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. 2025 Feb 17:55:e49.
doi: 10.1017/S0033291725000054.

Altered corticostriatal connectivity in long-COVID patients is associated with cognitive impairment

Marie Troll  1 , Meng Li  1   2   3 , Tara Chand  1   4   5 , Marlene Machnik  1 , Tonia Rocktäschel  1   2   3 , Antonia Toepffer  1 , Johanna Ballez  1 , Kathrin Finke  6 , Daniel Güllmar  7 , Jürgen R Reichenbach  3   7   8   9 , Martin Walter  1   2   3 , Bianca Besteher  1   2   3
Affiliations

Altered corticostriatal connectivity in long-COVID patients is associated with cognitive impairment

Marie Troll et al. Psychol Med. .

Abstract

Background: The COVID-19 pandemic has had a significant impact on the health of millions of people worldwide, and many manifest new or persistent symptoms long after the initial onset of the infection. One of the leading symptoms of long-COVID is cognitive impairment, which includes memory loss, lack of concentration, and brain fog. Understanding the nature and underlying mechanisms of cognitive impairment in long-COVID is important for developing preventive and therapeutic interventions.

Methods: Our present study investigated functional connectivity (FC) changes in patients with long-COVID and their associations with cognitive impairment. Resting-state functional MRI data from 60 long-COVID patients and 52 age- and sex-matched healthy controls were analyzed using seed-based functional connectivity analysis.

Results: We found increased FC between the right caudate nucleus and both the left and right precentral gyri in long-COVID patients compared with healthy controls. In addition, elevated FC was observed between the right anterior globus pallidus and posterior cingulate cortex as well as the right temporal pole in long-COVID patients. Importantly, the magnitude of FC between the caudate and the left precentral gyrus showed a significant negative correlation with Montreal Cognitive Assessment (MoCA) scores and a negative correlation with Trail Making Test B performance in the patient group.

Conclusion: Patients with long-COVID present enhanced FC between the caudate and the left precentral gyrus. Furthermore, those FC alterations are related to the severity of cognitive impairment, particularly in the domain of executive functions.

Keywords: COVID-19; basal ganglia; corticostriatal loop; long-COVID; post-COVID-19 condition; resting-state fMRI.

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Figures

Figure 1.
Figure 1.
Obtained significant clusters of the basal ganglia. Note: pCAU, neon green; aCAU, light green; pGB, light blue; and aGB, dark green (right hemisphere).
Figure 2.
Figure 2.
Increased FC between the posterior caudate and both the left and right precentral gyri in patients with long-COVID compared with controls. Right precentral gyrus (x = 48, y = −4, z = 38, k = 828, pFWEc < 0.001), left precentral gyrus (x = −60, y = 2, z = 22, k = 923, pFWEc < 0.001). The results of two-sample t-tests (p < 0.05, FWE-corrected) between long-COVID patients and healthy controls are presented as overlays. Note: PCG, precentral gyrus.
Figure 3.
Figure 3.
Increased FC between the posterior globus pallidus and temporal pole and posterior cingulate cortex in patients with long-COVID compared with controls. Posterior cingulate cortex (x = −4, y = −60, z = 22, k = 3812, pFWEc < 0.001), temporal cortex (x = 40, y = 12, z = −28, k = 427, pFWEc = 0.011). The results of two-sample t-tests (p < 0.05, FWE-corrected) between long-COVID patients and healthy controls are presented as overlays.
Figure 4.
Figure 4.
Scatter plot for MoCA scores and FC of the posterior caudate to the left precentral gyrus in long-COVID patients.
Figure 5.
Figure 5.
Scatter plot for TMT B scores and FC of the posterior caudate to the left precentral gyrus in long-COVID patients.
See this image and copyright information in PMC

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