Cannabinoids, Neural Synchrony and Information Processing

说明(申请人提供)：背景：大麻类物质产生暂时性精神分裂效应以及注意力和记忆障碍的机制尚不清楚。知觉、记忆和注意功能是建立在分布式过程的基础上的，这些过程被认为是由同步的高频振荡活动“捆绑”在一起的。在人类中，宏观神经同步性可以通过EEG对不同频率的感觉(听觉)刺激的夹带来非侵入性地评估。大脑就像一个调谐振荡器，稳定状态的脑电波形引导到所呈现的刺激的频率和相位，提供支持同步的神经回路的功能状态的指示器。大麻素降低了大鼠海马片中的伽马频段功率，在听觉夹带范式中，大麻使用者表现出比对照组更低的β频段功率。我们不知道有任何研究检测大麻类物质对健康人类脑电神经同步性的急性影响。假设：9-THC以剂量相关的方式，将降低脑电对20、30和40赫兹的听觉稳态夹带反应的频谱功率。二次分析将检查？9-THC对稳态脑电反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)和试验间相位一致性(ITC)。9-THC引起的知觉改变、精神病样症状和认知障碍(注意力、言语回忆和工作记忆)的变化将与光谱能力的变化相关。方法：经过仔细筛选的健康受试者将完成3个试验日，在此期间，他们将以双盲、随机、平衡设计接受(0.015，0.03，0.03 mg/kg)9-THC。神经同步性指数将通过测量20、30和40赫兹的听觉咔哒声序列诱发的脑电频谱功率来评估。还将评估知觉变化、精神病样症状、持续注意力、即刻言语回忆、空间工作记忆和视觉物体识别记忆。初步结果：9-THC对30赫兹的听觉刺激(驾驶)有剂量相关的功率降低作用。？9-THC还将与事件相关的频谱扰动减少到20和30赫兹驱动。？9-THC将试验间相干性降低到40赫兹驱动，在较小程度上减少到20赫兹和30赫兹驱动。以剂量相关的方式，？9-THC增加了知觉改变和精神病测量的分数，并导致了言语记忆、空间工作记忆、视觉识别记忆和注意力测量的损害。相关性：该项目的目的是利用脑电来表征大麻类物质对大脑内电通讯(神经同步性)的影响，并将这些影响与其行为和认知影响联系起来。

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.