HUMAN PSYCHOPHYSIOLOGICAL CORRELATES OF SENSORIMOTOR FUNCTIONING

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 a）某些神经精神障碍的特征在于基于大脑的有效抑制或“门控”感觉、认知或运动信息的能力的缺陷。为了研究这种抑制缺陷的生理基础，我们使用声惊吓反射的前脉冲抑制作为感觉运动门控的操作措施。我们在精神病和神经病患者（强迫症、亨廷顿病、精神分裂症、冲动控制障碍、图雷特综合征和注意力缺陷障碍）以及适当的对照比较人群中研究了声惊吓反射，包括惊吓的前脉冲抑制（PPI）和前脉冲易化。 大量临床前研究文献表明，惊吓反射（包括PPI）的前脉冲修饰受特定神经化学底物的调节。其中，已知脑多巴胺（DA）活性通过纹状体部分中的D2家族受体调节PPI。PPI被破坏或消除大鼠全身或脑内治疗DA受体激动剂。这些和相关的动物研究使我们能够确定一个特定的神经回路，连接边缘皮层结构，通过其基底神经节传出，脑桥结构，调节量的感觉运动门控，测量PPI。 这将是至关重要的，以确定是否这些相同的底物调节PPI在大鼠中，可以外推到人类，从而使我们能够解释神经系统和精神病患者的PPI异常模式的神经基础。 在一系列研究中，我们研究了PPI在人体中的神经化学，通过记录PPI对特定药理学探针的反应变化，尽可能使用足够的样本量、激动剂-拮抗剂相互作用和信息量-反应曲线。人类和大鼠对药理学操作的反应之间的相似性和差异为理解人类PPI的神经回路底物提供了重要证据。 B）感觉运动门控的差异也可以区分某些正常受试者群体。具体来说，前脉冲抑制是性二态性的，并且在某些正常人格维度上以系统和可预测的方式存在差异。为了促进这些“正常”的差异，在感觉运动门控的生物基板的研究，我们的研究已经确定了最佳的刺激参数，研究性别差异的前脉冲调制的惊吓在男性和女性的控制和患者人群。 c）感觉运动抑制的差异将通过一些而不是其他基于实验室的测量来检测，反映了测量的特定心理物理要求的差异。为了增加我们对患者和正常人群感觉运动抑制模式的理解，以及对被认为调节一种形式的感觉运动抑制（PPI）的脑回路的特定操作的感觉运动抑制变化的理解，我们还评估了受试者的潜在抑制，负启动和Stroop测试。 d）测试对象的特定特征是有用的分组变量，用于理解对照人群中的感觉运动门控模式。具体的问卷调查被用来评估控制人群的个性和行为特征。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. a) Certain neuropsychiatric disorders are characterized by a brain-based deficit in the ability to effectively inhibit, or "gate" sensory, cognitive or motor information. To study the physiological basis of this inhibitory deficit, we use prepulse inhibition of the acoustic startle reflex as an operational measure of sensorimotor gating. We study the acoustic startle reflex, including prepulse inhibition (PPI) and prepulse facilitation of startle, in Psychiatric and Neurologic patients (Obsessive Compulsive Disorder, Huntington's Disease, Schizophrenia, Impulse Control Disorders, Tourette's Syndrome, and Attention Deficit Disorder), and in appropriate control comparison populations. A substantial literature of preclinical studies demonstrates that prepulse modification of the startle reflex, including PPI, is regulated by specific neurochemical substrates. Among these, brain dopamine (DA) activity is known to regulate PPI via D2-family receptors in portions of the striatum. PPI is disrupted or eliminated in rats by systemic or intracerebral treatment with DA agonists. These and related animal studies have allowed us to identify a specific neural circuitry, connecting limbic cortical structures, through their basal ganglia efferents, to pontine structures, that regulates the amount of sensorimotor gating, as measured by PPI. It would be critically important to determine whether these same substrates regulating PPI in rats, could be extrapolated to humans, and thus allow us to interpret the neural basis for abnormal patterns of PPI in neurologic and psychiatric patients. In a series of studies, we investigated the neurochemistry of PPI in humans, by documenting changes in PPI in response to specific pharmacologic probes, using adequate sample sizes, agonist-antagonist interactions and informative dose-response profiles where possible. The similarities and differences between the responses to pharmacological manipulations in humans and rats provide important evidence for understanding the neural circuit substrates of PPI in humans. b) Differences in sensorimotor gating also distinguish certain groups of normal subjects. Specifically, prepulse inhibition is sexually dimorphic, and differs in systematic and predictable ways across certain normal personality dimensions. To facilitate studies of the biological substrates for these "normal" differences in sensorimotor gating, our studies have identified the optimal stimulus parameters for studying sex differences in prepulse modulation of startle in men and women in control and patient populations. c) Differences in sensorimotor inhibition will be detected by some, but not other laboratory-based measures, reflecting differences in the particular psychophysical demands of the measure. To add to our understanding of patterns of sensorimotor inhibition across patient and normal populations, and of changes in sensorimotor inhibition in response to specific manipulations of brain circuitry thought to regulate one form of sensorimotor inhibition (PPI), we also assess Latent Inhibition, Negative Priming and the Stroop Test in our subjects. d) Particular characteristics of the test subjects are useful grouping variables for understanding patterns of sensorimotor gating in control populations. Specific questionnaires are used to evaluate personality and behavioral characteristics of the control populations.