Deficits In Motor Performance Research Articles

Robotic exoskeleton assessment of transient ischemic attack.

We used a robotic exoskeleton to quantify specific patterns of abnormal upper limb motor behaviour in people who have had transient ischemic attack (TIA). A cohort of people with TIA was recruited within two weeks of symptom onset. All individuals completed a robotic-based assessment of 8 behavioural tasks related to upper limb motor and proprioceptive function, as well as cognitive function. Robotic task performance was compared to a large cohort of controls without neurological impairments corrected for the influence of age. Impairment in people with TIA was defined as performance below the 5th percentile of controls. Participants with TIA were also assessed with the National Institutes of Health Stroke Scale (NIHSS) score, Chedoke-McMaster Stroke Assessment (CMSA) of the arm, the Behavioural Inattention Test (BIT), the Purdue pegboard test (PPB), and the Montreal Cognitive Assessment (MoCA). Age-related white matter change (ARWMC), prior infarction and cella-media index (CMI) were assessed from baseline CT scan that was performed within 24 hours of TIA. Acute infarction was assessed from diffusion-weighted imaging in a subset of people with TIA. Twenty-two people with TIA were assessed. Robotic assessment showed impaired upper limb motor function in 7/22 people with TIA patients and upper limb sensory impairment in 4/22 individuals. Cognitive tasks involving robotic assessment of the upper limb were completed in 13 participants, of whom 8 (61.5%) showed significant impairment. Abnormal performance in the CMSA arm inventory was present in 12/22 (54.5%) participants. ARWMC was 11.8 ± 6.4 and CMI was 5.4 ± 1.5. DWI was positive in 0 participants. Quantitative robotic assessment showed that people who have had a TIA display a spectrum of upper limb motor and sensory performance deficits as well as cognitive function deficits despite resolution of symptoms and no evidence of tissue infarction.

Reduced muscle strength in ether lipid-deficient mice is accompanied by altered development and function of the neuromuscular junction.

Inherited deficiency in ether lipids, a subgroup of phospholipids whose biosynthesis needs peroxisomes, causes the fatal human disorder rhizomelic chondrodysplasia punctata. The exact roles of ether lipids in the mammalian organism and, therefore, the molecular mechanisms underlying the disease are still largely enigmatic. Here, we used glyceronephosphate O‐acyltransferase knockout (Gnpat KO) mice to study the consequences of complete inactivation of ether lipid biosynthesis and documented substantial deficits in motor performance and muscle strength of these mice. We hypothesized that, probably in addition to previously described cerebellar abnormalities and myelination defects in the peripheral nervous system, an impairment of neuromuscular transmission contributes to the compromised motor abilities. Structurally, a morphologic examination of the neuromuscular junction (NMJ) in diaphragm muscle at different developmental stages revealed aberrant axonal branching and a strongly increased area of nerve innervation in Gnpat KO mice. Post‐synaptically, acetylcholine receptor (AChR) clusters colocalized with nerve terminals within a widened endplate zone. In addition, we detected atypical AChR clustering, as indicated by decreased size and number of clusters following stimulation with agrin, in vitro. The turnover of AChRs was unaffected in ether lipid‐deficient mice. Electrophysiological evaluation of the adult diaphragm indicated that although evoked potentials were unaltered in Gnpat KO mice, ether lipid deficiency leads to fewer spontaneous synaptic vesicle fusion events but, conversely, an increased post‐synaptic response to spontaneous vesicle exocytosis. We conclude from our findings that ether lipids are essential for proper development and function of the NMJ and may, therefore, contribute to motor performance. Read the Editorial Highlight for this article on page 463.

Cervical Joint Position Sense in Hypobaric Conditions: A Randomized Double-Blind Controlled Trial.

