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

Abstract

<h3>Background and Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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 <i>p</i> = 0.003, Tmax = 4.17), with greater activation in the right superior frontal gyrus (<i>p</i> = 0.009, Cohen <i>d</i> = 0.81, 95% CI 0.15–1.46) but lesser deactivation in the default mode regions (<i>p</i> = 0.001, <i>d</i> = 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 <i>T</i> scores for negative affect and perceived stress, but lower <i>T</i> 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. <h3>Discussion</h3> 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.

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