Acute neural effects of the mood stabiliser lamotrigine on emotional processing in healthy volunteers: a randomised control trial.

Lamotrigine is an effective mood stabiliser, largely used for the management and prevention of depression in bipolar disorder. The neuropsychological mechanisms by which lamotrigine acts to relieve symptoms as well as its neural effects on emotional processing remain unclear. The primary objective of this current study was to investigate the impact of an acute dose of lamotrigine on the neural response to a well-characterised fMRI task probing implicit emotional processing relevant to negative bias. 31 healthy participants were administered either a single dose of lamotrigine (300 mg, n = 14) or placebo (n = 17) in a randomized, double-blind design. Inside the 3 T MRI scanner, participants completed a covert emotional faces gender discrimination task. Brain activations showing significant group differences were identified using voxel-wise general linear model (GLM) nonparametric permutation testing, with threshold free cluster enhancement (TFCE) and a family wise error (FWE)-corrected cluster significance threshold of p < 0.05. Participants receiving lamotrigine were more accurate at identifying the gender of fearful (but not happy or angry) faces. A network of regions associated with emotional processing, including amygdala, insula, and the anterior cingulate cortex (ACC), was significantly less activated in the lamotrigine group compared to the placebo group across emotional facial expressions. A single dose of lamotrigine reduced activation in limbic areas in response to faces with both positive and negative expressions, suggesting a valence-independent effect. However, at a behavioural level lamotrigine appeared to reduce the distracting effect of fear on face discrimination. Such effects may be relevant to the mood stabilisation effects of lamotrigine.

Acute Angiotensin II Receptor Blockade Facilitates Parahippocampal Processing During Memory Encoding in High-Trait-Anxious Individuals.

Background: Angiotensin II receptor blockers (ARBs) have been associated with preventing posttraumatic stress disorder symptom development and improving memory. However, the underlying neural mechanisms are poorly understood. This study investigated ARB effects on memory encoding and hippocampal functioning that have previously been implicated in posttraumatic stress disorder development. Methods: In a double-blind randomized design, 40 high-trait-anxious participants (33 women) received the ARB losartan (50 mg) or placebo. At drug peak level, participants encoded images of animals and landscapes before undergoing functional magnetic resonance imaging, where they viewed the encoded familiar images and unseen novel images to be memorized and classified as animals/landscapes. Memory recognition was assessed 1 hour after functional magnetic resonance imaging. To analyze neural effects, whole-brain analysis, hippocampus region-of-interest analysis, and exploratory multivariate pattern similarity analysis were employed. Results: ARBs facilitated parahippocampal processing. In the whole-brain analysis, losartan enhanced brain activity for familiar images in the parahippocampal gyrus (PHC), anterior cingulate cortex, and caudate. For novel images, losartan enhanced brain activity in the PHC only. Pattern similarity analysis showed that losartan increased neural stability in the PHC when processing novel and familiar images. However, there were no drug effects on memory recognition or hippocampal activation. Conclusions: Given that the hippocampus receives major input from the PHC, our findings suggest that ARBs may modulate higher-order visual processing through parahippocampal involvement, potentially preserving intact memory input. Future research needs to directly investigate whether this effect may underlie the preventive effects of ARBs in the development of posttraumatic stress disorder.

Pramipexole Enhances Reward Learning by Preserving Value Estimates.

