Increased variability but intact integration during visual navigation in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disturbance afflicting a variety of functions. The recent computational focus suggesting aberrant Bayesian inference in ASD has yielded promising but conflicting results in attempting to explain a wide variety of phenotypes by canonical computations. Here, we used a naturalistic visual path integration task that combines continuous action with active sensing and allows tracking of subjects' dynamic belief states. Both groups showed a previously documented bias pattern by overshooting the radial distance and angular eccentricity of targets. For both control and ASD groups, these errors were driven by misestimated velocity signals due to a nonuniform speed prior rather than imperfect integration. We tracked participants' beliefs and found no difference in the speed prior, but there was heightened variability in the ASD group. Both end point variance and trajectory irregularities correlated with ASD symptom severity. With feedback, variance was reduced, and ASD performance approached that of controls. These findings highlight the need for both more naturalistic tasks and a broader computational perspective to understand the ASD phenotype and pathology.

Causal inference accounts for heading perception in the presence of object motion.

The brain infers our spatial orientation and properties of the world from ambiguous and noisy sensory cues. Judging self-motion (heading) in the presence of independently moving objects poses a challenging inference problem because the image motion of an object could be attributed to movement of the object, self-motion, or some combination of the two. We test whether perception of heading and object motion follows predictions of a normative causal inference framework. In a dual-report task, subjects indicated whether an object appeared stationary or moving in the virtual world, while simultaneously judging their heading. Consistent with causal inference predictions, the proportion of object stationarity reports, as well as the accuracy and precision of heading judgments, depended on the speed of object motion. Critically, biases in perceived heading declined when the object was perceived to be moving in the world. Our findings suggest that the brain interprets object motion and self-motion using a causal inference framework.

Measuring Habitual Arm Use Post-stroke With a Bilateral Time-Constrained Reaching Task.

Background: Spontaneous use of the more-affected arm is a meaningful indicator of stroke recovery. The Bilateral Arm Reaching Test (BART) was previously developed to quantify arm use by measuring arm choice to targets projected over a horizontal hemi-workspace. In order to improve clinical validity, we constrained the available movement time, thereby promoting more spontaneous decision making when selecting between the more-affected and less affected arm during the BART. Methods: Twenty-two individuals with mild to moderate hemiparesis were tested with the time-based BART in three time-constraint conditions: no-time constraint, medium, and fast conditions. Arm use was measured across three sessions with a 2-week interval in a spontaneous choice block, in which participants were instructed to use either the more-affected or the less-affected arm to reach targets. We tested the effect of time-constraint condition on the more-affected arm use, external validity of the BART with the Actual Amount of Use Test (AAUT), and test-retest reliability across the three test sessions. Results: The fast condition in the time-based BART showed reduced use of the more-affected arm compared to the no-time constraint condition P < 0.0001) and the medium condition P = 0.0006; Tukey post hoc analysis after mixed-effect linear regression). In addition, the fast condition showed strong correlation with the AAUT r = 0.829, P < 0.001), and excellent test-retest reliability (ICC = 0.960, P < 0.0001). Conclusion: The revised BART with a time-restricted fast condition provides an objective, accurate, and repeatable measure of spontaneous arm use in individuals with chronic stroke hemiparesis.

A Dynamic Bayesian Observer Model Reveals Origins of Bias in Visual Path Integration.

Path integration is a strategy by which animals track their position by integrating their self-motion velocity. To identify the computational origins of bias in visual path integration, we asked human subjects to navigate in a virtual environment using optic flow and found that they generally traveled beyond the goal location. Such a behavior could stem from leaky integration of unbiased self-motion velocity estimates or from a prior expectation favoring slower speeds that causes velocity underestimation. Testing both alternatives using a probabilistic framework that maximizes expected reward, we found that subjects' biases were better explained by a slow-speed prior than imperfect integration. When subjects integrate paths over long periods, this framework intriguingly predicts a distance-dependent bias reversal due to buildup of uncertainty, which we also confirmed experimentally. These results suggest that visual path integration in noisy environments is limited largely by biases in processing optic flow rather than by leaky integration.

Subantibiotic dose of azithromycin attenuates alveolar bone destruction and improves trabecular microarchitectures in a rat model of experimental periodontitis: A study using micro-computed tomography.

