Motor Memory Assessment for Post-COVID Syndrome

Overseen By Leonardo G Cohen, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Disqualifiers: Neurologic conditions, Severe psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how motor memory (the brain's ability to remember movements) is affected in people with long COVID compared to healthy individuals. It aims to determine if long COVID impacts tasks like typing sequences on a keyboard. The study seeks individuals recovering from COVID-19 who experience lingering symptoms, as well as healthy adults without post-COVID symptoms. Participants will perform simple typing tasks online using their nondominant hand. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research on the cognitive effects of long COVID.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It seems likely that you can continue your medications, but you should confirm with the study team.

What prior data suggests that this method is safe for assessing motor memory in post-COVID syndrome?

Research has shown that the treatment in this study is safe. The study examines how people remember movements by having them perform simple typing tasks on a computer. Typing on a keyboard is a common daily activity, and no evidence suggests it causes harm.

This trial does not test any drugs or medical devices, so there are no concerns about side effects. Participants will only complete typing tasks and fill out a short questionnaire. These activities are safe and are part of everyday life without risk.

The trial aims to observe motor memory in people with long COVID through harmless typing exercises. No safety issues have been identified for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Motor Memory Assessment for Post-COVID Syndrome trial because it explores how simple keypress tasks might reveal differences in motor memory between those with Long COVID and healthy individuals. Unlike current treatments that focus on alleviating symptoms like fatigue or breathing difficulties, this approach aims to understand the neurological impacts of Long COVID directly. By analyzing motor memory through keypresses, the trial could uncover new insights into how COVID-19 affects brain function, potentially leading to more targeted and effective treatments in the future.

What evidence suggests that this trial's method could be effective for assessing motor memory in long COVID?

Research has shown that people with long COVID can struggle with motor memory, the ability to learn and repeat movements. In earlier studies, participants with long COVID found it harder to learn a sequence of keypresses compared to healthy individuals. This trial will assess motor memory differences by comparing participants with long COVID, divided into right-handed and left-handed groups, with healthy controls also divided by handedness. The typing test used in this research measures this difference in motor memory. Although no direct proof yet exists that this test will improve symptoms, it helps researchers understand how long COVID affects motor skills. Understanding these differences can be a step towards finding ways to help those with long COVID. ^{6 7 8 9 10}

Who Is on the Research Team?

Leonardo G Cohen, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

This trial is for adults aged 18-90 who have recovered from COVID-19 but may experience long-term effects, known as long COVID. Participants must be able to type with their nondominant hand and have internet access. They cannot join if they've had recent fever or respiratory symptoms, unresolved neurologic symptoms post-COVID, or pre-existing conditions like large strokes or severe psychiatric disorders.

Inclusion Criteria

I can type comfortably with my non-dominant hand.

I do not have COVID-19 and am not experiencing lingering symptoms.

Which hand you use the most.

Exclusion Criteria

I haven't had a fever, respiratory symptoms, or COVID-19 in the last 14 days.

I had COVID-19 and still have nerve-related symptoms that didn't go away after 2 weeks.

You have a medical condition, such as a major stroke, Alzheimer's disease, Parkinson's disease, or severe psychiatric condition, that could make it hard to understand or complete the tasks in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (virtual)

Initial Task Completion

Participants complete a typing task and a questionnaire online

2 days

Online participation

Follow-up Task

Participants repeat the typing task 22 hours after the first task

1 day

Online participation

Follow-up

Participants are monitored for data analysis completion

Until December 2023

What Are the Treatments Tested in This Trial?

Interventions

• Keypresses

Trial Overview The study aims to test motor memory in people with long COVID by having them perform typing tasks using their nondominant hand over two days. The tasks are completed online and involve repeatedly typing a number sequence within specific time intervals followed by questionnaires about their experiences.

How Is the Trial Designed?

Group I: Arm 2 Healthy Controls right handed Experimental Treatment 1 Intervention

healthy right handed

Group II: Arm 2 Healthy Controls left handed Experimental Treatment 1 Intervention

healthy left handed

Group III: Arm 1 Long COVID right handed Experimental Treatment 1 Intervention

Long COVID right handed

Group IV: Arm 1 Long COVID left handed Experimental Treatment 1 Intervention

Long COVID left handed

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a study of 16 patients with diffuse axonal injury (DAI) and memory impairment, short latency afferent inhibition (SAI) was significantly reduced compared to healthy controls, indicating altered motor cortex excitability in these patients.

