Butler P Monroe, Chiong Winston
Department of Neurology, UCSF Memory and Aging Center, UCSF School of Medicine, San Francisco, CA, United States.
Department of Neurology, UCSF Memory and Aging Center, UCSF School of Medicine, San Francisco, CA, United States.
Handb Clin Neurol. 2019;163:391-410. doi: 10.1016/B978-0-12-804281-6.00021-5.
The frontal lobes play an integral role in human socioemotional and cognitive function. Sense of self, moral decisions, empathy, and behavioral monitoring of goal-states all depend on key nodes within frontal cortex. While several neurodegenerative diseases can affect frontal function, frontotemporal dementia (FTD) has particularly serious and specific effects, which thus provide insights into the role of frontal circuits in homeostasis and adaptive behavior. FTD represents a collection of disorders with specific clinical-pathologic correlates, imaging, and genetics. Patients with FTD and initial prefrontal degeneration often present with neuropsychiatric symptoms such as loss of social decorum, new obsessions, or lack of empathy. In those patients with early anterior temporal degeneration, language (particularly in patients with left-predominant disease) and socioemotional changes (particularly in patients with right-predominant disease) precede eventual frontal dysregulation. Herein, we review a brief history of FTD, initial clinical descriptions, and the evolution of nomenclature. Next, we consider clinical features, neuropathology, imaging, and genetics in FTD-spectrum disorders in relation to the integrity of frontal circuits. In particular, we focus our discussion on behavioral variant FTD given its profound impact on cortical and subcortical frontal structures. This review highlights the clinical heterogeneity of behavioral phenotypes as well as the clinical-anatomic convergence of varying proteinopathies at the neuronal, regional, and network level. Recent neuroimaging and modeling approaches in FTD reveal varying network dysfunction centered on frontal-insular cortices, which underscores the role of the human frontal lobes in complex behaviors. We conclude the chapter reviewing the cognitive and behavioral neuroscience findings furnished from studies in FTD related to executive and socioemotional function, reward-processing, decision-making, and sense of self.
额叶在人类社会情感和认知功能中发挥着不可或缺的作用。自我意识、道德决策、同理心以及对目标状态的行为监测均依赖于额叶皮质内的关键节点。虽然几种神经退行性疾病会影响额叶功能，但额颞叶痴呆（FTD）具有尤为严重且特定的影响，从而为额叶回路在体内平衡和适应性行为中的作用提供了见解。FTD代表了一系列具有特定临床病理关联、影像学特征和遗传学特征的疾病。患有FTD且最初出现前额叶变性的患者常表现出神经精神症状，如社交礼仪丧失、新的强迫观念或缺乏同理心。在那些早期出现颞叶前部变性的患者中，语言障碍（特别是在左侧病变为主的患者中）和社会情感变化（特别是在右侧病变为主的患者中）先于最终的额叶功能失调出现。在此，我们回顾FTD的简要历史、最初的临床描述以及命名法的演变。接下来，我们考虑FTD谱系障碍的临床特征、神经病理学、影像学和遗传学与额叶回路完整性的关系。特别是，鉴于行为变异型FTD对皮质和皮质下额叶结构有深远影响，我们将讨论重点放在该类型上。本综述强调了行为表型的临床异质性以及不同蛋白病在神经元、区域和网络水平上的临床解剖学趋同性。FTD中最近的神经影像学和建模方法揭示了以额叶 - 岛叶皮质为中心的不同网络功能障碍，这突出了人类额叶在复杂行为中的作用。我们在本章结尾回顾了从FTD相关研究中得出的关于执行功能和社会情感功能、奖赏处理、决策制定以及自我意识的认知和行为神经科学研究结果。
