A Simple and Accurate onset Detection Method for a Measured Bell-shaped Speed Profile

Motor control neuroscientists measure limb trajectories and extract the onset of the movement for a variety of purposes. Such trajectories are often aligned relative to the onset of individual movement before the features of that movement are extracted and their properties are inspected. Onset detection is performed either manually or automatically, typically by selecting a velocity threshold. Here, we present a simple onset detection algorithm that is more accurate than the conventional velocity threshold technique. The proposed method is based on a simple regression and follows the minimum acceleration with constraints model, in which the initial phase of the bell-shaped movement is modeled by a cubic power of the time. We demonstrate the performance of the suggested method and compare it to the velocity threshold technique and to manual onset detection by a group of motor control experts. The database for this comparison consists of simulated minimum jerk trajectories and recorded reaching movements

A Robotic Test of Proprioception within the Hemiparetic Arm Post-stroke

Background: Proprioception plays important roles in planning and control of limb posture and movement. The impact of proprioceptive deficits on motor function post-stroke has been difficult to elucidate due to limitations in current tests of arm proprioception. Common clinical tests only provide ordinal assessment of proprioceptive integrity (eg. intact, impaired or absent). We introduce a standardized, quantitative method for evaluating proprioception within the arm on a continuous, ratio scale. We demonstrate the approach, which is based on signal detection theory of sensory psychophysics, in two tasks used to characterize motor function after stroke. Methods: Hemiparetic stroke survivors and neurologically intact participants attempted to detect displacement- or force-perturbations robotically applied to their arm in a two-interval, two-alternative forced-choice test. A logistic psychometric function parameterized detection of limb perturbations. The shape of this function is determined by two parameters: one corresponds to a signal detection threshold and the other to variability of responses about that threshold. These two parameters define a space in which proprioceptive sensation post-stroke can be compared to that of neurologically-intact people. We used an auditory tone discrimination task to control for potential comprehension, attention and memory deficits. Results: All but one stroke survivor demonstrated competence in performing two-alternative discrimination in the auditory training test. For the remaining stroke survivors, those with clinically identified proprioceptive deficits in the hemiparetic arm or hand had higher detection thresholds and exhibited greater response variability than individuals without proprioceptive deficits. We then identified a normative parameter space determined by the threshold and response variability data collected from neurologically intact participants. By plotting displacement detection performance within this normative space, stroke survivors with and without intact proprioception could be discriminated on a continuous scale that was sensitive to small performance variations, e.g. practice effects across days. Conclusions: The proposed method uses robotic perturbations similar to those used in ongoing studies of motor function post-stroke. The approach is sensitive to small changes in the proprioceptive detection of hand motions. We expect this new robotic assessment will empower future studies to characterize how proprioceptive deficits compromise limb posture and movement control in stroke survivors

A Quantitative and Standardized Robotic Method for the Evaluation of Arm Proprioception After Stroke

Stroke often results in both motor and sensory deficits, which may interact in the manifested functional impairment. Proprioception is known to play important roles in the planning and control of limb posture and movement; however, the impact of proprioceptive deficits on motor function has been difficult to elucidate due in part to the qualitative nature of available clinical tests. We present a quantitative and standardized method for evaluating proprioception in tasks directly relevant to those used to assess motor function. Using a robotic manipulandum that exerted controlled displacements of the hand, stroke participants were evaluated, and compared with a control group, in their ability to detect such displacements in a 2-alternative, forced-choice paradigm. A psychometric function parameterized the decision process underlying the detection of the hand displacements. The shape of this function was determined by a signal detection threshold and by the variability of the response about this threshold. Our automatic procedure differentiates between participants with and without proprioceptive deficits and quantifies functional proprioceptive sensation on a magnitude scale that is meaningful for ongoing studies of degraded motor function in comparable horizontal movements

The Arm Movement Detection (AMD) test: a fast robotic test of proprioceptive acuity in the arm

