Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder.

OBJECTIVE: There were more than 107,000 drug overdose deaths in the US in 2021, the most ever recorded. Despite advances in behavioral and pharmacological treatments, over 50% of those receiving treatment for opioid use disorder (OUD) experience drug use recurrence (relapse). Given the prevalence of OUD and other substance use disorders (SUDs), the high rate of drug use recurrence, and the number of drug overdose deaths, novel treatment strategies are desperately needed. The objective of this study was to evaluate the safety and feasibility of deep brain stimulation (DBS) targeting the nucleus accumbens (NAc)/ventral capsule (VC) and potential impact on outcomes in individuals with treatment-refractory OUD. METHODS: A prospective, open-label, single-arm study was conducted among participants with longstanding treatment-refractory OUD (along with other co-occurring SUDs) who underwent DBS in the NAc/VC. The primary study endpoint was safety; secondary/exploratory outcomes included opioid and other substance use, substance craving, and emotional symptoms throughout follow-up and 18FDG-PET neuroimaging. RESULTS: Four male participants were enrolled and all tolerated DBS surgery well with no serious adverse events (AEs) and no device- or stimulation-related AEs. Two participants sustained complete substance abstinence for > 1150 and > 520 days, respectively, with significant post-DBS reductions in substance craving, anxiety, and depression. One participant experienced post-DBS drug use recurrences with reduced frequency and severity. The DBS system was explanted in one participant due to noncompliance with treatment requirements and the study protocol. 18FDG-PET neuroimaging revealed increased glucose metabolism in the frontal regions for the participants with sustained abstinence only. CONCLUSIONS: DBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD. A randomized, sham-controlled trial in a larger cohort of patients is being initiated.

Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial.

Introduction: While current treatments for substance use disorder (SUD) are beneficial, success rates remain low and treatment outcomes are complicated by co-occurring SUDs, many of which are without available medication treatments. Research involving neuromodulation for SUD has recently gained momentum. This study evaluated two doses (60 and 90 W) of Low Intensity Focused Ultrasound (LIFU), targeting the bilateral nucleus accumbens (NAc), in individuals with SUD. Methods: Four participants (three male), who were receiving comprehensive outpatient treatment for opioid use disorder at the time of enrollment and who also had a history of excessive non-opioid substance use, completed this pilot study. After confirming eligibility, these participants received 10 min sham LIFU followed by 20 min active LIFU (10 min to left then right NAc). Outcomes were the safety, tolerability, and feasibility during the LIFU procedure and throughout the 90-day follow-up. Outcomes also included the impact of LIFU on cue-induced substance craving, assessed via Visual Analog Scale (VAS), both acutely (pre-, during and post-procedure) and during the 90-day follow-up. Daily craving ratings (without cues) were also obtained for one-week prior to and one-week following LIFU. Results: Both LIFU doses were safe and well-tolerated based on reported adverse events and MRI scans revealed no structural changes (0 min, 24 h, and 1-week post-procedure). For the two participants receiving "enhanced" (90 W) LIFU, VAS craving ratings revealed active LIFU attenuated craving for participants' primary substances of choice relative to sham sonication. For these participants, reductions were also noted in daily VAS craving ratings (0 = no craving; 10 = most craving ever) across the week following LIFU relative to pre-LIFU; Participant #3 pre- vs. post-LIFU: opioids (3.6 ± 0.6 vs. 1.9 ± 0.4), heroin (4.2 ± 0.8 vs. 1.9 ± 0.4), methamphetamine (3.2 ± 0.4 vs. 0.0 ± 0.0), cocaine (2.4 ± 0.6 vs. 0.0 ± 0.0), benzodiazepines (2.8 ± 0.5 vs. 0.0 ± 0.0), alcohol (6.0 ± 0.7 vs. 2.7 ± 0.8), and nicotine (5.6 ± 1.5 vs. 3.1 ± 0.7); Participant #4: alcohol (3.5 ± 1.3 vs. 0.0 ± 0.0) and nicotine (5.0 ± 1.8 vs. 1.2 ± 0.8) (all p's < 0.05). Furthermore, relative to screening, longitudinal reductions in cue-induced craving for several substances persisted during the 90-day post-LIFU follow-up evaluation for all participants. Discussion: In conclusion, LIFU targeting the NAc was safe and acutely reduced substance craving during the LIFU procedure, and potentially had longer-term impact on craving reductions. While early observations are promising, NAc LIFU requires further investigation in a controlled trial to assess the impact on substance craving and ultimately substance use and relapse.

