Synergic control in asymptomatic welders during multi-finger force exertion and load releasing while standing.

Motor synergies, i.e., neural mechanisms that organize multiple motor elements to ensure stability of actions, are affected by several neurological condition. Asymptomatic welders showed impaired synergy controlling the stability of multi-finger action compared to non-welders and this impairment was associated with microstructural damage in the globus pallidus. We further explored the effect of welding-related metal exposure on multi-finger synergy and extended our investigation to posture-stabilizing synergy during a standing task. Occupational, MRI, and performance-stabilizing synergies during multi-finger accurate force production and load releasing while standing were obtained from 29 welders and 19 age- and sex-matched controls. R2* and R1 relaxation rate values were used to estimate brain iron and manganese content, respectively, and diffusion tensor imaging was used to reflect brain microstructural integrity. Associations of brain MRI (caudate, putamen, globus pallidus, and red nucleus), and motor synergy were explored by group status. The results revealed that welders had higher R2* values in the caudate (p = 0.03), putamen (p = 0.01), and red nucleus (p = 0.08, trend) than controls. No group effect was revealed on multi-finger synergy index during steady-state phase of action (ΔVZss). Compared to controls, welders exhibited lower ΔVZss (-0.106 ± 0.084 vs. 0.160 ± 0.092, p = 0.04) and variance that did not affect the performance variable (VUCM, 0.022 ± 0.003 vs. 0.038 ± 0.007, p = 0.03) in the load releasing, postural task. The postural synergy index, ΔVZss, was associated negatively with higher R2* in the red nucleus in welders (r = -0.44, p = 0.03), but not in controls. These results suggest that the synergy index in the load releasing during a standing task may reflect welding-related neurotoxicity in workers with chronic metals exposure. This finding may have important clinical and occupational health implications.

Synergic control of action in levodopa-naïve Parkinson's disease patients: II. Multi-muscle synergies stabilizing vertical posture.

Postural instability is a major disabling feature in Parkinson's disease (PD). We quantified the organization of leg and trunk muscles into synergies stabilizing the center of pressure (COP) coordinate within the uncontrolled manifold hypothesis in levodopa-naïve patients with PD and age-matched control subjects. The main hypothesis was that changes in the synergic control of posture are present early in the PD process even before levodopa exposure. Eleven levodopa-naïve patients with PD and 11 healthy controls performed whole-body cyclical voluntary sway tasks and a self-initiated load-release task during standing on a force plate. Surface electromyographic activity in 13 muscles on the right side of the body was analyzed to identify muscle groups with parallel scaling of activation levels (M-modes). Data were collected both before ("off-drug") and approximately 60 min after the first dose of 25/100 carbidopa/levodopa ("on-drug"). COP-stabilizing synergies were quantified for the load-release task. Levodopa-naïve patients with PD showed no COP-stabilizing synergy "off-drug", whereas controls showed posture-stabilizing multi-M-mode synergy. "On-drug", patients with PD demonstrated a significant increase in the synergy index. There were no significant drug effects on the M-mode composition, anticipatory postural adjustments, indices of motor equivalence, or indices of COP variability. The results suggest that levodopa-naïve patients with PD already show impaired posture-stabilizing multi-muscle synergies that may be used as promising behavioral biomarkers for emerging postural disorders in PD. Moreover, levodopa modified synergy metrics differently in these levodopa-naïve patients compared to a previous study of patients on chronic antiparkinsonian medications (Falaki et al. in J Electromyogr Kinesiol 33:20-26, 2017a), suggesting different neurocircuitry involvement.

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

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.

Individual preferences in motor coordination seen across the two hands: relations to movement stability and optimality.

The framework of the uncontrolled manifold (UCM) hypothesis was used to explore variables related to stability of task performance in the two hands of young healthy individuals. Fourteen young adults performed four-finger accurate constant force production tasks interrupted by a voluntary quick force pulse production and by an externally imposed displacement of all fingers. Three groups of variables were used to quantify stability of steady force production: (1) indices of the inter-trial variance were computed within the UCM and orthogonal to the UCM; (2) indices of motor equivalence were computed between steady-state intervals separated by the force pulse and by the finger-lifting episode; and (3) referent coordinate and apparent stiffness were computed using the data during the ascending phase of the finger-lifting episode. In another task, the subjects performed accurate constant force production with visual feedback removal after the 8th second, and the drop in the total force after the removal was computed. There were differences between the right and left hand in some outcome variables such as variance within the UCM, and the timing of anticipatory synergy adjustments prior to the force pulse, consistent with the dynamic dominance hypothesis. There were significant correlations between the two hands for indices that were unrelated to accuracy of performance: variance within the UCM, index of motor equivalence, referent coordinate, apparent stiffness, and the drop of total force after visual feedback removal. We interpret these findings within the concept of stability-optimality trade-off. In particular, we conclude that individual subjects select particular, person-specific solutions within the spectrum allowed by the explicit task constraints, and this choice is consistent between the two hands. We conclude with a hypothesis that selecting specific solutions within the stability-optimality trade-off may represent an individual's personal preference consistent between the two hands.

