Osteoarthritic Tibiofemoral Joint Contact Characteristics During Weightbearing With Arch-Supported and Standalone Lateral Wedge Insoles.

Imbalanced joint load distribution across the tibiofemoral surface is a risk factor for osteoarthritic changes to this joint. Lateral wedge insoles, with and without arch support, are a form of biomechanical intervention that can redistribute tibiofemoral joint load, as estimated by external measures of knee load. The objective of this study was to examine the effect of these insoles on the internal joint contact characteristics of osteoarthritic knees during weightbearing. Fifteen adults with tibiofemoral osteoarthritis underwent magnetic resonance imaging of the affected knee, while standing under 3 insole conditions: flat control, lateral wedge alone, and lateral wedge with arch support. Images were processed, and the surface area and centroid location of joint contact were quantified separately for the medial and lateral tibiofemoral compartments. Medial contact surface area was increased with the 2 lateral wedge conditions compared with the control (P ≤ .012). A more anterior contact centroid was observed in the medial compartment in the lateral wedge with arch support compared with the lateral wedge alone (P = .009). Significant changes in lateral compartment joint contact outcomes were not observed. These findings represent early insights into how loading at the tibiofemoral interface may be altered by lateral wedge insoles as a potential intervention for knee osteoarthritis.

Posterior Parietal Cortex Guides Visual Decisions in Rats.

Neurons in putative decision-making structures can reflect both sensory and decision signals, making their causal role in decisions unclear. Here, we tested whether rat posterior parietal cortex (PPC) is causal for processing visual sensory signals or instead for accumulating evidence for decision alternatives. We disrupted PPC activity optogenetically during decision making and compared effects on decisions guided by auditory versus visual evidence. Deficits were largely restricted to visual decisions. To further test for visual dominance in PPC, we evaluated electrophysiological responses after individual sensory events and observed much larger response modulation after visual stimuli than auditory stimuli. Finally, we measured trial-to-trial spike count variability during stimulus presentation and decision formation. Variability decreased sharply, suggesting that the network is stabilized by inputs, unlike what would be expected if sensory signals were locally accumulated. Our findings suggest that PPC plays a causal role in processing visual signals that are accumulated elsewhere.SIGNIFICANCE STATEMENT Defining the neural circuits that support decision making bridges a gap between our understanding of simple sensorimotor reflexes and our understanding of truly complex behavior. However, identifying brain areas that play a causal role in decision making has proved challenging. We tested the causal role of a candidate component of decision circuits, the rat posterior parietal cortex (PPC). Our interpretation of the data benefited from our use of animals trained to make decisions guided by either visual or auditory evidence. Our results suggest that PPC plays a causal role specifically in visual decision making and may support sensory aspects of the decision, such as interpreting the visual signals so that evidence for a decision can be accumulated elsewhere.

From innate to instructed: A new look at perceptual decision-making.

Understanding how subjects perceive sensory stimuli in their environment and use this information to guide appropriate actions is a major challenge in neuroscience. To study perceptual decision-making in animals, researchers use tasks that either probe spontaneous responses to stimuli (often described as "naturalistic") or train animals to associate stimuli with experimenter-defined responses. Spontaneous decisions rely on animals' pre-existing knowledge, while trained tasks offer greater versatility, albeit often at the cost of extensive training. Here, we review emerging approaches to investigate perceptual decision-making using both spontaneous and trained behaviors, highlighting their strengths and limitations. Additionally, we propose how trained decision-making tasks could be improved to achieve faster learning and a more generalizable understanding of task rules.

Large scale, simultaneous, chronic neural recordings from multiple brain areas.

Understanding how brain activity is related to animal behavior requires measuring multi-area interactions on multiple timescales. However, methods to perform chronic, simultaneous recordings of neural activity from many brain areas are lacking. Here, we introduce a novel approach for independent chronic probe implantation that enables flexible, simultaneous interrogation of neural activity from many brain regions during head restrained or freely moving behavior. The approach, that we called indie (independent dovetail implants for electrophysiology), enables repeated retrieval and reimplantation of probes. The chronic implantation approach can be combined with other modalities such as skull clearing for cortex wide access and optogenetics with optic fibers. Using this approach, we implanted 6 probes chronically in one hemisphere of the mouse brain. The implant is lightweight, allows flexible targeting with different angles, and offers enhanced stability. Our approach broadens the applications of chronic recording while retaining its main advantages over acute recordings (superior stability, longitudinal monitoring of activity and freely moving interrogations) and provides an appealing venue to study processes not accessible by acute methods, such as the neural substrate of learning across multiple areas.

