Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials.

BACKGROUND: In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. AIM: To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. METHODS: 497 women (21-70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). OUTCOMES: The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. RESULTS: In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57-2.84, P = .004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44-3.45, P = .012; T: Δ = 1.69, 95% CI = 0.58-2.80, P = .003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17-1.82, P = .019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57-2.46, P = .002; T: Δ = 0.98, 95% CI = 0.17-1.78, P = .018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). CLINICAL IMPLICATIONS: T + S and T + B are promising treatments for women with FSIAD. STRENGTHS AND LIMITATIONS: The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. CONCLUSIONS: T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201-216.

The effect of attenuating noradrenergic neurotransmission by clonidine on brain activity measures of visuospatial attention.

OBJECTIVE: In the current study, we investigated the role of noradrenaline in directing (bias) and disengagement of visuospatial attention. METHODS: We assessed the effect of clonidine on event-related brain potential (ERP) reflections of bias and disengagement in a double-blind placebo-controlled crossover design. An initial dose of 200-µg clonidine was replaced by 100 µg because of marked side effects. Twenty-one healthy male participants performed the visual-spatial cueing task while an electroencephalogram (EEG) was recorded. The behavioral output is the validity effect (benefit of cueing in terms of reaction time to targets). ERP indices for bias were the cue-related early directing attention negativity and late directing attention positivity, and the target-elicited P1 and N1 modulations by validity ('validity-effect'). The ERP index for disengagement was the target-elicited 'late positive deflection' modulation by validity. Behavioral analyses were performed on 16 participants, electrophysiological analyses on a subset (n=9). RESULTS: Clonidine attenuated the N1 effect, albeit in a subsample. Neither cue-elicited ERPs nor the behavioral validity effect were affected. Clonidine-induced blood pressure reduction was correlated with the reduction of the late positive deflection effect under clonidine. CONCLUSION: Clonidine attenuated the result of bias in a subsample and may have a modulating effect on disengagement.

Healthcare utilization patterns of individuals with depression after national policy to increase the mental health workforce in primary care: a data linkage study.

BACKGROUND: The deployment of the mental health nurse, an additional healthcare provider for individuals in need of mental healthcare in Dutch general practices, was expected to substitute treatments from general practitioners and providers in basic and specialized mental healthcare (psychologists, psychotherapists, psychiatrists, etc.). The goal of this study was to investigate the extent to which the degree of mental health nurse deployment in general practices is associated with healthcare utilization patterns of individuals with depression. METHODS: We combined national health insurers' claims data with electronic health records from general practices. Healthcare utilization patterns of individuals with depression between 2014 and 2019 (N = 31,873) were analysed. The changes in the proportion of individuals treated after depression onset were assessed in association with the degree of mental health nurse deployment in general practices. RESULTS: The proportion of individuals with depression treated by the GP, in basic and specialized mental healthcare was lower in individuals in practices with high mental health nurse deployment. While the association between mental health nurse deployment and consultation in basic mental healthcare was smaller for individuals who depleted their deductibles, the association was still significant. Treatment volume of general practitioners was also lower in practices with higher levels of mental health nurse deployment. CONCLUSION: Individuals receiving care at a general practice with a higher degree of mental health nurse deployment have lower odds of being treated by mental healthcare providers in other healthcare settings. More research is needed to evaluate to what extent substitution of care from specialized mental healthcare towards general practices might be associated with waiting times for specialized mental healthcare.

Cannabinoid modulations of resting state EEG θ power and working memory are correlated in humans.

Object representations in working memory depend on neural firing that is phase-locked to oscillations in the theta band (4-8 Hz). Cannabis intake disrupts synchronicity of theta oscillations and interferes with memory performance. Sixteen participants smoked cigarettes containing 0.0, 29.3, 49.1, or 69.4 mg Delta(9)-tetrahydrocannabinol (THC) in a randomized crossover design and performed working memory and general attention tasks. Dose-dependent effects of THC were observed for resting state EEG theta and beta power, working memory (per-item search time), and attentional performance (percent errors and RT). The THC effects on EEG theta power and memory performance were correlated, whereas other EEG and behavioral effects were not. These findings confirm and extend previous results in rodents and humans, and corroborate a neurocomputational model that postulates that temporal aspects of information processing in working memory depend causally on nested oscillations in the theta and gamma (>30 Hz) bands.