BACKGROUND: Dopamine D2-like agonists show promise as treatments for depression. They are thought to act by enhancing reward learning; however, the mechanisms by which they achieve this are not clear. Reinforcement learning accounts describe 3 distinct candidate mechanisms: increased reward sensitivity, increased inverse decision-temperature, and decreased value decay. As these mechanisms produce equivalent effects on behavior, arbitrating between them requires measurement of how expectations and prediction errors are altered. We characterized the effects of 2 weeks of the D2-like agonist pramipexole on reward learning and used functional magnetic resonance imaging measures of expectation and prediction error to assess which of these 3 mechanistic processes were responsible for the behavioral effects. METHODS: Forty healthy volunteers (50% female) were randomized to 2 weeks of pramipexole (titrated to 1 mg/day) or placebo in a double-blind, between-subject design. Participants completed a probabilistic instrumental learning task before and after the pharmacological intervention, with functional magnetic resonance imaging data collected at the second visit. Asymptotic choice accuracy and a reinforcement learning model were used to assess reward learning. RESULTS: Pramipexole increased choice accuracy in the reward condition with no effect on losses. Participants who received pramipexole had increased blood oxygen level-dependent response in the orbital frontal cortex during the expectation of win trials but decreased blood oxygen level-dependent response to reward prediction errors in the ventromedial prefrontal cortex. This pattern of results indicates that pramipexole enhances choice accuracy by reducing the decay of estimated values during reward learning. CONCLUSIONS: The D2-like receptor agonist pramipexole enhances reward learning by preserving learned values. This is a plausible mechanism for pramipexole's antidepressant effect.

Trust in automated vehicles: constructs, psychological processes, and assessment.

There is a growing body of research on trust in driving automation systems. In this paper, we seek to clarify the way trust is conceptualized, calibrated and measured taking into account issues related to specific levels of driving automation. We find that: (1) experience plays a vital role in trust calibration; (2) experience should be measured not just in terms of distance traveled, but in terms of the range of situations encountered; (3) system malfunctions and recovery from such malfunctions is a fundamental part of this experience. We summarize our findings in a framework describing the dynamics of trust calibration. We observe that methods used to quantify trust often lack objectivity, reliability, and validity, and propose a set of recommendations for researchers seeking to select suitable trust measures for their studies. In conclusion, we argue that the safe deployment of current and future automated vehicles depends on drivers developing appropriate levels of trust. Given the potentially severe consequences of miscalibrated trust, it is essential that drivers incorporate the possibility of new and unexpected driving situations in their mental models of system capabilities. It is vitally important that we develop methods that contribute to this goal.

Effect of lithium administration on brain activity under an emotion regulation paradigm in healthy participants: a functional magnetic resonance imaging study.

RATIONALE: Emotion regulation (ER) difficulties have been previously described in bipolar disorder (BD). Whilst lithium has been shown to be effective in the treatment of BD, the mechanisms underlying lithium's effect on mood stabilisation remain unclear. OBJECTIVES: Unravelling lithium's effect on psychological processes impaired in BD, such as ER, could address this translational gap and inform the development of new treatments. METHODS: This study investigated the neural effects of lithium (800mg) on ER in 33 healthy volunteers in a double-blind between-groups design, randomised to lithium (n=17) or placebo (n=16) for 11 days. At treatment completion, participants underwent 3-Tesla fMRI scan whilst performing an ER task. RESULTS: Reappraisal reduced negative affect across groups and led to the expected increase in frontal brain activity. Participants receiving lithium showed (1) decreased activation in prefrontal and posterior parietal cortices and connectivity between the fronto-limbic network (Z>2.3, p<0.05 corrected); and (2) increased activity in the right superior temporal gyrus (Z>3.1, p<0.05 corrected) and connectivity between the right medial temporal gyrus (MTG) and left middle frontal gyrus (Z>2.3, p<0.05 corrected) during reappraisal. Further effects of lithium were found in response to negative picture presentation, whereby an anticorrelation was found between the left amygdala and the frontal cortex, and greater connectivity between the right MTG and the bilateral medial prefrontal cortex extending into the paracingulate gyrus, compared to placebo (Z>2.3, p < 0.05 corrected). CONCLUSIONS: These results show a potential effect of lithium on ER through its effects on activity and connectivity, and further elaborate the neural underpinnings of cognitive reappraisal. Future work should investigate longer term effects of lithium on ER in BD, ultimately benefitting the development of novel and more effective treatments.

5-HT4 Receptor Agonist Effects on Functional Connectivity in the Human Brain: Implications for Procognitive Action.