Identifying biomarkers of drug use recurrence using wearable device technologies and phone applications.

BACKGROUND: Identifying predictors of drug use recurrence (DUR) is critical to combat the addiction epidemic. Wearable devices and phone-based applications for obtaining self-reported assessments in the patient's natural environment (e.g., ecological momentary assessment; EMA) have been used in various healthcare settings. However, the utility of combining these technologies to predict DUR in substance use disorder (SUD) has not yet been explored. This study investigates the combined use of wearable technologies and EMA as a potential mechanism for identifying physiological/behavioral biomarkers of DUR. METHODS: Participants, recruited from an SUD treatment program, were provided with a commercially available wearable device that continuously monitors biometric signals (e.g., heart rate/variability [HR/HRV], sleep characteristics). They were also prompted daily to complete an EMA via phone-based application (EMA-APP) that included questionnaires regarding mood, pain, and craving. RESULTS: Seventy-seven participants are included in this pilot study (34 participants experienced a DUR during enrollment). Wearable technologies revealed that physiological markers were significantly elevated in the week prior to DUR relative to periods of sustained abstinence (p<0.001). Results from the EMA-APP revealed that those who experienced a DUR reported greater difficulty concentrating, exposure to triggers associated with substance use, and increased isolation the day prior to DUR (p<0.001). Compliance with study procedures during the DUR week was lower than any other period of measurement (p<0.001). CONCLUSIONS: These results suggest that data acquired via wearable technologies and the EMA-APP may serve as a method of predicting near-term DUR, thereby potentially prompting intervention before drug use occurs.

Vigilance to Spatialized Auditory Displays: Initial Assessment of Performance and Workload.

OBJECTIVE: The present study was designed to evaluate human performance and workload associated with an auditory vigilance task that required spatial discrimination of auditory stimuli. BACKGROUND: Spatial auditory displays have been increasingly developed and implemented into settings that require vigilance toward auditory spatial discrimination and localization (e.g., collision avoidance warnings). Research has yet to determine whether a vigilance decrement could impede performance in such applications. METHOD: Participants completed a 40-minute auditory vigilance task in either a spatial discrimination condition or a temporal discrimination condition. In the spatial discrimination condition, participants differentiated sounds based on differences in spatial location. In the temporal discrimination condition, participants differentiated sounds based on differences in stimulus duration. RESULTS: Correct detections and false alarms declined during the vigilance task, and each did so at a similar rate in both conditions. The overall level of correct detections did not differ significantly between conditions, but false alarms occurred more frequently within the spatial discrimination condition than in the temporal discrimination condition. NASA-TLX ratings and pupil diameter measurements indicated no differences in workload. CONCLUSION: Results indicated that tasks requiring auditory spatial discrimination can induce a vigilance decrement; and they may result in inferior vigilance performance, compared to tasks requiring discrimination of auditory duration. APPLICATION: Vigilance decrements may impede performance and safety in settings that depend on sustained attention to spatial auditory displays. Display designers should also be aware that auditory displays that require users to discriminate differences in spatial location may result in poorer discrimination performance than non-spatial displays.

Robot Authority in Human-Robot Teaming: Effects of Human-Likeness and Physical Embodiment on Compliance.

