scalp. All patients will receive 15 consecutive days of treatment, with each session lasting half an hour per day, followed by 8 weeks of follow-up. The primary outcome is the comparison of Oxford Depression Questionnaire (ODQ) scores between these two groups at different time points. The secondary outcomes include evaluating other clinical scales and assessing the differences in brain imaging changes between the two groups before and after treatment.DiscussionThis trial aims to examine the effects of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) intervention on depressed patients experiencing emotional blunting and to elucidate the potential mechanism behind it. The results will provide new evidence for using fMRI-rTMS in treating depression with emotional blunting in the future.Trial registrationClinicalTrials.gov INCT05555940. Registered on 13 September 2022 at http://clinicaltrials.gov .

Project description:ObjectivesIt is estimated that 30-40% of adolescents with major depressive disorder (MDD) do not receive full benefit from current antidepressant therapies. Repetitive transcranial magnetic stimulation (rTMS) is a novel therapy approved by the US Food and Drug Administration to treat adults with MDD. Research suggests rTMS is not associated with adverse neurocognitive effects in adult populations; however, there is no documentation of its neurocognitive effects in adolescents. This is a secondary post hoc analysis of neurocognitive outcome in adolescents who were treated with open-label rTMS in two separate studies.MethodsEighteen patients (mean age, 16.2 ± 1.1 years; 11 females, 7 males) with MDD who failed to adequately respond to at least one antidepressant agent were enrolled in the study. Fourteen patients completed all 30 rTMS treatments (5 days/week, 120% of motor threshold, 10 Hz, 3,000 stimulations per session) applied to the left dorsolateral prefrontal cortex. Depression was rated using the Children's Depression Rating Scale-Revised. Neurocognitive evaluation was performed at baseline and after completion of 30 rTMS treatments with the Children's Auditory Verbal Learning Test (CAVLT) and Delis-Kaplan Executive Function System Trail Making Test.ResultsOver the course of 30 rTMS treatments, adolescents showed a substantial decrease in depression severity. Commensurate with improvement in depressive symptoms was a statistically significant improvement in memory and delayed verbal recall. Other learning and memory indices and executive function remained intact. Neither participants nor their family members reported clinically meaningful changes in neurocognitive function.ConclusionThese preliminary findings suggest rTMS does not adversely impact neurocognitive functioning in adolescents and may provide subtle enhancement of verbal memory as measured by the CAVLT. Further controlled investigations with larger sample sizes and rigorous trial designs are warranted to confirm and extend these findings.

Project description:BackgroundRepetitive transcranial magnetic stimulation (rTMS) has the potential to treat brain disorders by modulating the activity of disease-specific brain networks, yet the rTMS frequencies used are delivered in a binary fashion - excitatory (>1 Hz) and inhibitory (≤1 Hz).ObjectiveTo assess the effective connectivity of the motor network at different rTMS stimulation rates during positron-emission tomography (PET) and confirm that not all excitatory rTMS frequencies act on the motor network in the same manner.MethodsWe delivered image-guided, supra-threshold rTMS at 3 Hz, 5 Hz, 10 Hz, 15 Hz and rest (in separate randomized sessions) to the primary motor cortex (M1) of the lightly anesthetized baboon during PET imaging. Each rTMS/PET session was analyzed using normalized cerebral blood flow (CBF) measurements. Path analysis - using structural equation modeling (SEM) - was employed to determine the effective connectivity of the motor network at all rTMS frequencies. Once determined, the final model of the motor network was used to assess any differences in effective connectivity at each rTMS frequency.ResultsThe exploratory SEM produced a very well fitting final network model (χ(2) = 18.04, df = 21, RMSEA = 0.000, p = 0.647, TLI = 1.12) using seven nodes of the motor network. 5 Hz rTMS produced the strongest path coefficients in four of the seven connections, suggesting that this frequency is the optimal rTMS frequency for stimulation the motor network (as a whole); however, the premotor cerebellum connection was optimally stimulated at 10 Hz rTMS and the supplementary motor area caudate connection was optimally driven at 15 Hz rTMS.Conclusion(s)We have demonstrated that 1) 5 Hz rTMS revealed the strongest path coefficients (i.e. causal influence) on the nodes of the motor network, 2) stimulation at "excitatory" rTMS frequencies did not produce increased CBF in all nodes of the motor network, 3) specific rTMS frequencies may be used to target specific none-to-node interactions in the stimulated brain network, and 4) more research needs to be performed to determine the optimum frequency for each brain circuit and/or node.

Dataset Information

Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder.

Publications

Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder.

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