Persistent Changes in Brain Function Observed in Persons with Long COVID

Among individuals experiencing neuropsychiatric symptoms associated with long COVID, investigators from the University of Maryland observed what they described as "compensatory neural processes" as study participants engaged in tasks requiring working memory.

Using blood-oxygenation-level-dependent functional MRI (BOLD-fMRI), the researchers noted decreased activity in brain regions associated with memory tasks but increased activity in alternate brain regions.

“The greater activity occurred outside of the normal working memory brain network. We often see such changes in patients with a brain injury: Deficits in the default mode network of the brain leads to an increase in activity in other regions to help maintain brain function,” said study leader Linda Chang, MD, MS, Professor of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine (UMSOM) in a statement. “While our study doesn’t prove that COVID caused these brain changes, there appears to be a strong association with these changes and lingering neuropsychiatric symptoms.”

Chang and colleagues identified 29 people who had COVID-19 an average of 7 months earlier and had at least 1 persistent neuropsychiatric symptom (eg, memory loss, depression, anxiety). Of these, 9 had experience infection serious enough to require hospitalization. The researchers compared this group with 21 healthy volunteers who had no history of COVID and were matched for age, health status, vaccination status and a range of sociodemographic factors.

Participants in both groups completed a battery of tests that assessed cognitive skills, emotional health, and motor function and were evaluated for symptoms of fatigue, depression, anxiety, and pain. All participants underwent BOLD-fMRI scans while performing tasks that required use of working memory, allowing the research team to observe brain activity during the performance.

FINDINGS

Chang et al reported that while a majority of participants with long COVID complained of problems with memory (79%) and concentration (93%), the group’s performance on various tests of thinking skills was similar to the group of healthy volunteers. “This could be because their brains were compensating for these deficits by using more of other parts of their networks to maintain their performance,” said Chang.

However, long COVID participants scored below non-COVID participants on tests of dexterity and motor endurance. They also had higher scores on measures of negative affect and perceived stress and lower scores for psychological wellbeing. Scores for anxiety, fatigue, and pain also were higher among those with long COVID. Chang and colleagues wrote that greater brain activation among these individuals was predictive of poorer scores in many of the domains evaluated.

Long COVID participants scored below non-COVID participants on tests of dexterity and motor endurance. They also had higher scores on measures of negative affect and perceived stress and lower scores for psychological wellbeing. Scores for anxiety, fatigue, and pain also were higher among those with long COVID.

The authors detail several study limitations including that it was conducted during the early part of the COVID-19 pandemic when the Delta variant was most prominent, making it unclear whether similar results would be observed in persons infected with more recent variants. Also, those included as healthy volunteers were not tested for antibodies, so it is possible they incurred infection without symptoms.

“While this study provides crucial information on brain function in those who suffer neuropsychiatric symptoms from long COVID, we now need longitudinal follow-up studies to determine whether or when these abnormal imaging patterns will normalize and whether that correlates to a resolution in symptoms,” said UMSOM Dean, Mark T. Gladwin, MD, who is also Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor, in a USOM statement.

Reference: Chang L, Ryan MC, Liang H, Zhang Z, et al. Changes in brain activation pattern during working memory tasks in people with post-COVID condition and persistent neuropsychiatric symptoms. Neurology. Published online April 26, 2023. doi:10.1212/WNL.0000000000207309