Slow Motor Research Articles

A slow limit: Extensive motor training can not overcome a limit on the production of slow and smooth motion.

Previous research from several paradigms indicated that people have difficulty in producing slow and smooth movements (SSM). It is not clear whether these difficulties are due to biomechanical constraints, planning constraints, or lack of experience with moving slowly. Here, we investigated the latter possibility: we empirically tested whether short-term practice and long-term expertise with moving slowly would result in an increased ability to perform SSM. In Study 1, novice participants completed 10 training sessions in which they moved a stylus on a digitizing tablet as they traced an ellipse that moved at different frequency/peak velocity combinations, with frequencies ranging from 0.25 Hz to 0.875 Hz. In Study 2, experts in slow movement (tai chi performers) and fast movement (karate performers) completed the same task in one session. The results indicated that all participants had difficulties in producing SSM, as evidenced by an increase in submovement rate with decreasing frequency. Participants in Study 1 did show a marked improvement in their ability to produce fewer submovements while reducing mean squared jerk (MSJ). These short-term improvements were not evident in long-term slow motor expertise (i.e., tai chi). Taken together, our results suggest that SSM are likely difficult to produce due to a combination of several factors: lack of experience, planning, biomechanical, and neural constraints.

Human motor learning dynamics in high-dimensional tasks.

Conventional approaches to enhance movement coordination, such as providing instructions and visual feedback, are often inadequate in complex motor tasks with multiple degrees of freedom (DoFs). To effectively address coordination deficits in such complex motor systems, it becomes imperative to develop interventions grounded in a model of human motor learning; however, modeling such learning processes is challenging due to the large DoFs. In this paper, we present a computational motor learning model that leverages the concept of motor synergies to extract low-dimensional learning representations in the high-dimensional motor space and the internal model theory of motor control to capture both fast and slow motor learning processes. We establish the model's convergence properties and validate it using data from a target capture game played by human participants. We study the influence of model parameters on several motor learning trade-offs such as speed-accuracy, exploration-exploitation, satisficing, and flexibility-performance, and show that the human motor learning system tunes these parameters to optimize learning and various output performance metrics.

Two Tetrahymena kinesin-9 family members exhibit slow plus-end-directed motility in vitro

The kinesin-9 family comprises two subfamilies specific to ciliated eukaryotic cells, and has recently attracted considerable attention because of its importance in ciliary bending and formation. However, only scattered data are available on the motor properties of kinesin-9 family members; these properties have not been compared under identical experimental conditions using kinesin-9 motors from the same species. Here, we report the comprehensive motor properties of two kinesin-9 molecules of Tetrahymena thermophila, TtK9A (Kif9/Klp1 ortholog) and TtK9B1 (Kif6 ortholog), using microtubule-based in vitro assays, including single-motor and multi-motor assays and microtubule-stimulated ATPase assays. Both subfamilies exhibit microtubule plus-end-directed, extremely slow motor activity, both in single and multiple molecules. TtK9A shows lower processivity than TtK9B1. Our findings indicate that the considerable slow movement of kinesin-9 that corresponds to low ATP hydrolysis rates is a common feature of the ciliary kinesin-9 family.

Dysregulation of muscle cholesterol transport in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons, with a typical lifespan of 3-5 years. Altered metabolism is a key feature of ALS that strongly influences prognosis, with an increase in whole-body energy expenditure and changes in skeletal muscle metabolism, including greater reliance on fat oxidation. Dyslipidemia has been described in ALS as part of the metabolic dysregulation, but its role in the pathophysiology of the disease remains controversial. Among the lipids, cholesterol is of particular interest as a vital component of cell membranes, playing a key role in signal transduction and mitochondrial function in muscle. The aim of this study was to investigate whether motor dysfunction in ALS might be associated with dysregulation of muscle cholesterol metabolism. We determined cholesterol content and analyzed the expression of key determinants of the cholesterol metabolism pathway in muscle biopsies from thirteen ALS patients and ten asymptomatic ALS-mutation gene carriers compared to sixteen controls. Using human control primary myotubes, we further investigated the potential contribution of cholesterol dyshomeostasis to reliance on mitochondrial fatty acid. We found that cholesterol accumulates in the skeletal muscle of ALS patients and that cholesterol overload significantly correlates with disease severity evaluated by the Revised ALS Functional Rating Scale. These defects are associated with overexpression of the genes of the lysosomal cholesterol transporters Niemann-Pick type C1 (NPC1) and 2 (NPC2), which are required for cholesterol transfer from late endosomes/lysosomes to cellular membranes. Most notably, a significant increase in NPC2 mRNA levels could be detected in muscle samples from asymptomatic ALS-mutation carriers, long before disease onset. We found that filipin-stained unesterified cholesterol accumulated in the lysosomal compartment in ALS muscle samples, suggesting dysfunction of the NPC1/2 system. Accordingly, we report here that experimental NPC1 inhibition or lysosomal pH alteration in human primary myotubes was sufficient to induce the overexpression of NPC1 and NPC2 mRNA. Finally, acute NPC1 inhibition in human control myotubes induced a shift towards a preferential use of fatty acids, thus reproducing the metabolic defect characteristic of ALS muscle. We conclude that cholesterol homeostasis is dysregulated in ALS muscle from the presymptomatic stage. Targeting NPC1/2 dysfunction may be a new therapeutic strategy for ALS to restore muscle energy metabolism and slow motor symptom progression.

