EEG/fMRI Controlled TMS Real-time Neural Feedback in Anti-Depressive Treatment

 描述(由申请人提供)：这笔R21/R33赠款将设计和建造一个神经成像仪/刺激器，在R21阶段将EEG、TMS和fMRI集成到一个仪器中。这将使EEG和fMRI能够结合TMS脉冲的应用被同时采集。该仪器将测试与大脑内部节律同步施加的TMS脉冲将产生比非同步刺激更大的局部和分布影响的假设，具体地说，了解和了解大脑节律并利用这种知识进行刺激是否会比目前的技术状态产生更大的大脑影响，在当前技术状态下，刺激主要是在不了解大脑内部状态的情况下进行的。R21阶段将在开发出完整的实时反馈系统后，在正常受试者中测试这些。在R33阶段，我们将测试同步TMS是否将在高比例的抗药性抑郁症患者中成功治疗，并将产生比目前采用的非同步刺激更好的临床结果。实现这些目标的具体具体目标是：R21阶段特定目标1：将EEG系统与我们现有的同步TMS和fMRI扫描仪集成在一起，以便最终的仪器能够采集和进行同步EEG-fMRI-TMS测量。具体目标2：开发必要的软件和接口硬件，以实时检测和使用阿尔法相位和/或频率，以提供对TMS脉冲定时的实时闭环控制。具体目标3：在一组正常受试者中表明，当施加到DLPFC的TMS脉冲的时间相对于个体阿尔法节律的相位和频率不同时，rACC抑制存在显著差异。R33阶段特定目标1：将类似的脑电系统与我们的治疗TMS扫描仪集成在一起，具有与R21中SA 3类似的反馈电路。具体目标2：在一组抑郁症患者中，在最佳时间TMS和标准化非同步TMS之间随机进行为期4周的抗抑郁治疗试验，以评估这种优化治疗的成功率。

 DESCRIPTION (provided by applicant): This R21/R33 grant will design and build a neural imager/stimulator which will integrate EEG, TMS and fMRI into a single instrument in the R21 phase. This will enable EEG and fMRI to be acquired simultaneously in conjunction with the application of TMS pulses. This instrument will test the hypothesis that TMS pulses applied in synchrony with the brain's internal rhythms will have greater local and distributed effects than will non-synchronized stimulation and specifically whether knowing and understanding the brain's rhythms and stimulating with this knowledge will have larger brain effects than the current state of the art, where stimulation is largely done without knowledge of internal brain state. The R21 phase will test these in normal subjects after the full real-time feedback system is developed. In the R33 phase we will test whether synchronized TMS will be a successful treatment in a high percentage of drug resistant depressed patients, and will result in better clinical outcomes than will non-synchronized stimulation, which is currently employed. The detailed Specific Aims to accomplish these goals are: R21 phase Specific Aim1: Integrate an EEG system with our existing simultaneous TMS and fMRI scanner so the final instrument is able to acquire and conduct simultaneous EEG-fMRI-TMS measurements. Specific Aim2: Develop the necessary software and interface hardware to detect and use in real-time the alpha phase and/or frequency to provide real-time closed loop control of the TMS pulse timing. Specific Aim 3: Show in a cohort of normal subjects that there is significant variation of rACC inhibition as the timing of TMS pulses applied to the DLPFC are varied with respect to the phase and frequency of an individual's alpha rhythms. R33 phase Specific Aim 1: Integrate a similar EEG system with our treatment TMS scanner with similar feedback circuitry as that in SA 3 in the R21. Specific Aim 2: Carry out a 4 week trial of anti-depressive therapy randomized between optimum timed TMS and standardized non-synchronous TMS in a cohort of depressed patients to estimate the success rate of such an optimized treatment.