Olfactory nerve as channel for Electrical Stimulation of the Salience Network

抑郁症是一种严重的精神障碍，在德国大约有700万人受到影响。除了导致严重的生活质量损害外，抑郁症的病死率也很高。因此，有效的抗抑郁治疗是有必要的。对于非常严重或耐药的病例，电休克治疗是最先进的选择，会导致杏仁核、海马体、前扣带回皮质(ACC)以及内侧和下部颞叶皮质突触、神经元和神经胶质细胞的起源发生改变。然而，这种治疗有副作用，这就是为什么更广泛的治疗选择是可取的。由于抑郁症与突显网络处理受损有关，因此一种聚焦的方法可能针对相关的大脑区域，如ACC、前脑岛和杏仁核。我们相信，通过嗅神经刺激是一种很有前途的途径。重度抑郁症在解剖和功能上与嗅觉有密切的重叠--嗅觉障碍患者对抑郁症的易感性增加了三倍，而且重度抑郁症通常伴随着嗅觉功能的降低。这种关系源于中央嗅觉结构和参与突显加工的结构之间的密切联系，并基于功能的共同进化。化学感觉是物种间最古老的交流形式，出现于5亿年前，最初专门用于嗅觉处理的中央结构，现在是情绪处理的关键。我们先前和初步的工作表明，刺激嗅束可以改变中枢突出结构对情绪刺激的反应性。另一个研究小组最近发表的一篇论文表明，嗅觉区域内的大脑连通性可以通过电刺激嗅觉上皮来改变。目前还没有人研究电刺激嗅神经是否影响神经功能，如杏仁核、前岛和ACC等与突起相关的结构的连通性或激活。我们的目标是通过检查鼻内电刺激如何改变行为情感反应和神经活动以及突出网络中的连通性，来检查健康参与者的这种可能性。我们的研究小组拥有成功刺激嗅觉上皮、大脑网络分析和研究情绪行为的知识和设备。此外，我们团队的跨学科使我们能够在这项基础研究提案中继续包含临床视角。这个项目有可能为对重度抑郁症患者的突出网络进行有针对性的、仅有轻微侵入性的刺激铺平道路。

Depression is a severe mental disorder, affecting about 7,000,000 people in Germany. Besides leading to significant impairments of quality of life, depression has a high case fatality. Hence, an effective anti-depressive treatment is warranted. For very severe or medication-resistant cases, electro-convulsive therapy is the state of the art option leading to alterations of the genesis of synapses, neurons and glia cells in the region of the amygdala, hippocampus, the anterior cingulate Cortex (ACC) and medial and inferior temporal cortex. This treatment has however side effects, which is why a broader variety of treatment options is desirable. Because depression is specifically related to impaired salience network processing, a focussed approach may target relevant brain regions, such as the ACC, the anterior insula and the amygdala. We are confident that stimulation via the olfactory nerve is a promising pathway. Major depressive disorder presents a close anatomical and functional overlap with olfaction - vulnerability to depression is enhanced by a factor of three in patients with smell disorders and major depression is often accompanied by reduced olfactory function. This relation originates from the close connection between central olfactory structures and structures involved in salience processing and is based on a co-evolution of functions. Chemosensation is the oldest form of communication between species, emerging 500 million years ago and the central structures, originally dedicated to olfactory processing, are now pivotal for emotion processing. Our previous and preliminary work suggests that stimulation of the olfactory tract can alter the reactivity of central salience structures to emotional stimuli. A recent publication from another group showed, that brain connectivity within olfactory regions can be altered by electrical stimulation of the olfactory epithelium. It has not been examined yet, whether electrical stimulation of the olfactory nerve impacts the neural functioning in terms of connectivity or activation of salience relevant structures, such as the amygdala, the anterior insula and the ACC. We aim to examine this possibility in healthy participants by examining how intranasal electrical stimulation alters behavioural emotion responses and neural activity and connectivity in the salience network. Our research group has both the knowledge and the equipment for successful stimulation of the olfactory epithelium, for brain network analysis and for studying emotion behavior. The interdisciplinary of our team furthermore allows us to continuously include a clinical perspective in this basic research proposal. This project has the potential to pave the way for a focused and only mildly invasive stimulation of the salience network in patients with severe depression.