Behavioral and electrophysiological evidence of residual cognitive impairment in post-covid brain fog: a visual P300 study
Wilson, Matthew J.; Hill, Christopher M.; Thornton, David M.; Stanley, Nicholas S.
Highlights
- COVID-19 “brain fog” describes a collection of symptoms that include difficulties with higher level cognitive functions, most notably those of attention, memory, and information processing speed.
- The P3b is a scalp-recorded, electrophysiological measurement that is useful for gauging subclinical abilities related to attention and memory.
- COVID-19 without brain fog does not produce changes in the P3b response when compared to healthy controls
- Subtle difficulties with attentional resource allocation abilities, as measured by reduced P3b amplitudes, may persist in individuals who experienced brain fog even after subjective symptoms have resolved.
Abstract
While known primarily for respiratory symptoms, COVID-19 has also been linked to cognitive impairments, or “brain fog”, which affects attention, memory, and processing speed.
Brain-fog related cognitive deficits are well-documented in hospitalized patients but less understood in non-hospitalized individuals.
Brain fog may reflect dysfunction in cortical structures supporting higher-level cognition, including hippocampal, frontotemporal, and cingulate areas.
These regions contribute to the P3b response, an electrophysiological measure of attention and memory used to assess cognitive deficits across neurological conditions, though sparingly in COVID-19.
This study examined P3b mean amplitudes in individuals with and without COVID-19-related brain fog and pre-pandemic controls using a visual n-back paradigm.
It was hypothesized that the brain fog group would show reduced amplitudes under higher cognitive loads.
Results revealed reduced target-related P3b mean amplitudes in the brain fog group relative to both comparison groups, with no group differences for non-targets.
This reduction was most apparent over parietal recording sites but did not significantly vary by scalp region.
The brain fog group demonstrated lower accuracy and slower reaction times relative to controls.
These differences persisted an average of 22.58 months following symptom resolution, suggesting brain fog may be associated with attentional resource deficits that extend beyond subjective recovery.
...suggesting brain fog may be associated with attentional resource deficits that extend beyond subjective recovery.
Which is why proper control is so important in science, the core of its methodology even. Including in clinical trials.
Without it we are just guessing.
DHagen
Senior Member (Voting Rights)
These differences persisted an average of 22.58 months following symptom resolution, suggesting brain fog may be associated with attentional resource deficits that extend beyond subjective recovery
Oof. That's a big fear when it comes to a lot of "recovery" - the actual function doesn't really return, it's just that the symptoms at their worst are so severe that we lose the ability to effectively evaluate that function and so any degree of improvement gets labelled "recovery."
As an index of cognitive function, the P3b subcomponent of the P300 response reflects the neural processes engaged when the brain detects, evaluates, and updates its working representation of task-relevant stimuli. P3b amplitude is believed to index allocation of attentional resources toward this process, such that larger amplitudes reflect a greater proportion of available resources devoted to stimulus evaluation and context updating, while reduced amplitude reflects either diminished resource availability or degraded engagement of the underlying evaluative network.
The P3b is thought to reflect activity within a diverse neural network including hippocampal and medial-temporal structures, the frontoparietal regions of the cortex, and the cingulate
This distributed, network-dependent architecture, together with the established sensitivity to attentional and memory-related processing, is what has made P3b useful for tracking global cognitive change in dementia, mild cognitive impairment, concussion, and schizophrenia.
Imaging studies indicate the regions and connective pathways on which the P3b depends are often altered by COVID-19 infection.
Diffusion tensor imaging studies in post-COVID patients have revealed reduced white matter integrity in tracts that connect the brain regions associated with P3b generation.
the P3b response is thought to arise from coordinated theta- and delta-band oscillatory activity distributed across frontoparietal, cingulate, and medial-temporal networks; consequently, disruption of the structural pathways linking these regions may impair the neural synchronization necessary for normal P3b generation.