The anticipated social capabilities of robots may allow them to serve in authority roles as part of human-machine teams. To date, it is unclear if, and to what extent, human team members will comply with requests from their robotic teammates, and how such compliance compares to requests from human teammates. This research examined how the human-likeness and physical embodiment of a robot affect compliance to a robot's request to perseverate utilizing a novel task paradigm. Across a set of two studies, participants performed a visual search task while receiving ambiguous performance feedback. Compliance was evaluated when the participant requested to stop the task and the coach urged the participant to keep practicing multiple times. In the first study, the coach was either physically co-located with the participant or located remotely via a live-video. Coach type varied in human-likeness and included either a real human (confederate), a Nao robot, or a modified Roomba robot. The second study expanded on the first by including a Baxter robot as a coach and replicated the findings in a different sample population with a strict chain of command culture. Results from both studies showed that participants comply with the requests of a robot for up to 11 min. Compliance is less than to a human and embodiment and human-likeness on had weak effects on compliance.

Deep brain stimulation of the nucleus accumbens/ventral capsule for severe and intractable opioid and benzodiazepine use disorder.

Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed for those who are treatment refractory. The objective of this study was to evaluate the safety of deep brain stimulation (DBS) for SUD and the effects of DBS on substance use, substance craving, emotional symptoms, and frontal/executive functions. DBS electrodes were implanted bilaterally within the Nucleus Accumbens/Ventral anterior internal capsule (NAc/VC) of a man in his early 30s with >10-year history of severe treatment refractory opioid and benzodiazepine use disorders. DBS of the NAc/VC was found to be safe with no serious adverse events noted and the participant remained abstinent and engaged in comprehensive treatment at the 12-week endpoint (and 12-month extended follow-up). Using a 0-100 visual analog scale, substance cravings decreased post-DBS implantation; most substantially in benzodiazepine craving following the final DBS titration (1.0 ± 2.2) compared to baseline (53.4 ± 29.5; p < .001). A trend toward improvement in frontal/executive function was observed on the balloon analog risk task performance following the final titration (217.7 ± 76.2) compared to baseline (131.3 ± 28.1, p = .066). FDG PET demonstrated an increase in glucose metabolism in the dorsolateral prefrontal and medial premotor cortices at the 12-week endpoint compared to post-surgery/pre-DBS titration. Heart Rate Variability (HRV) improved following the final titration (rMSSD = 56.0 ± 11.7) compared to baseline (19.2 ± 8.2; p < .001). In a participant with severe, treatment refractory opioid and benzodiazepine use disorder, DBS of the NAc/VC was safe, reduced substance use and craving, and improved frontal and executive functions. Confirmation of these findings with future studies is needed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Assessing the Accuracy of Popular Commercial Technologies That Measure Resting Heart Rate and Heart Rate Variability.

Commercial off-the shelf (COTS) wearable devices continue development at unprecedented rates. An unfortunate consequence of their rapid commercialization is the lack of independent, third-party accuracy verification for reported physiological metrics of interest, such as heart rate (HR) and heart rate variability (HRV). To address these shortcomings, the present study examined the accuracy of seven COTS devices in assessing resting-state HR and root mean square of successive differences (rMSSD). Five healthy young adults generated 148 total trials, each of which compared COTS devices against a validation standard, multi-lead electrocardiogram (mECG). All devices accurately reported mean HR, according to absolute percent error summary statistics, although the highest mean absolute percent error (MAPE) was observed for CameraHRV (17.26%). The next highest MAPE for HR was nearly 15% less (HRV4Training, 2.34%). When measuring rMSSD, MAPE was again the highest for CameraHRV [112.36%, concordance correlation coefficient (CCC): 0.04], while the lowest MAPEs observed were from HRV4Training (4.10%; CCC: 0.98) and OURA (6.84%; CCC: 0.91). Our findings support extant literature that exposes varying degrees of veracity among COTS devices. To thoroughly address questionable claims from manufacturers, elucidate the accuracy of data parameters, and maximize the real-world applicative value of emerging devices, future research must continually evaluate COTS devices.

Evaluations of Commercial Sleep Technologies for Objective Monitoring During Routine Sleeping Conditions.