A single oral dose of donepezil improved SAI in DAI patients, suggesting that this medication may help enhance cholinergic function in the injured brain, although individual responses varied widely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced short latency afferent inhibition in diffuse axonal injury patients with memory impairment. Fujiki, M., Hikawa, T., Abe, T., et al.[2018]

In patients with Wernicke-Korsakoff syndrome (WKS), a significant reduction in short latency afferent inhibition (SAI) was observed compared to healthy individuals, indicating potential cholinergic dysfunction.

Despite the cholinergic dysfunction suggested by reduced SAI, there was no significant correlation between SAI values and memory impairment, suggesting that other factors may contribute to the amnesia seen in WKS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholinergic dysfunction and amnesia in patients with Wernicke-Korsakoff syndrome: a transcranial magnetic stimulation study. Nardone, R., Bergmann, J., De Blasi, P., et al.[2021]

In a study involving 10 PTSD patients and matched controls, normal working memory updating was associated with activation in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe, which was absent in the PTSD group.

The PTSD group showed increased activation in the superior parietal lobe, indicating a reliance on visuospatial coding for working memory, suggesting altered brain function in PTSD that affects how they process and update information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Clark, CR., McFarlane, AC., Morris, P., et al.[2019]

A systematic review of 13 studies involving mainly middle-aged adults who were hospitalized for COVID-19 found that a significant percentage (6-58%) experienced poor verbal learning and memory impairments up to 6 months post-infection.

Verbal memory deficits were linked to higher levels of anxiety and depression, but the severity of COVID-19 during the acute phase did not consistently correlate with memory performance, indicating the need for further research into the long-term cognitive effects of the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory alterations after COVID-19 infection: a systematic review. Llana, T., Zorzo, C., Mendez-Lopez, M., et al.[2022]

COVID-19 survivors often experience memory impairments that may be linked to structural and functional brain abnormalities observed through neuroimaging techniques like MRI and PET, particularly in areas such as the frontal, parietal, and temporal regions.

While there is a correlation between these brain changes (like cortical atrophy and hypometabolism) and memory issues, the study emphasizes that more controlled and longitudinal research is needed to establish a clear causal relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-COVID-19 human memory impairment: A PRISMA-based systematic review of evidence from brain imaging studies. Shan, D., Li, S., Xu, R., et al.[2023]

In a study of 736 COVID-19 survivors, over one third exhibited cognitive impairment (CI) 11 months post-infection, with higher rates in older individuals and those with more severe COVID-19 symptoms.

Cognitive impairment was linked to increased levels of depression and anxiety, and was associated with specific cognitive deficits in areas like attention and memory, suggesting the need for regular cognitive assessments and potential cognitive training programs for affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive impairment after recovery from COVID-19: Frequency, profile, and relationships with clinical and laboratory indices. Galderisi, S., Perrottelli, A., Giuliani, L., et al.[2023]

In a study of 35 patients with moderate to severe traumatic brain injury, successful memory encoding was linked to activation of the dorsal attention network and suppression of the default mode network, indicating that these brain networks play crucial roles in memory processes.

Patients with memory impairment showed abnormal activation patterns in the dorsal attention network and reduced white matter integrity, suggesting that their difficulties with memory encoding may stem from ineffective control of attention and structural brain changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal dorsal attention network activation in memory impairment after traumatic brain injury. Mallas, EJ., De Simoni, S., Scott, G., et al.[2021]

Research indicates that NMDA receptors in the hippocampus, particularly in the CA1 region, play a crucial role in human verbal memory processes, as evidenced by changes in brain activity when words are presented.

The use of ketamine, an NMDA receptor antagonist, not only impairs memory but also alters brain responses to words, suggesting that these receptors are essential for normal memory function in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors. Grunwald, T., Beck, H., Lehnertz, K., et al.[2023]

War veterans with combat-related PTSD demonstrated significant short-term memory impairment, scoring lower on Immediate and Delayed Recall tests compared to control subjects, indicating a potential cognitive deficit associated with PTSD.

Additionally, veterans with PTSD made more errors on visual retention tasks, suggesting difficulties in visuoperceptive and visuoconstructional abilities, although the exact relationship to traumatic experiences remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term memory in Croatian war veterans with posttraumatic stress disorder. Sodić, L., Anticević, V., Britvić, D., et al.[2018]

Midazolam significantly impairs memory recall, as demonstrated in a study using arterial spin-labeling perfusion MRI with a double-blind, within-subject design involving subjects learning word-pairs.

The study found decreased cerebral blood flow in key brain areas, particularly the left dorsolateral prefrontal cortex, which correlates with the memory impairment, suggesting this region is crucial for forming new associations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia. Liang, P., Manelis, A., Liu, X., et al.[2021]

Propofol significantly inhibits memory consolidation processes in the cerebral cortex, as shown in an in vitro study using mouse neocortical slices, where it completely blocked the potentiation of cortical responses at a concentration of 2 µg/mL.