BACKGROUND: Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary mood symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT4 receptor agonists show promise as potential procognitive agents in animal and early human translational studies. Optimal cognitive performance in humans is directly associated with appropriate functional connectivity between specific resting-state neural networks. However, so far the effect of 5-HT4 receptor agonism on resting-state functional connectivity (rsFC) in the brain in humans is unknown. METHODS: We collected resting-state functional magnetic resonance imaging scans from 50 healthy volunteers, of whom 25 received 6 days × 1 mg prucalopride (a highly selective 5-HT4 receptor agonist) and 25 received placebo in a randomized double-blind design. RESULTS: Network analyses identified that participants in the prucalopride group had enhanced rsFC between the central executive network and the posterior/anterior cingulate cortex. Seed analyses also showed greater rsFC between the left and right rostral anterior cingulate cortex and the left lateral occipital cortex, and reduced rsFC between the hippocampus and other default mode network regions. CONCLUSIONS: Similar to other potentially procognitive medications, low-dose prucalopride in healthy volunteers appeared to enhance rsFC between regions involved in cognitive networks and reduce rsFC within the default mode network. This suggests a mechanism for the behavioral cognitive enhancement previously seen with 5-HT4 receptor agonists in humans and supports the potential for 5-HT4 receptor agonists to be used in clinical psychiatric populations.

The Effect of the 5-HT4 Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain.

Depression is a common and often recurrent illness with significant negative impact on a global scale. Current antidepressants are ineffective for up to one third of people with depression, many of whom experience persistent symptomatology. 5-HT4 receptor agonists show promise in both animal models of depression and cognitive deficit. We therefore studied the effect of the 5-HT4 partial agonist prucalopride (1 mg daily for 6 days) on the neural processing of emotional faces in 43 healthy participants using a randomised placebo-controlled design. Participants receiving prucalopride were more accurate at identifying the gender of emotional faces. In whole brain analyses, prucalopride was also associated with reduced activation in a network of regions corresponding to the default mode network. However, there was no evidence that prucalopride treatment produced a positive bias in the neural processing of emotional faces. Our study provides further support for a pro-cognitive effect of 5-HT4 receptor agonism in humans. While our current behavioural and neural investigations do not suggest an antidepressant-like profile of prucalopride in humans, it will be important to study a wider dose range in future studies.

Catechol-O-methyltransferase activity does not influence emotional processing in men.

BACKGROUND: Catechol-O-methyltransferase (COMT) regulates cortical dopaminergic transmission and prefrontal-dependent cognitive function. However, its role in other cognitive processes, including emotional processing, is relatively unexplored. We therefore investigated the separate and interactive influences of COMT inhibition and Val158Met (rs4680) genotype on performance on an emotional test battery. METHODS: We recruited 74 healthy men homozygous for the functional COMT Val158Met polymorphism. Volunteers were administered either a single 200 mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a double-blind, randomised manner. Emotional processing was assessed using the emotional test battery, and mood was rated using visual analogue scales and the Profile of Mood States (POMS) questionnaire across the test day. RESULTS: There were no main or interactive effects of Val158Met genotype or tolcapone on any of the emotional processing measures or mood ratings. CONCLUSIONS: Our findings suggest that, at least in healthy adult men, COMT has little or no effect on emotional processing or mood. These findings contrast with several neuroimaging studies that suggest that COMT modulates neural activity during emotional processing. Thus, further studies are required to understand how COMT impacts on the relationship between behavioural output and neural activity during emotional processing. Nevertheless, our data suggest that novel COMT inhibitors under development for treating cognitive dysfunction are unlikely to have acute off target effects on emotional behaviours.

Resting state functional connectivity patterns as biomarkers of treatment response to escitalopram in patients with major depressive disorder.