PURPOSE: The commercial market is saturated with technologies that claim to collect proficient, free-living sleep measurements despite a severe lack of independent third-party evaluations. Therefore, the present study evaluated the accuracy of various commercial sleep technologies during in-home sleeping conditions. MATERIALS AND METHODS: Data collection spanned 98 separate nights of ad libitum sleep from five healthy adults. Prior to bedtime, participants utilized nine popular sleep devices while concurrently wearing a previously validated electroencephalography (EEG)-based device. Data collected from the commercial devices were extracted for later comparison against EEG to determine degrees of accuracy. Sleep and wake summary outcomes as well as sleep staging metrics were evaluated, where available, for each device. RESULTS: Total sleep time (TST), total wake time (TWT), and sleep efficiency (SE) were measured with greater accuracy (lower percent errors) and limited bias by Fitbit Ionic [mean absolute percent error, bias (95% confidence interval); TST: 9.90%, 0.25 (-0.11, 0.61); TWT: 25.64%, -0.17 (-0.28, -0.06); SE: 3.49%, 0.65 (-0.82, 2.12)] and Oura smart ring [TST: 7.39%, 0.19 (0.04, 0.35); TWT: 36.29%, -0.18 (-0.31, -0.04); SE: 5.42%, 1.66 (0.17, 3.15)], whereas all other devices demonstrated a propensity to over or underestimate at least one if not all of the aforementioned sleep metrics. No commercial sleep technology appeared to accurately quantify sleep stages. CONCLUSION: Generally speaking, commercial sleep technologies displayed lower error and bias values when quantifying sleep/wake states as compared to sleep staging durations. Still, these findings revealed that there is a remarkably high degree of variability in the accuracy of commercial sleep technologies, which further emphasizes that continuous evaluations of newly developed sleep technologies are vital. End-users may then be able to determine more accurately which sleep device is most suited for their desired application(s).

Trust and Distrust of Automated Parking in a Tesla Model X.

OBJECTIVE: The present study aims to evaluate driver intervention behaviors during a partially automated parking task. BACKGROUND: Cars with partially automated parking features are becoming widely available. Although recent research explores the use of automation features in partially automated cars, none have focused on partially automated parking. Recent incidents and research have demonstrated that drivers sometimes use partially automated features in unexpected, inefficient, and harmful ways. METHOD: Participants completed a series of partially automated parking trials with a Tesla Model X and their behavioral interventions were recorded. Participants also completed a risk-taking behavior test and a post-experiment questionnaire that included questions about trust in the system, likelihood of using the Autopark feature, and preference for either the partially automated parking feature or self-parking. RESULTS: Initial intervention rates were over 50%, but declined steeply in later trials. Responses to open-ended questions revealed that once participants understood what the system was doing, they were much more likely to trust it. Trust in the partially automated parking feature was predicted by a model including risk-taking behaviors, self-confidence, self-reported number of errors committed by the Tesla, and the proportion of trials in which the driver intervened. CONCLUSION: Using partially automated parking with little knowledge of its workings can lead to high degree of initial distrust. Repeated exposure of partially automated features to drivers can greatly increase their use. APPLICATION: Short tutorials and brief explanations of the workings of partially automated features may greatly improve trust in the system when drivers are first introduced to partially automated systems.

Vigilance Tasks: Unpleasant, Mentally Demanding, and Stressful Even When Time Flies.

OBJECTIVE: To determine whether perceived time progression (PTP) moderates participants' negative reactions to vigilance tasks. BACKGROUND: Vigilance tasks are rated by participants to be unenjoyable and as having high levels of workload and stress. Based on the adage, "You are having fun when time flies," we tested the possibility that accelerating PTP might reduce these negative experiences. METHOD: Two studies were performed, involving a long 30-min and a short 12-min vigil. We manipulated participants' PTP by creating a mismatch between their expectations about how long they would perform the task and the actual time that they were engaged. RESULTS: PTP was significantly faster for participants who were led to expect that the vigilance task would last longer than it did relative to those led to expect that task duration would be shorter than it actually was and for controls for whom task duration was equal to the expected duration. However, accelerating PTP had no effect in either experiment on undesirable reactions to the vigilance tasks. Participants uniformly rated both tasks as unenjoyable, as having a high level of workload, and as stressful. Apparently, vigilance isn't fun even when time flies. CONCLUSION: Our findings greatly underscore the depth to which negative subjective reactions are embedded in the nature of vigilance tasks and therefore that these tasks can have potentially serious costs to participants in terms of health, safety, and productivity. APPLICATION: These costs must be considered at the operational level.

