Driving Safety and Real-Time Glucose Monitoring in Insulin-Dependent Diabetes.

Our goal is to address the need for driver-state detection using wearable and in-vehicle sensor measurements of driver physiology and health. To address this goal, we deployed in-vehicle systems, wearable sensors, and procedures capable of quantifying real-world driving behavior and performance in at-risk drivers with insulin-dependent type 1 diabetes mellitus (DM). We applied these methodologies over 4 weeks of continuous observation to quantify differences in real-world driver behavior profiles associated with physiologic changes in drivers with DM (N=19) and without DM (N=14). Results showed that DM driver behavior changed as a function of glycemic state, particularly hypoglycemia. DM drivers often drive during at-risk physiologic states, possibly due to unawareness of impairment, which in turn may relate to blunted physiologic responses (measurable heart rate) to hypoglycemia after repeated episodes of hypoglycemia. We found that this DM driver cohort has an elevated risk of crashes and citations, which our results suggest is linked to the DM driver's own momentary physiology. Overall, our findings demonstrate a clear link between at-risk driver physiology and real-world driving. By discovering key relationships between naturalistic driving and parameters of contemporaneous physiologic changes, like glucose control, this study directly advances the goal of driver-state detection through wearable physiologic sensors as well as efforts to develop "gold standard" metrics of driver safety and an individualized approach to driver health and wellness.

Driving performance of stable outpatients with depression undergoing real-world treatment.

AIM: Although the effects of psychotropics on driving ability have received much attention, little research is available on driving performance of stable outpatients with depression undergoing real-world treatment. This observational study investigated driving performance, cognitive functions, and depressive symptomatology of partly remitted outpatients with depression under daily-practice psychopharmacologic treatment. METHODS: Seventy stable outpatients with depression and 67 healthy volunteers were enrolled. Patients' prescriptions were not controlled in order to capture the real-world treatment environment. Participants underwent three driving tasks - road-tracking, car-following, and harsh-braking - using a driving simulator, and three cognitive tasks - Continuous Performance Test, Wisconsin Card Sorting Test, and Trail-Making Test. The Symptom Assessment Scale - Structured Interview Guide for the Hamilton Depression Rating Scale, Beck Depression Inventory-II, Social Adaptation Self-Evaluation Scale, and Stanford Sleepiness Scale were also completed. RESULTS: Although many patients received various pharmacologic treatments, there were no significant differences in the three driving tasks between outpatients with depression and healthy controls. Difficulty of maintaining set in the Wisconsin Card Sorting Test was significantly increased in patients with depression. Results on the Social Adaptation Self-Evaluation Scale were significantly associated with road-tracking and car-following performance, in contrast to results on the Hamilton Depression Rating Scale and the Beck Depression Inventory-II. CONCLUSION: We conclude that partly remitted depressive patients under steady-state pharmacologic treatment do not differ from healthy controls with respect to driving performance, which seems to be more affected by psychosocial functioning than by pharmacologic agents. This, however, should be investigated systematically in an off/on study.

Relationships Between Older Drivers' Cognitive Abilities as Assessed on the MoCA and Glance Patterns During Visual-Manual Radio Tuning While Driving.

Objective: Research has established that long off-road glances increase crash risk, and other work has shown increased off-road glance behavior in older drivers. This study investigated the relationship between older drivers' (M = 66.3, range 61-69 years) cognitive abilities and the duration of off-road glances while engaged in secondary visual-manual activities. Method: Twenty-two drivers completed the Montreal Cognitive Assessment (MoCA) prior to driving an instrumented vehicle and completing a set of radio-tuning tasks. Glance behavior was recorded and manually coded into 7 glance regions (toward the forward roadway, instrument cluster, center stack, rearview mirror, left, right, and other). Results: On average, older drivers with higher MoCA scores used shorter glances and glanced away from the forward roadway for less total time when manually tuning the radio. Discussion: These findings suggest that lower MoCA scores may represent a driving force behind the "age" differences reported in earlier studies of off-road glance behavior. Questions are raised concerning the identification of MoCA scores that might be used as inclusion cut-points in driving research and in identifying individuals needing further evaluation related to suitability for continuance of driving.

