title: Synergy as a new and sensitive marker of basal ganglia dysfunction: A study of asymptomatic welders.
abstract: Multi-digit synergies, a recently developed, theory-based method to quantify stability of motor action, are shown to reflect basal ganglia dysfunction associated with parkinsonian syndromes. In this study, we tested the hypothesis that multi-digit synergies may capture early and subclinical basal ganglia dysfunction. We chose asymptomatic welders to test the hypothesis because the basal ganglia are known to be most susceptible to neurotoxicity caused by welding-related metal accumulation (such as manganese and iron).
  
  
  
  Twenty right-handed welders and 13 matched controls were invited to perform single- and multi-finger pressing tasks using the fingers of the right or left hand. Unified Parkinson's Disease Rating Scale and Grooved Pegboard scores were used to gauge gross and fine motor dysfunction, respectively. High-resolution (3T) T1-weighted, T2-weighted, T1 mapping, susceptibility, and diffusion tensor MRIs were obtained to reflect manganese, iron accumulation, and microstructural changes in basal ganglia. The synergy index stabilizing total force and anticipatory synergy adjustments were computed, compared between groups, and correlated with estimates of basal ganglia manganese [the pallidal index, R1 (1/T1)], iron [R2* (1/T2*)], and microstructural changes [fractional anisotropy and mean diffusivity].
  
  
  
  There were no significant differences in Unified Parkinson's Disease Rating Scale (total or motor subscale) or Grooved Pegboard test scores between welders and controls. The synergy index during steady-state accurate force production was decreased significantly in the left hand of welders compared to controls (p=0.004) but did not reach statistical significance in the right hand (p=0.16). Anticipatory synergy adjustments, however, were not significantly different between groups. Among welders, higher synergy indices in the left hand were associated significantly with higher fractional anisotropy values in the left globus pallidus (R=0.731, p<0.001) but not with the pallidal index, R1, or R2* values in the basal ganglia.
  
  
  
  These data suggest that multi-digit synergy metrics may serve as preclinical markers for basal ganglia dysfunction in welders and other populations at risk for neurodegenerative diseases involving parkinsonian symptoms. This finding may have important clinical, scientific, and public/occupational health implications.
authors.affiliation: Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States; Department of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States.
authors.forename: Mechelle M
authors.initials: MM
authors.lastname: Lewis
authors.affiliation: Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Kinesiology, The Pennsylvania State University, University Park, PA 16802, United States.
authors.forename: Hang Jin
authors.initials: HJ
authors.lastname: Jo
authors.affiliation: Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Du
authors.affiliation: Institute of Sport Science, Seoul National University, Seoul, South Korea.
authors.forename: Jaebum
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Flynn
authors.affiliation: Department of Biostatistics, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States.
authors.forename: Lan
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Kinesiology, The Pennsylvania State University, University Park, PA 16802, United States. Electronic address: mll11@psu.edu.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Latash
authors.affiliation: Department of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States; Department of Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States; Department of Radiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States; Department of Neurosurgery, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA 17033, United States; Department of Kinesiology, The Pennsylvania State University, University Park, PA 16802, United States. Electronic address: Xuemei@psu.edu.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Huang
mesh_terms: D000328:Adult; D001480:Basal Ganglia Diseases / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D006225:Hand; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D011596:Psychomotor Disorders / Q000209:etiology*; D011795:Surveys and Questionnaires; D014896:Welding
keywords: Basal ganglia; Low-level exposure; MRI; Synergy; Welders