Thirty-six healthy subjects (Neck Disability Index < 5) volunteered to participate. Neck position sense was evaluated using a three-dimensional motion analyzer. To create the environment, a hypobaric chamber was used to simulate artificial moderate altitude. Head repositioning error was measured by asking the subject to perform a head-to-neutral task after submaximal flexion-extension and right/left rotation movements, and a head-to-target task, in which the subjects had to return to a 30° right and left rotation position. Exposure to artificial acute moderate altitude of 7,000 feet had no significant effects on cervical joint position sense measured by head repositioning accuracy in healthy subjects. Discussion/impact/recommendations: Postural control mechanisms are very sensitive to acute mild hypoxia and have been recently investigated. Acute hypobaric hypoxia at moderate and high altitudes has a negative effect on postural control. However, which part of the postural system is affected has not yet been determined and proprioception has been little investigated. The results from this study highlighted that in healthy subjects with good cervical spine proprioception at baseline, artificial hypoxia induced by the simulation of moderate altitude does not increase head repositioning error. Further studies should investigate cervical joint position sense in real aircraft, at different altitudes and in a group of experienced helicopter pilots, to evaluate the impact of moderate altitude on cervical joint position sense in a different population. Conducting the same experiments in a population of pilots and in real flight conditions should be considered, since various factors such as the level of proprioception, head posture, type of movement, head load, muscle fatigue, flight altitude, and the length of flight time might influence the kinesthetic sensitivity.

A reduced somatosensory gating response in individuals with multiple sclerosis is related to walking impairment.

When identical stimuli are presented in rapid temporal succession, neural responses to the second stimulation are often weaker than those observed for the first. This phenomenon is termed sensory gating and is believed to be an adaptive feature that helps prevent higher-order cortical centers from being flooded with unnecessary information. Recently, sensory gating in the somatosensory system has been linked to deficits in tactile discrimination. Additionally, studies have linked poor tactile discrimination with impaired walking and balance in individuals with multiple sclerosis (MS). In this study, we examine the neural basis of somatosensory gating in patients with MS and healthy controls and assess the relationship between somatosensory gating and walking performance. We used magnetoencephalography to record neural responses to paired-pulse electrical stimulation applied to the right posterior tibial nerve. All participants also walked across a digital mat, which recorded their spatiotemporal gait kinematics. Our results showed the amplitude of the response to the second stimulation was sharply reduced only in controls, resulting in a significantly reduced somatosensory gating in the patients with MS. No group differences were observed in the amplitude of the response to the first stimulation nor the latency of the neural response to either the first or second stimulation. Interestingly, the altered somatosensory gating responses were correlated with aberrant spatiotemporal gait kinematics in the patients with MS. These results suggest that inhibitory GABA circuits may be altered in patients with MS, which impacts somatosensory gating and contributes to the motor performance deficits seen in these patients.NEW & NOTEWORTHY We aimed to determine whether somatosensory gating in patients with multiple sclerosis (MS) differed compared with healthy controls and whether a relationship exists between somatosensory gating and walking performance. We found reduced somatosensory gating responses in patients with MS, and these altered somatosensory gating responses were correlated with the mobility impairments. These novel findings show that somatosensory gating is impaired in patients with MS and is related to the mobility impairments seen in these patients.

Functional Capacity Of Gastrointestinal Cancer Patients - A Pre-therapy Comparison To Breast Cancer Patients And Healthy Women

PURPOSE: Many studies of cancer patients report that frailty, cachexia and decreased physical function during chemotherapy (CT) predict a higher mortality risk. Although a high prevalence of these symptoms in gastrointestinal (GI) cancer patients is known, there is almost no data on functional status and body composition in this population. The aim of the study is to asses and compare the pre-therapy motor performance of advanced GI cancer patients in contrast to breast cancer patients and healthy controls. METHODS: In a 3-arm cross-sectional study female patients with advanced cancer (UICC ≥ III) (GI: n=17; 70.1±3.1 yrs; BMI 23.6±5.3 kg/m2; breast: n=17; 66.9±2.3 yrs; BMI 23.6±3.8 kg/m2) before first-line CT and 17 healthy age-matched women (69.4±1.4 yrs; BMI 24.2±3.3 kg/m2) are examined. Body composition was obtained from bioelectrical impedance analysis. The amount of daily physical activity (steps; MVPA/min·wk-1) was calculated from accelerometer (Actigraph) readings. A capacitive force platform (Zebris) was used for gait speed recordings during free level walking. Maximal isometric voluntary contraction force (MIVF) of the quadriceps muscle was assessed by a strain gauge force transducer (ASYS). RESULTS: ANOVA with post-hoc test and Bonferroni correction show significant differences in outcome measures of GI cancer patients compared to breast cancer patients and healthy women. GI cancer patients show lower values in phase angle (4.5±0.8°; 5.4±0.4°; 5.3±0.5°; p<.01) and isometric strength (5.5±2.2; 9.1±3.3; 8.4±1.8 N/kg; p<.01). Steps per day (3125±2396; 8703±4104 stp, p<.001), moderate to vigorous activity (7.3±11.9; 36.9±28.5 MVPA/min·wk-1; p=.001) and gait speed (3.5±1.1; 4.9±0.6 km/h; p<.001) are decreased compared to healthy women. CONCLUSIONS: Patients with advanced GI cancers demonstrate sufficient deficits in functional status and motor performance before CT compared to advanced breast cancer patients and healthy women. Gait speed, phase angle and force are below cut-off values for low prognosis of survival and may reflect a diminished tolerance of CT. Measures to improve muscle status, physical function and its effects on treatment is warranted in patients with advanced GI cancers.