Neural correlates of stopping and self-reported impulsivity.

OBJECTIVE: To examine the relation between self-reported impulsivity, inhibitory control, and the neural correlates of stopping performance within the normal population. METHODS: Healthy individuals scoring high and low on trait impulsivity performed an auditory stop-signal task. Stopping performance and neural correlates of stopping (i.e. N1 and stop P3) were compared between the impulsive groups as well as between participants who were slow and fast in stopping. RESULTS: As expected, N1 and stop P3 were larger for successful relative to failed stops (i.e. N1 and stop P3 effects). Participants scoring high relative to low on impulsivity showed equal stopping performance, had larger stop P3, but similar N1 effects. Slow as compared to fast stoppers had reduced stop P3, but similar N1 effects. CONCLUSIONS: Participants scoring high relative to low on impulsivity may need more effortful inhibitory control to yield equal stopping performance. Slow relative to fast stoppers may have weaker inhibition processes and abnormal error processing. In contrast to ADHD, both high impulsives as well as slow stoppers had an intact N1 effect. SIGNIFICANCE: Subjective impulsivity and slow stopping in healthy individuals cannot be generalized to ADHD.

Haloperidol 2 mg impairs inhibition but not visuospatial attention.

RATIONALE: The dopaminergic system has been implicated in visuospatial attention and inhibition, but the exact role has yet to be elucidated. Scarce literature suggests that attenuation of dopaminergic neurotransmission negatively affects attentional focusing and inhibition. To the best of our knowledge, this is the first study that evaluated the effect of dopaminergic antagonism on stopping performance. METHODS: Dopaminergic neurotransmission was attenuated in 28 healthy male participants by using 2 mg haloperidol. A repeated-measures placebo-controlled crossover design was implemented, and performance indices of attention and inhibition were assessed in the visual spatial cueing task (VSC) and stop signal task (SST). Additionally, the effect of haloperidol on motoric parameters was assessed. It was expected that haloperidol as contrasted to placebo would result in a reduction of the "validity effect," the benefit of valid cueing as opposed to invalid cueing of a target in terms of reaction time. Furthermore, an increase in stop signal reaction time (SSRT) in the SST was expected. RESULTS AND CONCLUSION: Results partially confirmed the hypothesis. Haloperidol negatively affected inhibitory motor control in the SST as indexed by SSRT, but there were no indications that haloperidol affected bias or disengagement in the VSC task as indicated by a lack of an effect on RTs. Pertaining to secondary parameters, motor activity increased significantly under haloperidol. Haloperidol negatively affected reaction time variability and errors in both tasks, as well as omissions in the SST, indicating a decreased sustained attention, an increase in premature responses, and an increase in lapses of attention, respectively.

Electrocortical correlates of control of selective attention to spatial frequency.

In the present study, we investigated control of selective attention to spatial frequency patterns, using a cueing paradigm. Subjects either used the instruction embedded in a word cue to prepare for the upcoming test stimulus (transient attention condition) or used the instruction they received before a block of trials (sustained reference condition), under completely similar stimulus conditions. The pattern of differential cue responses between these two conditions, reflecting top-down attentional control processes, was different between two groups of subjects, effectively canceling each other out. Despite comparable behavioral performance on both cues and targets, one group (n = 4) elicited a fronto-central-parietal positivity, starting 500 ms postcue over frontal and prefrontal areas, later including more central and posterior scalp sites, whereas another group (n = 8) started 400 ms postcue over central sites with a negativity, growing in strength over time and stabilizing over fronto-central sites. Only the group of eight subjects showed some evidence of occipital pretarget biasing activity. Independent of group, source modeling of the attentional control activity showed that attentional control was initiated in anterior, not posterior, parts of the brain. Furthermore, different underlying sources were found for both groups, in addition to signs of differential processing of target stimuli. Possible individual differences in attentional control ability and its relation to usage of different brain areas to deal with the task demands are discussed in more detail.

Prepulse inhibition and P50 suppression: commonalities and dissociations.

Patients with schizophrenia exhibit reduced levels of both prepulse inhibition of the startle reflex (PPI) and condition-test suppression of the P50 event-related potential. This study investigated the extent to which PPI and P50 suppression, which exhibit similar parametric sensitivities, are intrinsically auditory phenomena or can be induced cross-modally, and reflect common or distinct neural mechanisms of inhibition. PPI, N100, and P50 were assessed in 20 healthy male volunteers, using auditory test probes and both visual and auditory lead stimuli, separated by 100- or 500-ms interstimulus intervals (ISIs). PPI was found in the auditory-lead condition across the complete group, and with visual-lead stimuli in approximately half of the subjects. Intra-modal auditory PPI was significantly higher with the 100-ms ISI than with the 500-ms ISI. P50 suppression was found only with the 500-ms ISI, with no difference between the auditory and visual conditions. Source analyses revealed that suppression was associated with frontal cortical activity. N100 suppression was found only in the auditory condition, with no difference between 100- and 500-ms ISIs. Although both phenomena are considered to provide operational measures of gating, PPI and P50 suppression are differentially sensitive to ISI and therefore reflect partly different neural mechanisms. They are not intrinsically auditory phenomena, and both appear to involve frontal cortical activity. In contrast, N100 suppression is most likely based on refractory mechanisms intrinsic to the auditory system.

Chronic effects of social drinking in a card-sorting task: an event related potential study.

OBJECTIVE: The Wisconsin Card Sorting Task (WCST) is one of the most widely used neuropsychological tests of frontal lobe function, which is thought to be affected by regular alcohol use. The present study used a computer-adapted version of the WCST to assess the effects of chronic alcohol consumption on the brain. METHODS: Participants (N=59) sorted cards according to an initially unknown sorting rule, which referred to shape, number, or color. The correctness of the chosen sorting rule was indicated by a feedback stimulus. This correct sorting rule had to be followed for a number of stimuli, and when it changed participants had to find out which rule had to be followed next. A distinction was made between early (correct sorting rule is unknown) and late trials (correct sorting rule is known and applied). To measure brain activity related during the task event related potentials (ERPs) were recorded to the target and feedback stimulus in light (N=14), moderate (N=16) and heavy (N=19) social drinkers and excessive alcohol users (N=10). RESULTS: No differences in number of series completed or the reaction time in each trial, were found between the four groups. In contrast, a mid-frontal N1 component in reaction to the feedback stimuli did reveal differences between the four groups. In the light and moderate drinkers, on early feedback trials the N1 was larger relative to late feedback trials, but this effect was absent in the heavy social drinkers and excessive drinkers. CONCLUSIONS: The reduced N1 effect with increasing alcohol intake could reflect abnormal allocation of attention or impaired conflict monitoring, possibly based on activity in the anterior cingulate cortex. SIGNIFICANCE: Heavy social drinking and excessive drinking leads to changes in the mid-frontal N1 during feedback trials of the WCST.

Sources of auditory selective attention and the effects of methylphenidate in children with attention-deficit/hyperactivity disorder.

BACKGROUND: The aim of this study was to determine 1) whether abnormal auditory selective attention in children with attention-deficit/hyperactivity disorder (ADHD), as reflected in the processing negativity (PN) of the event-related potential, is related to impaired frontal functioning; and 2) how methylphenidate (MPh) affects attentional functioning in ADHD. METHODS: Sources of electrical brain activity were estimated in healthy control children, in ADHD children without medication, and in children with ADHD during a placebo-controlled medication trial involving MPh. RESULTS: The source models showed that the PN is generated in the auditory cortex. Children with ADHD showed less activity related to selective attention in this brain region. Administration of MPh resulted in more frontally located sources. CONCLUSIONS: The results showed no evidence for an important role of the frontal cortex in abnormalities in selective attention in children with ADHD. Also, the data did not indicate that MPh normalizes brain activity in these children.

