Context-dependent motor performance is a phenomenon in which people perform better in the environ... more Context-dependent motor performance is a phenomenon in which people perform better in the environmental context where they originally practiced a task. Some animal and computer simulation studies suggested that context-dependent performance may be associated with neural activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine the role of the DLPFC in context-dependent motor performance by perturbing the neural processing of the DLPFC with repetitive transcranial magnetic stimulation (rTMS) in healthy adults. Thirty healthy adults were recruited into the Control, rTMS DLPFC, and rTMS Vertex groups. The participants practiced three finger sequences associated with a specific incidental context (a colored circle and a location on the computer screen). One day following practice, the rTMS groups received 1 Hz rTMS prior to the testing conditions in which the sequence-context associations remained the same as practice (SAME) or changed (SWITCH). All three groups improved significantly over practice on day one. The second day testing results showed that the DLPFC group demonstrated significantly less decrement in motor performance under the SWITCH condition than the Control and Vertex groups. This finding suggests a specific role of the DLPFC in context-dependent motor performance. This article is protected by copyright. All rights reserved.
Background: Ankle sprains are common within the general population and can result in prolonged di... more Background: Ankle sprains are common within the general population and can result in prolonged disablement. Limited talocrural dorsiflexion range of motion (DF ROM) is a common consequence of ankle sprain. Limited talocrural DF ROM may contribute to persistent symptoms, disability, and an elevated risk for re-injury. As a result, many health care practitioners use hands-on passive procedures with the intention of improving talocrural joint DF ROM in individuals following ankle sprains. Dosage of passive hands-on procedures involves a continuum of treatment speeds. Recent evidence suggests both slow-and fast-speed treatments may be effective to address disablement following ankle sprains. However, these interventions have yet to be longitudinally compared against a placebo study condition.
Background: Many health care practitioners use a variety of hands-on treatments to improve sympto... more Background: Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.
Epidemiological and clinical trials have suggested that exercise is beneficial for patients with ... more Epidemiological and clinical trials have suggested that exercise is beneficial for patients with Parkinson's disease (PD). However, the underlying mechanisms and potential for disease modification are currently unknown. This review presents current findings from our laboratories in patients with PD and animal models. The data indicate that alterations in both dopaminergic and glutamatergic neurotransmission, induced by activity-depend-ent (exercise) processes, may mitigate the cortically driven hyper-excitability in the basal ganglia normally observed in the parkinsonian state. These insights have potential to identify novel therapeutic treatments capable of reversing or delaying disease progression in PD.
Proceedings of the 4th Conference on Wireless Health - WH '13, 2013
In this paper, we present PoCM 2 (Point-of-Care Mobility Monitoring), a generic and extensible at... more In this paper, we present PoCM 2 (Point-of-Care Mobility Monitoring), a generic and extensible at-home mobility evaluation and monitoring system. PoCM 2 uses both 3D visual sensors (such as Microsoft Kinect) and mobile sensors (i.e., internal and external sensors embedded with/connected to a mobile device such as a smartphone) for complementary data acquisition, as well as a series of analytics that allow evaluation of both archived and real-time mobility data. We demonstrate the performance of PoCM 2 with a specific application developed for freeze detection and quantification from Parkinson's Disease mobility data, as an approach to estimate the medication level of the PD patients and potentially recommend adjustments.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 8, 2014
Human pelvic floor muscles have been shown to operate synergistically with a wide variety of musc... more Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm...
Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's... more Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's disease, but the underlying molecular mechanisms responsible for these effects are poorly understood. Studies in rodent models provide a means to examine the effects of exercise on dopaminergic neurotransmission. Using intensive treadmill exercise, we determined changes in striatal dopamine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. C57BL/6J mice were divided into four groups: (1) saline, (2) saline plus exercise, (3) MPTP, and (4) MPTP plus exercise. Exercise was started 5 d after MPTP lesioning and continued for 28 d. Treadmill running improved motor velocity in both exercise groups. All exercised animals also showed increased latency to fall (improved balance) using the accelerating rotarod compared with nonexercised mice. Using HPLC, we found no difference in striatal dopamine tissue levels between MPTP plus exercise compared with MPTP mice. There was an increase detected in saline plus exercise mice. Analyses using fast-scan cyclic voltammetry showed increased stimulus-evoked release and a decrease in decay of dopamine in the dorsal striatum of MPTP plus exercise mice only. Immunohistochemical staining analysis of striatal tyrosine hydroxylase and dopamine transporter proteins showed decreased expression in MPTP plus exercise mice compared with MPTP mice. There were no differences in mRNA transcript expression in midbrain dopaminergic neurons between these two groups. However, there was diminished transcript expression in saline plus exercise compared with saline mice. Our findings suggest that the benefits of treadmill exercise on motor performance may be accompanied by changes in dopaminergic neurotransmission that are different in the injured (MPTP-lesioned) compared with the noninjured (saline) nigrostriatal system.
We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercis... more We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD), including an increase in the dopamine D2 receptor (DA-D2R), using noninvasive PET imaging with the radioligand [18F]fallypride. The purpose of this feasibility and translational study was to examine whether intensive exercise leads to similar alterations in DA-D2R expression using PET imaging with [18F]fallypride in individuals with early-stage PD. In this pilot study, four patients with early-stage PD were randomized to receive intensive exercise (treadmill training sessions three times/week for 8 weeks) or no exercise. Two healthy age-matched individuals participated in treadmill training. Alterations in the DA-D2R binding potential (BP) as a marker for receptor expression were determined using PET imaging with [18F]fallypride. Turning performance in the patients with PD as a measure of postural control and the Unified Parkinson's Disease Rating Scale scores pre-exercise and postexercise were determined. Our data showed an exercise-induced increase in [18F]fallypride BP as well as improved postural control in patients with PD who exercised. Changes in DA-D2R BP were not observed in patients with PD who did not exercise. These results suggest that exercise can lead to neuroplasticity in dopaminergic signaling and contribute to improved function that may be task specific (postural control) in early-stage PD.
We studied corticomotor excitability (CE) between the more and less affected sides in early Parki... more We studied corticomotor excitability (CE) between the more and less affected sides in early Parkinson's disease (PD) patients using transcranial magnetic stimulation (TMS). Sixteen-PD patients within the first 3 years of diagnosis were studied with single-pulse TMS over each motor cortex with intensities from 40% to 100% stimulator output. Active motor evoked potentials (MEP) and cortical silent period durations (CSP) were recorded, fitted with sigmoid curves, summarized as maximal MEP/CSP, maximal MEP/CSP slope, and intensity where MEP/CSP is half-maximal (MEP/CSP-Int50), and correlated with Unified Parkinson's Disease Rating Scale scores (UPDRS). On the more affected side, higher (worse) UPDRS scores were correlated with shorter maximal CSP (r ϭ Ϫ0.51, P ϭ 0.046). On the less affected side, higher UPDRS scores were correlated with higher MEP-Int50 (r ϭ 0.51, P ϭ 0.043) and CSP-Int50 (r ϭ 0.54, P ϭ 0.029). For the less affected side, altered CE, as indexed by higher MEP or CSP-Int50 intensities, may contribute to early clinical symptoms. On the more affected side, increases in CE, indexed by shorter CSP, may account for a greater proportion of PD symptoms. These findings are consistent with an evolution of neurophysiologic correlates in early PD patients from a less to more symptomatic state.
The purpose of the current study was to examine changes in dopamine D2 receptor (DA-D2R) expressi... more The purpose of the current study was to examine changes in dopamine D2 receptor (DA-D2R) expression within the basal ganglia of MPTP mice subjected to intensive treadmill exercise. Using Western immunoblotting analysis of synaptoneurosomes and in vivo positron emission tomography (PET) imaging employing the DA-D2R specific ligand [ 18 F]fallypride, we found that high intensity treadmill exercise led to an increase in striatal DA-D2R expression that was most pronounced in MPTP compared to saline treated mice. Exercise-induced changes in the DA-D2R in the dopamine-depleted basal ganglia are consistent with the potential role of this receptor in modulating medium spiny neurons (MSNs) function and behavioral recovery. Importantly, findings from this study support the rationale for using PET imaging with [ 18 F]fallypride to examine DA-D2R changes in individuals with Parkinson's Disease (PD) undergoing high-intensity treadmill training.