Abstract Background We examined the validity and reliability of a short robotic test of upper limb proprioception, the Arm Movement Detection (AMD) test, which yields a ratio-scaled, objective outcome measure to be used for evaluating the impact of sensory deficits on impairments of motor control, motor adaptation and functional recovery in stroke survivors. Methods Subjects grasped the handle of a horizontal planar robot, with their arm and the robot hidden from view. The robot applied graded force perturbations, which produced small displacements of the handle. The AMD test required subjects to respond verbally to queries regarding whether or not they detected arm motions. Each participant completed ten, 60s trials; in five of the trials, force perturbations were increased in small increments until the participant detected motion while in the others, perturbations were decreased until the participant could no longer detect motion. The mean and standard deviation of the 10 movement detection thresholds were used to compute a Proprioceptive Acuity Score (PAS). Based on the sensitivity and consistency of the estimated thresholds, the PAS quantifies the likelihood that proprioception is intact. Lower PAS scores correspond to higher proprioceptive acuity. Thirty-nine participants completed the AMD test, consisting of 25 neurologically intact control participants (NIC), seven survivors of stroke with intact proprioception in the more affected limb (HSS+P), and seven survivors of stroke with impaired or absent proprioception in the more affected limb (HSS-P). Results Significant group differences were found, with the NIC and HSS+P groups having lower (i.e., better) PAS scores than the HSS-P group. A subset of the participants completed the AMD test multiple times and the AMD test was found to be reliable across repetitions. Conclusions The AMD test required less than 15 min to complete and provided an objective, ratio-scaled measure of proprioceptive acuity in the upper limb. In the future, this test could be utilized to evaluate the contributions of sensory deficits to motor recovery following stroke

Additional file 1: of The Arm Movement Detection (AMD) test: a fast robotic test of proprioceptive acuity in the arm

Average AMDT thresholds and Z-scores; all data for all subjects. (XLSX 17 kb

Combined acetyl-11-keto-β-boswellic acid and radiation treatment inhibited glioblastoma tumor cells.

Glioblastoma multiforme (GBM) is the most common and most aggressive subtype of malignant gliomas. The current standard of care for newly diagnosed GBM patients involves maximal surgical debulking, followed by radiation therapy and temozolomide chemotherapy. Despite the advances in GBM therapy, its outcome remains poor with a median survival of less than two years. This poor outcome is partly due to the ability of GBM tumors to acquire adaptive resistance to therapy and in particular to radiation. One of the mechanisms contributing to GBM tumor progression and resistance is an aberrant activation of NF-ĸB, a family of inducible transcription factors that play a pivotal role in regulation of many immune, inflammatory and carcinogenic responses. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic terpenoid extracted from the gum Ayurvedic therapeutic plant Boswellia serrata. AKBA is anti-inflammatory agent that exhibits potent cytotoxic activities against various types of tumors including GBM. One of the mechanisms underlying AKBA anti-tumor activity is its ability to modulate the NF-ĸB signaling pathway. The present study investigated in vitro and in vivo the effect of combining AKBA with ionizing radiation in the treatment of GBM and assessed AKBA anti-tumor activity and radio-enhancing potential. The effect of AKBA and/or radiation on the survival of cultured glioblastoma cancer cells was evaluated by XTT assay. The mode of interaction of treatments tested was calculated using CalcuSyn software. Inducing of apoptosis following AKBA treatment was evaluated using flow cytometry. The effect of combined treatment on the expression of PARP protein was analysed by Western blot assay. Ectopic (subcutaneous) GBM model in nude mice was used for the evaluation of the effect of combined treatment on tumor growth. Immunohistochemical analysis of formalin-fixed paraffin-embedded tumor sections was used to assess treatment-related changes in Ki-67, CD31, p53, Bcl-2 and NF-ĸB-inhibitor IĸB-α. AKBA treatment was found to inhibit the survival of all four tested cell lines in a dose dependent manner. The combined treatment resulted in a more significant inhibitory effect compared to the effect of treatment with radiation alone. A synergistic effect was detected in some of the tested cell lines. Flow cytometric analysis with Annexin V-FITC/PI double staining of AKBA treated cells indicated induction of apoptosis. AKBA apoptotic activity was also confirmed by PARP cleavage detected by Western blot analysis. The combined treatment suppressed tumor growth in vivo compared to no treatment and each treatment alone. Immunohistochemical analysis showed anti-angiogenic and anti-proliferative activity of AKBA in vivo. It also demonstrated a decrease in p53 nuclear staining and in Bcl-2 staining and an increase in IĸB-α staining following AKBA treatment both alone and in combination with radiotherapy. In this study, we demonstrated that AKBA exerts potent anti-proliferative and apoptotic activity, and significantly inhibits both the survival of glioblastoma cells in vitro and the growth of tumors generated by these cells. Combination of AKBA with radiotherapy was found to inhibit factors which involved in cell death regulation, tumor progression and radioresistence, therefore it may serve as a novel approach for GBM patients

Effect of AKBA treatment on NF-ĸB-related protein expression in an ectopic GBM model.

<p>Formalin-fixed paraffin-embedded sections were stained immuno-histochemically for IĸB-α. Representative microphotographs from each treatment group are shown (original magnification x200).</p