Advertisement

Experimental Brain Research

, Volume 238, Issue 1, pp 229–245 | Cite as

Synergic control of action in levodopa-naïve Parkinson’s disease patients: I. Multi-finger interaction and coordination

  • Paulo B. de Freitas
  • Sandra M. S. F. Freitas
  • Sasha Reschechtko
  • Tyler Corson
  • Mechelle M. Lewis
  • Xuemei Huang
  • Mark L. LatashEmail author
Research Article

Abstract

We explored the origin of the impaired control of action stability in Parkinson’s disease (PD) by testing levodopa-naïve PD patients to disambiguate effects of PD from possible effects of long-term exposure to levodopa. Thirteen levodopa-naïve PD patients and 13 controls performed single- and multi-finger force production tasks, including producing a self-paced quick force pulse into a target. A subgroup of patients (n = 10) was re-tested about 1 h after the first dose of levodopa. Compared to controls, PD patients showed lower maximal forces and synergy indices stabilizing total force (reflecting the higher inter-trial variance component affecting total force). In addition, PD patients showed a trend toward shorter anticipatory synergy adjustments (a drop in the synergy index in preparation to a quick action) and larger non-motor equivalent finger force deviations. Lower maximal force, higher unintentional force production (enslaving) and higher inter-trial variance indices occurred in PD patients after one dosage of levodopa. We conclude that impairment in synergies is present in levodopa-naïve patients, mainly in indices reflecting stability (synergy index), but not agility (anticipatory synergy adjustments). A single dose of levodopa, however, did not improve synergy indices, as it did in PD patients on chronic anti-PD medication, suggesting a different mechanism of action. The results suggest that indices of force-stabilizing synergies may be used as an early behavioral sign of PD, although it may not be sensitive to acute drug effects in drug-naïve patients.

Keywords

Parkinson’s disease Synergy Fingers Hand Enslaving Uncontrolled manifold 

Abbreviations

ASA

Anticipatory synergy adjustment

FTOT

Total force

HY

Hoehn and Yahr

MVC

Maximal voluntary contraction

PD

Parkinson’s disease

UCM

Uncontrolled manifold

ME

Motor equivalent

nME

Non-motor equivalent

Notes

Acknowledgements

We would like to thank all the participants in the study. XH and MML were supported by NIH Grants NS060722, ES019672, and NS082151. MLL, XH, and MML were supported by NIH Grant NS095873.

Compliance with ethical standards

Conflict of interest

No conflicts of interest are claimed by any of the authors.