Cognitive Processing Speed across the Lifespan: Beyond the Influence of Motor Speed.

Traditional neuropsychological measurement of cognitive processing speed with tasks such as the Symbol Search and Coding subsets of the WAIS-IV, consistently show decline with advancing age. This is potentially problematic with populations where deficits in motor performance are expected, i.e., in aging or stroke populations. Thus, the aim of the current study was to explore the contribution of hand motor speed to traditional paper-and-pencil measures of processing speed and to a simple computer-customized non-motor perception decision task, the Inspection Time (IT) task. Participants were 67 young university students aged between 18 and 29 (59 females), and 40 older adults aged between 40 and 81 (31 females) primarily with a similar education profile. As expected, results indicated that age group differences were highly significant on the motor dexterity, Symbol Search and Coding tasks. However, no significant differences or correlations were seen between age groups and the simple visual perception IT task. Furthermore, controlling for motor dexterity did not remove significant age-group differences on the paper-and-pencil measures. This demonstrates that although much of past research into cognitive decline with age is confounded by use of motor reaction times as the operational measure, significant age differences in cognitive processing also exist on more complex tasks. The implications of the results are crucial in the realm of aging research, and caution against the use of traditional WAIS tasks with a clinical population where motor speed may be compromised, as in stroke.

AMETROPIA, VISUAL DEFICITS AND MOTOR PERFORMANCE IN SCHOOL SPORTS

BackgroundIn childhood/puberty essential physical and school developments take place. Poor eyesight in this phase represents a handicap, as is known. Concluding, the basic correlation between a good eyesight and a...

Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington's like symptoms in rats: Possible neurotransmitters modulation.

Huntington Disease is autosomal, fatal and progressive neurodegenerative disorder for which clinically available drugs offer only symptomatic relief. Emerging strides have indicated that antidepressants improve motor performance, restore neurotransmitters level, ameliorates striatal atrophy, increases BDNF level and may enhance neurogenesis. Therefore, we investigated sertraline and venlafaxine, clinically available drugs for depression with numerous neuroprotective properties, for their beneficial effects, if any, in quinolinic acid induced Huntington's like symptoms in rats. Rats were administered quinolinic acid (QA) (200 nmol/2μl saline) intrastriatal bilaterally on 0day. Sertraline and venlafaxine (10 and 20mg/kg, po) each were administered for 21days once a day. Motor performance was assessed using rotarod test, grip strength test, narrow beam walk test on weekly basis. On day 22, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH and Nitrite), neuroinflammation (TNF-α, IL-1β and IL-6) and neurochemical analysis (GABA, glutamate, norepinephrine, dopamine, serotonin, DOPAC, HVA and 5-HIAA). QA treatment significantly altered body weight, motor performance, oxidative defense (increased LPO, nitrite and decreased GSH), pro-inflammatory cytokines levels (TNF-α, IL-6 and IL-1β), neurochemical level (GABA, glutamate, nor-epinephrine, dopamine, serotonin, HVA, DOPAC, 5-HIAA). Sertraline and venlafaxine at selected doses significantly attenuated QA induced alterations in striatum. The present study suggests that modulation of monoamines level, normalization of GABA and glutamatergic signaling, anti-oxidant and anti-inflammatory properties could underlie the neuroprotective effect of sertraline and venlafaxine in QA induced Huntington's like symptoms.

