Olfactory dysfunction is often the earliest indicator of disease in a range of neurological and psychiatric disorders. One tempting working hypothesis is that pathological changes in the peripheral olfactory system where the body is exposed to many adverse environmental stressors may have a causal role for the brain alteration. Whether and how the peripheral pathology spreads to more central brain regions may be effectively studied in rodent models, and there is successful precedence in experimental models for Parkinson’s disease. It is of interest to study whether a similar mechanism may underlie the pathology of psychiatric illnesses, such as schizophrenia. However, direct comparison between rodent models and humans includes challenges under light of comparative neuroanatomy and experimental methodologies used in these two distinct species. We believe that neuroimaging modality that has been the main methodology of human brain studies may be a useful viewpoint to address and fill the knowledge gap between rodents and humans in this scientific question. Accordingly, in the present review article, we focus on brain imaging studies associated with olfaction in healthy humans and patients with neurological and psychiatric disorders, and if available those in rodents. We organize this review article at three levels: 1) olfactory bulb (OB) and peripheral structures of the olfactory system, 2) primary olfactory cortical and subcortical regions, and 3) associated higher-order cortical regions. This research area is still underdeveloped, and we acknowledge that further validation with independent cohorts may be needed for many studies presented here, in particular those with human subjects. Nevertheless, whether and how peripheral olfactory disturbance impacts brain function is becoming even a hotter topic in the ongoing COVID-19 pandemic, given the risk of long-term changes of mental status associated with olfactory infection of SARS-CoV-2. Together, in this review article, we introduce this underdeveloped but important research area focusing on its implications in neurological and psychiatric disorders, with several pioneered publications.

嗅觉功能障碍通常是一系列神经和精神疾病的最早指标。一个诱人的工作假设是，身体暴露于许多不利环境压力源的周围嗅觉系统的病理变化可能对大脑改变具有因果作用。外周病变是否以及如何扩散到更中央的大脑区域可以在啮齿动物模型中得到有效研究，并且在帕金森氏病的实验模型中有成功的先例。研究类似的机制是否可能是精神疾病（如精神分裂症）病理学的基础是很有意义的。然而，啮齿动物模型和人类之间的直接比较包括在这两个不同物种中使用的比较神经解剖学和实验方法的挑战。我们认为，神经成像模式一直是人类大脑研究的主要方法，可能是解决和填补啮齿动物和人类在这个科学问题上的知识差距的有用观点。因此，在本综述文章中，我们重点关注与健康人类和神经和精神疾病患者以及啮齿动物（如果有的话）的嗅觉相关的脑成像研究。我们将这篇评论文章分为三个层次：1) 嗅球 (OB) 和嗅觉系统的外围结构，2) 初级嗅觉皮层和皮层下区域，以及 3) 相关的高阶皮层区域。这个研究领域仍然不发达，我们承认这里介绍的许多研究可能需要独立队列的进一步验证，特别是那些与人类受试者相关的研究。然而，考虑到与嗅觉感染 SARS-CoV-2 相关的精神状态长期变化的风险，外周嗅觉障碍是否以及如何影响大脑功能正在成为正在进行的 COVID-19 大流行中的一个更热门的话题。在这篇评论文章中，我们一起介绍了这个不发达但重要的研究领域，重点关注其对神经和精神疾病的影响，并发表了几篇开创性的出版物。