School of Kinesiology, Western University, London, Ontario, Canada; Department of Clinical Neurological Sciences, University Hospital, London Health Sciences Centre, London, Ontario, Canada.
School of Kinesiology, Western University, London, Ontario, Canada; Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
Neuroimage Clin. 2019;23:101924. doi: 10.1016/j.nicl.2019.101924. Epub 2019 Jul 2.
Autonomic homeostasis is dependent upon several brainstem nuclei, as well as several cortical and subcortical structures. Together, these sites make up, in part, the central autonomic network. Neurogenic orthostatic hypotension (NOH) is a cardinal feature of autonomic failure that occurs due to a failure to increase sympathetic efferent activity in response to postural changes. Therefore, the purpose of the current study was to investigate brainstem functional connectivity in NOH patients with peripheral autonomic lesions resulting in autonomic failure. Fifteen controls (63 ± 13 years) and fifteen Neurogenic Orthostatic Hypotension patients (67 ± 6 years; p = .2) with peripheral autonomic dysfunction completed 5-min of rest and three Valsalva maneuvers during a functional brain scan. Functional connectivity from the brainstem to cortical and subcortical structures were contrasted between patients and controls. At rest controls had significantly greater brainstem connectivity to the anterior cingulate cortex (T-value: 4.29), left anterior insula (T-value:3.31), left putamen (T-value:3.31) and bilateral thalamus (T-value: 3.83; T-value:4.25) (p-FDR < 0.005). During Valsalva, controls showed significantly more connectivity between the brainstem and both the left anterior (cerebellum 4/5) and bilateral posterior cerebellum (cerebellar 9 and left cerebellar 6). Other cerebellar regions included brainstem-to-vermis. Other brainstem-to-cortical and subcortical regions included: bilateral putamen, posterior cingulate cortex (PCC), amygdala and medial prefrontal cortex. There was a significant negative correlation between the brainstem-cerebellar connectivity and severity of autonomic dysfunction (p < .01). During recovery phase of the Valsalva, controls had greater brainstem connectivity to the left thalamus (T-value:4.17); PCC (T-value:3.32); right putamen (T-value:3.28); right paracingulate gyrus (T-value:3.25) and left posterior cerebellum (C9) (T-value:3.21) (p-FDR < 0.05). The effect sizes for each brainstem connectivity during Valsalva and recovery ranged from moderate to strong. Patients with autonomic failure show reduced coupling between the brainstem and regions of the central autonomic network, including the cerebellum, insula, thalamus and cingulate cortices. Connectivity was associated with autonomic impairment. These findings may suggest impaired brainstem connectivity in patients with autonomic failure.
自主平衡依赖于几个脑干核团，以及几个皮质和皮质下结构。这些部位共同构成了部分中枢自主网络。神经源性直立性低血压（NOH）是自主衰竭的一个主要特征，它是由于姿势变化时交感传出活动增加失败引起的。因此，本研究的目的是研究外周自主神经病变导致自主衰竭的 NOH 患者的脑干功能连接。15 名对照者（63±13 岁）和 15 名神经源性直立性低血压患者（67±6 岁；p=0.2）完成了 5 分钟的休息和三次瓦尔萨尔瓦动作，同时进行功能脑扫描。将患者与对照组之间的脑干与皮质和皮质下结构的功能连接进行对比。在休息时，对照组与前扣带皮层（T 值：4.29）、左侧前岛叶（T 值：3.31）、左侧壳核（T 值：3.31）和双侧丘脑（T 值：3.83；T 值：4.25）的连接明显更强（p-FDR<0.005）。在瓦尔萨尔瓦期间，对照组显示出大脑与双侧前（小脑 4/5）和双侧后小脑（小脑 9 和左小脑 6）之间的连接明显增加。其他小脑区域包括脑干-蚓状核。其他脑干与皮质和皮质下区域包括：双侧壳核、后扣带皮层（PCC）、杏仁核和内侧前额叶皮质。脑干-小脑连接与自主神经功能障碍的严重程度呈显著负相关（p<0.01）。在瓦尔萨尔瓦的恢复阶段，对照组与左侧丘脑（T 值：4.17）、PCC（T 值：3.32）、右侧壳核（T 值：3.28）、右侧旁中央回（T 值：3.25）和左侧后小脑（C9）（T 值：3.21）的连接更强（p-FDR<0.05）。在瓦尔萨尔瓦和恢复期间，每个脑干连接的效应大小从中等到强不等。自主衰竭患者的脑干与中央自主网络的区域（包括小脑、岛叶、丘脑和扣带皮质）之间的耦合减少。连接与自主功能障碍有关。这些发现可能表明自主衰竭患者的脑干连接受损。