RATIONAL: With no available response biomarkers, matching an appropriate antidepressant to an individual can be a lengthy process. Improving understanding of processes underlying treatment responsivity in depression is crucial for facilitating work on response biomarkers. OBJECTIVES: To identify differences in patterns of pre-treatment resting-state functional connectivity (rsFC) that may underlie response to antidepressant treatment. METHODS: After a baseline MRI scan, thirty-four drug-free patients with depression were treated with an SSRI escitalopram 10 mg daily for 6 weeks; response was defined as ≥ 50% decrease in Hamilton Depression Rating Scale (HAMD) score. Thirty-one healthy controls had a baseline clinical assessment and scan. Healthy participants did not receive treatment. RESULTS: Twenty-one (62%) of patients responded to escitalopram. Treatment responsivity was associated with enhanced rsFC of the right fronto-parietal network (FPN)-with the posterior DMN, somatomotor network (SMN) and somatosensory association cortex. The lack of treatment response was characterized by reduced rsFC: of the bilateral FPN with the contralateral SMN, of the right FPN with the posterior DMN, and of the extended sensorimotor auditory area with the inferior parietal lobule (IPL) and posterior DMN. Reduced rsFC of the posterior DMN with IPL was seen in treatment responders, although only when compared with HC. CONCLUSIONS: The study supports the role of resting-state networks in response to antidepressant treatment, and in particular the central role of the frontoparietal and default mode networks.

The effects of atorvastatin on emotional processing, reward learning, verbal memory and inflammation in healthy volunteers: An experimental medicine study.

BACKGROUND: Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored. AIMS: In this experimental medicine trial, we investigated the 7-day effects of the lipophilic statin, atorvastatin on a battery of neuropsychological tests and inflammation in healthy volunteers. METHODS: Fifty healthy volunteers were randomised to either 7 days of atorvastatin 20 mg or placebo in a double-blind design. Participants were assessed with psychological questionnaires and a battery of well-validated behavioural tasks assessing emotional processing, which is sensitive to putative antidepressant effects, reward learning and verbal memory, as well as the inflammatory marker, C-reactive protein. RESULTS: Compared to placebo, 7-day atorvastatin increased the recognition (p = 0.006), discriminability (p = 0.03) and misclassifications (p = 0.04) of fearful facial expression, independently from subjective states of mood and anxiety, and C-reactive protein levels. Otherwise, atorvastatin did not significantly affect any other psychological and behavioural measure, nor peripheral C-reactive protein. CONCLUSIONS: Our results reveal for the first time the early influence of atorvastatin on emotional cognition by increasing the processing of anxiety-related stimuli (i.e. increased recognition, discriminability and misclassifications of fearful facial expression) in healthy volunteers, in the absence of more general effects on negative affective bias. Further studies exploring the effects of statins in depressed patients, especially with raised inflammatory markers, may clarify this finding and inform future clinical trials.

Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task.

Cognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT4 receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT4 receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating these effects to humans. We tested whether short-term administration of the 5-HT4 partial agonist, prucalopride, modified behavioural and neural (fMRI) memory processing in 44 healthy human volunteers using an experimental medicine model. We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images. At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo. Taken together, these findings demonstrate the potential of 5-HT4-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment.

An Experimental Medicine Investigation of the Effects of Subacute Pramipexole Treatment on Emotional Information Processing in Healthy Volunteers.

Treatment with the dopamine D2/D3 receptor agonist pramipexole has demonstrated promising clinical effects in patients with depression. However, the mechanisms through which pramipexole might alleviate depressive symptoms are currently not well understood. Conventional antidepressant drugs are thought to work by biasing the processing of emotional information in favour of positive relative to negative appraisal. In this study, we used an established experimental medicine assay to explore whether pramipexole treatment might have a similar effect. Employing a double-blind, parallel-group design, 40 healthy volunteers (aged 18 to 43 years, 50% female) were randomly allocated to 12 to 15 days of treatment with either pramipexole (at a peak daily dose of 1.0 mg pramipexole salt) or placebo. After treatment was established, emotional information processing was assessed on the neural level by measuring amygdala activity in response to positive and negative facial emotional expressions, using functional magnetic resonance imaging (MRI). In addition, behavioural measures of emotional information processing were collected at baseline and on drug, using an established computerized task battery, tapping into different cognitive domains. As predicted, pramipexole-treated participants, compared to those receiving placebo, showed decreased neural activity in response to negative (fearful) vs. positive (happy) facial expressions in bilateral amygdala. Contrary to our predictions, however, pramipexole treatment had no significant antidepressant-like effect on behavioural measures of emotional processing. This study provides the first experimental evidence that subacute pramipexole treatment in healthy volunteers modifies neural responses to emotional information in a manner that resembles the effects of conventional antidepressant drugs.

