Adaptive and Maladaptive Neural Network Responses to Inhibitory Challenges

摘要 冲动控制预示着无数严重的公共健康问题，这些问题大大减少了预期寿命， 包括自杀、暴力、吸毒和其他危险行为。尽管众所周知，抑制作用 控制缺陷增加了这些临床问题的风险，这一领域取得进展的一个关键障碍是 关于这一核心调控过程如何与其他认知和情感系统相互作用，人们知之甚少。 鉴于日常生活中发生的冲动控制故障反映了多种认知和行为的相互作用 情感系统，这种知识对于将脉冲控制故障映射到神经电路和 准确地将精神病理学中出现的冲动建模为神经系统的中断。这个 这项应用的目的是确定支持抑制控制的大脑功能网络如何响应 在认知上和情感上具有挑战性的环境，并评估这些网络对 用冲动解释临床问题。我们提出了一项新的调查，旨在更好地了解 已知的三种环境如何挑战冲动控制(认知资源耗尽、竞争欲望 暗示和负面情绪诱导)影响支持成功抑制的功能性大脑网络 控制，并最终在精神疾病中进行自我调节。首先，健康的成年人将接受彻底的临床检查 进行诊断评估并完成一系列功能磁共振成像(FMRI)任务 核磁共振扫描仪，评估在不同的挑战背景下的抑制控制。这些数据预计将 提供一个精确的工作模型，说明功能性大脑网络如何补偿以满足独特的抑制 控制需求出现在不同的挑战性环境中。他们还将上下文作为分析的一个级别添加到 现有的抑制神经模型，使它们更接近于捕捉抑制的多维本质 控制日常生活中的失败。接下来，鉴于复制失败在神经成像研究中很常见，一个 受试者将在三个月后接受第二次MRI扫描，以确定 我们建议研究的是抑制控制的新的脑功能指标。最后，美国政府的核心目标是 NIMH RDoC的倡议是将临床问题与神经系统联系起来(Cuthbert&Insel，2013)。与一致 在这一倡议中，我们建议将抑制控制网络的中断作为潜在的跨诊断风险进行检查 外化障碍的因素(例如，酒精/药物使用障碍、反社会人格障碍)和 作为识别抑制亚型的生物标志物。这种方法有可能创造出更多 以神经科学为基础对与冲动有关的临床问题进行分类。总的来说，这项研究是 有望通过加深对临床冲动的理解，最终有助于临床冲动的治疗 支持成功抑制控制的大脑网络。

ABSTRACT Impulse control predicts a myriad of serious public health problems that substantially reduce life expectancy, including suicide, violence, substance use, and other risky behaviors. Although it is known that inhibitory control deficits confer risk for these clinical problems, one critical barrier to progress in this field is that much less is known about how this core regulatory process interacts with other cognitive and affective systems. Given that impulse control failures that occur in everyday life reflect the interaction of multiple cognitive and affective systems, this knowledge is critical for mapping impulse control failures onto neural circuits and accurately modeling the impulsivity that occurs in psychopathology as disruptions in neural systems. The objective of this application is to determine how functional brain networks supporting inhibitory control respond to cognitively- and affectively-challenging contexts and to evaluate the relevance of these networks for explaining clinical problems with impulsivity. We propose a novel investigation aimed at better understanding how three contexts known to challenge impulse control (cognitive resource depletion, competing appetitive cues, and negative mood induction) impact the functional brain networks that support successful inhibitory control and, ultimately, self-regulation in mental illness. First, healthy adults will undergo a thorough clinical diagnostic assessment and complete a battery of functional magnetic resonance imaging (fMRI) tasks in the MRI scanner that assess inhibitory control in different challenging contexts. These data are expected to contribute a precise working model of how functional brain networks compensate to meet the unique inhibitory control demands present in different challenging contexts. They will also add context as a level of analysis to existing neural models of inhibition, bringing them closer to capturing the multidimensional nature of inhibitory control failures in everyday life. Next, given that replication failures are common in neuroimaging research, a subset of participants will undergo a second MRI scan after a three-month period to establish the reliability of the novel functional brain metrics of inhibitory control we propose to investigate. Finally, a central goal of the NIMH RDoC initiative is to link clinical problems to neural systems (Cuthbert & Insel, 2013). Consistent with this initiative, we propose to examine disruptions in inhibitory control networks as potential transdiagnostic risk factors for externalizing disorders (e.g., alcohol/ substance use disorders, antisocial personality disorder) and as biomarkers for identifying subtypes of inhibition. This approach has the potential to create a more neuroscience-based classification of clinical problems related to impulsivity. Together, this research is expected to ultimately aid in the treatment of clinical impulsivity by leading to a deeper understanding of the brain networks that support successful inhibitory control.