Prefrontal dysfunction in post-COVID-19 hyposmia: an EEG/fNIRS study, 2023, Tommaso

[EndME]

Prefrontal dysfunction in post-COVID-19 hyposmia: an EEG/fNIRS study


Introduction: Subtle cognitive dysfunction and mental fatigue are frequent after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, characterizing the so-called long COVID-19 syndrome. This study aimed to correlate cognitive, neurophysiological, and olfactory function in a group of subjects who experienced acute SARS-CoV-2 infection with persistent hyposmia at least 12 weeks before the observation.

Methods: For each participant (32 post-COVID-19 patients and 16 controls), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) data were acquired using an integrated EEG–fNIRS system during the execution of a P300 odd-ball task and a Stroop test. The Sniffin' Sticks test was conducted to assess subjects' olfactory performance. The Montreal Cognitive Assessment (MoCA) and the Frontal Assessment Battery (FAB) were also administered.

Results: The post-COVID-19 group consisted of 32 individuals (20 women and 12 men) with an average education level of 12.9 ± 3.12 years, while the control group consisted of 16 individuals (10 women and 6 men) with an average education level of 14.9 ± 3.2 years. There were no significant differences in gender (X2 = 0, p = 1) or age between the two groups (age 44.81 ± 13.9 vs. 36.62 ± 11.4, p = 0.058). We identified a lower concentration of oxyhemoglobin (p < 0.05) at the prefrontal cortical level in post-COVID-19 subjects during the execution of the Stroop task, as well as a reduction in the amplitude of the P3a response. Moreover, we found that post-COVID-19 subjects performed worst at the MoCA screening test (p = 0.001), Sniffin's Sticks test (p < 0.001), and Stroop task response latency test (p < 0.001).

Conclusions: This study showed that post-COVID-19 patients with persistent hyposmia present mild deficits in prefrontal function, even 4 months after the end of the infection. These deficits, although subtle, could have long-term implications for quality of life and cognitive wellbeing. It is essential to continue monitoring and evaluating these patients to better understand the extent and duration of cognitive impairments associated with long COVID-19.

https://www.frontiersin.org/articles/10.3389/fnhum.2023.1240831/full

 

[bobbler]

The post-COVID-19 group consisted of 32 individuals (20 women and 12 men) with an average education level of 12.9 ± 3.12 years, while the control group consisted of 16 individuals (10 women and 6 men) with an average education level of 14.9 ± 3.2 years.

That is actually quite a difference isn't it? The equivalent of the control group on average having 2yrs undergraduate study more than the post-covid group

They say there were no significant differences in age, but I'd be interested in the break down as the ave of 44.8 vs 36.6 years is also pretty key froma cognitive perspective.

The following link regarding the FAB test (frontotermporal assessment battery) mentioned (which can e.g. differentiate frontotermporal dementia from alzheimers) goes through the various motor and cognitive tasks in this battery, and also has the following table at the end specifically noting the differences re: education vs age: https://www.psychdb.com/cognitive-testing/fab

20-29 30-39 40-49 50-59 60-69 70-79 80-89 90-95 Total
1-3 years education - - - 18 14.5 14.0 13.5 - 14.6
4-5 years education - - 16.4 15.6 14.8 14.7 13.2 11.8 14.7
6-8 years education 15.9 16.2 16.7 16.6 16.2 15.4 12.0 14.7 15.8
9-13 years education 16.9 17.1 17.7 16.9 16.3 16.2 17.0 12.0 16.6
> 13 years education 17.9 17.6 17.7 17.5 17.1 15.9 16.0 15.0 17.2
Total 16.8 16.8 17.1 16.8 16 15.5 13.8 13.1 16.1

and also for the stroop test the following paper for example: https://journals.sagepub.com/doi/10.1177/1073191105283427#:~:text=This suggests that executive function,a low level of education.
notes that performance declines with age, and that the decline is more dramatic in those with lower levels of education.


On the other hand the tests themselves are interesting choices and if planned to be done properly longitudinally and for large numbers in a way that they are not 'just averaged' as people's symptoms might change at different times etc. and of course people go into these things with different capabilities pre-covid, and have different things like comorbidities and life events (having a baby that cries every night for example) meaning I don't think that 32 non-matched individuals cuts it over that longer term.