Postural Motor Learning Deficits in People With MS in Spatial but Not Temporal Control of Center of Mass

Background: Multiple sclerosis (MS) is associated with balance deficits resulting in falls and impaired mobility. Although rehabilitation has been recommended to address these balance deficits, the extent to which people with MS can learn and retain improvements in postural responses is unknown. Aim: To determine the ability of people with MS to improve postural control with surface perturbation training. Methods: A total of 24 patients with mild MS and 14 age-matched controls underwent postural control training with a set pattern of continuous, forward-backward, sinusoidal, and surface translations provided by a force platform. Postural control was then tested the following day for retention. The primary outcome measures were the relative phase and center-of-mass (CoM) gain between the body CoM and the platform motion. Results: People with MS demonstrated similar improvements in acquiring and retaining changes in the temporal control of the CoM despite significant deficits in postural motor performance at the baseline. Both MS and control groups learned to anticipate the pattern of forward-backward perturbations, so body CoM shifted from a phase-lag (age-matched controls [CS] = −7.1 ± 1.3; MS = −12.9 ± 1.0) toward a phase-lead (CS = −0.7 ± 1.8; MS = −6.1 ± 1.4) relationship with the surface oscillations. However, MS patients were not able to retain the changes in the spatial control of the CoM acquired during training. Conclusions: People with MS have the capacity to improve use of a feed-forward postural strategy with practice and retain the learned behavior for temporal not spatial control of CoM, despite their significant postural response impairments.

Sensorimotor cortex injury effects on recovery of contralesional dexterous movements in Macaca mulatta

The effects of primary somatosensory cortex (S1) injury on recovery of contralateral upper limb reaching and grasping were studied by comparing the consequences of isolated lesions to the arm/hand region of primary motor cortex (M1) and lateral premotor cortex (LPMC) to lesions of these same areas plus anterior parietal cortex (S1 and rostral area PE). We used multiple linear regression to assess the effects of gray and white matter lesion volumes on deficits in reaching and fine motor performance during the first month after the lesion, and during recovery of function over 3, 6 and 12months post-injury in 13 monkeys. Subjects with frontoparietal lesions exhibited larger deficits and poorer recovery as predicted, including one subject with extensive peri-Rolandic injury developing learned nonuse after showing signs of recovery. Regression analyses showed that total white matter lesion volume was strongly associated with initial post-lesion deficits in motor performance and with recovery of skill in reaching and manipulation. Multiple regression analyses using percent damage to caudal M1 (M1c), rostral S1 (S1r), LPMC and area PE as predictor variables showed that S1r lesion volumes were closely related to delayed post-lesion recovery of upper limb function, as well as lower skill level of recovery. In contrast, M1c lesion volume was related primarily to initial post-lesion deficits in hand motor performance. Overall, these findings demonstrate that frontoparietal injury impairs hand motor function more so than frontal motor injury alone, and results in slower and poorer recovery than lesions limited to frontal motor cortex.

Deficits in motor abilities for multi-finger force control in hemiparetic stroke survivors.

The ability to control redundant motor effectors is one of hallmarks in human motor control, and the topic has been studied extensively over several decades since the initial inquiries proposed by Nicholi Bernstein. However, our understanding of the influence of stroke on the control of redundant motor systems is very limited. This study aimed to investigate the effect of stroke-related constraints on multi-finger force control abilities in a visuomotor task. Impaired (IH) and less-impaired hands (LH) of 19 hemiparetic stroke survivors and 19 age-matched control subjects were examined. Each hand repeatedly produced isometric forces to match a target force of 5N shown on a computer screen using all four fingers. The hierarchical variability decomposition (HVD) model was used to separate force-matching errors (motor performance) into task-relevant measures (accuracy, steadiness, and reproducibility). Task-irrelevant sources of variability in individual finger force profiles within and between trials (flexibility and multiformity) were also quantified. The IH in the stroke survivors showed deficits in motor performance attributed mainly to lower accuracy and reproducibility as compared to control hands (p<0.05). The LH in stroke survivors showed lower reproducibility and both hands in stroke also had higher multiformity than the control hands (p<0.05). The findings from our HVD model suggest that accuracy, reproducibility, and multiformity were mainly impaired during force-matching task in the stroke survivors. The specific motor deficits identified through the HVD model with the new conceptual framework may be considered as critical factors for scientific investigation on stroke and evidence-based rehabilitation of this population.

Absence of Prenatal Forebrain Defects in the Dp(16)1Yey/+ Mouse Model of Down Syndrome.