Azithromycin, a macrolide antibiotic, has anti-inflammatory and immunomodulatory activities apart from its antibacterial properties. In this study, we examined the efficacy of subantibiotic dose of azithromycin on ligature-induced periodontitis in rats using micro-computed tomography (micro-CT) imaging and bone parameter analysis. Male Sprague-Dawley rats were allocated to the following four groups: non-ligation (NL) group; ligation-only (L) group; ligation-plus-subantibiotic dose azithromycin (SA) group; and 4) ligation-plus-antibiotic dose azithromycin (AA) group. The rats from Groups L, SA and AA were subjected to periodontitis by placing a ligature around lower right first molar. Immediately after ligation, the rats in SA and AA groups received daily intraperitoneal injections of azithromycin at a dosage of 3.5 or 10mg/kg body weight, respectively. The ligatures were maintained for 2weeks at which time the rats had their mandibles hemisected for micro-CT analysis. Subantibiotic dose of azithromycin strongly suppressed reductions in alveolar bone height and bone volume fraction caused by experimental periodontitis. When subantibiotic dosage of azithromycin was administered to rats, ligature-induced alterations in microarchitectural parameters of trabecular bone were significantly reversed. Rats treated with subantibiotic dose of azithromycin presented no significant difference compared to rats with antibiotic dosage in all parameters. While further studies are necessary, subantibiotic dose of azithromycin could be utilized as a host modulator for the treatment of periodontitis.

Nonlinear mixed-effects model reveals a distinction between learning and performance in intensive reach training post-stroke.

BACKGROUND: We recently showed that individuals with chronic stroke who completed two sessions of intensive unassisted arm reach training exhibited improvements in movement times up to one month post-training. Here, we study whether changes in movement times during training can predict long-term changes. METHODS: Sixteen participants with chronic stroke and ten non-disabled age-matched participants performed two sessions of reach training with 600 movements per session. Movement time data during training were fitted to a nonlinear mixed-effects model consisting of a decreasing exponential term to model improvements of performance due to learning and an increasing linear term to model worsening of performance due to activity-dependent fatigability and/or other factors unrelated to learning. RESULTS: For non-disabled age-matched participants, movement times gradually decreased overall during training and overall changes in movement times during training predicted long-term changes. In contrast, for participants post-stroke, movement times often worsened near the end of training. As a result, overall changes in movement times during training did not predict long-term changes in movement times in the stroke group. However, improvements in movement times due to training, as estimated by the exponential term of the model, predicted long-term changes in movement times. CONCLUSION: Participants post-stroke showed a distinction between learning and performance in unassisted intensive arm reach training. Despite worsening of performance in later trials, extended training was beneficial for long-term gains.

Short-Duration and Intensive Training Improves Long-Term Reaching Performance in Individuals With Chronic Stroke.

Previous studies have shown that multiple sessions of reach training lead to long-term improvements in movement time and smoothness in individuals post-stroke. Yet such long-term training regimens are often difficult to implement in actual clinical settings. In this study, we evaluated the long-term and generalization effects of short-duration and intensive reach training in 16 individuals with chronic stroke and mild to moderate impairments. Participants performed 2 sessions of unassisted intensive reach training, with 600 movements per session, and with display of performance-based feedback after each movement. The participants' trunks were restrained with a belt to avoid compensatory movements. Training resulted in significant and durable (1 month) improvements in movement time (20.4% on average) and movement smoothness (22.7% on average). The largest improvements occurred in individuals with the largest initial motor impairments. In addition, training induced generalization to nontrained targets, which persisted in 1-day and in 1-month retention tests. Finally, there was a significant improvement in the Box and Block test from baseline to 1-month retention test (23% on average). Thus, short-duration and intensive reach training can lead to generalized and durable benefits in individuals with chronic stroke and mild to moderate impairments.

Feasibility of the adaptive and automatic presentation of tasks (ADAPT) system for rehabilitation of upper extremity function post-stroke.

BACKGROUND: Current guidelines for rehabilitation of arm and hand function after stroke recommend that motor training focus on realistic tasks that require reaching and manipulation and engage the patient intensively, actively, and adaptively. Here, we investigated the feasibility of a novel robotic task-practice system, ADAPT, designed in accordance with such guidelines. At each trial, ADAPT selects a functional task according to a training schedule and with difficulty based on previous performance. Once the task is selected, the robot picks up and presents the corresponding tool, simulates the dynamics of the tasks, and the patient interacts with the tool to perform the task. METHODS: Five participants with chronic stroke with mild to moderate impairments (> 9 months post-stroke; Fugl-Meyer arm score 49.2 ± 5.6) practiced four functional tasks (selected out of six in a pre-test) with ADAPT for about one and half hour and 144 trials in a pseudo-random schedule of 3-trial blocks per task. RESULTS: No adverse events occurred and ADAPT successfully presented the six functional tasks without human intervention for a total of 900 trials. Qualitative analysis of trajectories showed that ADAPT simulated the desired task dynamics adequately, and participants reported good, although not excellent, task fidelity. During training, the adaptive difficulty algorithm progressively increased task difficulty leading towards an optimal challenge point based on performance; difficulty was then continuously adjusted to keep performance around the challenge point. Furthermore, the time to complete all trained tasks decreased significantly from pretest to one-hour post-test. Finally, post-training questionnaires demonstrated positive patient acceptance of ADAPT. CONCLUSIONS: ADAPT successfully provided adaptive progressive training for multiple functional tasks based on participant's performance. Our encouraging results establish the feasibility of ADAPT; its efficacy will next be tested in a clinical trial.