References

  1. Adler CH, Sethi KD, Hauser RA, Davis TL, Hammerstad JP, Bertoni J, Ropinirole Study Group (1997) Ropinirole for the treatment of early Parkinson’s disease. Neurology 49:393–399PubMedGoogle Scholar
  2. Binkofski F, Buccino G, Posse S, Seitz RJ, Rizzolatti G, Freund HJ (1999) A fronto-parietal circuit for object manipulation in man: evidence from an fMRI-study. Eur J Neurosci 11:3276–3286PubMedGoogle Scholar
  3. Bowler RM, Gysens S, Diamond E, Nakagawa S, Drezgic M, Roels HA (2006) Manganese exposure: neuropsychological and neurological symptoms and effects in welders. Neurotoxicology 27:315–326PubMedGoogle Scholar
  4. Brandauer B, Hermsdörfer J, Geissendoerfer T, Schoch B, Gizewski ER, Timmann D (2011) Impaired and preserved aspects of independent finger control in patients with cerebellar damage. J Neurophysiol 107:1080–1093PubMedGoogle Scholar
  5. Castiello U, Bennett KMB, Bonfiglioli C, Peppard RF (2000) The reach-to-grasp movement in Parkinson’s disease before and after dopaminergic medication. Neuropsychologia 38:46–59PubMedGoogle Scholar
  6. Cersosimo MG, Koller WC (2006) The diagnosis of manganese-induced parkinsonism. Neurotoxicol 27:340–346Google Scholar
  7. Danion F, Schöner G, Latash ML, Li S, Scholz JP, Zatsiorsky VM (2003) A force mode hypothesis for finger interaction during multi-finger force production tasks. Biol Cybern 88:91–98PubMedGoogle Scholar
  8. de Freitas PB, Freitas SMSF, Lewis MM, Huang X, Latash ML (2018) Stability of steady hand force production explored across spaces and methods of analysis. Exp Brain Res 236:1545–1562PubMedPubMedCentralGoogle Scholar
  9. Dorman DC, Struve MF, Marshall MW, Parkinson CU, James RA, Wong BA (2006) Tissue manganese concentrations in young male rhesus monkeys following subchronic manganese sulfate inhalation. Toxicol Sci 92:201–210PubMedGoogle Scholar
  10. Falaki A, Jo HJ, Lewis MM, O’Connell B, De Jesus S, McInerney J, Huang X, Latash ML (2018) Systemic effects of deep brain stimulation on synergic control in Parkinson’s disease. Clin Neurophysiol 129:1320–1332PubMedPubMedCentralGoogle Scholar
  11. Feigin A, Ghilardi MF, Fukuda M, Mentis MJ, Dhawan V, Barnes A, Ghez CP, Eidelberg D (2002) Effects of levodopa infusion on motor activation responses in Parkinson’s disease. Neurology 59:220–226PubMedGoogle Scholar
  12. Freitas SMSF, de Freitas PB, Lewis MM, Huang X, Latash ML (2019) Quantitative analysis of multi-element synergies stabilizing performance: comparison of three methods with respect to their use in clinical studies. Exp Brain Res 237:453–465PubMedGoogle Scholar
  13. Gentner R, Classen J (2006) Modular organization of finger movements by the human central nervous system. Neuron 52:731–742PubMedGoogle Scholar
  14. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Dubois B (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23:2129–2170PubMedGoogle Scholar
  15. Guilarte TR (2013) Manganese neurotoxicity: new perspectives from behavioral, neuroimaging, and neuropathological studies in humans and non-human primates. Front Aging Neurosci 5:23PubMedPubMedCentralGoogle Scholar
  16. Hershey T, Black KJ, Carl JL, McGee-Minnich L, Snyder AZ, Perlmutter JS (2003) Long term treatment and disease severity change brain responses to levodopa in Parkinson’s disease. J Neurol Neurosurg Psychiatry 74:844–851PubMedPubMedCentralGoogle Scholar
  17. Hoehn M, Yahr M (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMedGoogle Scholar
  18. Houk JC, Buckingham JT, Barto AG (1996) Models of the cerebellum and motor learning. Behav Brain Sci 19:368–383Google Scholar
  19. Howell MJ, Schenck CH (2015) Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol 72:707–712PubMedGoogle Scholar
  20. Hummel T (1999) Olfactory evoked potentials as a tool to measure progression of Parkinson’s disease. In: Chase TN, Bedard P (eds) Focus on medicine Vol 14—new developments in the drug therapy of Parkinson’s disease. Blackwell Science, Oxford, pp 47–53Google Scholar
  21. Jo HJ, Park J, Lewis MM, Huang X, Latash ML (2015) Prehension synergies and hand function in early-stage Parkinson’s disease. Exp Brain Res 233:425–440PubMedGoogle Scholar
  22. Jo HJ, Maenza C, Good DC, Huang X, Park J, Sainburg RL, Latash ML (2016) Effects of unilateral stroke on multi-finger synergies and their feed-forward adjustments. Neuroscience 319:194–205PubMedPubMedCentralGoogle Scholar
  23. Kelly VE, Hyngstrom AS, Rundle MM, Bastian AJ (2002) Interaction of levodopa and cues on voluntary reaching in Parkinson’s disease. Mov Disord 17:38–44PubMedGoogle Scholar
  24. Latash ML, Huang X (2015) Neural control of movement stability: lessons from studies of neurological patients. Neurosci 301:39–48Google Scholar
  25. Latash ML, Zatsiorsky VM (2016) Biomechanics and motor control: defining central concepts. Academic Press, New YorkGoogle Scholar
  26. Latash ML, Scholz JF, Danion F, Schöner G (2001) Structure of motor variability in marginally redundant multi-finger force production tasks. Exp Brain Res 141:153–165PubMedGoogle Scholar
  27. Lewis MM, Lee E-Y, Jo HJ, Park J, Latash ML, Huang X (2016) Synergy as a new and sensitive marker of basal ganglia dysfunction: a study of asymptomatic welders. Neurotoxicol 56:76–85Google Scholar
  28. Marsden CD, Parkes JD (1977) Success and problems of long-term levodopa therapy in Parkinson’s disease. Lancet 309:345–349Google Scholar
  29. Mathiowetz V, Weber K, Kashman N, Volland G (1985) Adult norms for the nine hole peg test of finger dexterity. OTJR (Thorofare NJ) 5:24–38Google Scholar
  30. Mattos DJ, Latash ML, Park E, Kuhl J, Scholz JP (2011) Unpredictable elbow joint perturbation during reaching results in multijoint motor equivalence. J Neurophysiol 106:1424–1436PubMedPubMedCentralGoogle Scholar
  31. Mattos D, Schöner G, Zatsiorsky VM, Latash ML (2015) Motor equivalence during accurate multi-finger force production. Exp Brain Res 233:487–502PubMedGoogle Scholar
  32. Menon V, Adleman NE, White CD, Glover GH, Reiss AL (2001) Error-related brain activation during a Go/NoGo response inhibition task. Hum Brain Mapp 12:131–143PubMedGoogle Scholar
  33. Merello M, Gerschcovich ER, Ballesteros D, Cerquetti D (2011) Correlation between the Movement Disorders Society Unified Parkinson’s Disease rating scale (MDS-UPDRS) and the Unified Parkinson’s Disease rating scale (UPDRS) during L-dopa acute challenge. Parkinsonism Relat Disord 17:705–707PubMedGoogle Scholar
  34. Michely J, Barbe MT, Hoffstaedter F, Timmermann L, Eickhoff SB, Fink GR et al (2012) Differential effects of dopaminergic medication on basic motor performance and executive functions in Parkinson’s disease. Neuropsychologia 50:2506–2514PubMedGoogle Scholar
  35. Morris ME, Iansek R, Galna B (2008) Gait festination and freezing in Parkinson’s disease: pathogenesis and rehabilitation. Mov Disord 23(Suppl 2):S451–S460PubMedGoogle Scholar
  36. Nutt JG, Holford NH (1996) The response to levodopa in Parkinson’s disease: imposing pharmacological law and order. Ann Neurol 39:561–573PubMedGoogle Scholar
  37. Olafsdottir H, Yoshida N, Zatsiorsky VM, Latash ML (2005) Anticipatory covariation of finger forces during self-paced and reaction time force production. Neurosci Lett 381:92–96PubMedPubMedCentralGoogle Scholar
  38. Overduin SA, d’Avella A, Carmena JM, Bizzi E (2012) Microstimulation activates a handful of muscle synergies. Neuron 76:1071–1077PubMedPubMedCentralGoogle Scholar
  39. Palmer SJ, Eigenraam L, Hoque T, McCaig RG, Troiano A, McKeown MJ (2009) Levodopa-sensitive, dynamic changes in effective connectivity during simultaneous movements in Parkinson’s disease. Neurosci 158:693–704Google Scholar
  40. Park J, Zatsiorsky VM, Latash ML (2010) Optimality vs. variability: an example of multi-finger redundant tasks. Exp Brain Res 207:119–132PubMedPubMedCentralGoogle Scholar
  41. Park J, Wu YH, Lewis MM, Huang X, Latash ML (2012) Changes in multifinger interaction and coordination in Parkinson’s disease. J Neurophysiol 108:915–924PubMedPubMedCentralGoogle Scholar
  42. Park J, Lewis MM, Huang X, Latash ML (2013) Effects of olivo-ponto-cerebellar atrophy (OPCA) on finger interaction and coordination. Clin Neurophysiol 124(5):991–998PubMedGoogle Scholar
  43. Park J, Lewis MM, Huang X, Latash ML (2014) Dopaminergic modulation of motor coordination in Parkinson’s disease. Parkinsonism Rel Disord 20:64–68Google Scholar
  44. Politis M, Wilson H, Wu K, Brooks DJ, Piccini P (2017) Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson’s patients. Neuroimage Clin 16:455–460PubMedPubMedCentralGoogle Scholar
  45. Rocchi L, Chiari L, Horak FB (2002) Effects of deep brain stimulation and levodopa on postural sway in Parkinson’s disease. J Neurol Neurosurg Psychiatry 73:267–274PubMedPubMedCentralGoogle Scholar
  46. Schaafsma JD, Balash Y, Gurevich T, Bartels AL, Hausdorff JM, Giladi N (2003) Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson’s disease. Eur J Neurol 10:391–398PubMedGoogle Scholar
  47. Schade S, Sixel-Döring F, Ebentheuer J, Schulz X, Trenkwalder C, Mollenhauer B (2017) Acute levodopa challenge test in patients with de novo parkinson’s disease: data from the DeNoPa Cohort. Mov Disord Clin Pract 4:755–762PubMedPubMedCentralGoogle Scholar
  48. Schettino LF, Adamovich SV, Hening W, Tunik E, Sage J, Poizner H (2006) Hand preshaping in Parkinson’s disease: effects of visual feedback and medication state. Exp Brain Res 168:186–202PubMedGoogle Scholar
  49. Scholz JP, Schoner G (1999) The uncontrolled manifold concept: identifying control variables for a functional task. Exp Brain Res 126:289–306PubMedGoogle Scholar
  50. Scholz JP, Danion F, Latash ML, Schöner G (2002) Understanding finger coordination through analysis of the structure of force variability. Biol Cybern 86:29–39PubMedGoogle Scholar
  51. Schöner G (1995) Recent developments and problems in human movement science and their conceptual implications. Ecol Psychol 8:291–314Google Scholar
  52. Smulders K, Dale ML, Carlson-Kuhta P, Nutt JG, Horak FB (2016) Pharmacological treatment in Parkinson’s disease: effects on gait. Parkinsonism Relat Disord 31:3–13PubMedPubMedCentralGoogle Scholar
  53. Snijders AH, Takakusaki K, Debu B, Lozano AM, Krishna V, Fasano A, Aziz TZ, Papa SM, Factor SA, Hallett M (2016) Physiology of freezing of gait. Ann Neurol 80:644–659PubMedGoogle Scholar
  54. Takei T, Confais J, Tomatsu S, Oya T, Seki K (2017) Neural basis for hand muscle synergies in the primate spinal cord. Proc Natl Acad Sci 114:8643–8648PubMedGoogle Scholar
  55. Thach WT, Goodkin HG, Keating JG (1992) Cerebellum and the adaptive coordination of movement. Ann Rev Neurosci 15:403–442PubMedGoogle Scholar
  56. Tissingh G, Berendse HW, Bergmans P, DeWaard R, Drukarch B, Stoof JC, Wolters EC (2001) Loss of olfaction in de novo and treated Parkinson’s disease: possible implications for early diagnosis. Mov Disord 16:41–46PubMedGoogle Scholar
  57. Trenkwalder C, Kies B, Rudzinska M, Fine J, Nikl J, Honczarenko K, Kassubek J (2011) Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord 26:90–99PubMedGoogle Scholar
  58. Wilhelm L, Zatsiorsky VM, Latash ML (2013) Equifinality and its violations in a redundant system: multi-finger accurate force production. J Neurophysiol 110:1965–1973PubMedPubMedCentralGoogle Scholar
  59. Wu T, Wang L, Hallett M, Chen Y, Li K, Chan P (2011) Effective connectivity of brain networks during self-initiated movement in Parkinson’s disease. Neuroimage 55:204–215PubMedGoogle Scholar
  60. Zatsiorsky VM, Li ZM, Latash ML (2000) Enslaving effects in multi-finger force production. Exp Brain Res 131:187–195PubMedGoogle Scholar
  61. Zhou T, Solnik S, Wu Y-H, Latash ML (2014) Equifinality and its violations in a redundant system: control with referent configurations in a multi-joint positional task. Mot Control 18:405–424Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Paulo B. de Freitas
    • 1
    • 2
    • 3
  • Sandra M. S. F. Freitas
    • 2
    • 3
    • 4
  • Sasha Reschechtko
    • 2
    • 8
  • Tyler Corson
    • 3
  • Mechelle M. Lewis
    • 3
    • 5
  • Xuemei Huang
    • 3
    • 5
    • 6
    • 7
  • Mark L. Latash
    • 2
    Email author
  1. 1.Interdisciplinary Graduate Program in Healthy SciencesCruzeiro do Sul UniversitySão PauloBrazil
  2. 2.Department of KinesiologyThe Pennsylvania State UniversityUniversity ParkUSA
  3. 3.Department of Neurology, Milton S. Hershey Medical CenterThe Pennsylvania State UniversityHersheyUSA
  4. 4.Master and Doctoral Program in Physical TherapyCity University of São PauloSão PauloBrazil
  5. 5.Department of Pharmacology, Milton S. Hershey Medical CenterThe Pennsylvania State UniversityHersheyUSA
  6. 6.Department of Radiology, Milton S. Hershey Medical CenterThe Pennsylvania State UniversityHersheyUSA
  7. 7.Department of Neurosurgery, Milton S. Hershey Medical CenterThe Pennsylvania State UniversityHersheyUSA
  8. 8.Department of Physiology and PharmacologyUniversity of Western OntarioLondonCanada

Personalised recommendations