Benzodiazepines have no effect on fear-potentiated startle in humans.

RATIONALE: Pre-clinical and clinical investigations have provided a great deal of evidence that the fear-potentiated startle paradigm represents a valid model for the objective assessment of emotional states of anxiety and fear. OBJECTIVE: The four studies presented in this report sought to further validate the "threat of shock" paradigm as a human analogue to fear-potentiated startle in rats, by examining the effect of benzodiazepine administration on both baseline and fear-potentiated startle. METHODS: Three studies, conducted at Utrecht University, evaluated the effects of oxazepam and of diazepam on baseline and fear-potentiated startle, whereas a fourth study, conducted at Yale University, evaluated the effect of diazepam on baseline, contextual and cue-specific fear-potentiated startle. The threat of shock paradigm consisted of verbal instruction about two visual cues (the threat cue predicted the possible administration of electric shock, the other predicted a safe period), followed by a series of presentations of these cues. During these conditions, acoustic startle stimuli were presented in order to elicit startle responses. The magnitude of the startle response was used to index the degree of fear or alarm experienced during the periods of threat and safety. The fourth study examined the effect of IV administration of diazepam in a similar threat of shock paradigm except that there were two additional context manipulations: electrode placement and darkness. RESULTS: None of the drug manipulations affected specific threat-cue potentiation of startle. However, reductions in baseline startle were observed. Further, startle potentiation by darkness was inhibited by diazepam. CONCLUSIONS: At least one type of fear-potentiated startle, i.e. potentiation by a cue-specific fear manipulation, is not susceptible to benzodiazepine treatment. In contrast, effects of manipulations more akin to anxiety (darkness, context) appear sensitive to benzodiazepines. Human experimental models differentiating between these cue specific and contextual responses are needed to shed more light on differences in the anatomy and pharmacology of anxiety disorders.

Cognitive basis of hallucinations in schizophrenia: role of top-down information processing.

Hallucinations in schizophrenia have been regarded to result from the erroneous attribution of internally generated information to an external source. Distortions in mental imagery may underlie such confusions. We investigated performance of 77 subjects on multiple behavioral measures of auditory and visual mental imagery and perception, and a measure of reality monitoring. Comparisons were made between performance of schizophrenia patients with (N=22) and without (N=35) hallucinations and matched normal comparison subjects (N=20), after controlling for attentional factors. No differences emerged on any of the mental imagery measures, nor on reality monitoring accuracy. This suggests that there is no stable disposition towards abnormal mental imagery associated with hallucinations. However, for patients with active hallucinations (N=12), hallucination severity correlated positively with a measure of imagery-perception interaction in the auditory modality, r=0.70, p=0.01. Although preliminary, this finding is consistent with recent theoretical proposals in which hallucinations have been suggested to result from an increased influence of top-down sensory expectations on conscious perception.

Abnormal EEG synchronisation in heavily drinking students.

OBJECTIVE: In alcoholics, grey and white brain matter is damaged. In addition, functional brain connectivity as measured by EEG coherence is abnormal. We investigated whether heavily drinking students, although drinking for a shorter period than alcoholics, already show differences in functional connectivity compared to light-drinking controls. METHODS: EEG was recorded in 11 light and 11 heavy male student drinkers during eyes closed, and eyes closed plus mental rehearsal of pictures. Functional connectivity was assessed with the Synchronisation Likelihood method. RESULTS: Heavily drinking students had more synchronisation in the theta (4-8 Hz) and gamma (30-45 Hz) band than lightly drinking students during eyes closed, both with and without a mental-rehearsal task. CONCLUSIONS: Heavy student drinkers have increases in EEG synchronisation that are indicative of changes in hippocampal-neocortical connectivity. SIGNIFICANCE: Heavy student drinkers show differences in functional connectivity as compared to their lightly drinking counterparts, even though they have a relatively short drinking history.

Differences in startle modulation during instructed threat and selective attention.