... PURPOSe: the aim of this study was to evaluate the effect of physical training on the reactiv... more ... PURPOSe: the aim of this study was to evaluate the effect of physical training on the reactivity of pulmonary artery rings from rats submitted to a pulmonary IR. MeTHOdS:Wistar male rats were divided into five groups named: control sedentary (SD); Trained (TR); sham ...
Journal of Orthopaedic & Sports Physical Therapy, 2013
T T RESULTS: It is feasible to measure the CE of the gluteus maximus with TMS. The intraclass cor... more T T RESULTS: It is feasible to measure the CE of the gluteus maximus with TMS. The intraclass correlation coefficients for all TMS outcome measures ranged from 0.73 to 0.97. The ranges of minimal detectable change, with respect to mean values for each TMS variable, were larger for MEP amplitude (304.7-585.4 µV) compared to those for cortical silent period duration (25.3-40.8 milliseconds) and MEP latency (1.1-2.1 milliseconds).
The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) provides an excellent oppor... more The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) provides an excellent opportunity to study repair and response to injury in the basal ganglia. Administration to mammals leads to the destruction of nigrostriatal dopaminergic neurons and depletion of striatal dopamine. In the squirrel monkey (Saimiri sciureus), MPTP-lesioning results in parkinsonian motor symptoms including bradykinesia, postural instability, and rigidity. Over time animals display motor behavioral recovery. To better understand this mechanism we employed a lesioning regimen of two or six subcutaneous injections of MPTP (2.0 mg/kg, free-base) to generate mild or moderate parkinsonism. Brain tissue was harvested at 6 weeks or 9 months after the last injection and analyzed for dopamine and its metabolites by high performance liquid chromatography (HPLC), and by immunohistochemical staining and Western immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine-and cAMPresponsive protein phosphatase of 32 kDa (DARPP-32), an effector molecule enriched in striatal medium spiny neurons. Several months after MPTP-lesioning, when squirrel monkeys displayed full motor behavioral recovery, striatal dopamine levels remained low with a greater return in the ventral striatum. This finding is consistent with other reports using neurotoxicantlesioning models of the basal ganglia in rodents and other species of nonhuman primates. Elevated dopamine turnover ratio and decreased DAT expression appeared in early behavioral recovery at the 6-week time point in both mild-and moderate-parkinsonian monkeys. Tyrosine hydroxylase and DAT expression was increased in late stage recovery even within dopa-mine-depleted regions and supports sprouting. Altered DARPP-32 expression suggests a role of medium spiny neurons in recovery. V V C 2005 Wiley-Liss, Inc.
Physical activity has been shown to be neuroprotective in lesions affecting the basal ganglia. Us... more Physical activity has been shown to be neuroprotective in lesions affecting the basal ganglia. Using a treadmill exercise paradigm, we investigated the effect of exercise on neurorestoration. The 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-lesioned mouse model provides a means to investigate the effect of exercise on neurorestoration because 30 -40% of nigrostriatal dopaminergic neurons survive MPTP lesioning and may provide a template for neurorestoration to occur. MPTPlesioned C57 BL/6J mice were administered MPTP (four injections of 20 mg/kg free-base, 2 hr apart) or saline and divided into the following groups: (1) saline; (2) saline ϩ exercise; (3) MPTP; and (4) MPTP ϩ exercise. Mice in exercise groups were run on a motorized treadmill for 30 days starting 4 days after MPTP lesioning (a period after which MPTP-induced cell death is complete). Initially, MPTP-lesioned ϩ exercise mice ran at slower speeds for a shorter amount of time compared to saline ϩ exercise mice. Both velocity and endurance improved in the MPTP ϩ exercise group to near normal levels over the 30-day exercise period. The expression of proteins and genes involved in basal ganglia function including the dopamine transporter (DAT), tyrosine hydroxylase (TH), and the dopamine D1 and D2 receptors, as well as alterations on glutamate immunolabeling were determined. Exercise resulted in a significant downregulation of striatal DAT in the MPTP ϩ exercise compared to MPTP nonexercised mice and to a lesser extent in the saline ϩ exercised mice compared to their no-exercise counterparts. There was no significant difference in TH protein levels between MPTP and MPTP ϩ exercise groups at the end of the study. The expression of striatal dopamine D1 and D2 receptor mRNA transcript was suppressed in the saline ϩ exercise group; however, dopamine D2 transcript expression was increased in the MPTP ϩ exercise mice. Immunoelectron microscopy indicated that treadmill exercise reversed the lesionedinduced increase in nerve terminal glutamate immunola-beling seen after MPTP administration. Our data demonstrates that exercise promotes behavioral recovery in the injured brain by modulating genes and proteins important to basal ganglia function.