Functional Connectivity between Task-Positive Networks and the Left Precuneus as a Biomarker of Response to Lamotrigine in Bipolar Depression: A Pilot Study.

Treatment of bipolar depression poses a significant clinical challenge. Lamotrigine is one of a few efficacious drugs, however, it needs to be titrated very slowly and response can only be assessed after 10-12 weeks. With only a proportion of patients responding, an exploration of factors underlying treatment responsivity is of paramount clinical importance, as it may lead to an allocation of the drug to those most likely to respond to it. This study aimed at identifying differences in patterns of pre-treatment resting state functional connectivity (rsFC) that may underlie response to lamotrigine in bipolar depression. After a baseline MRI scan, twenty-one patients with bipolar depression were treated with lamotrigine in an open-label design; response, defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score, was assessed after 10-12 weeks of treatment. Twenty healthy controls had a baseline clinical assessment and scan but did not receive any treatment. Fifteen out of 21 (71%) patients responded to lamotrigine. Treatment responsivity was associated with enhanced pre-treatment rsFC of the right fronto-parietal network (FPN) and dorsal attention network (DAN) with left precuneus. The lack of treatment response was additionally characterised by reduced rsFC: of the DAN with right middle temporal gyrus; of the default mode network (DMN) with left precuneus; of the extended sensory-motor area with areas including the left hippocampus/left amygdala and left subcallosal cortex/nucleus accumbens; and of the left FPN with left inferior temporal gyrus/occipital fusiform gyrus/lateral occipital cortex. The results suggest that preserved rsFC between the FPN and DAN, the networks involved in cognitive control, and the hub of the posterior DMN, the left precuneus, may be critical for good response to lamotrigine as an add-on treatment in patients with bipolar depression. The study also suggests a more general decrease in rsFC to be related to poor treatment responsivity.

Statins for major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The burden of depressive disorder is large and new treatment approaches are required. Repurposing widely available drugs such as statins may be a time- and cost-effective solution. Statins have anti-inflammatory and anti-oxidant properties which have been shown to be relevant to the pathophysiology of depression. This study assesses the efficacy, acceptability, tolerability, and safety of statins in major depressive disorder. METHODS: Our study is an update and extension of a previous meta-analysis published in 2016 by Salagre et al. We performed a systematic review (PubMed/MEDLINE, Cochrane CENTRAL, ISI Web of Science, CINAHL, and ClinicalTrials.gov until the 1st September 2020) and meta-analysis of randomized controlled trials using any statin against placebo or any other statin in the treatment of major depressive disorder. Our primary efficacy outcome measure was the mean value on any standardized scale for depressive symptoms at 8 weeks of treatment. We also calculated outcomes for efficacy, response, and remission at 2, 4, and 12 weeks, as well as acceptability (dropouts for any cause), tolerability (dropouts due to any adverse event), and safety (any adverse event) outcomes at the studies' endpoints. Furthermore, we conducted an exploratory network meta-analysis for the primary efficacy outcome to identify potential differences between statins. RESULTS: We retrieved five randomized controlled trials meeting our inclusion criteria: four used a statin in addition to an antidepressant and compared it to placebo plus antidepressant, and one compared two statins alone. and one comparing one statin with another. Statins compared to placebo in addition to antidepressants were efficacious at 8 weeks (N = 255, SMD = -0.48, 95% CI = -0.74 to -0. 22) and 12 weeks (N = 134, SMD = -0.47, 95% CI = -0.89 to -0.05, moderate certainty) with no difference for acceptability, tolerability, and safety (low certainty). An exploratory network meta-analysis suggested that the most lipophilic statins, especially simvastatin, could be more efficacious than less lipophilic or hydrophilic molecules. CONCLUSIONS: This systematic review suggests the efficacy, acceptability, tolerability, and safety of statins in addition to antidepressants in patients with major depressive disorder. Further clinical trials in different settings are required to test this result. TRIAL RGISTRATION: PROSPERO registration: CRD42020170938.

