The Locus Coeruleus (LC) is the major source of noradrenergic neurotransmission. Structural alterations in the LC have been observed in neurodegenerative disorders and at-risk individuals, although functional connectivity studies between the LC and other brain areas have not been yet performed in these populations. Patients with late-life major depressive disorder (MDD) are indeed at increased risk for neurodegenerative disorders, and here we investigated LC connectivity in late-life MDD in comparison to individuals with amnestic type mild cognitive impairment (aMCI) and healthy controls (HCs). We assessed 20 patients with late-life MDD, 16 patients with aMCI, and 26 HCs, who underwent a functional magnetic resonance scan while performing a visual oddball task. We assessed task-related modulations of LC connectivity (i.e., Psychophysiological Interactions, PPI) with other brain areas. A T1-weighted fast spin-echo sequence for LC localization was also obtained. Patients with late-life MDD showed lower global connectivity during target detection in a cluster encompassing the right caudal LC. Specifically, we observed lower LC connectivity with the left anterior cingulate cortex (ACC), the right fusiform gyrus, and different cerebellar clusters. Moreover, alterations in LC-ACC connectivity correlated negatively with depression severity (i.e., Geriatric Depression Scale and number of recurrences). Reduced connectivity of the LC during oddball performance seems to specifically characterize patients with late-life MDD, but not other populations of aged individuals with cognitive alterations. Such alteration is associated with different measures of disease severity, such as the current presence of symptoms and the burden of disease (number of recurrences).

蓝斑轨迹（LC）是去甲肾上腺素能神经传递的主要来源。尽管尚未在这些人群中进行LC和其他大脑区域之间的功能连接研究，但在神经退行性疾病和高危人群中已观察到LC的结构改变。患有晚期重度抑郁症（MDD）的患者确实存在神经退行性疾病的风险增加，在这里，我们与患有记忆删除型轻度认知障碍（aMCI）和健康对照（HCs）的个体相比，研究了晚期MDD中的LC连通性。我们评估了20例晚期MDD患者，16例aMCI患者和26例HC，他们在执行视觉奇数球任务时进行了功能磁共振扫描。我们评估了与任务相关的LC连接调制（即 与其他大脑区域的心理生理相互作用（PPI）。还获得了用于LC定位的T1加权快速自旋回波序列。晚期MDD患者在目标检测过程中，在包含右尾LC的簇中显示出较低的整体连通性。具体来说，我们观察到左前扣带回皮层（ACC），右梭状回和不同小脑簇的LC连接性较低。此外，LC-ACC连接性的改变与抑郁症的严重程度呈负相关（即老年抑郁量表和复发次数）。奇怪的比赛中，LC的连通性降低似乎是MDD晚期患者的特有特征，但其他年龄段的具有认知改变的人群则无此特征。这种变化与疾病严重程度的不同衡量指标有关，