Foot placement during error and pedal applications in naturalistic driving.

Data from a naturalistic driving study was used to examine foot placement during routine foot pedal movements and possible pedal misapplications. The study included four weeks of observations from 30 drivers, where pedal responses were recorded and categorized. The foot movements associated with pedal misapplications and errors were the focus of the analyses. A random forest algorithm was used to predict the pedal application types based the video observations, foot placements, drivers' characteristics, drivers' cognitive function levels and anthropometric measurements. A repeated multinomial logit model was then used to estimate the likelihood of the foot placement given various driver characteristics and driving scenarios. The findings showed that prior foot location, the drivers' seat position, and the drive sequence were all associated with incorrect foot placement during an event. The study showed that there is a potential to develop a driver assistance system that can reduce the likelihood of a pedal error.

Individual differences in cognitive functioning predict effectiveness of a heads-up lane departure warning for younger and older drivers.

The effectiveness of an idealized lane departure warning (LDW) was evaluated in an interactive fixed base driving simulator. Thirty-eight older (mean age=77years) and 40 younger drivers (mean age=35years) took four different drives/routes similar in road culture composition and hazards encountered with and without LDW. The four drives were administered over visits separated approximately by two weeks to examine changes in long-term effectiveness of LDW. Performance metrics were number of LDW activations and average correction time to each LDW. LDW reduced correction time to re-center the vehicle by 1.34s on average (95% CI=1.12-1.57s) but did not reduce the number of times the drivers drifted enough in their lanes to activate the system (LDW activations). The magnitude of reductions in average correction RT was similar for older and younger drivers and did not change with repeated exposures across visits. The contribution of individual differences in basic visual and motor function, as well as cognitive function to safety gains from LDW was also examined. Cognitive speed of processing predicted lane keeping performance for older and younger drivers. Differences in memory, visuospatial construction, and executive function tended to predict performance differences among older but not younger drivers. Cognitive functioning did not predict changes in the magnitude of safety benefits from LDW over time. Implications are discussed with respect to real-world safety systems.

Creation of the Naturalistic Engagement in Secondary Tasks (NEST) distracted driving dataset.

PROBLEM: Distracted driving has become a topic of critical importance to driving safety research over the past several decades. Naturalistic driving data offer a unique opportunity to study how drivers engage with secondary tasks in real-world driving; however, the complexities involved with identifying and coding relevant epochs of naturalistic data have limited its accessibility to the general research community. METHOD: This project was developed to help address this problem by creating an accessible dataset of driver behavior and situational factors observed during distraction-related safety-critical events and baseline driving epochs, using the Strategic Highway Research Program 2 (SHRP2) naturalistic dataset. The new NEST (Naturalistic Engagement in Secondary Tasks) dataset was created using crashes and near-crashes from the SHRP2 dataset that were identified as including secondary task engagement as a potential contributing factor. Data coding included frame-by-frame video analysis of secondary task and hands-on-wheel activity, as well as summary event information. In addition, information about each secondary task engagement within the trip prior to the crash/near-crash was coded at a higher level. Data were also coded for four baseline epochs and trips per safety-critical event. RESULTS: 1,180 events and baseline epochs were coded, and a dataset was constructed. The project team is currently working to determine the most useful way to allow broad public access to the dataset. DISCUSSION: We anticipate that the NEST dataset will be extraordinarily useful in allowing qualified researchers access to timely, real-world data concerning how drivers interact with secondary tasks during safety-critical events and baseline driving. PRACTICAL APPLICATIONS: The coded dataset developed for this project will allow future researchers to have access to detailed data on driver secondary task engagement in the real world. It will be useful for standalone research, as well as for integration with additional SHRP2 data to enable the conduct of more complex research.

Modeling Types of Pedal Applications Using a Driving Simulator.