The Diversity of Skeletal Muscle Fiber Types.

The widespread presence of slow-red and fast-white muscles in all vertebrates supports the evolutionary advantage of having two types of motors available for animal movement-a slow economical motor used for most activities, and a fast energetically costly motor used for rapid movements and emergency actions, and actions that require a lot of force. Skeletal muscles are composed of multiple fiber types whose structural and functional properties have only in part been characterized. Further progress in this field is mainly occurring along two directions: Multiomics approaches are providing a global picture of the molecular composition of muscle fibers up to the single fiber and single nucleus level. Signaling studies are identifying many transcription factors and pathways controlling fiber-type specification. These new data should now be integrated into a wider whole-body context by defining the matching between muscle fiber and motor neuron heterogeneity in the neuromuscular system, as well as the relevance of muscle fiber types in systemic homeostatic functions, including metabolism and thermogenesis.

Neurodevelopmental Outcomes of Very Low Birth Weight Preterm Infants in the Regional Pediatric Clinic

Aim: To examine the incidence and etiology of neurodevelopmental outcomes in very low birth weight preterm infants, maternal and perinatal risk factors, comorbidities, and clinical presentation and compare with newborns of the same gestational age who did not develop a neurodevelopmental disorder.Methods: The research was conducted at the Pediatric Clinic in KBC (Clinical Hospital Center) Osijek. All newborns born from 1 January 2018 to 31 December 2019 with birth weight < 1,500 g and gestational age < 37 weeks are included in the research. The data were collected by reviewing medical records and the hospital’s IT system.Results: In the observed period, 120 children with birth weight < 1,500 g and gestational age < 37 weeks were born. Maternal and perinatal risk factors for premature birth include autoimmune diseases of the mother, infections during pregnancy and birth complications. Early complications that accompany the selected group are RDS, ROP, NEC, IVH, sepsis, congenital heart defects and glucose metabolism disorder. Slowed motor, cognitive and speech development are mostly influenced by low body weight, higher degree of IVH, lower AS in the first minute and the presence of NEC. Significant risk factors for death are gestational age < 25 weeks, body weight < 800 g, infections in pregnancy and autoimmune diseases of the mother.Conclusion: The neurodevelopmental outcome of very low birth weight preterm infants depends on a combination of comorbidities, as well as maternal, perinatal and neonatal risk factors.

Negative features of sporadic amyotrophic lateral sclerosis: Motor neurons of Onuf's nucleus survive in ADAR2-conditional knockout mice

