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. 2020 Jun;27(6):985-994.
doi: 10.1111/ene.14189. Epub 2020 Apr 14.

Contingent negative variation: a biomarker of abnormal attention in functional movement disorders

T Teodoro  1   2   3   4 , A Koreki  1   5 , A M Meppelink  6 , S Little  7 , G Nielsen  1 , A Macerollo  8 , J J Ferreira  4   9 , I Pareés  10   11 , A Lang  12   13 , M J Edwards  1   2   3
Affiliations

Contingent negative variation: a biomarker of abnormal attention in functional movement disorders

T Teodoro et al. Eur J Neurol. 2020 Jun.

Abstract

Background and purpose: Contingent negative variation (CNV) is a negative cortical wave that precedes a pre-cued imperative stimulus requiring a quick motor response. It has been related to motor preparation and anticipatory attention. The aim was to ascertain whether the clinical improvement of functional movement disorders after physiotherapy would be associated with faster reaction times and modulation of CNV.

Methods: Motor performance and CNV were analysed during a pre-cued choice reaction time task with varying cue validity. Twenty-one patients with functional movement disorders and 13 healthy controls at baseline were compared. Patients then underwent physiotherapy. At follow-up after physiotherapy, patients were categorized as clinically improved (responders) or not improved (non-responders) and retested.

Results: At baseline, patients did not generate CNV, contrary to controls [mean amplitude (µV) at the end of preparation to move: patients -0.47 (95% CI -1.94, 1.00) versus controls -2.59 (95% CI -4.46, -0.72)]. Responders performed faster after physiotherapy [mean natural logarithm (ln) reaction time (RT) (ms): follow-up 6.112 (95% CI 5.923, 6.301) versus baseline 6.206 (95% CI 6.019, 6.394), P = 0.010], contrary to non-responders. Simultaneously, responders showed a recovery of CNV after physiotherapy [follow-up -1.95 (95% CI -3.49, -0.41) versus baseline -0.19 (95% CI -1.73, 1.35), P < 0.001], contrary to non-responders [follow-up -0.32 (95% CI -1.79, 1.14) versus baseline -0.72 (95% CI -2.19, 0.75), P = 0.381].

Conclusions: Clinical improvement of functional movement disorders after physiotherapy was associated with faster reaction times and normalization of CNV, which was absent at baseline. These findings suggest that CNV may constitute a useful neurophysiological biomarker related to abnormal attention in functional movement disorders.

Keywords: biomarkers; functional neurological disorders; functional movement disorders; psychogenic disorders.

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Conflict of interest statement

Tiago Teodoro, Akihiro Koreki, Anne Marthe Meppelink, Simon Little, Glenn Nielsen, Antonella Macerollo and Mark J Edwards: no disclosures. Joaquim J Ferreira: stock ownership in medically related fields – none; intellectual property rights – none; consultancies – GlaxoSmithKline, Novartis, TEVA, Lundbeck, Solvay, Abbvie, BIAL, Merck‐Serono, Merz, Ipsen, Biogen, Sunovion Pharmaceuticals, Zambon; expert testimony – BIAL, Novartis; advisory boards – BIAL, Sunovion Pharmaceuticals; employment – Faculdade de Medicina de Lisboa, CNS – Campus Neurológico Sénior; partnerships – none; contracts – none; honoraria – none; royalties – none; grants – GlaxoSmithKline, Grunenthal, Fundação MSD (Portugal), TEVA, MSD, Allergan, Ipsen, Novartis, Medtronic; other – none. Isabel Pareés: has received honoraria and/or travel expenses from Allergan, Abbvie, Alter, TEVA and Italfarmaco for attending and/or speaking at meetings. Anthony Lang: stock ownership in medically related fields – none; consultancies – Abbvie, Acorda, Biogen, Janssen, Jazz Pharma, Sun Pharma, Kallyope, Merck, Paladin, Theravance and Corticobasal Degeneration Solutions; advisory boards – Jazz Pharma, PhotoPharmics; partnerships – none; honoraria – Sun Pharma, Medichem, Medtronic, AbbVie and Sunovion; grants – Brain Canada, Canadian Institutes of Health Research, Corticobasal Degeneration Solutions, Edmond J Safra Philanthropic Foundation, Michael J. Fox Foundation, the Ontario Brain Institute, National Parkinson Foundation, Parkinson Society Canada, and W. Garfield Weston Foundation; intellectual property rights – none; expert testimony – none; employment –University Health Network, University of Toronto; contracts – none; royalties – Elsevier, Saunders, Wiley‐Blackwell, Johns Hopkins Press and Cambridge University Press; other – none.

Figures

Figure 1
Figure 1
Natural logarithm of reaction time per group, predictability and cue congruence. 50%, 50% congruence blocks (including congruent cues in 50% trials); 95%, 95% congruence blocks; C, trials with congruent cues; I, trials with incongruent cues. [Colour figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
End‐of‐preparation CNV: FMD patients at baseline versus healthy controls. [Colour figure can be viewed at wileyonlinelibrary.com]
Figure 3
Figure 3
End‐of‐preparation CNV: FMD responders and non‐responders at baseline versus follow‐up. [Colour figure can be viewed at wileyonlinelibrary.com]
Figure 4
Figure 4
Relationship between changes in RT and in CNV at follow‐up. [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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