OBJECTIVE: The aim of this study was to examine variations in drivers' foot behavior and identify factors associated with pedal misapplications. BACKGROUND: Few studies have focused on the foot behavior while in the vehicle and the mishaps that a driver can encounter during a potentially hazardous situation. METHOD: A driving simulation study was used to understand how drivers move their right foot toward the pedals. The study included data from 43 drivers as they responded to a series of rapid traffic signal phase changes. Pedal application types were classified as (a) direct hit, (b) hesitated, (c) corrected trajectory, and (d) pedal errors (incorrect trajectories, misses, slips, or pressed both pedals). A mixed-effects multinomial logit model was used to predict the likelihood of one of these pedal applications, and linear mixed models with repeated measures were used to examine the response time and pedal duration given the various experimental conditions (stimuli color and location). RESULTS: Younger drivers had higher probabilities of direct hits when compared to other age groups. Participants tended to have more pedal errors when responding to a red signal or when the signal appeared to be closer. Traffic signal phases and locations were associated with pedal response time and duration. The response time and pedal duration affected the likelihood of being in one of the four pedal application types. CONCLUSION AND APPLICATION: Findings from this study suggest that age-related and situational factors may play a role in pedal errors, and the stimuli locations could affect the type of pedal application.

Covert effects of "one drink" of alcohol on brain processes related to car driving: an event-related potential study.

The effects of a low dose of alcohol on car driving remain controversial. To address this issue, event-related potentials were recorded while subjects performed a simple car-following task in a driving simulator before and after consuming either "one drink" of beer (representing one standard alcoholic beverage containing 14 g of alcohol) or mineral water (control condition). Subjects who had consumed the determined amount of alcohol demonstrated no detectable outward behavioral signs of intoxication while performing the driving task, an observation in agreement with previous findings. However, the parietal P3 elicited by the brake lights of the preceding car was significantly reduced in amplitude, approximately 50% that observed under the control condition, likely indicating alteration of the neural processing of visual information critical for safe driving. The finding suggests that alcohol begins to affect neural processes for driving even at quantities too low to modify behavior.

The effects of acute treatment with ramelteon, triazolam, and placebo on driving performance, cognitive function, and equilibrium function in healthy volunteers.

RATIONALE: Hypnotics are widely used to treat insomnia but adverse effects of different hypnotics, especially benzodiazepine receptor agonists, are getting more attention lately. The effects of novel hypnotics have not been fully examined. OBJECTIVE: This study aims to assess the effects of two hypnotics, ramelteon and triazolam, on driving performance, cognitive function, and equilibrium function. METHODS: In this double-blinded, three-way crossover trial, 17 healthy males received acute doses of 8 mg ramelteon, 0.125 mg triazolam, and placebo. The subjects were administered three driving tasks-road-tracking, car-following, and harsh-braking-using a driving simulator and three cognitive tasks-Continuous Performance Test, N-back Test, and Trail-Making Test-at baseline and at 1 and 4 h post-dosing. The Stanford Sleepiness Scale scores and computerized posturography were also assessed. RESULTS: In the driving simulations, ramelteon and triazolam increased the number of subjects who slid off the road. Triazolam increased the standard deviation of lateral position compared to ramelteon and placebo at 1 h post-dosing. Ramelteon and triazolam significantly increased the time to complete of Trail-Making Test part A and the environmental area in posturography compared to placebo at 1 and 4 h post-dosing. Ramelteon and triazolam significantly increased subjective sleepiness compared to placebo at 1 h post-dosing. CONCLUSIONS: Ramelteon may affect road-tracking performance, visual attention and/or psychomotor speed measured by Trail-Making Test part A, and body balance in acute dosing. Lower dose of triazolam also impaired performance worse than ramelteon. Physicians should consider risks and benefits when prescribing both drugs, especially in the initial period of administration.

Cerebral oscillatory activity during simulated driving using MEG.

