Matar Elie, Ehgoetz Martens Kaylena A, Phillips Joseph R, Wainstein Gabriel, Halliday Glenda M, Lewis Simon J G, Shine James M
Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Forefront Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
NPJ Parkinsons Dis. 2022 Feb 17;8(1):16. doi: 10.1038/s41531-022-00279-x.
Cognitive fluctuations are a characteristic and distressing disturbance of attention and consciousness seen in patients with Dementia with Lewy bodies and Parkinson's disease dementia. It has been proposed that fluctuations result from disruption of key neuromodulatory systems supporting states of attention and wakefulness which are normally characterised by temporally variable and highly integrated functional network architectures. In this study, patients with DLB (n = 25) and age-matched controls (n = 49) were assessed using dynamic resting state fMRI. A dynamic network signature of reduced temporal variability and integration was identified in DLB patients compared to controls. Reduced temporal variability correlated significantly with fluctuation-related measures using a sustained attention task. A less integrated (more segregated) functional network architecture was seen in DLB patients compared to the control group, with regions of reduced integration observed across dorsal and ventral attention, sensorimotor, visual, cingulo-opercular and cingulo-parietal networks. Reduced network integration correlated positively with subjective and objective measures of fluctuations. Regions of reduced integration and unstable regional assignments significantly matched areas of expression of specific classes of noradrenergic and cholinergic receptors across the cerebral cortex. Correlating topological measures with maps of neurotransmitter/neuromodulator receptor gene expression, we found that regions of reduced integration and unstable modular assignments correlated significantly with the pattern of expression of subclasses of noradrenergic and cholinergic receptors across the cerebral cortex. Altogether, these findings demonstrate that cognitive fluctuations are associated with an imaging signature of dynamic network impairment linked to specific neurotransmitters/neuromodulators within the ascending arousal system, highlighting novel potential diagnostic and therapeutic approaches for this troubling symptom.
认知波动是路易体痴呆和帕金森病痴呆患者中出现的一种特征性且令人苦恼的注意力和意识障碍。有人提出，波动是由于支持注意力和觉醒状态的关键神经调节系统受到破坏所致，这些状态通常以时间上可变且高度整合的功能网络架构为特征。在本研究中，使用动态静息态功能磁共振成像对25例路易体痴呆（DLB）患者和49例年龄匹配的对照者进行了评估。与对照组相比，在DLB患者中发现了时间变异性和整合性降低的动态网络特征。使用持续注意力任务，时间变异性降低与波动相关指标显著相关。与对照组相比，DLB患者的功能网络架构整合性较低（分离性较高），在背侧和腹侧注意力、感觉运动、视觉、扣带回-脑岛和扣带回-顶叶网络中均观察到整合性降低的区域。网络整合性降低与波动的主观和客观指标呈正相关。整合性降低和区域分配不稳定的区域与大脑皮层中特定类别的去甲肾上腺素能和胆碱能受体的表达区域显著匹配。将拓扑测量与神经递质/神经调节受体基因表达图谱相关联，我们发现整合性降低和模块化分配不稳定的区域与大脑皮层中去甲肾上腺素能和胆碱能受体亚类的表达模式显著相关。总之，这些发现表明，认知波动与与上行觉醒系统内特定神经递质/神经调节因子相关的动态网络损伤的成像特征有关，突出了针对这一令人困扰症状的新的潜在诊断和治疗方法。
