Statistical measures of motor, sensory and cognitive performance across repeated robot-based testing.

BACKGROUND: Traditional clinical assessments are used extensively in neurology; however, they can be coarse, which can also make them insensitive to change. Kinarm is a robotic assessment system that has been used for precise assessment of individuals with neurological impairments. However, this precision also leads to the challenge of identifying whether a given change in performance reflects a significant change in an individual's ability or is simply natural variation. Our objective here is to derive confidence intervals and thresholds of significant change for Kinarm Standard Tests™ (KST). METHODS: We assessed participants twice within 15 days on all tasks presently available in KST. We determined the 5-95% confidence intervals for each task parameter, and derived thresholds for significant change. We tested for learning effects and corrected for the false discovery rate (FDR) to identify task parameters with significant learning effects. Finally, we calculated intraclass correlation of type ICC [1, 2] (ICC-C) to quantify consistency across assessments. RESULTS: We recruited an average of 56 participants per task. Confidence intervals for Z-Task Scores ranged between 0.61 and 1.55, and the threshold for significant change ranged between 0.87 and 2.19. We determined that 4/11 tasks displayed learning effects that were significant after FDR correction; these 4 tasks primarily tested cognition or cognitive-motor integration. ICC-C values for Z-Task Scores ranged from 0.26 to 0.76. CONCLUSIONS: The present results provide statistical bounds on individual performance for KST as well as significant changes across repeated testing. Most measures of performance had good inter-rater reliability. Tasks with a higher cognitive burden seemed to be more susceptible to learning effects, which should be taken into account when interpreting longitudinal assessments of these tasks.

Assessment of upper-limb sensorimotor function of subacute stroke patients using visually guided reaching.

OBJECTIVE: Using robotic technology, we examined the ability of a visually guided reaching task to assess the sensorimotor function of patients with stroke. METHODS: Ninety-one healthy participants and 52 with subacute stroke of mild to moderate severity (26 with left- and 26 with right-affected body sides) performed an unassisted reaching task using the KINARM robot. Each participant was assessed using 12 movement parameters that were grouped into 5 attributes of sensorimotor control. RESULTS: A number of movement parameters individually identified a large number of stroke participants as being different from 95% of the controls-most notably initial direction error, which identified 81% of left-affected patients. We also found interlimb differences in performance between the arms of those with stroke compared with controls. For example, whereas only 31% of left-affected participants showed differences in reaction time with their affected arm, 54% showed abnormal interlimb differences in reaction time. Good interrater reliability (r > 0.7) was observed for 9 of the 12 movement parameters. Finally, many stroke patients deemed impaired on the reaching task had been scored 6 or less on the arm portion of the Chedoke-McMaster Stroke Assessment Scale, but some who scored a normal 7 were also deemed impaired in reaching. CONCLUSIONS: Robotic technology using a visually guided reaching task can provide reliable information with greater sensitivity about a patient's sensorimotor impairments following stroke than a standard clinical assessment scale.

Quantitative assessment of limb position sense following stroke.

BACKGROUND: Impairment of position sense of the upper extremity (UE) may impede activities of daily living and limit motor gains after stroke. Most clinical assessments of position sense rely on categorical or ordinal ratings by clinicians that lack sensitivity to change or the ability to discriminate subtle deficits. OBJECTIVE: Use robotic technology to develop a reliable, quantitative technique with a continuous scale to assess UE position sense following stroke. METHODS: Forty-five patients recruited from an inpatient stroke rehabilitation service and 65 age-matched healthy controls performed an arm position matching task. Each UE was fitted in the exoskeleton of a KINARM device. One UE was passively placed in one of 9 positions, and the subject was told to match his or her position with the other UE. Patients were compared with statistical distributions of control data to identify those with deficits in UE position sense. Test-retest sessions using 2 raters established interrater reliability. RESULTS: Two thirds of left hemiparetic and one third of right hemiparetic patients had deficits in limb position sense. Left-affected stroke subjects demonstrated significantly more trial-to-trial variability than right-affected or control subjects. The robotic assessment technique demonstrated good interrater reliability but limited agreement with the clinical thumb localizing test. CONCLUSIONS: Robotic technology can provide a reliable quantitative means to assess deficits in limb position sense following stroke.

Determination of 8-oxoguanine and 8-hydroxy-2'-deoxyguanosine in the rat cerebral cortex using microdialysis sampling and capillary electrophoresis with electrochemical detection.