The elaborative-processing and forgetting-reconstruction hypotheses are the 2 principal explanati... more The elaborative-processing and forgetting-reconstruction hypotheses are the 2 principal explanations for the contextual interference (CI) effect. The present authors' purpose was to identify which of these 2 hypotheses better accounts for the CI effect. They synchronized single transcranial magnetic stimulation (TMS) pulses to each intertrial interval to modulate information processing during Blocked and Random Practice conditions. Participants practiced 3 arm tasks with either a Blocked or Random Practice order. The 3 stimulation conditions (No TMS, TMS, Sham TMS) by 2-practice order (Blocked, Random) between-participant design resulted in 6 experimental groups. Without TMS, motor learning increased under Random Practice. With TMS, this learning benefit diminished. These results support the elaborative-processing hypothesis by showing that perturbing information processing, evoked by Random Practice, deteriorates the learning benefit. Unlike the prediction of the forgettingreconstruction hypothesis, adding perturbation during Blocked Practice did not significantly enhance motor learning.
Context-dependent motor performance is a phenomenon in which people perform better in the environ... more Context-dependent motor performance is a phenomenon in which people perform better in the environmental context where they originally practiced a task. Some animal and computer simulation studies suggested that context-dependent performance may be associated with neural activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine the role of the DLPFC in context-dependent motor performance by perturbing the neural processing of the DLPFC with repetitive transcranial magnetic stimulation (rTMS) in healthy adults. Thirty healthy adults were recruited into the Control, rTMS DLPFC, and rTMS Vertex groups. The participants practiced three finger sequences associated with a specific incidental context (a colored circle and a location on the computer screen). One day following practice, the rTMS groups received 1 Hz rTMS prior to the testing conditions in which the sequence-context associations remained the same as practice (SAME) or changed (SWITCH). All three groups improved significantly over practice on day one. The second day testing results showed that the DLPFC group demonstrated significantly less decrement in motor performance under the SWITCH condition than the Control and Vertex groups. This finding suggests a specific role of the DLPFC in context-dependent motor performance. This article is protected by copyright. All rights reserved.
Background: Ankle sprains are common within the general population and can result in prolonged di... more Background: Ankle sprains are common within the general population and can result in prolonged disablement. Limited talocrural dorsiflexion range of motion (DF ROM) is a common consequence of ankle sprain. Limited talocrural DF ROM may contribute to persistent symptoms, disability, and an elevated risk for re-injury. As a result, many health care practitioners use hands-on passive procedures with the intention of improving talocrural joint DF ROM in individuals following ankle sprains. Dosage of passive hands-on procedures involves a continuum of treatment speeds. Recent evidence suggests both slow-and fast-speed treatments may be effective to address disablement following ankle sprains. However, these interventions have yet to be longitudinally compared against a placebo study condition.
Background: Many health care practitioners use a variety of hands-on treatments to improve sympto... more Background: Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.
