Cannabinoids, Neural Synchrony and Information Processing

大麻素、神经同步和信息处理

• 批准号: 7487069
• 负责人: DEEPAK Cyril D'SOUZA
• 金额: $ 15.9万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-20 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7487069
• 关键词: Acoustic Stimulation; Acute; Attention; Auditory; Automobile Driving; Behavioral; Binding; Brain; Cannabinoids; Cannabis; Cognitive; Communication; Computer information processing; Dose; Double-Blind Method; Electroencephalography; Event; Frequencies; Hippocampus (Brain); Human; Impaired cognition; Impairment; Individual; Measurement; Measures; Memory; Methods; Phase; Process; Psychotic Disorders; Randomized; Rattus; Relative (related person); Score; Sensory; Short-Term Memory; Slice; Stimulus; Symptoms; Testing; Training; Visual; auditory stimulus; base; day; design; indexing; memory recognition; neural circuit; object recognition; relating to nervous system; response

DESCRIPTION (provided by applicant): Background: The mechanisms by which cannabinoids produce transient psychotomimetic effects and impairments in attention and memory are not clear. Perceptual, memory and attentional functions are based on distributed processes that are believed to be "bound" together by synchronous high frequency oscillatory activity. In humans, macroscopic neural synchrony can be evaluated non-invasively by entrainment of the EEG to sensory (auditory) stimuli presented of various frequencies. The brain acts as a tuned oscillator, and the steady-state EEG waveform entrains to the frequency and phase of the presented stimulus, providing an indicator of the functioning state of the neural circuits supporting synchrony. Cannabinoids decrease gamma band power in rat hippocampal slices and cannabis users show reduced power in the beta band relative to controls during an auditory entrainment paradigm. We are unaware of any studies examining the acute effects of cannabinoids on EEG neural synchrony in healthy humans. Hypothesis: ?9-THC, in a dose-related manner, will reduce spectral power of the EEG response to an auditory steady state entrainment at 20, 30 and 40 Hz. Secondary analyses will examine the effects of ?9-THC on specific features of the steady state EEG response that may contribute to spectral power reductions including event spectral perturbations (ERSP) and inter-trial phase coherence (ITC). Changes in perceptual alterations, psychotic-like symptoms, and cognitive impairments (attention, verbal recall and working memory) induced by ?9-THC will correlate with changes in spectral power. Methods: Carefully screened healthy individuals will complete 3 test days during which they will receive (0, 0.015, 0.03 mg/kg) ?9-THC in a double-blind, randomized, counterbalanced design. Indices of neural synchrony will be assessed by measurement of EEG spectral power evoked by presentation of auditory click trains at 20, 30 and 40 Hz. Perceptual alterations, psychotic-like symptoms, sustained attention, immediate verbal recall, spatial working memory and visual object recognition memory will also be assessed. Preliminary results: ?9-THC produced a dose-related reduction in power at 30 HZ in response to 30 Hz auditory stimulation (driving). ?9-THC also reduced event related spectral perturbation to 20 and 30 Hz driving. ?9-THC reduced intertrial coherence to 40 Hz driving and to a lesser extent 20 and 30 Hz driving. In a dose- related manner, ?9-THC increased scores on measures of perceptual alterations and psychosis, and induced impairments in measures of verbal recall, spatial working memory, visual recognition memory and attention. Relevance: The aim of this project is to characterize the effects of cannabinoids on electrical communication within the brain (neural synchrony) using EEG in healthy humans and to relate these effects to their behavioral and cognitive effects.

描述（由申请人提供）：背景：大麻素产生短暂拟精神病效应和注意力和记忆力受损的机制尚不清楚。知觉、记忆和注意力功能基于分布式过程，这些过程被认为是通过同步高频振荡活动“绑定”在一起的。在人类中，宏观神经同步性可以通过将EEG夹带到各种频率的感官（听觉）刺激来非侵入性地评估。大脑充当调谐振荡器，并且稳态EEG波形跟随所呈现的刺激的频率和相位，从而提供支持同步的神经回路的功能状态的指示。大麻类药物降低大鼠海马切片中的γ波段功率，大麻使用者在听觉夹带范例期间相对于对照显示β波段功率降低。我们不知道有任何研究检查大麻素对健康人EEG神经同步的急性影响。假设：？9-THC以剂量相关的方式将降低EEG响应于20、30和40 Hz听觉稳态夹带的频谱功率。次要分析将检查的影响？9-THC对稳态EEG响应的特定特征的影响，这些特征可能有助于频谱功率降低，包括事件频谱扰动（ERSP）和试验间相位相干性（ITC）。在知觉改变的变化，精神病样症状，和认知障碍（注意力，言语回忆和工作记忆）引起的？9-THC将与光谱功率的变化相关。方法：仔细筛选的健康个体将完成3个试验日，在此期间，他们将接受（0，0.015，0.03 mg/kg）？9-THC采用双盲、随机、平衡设计。将通过测量20、30和40 Hz听觉咔哒声串诱发的EEG频谱功率来评估神经同步性指数。还将评估感知改变、精神病样症状、持续注意力、即时言语回忆、空间工作记忆和视觉物体识别记忆。初步结果：？9-THC在30 Hz听觉刺激（驾驶）下产生了与剂量相关的30 Hz功率降低。? 9-THC还将事件相关的光谱扰动减少到20和30 Hz驱动。? 9-THC降低了40 Hz驾驶的试验间相干性，并在较小程度上降低了20和30 Hz驾驶的试验间相干性。与剂量有关，？9-四氢大麻酚增加了知觉改变和精神病的评分，并导致言语回忆，空间工作记忆，视觉识别记忆和注意力的损害。相关性：该项目的目的是使用健康人的EEG来表征大麻素对大脑内电通信（神经同步）的影响，并将这些影响与其行为和认知影响联系起来。