Targeting Functional Improvement in rTMS Therapy

rTMS 治疗以功能改善为目标

• 批准号: 10663803
• 负责人: ALLYSON C ROSEN
• 金额: --
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10663803
• 关键词: Address; Adopted; Area; Autopsy; Brain; Brain region; Clinic; Clinical; Clinical Trials; Collaborations; Cranial Nerves; Data; Depressed mood; Diagnosis; Disease remission; Effectiveness; Electrodes; Electroencephalography; Emotional; Equipment; FDA approved; Face; Facial Muscles; Facial nerve structure; Functional Magnetic Resonance Imaging; Functional disorder; Head; Health Surveys; Histology; Individual; Left; Location; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mental Depression; Methods; Outcome; Outcome Measure; Outcome Study; Pain; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Physiologic pulse; Prefrontal Cortex; Process; Psychotherapy; Publishing; Quality of life; Recovery; Reporting; Research Personnel; Resistance; Resolution; Rest; Sampling; Scalp structure; Severities; System; Testing; Therapeutic; Training; Training Programs; Transcranial magnetic stimulation; Treatment Failure; Validation; Veterans; Vision; World Health Organization Disability Assessment Schedule; alternative treatment; biomarker identification; clinical practice; clinically significant; cognitive control; cost; depressed patient; detection limit; distraction; experimental study; feasibility testing; functional improvement; functional outcomes; image guided; improved; innovation; model development; psychosocial; repetitive transcranial magnetic stimulation; response; standard of care; tool; virtual

Depressed patients inadequately responsive to medication and psychotherapy often live with serious difficulties in psychosocial functioning; thus, repetitive transcranial magnetic stimulation (rTMS) is an important, alternative, FDA approved therapy. During typical rTMS therapy, clinicians place a stimulation coil on the patient's scalp that focally modulates the underlying cortical areas. The left dorsolateral prefrontal cortex region (DLPFC) is the most established target for treating depression; however, clinicians miss this target in a third of patients and treatment fails, likely contributing to the relatively low remission rate of 31%. The reason for errors in targeting the DLPFC is that clinicians typically do not have access to MR image-guidance to identify the underlying brain regions they target. Instead they use the current standard-of-care method to identify the stimulation location that uses scalp landmarks and moves a fixed distance over the scalp. A new, promising alternative scalp targeting approach based on EEG electrode placement, the Beam F3 accurately targeted the DLPFC in 92% of Veterans from our pilot data (n=12). Our collaborator has adopted the Beam F3 as his clinical standard and showed improved depression severity and changes in associated functional Magnetic Resonance Imaging (fMRI) data. Other labs also, have indirect evidence that the Beam F3 scalp targeting approach places the rTMS stimulation coil near an fMRI identified optimal subregion within the DLPFC that involves control over emotional distraction and reactivity. The overall aim of the current proposal is to test the feasibility of accurately reaching this fMRI based optimal subregion using the Beam F3 scalp-based targeting approach. We further hypothesize that, since psychosocial functioning is related to cognitive control that accurate stimulation of this fMRI region could also lead to improved psychosocial functioning (i.e. reduced functional limitations and improved quality of life). Our plan is to collect fMRI and MRI's with markers identifying where clinicians place the Beam F3 location in depressed Veterans. Our strategy is to test whether the Beam F3 rule places the coil close enough (i.e. within the spatial resolution of rTMS) to reach an optimal DLPFC subregion in 95% of Veterans. In Aim 1 we propose to use image-guidance to test with high precision how accurately the Beam F3 targets this optimal, fMRI defined, brain region. In Aim 2 we demonstrate the accuracy of the Beam F3 in rTMS clinic patients where treaters typically deviate from scalp rules to accommodate patient comfort since frontal stimulation causes facial twitches and painful cranial nerve stimulation in some scalp locations. To address clinical importance of our choice of brain targets, in our clinic-based sample we will evaluate whether spatial deviations from the optimal brain target correlate with improvements in psychosocial functioning on a composite score of the World Health Organization Disability Assessment Schedule 2.0 and the Veterans RAND 12-item health survey of quality of life. We will perform several additional analyses on the acquired data. We will use precise image-guidance and directly compare in the same patients the accuracy of the Beam F3 scalp targeting to that of the clinical standard to provide clinicians with compelling evidence of which approach is more accurate. If we discover a systematic deviation in the Beam F3 rule, we can identify how to adapt it to improve accuracy. Results from this proposal will improve the implementation of rTMS therapy for depressed Veterans. We will disseminate our findings through our clinical rTMS VA training to improve targeting accuracy at VA clinics nationwide. Our vision is that this image-guidance approach to validation of scalp-based targets will serve as a model for the development of new brain-informed scalp targets and will guide innovative large scale clinical trials to study the relationship between brain predictors, changes, and clinically meaningful outcomes. The tools developed in this proposal can thus enable large-scale collaborations between VA rTMS clinics that can identify brain and scalp targets treat dysfunction in Veterans they find clinically meaningful.

对药物和心理治疗反应不充分的抑郁症患者往往生活在严重的抑郁症中