Brain mechanisms underlying selective attention in IBS

描述(由申请人提供)： 症状相关的恐惧和对疾病相关刺激(胃肠道[GI]感觉、症状或背景)的高度警惕可能在触发肠易激综合征(IBS)的中枢疼痛放大系统中发挥重要作用。这个R03测试了一个普遍的假设，即IBS的中枢疼痛放大部分与负责调节注意力的大脑机制的损害有关。注意是一个过程，涉及选择相互竞争的感觉信息，以优化当前对与有机体相关的特定刺激的行为反应。我假设IBS的中枢疼痛放大与负责过滤分散注意力的信息，即与症状相关的刺激的注意过程中的损害有关。我将测试一个特定的假设，即减少前额叶皮质(PFC)控制机制的参与将导致PFC对威胁相关分心因素的控制减弱，并使情绪唤醒回路(以杏仁核为中心的预注意威胁机制)失去抑制。功能磁共振成像将被用来评估IBS患者与健康对照组在情绪和威胁相关刺激时选择性注意网络参与的差异。比较了IBS和对照组在一般注意(警示、定向、执行)和选择性注意与疾病相关的GI单词和威胁刺激任务中的大脑反应和行为表现。为了对大脑区域/网络和行为做出有效的因果推断，将应用经颅磁刺激来产生对照组背外侧PFC的暂时和完全可逆的失活。拟议的研究是我的K08奖的延伸，该奖项旨在确定IBS患者认知、行为、情感和生理变化的神经解剖学基础。这项研究将为一项计划中的R01拨款提案提供初步数据，该提案的重点是描绘IBS患者PFC功能障碍的机制。更全面地了解中枢疼痛放大的认知机制将有助于更好地理解认知行为疗法等非药物治疗方法。 公共卫生相关性：肠易激综合征是一种常见的慢性功能性胃肠道疾病，以腹痛和排便习惯改变为特征，严重影响与健康相关的生活质量和医疗保健利用。更好地了解腹痛中枢放大的生物学机制可能会促进更有效的药物治疗的发展。目前的研究评估了从肠道过滤无关信息所需的注意力机制和潜在的大脑回路，并将测试这些功能是否在IBS中受损。

DESCRIPTION (provided by applicant): Symptom-related fears and associated hypervigilance toward disease-related stimuli (gastrointestinal [GI] sensations, symptoms or contexts) may play an important role in triggering central pain amplification systems in irritable bowel syndrome (IBS). This R03 tests the general hypothesis that central pain amplification in IBS is in part related to impairment in brain mechanisms responsible for regulating attention. Attention is a process involving the selection of competing sensory information to optimize current behavioral responses to specific stimuli relevant for the organism. I hypothesize that central pain amplification in IBS is related to impairment in attention processes responsible for filtering distracting information, i.e., symptom-related stimuli. I will test the specific hypothesis that decreased engagement of prefrontal cortical (PFC) control mechanisms will result in diminished PFC control over threat-related distracters and disinhibition of emotional arousal circuits (amygdala-centered pre-attentive threat mechanisms). Functional magnetic resonance imaging will be used to evaluate differences in the engagement of selective attention networks during emotional and threat-related stimuli in IBS patients versus healthy control subjects. Brain responses and behavioral performance on tasks indexing general attention (alerting, orienting, executive) and selective attention to disease-relevant GI words and threatening stimuli are compared between IBS and control subjects. To make valid causal inferences regarding the brain regions/networks and behavior, transcranial magnetic stimulation will be applied to produce temporary and fully reversible inactivation of the dorsolateral PFC in controls. The proposed studies are an extension of my K08 award that aims to identify the neuroanatomical substrates of the cognitive, behavioral, affective and physiologic alterations in IBS patients. This research will provide preliminary data for a planned R01 grant proposal focused on delineating the mechanism of PFC dysfunction in IBS. More complete understanding of cognitive mechanisms involved in central pain amplification will provide a better understanding of non-pharmacological treatment approaches such as cognitive behavioral therapy. PUBLIC HEALTH RELEVANCE: Irritable bowel syndrome is a common, chronic functional gastrointestinal disorder, characterized by abdominal pain and altered bowel habits, with significant impact on health-related quality of life and health care utilization. A better understanding of the biological mechanisms underlying central amplification of abdominal pain may increase progress in the development of more effective pharmacological therapies. The current research evaluates the attentional mechanisms and underlying brain circuits necessary to filter non-relevant information from the gut, and will test whether these functions are impaired in IBS.