The Independence and Interdependence of Coacting Observers in Regard to Performance Efficiency, Workload, and Stress in a Vigilance Task.

OBJECTIVE: We investigated performance, workload, and stress in groups of paired observers who performed a vigilance task in a coactive (independent) manner. BACKGROUND: Previous studies have demonstrated that groups of coactive observers detect more signals in a vigilance task than observers working alone. Therefore, the use of such groups might be effective in enhancing signal detection in operational situations. However, concern over appearing less competent than one's cohort might induce elevated levels of workload and stress in coactive group members and thereby undermine group performance benefits. Accordingly, we performed the initial experiment comparing workload and stress in observers who performed a vigilance task coactively with those of observers who performed the vigilance task alone. METHOD: Observers monitored a video display for collision flight paths in a simulated unmanned aerial vehicle control task. Self-reports of workload and stress were secured via the NASA-Task Load Index and the Dundee Stress State Questionnaire, respectively. RESULTS: Groups of coactive observers detected significantly more signals than did single observers. Coacting observers did not differ significantly from those operating by themselves in terms of workload but did in regard to stress; posttask distress was significantly lower for coacting than for single observers. CONCLUSION: Performing a visual vigilance task in a coactive manner with another observer does not elevate workload above that of observers working alone and serves to attenuate the stress associated with vigilance task performance. APPLICATION: The use of coacting observers could be an effective vehicle for enhancing performance efficiency in operational vigilance.

Effects of Stereoscopic Depth on Vigilance Performance and Cerebral Hemodynamics.

OBJECTIVE: We tested the possibility that monitoring a display wherein critical signals for detection were defined by a stereoscopic three-dimensional (3-D) image might be more resistant to the vigilance decrement, and to temporal declines in cerebral blood flow velocity (CBFV), than monitoring a display featuring a customary two-dimensional (2-D) image. BACKGROUND: Hancock has asserted that vigilance studies typically employ stimuli for detection that do not exemplify those that occur in the natural world. As a result, human performance is suboptimal. From this perspective, tasks that better approximate perception in natural environments should enhance performance efficiency. To test that possibility, we made use of stereopsis, an important means by which observers interact with their everyday surroundings. METHOD: Observers monitored a circular display in which a vertical line was embedded. Critical signals for detection in a 2-D condition were instances in which the line was rotated clockwise from vertical. In a 3-D condition, critical signals were cases in which the line appeared to move outward toward the observer. RESULTS: The overall level of signal detection and the stability of detection over time were greater when observers monitored for 3-D changes in target depth compared to 2-D changes in target orientation. However, the 3-D display did not retard the temporal decline in CBFV. CONCLUSION: These results provide the initial demonstration that 3-D displays can enhance performance in vigilance tasks. APPLICATION: The use of 3-D displays may be productive in augmenting system reliability when operator vigilance is vital.

The sustained attention to response task (SART) does not promote mindlessness during vigilance performance.

OBJECTIVE: In this study, we evaluated the validity of the Sustained Attention to Response Task (SART) as a means for promoting mindlessness in vigilance performance. BACKGROUND: Vigilance tasks typically require observers to respond to critical signals and to withhold responding to neutral events. The SART features the opposite response requirements, which supposedly leads it to promote a mindless, non-thoughtful approach to the vigilance task To test that notion, we compared the SART to the traditional vigilance format (TVF) in terms of diagnostic accuracy assessed through decision theory measures of positive and negative predictive power (PPP and NPP), perceived mental workload indexed by the Multiple Resource Questionnaire, and oculomotor activity reflected in the Nearest Neighbor Index and fixation dwell times. METHOD: Observers in TVF and SART conditions monitored a video display for collision flight paths in a simulated air traffic control task. RESULTS: Diagnostic accuracy in terms of NPP was high in both format conditions. While PPP was poorer in the SART than in the TVF, that result could be accounted for by a loss of motor control rather than a lack of mindfulness. Identical high levels of workload were generated by the TVF and SART tasks, and observers in both conditions showed similar dynamic scanning of the visual scene. CONCLUSION: The data indicate that the SART is not an engine of mindlessness. APPLICATION: The results challenge the widespread use of the SART to support a model in which mindlessness is considered to be the principal root of detection failures in vigilance.