I'm curious why the focus was only on prefrontal function and assume given the cohort has issues with sense of smell from covid they've chosen these thinking there is some connection but am struggling with the Stroop test specifically vs olfactory system connection vs oxyhaemoglobin in prefrontal cortex etc and found the following paragraphs very interesting:

Recent research on the spatial distribution of cortical and subcortical activation during cognitive tasks has generated considerable interest in the simultaneous recording of event-related potentials (ERP) and the related functional near-infrared spectroscopy (fNIRS) response (Jaquerod et al., 2021). This method could be focalized on the frontal regions, which could be easily aggressed by the direct viral entry through the nasal mucosa (Meinhardt et al., 2021). Sato et al. (2013) recently investigated prefrontal cortex (PFC) activity in healthy controls using simultaneous NIRS-fMRI measurements. They found that prefrontal NIRS-Hb signals exhibited a significant correlation with blood oxygen level-dependent (BOLD) signals in the activation area. This finding, combined with the simultaneous use of EEG-fNIRS for performing accurate mental workload classification (Liu et al., 2017), led us to employ an integrated EEG-fNIRS recording system in our study.

We hypothesize that patients with previous SARS-CoV-2 infection experiencing protracted smell impairment might have residual prefrontal functional alterations; therefore, the purpose of our study was to evaluate functional brain analysis and frontal cognitive performance in subjects with mild protracted hyposmia compared to subjects with no previous COVID-19 infection.

I'm not on top form enough to completely see through if this is 'flawed' but from a very top-level scan I like the way they have layered their elements to do this testing methodologically, whether or not the exact hypothesis turns out to be 'what it is' and just hope and look forward to the idea that research taking similar approaches might get funded enough and choose to go far enough to actually test at decent numbers both the null and hypothesis for e.g. such defined areas in quite an extensive way so that we can start feeling like aspects are ruled-in or ruled-out. It is interesting either way - whatever pattern they find of whether there are indications of the sense of smell-related aspects being battered but/and none, some or many of the other areas having their various findings.

- I'm slightly conscious that performance on some of these other tests could indeed be affected by systemic things that aren't specific to the theory of it being mucosal virus entry etc and so am hoping this is aiming to contributing to building a library of data fine-tuned and well-categorised enough that such layered nuances might be possible to differentiate if other teams are looking at other areas.

And importantly of course on the basis of a really-well defined cohort so that we know replications are genuinely like-for-like individuals who have had similar sets of symptoms (and areas where they don't have symptoms/have additional comorbidities being controlled for) rather than the lump-and-dump that works so well for the BPSm in muddying up all conditions and the underlying aspects going on in them.

Which throws up perhaps another question about literature and issues for those with ME/CFS as much as LC of whether if different techniques and journals are being used by different specialisms to look into one condition then how can a literature be combining these different 'inputs' - and probably does further the argument for discussion to be had about if there not being a 'new subject' or category being created then something that makes the interdisciplinary more possible in building and comparing data seems to be needed. ie a new 'level' of journals that is able to ask the questions like 'if something were found that affected mitochondria in certain individuals or after certain activities or severities then how does this impact on homogeinity of cohort, and ergo research design and interpretation of results etc when studying other areas like the brain where different things might be the focus of what was being measured?'.

 

[SNT Gatchaman]

This study showed that post-COVID-19 patients with persistent hyposmia present mild deficits in prefrontal function, even 4 months after the end of the infection.

The present study indicated that most patients who recovered from COVID-19 with persistent hyposmia 4 months after the end of the infection still presented with mild prefrontal function deficits, confirming the hypothesis about a retrograde effect of the SARS-CoV-2 virus on the brain regions contiguous to the entry zone. Recent studies confirmed the long-term persistence of both smell and cognitive dysfunction as brain fog in post-COVID-19 patients (García-Meléndez et al., 2023).

While the examined subjects had mild long COVID-19 symptoms, the presence of subtle cognitive deficits indicates the opportunity to evaluate cortical functions by means of neuropsychological and neurophysiological procedures in cases with residual hyposmia, possibly within a prospective clinical assessment.

The present study indicated that most patients who recovered from COVID-19 with persistent hyposmia 4 months after the end of the infection still presented with mild prefrontal function deficits, confirming the hypothesis about a retrograde effect of the SARSCoV-2 virus on the brain regions contiguous to the entry zone.

While the examined subjects had mild long COVID-19 symptoms, the presence of subtle cognitive deficits indicates the opportunity to evaluate cortical functions by means of neuropsychological and neurophysiological procedures in cases with residual hyposmia, possibly within a prospective clinical assessment.

"the presence of subtle cognitive deficits"
Physician, heal thyself