Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington\u27s Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington\u27s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington\u27s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression

The Electrooculogram and a New Blink Detection Algorithm

Accurate and efficient real-time cognitive workload assessment has many important applications, and physiological monitoring has proven quite helpful with this assessment. One such physiological signal, the electrooculogram (EOG), can provide blink rate and blink duration measures. In a recent study, we developed and validated a robust blink detection algorithm based on the vertical EOG (VEOG). This algorithm does not require baseline data and is adaptive in the sense that it works for a wide variety of individuals without any experimenter adjustments. The performance of the algorithm is quantified using truth data based on video recordings. The algorithm produced blink rate and blink duration data for participants in a simulated remotely piloted aircraft experiment. Although this paper focuses on the blink detection algorithm, some results from the study will be included. Specifically, it was found that participants blinked fewer times and with a shorter duration in the more difficult experimental conditions

Investigating Facial Electromyography as an Indicator of Cognitive Workload

Facial electromyography (fEMG) is an electromyographic measurement technique that has primarily been used as a tool for measuring affect, but previous experiments suggest that it also has the potential to help quantify cognitiveworkload. In the current study, two task-irrelevant facial muscles, corrugator supercilli and lateral frontalis, were monitored in real-time to determine whether they were sensitive to workload changes in a remotely piloted aircraft (RPA) task environment. Real-time signal processing techniques were applied to derive the median amplitude and zero-crossing rate from windowed fEMG data. Statistical analysis of these features determined that both muscles were sensitive to variations in specific workload manipulations. This research suggests that real-time fEMG features extracted from the aforementionedmuscles possess the potential to serve as, or contribute to, anindex of cognitiveworkload. Future work aims to refine fEMG data collection techniques to produce a more responsive and representative measure suitable for workload assessment

Using Pair-Wise Rankings in the Assessment of Adaptive Aiding

In remotely piloted aircraft (RPA) operations, operator cognitive workload is an important concern. High workload couldresult in performance decrements and operational mishaps. In research, physiological data can beused by models to assess the operator’s cognitive state. When a model detects the onset of cognitive overload, assistance could thenbe provided to the operator to help mitigate the overload in some form of augmentation. However, it is imperative that the assessment is accurate and completed in a timely manner. The accuracy of a workload assessment model and augmentation application canbe evaluated using a psychometrically determined scale of man/machine conditions. Both the operator and machine can be in various conditions at any point in time.In three prior studies, eighteen participants were asked to perform pair-wise rankings of sixteen conditions to generate therankings. These rankings will be used to evaluate the accuracy ofthe workload assessment model in future research

Saccade Detection Using Polar Coordinates – a New Algorithm

Over the past few decades substantial research has been conducted regarding saccades (rapid eye movements). There are two components of this research. First there is the detection of the saccades, and second how to interpret the saccades features (amplitude, length, and velocity) to inform specific areas of research. This involves both experimental research and clinical applications. The detection of saccades is typically accomplished using two approaches, including cameras and the electrooculogram (EOG). Both of these approaches require algorithms to process the raw data, detect saccades, and calculate the saccade features. The current effort focuses on detecting saccades in the EOG using a new algorithm based on polar coordinates. The details of this algorithm will be presented, as will a calibration procedure and validation of the algorithm’s accuracy. This algorithm was used in a recent study in which operator workload was manipulated. The saccade features produced by the algorithm were analyzed with respect to the workload manipulations. These results will be discussed

Periodic Blink Measures Using Dynamic Windowing

Artificial neural network (ANN) modelsare a common tool forcognitive state assessment. It is best if the inputs to the model are periodic. Typically, these inputs are extractedfrom physiological signals such as the electroencephalogram (EEG), electrocardiogram (ECG), electrooculogram (EOG), and others. Spectral measures derived from EEG data are periodic due to the signal processing. Features based on heart activity and respiration are quasi-periodic by nature. Features extracted from EOG, such as blink rate, can be especiallynon-periodic and can contain outliers. One approach to deal with this problem is to use static windows to compute average blink rate. This approach has some shortcomings. A new approach that uses dynamic windowing, filtering, and sampling is presentedhere. Thisnew approach produces periodic data that aredynamic, adaptive to the individual, and well suited for ANN model use

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington’s Disease Patients—A Randomized Phase 2 Clinical Trial

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington’s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington’s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression