Functional and microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19, 2021, Silva et al

[rvallee]

(Paragraphed for clarity)

Although post-acute cognitive dysfunction and neuroimaging abnormalities have been reported after hospital discharge in patients recovered from COVID-19, little is known about persistent, long-term alterations in people without hospitalization.

We conducted a cross-sectional study of 87 non-hospitalized recovered individuals 54 days after the laboratory confirmation of COVID-19. We performed structured interviews, neurological examination, 3T-MRI scans with diffusion tensor images (DTI) and functional resting-state images (fMRI).

Also, we investigated fatigue, anxiety, depression, somnolence, language, memory, and cognitive flexibility, using validated instruments. Individuals self-reported a high frequency of headache (40%) and memory difficulties (33%). The quantitative analyses confirmed symptoms of fatigue (68%), excessive somnolence (35%), anxiety (29%), impaired cognitive flexibility (40%) and language impairment (33%).

There were widespread cerebral white matter alterations (mainly characterized by increased fractional anisotropy), which correlated with abnormal attention and cognitive flexibility. The resting-state fMRI networks analysis showed severely disrupted brain hyperconnectivity and loss of resting-state networks specificity.


Pre-print: https://www.medrxiv.org/content/10.1101/2021.03.20.21253414v1

 

[rvallee]

I'm not really clear on what "quantitative analyses confirmed symptoms of" means. There is no means to verify any of those symptoms beyond self-reports. Also fatigue was "validated" with CFQ.

Discussion:

Cerebral white matter alterations were widespread and correlated with abnormal attention and cognitive flexibility. Brain connectivity was severely disrupted, with excessively and chaotically connected regions associated with significant loss of specificity of eleven (out of twelve investigated) individual standard resting-state networks (anterior and posterior salience, basal ganglia, ventral and dorsal DMN, language, left and right executive control networks, sensorimotor, visual and mostly, the visuospatial network).

 

[Arnie Pye]

functional resting-state images

I'm not clear what the above phrase means. "Functional" means that something is, effectively, made up. So how can imaging show up something imaginary?

 

[Ravn]

Haven't read the paper, only looked at the graphs, one of which showed the results of a "trail making test". No idea what that was so looked it up. Wikipedia says:

The task requires a subject to connect a sequence of 25 consecutive targets on a sheet of paper or computer screen, in a similar manner to a child's connect-the-dots puzzle. There are two parts to the test: in the first, the targets are all numbers from 1 to 25 and the test taker needs to connect them in sequential order; in the second part, the dots go from 1 to 13 and include letters from A to L. As in the first part, the patient must connect the dots in order while alternating letters and numbers, as in 1-A-2-B-3-C..., in the shortest time possible without lifting the pen from the paper. .[6] If the subject makes an error, the test administrator corrects them before the subject moves on to the next dot.[6]

The goal of the test is for the subject to finish both parts as quickly as possible, with the time taken to complete the test being used as the primary performance metric. The error rate is not recorded in the paper and pencil version of the test, however, it is assumed that if errors are made it will be reflected in the completion time. If the patient makes a mistake, the person administering the test tells them immediately and the patient is allowed to correct it. These mistakes affect scoring only if the time taken to correct them occurs within the time it takes to complete the task as a whole. [3] The second part of the test, in which the subject alternates between numbers and letters, is used to examine executive functioning.[3] The first part is used primarily to examine cognitive processing speed.[3]

https://en.wikipedia.org/wiki/Trail_Making_Test

The highly educated Covid cohort in this study did particularly badly at the second one.

I suspect this trail making test would show cognitive deficit in ME, too. I've never taken the test but would predict that I'd do ok on the numbers-only one as long as I took it on a better day when well rested but that I'd slow down noticeably in PEM.

The combined numbers-letters test I suspect I'd struggle with even on a good day. And on a bad day I'm not sure I can recall the order of the alphabet, certainly not at speed.

 

[adambeyoncelowe]

I'm not clear what the above phrase means. "Functional" means that something is, effectively, made up. So how can imaging show up something imaginary?

Functional has at least two meanings in science. It can mean the function of on organ or bodily system, such as the brain, or functional in the sense of FND. In this case, they seem to mean functional in terms of connectivity and the results of a fMRI.

Technically, FND is supposed to be a problem with functioning as opposed to structure ('software versus hardware'), but there's loads of additional baggage layered on top from when it was called conversion disorder, so it simultaneously means more and less than the normal meaning.

 

[Ravn]

I'm not clear what the above phrase means. "Functional" means that something is, effectively, made up. So how can imaging show up something imaginary?

I think 'functional' in this context just refers to the images you get from fMRI. I've only a vague notion of what fMRIs show but broadly speaking they show brain activity(=function) as opposed to (or in addition to?) brain structure.

'Functional' is one of those words that are perfectly fine in their original sense but whose meaning has been badly twisted by those with an interest in sowing confusion.

ETA: cross-posted with @adambeyoncelowe

 

[EndME]

Now published in Nature Scientific Reports as Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19.

There's substantial changes when compared to the 3 year older preprint.

 

[SNT Gatchaman]

There's substantial changes when compared to the 3 year older preprint.

Re-listing —

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19
Scardua-Silva, Lucas; Amorim da Costa, Beatriz; Karmann Aventurato, Ítalo; Batista Joao, Rafael; Machado de Campos, Brunno; Rabelo de Brito, Mariana; Bechelli, José Flávio; Santos Silva, Leila Camila; Ferreira dos Santos, Alan; Koutsodontis Machado Alvim, Marina; Vieira Nunes Ludwig, Guilherme; Rocha, Cristiane; Kaue Alves Silva Souza, Thierry; Mendes, Maria Julia; Waku, Takeshi; de Oliveira Boldrini, Vinicius; Silva Brunetti, Natália; Nora Baptista, Sophia; da Silva Schmitt, Gabriel; Duarte de Sousa, Jhulia Gabriela; Marchiori de Oliveira Cardoso, Tânia Aparecida; Schwambach Vieira, André; Barbosa Santos, Leonilda Maria; dos Santos Farias, Alessandro; Nogueira, Mateus Henrique; Cendes, Fernando; Lin Yasuda, Clarissa

Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection.

Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects (median age of 41 years) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection, with a median of 79 days (and mean of 97 days) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. For MRI analyses, we included a group of non-infected 77 controls. The MRI study included white matter (WM) investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI).

The patients reported memory loss (36%), fatigue (31%) and headache (29%). The quantitative analyses confirmed symptoms of fatigue (83% of participants), excessive somnolence (35%), impaired phonemic verbal fluency (21%), impaired verbal categorical fluency (13%) and impaired logical memory immediate recall (16%). The WM analyses with DTI revealed higher axial diffusivity values in post-infected patients compared to controls. Compared to controls, there were no significant differences in the functional connectivity of the posterior cingulum cortex. There were no significant correlations between neuropsychological scores and neuroimaging features (including DTI and RS-fMRI).

Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected without anxiety or depression symptoms. The longitudinal analyses will clarify whether these alterations are temporary or permanent.

Link | PDF (Nature Scientific Reports)