A region-specific brain dysfunction underlies cognitive impairment in long COVID brain fog

Fuente: arXiv
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Autores principales: Yang, Jinhao, Zhou, Shaojiong, Wang, Zhibin, Xu, Jiahua, Chen, Jia, Yin, Zhouqian, Wei, Tao, Geng, Chaofan, Liu, Xiaoduo, Li, Xiang, Zhou, Xiaoyu, Li, Kun, Gu, Ruolei, Dolan, Raymond, Tang, Yi, Liu, Yunzhe
Formato: Preprint
Publicado: 2025
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author Yang, Jinhao
Zhou, Shaojiong
Wang, Zhibin
Xu, Jiahua
Chen, Jia
Yin, Zhouqian
Wei, Tao
Geng, Chaofan
Liu, Xiaoduo
Li, Xiang
Zhou, Xiaoyu
Li, Kun
Gu, Ruolei
Dolan, Raymond
Tang, Yi
Liu, Yunzhe
author_facet Yang, Jinhao
Zhou, Shaojiong
Wang, Zhibin
Xu, Jiahua
Chen, Jia
Yin, Zhouqian
Wei, Tao
Geng, Chaofan
Liu, Xiaoduo
Li, Xiang
Zhou, Xiaoyu
Li, Kun
Gu, Ruolei
Dolan, Raymond
Tang, Yi
Liu, Yunzhe
contents Long COVID "brain fog" is a common and debilitating subjective syndrome often associated with persistent cognitive impairment after COVID-19 infection. Here we identify a specific regional brain dysfunction that mediates this cognitive impairment and provide evidence that targeted neuromodulation improves this deficit. In 120 patients with long COVID brain fog, we found an aberrant perceptual processing pattern. Patients with more severe brain fog committed significantly more false alarms (impulsive responses to non-signals) despite preserved overall accuracy. Both high-density (128-channel) EEG and structural MRI analyses provided converging evidence of a right inferior insula deficit, characterized by a blunted neural monitoring signal and cortical atrophy. We confirmed this deficit in a separate 796-participant UK Biobank longitudinal COVID re-imaging cohort, where COVID-19 survivors also showed selective impairment on a perceptual processing task and corresponding longitudinal atrophy of the right inferior insula compared with healthy controls. Finally, in a proof-of-principle randomized, sham-controlled trial (n = 40), a non-invasive, excitatory theta-burst ultrasound stimulation protocol targeting the right inferior insula rescued the perceptual deficit by reducing false alarms. These findings provide evidence of a causal role for right inferior insula dysfunction in long COVID-related perceptual impairment and show that modulation of this region can rescue the deficit, establishing it as a novel therapeutic target for long COVID cognitive impairment.
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publishDate 2025
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spellingShingle A region-specific brain dysfunction underlies cognitive impairment in long COVID brain fog
Yang, Jinhao
Zhou, Shaojiong
Wang, Zhibin
Xu, Jiahua
Chen, Jia
Yin, Zhouqian
Wei, Tao
Geng, Chaofan
Liu, Xiaoduo
Li, Xiang
Zhou, Xiaoyu
Li, Kun
Gu, Ruolei
Dolan, Raymond
Tang, Yi
Liu, Yunzhe
Neurons and Cognition
Long COVID "brain fog" is a common and debilitating subjective syndrome often associated with persistent cognitive impairment after COVID-19 infection. Here we identify a specific regional brain dysfunction that mediates this cognitive impairment and provide evidence that targeted neuromodulation improves this deficit. In 120 patients with long COVID brain fog, we found an aberrant perceptual processing pattern. Patients with more severe brain fog committed significantly more false alarms (impulsive responses to non-signals) despite preserved overall accuracy. Both high-density (128-channel) EEG and structural MRI analyses provided converging evidence of a right inferior insula deficit, characterized by a blunted neural monitoring signal and cortical atrophy. We confirmed this deficit in a separate 796-participant UK Biobank longitudinal COVID re-imaging cohort, where COVID-19 survivors also showed selective impairment on a perceptual processing task and corresponding longitudinal atrophy of the right inferior insula compared with healthy controls. Finally, in a proof-of-principle randomized, sham-controlled trial (n = 40), a non-invasive, excitatory theta-burst ultrasound stimulation protocol targeting the right inferior insula rescued the perceptual deficit by reducing false alarms. These findings provide evidence of a causal role for right inferior insula dysfunction in long COVID-related perceptual impairment and show that modulation of this region can rescue the deficit, establishing it as a novel therapeutic target for long COVID cognitive impairment.
title A region-specific brain dysfunction underlies cognitive impairment in long COVID brain fog
topic Neurons and Cognition
url https://arxiv.org/abs/2511.14188