AFFECTIVE AND COGNITIVE CONSEQUENCES OF ECT

描述(改编自申请者摘要)：本R01是一款竞争性的 续展优异奖。当这个项目开始时(1981)，普遍的观点是 ECT的疗效取决于全身性发作，而 它的认知效果在很大程度上取决于电剂量。 尽管如此，标准做法包括对所有患者进行相同的治疗 电剂量，通常为设备最大值。在三项研究中，我们 发作阈值(ST)有明显的个体差异。许多 患者接受的治疗比ST段高几个数量级，占大部分 ECT对认知的不良影响。我们还证明了 右侧单侧(RUL)ECT高度依赖于剂量 超过ST。这些发现已被广泛复制。在我们最新的 研究(在优秀奖期间开始和完成)，高剂量RUL ECT与健壮形式的双侧(BL)ECT的疗效相当， 急性认知、短期认知和长期认知的临床显著优势 副作用。这些发现已经对实践产生了影响，应该 帮助解决长达40年的关于RUL和RUL的相对优点的争议 BL ECT。 拟议的研究(研究4)在荣誉奖期间开始，这 应用程序请求支持其完成。除了复制 关于大剂量RUL与BL相比的相对优点的关键发现 ECT，这项研究有了新的方向。传统的ECT刺激 构型是非生理学的。ECT中使用的标准脉冲宽度(PW)(1-2 Ms)大大超过了所需的最佳刺激的时间轴 神经元去极化和惊厥产生(如0.04-0.2ms)。PW过多 在神经元后长时间不应期的刺激 出院。通过减少ECT刺激的PW，我们应该保持疗效， 但大大减少了认知副作用。我们的初步数据显示 这种影响的大小等于或超过了认知能力的差异 RUL和BLECT之间的影响，事实上，非常不同 在正弦波和短暂脉冲刺激之间。这项新研究使用了一种 随机、双掩码、平行组、完全阶乘[RUL与BLECT和 UltraBrief PW(0 Ms)与传统PW(1.5 ms)]设计，采用两种RUL 以6倍初始ST处理的条件和以2.5倍处理的两个BL条件 乘以首字母ST。我们假设高剂量RUL ECT有重要意义 比中等剂量的BLECT更有优势[两者都是传统的PW]。多数 重要的是，使用超短PW与使用长PW一样有效，但 显著减轻ECT的短期和长期认知负担，还 在功能状态、主观认知结果和 神经生理学改变。这些发现应该对以下方面产生根本性影响 我们对ECT的机理和实践的理解。

DESCRIPTION (Adapted from the Applicant's Abstract): This R01 is a competitive renewal of a MERIT Award. When this project started (1981), the universal view was that the efficacy of ECT was dependent on the generalized seizure, while its cognitive effects were largely determined by electrical dosage. Nonetheless, standard practice involved treating all patients with the same electrical dose, typically at device maximum. Across three studies, we demonstrated marked individual differences in seizure threshold (ST). Many patients were treated orders of magnitude above ST, accounting for much of the adverse cognitive effects of ECT. We also demonstrated that the efficacy of right unilateral (RUL)ECT is highly dependent on the degree to which dosage exceeds ST. These findings have been widely replicated. In our most recent study (started and completed during the MERIT Award period), high dosage RUL ECT equaled the efficacy of a robust form of bilateral (BL) ECT, and had clinically significant advantages in acute, short-term, and long-term cognitive side effects. These findings have already had impact on practice, and should help resolve the > 40 year controversy regarding the relative merits of RUL and BL ECT. The proposed study (Study 4) began during the MERIT Award period, and this application requests support for its completion. In addition to replicating the key findings regarding the relative merits of high dosage RUL compared to BL ECT, this study takes a new direction. The traditional ECT stimulus configuration is nonphysiologic. The standard pulse width (PW) used in ECT (1-2 ms) greatly exceeds the chronaxie for the optimal stimulation necessary for neuronal depoladzation and seizure production (eg, 0.04-0.2 ms). Excessive PW results in stimulation during refractory periods long following neuronal discharge. By reducing the PW of the ECT stimulus, we should maintain efficacy, but substantially reduce cognitive side effects. Our preliminary data suggest that the magnitude of this effect equals or exceeds the difference in cognitive effects between RUL and BL ECT, and, in fact, the extraordinary difference between sine wave and brief pulse stimulation. This new study uses a randomized, double-masked, parallel group, fully factorial [RUL vs. BL ECT and ultrabrief PW (0 ms) vs. traditional PW (1.5 ms)] design, with both RUL conditions treated at 6 times initial ST and both BL conditions treated at 2.5 times initial ST. We hypothesize that high dose RUL ECT has significant advantages over moderate dose BL ECT [with both at traditional PW]. Most critically, use of an ultrabrief PW is equally effective as a long PW, but markedly reduces the short- and long-term cognitive burden of ECT, and is also superior in effects on functional status, subjective cognitive outcome, and neurophysiological alterations. Such findings should have fundamental impact on our understanding of mechanisms and on the practice of ECT.