Magnetic resonance T1w/T2w ratio: A parsimonious marker for Parkinson disease.

OBJECTIVE: Newer magnetic resonance imaging (MRI) techniques have shown promise in capturing early Parkinson disease (PD)-related changes in the substantia nigra pars compacta (SNc), the key pathological loci. Their translational value, however, is hindered by technical complexity and inconsistent results. METHODS: A novel yet simple MRI contrast, the T1w/T2w ratio, was used to study 76 PD patients and 70 controls. The T1w/T2w ratio maps were analyzed using both voxel-based and region-of-interest approaches in normalized space. The sensitivity and specificity of the SNc T1w/T2w ratio in discriminating between PD and controls also were assessed. In addition, its diagnostic performance was tested in a subgroup of PD patients with disease duration ≤2 years (PDE). A second independent cohort of 73 PD patients and 49 controls was used for validation. RESULTS: Compared to controls, PD patients showed a higher T1w/T2w ratio in both the right (cluster size = 164mm3 , p < 0.0001) and left (cluster size = 213mm3 , p < 0.0001) midbrain that was located ventrolateral to the red nucleus and corresponded to the SNc. The region-of-interest approach confirmed the group difference in the SNc T1w/T2w ratio between PD and controls (p < 0.0001). The SNc T1w/T2w ratio had high sensitivity (0.908) and specificity (0.80) to separate PD and controls (area under the curve [AUC] = 0.926), even for PDE patients (AUC = 0.901, sensitivity = 0.857, specificity = 0.857). These results were validated in the second cohort. INTERPRETATION: The T1w/T2w ratio can detect PD-related changes in the SNc and may be used as a novel, parsimonious in vivo biomarker for the disease, particularly for early stage patients, with high translational value for clinical practice and research. ANN NEUROL 2019;85:96-104.

Quantitative analysis of multi-element synergy stabilizing performance: comparison of three methods with respect to their use in clinical studies.

A number of analyses associated with the uncontrolled manifold (UCM) hypothesis have been used recently to investigate stability of actions across populations. We explored whether some of those methods have an advantage for clinical studies because they require fewer trials to achieve consistent findings. We compared the number of trials needed for the analysis of inter-trial variance, analysis of motor equivalence, and analysis in the space of referent coordinates. Young healthy adults performed four-finger accurate force production tasks under visual feedback with the right (dominant) and left hand over three days. Three methods [analytical (M1), experimental (M2), and cumulative mean (M3) methods] were used to define the minimal number of trials required to reach certain statistical criteria. Two of these methods, M1 and M2, showed qualitatively similar results. Fewer trials (M1: 5-13, M2: 4-10) were needed for analysis of motor equivalence compared to inter-trial variance analysis (M1: 14-24, M2: 10-14). The third method (M3) showed no major differences among the outcome variables. The index of synergy in the inter-trial variance analysis required a very small number of trials (M1, M2: 2-4). Variables related to referent coordinates required only a few trials (under 3), whereas the synergy index in this analysis required the largest number of trials (M1: 24-34, M2: 12-16). This is the first study to quantify the number of trials needed for UCM-based methods of assessing motor coordination broadly used in clinical studies. Clinical studies can take advantage of specific recommendations based on the current data regarding the number of trials needed for each analysis thus allowing minimizing the test session duration without compromising data reliability.

Stability of steady hand force production explored across spaces and methods of analysis.

We used the framework of the uncontrolled manifold (UCM) hypothesis and explored the reliability of several outcome variables across different spaces of analysis during a very simple four-finger accurate force production task. Fourteen healthy, young adults performed the accurate force production task with each hand on 3 days. Small spatial finger perturbations were generated by the "inverse piano" device three times per trial (lifting the fingers 1 cm/0.5 s and lowering them). The data were analyzed using the following main methods: (1) computation of indices of the structure of inter-trial variance and motor equivalence in the space of finger forces and finger modes, and (2) analysis of referent coordinates and apparent stiffness values for the hand. Maximal voluntary force and the index of enslaving (unintentional finger force production) showed good to excellent reliability. Strong synergies stabilizing total force were reflected in both structure of variance and motor equivalence indices. Variance within the UCM and the index of motor equivalent motion dropped over the trial duration and showed good to excellent reliability. Variance orthogonal to the UCM and the index of non-motor equivalent motion dropped over the 3 days and showed poor to moderate reliability. Referent coordinate and apparent stiffness indices co-varied strongly and both showed good reliability. In contrast, the computed index of force stabilization showed poor reliability. The findings are interpreted within the scheme of neural control with referent coordinates involving the hierarchy of two basic commands, the r-command and c-command. The data suggest natural drifts in the finger force space, particularly within the UCM. We interpret these drifts as reflections of a trade-off between stability and optimization of action. The implications of these findings for the UCM framework and future clinical applications are explored in the discussion. Indices of the structure of variance and motor equivalence show good reliability and can be recommended for applied studies.