This study investigated whether attentional processes contribute to fear-potentiated startle. Ten subjects participated in a threat of shock experiment and an attentional control condition. In the threat of shock experiment, visual cues indicated whether or not an aversive shock might occur. In the attentional control, the shocks were replaced by faint vibrotactile stimuli that had to be counted. The P300 amplitudes of the ERP evoked by the visual cues did not differ under threat and counting, which suggested that both conditions engaged attention to the same extent. In contrast, startle potentiation in the threat condition was an order of magnitude larger than the marginally significant attentional startle facilitation in the counting condition. These results indicate that an attentional contribution to fear-potentiated startle under the present experimental conditions is small. In addition, contextual effects of threat of shock became manifest as baseline startle was facilitated relative to the attention condition. This may reflect a more sustained state of anxiety on which cue-specific fear responses are superimposed.

Frequency domain simultaneous source and source coherence estimation with an application to MEG.

Interactions between cortical areas are crucial for cognitive functioning. Methods currently in use to assess such interactions are not well suited for this task because they lack timing precision, localization precision, or both. We present a method for simultaneous estimation of source location and orientation parameters and cross-spectral parameters to overcome these problems. Different estimators are evaluated for their performance. From a simulation study, we conclude that the estimators derived from the maximum-likelihood procedure have good statistical properties with moderate sample sizes, whereas those obtained from the generalized least squares procedure are biased and give poor-quality standard errors. The method is illustrated with visually evoked field data, with inconclusive results.

Model selection in electromagnetic source analysis with an application to VEFs.

In electromagnetic source analysis, it is necessary to determine how many sources are required to describe the electroencephalogram or magnetoencephalogram adequately. Model selection procedures (MSPs) or goodness of fit procedures give an estimate of the required number of sources. Existing and new MSPs are evaluated in different source and noise settings: two sources which are close or distant and noise which is uncorrelated or correlated. The commonly used MSP residual variance is seen to be ineffective, that is it often selects too many sources. Alternatives like the adjusted Hotelling's test, Bayes information criterion and the Wald test on source amplitudes are seen to be effective. The adjusted Hotelling's test is recommended if a conservative approach is taken and MSPs such as Bayes information criterion or the Wald test on source amplitudes are recommended if a more liberal approach is desirable. The MSPs are applied to empirical data (visual evoked fields).

Acute subjective effects after smoking joints containing up to 69 mg Δ9-tetrahydrocannabinol in recreational users: a randomized, crossover clinical trial.

RATIONALE: An increase in the potency of the cannabis cigarettes has been observed over the past three decades. OBJECTIVES: In this study, we aimed to establish the impact of Δ9-tetrahydrocannabinol (THC) on the rating of subjective effects (intensity and duration of the effects), up to 23 % THC potency (69 mg THC) among recreational users. METHODS: Recreational users (N = 24) smoked cannabis cigarettes with four doses of THC (placebo 29, 49 and 69 mg of THC) on four separate test days in a randomized, double-blind, placebo-controlled, crossover study. The participants filled in three different questionnaires measuring subjective effects during the exposure up to 8 h post-smoking. The 'high' feeling, heart rate, blood pressure and THC serum concentrations were also regularly recorded during these 8 h. RESULTS: THC significantly increased the high feeling, dizziness, dry-mouthed feeling, palpitations, impaired memory and concentration, and 'down', 'sedated' and 'anxious' feelings. In addition, THC significantly decreased alertness, contentment and calmness. A cubic relationship was observed between 'feeling the drug' and 'wanting more'. The THC-induced decrease in 'feeling stimulated' and increase in anxiety lasted up to 8 h post-smoking. Sedation at 8 h post-smoking was increased by a factor of 5.7 with the highest THC dose, compared to the placebo. CONCLUSIONS: This study shows a strong effect of cannabis containing high percentages of THC on the rating of subjective effects. Regular users and forensic toxicologists should be aware that the THC-induced increase in 'feeling sedated' continues longer with a 69 mg THC dose than with a 29 mg THC dose.

The effect of noradrenergic attenuation by clonidine on inhibition in the stop signal task.