We aimed to examine cerebral oscillatory differences associated with psychological processes during simulated car driving. We recorded neuromagnetic signals in 14 healthy volunteers using magnetoencephalography (MEG) during simulated driving. MEG data were analyzed using synthetic aperture magnetometry to detect the spatial distribution of cerebral oscillations. Group effects between subjects were analyzed statistically using a non-parametric permutation test. Oscillatory differences were calculated by comparison between "passive viewing" and "active driving." "Passive viewing" was the baseline, and oscillatory differences during "active driving" showed an increase or decrease in comparison with a baseline. Power increase in the theta band was detected in the superior frontal gyrus (SFG) during active driving. Power decreases in the alpha, beta, and low gamma bands were detected in the right inferior parietal lobe (IPL), left postcentral gyrus (PoCG), middle temporal gyrus (MTG), and posterior cingulate gyrus (PCiG) during active driving. Power increase in the theta band in the SFG may play a role in attention. Power decrease in the right IPL may reflect selectively divided attention and visuospatial processing, whereas that in the left PoCG reflects sensorimotor activation related to driving manipulation. Power decreases in the MTG and PCiG may be associated with object recognition.

Effects of low-dose mirtazapine on driving performance in healthy volunteers.

OBJECTIVE: This study aimed to assess whether a lower initial dose of mirtazapine can lessen the harmful effect on driving performance or not in a double-blinded, placebo-controlled crossover trial. METHODS: Thirteen healthy men received 8 days of continuous nocturnal doses of mirtazapine at 7.5 mg or 15 mg, or placebo. At baseline and on days 2 and 9, subjects performed three driving tasks (road-tracking, car-following, and harsh-braking tasks) using a driving simulator and a Continuous Performance Test. Stanford Sleepiness Scale (SSS) scores were also assessed. In the mirtazapine 7.5 mg series, 15 mg of mirtazapine was additionally administered on day 9, followed by all the same assessments on day 10. RESULTS: Mirtazapine 7.5 mg had no significant effects on any tasks except for SSS compared with placebo. Mirtazapine 15 mg impaired road-tracking task and SSS. The increase in mirtazapine dose also had no significant effects on any tasks compared with those before dose increase. CONCLUSIONS: Mirtazapine 7.5 mg did not cause driving impairment compared with mirtazapine 15 mg, while both doses of mirtazapine produced subjective somnolence. The increase in mirtazapine had no detrimental effects on psychomotor performance. Initial low-dose mirtazapine may be safer for automobile driving than the normal starting dose.

Effects of repeated dosing with mirtazapine, trazodone, or placebo on driving performance and cognitive function in healthy volunteers.

OBJECTIVE: This study aimed to evaluate the effects of repeated treatments with the sedative antidepressants mirtazapine and trazodone on driving performance and cognitive function. METHODS: Nineteen healthy men received continuous nocturnal doses of 15-mg mirtazapine , 25-mg trazodone, or placebo for 8 days in a double-blinded, three-way crossover trial. Subjects were asked to perform three driving tasks (road tracking, car following, and harsh braking) using a driving simulator and cognitive tasks (the Wisconsin Card Sorting Test, Continuous Performance Test, and N-back Test) at baseline and on Days 2 and 9. Stanford Sleepiness Scale scores were also assessed. RESULTS: Mirtazapine significantly increased the standard deviation of lateral position in the road-tracking task as compared with trazodone on Day 2. Mirtazapine significantly increased Stanford Sleepiness Scale scores as compared with trazodone and placebo. For the remaining tasks, no significant effects of treatment were observed. CONCLUSIONS: Acute treatment of mirtazapine impaired road-tracking performance and increased sleepiness, but sedative effects disappeared under repeated administrations. Trazodone did not affect driving performance or cognitive function under acute or repeated administrations. Both initial sedative effects and pharmacological profiles should be taken into consideration when using sedative antidepressants.

Slower adaptation to driving simulator and simulator sickness in older adults.