Epidemiological and clinical trials have suggested that exercise is beneficial for patients with ... more Epidemiological and clinical trials have suggested that exercise is beneficial for patients with Parkinson's disease (PD). However, the underlying mechanisms and potential for disease modification are currently unknown. This review presents current findings from our laboratories in patients with PD and animal models. The data indicate that alterations in both dopaminergic and glutamatergic neurotransmission, induced by activity-depend-ent (exercise) processes, may mitigate the cortically driven hyper-excitability in the basal ganglia normally observed in the parkinsonian state. These insights have potential to identify novel therapeutic treatments capable of reversing or delaying disease progression in PD.
Proceedings of the 4th Conference on Wireless Health - WH '13, 2013
In this paper, we present PoCM 2 (Point-of-Care Mobility Monitoring), a generic and extensible at... more In this paper, we present PoCM 2 (Point-of-Care Mobility Monitoring), a generic and extensible at-home mobility evaluation and monitoring system. PoCM 2 uses both 3D visual sensors (such as Microsoft Kinect) and mobile sensors (i.e., internal and external sensors embedded with/connected to a mobile device such as a smartphone) for complementary data acquisition, as well as a series of analytics that allow evaluation of both archived and real-time mobility data. We demonstrate the performance of PoCM 2 with a specific application developed for freeze detection and quantification from Parkinson's Disease mobility data, as an approach to estimate the medication level of the PD patients and potentially recommend adjustments.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 8, 2014
Human pelvic floor muscles have been shown to operate synergistically with a wide variety of musc... more Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm...
Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's... more Studies have suggested that there are beneficial effects of exercise in patients with Parkinson's disease, but the underlying molecular mechanisms responsible for these effects are poorly understood. Studies in rodent models provide a means to examine the effects of exercise on dopaminergic neurotransmission. Using intensive treadmill exercise, we determined changes in striatal dopamine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. C57BL/6J mice were divided into four groups: (1) saline, (2) saline plus exercise, (3) MPTP, and (4) MPTP plus exercise. Exercise was started 5 d after MPTP lesioning and continued for 28 d. Treadmill running improved motor velocity in both exercise groups. All exercised animals also showed increased latency to fall (improved balance) using the accelerating rotarod compared with nonexercised mice. Using HPLC, we found no difference in striatal dopamine tissue levels between MPTP plus exercise compared with MPTP mice. There was an increase detected in saline plus exercise mice. Analyses using fast-scan cyclic voltammetry showed increased stimulus-evoked release and a decrease in decay of dopamine in the dorsal striatum of MPTP plus exercise mice only. Immunohistochemical staining analysis of striatal tyrosine hydroxylase and dopamine transporter proteins showed decreased expression in MPTP plus exercise mice compared with MPTP mice. There were no differences in mRNA transcript expression in midbrain dopaminergic neurons between these two groups. However, there was diminished transcript expression in saline plus exercise compared with saline mice. Our findings suggest that the benefits of treadmill exercise on motor performance may be accompanied by changes in dopaminergic neurotransmission that are different in the injured (MPTP-lesioned) compared with the noninjured (saline) nigrostriatal system.
We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercis... more We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD), including an increase in the dopamine D2 receptor (DA-D2R), using noninvasive PET imaging with the radioligand [18F]fallypride. The purpose of this feasibility and translational study was to examine whether intensive exercise leads to similar alterations in DA-D2R expression using PET imaging with [18F]fallypride in individuals with early-stage PD. In this pilot study, four patients with early-stage PD were randomized to receive intensive exercise (treadmill training sessions three times/week for 8 weeks) or no exercise. Two healthy age-matched individuals participated in treadmill training. Alterations in the DA-D2R binding potential (BP) as a marker for receptor expression were determined using PET imaging with [18F]fallypride. Turning performance in the patients with PD as a measure of postural control and the Unified Parkinson's Disease Rating Scale scores pre-exercise and postexercise were determined. Our data showed an exercise-induced increase in [18F]fallypride BP as well as improved postural control in patients with PD who exercised. Changes in DA-D2R BP were not observed in patients with PD who did not exercise. These results suggest that exercise can lead to neuroplasticity in dopaminergic signaling and contribute to improved function that may be task specific (postural control) in early-stage PD.