Patients with amyotrophic lateral sclerosis (ALS) do not develop oculomotor disturbances and vesicorectal dysfunction until end-stage disease owing to the survival of certain motor neurons (MNs), including oculomotor neurons and MNs within Onuf's nucleus. In sporadic ALS, adenosine deaminase acting on RNA 2 (ADAR2)-mediated editing of GluA2 mRNA at the Q/R site is compromised in lower MNs. We previously developed genetically modified mice with a conditional knockout of ADAR2 in cholinergic neurons (ADAR2flox/flox/VAChT-Cre, Fast; AR2). These mice displayed slow and progressive lower motor neuron death with TAR DNA-binding protein 43 (TDP-43) pathology, attributable to insufficient editing at the GluA2 Q/R site due to ADAR2 deficiency. MN death was more common in fast-fatigable MNs owing to differential vulnerability under conditions of ADAR2 deficiency. Although facial and hypoglossal nerves were impaired in AR2 mice, cell death did not occur within the oculomotor nerve nucleus, as observed in patients with sporadic ALS. Since the basis for avoiding cystorectal damage in ALS is unknown, we compared the features of Onuf's nucleus MNs in 12-month-old AR2 mice with those in age-matched wild-type mice. Although the number of MNs was not significantly lower in AR2 mice, the neurons exhibited a shrunken morphology and TDP-43 pathology. Onuf's nucleus MNs could survive in an ADAR2-deficient state and mainly included fast fatigue-resistant (FR) and slow (S) MNs. In summary, FR and S MNs show increased resilience to ADAR2 deficiency, potentially participating in an important neuronal death avoidance mechanism in ALS.

Cognitive Disengagement Syndrome in Young Autistic Children, Children with ADHD, and Autistic Children with ADHD

ABSTRACT Objective Cognitive Disengagement Syndrome (CDS; previously called Sluggish Cognitive Tempo) refers to a constellation of cognitive and motor behaviors characterized by a predisposition toward mind wandering (cognitive subdomain) and slowed motor behavior (hypoactive). While there are a number of studies linking CDS traits to greater global impairment in children with attention-deficit/hyperactivity disorder (ADHD) and autistic children, there are few studies examining the prevalence and impact of CDS traits in autistic children with co-occurring ADHD (Autistic+ADHD). The current study explored CDS traits in autistic children with and without co-occurring ADHD, children with ADHD, and neurotypical children. Methods Participants were 196 children between 3- and 7-years-of-age comprising four groups: Neurotypical (N = 44), ADHD (N = 51), Autistic (N = 55), and Autistic+ADHD (N = 46). CDS traits, social and communication skills, repetitive behaviors, and sensory processing were all assessed via parent report. Results Children diagnosed with ADHD, autistic children, and Autistic+ADHD children exhibited similar levels of overall CDS traits. However, when explored separately, Autistic+ADHD children had higher cognitive CDS trait scores compared to children with ADHD alone. Both overall CDS traits and the cognitive subdomain were associated with greater social difficulties, particularly social withdrawal, higher levels of repetitive behaviors, and more sensory sensitivities, regardless of diagnosis. Conclusions Findings suggest that CDS traits may be an additional factor directly impact functional outcomes in both autistic and ADHD children. As such, clinicians should be assessing CDS traits in addition to other clinical domains associated with ADHD and autism when developing intervention plans for young neurodiverse children.

Influence of 21-day antiortostatic hypokinesia on the functional state of the musculoskeletal system of human

The influence of antiorthostatic hypokinesia with an inclination angle relative to the horizon of -6 degrees for 21 days was used as a ground model of the physiological effects of weightlessness. 10 practically healthy male volunteers (30.7 ± 5.4 years, 78.0 ± 8.5 kg, 179.7 ± 5.3 cm) took part in the experimental study, who successfully passed the medical expert commission of the SSC RF-IMBP RAS, familiarized with the study program and signed a voluntary informed consent to participate in the study. The state of the musculoskeletal system was assessed according to the results of speed-strength testing on an isokinetic dynamometer before hypokinesia and on the 3rd day after its completion. Staying in conditions of 21-day anti-orthostatic hypokinesia with a body inclination angle of –6° relative to the horizon, as a model of the physiological effects of weightlessness, leads to changes in the functional state of the musculoskeletal lower limbs which manifests itself during speed-strength testing after hypokinesia by a decrease in maximum voluntary force (MPF) of the knee joint extensor muscles from 9 to 15% compared with the base level. The decrease in MPF did not depend on a change in the force gradient, which reflects the ability to exert greater force in the shortest possible time. This indicated that the decrease in the MPF level after hypokinesia was mainly due to a change in the activity of slow motor units. At the same time, we assume that exposure to hypokinesia did not cause a significant change in the activity of fast motor units. This is confirmed by the results of the analysis of the electromyographic activity of the extensor muscles of the knee joint during testing on an isokinetic dynamometer. Also, after hypokinesia, the possibility of using muscle potential significantly decreased - the physiological cost of work increased with a decrease in strength indicators.