Studies in humans with Down syndrome (DS) show that alterations in fetal brain development are followed by postnatal deficits in neuronal numbers, synaptic plasticity, and cognitive and motor function. This same progression is replicated in several mouse models of DS. Dp(16)1Yey/+ (hereafter called Dp16) is a recently developed mouse model of DS in which the entire region of mouse chromosome 16 that is homologous to human chromosome 21 has been triplicated. As such, Dp16 mice may more closely reproduce neurodevelopmental changes occurring in humans with DS. Here, we present the first comprehensive cellular and behavioral study of the Dp16 forebrain from embryonic to adult stages. Unexpectedly, our results demonstrate that Dp16 mice do not have prenatal brain defects previously reported in human fetal neocortex and in the developing forebrains of other mouse models, including microcephaly, reduced neurogenesis, and abnormal cell proliferation. Nevertheless, we found impairments in postnatal developmental milestones, fewer inhibitory forebrain neurons, and deficits in motor and cognitive performance in Dp16 mice. Therefore, although this new model does not express prenatal morphological phenotypes associated with DS, abnormalities in the postnatal period appear sufficient to produce significant cognitive deficits in Dp16.

Antidyskinetic effect of A2A and 5HT1A/1B receptor ligands in two animal models of Parkinson's disease.

The serotonin 5-HT1A/1B receptor agonist eltoprazine suppressed dyskinetic-like behavior in animal models of Parkinson's disease (PD) but simultaneously reduced levodopa (l-dopa)-induced motility. Moreover, adenosine A2A receptor antagonists, such as preladenant, significantly increased l-dopa efficacy in PD without exacerbating dyskinetic-like behavior. We evaluated whether a combination of eltoprazine and preladenant may prevent or suppress l-dopa-induced dyskinesia, without impairing l-dopa's efficacy in relieving motor signs, in 2 PD models: unilateral 6-hydroxydopamine-lesioned rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Rotational behavior and abnormal involuntary movements, or disability and l-dopa-induced dyskinesia were evaluated in 6-hydroxydopamine-lesioned rats and MPTP-treated monkeys, respectively. Moreover, in the rodent striatum, induction of immediate-early gene zif-268, an index of long-term changes, was correlated with dyskinesia. In 6-hydroxydopamine-lesioned rats, combined administration of l-dopa (4 mg/kg) plus eltoprazine (0.6 mg/kg) plus preladenant (0.3 mg/kg) significantly prevented or reduced dyskinetic-like behavior without impairing motor activity. Zif-268 was increased in the striatum of rats treated with l-dopa and l-dopa plus preladenant compared with vehicle. In contrast, rats treated with eltoprazine (with or without preladenant) had lower zif-268 activation after chronic treatment in both the dyskinetic and l-dopa-non-primed groups. Moreover, acute l-dopa plus eltoprazine plus preladenant prevented worsening of motor performance (adjusting step) and sensorimotor integration deficit. Similar results were obtained in MPTP-treated monkeys, where a combination of preladenant with eltoprazine was found to counteract dyskinesia and maintain the full therapeutic effects of a low dose of l-dopa. Our results suggest a promising nondopaminergic pharmacological strategy for the treatment of dyskinesia in PD. © 2016 International Parkinson and Movement Disorder Society.

Neonatal Extracorporeal Membrane Oxygenation: Update on Management Strategies and Long-Term Outcomes.

Extracorporeal membrane oxygenation (ECMO) can be deployed to support patients with severe cardiorespiratory failure unresponsive to conventional medical interventions. Neonatal trials have demonstrated that ECMO is an effective treatment of severe respiratory failure, with acceptable cognitive and functional outcomes. Technological advances in ECMO have resulted in improved safety and accessibility, contributing to decreased morbidity and improved survival of increasingly complex patients requiring ECMO support. This review aims to describe the innovations in ECMO technology and management in the neonatal population in the last decade. The long-term outcomes of neonatal patients requiring ECMO support will be discussed. Relevant clinical trials from MEDLINE and the Cochrane Library were identified. The following key words were used: ECMO, infant, neonate, and outcomes. Challenges still remain in supporting the premature and/or low-birth-weight infant with severe respiratory failure, as well as infants with congenital diaphragmatic hernia. Neonatal ECMO survivors can present with neurodevelopmental and respiratory problems, which become more prominent with time. While newer technologies have led to fewer neonates with respiratory failure progressing to ECMO, it remains an important tool to in those who have failed conventional therapies. Given the presence of neurodevelopmental problems in neonatal ECMO survivors, multidisciplinary follow-up targeting motor performance, exercise capacity, behavior, and subtle learning deficits is warranted. With the overall decreasing use of neonatal ECMO, ECMO centers must find ways to maintain their expertise in the light of lower patient volumes amidst complex patient physiology.