Google glass: a driver distraction cause or cure?

OBJECTIVE: We assess the driving distraction potential of texting with Google Glass (Glass), a mobile wearable platform capable of receiving and sending short-message-service and other messaging formats. BACKGROUND: A known roadway danger, texting while driving has been targeted by legislation and widely banned. Supporters of Glass claim the head-mounted wearable computer is designed to deliver information without concurrent distraction. Existing literature supports the supposition that design decisions incorporated in Glass might facilitate messaging for drivers. METHOD: We asked drivers in a simulator to drive and use either Glass or a smartphone-based messaging interface, then interrupted them with an emergency brake event. Both the response event and subsequent recovery were analyzed. RESULTS: Glass-delivered messages served to moderate but did not eliminate distracting cognitive demands. A potential passive cost to drivers merely wearing Glass was also observed. Messaging using either device impaired driving as compared to driving without multitasking. CONCLUSION: Glass in not a panacea as some supporters claim, but it does point the way to design interventions that effect reduced load in multitasking. APPLICATION: Discussions of these identified benefits are framed within the potential of new in-vehicle systems that bring both novel forms of distraction and tools for mitigation into the driver's seat.

Predicting battlefield vigilance: a multivariate approach to assessment of attentional resources.

Technological innovation increasingly requires operators in various applied settings to maintain vigilance for extended periods. However, standard psychometric tests typically predict less than 10% of performance variance. The present study (N = 462) aimed to apply the resource theory of sustained attention to construct a multivariate test battery for predicting battlefield vigilance. The battery included cognitive ability tests, a high-workload short vigilance task and subjective measures of stress response. Four versions of a 60- min simulated military battlefield monitoring task were constructed to represent different operational requirements. The test battery predicted 24-44% of criterion variance, depending on task version, suggesting that it may identify vigilant operators in military and other applied contexts. A multiple-groups path analysis showed that relationships between ability and vigilance were moderated by working memory demands. Findings are consistent with a diffuse theoretical concept of 'resources' in which performance energisation depends on multiple, loosely coupled processes.

Viewing the workload of vigilance through the lenses of the NASA-TLX and the MRQ.

OBJECTIVE: The aim of this study was to compare the effectiveness of a new index of perceived mental workload, the Multiple Resource Questionnaire (MRQ), with the standard measure of workload used in the study of vigilance, the NASA Task Load Index (NASA-TLX). BACKGROUND: The NASA-TLX has been used extensively to demonstrate that vigilance tasks impose a high level of workload on observers. However, this instrument does not specify the information-processing resources needed for task performance. The MRQ offers a tool to measure the workload associated with vigilance assignments in which such resources can be identified. METHOD: Two experiments were performed in which factors known to influence task demand were varied. Included were the detection of stimulus presence or absence, detecting critical signals by means of successive-type (absolute judgment) and simultaneous-type (comparative judgment) discriminations, and operating under multitask vs. single-task conditions. RESULTS: The MRQ paralleled the NASA-TLX in showing that vigilance tasks generally induce high levels of workload and that workload scores are greater in detecting stimulus absence than presence and in making successive as compared to simultaneous-type discriminations. Additionally, the MRQ was more effective than the NASA-TLX in reflecting higher workload in the context of multitask than in single-task conditions. The resource profiles obtained with MRQ fit well with the nature of the vigilance tasks employed, testifying to the scale's content validity. CONCLUSION: The MRQ may be a meaningful addition to the NASA-TLX for measuring the workload of vigilance assignments. APPLICATION: By uncovering knowledge representation associated with different tasks, the MRQ may aid in designing operational vigilance displays.