We studied corticomotor excitability (CE) between the more and less affected sides in early Parki... more We studied corticomotor excitability (CE) between the more and less affected sides in early Parkinson's disease (PD) patients using transcranial magnetic stimulation (TMS). Sixteen-PD patients within the first 3 years of diagnosis were studied with single-pulse TMS over each motor cortex with intensities from 40% to 100% stimulator output. Active motor evoked potentials (MEP) and cortical silent period durations (CSP) were recorded, fitted with sigmoid curves, summarized as maximal MEP/CSP, maximal MEP/CSP slope, and intensity where MEP/CSP is half-maximal (MEP/CSP-Int50), and correlated with Unified Parkinson's Disease Rating Scale scores (UPDRS). On the more affected side, higher (worse) UPDRS scores were correlated with shorter maximal CSP (r ϭ Ϫ0.51, P ϭ 0.046). On the less affected side, higher UPDRS scores were correlated with higher MEP-Int50 (r ϭ 0.51, P ϭ 0.043) and CSP-Int50 (r ϭ 0.54, P ϭ 0.029). For the less affected side, altered CE, as indexed by higher MEP or CSP-Int50 intensities, may contribute to early clinical symptoms. On the more affected side, increases in CE, indexed by shorter CSP, may account for a greater proportion of PD symptoms. These findings are consistent with an evolution of neurophysiologic correlates in early PD patients from a less to more symptomatic state.
The purpose of the current study was to examine changes in dopamine D2 receptor (DA-D2R) expressi... more The purpose of the current study was to examine changes in dopamine D2 receptor (DA-D2R) expression within the basal ganglia of MPTP mice subjected to intensive treadmill exercise. Using Western immunoblotting analysis of synaptoneurosomes and in vivo positron emission tomography (PET) imaging employing the DA-D2R specific ligand [ 18 F]fallypride, we found that high intensity treadmill exercise led to an increase in striatal DA-D2R expression that was most pronounced in MPTP compared to saline treated mice. Exercise-induced changes in the DA-D2R in the dopamine-depleted basal ganglia are consistent with the potential role of this receptor in modulating medium spiny neurons (MSNs) function and behavioral recovery. Importantly, findings from this study support the rationale for using PET imaging with [ 18 F]fallypride to examine DA-D2R changes in individuals with Parkinson's Disease (PD) undergoing high-intensity treadmill training.
... PURPOSe: the aim of this study was to evaluate the effect of physical training on the reactiv... more ... PURPOSe: the aim of this study was to evaluate the effect of physical training on the reactivity of pulmonary artery rings from rats submitted to a pulmonary IR. MeTHOdS:Wistar male rats were divided into five groups named: control sedentary (SD); Trained (TR); sham ...
Journal of Orthopaedic & Sports Physical Therapy, 2013
T T RESULTS: It is feasible to measure the CE of the gluteus maximus with TMS. The intraclass cor... more T T RESULTS: It is feasible to measure the CE of the gluteus maximus with TMS. The intraclass correlation coefficients for all TMS outcome measures ranged from 0.73 to 0.97. The ranges of minimal detectable change, with respect to mean values for each TMS variable, were larger for MEP amplitude (304.7-585.4 µV) compared to those for cortical silent period duration (25.3-40.8 milliseconds) and MEP latency (1.1-2.1 milliseconds).