BACKGROUND AND AIMS: Methods of assessing driving abilities in the elderly are urgently needed. Although the driving simulator (DS) appears to be a safe and cost-effective method of objectively evaluating driving performance, it may pose adaptation problems for elderly adults. In this study, we examined age-related adaptation deficits on the DS. METHODS: Healthy young adults (n=15) and healthy elderly persons (n=17) completed some neuropsychological tests, and then performed a road-tracking task with the DS, which was repeated four times (Trials 1-4). RESULTS: After simulated driving in DS, simulator sickness (SS) was observed in 18.8% of participants. The frequency of SS was 29.4% in elderly adults and 6.7% in young adults, and 17.6% of the elderly participants dropped out of the experiment. Performance on the Necker cube copying task was significantly correlated with the onset of SS. Driving performance also showed a significant interaction between group and trial, for both driving accuracy and vehicle speed. In addition, the performance of elderly adults significantly improved between trials 1 and 4, reaching a plateau in trial 4, whereas that of young adults did not change across trials. CONCLUSION: This study provides preliminary evidence of slower adaptation to a DS-based driving task by older adults, which was associated with cognitive aging. Age affected driving accuracy and velocity when a road-tracking task was simply repeated. It is concluded that the capacity of elderly people to adapt to DS environments should be taken into consideration when evaluating their performance on DS tasks.

Differential effects of diazepam, tandospirone, and paroxetine on plasma brain-derived neurotrophic factor level under mental stress.

OBJECTIVES: Serum brain-derived neurotrophic factor (BDNF) levels are reduced in depressed patients, and successful antidepressant treatment leads to increases in BDNF levels. However, little is known about how psychotropic drugs affect the mechanism of the human response to mental stress. We investigated the influence of psychotropic drugs on plasma BDNF levels under mental stress using a driving simulator (DS) task. METHODS: Fourteen healthy male volunteers received one of four drugs, diazepam (5 mg), tandospirone (20 mg), paroxetine (10 mg), and matched placebo, in a double-blind, crossover manner. Subjects were asked to perform the DS task 4 h post-dosing. Plasma BDNF levels were measured before and after the DS task. RESULTS: Plasma BDNF levels under the placebo, diazepam, and tandospirone conditions significantly decreased after the DS task compared with before the task. Conversely, no significant differences in plasma BDNF levels were detected under the paroxetine condition. CONCLUSION: As these three psychotropic drugs have differential effects on plasma BDNF levels under mental stress after 4 h post-dosing, antidepressants, unlike anxiolytics, might have a prompt positive effect on the mental stress response.

The effects of acute treatment with tandospirone, diazepam, and placebo on driving performance and cognitive function in healthy volunteers.

OBJECTIVE: To assess the effects of two anxiolytics, diazepam and tandospirone, on driving performance from methodological viewpoints taking frequent rear-end collisions into account. METHODS: In this double-blinded, three-way crossover trial, 18 healthy males received acute doses of 20 mg tandospirone (TSP), 5 mg diazepam (DZP), and placebo (PCB). The subjects were administered three driving tasks-road tracking, car following, and harsh braking-performed using a driving simulator and three cognitive tasks-Wisconsin Card Sorting Test, Continuous Performance Test, and N-back test-at baseline and at 1 and 4 h post-dosing. The Stanford Sleepiness Scale scores were also assessed. RESULTS: DZP nonsignificantly increased the percent change of brake reaction time (BRT) as compared to PCB at 4 h post-dosing. TSP nonsignificantly decreased the percent change of BRT as compared to PCB. Consequently, there was a significant difference in the percent change of BRT between DZP and TSP at 4 h post-dosing. For the remaining tasks, no statistically significant effects of treatment were observed. CONCLUSIONS: Acute doses of DZP significantly impaired the harsh-braking performance as compared to acute doses of TSP. These findings suggest that TSP may be used more safely in patients' driving activities.

Plasma amitriptyline level after acute administration, and driving performance in healthy volunteers.