The association of interlimb coordination and temporal symmetry with walking function and motor impairment after stroke.

Interlimb coordination during walking is impaired after stroke, with unknown effects on walking function. This cross-sectional study determined associations of interlimb coordination and temporal symmetry with walking function and motor impairment. During walking, participants wore wireless sensors to detect heel strikes. We calculated interlimb coordination as the phase coordination index and temporal symmetry as the ratio of contralesional (i.e., paretic) to ipsilesional (i.e., non-paretic) stance times. Associations with walking speed (10-meter walk test), walking endurance (6-minute walk test), dynamic balance (Mini Balance Evaluation Systems Test), and motor impairment (Fugl Meyer Lower Extremity assessment) were assessed. 56 individuals with chronic stroke were tested. Worse interlimb coordination was correlated with slower comfortable (R = -0.38, p = 0.004) and maximal (R = -0.36, p = 0.006) walking speed and worse motor function (R = -0.45, p = 0.001). Worse temporal symmetry was correlated with worse motor function (R = 0.39, p = 0.004). Interlimb coordination had stronger associations than temporal symmetry with comfortable (R: -0.38 vs. 0.08) and maximal walking speeds (R: -0.36 vs. 0.12). Poor interlimb coordination was associated with slow walking and motor impairment and had stronger associations with walking speeds than temporal symmetry did. Interlimb coordination may provide unique insights into walking function and a target for walking rehabilitation after stroke.

Can a specific deep brain stimulation paradigm slow motor progression and provide long-term motor benefit in Parkinson’s disease?

Can a specific deep brain stimulation paradigm slow motor progression and provide long-term motor benefit in Parkinson’s disease?

Activities of daily living, self-efficacy and motor skill related fitness and the interrelation in children with moderate and severe Developmental Coordination Disorder.

Children with Developmental Coordination Disorder (DCD) are diagnosed based on poor motor skills that impact their daily activities. However, this may also lead to lower predilection and participation in physical activities and a higher risk to develop health problems. To determine motor skill related levels in children with moderate and severe DCD and compare that to typically developing children (TD). The study also aimed to determine the level of activities of daily living (ADL) as reported by their parent and self-efficacy as reported by the children. Lastly, the relation of motor skill related fitness, ADL, and self-efficacy has been examined. A cross-sectional study has compared TD children (n = 105) and children with DCD (n = 109; 45 moderate DCD and 64 severe DCD) from elementary schools in Tunisia between 7 and 10 years of age. The DCDDaily-Questionnaire and Children's Self-perceptions of Adequacy in and Predilection for Physical Activity Questionnaire have been used to determine ADL and adequacy towards physical activity, respectively. The PERF-FIT has been used to measure motor skill related fitness levels. Large group differences (p = 0.001) were found for ADL and all domains of self-efficacy between TD and DCD children. However, ADL and self-efficacy were not different between moderate and severe DCD. Motor skill related fitness was significantly lower (p = 0.01) for children with DCD than TD children, and between children with moderate and severe DCD. The relation between self-efficacy and DCDDaily-Q was different in the two DCD groups. Slow motor learning was associated with lower perceived enjoyment in physical education in the moderate DCD group, and with lower perceived adequacy in physical education in the severe DCD group. Children with DCD participate and enjoy physical activity less than their peers. This combination of lower participation, lower predilection to physical activity and lowered motor skill-related fitness is a concern for the present and future health status of children with DCD.

Type selective ablation of postnatal slow and fast fatigue-resistant motor neurons in mice induces late onset kinetic and postural tremor following fiber-type transition and myopathy

