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

 描述（由申请人提供）：该R21/R33赠款将设计和建造一个神经成像仪/刺激器，将EEG，TMS和fMRI集成到R21阶段的单个仪器中。这将使脑电图和功能磁共振成像能够同时采集与TMS脉冲的应用。该仪器将测试以下假设：与大脑的内部节律同步地施加的TMS脉冲将比非同步刺激具有更大的局部和分布式效应，并且具体地，知道和理解大脑的节律并利用该知识进行刺激是否将比现有技术具有更大的大脑效应，其中刺激在很大程度上在不知道内部大脑状态的情况下进行。R21阶段将在开发出全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是否会成功治疗高比例的耐药抑郁症患者，并将导致比目前采用的非同步刺激更好的临床结果。实现这些目标的详细具体目标是：R21阶段具体目标1：将EEG系统与我们现有的同步TMS和fMRI扫描仪集成，以便最终仪器能够采集并进行同步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α相位和/或频率，从而提供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显示，rACC抑制存在显著变化，因为施加于DLPFC的TMS脉冲的时间相对于个体α节律的相位和频率而变化。 R33阶段具体目标1：将类似的EEG系统与我们的治疗TMS扫描仪集成，其反馈电路与R21中SA 3中的反馈电路类似。具体目标二：在一组抑郁症患者中进行为期4周的抗抑郁治疗试验，随机分为最佳定时TMS和标准化非同步TMS，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.