Beliveau Vincent, Svarer Claus, Frokjaer Vibe G, Knudsen Gitte M, Greve Douglas N, Fisher Patrick M
Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark.
Neuroimage. 2015 Aug 1;116:187-95. doi: 10.1016/j.neuroimage.2015.04.065. Epub 2015 May 9.
Serotonin (5-HT) is a neurotransmitter critically involved in a broad range of brain functions and implicated in the pathophysiology of neuropsychiatric illnesses including major depression, anxiety and sleep disorders. Despite being widely distributed throughout the brain, there is limited knowledge on the contribution of 5-HT to intrinsic brain activity. The dorsal raphe (DR) and median raphe (MR) nuclei are the source of most serotonergic neurons projecting throughout the brain and thus provide a compelling target for a seed-based probe of resting-state activity related to 5-HT. Here we implemented a novel multimodal neuroimaging approach for investigating resting-state functional connectivity (FC) between DR and MR and cortical, subcortical and cerebellar target areas. Using [(11)C]DASB positron emission tomography (PET) images of the brain serotonin transporter (5-HTT) combined with structural MRI from 49 healthy volunteers, we delineated DR and MR and performed a seed-based resting-state FC analysis. The DR and MR seeds produced largely similar FC maps: significant positive FC with brain regions involved in cognitive and emotion processing including anterior cingulate, amygdala, insula, hippocampus, thalamus, basal ganglia and cerebellum. Significant negative FC was observed within pre- and postcentral gyri for the DR but not for the MR seed. We observed a significant association between DR and MR FC and regional 5-HTT binding. Our results provide evidence for a resting-state network related to DR and MR and comprising regions receiving serotonergic innervation and centrally involved in 5-HT related behaviors including emotion, cognition and reward processing. These findings provide a novel advance in estimating resting-state FC related to 5-HT signaling, which can benefit our understanding of its role in behavior and neuropsychiatric illnesses.
血清素（5-羟色胺，5-HT）是一种神经递质，在广泛的脑功能中起关键作用，并与包括重度抑郁症、焦虑症和睡眠障碍在内的神经精神疾病的病理生理学有关。尽管5-HT在整个大脑中广泛分布，但关于其对大脑内在活动的贡献的了解有限。中缝背核（DR）和中缝正中核（MR）是投射到整个大脑的大多数5-羟色胺能神经元的来源，因此为基于种子点的与5-HT相关的静息态活动探测提供了一个有吸引力的靶点。在这里，我们实施了一种新颖的多模态神经成像方法，用于研究DR和MR与皮质、皮质下和小脑目标区域之间的静息态功能连接（FC）。使用49名健康志愿者的大脑血清素转运体（5-HTT）的[(11)C]DASB正电子发射断层扫描（PET）图像与结构MRI相结合，我们勾勒出DR和MR，并进行了基于种子点的静息态FC分析。DR和MR种子点产生的FC图谱在很大程度上相似：与参与认知和情绪处理的脑区有显著的正FC，包括前扣带回、杏仁核、岛叶、海马体、丘脑、基底神经节和小脑。在中央前回和中央后回内，DR种子点观察到显著的负FC，而MR种子点未观察到。我们观察到DR和MR的FC与区域5-HTT结合之间存在显著关联。我们的结果为与DR和MR相关的静息态网络提供了证据，该网络包括接受5-羟色胺能神经支配且在包括情绪、认知和奖赏处理在内的与5-HT相关行为中起核心作用的区域。这些发现为估计与5-HT信号相关的静息态FC提供了新的进展，这有助于我们理解其在行为和神经精神疾病中的作用。
