Electrophysiological Probes And Treatments In Neurobehav

神经行为的电生理学探针和治疗

• 批准号: 6675687
• 负责人: Eric M Wassermann
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6675687
• 关键词: anxiety; behavioral /social science research tag; brain electronic stimulator; clinical research; depression; epilepsy; estrogens; female; hippocampus; hormone regulation /control mechanism; human subject; human therapy evaluation; menstrual cycle; mood disorders; motor cortex; neurophysiology; neuropsychology; obsessive compulsive disorder; personality; progesterone; psychotherapy; steroid hormone metabolism; transcranial magnetic stimulation

High-frequency priming stimulation has been shown repeatedly to increase the ability of 1 Hz stimulation to produce long-term depression in hippocampal synapses. Since 1 Hz repetitive transcranial magnetic stimulation (TMS) produces robust depression of the excitability in the motor cortex, we have studied healthy individuals to look at the effect of 6 Hz priming stimulation on this effect. Preliminary data suggest that motor cortex depression from 1 Hz stimulation is longer-lasting when preceded 6 Hz priming. If borne out in more subjects, priming stimulation may make TMS treatments more effective in disorders such as epilepsy and chronic pain. Steroid hormones are known to exert powerful influences on neural function and behavior, but direct physiological evidence has not been found in humans. We have continued our studies of the effects of estrogen and progesterone in the human motor cortex, confirming our earlier findings of excitatory effects of estrogen and inhibition from progesterone. This year we completed a study of women with premenstrual syndrome and showed that they have an abnormal response to the rising progesterone levels in the luteal phase of the menstrual cycle. Where control women showed decreasing excitability in the luteal phase, the women with PMS showed an increase. This finding is compatible with either a defect in the GABA-A receptor system or altered metabolism of progesterone in the central nervous system. While it is known that patients with Parkinson disease and other movement disorders have an altered response to paired TMS of the motor cortex, it is not known whether this measure correlates with disease severity or whether the pattern of findings is specific to the disorder. This uncertainty is due largely to the lack of large and well-controlled studies. In order to answer this question, we initiated two large studies, one in Parkinson disease and one in tic disorder with age-matched healthy controls. These conditions were chosen because the differ widely in their physiology and clinical phenotype. We took measures of clinical severety and administered multiple psychological and cognitive tests in order to look for individual characteristics, independent of disease, that might interact with the physiological dependent variables. In a preliminary analysis, the patterns of physiological response differ significantly among the disease and control groups.

已经反复显示高频启动刺激，以提高1 Hz刺激在海马突触中长期抑郁的能力。由于1 Hz重复的经颅磁刺激（TMS）会产生运动皮层兴奋性的稳健抑郁，因此我们研究了健康个体，以研究6 Hz启动刺激对这种效果的影响。初步数据表明，在6 Hz启动之前，1 Hz刺激的运动皮层抑郁症更长。如果在更多受试者中表现出来，启动刺激可能会使TMS治疗在癫痫和慢性疼痛等疾病中更有效。 已知类固醇激素对神经功能和行为产生强大的影响，但在人类中尚未发现直接的生理证据。我们继续研究雌激素和孕激素对人体运动皮质的影响，证实了我们先前对雌激素和孕酮抑制作用的兴奋作用的发现。今年，我们完成了一项对女性经前综合症的研究，并表明她们对月经周期的黄体期对孕酮水平上升的反应异常。在对照妇女在黄体期显示兴奋性降低的地方，患有PMS的妇女显示出增加。这一发现与GABA-A受体系统中的缺陷或中枢神经系统中孕激素的代谢改变兼容。 虽然众所周知，患有帕金森氏病和其他运动障碍的患者对运动皮层的配对TMS的反应改变了，但尚不清楚该措施是否与疾病的严重程度相关，还是发现的模式是否特定于该疾病。这种不确定性主要是由于缺乏大型且控制良好的研究。为了回答这个问题，我们启动了两项大型研究，一项在帕金森氏病和一种伴随年龄匹配的健康对照中进行。之所以选择这些条件，是因为它们的生理和临床表型差异很大。我们采取了临床严重性的衡量标准，并进行了多次心理和认知测试，以寻找与生理依赖变量相互作用的个人特征，与疾病无关。在初步分析中，疾病和对照组之间的生理反应模式显着不同。