ECT current amplitude and medial temporal lobe engagement

ECT 电流幅度和内侧颞叶接合

• 批准号: 9357705
• 负责人: Christopher C Abbott
• 金额: $ 51.21万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-26 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9357705
• 关键词: Adverse effects; Affect; Attentional deficit; Bilateral; Brain; Brain region; Characteristics; Charge; Clinical; Cognitive; Cognitive deficits; Data; Depressive disorder; Devices; Disease remission; Dose; Electroconvulsive Therapy; Electrodes; Exhibits; Frequencies; Generalized seizures; Goals; Gold; Handedness; Hippocampus (Brain); Impaired cognition; Individual; Individual Differences; Investigation; Left; Link; Long-Term Potentiation; Magnetic Resonance Imaging; Measures; Medial; Mediating; Memory impairment; Mental Depression; Methods; Modeling; Moods; Neurocognitive; Neurocognitive Deficit; Neurofibrillary Tangles; Neuronal Plasticity; Outcome; Patients; Physiologic pulse; Physiological; Randomized; Regression Analysis; Research; Risk; Safety; Scalp structure; Seizures; Series; Stimulus; Symptoms; Temporal Lobe; Therapeutic Effect; Thick; Training; Treatment Efficacy; Width; Work; antidepressant effect; brain tissue; cognitive change; cognitive function; cranium; depressed patient; depressive symptoms; dosage; electric field; entorhinal cortex; experience; improved; individual patient; neural circuit; neural correlate; neuroimaging; neuroregulation; older patient; response; standard care; suicidal; synergism; theories

1. Project Summary/Abstract Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes. During a typical four-week ECT series, most depressive episodes remit, and formerly suicidal or psychotically depressed patients will resume their premorbid levels of functioning. Independent of the antidepressant effect of ECT, many patients experience debilitating but transient cognitive effects such as attention and memory def- icits. These unwanted side effects are particularly troubling for older patients who are more likely to have exist- ing cognitive deficits. Both the stimulus delivery (electrode placement, pulse amplitude, and pulse width) and seizure induction appear to work in synergy, but the underlying mechanism of action for successful response has yet to be fully elucidated. Moreover, further work is needed to understand the relationship between clinical improvement and cognitive impairment. This investigation will examine the clinical and neurocognitive impact of targeted medial temporal lobe engagement as a function of pulse amplitude, one of several variable factors influencing the ECT charge. The ECT charge is measured in millicoulombs (mC) and derived from multiplying pulse train duration, pulse-pair frequency, pulse width, and pulse amplitude. Pulse amplitude determines the induced electric field strength in the brain and is presently fixed at 900 milliamperes (mA) with no clinical or scientific justification. The central hypothesis of this investigation is that the optimal pulse amplitude for an indi- vidual patient will enhance neuroplasticity (clinical response) while minimizing the disruption of dominant hemi- sphere hippocampal cognitive circuitry (resulting in cognitive stability). Our preliminary data informs the dosage range between 600 and 800 mA. Pulse amplitudes outside of this range compromise efficacy (500 mA) or may increase risk of cognitive impairment (900 mA). The first aim of this investigation will identify the electric field strength and neuroplasticity associated with clinical response. Critically, this aim will establish the neuroplas- ticity threshold, which is defined as the electric field strength necessary to induce neuroplasticity. The second aim will detect the neural correlates of ECT-mediated cognitive changes, which may be related to disrupted dominant hemisphere long-term potentiation. The third aim will use data-driven dual regression to predict the optimal pulse amplitude for an individual patient. This contribution will be significant because the electric field, when manipulated by pulse amplitude, can subsequently maximize hippocampal neuroplasticity (efficacy) and minimize disrupted connectivity (cognitive stability) thus improving clinical outcomes. 2 !

1.项目总结/摘要 电休克治疗（ECT）仍然是抑郁发作患者的金标准治疗。 在一个典型的为期四周的ECT系列，大多数抑郁发作缓解，以前自杀或精神病 抑郁症患者会恢复他们发病前的功能水平。与抗抑郁作用无关 ECT的许多患者经历衰弱，但短暂的认知影响，如注意力和记忆力障碍， - 是的这些不必要的副作用对老年患者来说尤其令人不安，他们更有可能存在- 认知缺陷刺激递送（电极放置、脉冲幅度和脉冲宽度）和 癫痫发作诱导似乎协同工作，但成功响应的潜在作用机制 还没有完全阐明。此外，还需要进一步的工作来了解临床之间的关系。 改善和认知障碍。这项研究将检查临床和神经认知的影响 有针对性的内侧颞叶参与作为脉冲幅度的函数，几个可变因素之一， 影响ECT充电。ECT电荷以毫库仑（mC）为单位测量，并由以下公式得出： 脉冲串持续时间、脉冲对频率、脉冲宽度和脉冲幅度。脉冲幅度决定了 在大脑中的感应电场强度，目前固定在900毫安（mA），没有临床或 科学论证这项研究的中心假设是，最佳脉冲幅度为indi- 单个患者将增强神经可塑性（临床反应），同时最大限度地减少显性半脑的破坏。 球形海马认知回路（导致认知稳定）。我们的初步数据显示 范围在600到800 mA之间。脉冲幅度超出此范围会影响功效（500 mA）或可能 认知障碍风险增加（900 mA）。这项研究的第一个目的是确定电场 强度和神经可塑性与临床反应。关键是，这一目标将建立神经细胞- 活性阈值，其被定义为诱导神经可塑性所需的电场强度。第二 目的是检测ECT介导的认知变化的神经相关性，这可能与破坏 优势半球长时程增强。第三个目标将使用数据驱动的二元回归来预测 最佳的脉冲幅度为个别病人。这种贡献将是显著的，因为电场， 当通过脉冲幅度操纵时，可以随后使海马神经可塑性（功效）最大化， 最大限度地减少中断的连接（认知稳定性），从而改善临床结果。 2 !