At a higher concentration of 4 µg/mL, propofol not only inhibited memory consolidation but also caused a small depressant effect, indicating that it actively facilitates memory decay in the cerebral cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The general anaesthetic propofol prevents cerebrocortical potentiation in neocortical mouse brain slices. Voss, LJ.[2022]

In a study of 54 COVID-19-recovered patients, mild-to-moderate long-term memory (LTM) deficits were found in both those at risk for cognitive decline and those not at risk, indicating a significant prevalence of memory issues post-infection.

The study suggests that LTM deficits in these patients may arise from both primary amnesic features and secondary cognitive processes, highlighting the need for screening, especially in those with moderate COVID-19 symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Episodic long-term memory in post-infectious SARS-CoV-2 patients. Aiello, EN., Fiabane, E., Manera, MR., et al.[2022]

A study involving 428 participants (319 post-COVID individuals and 109 healthy controls) found that those with post-COVID conditions exhibited significant cognitive impairments across various functions, including attention, memory, and executive function, compared to healthy controls.

Routine cognitive tests like the Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were effective in distinguishing cognitive impairment in post-COVID patients, suggesting these assessments should be administered to all patients with post-COVID symptoms, regardless of their self-reported cognitive complaints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints. Ariza, M., Cano, N., Segura, B., et al.[2022]

In a study involving 15 healthy volunteers, subanesthetic doses of ketamine, which blocks NMDA receptors, led to significant impairments in free recall and recognition memory, as well as attention.

The memory deficits caused by ketamine were not linked to changes in attention or psychosis symptoms, indicating a direct role of NMDA receptors in explicit memory processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Malhotra, AK., Pinals, DA., Weingartner, H., et al.[2022]

In a study involving 7 adult male rhesus monkeys, ketamine was found to impair cognitive functions such as memory, reaction time, and fine motor skills at subanesthetic doses, particularly affecting more difficult tasks.

The research highlights that ketamine's negative impact on cognitive abilities occurs in a dose-dependent manner, with significant disruptions observed at doses of 1.0 and 1.78 mg/kg, indicating potential risks associated with recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine impairs multiple cognitive domains in rhesus monkeys. Taffe, MA., Davis, SA., Gutierrez, T., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11097756/

Procedural Motor Memory Deficits in Patients With Long- ... In this prospective, cross-sectional, online, case-control study, participants learned a sequential motor skill over 2 consecutive days ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05746624

Procedural Motor Memory in Long COVID-19 This study will objectively test procedural motor memory in a group of people with ongoing symptoms following recovery from acute COVID-19 infection. Primary ...

3. withpower.com withpower.com/trial/phase-encephalitis-viral-2-2023-bb5b8

Motor Memory Assessment for Post-COVID Syndrome The available research does not provide direct evidence supporting the effectiveness of Motor Memory Assessment for Post-COVID Syndrome. The studies mentioned ...

4. nature.com nature.com/articles/s41598-025-85919-x

Neurological post-COVID syndrome is associated with ... Neurologic PCS patients showed impaired mental flexibility as an executive subfunction, verbal short-term memory, working memory and general reactivity.

5. academic.oup.com academic.oup.com/acn/article/40/1/125/7689909

Neurocognitive Impairment in Long COVID - Oxford Academic Executive function, memory, attention, and processing speed appear to be the cognitive domains that are predominantly associated with long-COVID syndrome.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12474489/

Long COVID Syndrome Prevalence in 2025 in an Integral ... This study examines the prevalence of long COVID in association with the number of infections and vaccination status. Methods: We analyzed ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S120197122500236X

Long COVID risk and severity after COVID-19 infections ... Cumulative risk seems higher among individuals who have had multiple infections [3,4], but recent studies suggest that the risk would be lower following COVID- ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05746624?term=AREA%5BConditionSearch%5D(%22Brain%20Diseases,%20Metabolic%22)&rank=8

Procedural Motor Memory in Long COVID-19 Primary endpoint measure: Early procedural memory formation, as measured by the difference in tapping speed (keypresses/second) between the first and last ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9846887/

Epidemiological and clinical perspectives of long COVID ... Overall, 10–35% of COVID survivors develop long COVID, with common symptoms including fatigue, dyspnea, chest pain, cough, depression, anxiety, post-traumatic ...

10. bmcpublichealth.biomedcentral.com bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-024-19264-5

Post-COVID syndrome prevalence: a systematic review and ... We systematically reviewed and determined the pooled prevalence estimate of PCS worldwide based on published literature.