Understanding the neuropharmacology of inhibition is of importance to fuel optimal treatment for disorders such as Attention Deficit/Hyperactivity Disorder. The aim of the present study was to assess the effect of noradrenergic antagonism by clonidine on behavioral-performance and brain-activity indices of inhibition. A placebo-controlled, double-blind, randomized, crossover design was implemented. Male (N=21) participants performed in a visual stop signal task while EEG was recorded under clonidine in one session and under placebo in another. We expected that 100 µg clonidine would have a negative effect on EEG indices of inhibition, the Stop N2 and Stop P3. Furthermore, we expected that clonidine would negatively affect the behavioral measure of inhibition, the stop signal reaction time (SSRT). Behavioral analyses were performed on data of 17 participants, EEG analyses on a subset (N=13). Performance data suggested that clonidine negatively affected attention (response variability, omissions) without affecting inhibition as indexed by SSRT. Electrophysiological data show that clonidine reduced the Stop P3, but not the Stop N2, indicating a partial negative effect on inhibition. Results show that it is unlikely that the Stop P3 reduction was related to the effect of clonidine on lapses of attention and on peripheral cardiovascular functioning. In conclusion, the current dose of clonidine had a negative effect on attention and a partial effect on inhibitory control. This inhibitory effect was restricted to the dorsal region of the prefrontal cortex (presumably the superior frontal gyrus) as opposed to the ventral region of the prefrontal cortex (right inferior frontal gyrus).

The effectiveness of EEG-feedback on attention, impulsivity and EEG: a sham feedback controlled study.

EEG-feedback, also called neurofeedback, is a training procedure aimed at altering brain activity, and is used as a treatment for disorders like Attention Deficit/Hyperactivity Disorder (ADHD). Studies have reported positive effects of neurofeedback on attention and other dependent variables. However, double-blind studies including a sham neurofeedback control group are lacking. The inclusion of such group is crucial to control for unspecific effects. The current work presents a sham-controlled, double-blind evaluation. The hypothesis was that neurofeedback enhances attention and decreases impulsive behavior. Participants (n=27) were students selected on relatively high scores on impulsivity/inattention questionnaires (Barrat Impulsivity Scale and Broadbent CFQ). They were assigned to a neurofeedback treatment or a sham group. (sham)Neurofeedback training was planned for 15 weeks consisting of a total of 30 sessions, each lasting 22 min. Before and after 16 sessions (i.e., interim analyses), qEEG was recorded and impulsivity and inattention was assessed using a stop signal task and reversed continuous performance task and two questionnaires. Results of the interim analyses showed that participants were blind with respect to group inclusion, but no trend towards an effect of neurofeedback on behavioral measures was observed. Therefore in line with ethical guidelines the experiment was ceased. These results implicate a possible lack of effect of neurofeedback when one accounts for non-specific effects. However, the specific form of feedback and application of the sham-controlled double-blind design may have diminished the effect of neurofeedback.

Effects of alcohol on attention orienting and dual-task performance during simulated driving: an event-related potential study.

Driving is a complex task and is susceptible to inattention and distraction. Moreover, alcohol has a detrimental effect on driving performance, possibly due to alcohol-induced attention deficits. The aim of the present study was to assess the effects of alcohol on simulated driving performance and attention orienting and allocation, as assessed by event-related potentials (ERPs). Thirty-two participants completed two test runs in the Divided Attention Steering Simulator (DASS) with blood alcohol concentrations (BACs) of 0.00%, 0.02%, 0.05%, 0.08% and 0.10%. Sixteen participants performed the second DASS test run with a passive auditory oddball to assess alcohol effects on involuntary attention shifting. Sixteen other participants performed the second DASS test run with an active auditory oddball to assess alcohol effects on dual-task performance and active attention allocation. Dose-dependent impairments were found for reaction times, the number of misses and steering error, even more so in dual-task conditions, especially in the active oddball group. ERP amplitudes to novel irrelevant events were also attenuated in a dose-dependent manner. The P3b amplitude to deviant target stimuli decreased with blood alcohol concentration only in the dual-task condition. It is concluded that alcohol increases distractibility and interference from secondary task stimuli, as well as reduces attentional capacity and dual-task integrality.