Rhythmic interlimb coordination of the lower limbs in multiple sclerosis during auditory pacing to three different frequencies
Authors: Mieke Goetschalckx
Raf Meesen
Marc Geraerts
Lousin Moumdjian
Fanny Van Geel
Peter Feys
Journal: Gait & Posture (2021)
Discipline: CLINICAL MEDICINE
Keywords: Attention; Central information processing; Coordination; Metronome frequency; Multiple sclerosis
Affiliations: REVAL Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt University, Hasselt, Belgium. Electronic address: ., REVAL Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt University, Hasselt, Belgium; IPEM, Institute of Psychoacoustic and Electronic Music, Faculty of Art and Philosophy, Gent University, Gent, Belgium; UMSC Pelt-Hasselt, Belgium. Electronic address: ., REVAL Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt University, Hasselt, Belgium; UMSC Pelt-Hasselt, Belgium. Electronic address: .

Abstract:  Background: Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system with heterogeneous symptoms. Persons with MS (PwMS) show reduced walking capacity with changes in their gait pattern. It is unknown to which extent coordination deficits are present in PwMS, which can be measured by seated lower leg interlimb coordination tasks, and to which extent they are related to motor and cognitive function. Research question: How is the control of interlimb coordination of the lower limbs characterized in PwMS compared to healthy controls (HC) during a seated rhythmical coordination task and what is the relationship between interlimb coordination, motor or cognitive function? Methods: Rhythmical interlimb coordination was assessed during a single session in 38 PwMS and 13 HC, using a seated rhythmical coordination task, comprising of antiphase flexion-extension of the lower limbs, to metronomes at 0.75 Hz, 1.00 Hz, 1.50 Hz. Outcomes were phase coordination index (PCI), movement amplitude and movement frequency. Correlations between interlimb coordination, motor, and cognitive function were examined. Results: PwMS showed impaired walking capacity but preserved cognitive function. Mixed model analysis revealed a significant effect of group and metronome frequency for PCI, attenuated by the variability in generating knee (antiphase flexion-extension) movements. Movement amplitude was highest at metronome frequency 1.00 Hz. In PwMS significant correlations were found between PCI and cognitive function when performing the task at metronome frequencies 0.75 Hz and 1.50 Hz, as well as motor function at 1.50 Hz. Significance: PwMS had a higher variability in interlimb coordination compared to HC. The most stable interlimb antiphase coordination mode was performed at 1.00 Hz. Significant correlations support the existence of a relationship between information processing speed, as well as walking impairment, with interlimb coordination. While cognitive and motor control are always needed for interlimb coordination movements, associations are strongest in the deviant higher and lower metronome rhythms. 

Retracted: No

PubPeer comments:
 This is one of several papers from different author teams that report using the same forward and reverse primers for quantitative PCR of miR-296-5p or miR-296-3p. Here, the miR-296-5p specific primers are described as Forward, 5u02b9-TGCCTAATTCAGAGGGTTGG-3u02b9; Reverse, 5u02b9-CTCCACTCCTGGCACACAG-3u02b9. No reliable results for the mature miR-296-5p would have been obtained with the described methods. First, no reverse transcription method is mentioned. One cannot simply input a mature miRNA into a qPCR reaction. Because miRNAs are very short (miR-296-5p is 21 nucleotides long), traditional RT methods also do not work. One must use the RT step to add sequence to the miRNA by ligation, stem-loop primers, or tailing. However, even if the correct RT step was just inadvertently omitted from the methods, the primers would still not amplify mature miR-296-5p. Here is the precursor sequence for miR-296, with the miR-296-5p arm (the one that is supposed to be amplified in this paper) in bold: AGGACCCUUCCAG**AGGGCCCCCCCUCAAUCCUGU**UGUGCCUAAUUCAGAGGGUUGGGUGGAGGCUCUCCUGAAGGGCUCU And here in bold is where the published  forward primer sequence would bind: AGGACCCUUCCAGAGGGCCCCCCCUCAAUCCUGUUG**UGCCUAAUUCAGAGGGUUGG**GUGGAGGCUCUCCUGAAGGGCUCU Obviously, this forward primer does not capture miR-296-5p at all. Also, the reverse primer recognizes a sequence adjacent to the miR-296 precursor in the genome, but this is not part of the precursor RNA. These forward and reverse primers might amplify genomic DNA, or perhaps a long primary molecule upstream of the precursor and the mature miRNA. They would not give any information about the mature miRNA that is supposed to be the subject of this paper. , 
 we found the Primer sequence wasu00a0 written error when querying the original data.u00a0 The primer sequence we actually usedu00a0 was miR-296-5p forward, 5u2032-CTCAACTGGTGTCGTGGAGTCGGCAATTCAGTTGAGACAGGATT-3u2032; and miR-296-5p reverse, 5 -ACACTCCAGCTGGGAGGGCCCCCCCTCAA-3 . We have mailed a request for editors to correct printing errors. Thank you for your attention. , 
 #1 we found the Primer sequence was written error when querying the original data. The primer sequence we actually used was miR-296-5p forward, 5u2032-CTCAACTGGTGTCGTGGAGTCGGCAATTCAGTTGAGACAGGATT-3u2032; and miR-296-5p reverse, 5 -ACACTCCAGCTGGGAGGGCCCCCCCTCAA-3 . We have mailed a request for editors to correct printing errors. Thank you for your attention. ,