Excessive firing of dyskinesia-associated striatal direct pathway neurons is gated by dopamine and excitatory synaptic input.

The striatum integrates dopaminergic and glutamatergic inputs to select preferred versus alternative actions. However, the precise mechanisms underlying this process remain unclear. One way to study action selection is to understand how it breaks down in pathological states. Here, we explored the cellular and synaptic mechanisms of levodopa-induced dyskinesia (LID), a complication of Parkinson's disease therapy characterized by involuntary movements. We used an activity-dependent tool (FosTRAP) in conjunction with a mouse model of LID to investigate functionally distinct subsets of striatal direct pathway medium spiny neurons (dMSNs). In vivo, levodopa differentially activates dyskinesia-associated (TRAPed) dMSNs compared to other dMSNs. We found this differential activation of TRAPed dMSNs is likely to be driven by higher dopamine receptor expression, dopamine-dependent excitability, and excitatory input from the motor cortex and thalamus. Together, these findings suggest how the intrinsic and synaptic properties of heterogeneous dMSN subpopulations integrate to support action selection.

Clinically-accessible and laboratory-derived predictors of biomechanical response to standalone and supported lateral wedge insoles in people with knee osteoarthritis.

BACKGROUND: Lateral wedge insoles (both standalone and those incorporating individualized arch support) have been frequently studied for the effects on knee joint loading and pain in people with knee osteoarthritis. It has been shown that many people who use these insoles do not obtain the intended biomechanical effect, and thus may not experience a clinical benefit. The ability to identify biomechanical responders to lateral wedge insoles before research or clinical intervention is an important objective for efficient resource use and optimizing patient outcomes. The purpose of our exploratory, hypothesis-generating study was to provide an initial assessment of variables that are associated with the biomechanical response to lateral wedge insoles in people with knee osteoarthritis. METHODS: We collected a number of demographic (age, sex, body mass index, foot posture), clinical (knee pain, foot pain, radiographic disease severity), and walking-related (speed, knee alignment, frontal plane subtalar movement, and foot rotation) outcomes from 53 individuals with painful, radiographically-confirmed knee osteoarthritis. The walking-related outcomes were obtained using equipment both from the research laboratory and the clinical setting. We used logistic regression to generate predictive models to determine candidate variables associated with a reduction in the knee adduction moment during walking - a surrogate for tibiofemoral load distribution, and a known biomechanical risk factor for osteoarthritis progression - with the use of standalone and arch-supported lateral wedge insoles. Three different response thresholds (2%, 6%, and 10% reductions in the knee adduction moment) were used. RESULTS: In general, biomechanical responders were those who walked faster, were female, had less varus alignment, and had less severe radiographic severity. Findings were similar between the standalone and arch-supported lateral wedge insoles, as well as between models using the laboratory-derived or clinically-available measures of walking performance. CONCLUSIONS: Our hypothesis-generating study provides valuable information that will inform future research into the efficient and effective use of lateral wedge insoles in the conservative management of knee osteoarthritis.

The effect of three different levels of footwear stability on pain outcomes in women runners: a randomised control trial.

BACKGROUND: The present study examines the injury status in women runners who are randomised to receive a neutral, stability or motion control running shoe. METHODS: 81 female runners were categorised into three different foot posture types (39 neutral, 30 pronated, 12 highly pronated) and randomly assigned a neutral, stability or motion control running shoe. Runners underwent baseline testing to record training history, as well as leg alignment, before commencing a 13-week half marathon training programme. Outcome measures included number of missed training days due to pain and three visual analogue scale (VAS) items for pain during rest, activities of daily living and with running. RESULTS: 194 missed training days were reported by 32% of the running population with the stability shoe reporting the fewest missed days (51) and the motion control shoe (79) the most. There was a significant main effect (p<0.001) for footwear condition in both the neutral and pronated foot types: the motion control shoe reporting greater levels of pain in all three VAS items. In neutral feet, the neutral shoe reported greater values of pain while running than the stability shoe; in pronated feet, the stability shoe reported greater values of pain while running than the neutral shoe. No significant effects were reported for the highly pronated foot, although this was limited by an inadequate sample size. CONCLUSION: The findings of this study suggest that our current approach of prescribing in-shoe pronation control systems on the basis of foot type is overly simplistic and potentially injurious.

