Data_Sheet_1_Neural evidence for non-orofacial triggers in mild misophonia.pdf

Misophonia, an extreme aversion to certain environmental sounds, is a highly prevalent yet understudied condition plaguing roughly 20% of the general population. Although neuroimaging research on misophonia is scant, recent work showing higher resting-state functional connectivity (rs-fMRI) between auditory cortex and orofacial motor cortex in misophonia vs. controls has led researchers to speculate that misophonia is caused by orofacial mirror neurons. Since orofacial motor cortex was defined using rs-fMRI, we attempted to theoretically replicate these findings using orofacial cortex defined by task-based fMRI instead. Further, given our recent work showing that a wide variety of sounds can be triggering (i.e., not just oral/nasal sounds), we investigated whether there is any neural evidence for misophonic aversion to non-orofacial stimuli. Sampling 19 adults with varying misophonia from the community, we collected resting state data and an fMRI task involving phoneme articulation and finger-tapping. We first defined “orofacial” cortex in each participant using rs-fMRI as done previously, producing what we call resting-state regions of interest (rsROIs). Additionally, we functionally defined regions (fROIs) representing “orofacial” or “finger” cortex using phoneme or finger-tapping activation from the fMRI task, respectively. To investigate the motor specificity of connectivity differences, we subdivided the rsROIs and fROIs into separate sensorimotor areas based on their overlap with two common atlases. We then calculated rs-fMRI between each rsROI/fROI and a priori non-sensorimotor ROIs. We found increased connectivity in mild misophonia between rsROIs and both auditory cortex and insula, theoretically replicating previous results, with differences extending across multiple sensorimotor regions. However, the orofacial task-based fROIs did not show this pattern, suggesting the “orofacial” cortex described previously was not capturing true orofacial cortex; in fact, using task-based fMRI evidence, we find no selectivity to orofacial action in these previously described “orofacial” regions. Instead, we observed higher connectivity between finger fROIs and insula in mild misophonia, demonstrating neural evidence for non-orofacial triggers. These results provide support for a neural representation of misophonia beyond merely an orofacial/motor origin, leading to important implications for the conceptualization and treatment of misophonia.

米索福尼亚，一种对特定环境声音的极端厌恶，是一种高度普遍但研究不足的状况，困扰着大约20%的普通人群。尽管关于米索福尼亚的神经影像学研究为数不多，但近期研究表明，与对照者相比，米索福尼亚患者的听觉皮层与口腔面部运动皮层在静息态功能连接性（rs-fMRI）方面更高，这促使研究者推测米索福尼亚可能是由口腔面部镜像神经元引起的。鉴于口腔面部运动皮层是通过rs-fMRI定义的，我们试图利用基于任务的fMRI定义的口腔面部皮层，从理论上复制这些发现。此外，鉴于我们近期的工作表明，各种声音都可能成为触发因素（即，不仅仅是口腔/鼻腔声音），我们研究了是否存在对非口腔面部刺激的米索福尼亚厌恶的神经证据。我们从社区中选取了19名具有不同程度米索福尼亚的成年人，收集了静息态数据和涉及音素发音和手指敲击的fMRI任务。我们首先使用与先前相同的方法，通过rs-fMRI在每个参与者中定义了“口腔面部”皮层，产生了我们所谓的静息态感兴趣区域（rsROIs）。此外，我们使用音素或手指敲击激活从fMRI任务中分别功能性地定义了代表“口腔面部”或“手指”皮层的区域（fROIs）。为了探究连接性差异的运动特异性，我们根据与两个常见图谱的重叠，将rsROIs和fROIs细分为独立的本体感觉运动区域。然后，我们计算了每个rsROI/fROI与先验非本体感觉ROI之间的rs-fMRI。我们发现，在轻度米索福尼亚患者中，rsROIs与听觉皮层和岛叶之间的连接性增加，从理论上复制了先前的研究结果，差异扩展到多个本体感觉区域。然而，口腔面部任务基础的fROIs并未显示出这种模式，这表明先前描述的“口腔面部”皮层并未捕捉到真正的口腔面部皮层；事实上，使用基于任务的fMRI证据，我们发现这些先前描述的“口腔面部”区域对口腔面部动作没有选择性。相反，我们在轻度米索福尼亚患者中观察到手指fROIs与岛叶之间的连接性更高，这表明了非口腔面部触发因素的神经证据。这些结果为米索福尼亚的神经表征提供了支持，超出了仅仅口腔/运动起源的范畴，对米索福尼亚的概念化和治疗具有重要启示。