Animals on Earth need to hold postures and execute a series of movements under gravity and atmospheric pressure. VAChT-Cre is a transgenic Cre driver mouse line that expresses Cre recombinase selectively in motor neurons of S-type (slow-twitch fatigue-resistant) and FR-type (fast-twitch fatigue-resistant). Sequential motor unit recruitment is a fundamental principle for fine and smooth locomotion; smaller-diameter motor neurons (S-type, FR-type) first contract low-intensity oxidative type I and type IIa muscle fibers, and thereafter larger-diameter motor neurons (FInt-type, FF-type) are recruited to contract high-intensity glycolytic type IIx and type IIb muscle fibers. To selectively eliminate S- and FR-type motor neurons, VAChT-Cre mice were crossbred with NSE-DTA mice in which the cytotoxic diphtheria toxin A fragment (DTA) was expressed in Cre-expressing neurons. The VAChT-Cre;NSE-DTA mice were born normally but progressively manifested various characteristics, including body weight loss, kyphosis, kinetic and postural tremor, and muscular atrophy. The progressive kinetic and postural tremor was remarkable from around 20 weeks of age and aggravated. Muscular atrophy was apparent in slow muscles, but not in fast muscles. The increase in motor unit number estimation was detected by electromyography, reflecting compensatory re-innervation by remaining FInt- and FF-type motor neurons to the orphaned slow muscle fibers. The muscle fibers gradually manifested fast/slow hybrid phenotypes, and the remaining FInt-and FF-type motor neurons gradually disappeared. These results suggest selective ablation of S- and FR-type motor neurons induces progressive muscle fiber-type transition, exhaustion of remaining FInt- and FF-type motor neurons, and late-onset kinetic and postural tremor in mice.

Genotype–phenotype correlation in PRKN-associated Parkinson’s disease

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson’s disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p < 0.05). Furthermore, variants located in the N-terminus of the protein, a region enriched with frameshift variants, were associated with an earlier age at onset. The phenotype of PRKN-PD was characterised by slow motor progression, preserved cognition, an excellent motor response to levodopa therapy and later development of motor complications compared to early-onset PD. Non-motor symptoms were however common in PRKN-PD. Our findings on the relationship between the type of variant in PRKN and the phenotype of the disease may have implications for both genetic counselling and the design of precision clinical trials.

Comprehensive phenotypic characterization of an allelic series of zebrafish models of NEB-related nemaline myopathy.

Nemaline myopathy (NM) is a rare congenital neuromuscular disorder characterized by muscle weakness and hypotonia, slow gross motor development, and decreased respiratory function. Mutations in at least twelve genes, all of each encode proteins that are either components of the muscle thin filament or regulate its length and stability, have been associated with NM. Mutations in Nebulin (NEB), a giant filamentous protein localized in the sarcomere, account for more than 50% of NM cases. At present, there remains a lack of understanding of whether NEB genotype influences nebulin function and NM-patient phenotypes. In addition, there is a lack of therapeutically tractable models that can enable drug discovery and address the current unmet treatment needs of patients. To begin to address these gaps, here we have characterized five new zebrafish models of NEB-related NM. These mutants recapitulate most aspects of NEB-based NM, showing drastically reduced survival, defective muscle structure, reduced contraction force, shorter thin filaments, presence of electron-dense structures in myofibers, and thickening of the Z-disks. This study represents the first extensive investigation of an allelic series of nebulin mutants, and thus provides an initial examination in pre-clinical models of potential genotype-phenotype correlations in human NEB patients. It also represents the first utilization of a set of comprehensive outcome measures in zebrafish, including correlation between molecular analyses, structural and biophysical investigations, and phenotypic outcomes. Therefore, it provides a rich source of data for future studies exploring the NM pathomechanisms, and an ideal springboard for therapy identification and development for NEB-related NM.

Myosin 16a is a slow ATPase motor

Myosin 16a is a slow ATPase motor

Motor protein Kif6 regulates cilia motility and polarity in brain ependymal cells.

Motile cilia on ependymal cells that line brain ventricular walls beat in concert to generate a flow of laminar cerebrospinal fluid (CSF). Dyneins and kinesins are ATPase microtubule motor proteins that promote the rhythmic beating of cilia axonemes. Despite common consensus about the importance of axonemal dynein motor proteins, little is known about how kinesin motors contribute to cilia motility. Here, we show that Kif6 is a slow processive motor (12.2±2.0 nm/s) on microtubules in vitro and localizes to both the apical cytoplasm and the axoneme in ependymal cells, although it does not display processive movement in vivo. Using a mouse mutant that models a human Kif6 mutation in a proband displaying macrocephaly, hypotonia and seizures, we found that loss of Kif6 function causes decreased ependymal cilia motility and, subsequently, decreases fluid flow on the surface of brain ventricular walls. Disruption of Kif6 also disrupts orientation of cilia, formation of robust apical actin networks and stabilization of basal bodies at the apical surface. This suggests a role for the Kif6 motor protein in the maintenance of ciliary homeostasis within ependymal cells.