To our knowledge, no prior study has combined the n-back task with P3b measurement to examine COVID-19-related brain fog. Accordingly, this preliminary study compared P3b responses elicited during an n-back task between individuals with a history of COVID-19 and brain fog and individuals with a history of COVID-19 without brain fog. For comparison, data from a pre-pandemic control group are also presented.
It was hypothesized that P3b mean amplitude would be reduced in individuals with brain fog relative to the other two groups. Since target-stimulus processing places substantial demands on working memory maintenance and updating, group differences were expected to be most evident for target stimuli and more pronounced at higher cognitive loads, when working memory demands were greatest. […] Consistent with prior P300 studies in individuals with neurological injury, including concussion and HIV, it was hypothesized that individuals with COVID-related brain fog would show comparable behavioral performance to the other two groups, as accuracy and reaction time can remain statistically normal even when P300 amplitude is abnormal.
Contrary to expectations, behavioral performance differed between groups. The COV+BF group demonstrated significantly lower n-back accuracy and slower reaction times relative to the CONTROL group, while the COV-BF group did not differ significantly from either group.
The absence of performance deficits in the COV-BF group suggests that infection alone may be insufficient to produce detectable behavioral impairments on a working memory task of this nature. […] Together, these behavioral and electrophysiological findings suggest that individuals with a history of COVID-19 related brain fog may represent a distinct subset within the post-COVID population, rather than simply a more severe expression of COVID-19 infection history alone.
Beyond the behavioral findings, participants with a history of COVID-19-related brain fog also exhibited reduced target-related P3b mean amplitudes […] even after accounting for the age difference between groups and including biological sex as a covariate.
Although P3b amplitude decreased as working-memory load increased, the target-specific group difference did not become significantly larger at higher load. Thus, the data supported a target-processing deficit in the COV+BF group, but not the predicted load-dependent increase of that deficit. One possibility for this finding is that the reduced amplitude in the COV+BF group reflects an overall reduction in additional resource availability rather than a load specific deficit.
This is consistent with the interpretation that COV+BF individuals were already operating near their attentional resource ceiling even under lower task demands.
This pattern is similar to the relationship reported by Polich et al (Polich et al., 2000),. who found that P300 latency increased systematically with HIV viral load, suggesting that greater viral burden was associated with greater electrophysiological disruption. The present finding raises the possibility that repeated COVID-19 infection may compound neural resource impairment, particularly in individuals who develop brain fog.
Individuals with a history of COVID-19-related brain fog demonstrated persistently reduced target-related P3b mean amplitudes relative to both COVID-19-recovered individuals without brain fog and healthy controls, even after accounting for age differences and an average of 22.58 months following brain fog recovery. The reduction was observed for task-relevant target stimuli but not non-target stimuli, suggesting that the effect reflects altered engagement of target-related evaluative or context-updating processes
Because this amplitude reduction was accompanied by, and not separate from, concurrent behavioral performance decrements, these findings should be interpreted as converging evidence of attentional resource impairment rather than as support for P3b amplitude as an independent or standalone biomarker of cognitive decline in this population. Further, individuals with a COVID-19 history but no brain fog were indistinguishable from healthy controls […] suggesting that brain fog may represent a neurologically distinct outcome of infection rather than a more severe expression of a common post-COVID process.
This is consistent with the interpretation that COV+BF individuals were already operating near their attentional resource ceiling even under lower task demands.
Worth repeating.
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In the present study, this correlation was also confirmed in cases of cognitive fog, showing a longer latency and reduced amplitude of the P300 compared to the control group. This data suggests a slowdown in the brain’s response to significant stimuli, indicating possible impairment or deterioration of cognitive functions. The prolonged latency of P300 may reflect reduced efficiency in information processing or a diminished capacity of the central nervous system to promptly detect and respond to stimuli. This slowdown could negatively impact the ability to process information, maintain attention, and make decisions, thus contributing to cognitive fog symptoms.
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