Background and Objectives: Post-COVID condition (PCC) is common and often involves neuropsychiatric symptoms. This study aimed to use blood-oxygenation-level-dependent functional MRI (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. Methods: The PCC participants had documented COVID-19 at least 6 weeks prior to enrollment. Healthy control participants had no prior history of COVID-19 and negative tests for SARS-CoV-2. Participants were assessed using three NIH-Toolbox (NIHTB) batteries for Cognition (NIHTB-CB), Emotion (NIHTB-EB) and Motor function (NIHTB-MB), as well as selected tests from the Patient-Reported Outcomes Measurement Information System (PROMIS). Each had BOLD-fMRI at 3 Tesla, during WM (N-back) tasks with increasing attentional/WM load. Results: 169 participants were screened; 50 fulfilled the study criteria and had complete and usable datasets for this cross-sectional cohort study. 29 PCC participants were diagnosed with COVID-19 242±156 days earlier, 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 and normal performance on the NIHTB-CB as the controls. However, PCC participants had greater brain activation than the controls across the network (p-FDR-corrected=0.003, T-max=4.17), with greater activation in the right superior frontal gyrus (p=0.009, Cohen’s-d=0.81, 95%CI [0.15-1.46]) but lesser deactivation in the default mode regions (p=0.001, d=1.03, 95%CI [0.61-1.99]). Compared to controls, PCC participants also had poorer dexterity and endurance on the NIHTB-MB, higher T-scores for negative affect and perceived stress, but lower T-scores for psychological well-being on the NIHTB-EB, as well as more pain symptoms and poorer mental and physical health on measures from PROMIS. Greater brain activation also predicted poorer scores on measures that were abnormal on the NIHTB-EB. Discussion: PCC participants with 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.

BACKGROUND AND PURPOSE: White matter abnormalities have been demonstrated to play an important role in minimal hepatic encephalopathy. In this study, we aimed to evaluate whether WM diffusion tensor imaging can be used to identify minimal hepatic encephalopathy among patients with cirrhosis. MATERIALS AND METHODS: Our study included 65 patients with cirrhosis with covert hepatic encephalopathy (29 with minimal hepatic encephalopathy and 36 without hepatic encephalopathy). Participants underwent DTI, from which we generated mean diffusivity and fractional anisotropy maps. We used a Bayesian machine-learning technique, called Graphical-Model-based Multivariate Analysis, to determine WM regions that characterize group differences. To further test the clinical significance of these potential biomarkers, we performed Cox regression analysis to assess the potential of these WM regions in predicting survival. RESULTS: In mean diffusivity or fractional anisotropy maps, 2 spatially distributed WM regions (predominantly located in the bilateral frontal lobes, corpus callosum, and parietal lobes) were consistently identified as differentiating minimal hepatic encephalopathy from no hepatic encephalopathy and yielded 75.4%–81.5% and 83.1%–92.3% classification accuracy, respectively. We were able to follow 55 of 65 patients (median = 18 months), and 15 of these patients eventually died of liver-related causes. Survival analysis indicated that mean diffusivity and fractional anisotropy values in WM regions were predictive of survival, in addition to the Child-Pugh score. CONCLUSIONS: Our findings indicate that WM DTI can provide useful biomarkers differentiating minimal hepatic encephalopathy from no hepatic encephalopathy, which would be helpful for minimal hepatic encephalopathy detection and subsequent treatment.