Great Lakes NeuroTechnologies (United States)

The aim of the study is to identify the mechanisms mediating differences in sexual behavior between Sprague Dawley and Wistar rats, in order to choose the optimal stock for research into pharmacological correction of male sexual dysfunction.Materials and MethodsThe experiments were carried out on sexually mature male rats of two stocks (Sprague Dawley and Wistar) weighing 350–450 g and aged 3 to 6 months. The comparative study of animal behavior was performed using standard tests for social interaction, locomotor activity, and anxiety level, as well as male mating behavior patterns. In order to determine the role of hypothalamic glycine receptors in the male sexual behavior, pharmacological manipulations of glycine receptor activity during mating with receptive females were conducted via bilateral intracerebral microcannulas implanted in the medial preoptic area (mPOA) of the male rat anterior hypothalamus.ResultsThe obtained results revealed statistically significant inter-stock differences in sexual behavior at the final consummatory stage of both intact animals and those after pharmacological activation of glycine receptors in the mPOA. The number of anxiety-related grooming patterns in the Open Field test significantly differed between the stocks for both intact animals and those after pharmacological activation of glycine receptors; the observed differences disappeared after the mPOA glycine receptors were blocked. In the Crowley test of social interaction, no significant difference was found between the stocks.Thus, the revealed difference in sexual behavior between Sprague Dawley and Wistar male rats is likely due to the difference in the level of anxiety, which, in turn, may be associated with difference in the mechanisms of glycinergic neurotransmission in the hypothalamic mPOAs of these rats.ConclusionTo study the relationship between the level of anxiety and sexual behavior, the choice of the Wistar rat stock is optimal since the male sexual behavior in this stock is more sensitive to stress than that in Sprague Dawley rats. However, to model male sexual dysfunction not associated with anxiety, the use of Sprague Dawley male rats should be preferred as these animals show more stable sexual behavior, which is less dependent on the level of anxiety.

Introduction: Parkinson’s disease (PD) is poorly quantified by patients outside the clinic, and paper diaries have problems with subjective descriptions and bias. Wearable sensor platforms; however, can accurately quantify symptoms such as tremor, dyskinesia, and bradykinesia. Commercially available smartwatches are equipped with accelerometers and gyroscopes that can measure motion for objective evaluation. We sought to evaluate the clinical utility of a prescription smartwatch-based monitoring system for PD utilizing periodic task-based motor assessment. Methods: Sixteen patients with PD used a smartphone- and smartwatch-based monitoring system to objectively assess motor symptoms for 1 week prior to instituting a doctor recommended change in therapy and for 4 weeks after the change. After 5 weeks the participants returned to the clinic to discuss their results with their doctor, who made therapy recommendations based on the reports and his clinical judgment. Symptom scores were synchronized with the medication diary and the temporal effects of therapy on weekly and hourly timescales were calculated. Results: Thirteen participants successfully completed the study and averaged 4.9 assessments per day for 3 days per week during the study. The doctor instructed 8 participants to continue their new regimens and 5 to revert to their previous regimens. The smartwatch-based assessments successfully captured intraday fluctuations and short- and long-term responses to therapies, including detecting significant improvements (p < 0.05) in at least one symptom in 7 participants. Conclusions: The smartwatch-based app successfully captured temporal trends in symptom scores following application of new therapy on hourly, daily, and weekly timescales. These results suggest that validated smartwatch-based PD monitoring can provide clinically relevant information and may reduce the need for traditional office visits for therapy adjustment.

Fluctuations in response to levodopa in Parkinson's disease (PD) are difficult to treat as tools to monitor temporal patterns of symptoms are hampered by several challenges. The objective was to use wearable sensors to quantify the dose response of tremor, bradykinesia, and dyskinesia in individuals with PD. Thirteen individuals with PD and fluctuating motor benefit were instrumented with wrist and ankle motion sensors and recorded by video. Kinematic data were recorded as subjects completed a series of activities in a simulated home environment through transition from off to on medication. Subjects were evaluated using the unified Parkinson disease rating scale motor exam (UPDRS-III) at the start and end of data collection. Algorithms were applied to the kinematic data to score tremor, bradykinesia, and dyskinesia. A blinded clinician rated severity observed on video. Accuracy of algorithms was evaluated by comparing scores with clinician ratings using a receiver operating characteristic (ROC) analysis. Algorithm scores for tremor, bradykinesia, and dyskinesia agreed with clinician ratings of video recordings (ROC area > 0.8). Summary metrics extracted from time intervals before and after taking medication provided quantitative measures of therapeutic response (p < 0.01). Radar charts provided intuitive visualization, with graphical features correlated with UPDRS-III scores (R = 0.81). A system with wrist and ankle motion sensors can provide accurate measures of tremor, bradykinesia, and dyskinesia as patients complete routine activities. This technology could provide insight on motor fluctuations in the context of daily life to guide clinical management and aid in development of new therapies.

Neurological disorders such as cerebral palsy commonly result in abnormal muscle hyperactivity that negatively effects functional use of the affected limbs. Individuals with cerebral palsy often present with a mix of spasticity and dystonia, and it can be difficult to distinguish between the effects of these types of abnormal tone. Different types of abnormal tone respond differently to treatments such as deep brain stimulation and baclofen. Conventional clinical evaluation techniques provide minimal information for distinguishing abnormal tone characteristics and changes from treatment. Devices that quantify abnormal tone characteristics can help distinguish between the effects of different types of abnormal muscle tone, and help to quantify treatment effects. This paper discusses the development and initial evaluation of MyoSense(TM), a clinician worn device for the quantification and differentiation of abnormal muscle tone. MyoSense evaluates the orientation, speed, and force during clinician manipulation of the affected limbs with a protocol that is similar to conventional practice for evaluating abnormal tone. Evaluation of the MyoSense device, using a mechanical apparatus to simulate abnormal muscle tone, showed good resolution of abnormal tone characteristics. Using a procedure directly modeled after conventional clinical evaluation of abnormal tone, MyoSense data showed good correlation with simulated profiles, 0.8 for spasticity and 0.93 for hypertonia. Evaluation of average change across different limb manipulation speeds, to mitigate acceleration and mechanical effects, resulted in MyoSense data correlations to simulated profiles of 0.99 for spasticity, spasticity with a catch, and dystonia. Overall these results show promise for future clinical evaluation of the MyoSense device.

OBJECTIVE: To capture Parkinson's disease (PD) motor symptom severities across a range of deep brain stimulation (DBS) settings during outpatient programming and determine how these functional motor responses change across programming sessions.