From the Diagnostic Radiology and Nuclear Medicine (L.C., M.C.R., H.L., X.Z., E.C., J.W., E.H.H., T.M.E.), and Department of Neurology (L.C.), University of Maryland School of Medicine; Department of Neurology (L.C., T.M.E.), Johns Hopkins University School of Medicine, Baltimore; Program in Neuroscience (L.C., M.C.R.), Institute of Human Virology (L.C., E.W., S.K.), and Division of Infectious Disease (E.W., S.K.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Neurology. 2023 Jun 6;100(23):e2409-e2423. doi: 10.1212/WNL.0000000000207309. Epub 2023 Apr 26.
Post-COVID condition (PCC) is common and often involves neuropsychiatric symptoms. This study aimed to use blood oxygenation level-dependent fMRI (BOLD-fMRI) to assess whether participants with PCC had abnormal brain activation during working memory (WM) and whether the abnormal brain activation could predict cognitive performance, motor function, or psychiatric symptoms.
The participants with PCC had documented coronavirus disease 2019 (COVID-19) at least 6 weeks before enrollment. Healthy control participants had no prior history of COVID-19 and negative tests for severe acute respiratory syndrome coronavirus 2. Participants were assessed using 3 NIH Toolbox (NIHTB) batteries for Cognition (NIHTB-CB), Emotion (NIHTB-EB), and Motor function (NIHTB-MB) and selected tests from the Patient-Reported Outcomes Measurement Information System (PROMIS). Each had BOLD-fMRI at 3T, during WM (N-back) tasks with increasing attentional/WM load.
One hundred sixty-nine participants were screened; 50 fulfilled the study criteria and had complete and usable data sets for this cross-sectional cohort study. Twenty-nine participants with PCC were diagnosed with COVID-19 242 ± 156 days earlier; they had similar ages (42 ± 12 vs 41 ± 12 years), gender proportion (65% vs 57%), racial/ethnic distribution, handedness, education, and socioeconomic status, as the 21 uninfected healthy controls. Despite the high prevalence of memory (79%) and concentration (93%) complaints, the PCC group had similar performance on the NIHTB-CB as the controls. However, participants with PCC had greater brain activation than the controls across the network (false discovery rate-corrected = 0.003, Tmax = 4.17), with greater activation in the right superior frontal gyrus ( = 0.009, Cohen = 0.81, 95% CI 0.15-1.46) but lesser deactivation in the default mode regions ( = 0.001, = 1.03, 95% CI 0.61-1.99). Compared with controls, participants with PCC also had poorer dexterity and endurance on the NIHTB-MB, higher scores for negative affect and perceived stress, but lower scores for psychological well-being on the NIHTB-EB, as well as more pain symptoms and poorer mental and physical health on measures from the PROMIS. Greater brain activation predicted poorer scores on measures that were abnormal on the NIHTB-EB.
Participants with PCC and neuropsychiatric symptoms demonstrated compensatory neural processes with greater usage of alternate brain regions, and reorganized networks, to maintain normal performance during WM tasks. BOLD-fMRI was sensitive for detecting brain abnormalities that correlated with various quantitative neuropsychiatric symptoms.
新冠后状况（PCC）很常见，常伴有神经精神症状。本研究旨在使用血氧水平依赖功能磁共振成像（BOLD-fMRI）来评估患有 PCC 的患者在工作记忆（WM）期间是否存在大脑激活异常，以及异常的大脑激活是否可以预测认知表现、运动功能或精神症状。
PCC 患者在入组前至少 6 周有记录的 2019 年冠状病毒病（COVID-19）。健康对照组没有 COVID-19 既往史，且严重急性呼吸综合征冠状病毒 2 检测为阴性。使用 NIH 工具箱（NIHTB）认知（NIHTB-CB）、情绪（NIHTB-EB）和运动功能（NIHTB-MB）的 3 个电池以及来自患者报告的结果测量信息系统（PROMIS）的选定测试对参与者进行评估。每个人都在 3T 下进行 BOLD-fMRI，在 WM（N-back）任务中，注意力/WM 负荷逐渐增加。
共筛选出 169 名参与者；50 名符合研究标准，并完成了这项横断面队列研究的完整且可用的数据集。29 名患有 PCC 的患者在 242 ± 156 天前被诊断为 COVID-19；他们的年龄（42 ± 12 岁与 41 ± 12 岁）、性别比例（65%与 57%）、种族/民族分布、利手性、教育程度和社会经济地位与 21 名未感染的健康对照组相似。尽管记忆力（79%）和注意力（93%）的抱怨很常见，但 PCC 组在 NIHTB-CB 上的表现与对照组相似。然而，与对照组相比，患有 PCC 的患者在整个网络中大脑激活更强（经假发现率校正， = 0.003，Tmax = 4.17），右侧额上回的激活更强（ = 0.009，Cohen's d = 0.81，95%CI 0.15-1.46），默认模式区域的去激活更少（ = 0.001， = 1.03，95%CI 0.61-1.99）。与对照组相比，PCC 患者在 NIHTB-MB 上的灵活性和耐力也较差，负面情绪和感知压力的 评分较高，而 NIHTB-EB 上的心理健康评分较低，以及 PROMIS 测量中的更多疼痛症状和较差的身心健康。大脑激活增加预示着在 NIHTB-EB 上异常的测量值得分较差。
患有 PCC 和神经精神症状的患者表现出代偿性神经过程，更多地使用替代大脑区域，重新组织网络，以在 WM 任务中保持正常表现。BOLD-fMRI 对检测与各种定量神经精神症状相关的大脑异常很敏感。
