Resilience of Neural Networks Underlying the Stroop Effect in the Aftermath of Severe COVID-19: fMRI Pilot Study

Abstract

Background: Alterations in resting-state functional connectivity and in activation patterns elicited during cognitive tasks were reported in acute to chronic stages of mild, moderate and critical SARS-CoV-2 infection, suggesting the dysregulation of specialised neural networks. In this pilot study, we report on activation patterns elicited by the colour-word Stroop task in patients who suffered from severe COVID-19 requiring Intensive Care Unit hospitalisation but who had no prior or COVID-19-related brain damage.

Methods: Neural activity elicited during a 16 min long colour-word Stroop task was investigated with 3T fMRI 9 months after severe SARS-CoV-2 infection in six patients and in twenty-four control subjects.

Results: Patients' performance in the Stroop task was within normal limits, with the exception of one (out of six) response time in one patient and one (out of six) accuracy measure in another patient. Activation elicited by the Stroop effect, i.e., the contrasting Incongruent vs. Congruent condition, differed between the first and second parts of the task. In controls, the Stroop effect yielded an increase in activity in prefrontal, cingulate and parieto-temporal clusters as well as in the nucleus accumbens during the first part, and the activity receded during the second part in most regions. Two distinct response profiles were found among patients: (i) a Stroop effect-linked increase during the first part followed by a partial decrease during the second part, as in healthy subjects; and (ii) a weak or absent Stroop effect increase during the first part followed by a partial increase during the second part.

Conclusions: The normal performance presented by patients on the Stroop task was associated with two distinct activation patterns. They may represent different resilience profiles of the corresponding neural networks and be indicative of propensity for further recovery and/or susceptibility to therapeutic interventions.

Keywords: Stroop task; brain plasticity; fMRI; fatigue; severe COVID-19.

Figure 1

Regions implicated in the cascade-of-control model of the Stroop effect [29]. (A) Regions involved in establishing a bias towards task-relevant sensory or perceptual information (red dots). (B) Regions maintaining the relevant information in working memory (yellow dots). (C) Regions involved in response selection (purple dots). (D) Regions involved in response evaluation and feedback (green dots). Lateral and upper views of the right and left hemispheres. Coloured dots mark coordinates of significant effects as described in prior studies (Supplemental Table S1).

Figure 2

Top: Surface renderings (lateral and medial views of left and right hemispheres) and coronal sections (+10, +20; left on the left) of activation showing in healthy subjects a significant interaction in the mixed-design ANOVA with condition and part as the within-subject factors. All maps thresholded at p < 0.01 and with a cluster extent of k > 17. Key regions of the cascade-of-control model are circled in colour (same code as in Figure 1, with MNI coordinates): inferior frontal gyrus in red; middle frontal gyrus in yellow; middle cingulate cortex in purple; and anterior cingulate cortex in green. In addition, nucleus accumbens is highlighted, circled in blue. Bottom: Graphs (mean and SEM) of the percentage of BOLD signal changes for Incongruent (I), Congruent (C) and Neutral (N) conditions during Part 1 and Part 2 in the key regions of the cascade-of-control model (outlined in colour; [29]) and in the nucleus accumbens. One (*) to four (****) asterisks mark a significant difference in activation during the Incongruent condition and during the Congruent condition in Part 1 vs. Part 2 (t test, p < 0.05/0.01/0.001, respectively; Bonferroni corrected by ROI). ACC: anterior cingulate cortex; IFG: inferior frontal gyrus; MCC: middle cingulate cortex; MFG: middle frontal gyrus.

Figure 3

Surface renderings (lateral and medial views of left and right hemispheres) and coronal sections (+10, +20; left on the left) of activation patterns elicited by the comparison of Incongruent vs. Congruent during Part 1 (left column), Part 2 (middle column) and the change between Part 1 and Part 2 (right column; clusters with Part 1 > Part 2 are in cold colours; clusters with Part 1 < Part 2 are in warm colours) in healthy subjects. (A) Group analysis of 24 control subjects. Maps thresholded at p < 0.01 and cluster extent of k > 27. (B) Typical control subject (C19). Maps thresholded at p < 0.05 and cluster extent of k > 62.

Figure 4

(A) Perceived mental fatigue before and after the fMRI paradigm; perceived mental effort during the Stroop task. (B) Duration of perceived mental fatigue after the experimental paradigm. (C) Perceived decrease in motivation and performance related to fatigue during the Stroop task, parasite thoughts occurring during the Stroop task and pain felt during the fMRI paradigm. (D) Stroop effect as assessed by the difference in response times between the Incongruent and Congruent condition, normalised to the mean of response times of the Incongruent, Congruent and Neutral conditions (in %). Black dots (A–C) and black line (D) indicate mean and vertical grey lines standard deviation of scores of the control population (CTL), colour dots and lines those of individual patients.

Figure 5

Surface renderings (lateral and medial views of left and right hemispheres) and coronal sections (+10, +20; left on the left) of activation patterns elicited by the comparison of Incongruent vs. Congruent during Part 1 (left column) and Part 2 (middle column), and the change between Part 1 and Part 2 (Part 2 minus Part 1, right column) in individual patients. Maps thresholded at p < 0.05 and cluster extent of k > 62.

Figure 6

Graph showing the percentage of BOLD signal changes in the contrast of Incongruent minus Congruent condition between Part 1 and Part 2 in the key regions of the cascade-of-control model. For each individual patient (P1–P6) the 9 ROIs are shown from left to right: left IFG, right IFG, left MFG, left MCC, right MCC, left ACC, right ACC, left nucleus accumbens, right nucleus accumbens. Same abbreviations and MNI coordinates as in Figure 2. ROIs of P1, P3 and P5 are on yellow and those of P2, P4 and P6 on white background.