Hvilke input påvirker motor cortex hos ME patienter?

En af konklusionerne fra NIHs omfattende ME studie var (1): "Thus, the fatigue of PI-ME/CFS participants is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored."

Motor cortex er et område i hjernen, de styrer bevægelse og hermed udøvelse af motion. Motor cortex er igen styret af andre dele af hjernen. Og det hele forgår i et kompleks samspil med feedback fra musklerne. 

Her er en artikel. hvor man kan hente basisviden (2):

Neural Contributions to Muscle Fatigue: From the Brain to the Muscle and Back Again

Og her er link til figur, hvor hjerne-muskel samarbejdet er enkelt skematiseret (2):

Schematic of neural contributions to muscle fatigue in single joint exercise

Bemærk at nerver, der sender signaler fra muskler til rygmarv og hjerne kaldes muskel afferente. Nerver der sender signaler fra hjerne til muskler kaldes efferente. 

Det kræver et indgående kendskab til det komplekse system og til ME forskningen som helhed, hvis ME sygdomsmekanismen skal afdækkes. Hvad betyder f. eks. feedback fra ME muskel afferente, når der er påvist flere afvigelser i muskelstudier af ME patienter? Se oversigt:
Undersøgelser af muskler i Long Covid og Myalgic encephalomyelitis - OVERBLIK

Basisviden om hvordan muskel afferente påvirker evnen til motion kan hentes her (3):

On the Influence of Group III/IV Muscle Afferent Feedback on Endurance Exercise Performance

Denne artikel nævner, at afferent feedback påvirker upstream mortor cortex (med "upstream motor cortex" menes, hjerneområder, der sender signaler til motor cortex)  (3): 

"Group III/IV muscle afferents restrict motoneuronal output and locomotor muscle activation and therefore limit exercise performance by facilitating central fatigue. This impact results from the group III/IV-mediated inhibition of voluntary descending drive ‘upstream’ of the motor cortex and the group III/IV-mediated depression of motor cortical excitability."

Videre nævner artiklen også, at primary sensory cortex og prefrontal cortex er upstream motor cortex (3):

"Little is known about the mechanisms mediating the impact of group III/IV muscle afferents on voluntary descending drive upstream of the motor cortex, i.e. the effect of afferent feedback on mechanisms driving the motor cortex. Studies focusing on experimental muscle pain, which engages sensory neurons with little activity during conventional whole body exercise, document significant effects of nociceptive muscle afferents on various brain structures including the primary sensory cortex and motor regions (64). Although direct evidence is currently missing, findings from fMRI studies have led to the hypothesis that fatigue-related group III/IV muscle afferent feedback limits motor cortical activation via their inhibitory influence on the prefrontal cortex, which plays an important role in goal directed movements and thus maximizing exercise performance (65), and the cingulate and insular cortices (66–68). "

Et nyt studie har påvist, at primary sensory cortex og prefrontal cortex har nedsat blodgennemstrømning hos POTS patienter og ME/POTS patienter (4). Se figur:

Cerebral blood flow abnormalities in POTS assessed by brain SPECT

Citat fra artiklen (4): "There is a high prevalence of reduced cerebral perfusion in those with POTS, which is detectable with supine brain SPECT imaging and is associated with diminished quality of life. The most frequently affected areas are prefrontal lateral and sensorimotor cortices."

Og så kan man spørge, om det har nogen betydning for motorcortex, at primary sensory cortex og prefrontal cortex har nedsat blodgennemstrømning hos ME/POTS patienter? 

Referencer:

1) Walitt, B., Singh, K., LaMunion, S.R. et al. Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome. Nat Commun 15, 907 (2024). https://doi.org/10.1038/s41467-024-45107-3

2) Taylor JL, Amann M, Duchateau J, Meeusen R, Rice CL. Neural Contributions to Muscle Fatigue: From the Brain to the Muscle and Back Again. Med Sci Sports Exerc. 2016 Nov;48(11):2294-2306. doi: 10.1249/MSS.0000000000000923. PMID: 27003703; PMCID: PMC5033663.

https://pubmed.ncbi.nlm.nih.gov/27003703/

3) Amann M, Wan HY, Thurston TS, Georgescu VP, Weavil JC. On the Influence of Group III/IV Muscle Afferent Feedback on Endurance Exercise Performance. Exerc Sport Sci Rev. 2020 Oct;48(4):209-216. doi: 10.1249/JES.0000000000000233. PMID: 32658041; PMCID: PMC7492373.

https://pubmed.ncbi.nlm.nih.gov/32658041/

4) Seeley MC, O'Brien H, Wilson G, Coat C, Smith T, Hickson K, Casse R, Page AJ, Gallagher C, Lau DH. Novel brain SPECT imaging unravels abnormal cerebral perfusion in patients with postural orthostatic tachycardia syndrome and cognitive dysfunction. Sci Rep. 2025 Jan 28;15(1):3487. doi: 10.1038/s41598-025-87748-4. PMID: 39875497; PMCID: PMC11775248.

https://pubmed.ncbi.nlm.nih.gov/39875497/