A40: An Experimental Study on the Effect of Intelligent Motor Intervention on Motor Ability of Infants with Motor Retardation

Purpose: Early exercise intervention is particularly important for the improvement of motor ability in young children with delayed motor development. In this study, the effect of intelligent exercise online intervention on the motor ability of slow motor development in children aged 3 to 6 years was verified by arranging interesting sports games in the sports APP. Methods: Using the experimental method, interview method and mathematical statistics method, 37 children aged 3-6 years were selected through the motor development questionnaire, and online exercise intervention was carried out around the six themes of balance, coordination, sensitivity, flexibility, jumping and strength. There is a sports theme cycle every week, and the weekend is a parent-child sports game. The overall intervention lasts for 6 months, lasting from 15 to 20 minutes per day. Results: There were highly significant differences in children's exercise ability before and after the experiment (t= -24.859, P &lt; 0.01); the sensitivity, flexibility and coordination were particularly improved, with highly significant differences (t= -25.147, P &lt; 0.01); interviews found that through weekly parent-child exercise games, children and parents increased physical interaction and language communication compared with before intervention. Conclusion: Intelligent exercise online intervention can effectively improve the motor ability of children aged 3 to 6 years, especially the sensitivity, flexibility, and coordination ability. Meanwhile, regular parent-child exercise can improve communication between parents and children and improve the parent-child relationship.

A model for the contraction kinetics of cytoskeletal gel slabs

Cytoskeletal gels are engineered prototypes that mimic the contractile behavior of a cell in vitro. They are composed of an active polymer matrix and a liquid solvent. Their contraction kinetics is governed by two dynamic phenomena: mechanotransduction (molecular motor activation) and solvent diffusion. In this paper, we solve the transient problem for the simple case of a thin gel slab in uniaxial contraction under two extreme conditions: motor-limited or slow motor (SM) activation regime, and diffusion-limited or fast motor (FM) activation regime. The former occurs when diffusion is much faster than mechanotransduction, while the latter occurs in the opposite case. We observe that in the SM regime, the contraction time scales as t/t0∼(λ/λ0)−3, with t0 being the nominal contraction time, and λ and λ0 being the final and initial stretches of the slab. t0 is proportional to 1/w˙, where w˙ is the average mechanical power generated by the molecular motors per unit reference (dry polymer) volume. In the FM regime, the contraction time scales as t/t1∼(1−λ/λ0)2, with t1 being the nominal contraction time, here proportional to the ratio L2/D, where L is the reference (dry polymer) thickness, and D is the diffusivity of the solvent in the gel. The transition between the SM and FM regimes is defined by a characteristic power density w˙∗, where w˙≪w˙∗ gives the SM regime and w˙≫w˙∗ gives the FM regime. Intuitively, w˙∗ is proportional to D/L2, where, at a given power density w˙, a thinner gel slab (smaller L) or including smaller solvent molecules (higher D) is more likely to be in the SM regime given that solvent diffusion will occur faster than motor activation.

Correlation of slow-wave sleep with motor and nonmotor progression in Parkinson's disease.

This study aimed to explore the association between slow-wave sleep and the progression of motor and nonmotor symptoms in patients with PD. Data were collected from the Parkinson's Progression Markers Initiative study. Slow-wave sleep, also known as deep non-rapid eye movement (DNREM) sleep, was objectively assessed using the Verily Study Watch. Motor function was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III score, Hoehn and Yahr stage, freezing of gait, motor fluctuations, and dyskinesia severity. Comprehensive assessments were conducted on nonmotor symptoms, including depression, anxiety, global cognitive function, and autonomic dysfunction. Statistical analyses involved repeated-measures analysis of variance and linear regression. A total of 102 patients with PD were included in the study, with a median follow-up duration of 3.4 years. In the long DNREM sleep duration group (n = 55), better motor function (DNREM × time interaction: F(1,100) = 4.866, p = 0.030), less severe sexual dysfunction (p = 0.026), and improved activities of daily living (p = 0.033) were observed at the last follow-up visit compared with the short DNREM sleep duration group (n = 47). Reduced DNREM sleep duration is a risk factor for motor progression (β = -0.251, p = 0.021; 95% confidence interval = -0.465 to -0.038). The findings suggest an association between longer DNREM sleep duration and slower motor and nonmotor progression in patients with PD.