A rapid and sensitive method to determine 8-oxoguanine (8oxoG) and 8-hydroxydeoxyguanosine (8OHdG), biomarkers for oxidative DNA damage, in cerebral cortex microdialysate samples using capillary electrophoresis (CE) with electrochemical detection (CEEC) was developed. Samples were concentrated on-column using pH-mediated stacking for anions. On-column anodic detection was performed with a carbon fiber working electrode and laser-etched decoupler. The method is linear over the expected extracellular concentration range for 8oxoG and 8-OHdG during induced ischemia-reperfusion, with R.S.D. values

Effects of acidic N + 1 residues on asparagine deamidation rates in solution and in the solid state.

The deamidation kinetics of four model peptides (AcGQNGG, AcGQNDG, AcGQNEG, and AcGQNQG) were studied in solution (70 degrees C, pH 5-10) and in lyophilized solids [70 degrees C, 50% relative humidity, "effective pH" ('pH') 5-10] containing polyvinyl pyrrolidone. AcGQNGG, AcGQNEG, and AcGQNQG degraded exclusively through Asn deamidation, whereas AcGQNDG also displayed Asp isomerization, and Asp-Gly peptide bond cleavage. The pH/'pH'-rate profiles were consistent with a shift in the rate-determining step of Asn deamidation from carbonyl addition to expulsion of ammonia with increasing pH. In solution, AcGQNGG deamidated up to 38-fold faster than the other peptides, indicating the importance of steric effects of the N + 1 residue. AcGQNGG and AcGQNQG had up to 60 times slower rates of deamidation in the solid state than in solution. In contrast, the deamidation rates of AcGQNEG and AcGQNDG in the solid state were similar to those in solution. N + 1 Glu or Asp residue may enhance local hydration, so that the deamidation of Asn in the solid formulations actually proceeds in a solution-like environment.

Altered control of visual fixation and saccadic eye movements in attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is characterized by the overt symptoms of impulsiveness, hyperactivity, and inattention. A frontostriatal pathophysiology has been hypothesized to produce these symptoms and lead to reduced ability to inhibit unnecessary or inappropriate behavioral responses. Oculomotor tasks can be designed to probe the ability of subjects to generate or inhibit reflexive and voluntary responses. Because regions of the frontal cortex and basal ganglia have been identified in the control of voluntary responses and saccadic suppression, we hypothesized that children and adults diagnosed with ADHD may have specific difficulties in oculomotor tasks requiring the suppression of reflexive or unwanted saccadic eye movements. To test this hypothesis, we measured eye movement performance in pro- and anti-saccade tasks of 114 ADHD and 180 control participants ranging in age from 6 to 59 yr. In the pro-saccade task, participants were instructed to look from a central fixation point toward an eccentric visual target. In the anti-saccade task, stimulus presentation was identical, but participants were instructed to suppress the saccade to the stimulus and instead look from the central fixation point to the side opposite the target. The state of fixation was manipulated by presenting the target either when the central fixation point was illuminated (overlap condition) or at some time after it disappeared (gap condition). In the pro-saccade task, ADHD participants had longer reaction times, greater intra-subject variance, and their saccades had reduced peak velocities and increased durations. In the anti-saccade task, ADHD participants had greater difficulty suppressing reflexive pro-saccades toward the eccentric target, increased reaction times for correct anti-saccades, and greater intra-subject variance. In a third task requiring prolonged fixation, ADHD participants generated more intrusive saccades during periods when they were required to maintain steady fixation. The results suggest that ADHD participants have reduced ability to suppress unwanted saccades and control their fixation behavior voluntarily, a finding that is consistent with a fronto-striatal pathophysiology. The findings are discussed in the context of recent neurophysiological data from nonhuman primates that have identified important control signals for saccade suppression that emanate from frontostriatal circuits.

Kinematics and kinetics of multijoint reaching in nonhuman primates.

The present study identifies the mechanics of planar reaching movements performed by monkeys (Macaca mulatta) wearing a robotic exoskeleton. This device maintained the limb in the horizontal plane such that hand motion was generated only by flexor and extensor motions at the shoulder and elbow. The study describes the kinematic and kinetic features of the shoulder, elbow, and hand during reaching movements from a central target to peripheral targets located on the circumference of a circle: the center-out task. While subjects made reaching movements with relatively straight smooth hand paths and little variation in peak hand velocity, there were large variations in joint motion, torque, and power for movements in different spatial directions. Unlike single-joint movements, joint kinematics and kinetics were not tightly coupled for these multijoint movements. For most movements, power generation was predominantly generated at only one of the two joints. The present analysis illustrates the complexities inherent in multijoint movements and forms the basis for understanding strategies used by the motor system to control reaching movements and for interpreting the response of neurons in different brain regions during this task.