Modulation of motor vigour by expectation of reward probability trial-by-trial is preserved in healthy ageing and Parkinson's disease patients

Motor improvements, such as faster movement times or increased velocity, have been associated with reward magnitude in deterministic contexts. Yet whether individual inferences on reward probability influence motor vigour dynamically remains undetermined. We investigated how dynamically inferring volatile action-reward contingencies modulated motor performance trial-by-trial. We conducted three studies that coupled a one-armed bandit decision-making paradigm with a motor sequence task and used a validated hierarchical Bayesian model to fit trial-by-trial data. In Study 1, we tested healthy younger (HYA, 37 [13 males]) and older adults (HOA, 37 [20 males]), and medicated Parkinson’s Disease patients (PD, 20 [13 males]). We showed that stronger predictions about the tendency of the action-reward contingency led to faster performance tempo—commensurate with movement time—on a trial-by-trial basis without robustly modulating reaction time (RT). Using Bayesian linear mixed models, we demonstrated a similar invigoration effect on performance tempo in HYA, HOA and PD, despite HOA and PD being slower than HYA. In Study 2 (HYA, 39 [10 males]), we additionally showed that retrospective subjective inference about credit assignment did not contribute to differences in motor vigour effects. Last, Study 3 (HYA, 33 [6 males]) revealed that explicit beliefs about the reward tendency (confidence ratings) modulated performance tempo trial-by-trial. Our study is the first to reveal that the dynamic updating of beliefs about volatile action-reward contingencies positively biases motor performance through faster tempo. We also provide robust evidence for a preserved sensitivity of motor vigour to inferences about the action-reward mapping in ageing and medicated PD

Predicting the Need for Surgery in Patients with Lumbar Disc Herniation: A New Internally Validated Scoring System

Study Design Prospective study. Purpose To propose a scoring system for predicting the need for surgery in patients with lumbar disc herniation (LDH). Overview of Literature The indications for surgery in patients with LDH are well established. However, the exact timing of surgery is not. According to surgeons, patients with failed conservative treatment who underwent delayed surgery, often after 6 months post-symptom initiation, have poor functional recovery and outcome. Methods The current study included patients with symptomatic LDH. Patients with an indication for emergent surgery such as profound or progressive motor deficit, cauda equina syndrome, and diagnoses other than single-level LDH were excluded from the analysis. All patients followed a conservative treatment regimen (a combination of physical therapy, pain medications, and/or spinal epidural steroid injections). Surgery was indicated for patients who continuously experienced pain despite maximal conservative therapy. Results In total, 134 patients met the inclusion and exclusion criteria. Among them, 108 (80.6%) responded to conservative management, and 26 (19.4%) underwent unilateral laminotomy and microdiscectomy. The symptom duration, disc degeneration grade on magnetic resonance imaging (Pfirrmann disc grade), herniated disc location and type, fragment size, and thecal sac diameter significantly differed between patients who responded to conservative treatment and those requiring surgery. The area under the receiver operating characteristic curve of the scoring system based on the anteroposterior size of the herniated disc fragment and herniated disc location and type was 0.81. Conclusions A scoring system based on herniated disc/fragment size, location, and type can be applied to predict the need for surgery in patients with LDH. In the future, this tool can be used to prevent unnecessarily prolonged conservative management (>4–8 weeks)

In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation

In humans, aggregation of polyglutamine repeat (polyQ) proteins causes disorders such as Huntington’s disease. Although plants express hundreds of polyQ-containing proteins, no pathologies arising from polyQ aggregation have been reported. To investigate this phenomenon, we expressed an aggregation-prone fragment of human huntingtin (HTT) with an expanded polyQ stretch (Q69) in Arabidopsis thaliana plants. In contrast to animal models, we find that Arabidopsis sp. suppresses Q69 aggregation through chloroplast proteostasis. Inhibition of chloroplast proteostasis diminishes the capacity of plants to prevent cytosolic Q69 aggregation. Moreover, endogenous polyQ-containing proteins also aggregate on chloroplast dysfunction. We find tha

Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis

PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known

Ratz

Three kids at summer camp venture out into the woods to find a man who they were told lives there

Carotid Artery Stenosis: What You Should Know

The information provided in this handout does not necessarily reflect the views of the University of Minnesota Medical School physicians and faculty. These materials are provided for informational purposes only and are in no way intended to take the place of the advice and recommendations of your personal health care provider. You use the information provided in these handouts at your own risk.Carotid artery stenosis, or CAS, can increase you risk of having a stroke. There are several things you can do to lower your risk including stopping smoking, controlling your weight, eating a good diet, and exercising regularly. Currently it is not recommended that you get screened for CAS if you are not having symptoms. If you are found to have CAS, there are several treatment options available to lower your risk of stroke