Subcortical Volume Loss in the Thalamus, Putamen, and Pallidum, Induced by Traumatic Brain Injury, Is Associated With Motor Performance Deficits

Background. Traumatic brain injury (TBI) has been associated with altered microstructural organization of white matter (WM) and reduced gray matter (GM). Although disrupted WM organization has been linked to poorer motor performance, the predictive value of GM atrophy for motor impairments in TBI remains unclear. Objective. Here, we investigated TBI-induced GM volumetric abnormalities and uniquely examined their relationship with bimanual motor impairments. Methods. 22 moderate to severe TBI patients (mean age = 25.9 years, standard deviation [SD] = 4.9 years; time since injury = 4.7 years, SD = 3.7 years) and 27 age- and gender-matched controls (mean age = 23.4 years; SD = 3.8 years) completed bimanual tasks and a structural magnetic resonance imaging scan. Cortical and subcortical GM volumes were extracted and compared between groups using FreeSurfer. The association between bimanual performance and GM volumetric measures was investigated using partial correlations. Results. Relative to controls, patients performed significantly poorer on the bimanual tasks and demonstrated significantly smaller total GM as well as overall and regional subcortical GM. However, the groups did not show significant differences in regional cortical GM volume. The majority of the results remained significant even after excluding TBI patients with focal lesions, suggesting that TBI-induced volume reductions were predominantly caused by diffuse injury. Importantly, atrophy of the thalamus, putamen, and pallidum correlated significantly with poorer bimanual performance within the TBI group. Conclusions. Our results reveal that GM atrophy is associated with motor impairments in TBI, providing new insights into the etiology of motor control impairments following brain trauma.

A proteomic approach to understand MMP-3-driven developmental processes in the postnatal cerebellum: Chaperonin CCT6A and MAP kinase as contributing factors.

Matrix metalloproteinase-3 (MMP-3) deficiency in mice was previously reported to result in a transiently retarded granule cell migration at postnatal day 8 (P8) and a sustained disturbed arborization of Purkinje cell dendrites from P8 on, concomitant with a delayed synapse formation between granule cells and Purkinje cells and resulting in mild deficits in motor performance in adult animals. However, the molecular mechanisms by which MMP-3 contributes to proper development of the cerebellar cortex during the first postnatal weeks remains unknown. In this study, we used a functional proteomics approach to investigate alterations in protein expression in postnatal cerebella of wild-type versus MMP-3 deficient mice, and to further elucidate MMP-3-dependent pathways and downstream targets in vivo. At P8, two-dimensional difference gel electrophoresis and mass spectrometry identified 20 unique proteins with a different expression between the two genotypes. Subsequent "Ingenuity Pathway Analysis" and Western blotting indicate that the chaperonin containing T-complex polypeptide 1, subunit 6A and the MAP kinase signaling pathway play a key role in the MMP-3-dependent regulation of neurite outgrowth and neuronal migration in the developing brain.

Changes in sensory function and force production in adults with type II diabetes

The purpose of this study was to evaluate the relationship among sensory function, disease severity, and upper extremity force production in adults with type II diabetes (T2D) as compared with healthy age- and gender-matched controls. Ten adults with T2D and 10 healthy age- and gender-matched control subjects underwent a battery of sensory and motor function evaluations. Data on disease severity and duration were also collected. The T2D group exhibited sensory deficits and altered force production as compared with healthy controls. Sensory function correlated with disease severity, as did signal predictability of kinetic output during submaximal force production tasks. Maximal force production tasks were associated with altered output in T2D, but these data did not correlate with disease severity or sensory dysfunction. Some, not all, motor performance deficits in T2D are associated with sensory dysfunction. Mechanisms responsible for these changes in adult-onset T2D are described.

Effects of local and widespread muscle fatigue on movement timing.