It feels real: physiological responses to a stressful virtual reality environment and its impact on working memory.

BACKGROUND: Virtual reality (VR) is increasingly used to study and treat psychiatric disorders. Its fidelity depends in part on the extent to which the VR environment provides a convincing simulation, for example whether a putatively stressful VR situation actually produces a stress response. METHODS: We studied the stress response in 28 healthy men exposed either to a stressor VR elevator (which simulated travelling up the outside of a tall building and culminated in the participant being asked to step off the elevator platform), or to a control elevator. We measured psychological and physiological (salivary cortisol and alpha-amylase, blood pressure, pulse, skin conductance) stress indices. We also measured subsequent performance on the N-back task because acute stress has been reported to impact on working memory. RESULTS: Compared to participants in the control elevator, those in the external elevator had increases in skin conductance, pulse and subjective stress and anxiety ratings, altered heart rate variability, and a delayed rise in cortisol. N-back performance was unaffected. CONCLUSIONS: A putatively stressful VR elevator produces a physiological as well as a psychological stress response, supporting its use in the investigation and treatment of stress-related disorders, and its potential value as an experimental laboratory stressor.

Landmark Agnosia: Evaluating the Definition of Landmark-based Navigation Impairment.

OBJECTIVE: Landmark agnosia is a rare type of navigation impairment, for which various definitions have been presented. From a clinical as well as theoretical perspective, consensus on the characteristics of landmark agnosia would be valuable. In the current study we review the literature concerning landmark agnosia and present a new case study. Existing literature highlights the importance of examining familiar as well as novel landmark processing and substantial variation in performance patterns of individual patients. METHOD: We performed a case study with patient KS, a 53-year-old male, suffering from landmark agnosia, making use of elaborate neuropsychological screening and virtual reality-based tests of navigation ability. RESULTS: Our extensive examination of his impairment shows that landmark agnosia can be very narrow; in KS it is restricted to recognition of newly learned landmarks only. Also, he has no trouble recognizing familiar landmarks that are not part of a navigated route. CONCLUSIONS: The literature review shows that the right temporal lobe, and the right hippocampus in particular are the main lesion sites for landmark agnosia. Furthermore, our case study substantiates that this disorder can occur for both familiar and novel landmarks, and can affect novel landmarks in isolation from familiar landmarks. Moreover, it can occur in isolation from problems with processing route information.

Drowsy drivers' under-performance in lateral control: How much is too much? Using an integrated measure of lateral control to quantify safe lateral driving.

Internationally, drowsy driving is associated with around 20% of all crashes. Despite the development of different detection methods, driver drowsiness remains a disconcerting public health issue. Detection methods can estimate drowsiness by directly measuring the physiology of the driver, or they can measure the effect that drowsiness has on the state of the vehicle due to the behavioural changes that drowsiness elicits in the driver. The latter has the benefit that it could measure the net effect that drowsiness has on driving performance which links to the actual safety risk. Fusing multiple sources of driving performance indicators like lane position and steering wheel metrics in order to detect drowsiness has recently gained increased attention. However, not much research has been conducted with regard to using integrated measures to detect increased drowsiness within an individual driver. Different levels of drowsiness are also rarely classified in terms of safe or unsafe. In the present study, we attempt to slowly induce drowsiness using a monotonous driving task in a simulator, and fuse lane position and steering wheel angle data into a single measure for lateral control performance. We argue that this measure is applicable in real-time detection systems, and quantitatively link it to different levels of drowsiness by validating it to two established drowsiness metrics (KSS and PERCLOS). Using level of drowsiness as a surrogate for safety we are then able to set simple criteria for safe and unsafe lateral control performance, based on individual driving behaviour.