An exploration of changes in plantar pressure distributions during walking with standalone and supported lateral wedge insole designs.

BACKGROUND: Lateral wedge insoles (LWI), standalone or with medial arch support (supported-LWI), have been thoroughly investigated for their effects on modifying gait biomechanics for people with knee osteoarthritis. However, plantar pressure distribution between these insole types has not been investigated and could provide insight towards insole prescription with concomitant foot symptoms taken into consideration. METHODS: In a sample of healthy individuals (n = 40), in-shoe plantar pressure was measured during walking with LWI, with or without medial arch support (variable- and uniform-stiffness designs), and a flat control insole condition. Pressure data from the plantar surface of the foot were divided into seven regions: medial/lateral rearfoot, midfoot, medial/central/lateral forefoot, hallux. Plantar pressure outcomes assessed were the medial-lateral pressure index (MLPI) for the whole foot, and the peak pressure, pressure-time integral (PTI), and contact area in each plantar region. Comfort in each insole condition was rated as a change relative to the flat control insole condition. Repeated-measures analyses of variance were calculated to compare the plantar pressure outcomes between insole conditions. RESULTS: Regionally, medial rearfoot and forefoot pressure were reduced by all wedged insoles, with the variable-stiffness supported-wedge showing greater reductions than the standalone wedge. Lateral rearfoot and forefoot pressure were reduced by both supported-LWI, but unchanged by the standalone wedge. In the midfoot, the standalone wedge maintained pressure but reduced regional contact area, while both supported-LWI increased midfoot pressure and contact area. All LWI increased the MLPI, indicating a lateral shift in plantar pressure distribution throughout the weightbearing phase of gait. Comfort ratings were not significantly different between insole conditions. CONCLUSIONS: Regional differences in plantar pressure may help determine an appropriate lateral wedge insole variation to avoid exacerbation of concomitant foot symptoms by minimizing pressure in symptomatic regions. Lateral shifts in plantar pressure distribution were observed in all laterally wedged conditions, including one supported-LWI that was previously shown to be biomechanically ineffective for modifying knee joint load distribution. Thus, shifts in foot centre of pressure may not be a primary mechanism by which LWI can modify knee joint load distribution for people with knee osteoarthritis.

Influence of foot posture on immediate biomechanical responses during walking to variable-stiffness supported lateral wedge insole designs.

BACKGROUND: Novel designs of lateral wedge insoles with arch support can alter walking biomechanics as a conservative treatment option for knee osteoarthritis. However, variations in foot posture may influence individual responses to insole intervention and these effects are not yet known. RESEARCH QUESTION: How does foot posture influence biomechanical responses to novel designs of lateral wedge insoles with arch support? METHODS: This exploratory biomechanical investigation categorized forty healthy volunteers (age 23-34) into pronated (n = 16), neutral (n = 15), and supinated (n = 9) foot posture groups based on the Foot Posture Index. Three-dimensional gait analysis was conducted during walking with six orthotic insole conditions: flat control, lateral wedge, uniform-stiffness arch support, variable-stiffness arch support, and lateral wedge + each arch support. Frontal plane knee and ankle/subtalar joint kinetic and kinematic outcomes were compared among insole conditions and foot posture groups using a repeated measures analysis of variance. RESULTS: The lateral wedge alone and lateral wedge + variable-stiffness arch support were the only insole conditions effective at reducing the knee adduction moment. However, the lateral wedge + variable-stiffness arch support had a smaller increase in peak ankle/subtalar eversion moment than the lateral wedge alone. Supinated feet had smaller ankle/subtalar eversion excursion and moment impulse than neutral and pronated feet, across all insole conditions. SIGNIFICANCE: Supinated feet have less mobile ankle/subtalar joints than neutral and pronated feet and, as a result, may be less likely to respond to biomechanical intervention from orthotic insoles. Supported lateral wedge insoles incorporating an arch support design that is variable-stiffness may be better than uniform-stiffness since reductions in the knee adduction moment can be achieved while minimizing increases in the ankle/subtalar eversion moment.

Aberrant Striatal Activity in Parkinsonism and Levodopa-Induced Dyskinesia.