Repetitive movements can cause muscle fatigue, leading to motor reorganization, performance deficits, and/or possible injury. The effects of fatigue may depend on the type of fatigue task employed, however. The purpose of this study was to determine how local fatigue of a specific muscle group versus widespread fatigue of various muscle groups affected the control of movement timing. Twenty healthy subjects performed an upper extremity low-load work task similar to sawing for 5 continuous minutes both before and after completing a protocol that either fatigued all the muscles used in the task (widespread fatigue) or a protocol that selectively fatigued the primary muscles used to execute the pushing stroke of the sawing task (localized fatigue). Subjects were instructed to time their movements with a metronome. Timing error, movement distance, and speed were calculated for each movement. Data were then analyzed using a goal-equivalent manifold approach to quantify changes in goal-relevant and non-goal-relevant variability. We applied detrended fluctuation analysis to each time series to quantify changes in fluctuation dynamics that reflected changes in the control strategies used. After localized fatigue, subjects made shorter, slower movements and exerted greater control over non-goal-relevant variability. After widespread fatigue, subjects exerted less control over non-goal-relevant variability and did not change movement patterns. Thus, localized and widespread muscle fatigue affected movement differently. Local fatigue may reduce the available motor solutions and therefore cause greater movement reorganization than widespread muscle fatigue. Subjects altered their control strategies but continued to achieve the timing goal after both fatigue tasks.

Deficits in motor performance after pedunculopontine lesions in rats--impairment depends on demands of task.

Anatomically and functionally located between basal ganglia and brainstem circuitry, the pedunculopontine tegmental nucleus (PPTg) is in a pivotal position to contribute to motor behavior. Studies in primates have reported akinesia and postural instability following destruction of the PPTg. In humans, the PPTg partially degenerates in Parkinson's disease and stimulation of this region is under investigation as a possible therapeutic. Studies in rats report no crude motor impairment following PPTg lesion, although a detailed assessment of the role of the PPTg in rat motor function has not been reported. Our studies applied motor tests generally used in rodent models of Parkinson's disease to rats bearing either excitotoxic damage to all neuronal populations within PPTg, or selective destruction of the cholinergic subpopulation created with the toxin Dtx-UII. Neither lesion type altered baseline locomotion. On the rotarod, excitotoxic lesions produced a persistent impairment on the accelerating, but not fixed speed, conditions. In the vermicelli handling task (a quantitative measure of fine motor control and effective behavioral sequencing) excitotoxic lesions produced no single impairment, but globally increased the number of normal and abnormal behaviors. In contrast, depletion of cholinergic PPTg neurons produced impairment on the accelerating rotarod but no changes in vermicelli handling. Together, these results show that while PPTg lesions produce no impairment in the execution of individual motor actions, impairments emerge when the demands of the task increase. Results are discussed in terms of PPTg acting as part of a rapid action selection system, which integrates sensory information into motor output.

Poster #S23 UPREGULATION OF STRIATAL DOPAMINE D2 RECEPTORS RESULTS IN PERSISTENT ALTERATIONS IN PRE-SYNAPTIC DOPAMINE FUNCTION

Huntington's disease (HD) is an inherited neurodegenerative disorder that is classically defined by a triad of movement and cognitive and psychiatric abnormalities with a well-established pathology that affects the dopaminergic systems of the brain. This has classically been described in terms of an early loss of dopamine D2 receptors (D2R), although interestingly the treatments most effectively used to treat patients with HD block these same receptors. We therefore sought to examine the dopaminergic system in HD not only in terms of striatal function but also at extrastriatal sites especially the hippocampus, given that transgenic (Tg) mice also exhibit deficits in hippocampal-dependent cognitive tests and a reduction in adult hippocampal neurogenesis. We showed that there was an early reduction of D2R in both the striatum and dentate gyrus (DG) of the hippocampus in the R6/1 transgenic HD mouse ahead of any overt motor signs and before striatal neuronal loss. Despite downregulation of D2Rs in these sites, further reduction of the dopaminergic input to these sites by either medial forebrain bundle lesions or receptor blockade using sulpiride was able to improve both deficits in motor performance and adult hippocampal neurogenesis. In contrast, a reduction in dopaminergic innervation of the neurogenic niches resulted in impaired neurogenesis in healthy WT mice. This study therefore provides evidence that D2R blockade improves hippocampal and striatal deficits in HD mice although the underlying mechanism for this is unclear, and suggests that agents working within this network may have greater effects than previously thought.