Supporting driver headway choice: the effects of discrete headway feedback when following headway instructions.

With specific headway instructions drivers are not able to attain the exact headways as instructed. In this study, the effects of discrete headway feedback (and the direction of headway adjustment) on headway accuracy for drivers carrying out time headway instructions were assessed experimentally. Two groups of each 10 participants (one receiving headway feedback; one control) carried out headway instructions in a driving simulator; increasing and decreasing their headway to a target headway of 2 s at speeds of 50, 80, and 100 km/h. The difference between the instructed and chosen headway was a measure for headway accuracy. The feedback group heard a sound signal at the moment that they crossed the distance of the instructed headway. Unsupported participants showed no significant difference in headway accuracy when increasing or decreasing headways. Discrete headway feedback had varying effects on headway choice accuracy. When participants decreased their headway, feedback led to higher accuracy. When increasing their headway, feedback led to a lower accuracy, compared to no headway feedback. Support did not affect driver's performance in maintaining the chosen headway. The present results suggest that (a) in its current form discrete headway feedback is not sufficient to improve the overall accuracy of chosen headways when carrying out headway instructions; (b) the effect of discrete headway feedback depends on the direction of headway adjustment.

Effects of dexamphetamine with and without alcohol on simulated driving.

RATIONALE: In party circuits dexamphetamine is frequently used in combination with alcohol. It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol, but may potentiate risk-taking behaviour. OBJECTIVES: The study was aimed at assessing the effects of alcohol, dexamphetamine and the combination of both on simulated driving and cognitive performance. METHOD: Eighteen subjects participated in a randomized, crossover, placebo-controlled study employing four conditions: 10 mg dexamphetamine, 0.8 g/kg alcohol, 10 mg dexamphetamine + 0.8 g/kg alcohol, and placebo. Fundamental driving skills and risk-taking behaviour were assessed in a driving simulator. Subjects also completed vigilance and divided attention tasks, and subjective ratings. RESULTS: Mean BAC levels during simulated driving were between 0.91‰ and 0.64‰. Subjects using alcohol showed a significantly larger mean standard deviation of lateral position and shorter accepted gap time and distance. Use of alcohol or dexamphetamine + alcohol was associated with a higher frequency of red light running and collisions than the dexamphetamine or placebo conditions. Performance of vigilance and divided attention tasks was significantly impaired in the alcohol condition and, to a lesser degree, in the dexamphetamine + alcohol condition. CONCLUSION: Single doses of 0.8 g/kg alcohol increased risk-taking behaviours and impaired tracking, attention and reaction time during a 3-h period after drinking when BACs declined from 0.9 to 0.2 mg/ml. The stimulatory effects of co-administration of dexamphetamine 10 mg were not sufficient to overcome the impairing effects of alcohol on skills related to driving.

Stimuli fixation and manual response as a function of expectancies.

Two experiments investigated effects of expectations on eye fixations and responses to expected and unexpected information in a laboratory setting. Stimulus fixation and manual responses to predefined targets among distractors were measured in a dynamic environment shown on a monitor. Participants were part of either a predictable condition (predictable sequence of targets and distractors) or a random condition. In the predictable condition, participants fixated expected distractors less than targets, with similar fixation times in the random condition. Responses to targets were faster in the predictable condition than in the random condition. Irregularities were either missed or responses were slow. This indicates that incorrect expectations may have negative consequences, with practical implications for skill-based tasks such as operator monitoring and driving. Actual or potential applications of this research include introducing operator support for tasks in which the risk of missing unexpected information or of slow responses may be dramatic.