Action selection relies on the coordinated activity of striatal direct and indirect pathway medium spiny neurons (dMSNs and iMSNs, respectively). Loss of dopamine in Parkinson's disease is thought to disrupt this balance. While dopamine replacement with levodopa may restore normal function, the development of involuntary movements (levodopa-induced dyskinesia [LID]) limits therapy. How chronic dopamine loss and replacement with levodopa modulate the firing of identified MSNs in behaving animals is unknown. Using optogenetically labeled striatal single-unit recordings, we assess circuit dysfunction in parkinsonism and LID. Counter to current models, we found that following dopamine depletion, iMSN firing was elevated only during periods of immobility, while dMSN firing was dramatically and persistently reduced. Most notably, we identified a subpopulation of dMSNs with abnormally high levodopa-evoked firing rates, which correlated specifically with dyskinesia. These findings provide key insights into the circuit mechanisms underlying parkinsonism and LID, with implications for developing targeted therapies.

Sonographically guided intratendinous injection of hyperosmolar dextrose to treat chronic tendinosis of the Achilles tendon: a pilot study.

OBJECTIVE: Chronic tendinosis of the Achilles tendon is a common overuse injury that is difficult to manage. We report on a new injection treatment for this condition. SUBJECTS AND METHODS: Thirty-six consecutive patients (25 men, 11 women; mean age, 52.6 years) with symptoms for more than 3 months (mean, 28.6 months) underwent sonography-guided intratendinous injection of 25% hyperosmolar dextrose every 6 weeks until symptoms resolved or no improvement was shown. At baseline and before each injection, clinical assessment was performed using a visual analogue scale (VAS) for pain at rest (VAS1), pain during normal daily activity (VAS2), and pain during or after sporting or other physical activity (VAS3). Sonographic parameters including tendon thickness, echogenicity, and neovascularity were also recorded. Posttreatment clinical follow-up was performed via telephone interview. RESULTS: Thirty-three tendons in 32 patients were successfully treated. The mean number of treatment sessions was 4.0 (range, 2-11). There was a mean percentage reduction for VAS1 of 88.2% (p < 0.0001), for VAS2 of 84.0% (p < 0.0001), and for VAS3 of 78.1% (p < 0.0001). The mean tendon thickness decreased from 11.7 to 11.1 mm (p < 0.007). The number of tendons with anechoic clefts or foci was reduced by 78%. Echogenicity improved in six tendons (18%) but was unchanged in 27 tendons (82%). Neovascularity was unchanged in 11 tendons (33%) but decreased in 18 tendons (55%); no neovascularity was present before or after treatment in the four remaining tendons. Follow-up telephone interviews of the 30 available patients a mean of 12 months after treatment revealed that 20 patients were still asymptomatic, nine patients had only mild symptoms, and one patient had moderate symptoms. CONCLUSION: Intratendinous injections of hyperosmolar dextrose yielded a good clinical response--that is, a significant reduction in pain at rest and during tendon-loading activities--in patients with chronic tendinosis of the Achilles tendon.

Effects of step rate manipulation on joint mechanics during running.

PURPOSE: the objective of this study was to characterize the biomechanical effects of step rate modification during running on the hip, knee, and ankle joints so as to evaluate a potential strategy to reduce lower extremity loading and risk for injury. METHODS: three-dimensional kinematics and kinetics were recorded from 45 healthy recreational runners during treadmill running at constant speed under various step rate conditions (preferred, ± 5%, and ± 10%). We tested our primary hypothesis that a reduction in energy absorption by the lower extremity joints during the loading response would occur, primarily at the knee, when step rate was increased. RESULTS: less mechanical energy was absorbed at the knee (P < 0.01) during the +5% and +10% step rate conditions, whereas the hip (P < 0.01) absorbed less energy during the +10% condition only. All joints displayed substantially (P < 0.01) more energy absorption when preferred step rate was reduced by 10%. Step length (P < 0.01), center of mass vertical excursion (P < 0.01), braking impulse (P < 0.01), and peak knee flexion angle (P < 0.01) were observed to decrease with increasing step rate. When step rate was increased 10% above preferred, peak hip adduction angle (P < 0.01) and peak hip adduction (P < 0.01) and internal rotation (P < 0.01) moments were found to decrease. CONCLUSION: we conclude that subtle increases in step rate can substantially reduce the loading to the hip and knee joints during running and may prove beneficial in the prevention and treatment of common running-related injuries.