AIMS: Amitriptyline triggers the impairment of cognitive and motor functions and has been confirmed to have harmful effects on driving performance. Although interindividual differences in plasma concentration may cause variations in driving performance, the relationship between plasma amitriptyline concentration and its effect on driving performance has not been completely elucidated. Thus, the aim of the present study was to assess the influence of individual pharmacokinetic differences on driving performance and cognitive functions. METHODS: In this double-blinded study, 17 healthy male volunteers were given an acute, single, 25-mg dose of amitriptyline. The subjects were assigned three driving simulator tasks, three cognitive tasks, and the questionnaire of the Stanford Sleepiness Scale at the baseline and at 4 h after dosing. The plasma amitriptyline concentrations were measured on high-performance liquid chromatography. RESULTS: A significant positive correlation was observed between the plasma amitriptyline concentration and road-tracking performance (r = 0.543, P < 0.05). There was no significant correlation between the plasma amitriptyline concentration and other driving performance, cognitive functions, and subjective somnolence. CONCLUSIONS: Amitriptyline produces a concentration-related impairment on road-tracking performance. Therapeutic monitoring of amitriptyline would be useful for predicting the difficulties involved while driving.

Functional segregation of the inferior frontal gyrus for syntactic processes: a functional magnetic-resonance imaging study.

We used functional magnetic resonance imaging in 18 normal volunteers to determine whether there is separate representation of syntactic, semantic, and verbal working memory processing in the left inferior frontal gyrus (GFi). We compared a sentence comprehension task with a short-term memory maintenance task to identify syntactic and semantic processing regions. To investigate the effects of syntactic and verbal working memory load while minimizing the differences in semantic processes, we used comprehension tasks with garden-path (GP) sentences, which require re-parsing, and non-garden-path (NGP) sentences. Compared with the short-term memory task, sentence comprehension activated the left GFi, including Brodmann areas (BAs) 44, 45, and 47, and the left superior temporal gyrus. In GP versus NGP sentences, there was greater activity in the left BAs 44, 45, and 46 extending to the left anterior insula, the pre-supplementary motor area, and the right cerebellum. In the left GFi, verbal working memory activity was located more dorsally (BA 44/45), semantic processing was located more ventrally (BA 47), and syntactic processing was located in between (BA 45). These findings indicate a close relationship between semantic and syntactic processes, and suggest that BA 45 might link verbal working memory and semantic processing via syntactic unification processes.

The effects of acute treatment with paroxetine, amitriptyline, and placebo on driving performance and cognitive function in healthy Japanese subjects: a double-blind crossover trial.

OBJECTIVE: To assess the effects of antidepressants on driving performance from a different methodological viewpoint in light of the recent traffic accidents. METHODS: In this double-blinded, 3-way crossover trial, 17 healthy males received acute doses of 10 mg paroxetine, 25 mg amitriptyline, and placebo. The subjects were administered three driving tasks--road tracking, car following, and harsh braking--performed using a driving simulator and three cognitive tasks--Wisconsin Card Sorting Test, Continuous Performance Test, and N-back test at baseline and at 1 h and 4 h post-dosing. The Stanford Sleepiness Scale scores were also assessed. RESULTS: At 4 h post-dosing, amitriptyline significantly impaired road-tracking and car-following performance, reduced driver vigilance, and caused subjective somnolence. Paroxetine impaired neither driving performance nor cognitive function. CONCLUSIONS: Acute doses of amitriptyline significantly impaired driving performance in the context of driving on crowded urban roads at relatively low speeds. This setting is important with respect to skills necessary for daily driving and may be difficult to measure in actual driving tests. This simulator-based study replicated the results of previous studies and could be considered complementary to them. This method may enable easy and safe screening of the driving hazard potential of drugs.

The neural substrates of driving at a safe distance: a functional MRI study.

An important driving skill is the ability to maintain a safe distance from a preceding car. To determine the neural substrates of this skill we performed functional magnetic resonance imaging of simulated driving in 21 subjects. Subjects used a joystick to adjust their own driving speed in order to maintain a constant distance from a preceding car traveling at varying speeds. The task activated multiple brain regions. Activation of the cerebellum may reflect visual feedback during smooth tracking of the preceding car. Co-activation of the basal ganglia, thalamus and premotor cortex is related to movement selection. Activation of a premotor-parietal network is related to visuo-motor co-ordination. Task performance was negatively correlated with anterior cingulate activity, consistent with the role of this region in error detection and response selection.