Changes in Brain Activation Pattern During Working Memory Tasks in People With Post-COVID Condition and Persistent Neuropsychiatric Symptoms

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.