The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) provides an excellent oppor... more The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) provides an excellent opportunity to study repair and response to injury in the basal ganglia. Administration to mammals leads to the destruction of nigrostriatal dopaminergic neurons and depletion of striatal dopamine. In the squirrel monkey (Saimiri sciureus), MPTP-lesioning results in parkinsonian motor symptoms including bradykinesia, postural instability, and rigidity. Over time animals display motor behavioral recovery. To better understand this mechanism we employed a lesioning regimen of two or six subcutaneous injections of MPTP (2.0 mg/kg, free-base) to generate mild or moderate parkinsonism. Brain tissue was harvested at 6 weeks or 9 months after the last injection and analyzed for dopamine and its metabolites by high performance liquid chromatography (HPLC), and by immunohistochemical staining and Western immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine-and cAMPresponsive protein phosphatase of 32 kDa (DARPP-32), an effector molecule enriched in striatal medium spiny neurons. Several months after MPTP-lesioning, when squirrel monkeys displayed full motor behavioral recovery, striatal dopamine levels remained low with a greater return in the ventral striatum. This finding is consistent with other reports using neurotoxicantlesioning models of the basal ganglia in rodents and other species of nonhuman primates. Elevated dopamine turnover ratio and decreased DAT expression appeared in early behavioral recovery at the 6-week time point in both mild-and moderate-parkinsonian monkeys. Tyrosine hydroxylase and DAT expression was increased in late stage recovery even within dopa-mine-depleted regions and supports sprouting. Altered DARPP-32 expression suggests a role of medium spiny neurons in recovery. V V C 2005 Wiley-Liss, Inc.
Physical activity has been shown to be neuroprotective in lesions affecting the basal ganglia. Us... more Physical activity has been shown to be neuroprotective in lesions affecting the basal ganglia. Using a treadmill exercise paradigm, we investigated the effect of exercise on neurorestoration. The 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-lesioned mouse model provides a means to investigate the effect of exercise on neurorestoration because 30 -40% of nigrostriatal dopaminergic neurons survive MPTP lesioning and may provide a template for neurorestoration to occur. MPTPlesioned C57 BL/6J mice were administered MPTP (four injections of 20 mg/kg free-base, 2 hr apart) or saline and divided into the following groups: (1) saline; (2) saline ϩ exercise; (3) MPTP; and (4) MPTP ϩ exercise. Mice in exercise groups were run on a motorized treadmill for 30 days starting 4 days after MPTP lesioning (a period after which MPTP-induced cell death is complete). Initially, MPTP-lesioned ϩ exercise mice ran at slower speeds for a shorter amount of time compared to saline ϩ exercise mice. Both velocity and endurance improved in the MPTP ϩ exercise group to near normal levels over the 30-day exercise period. The expression of proteins and genes involved in basal ganglia function including the dopamine transporter (DAT), tyrosine hydroxylase (TH), and the dopamine D1 and D2 receptors, as well as alterations on glutamate immunolabeling were determined. Exercise resulted in a significant downregulation of striatal DAT in the MPTP ϩ exercise compared to MPTP nonexercised mice and to a lesser extent in the saline ϩ exercised mice compared to their no-exercise counterparts. There was no significant difference in TH protein levels between MPTP and MPTP ϩ exercise groups at the end of the study. The expression of striatal dopamine D1 and D2 receptor mRNA transcript was suppressed in the saline ϩ exercise group; however, dopamine D2 transcript expression was increased in the MPTP ϩ exercise mice. Immunoelectron microscopy indicated that treadmill exercise reversed the lesionedinduced increase in nerve terminal glutamate immunola-beling seen after MPTP administration. Our data demonstrates that exercise promotes behavioral recovery in the injured brain by modulating genes and proteins important to basal ganglia function.
The elaborative-processing and forgetting-reconstruction hypotheses are the 2 principal explanati... more The elaborative-processing and forgetting-reconstruction hypotheses are the 2 principal explanations for the contextual interference (CI) effect. The present authors' purpose was to identify which of these 2 hypotheses better accounts for the CI effect. They synchronized single transcranial magnetic stimulation (TMS) pulses to each intertrial interval to modulate information processing during Blocked and Random Practice conditions. Participants practiced 3 arm tasks with either a Blocked or Random Practice order. The 3 stimulation conditions (No TMS, TMS, Sham TMS) by 2-practice order (Blocked, Random) between-participant design resulted in 6 experimental groups. Without TMS, motor learning increased under Random Practice. With TMS, this learning benefit diminished. These results support the elaborative-processing hypothesis by showing that perturbing information processing, evoked by Random Practice, deteriorates the learning benefit. Unlike the prediction of the forgettingreconstruction hypothesis, adding perturbation during Blocked Practice did not significantly enhance motor learning.
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