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.

Identification of over- and undertreatment in the Dutch national cervical cancer screening program: A data linkage study at the hospital level.

Research into the quality of cancer screening programs often lacks the perspective of clinicians, missing insights into the performance of individual hospitals. This retrospective cohort study aimed to identify guideline deviation (specifically, overtreatment and undertreatment) related to the cervical cancer screening program in Dutch hospitals by deterministically linking nationwide insurance data with pathology data for cervical intraepithelial neoplasia (CIN). We then constructed quality indicators using the Dutch CIN guideline and National Health Care Institute recommendations to assess compliance with CIN management, treatment outcomes, and follow-up, using an empirical Bayes shrinkage model to correct for case-mix variation and hospitals with few observations. Data were linked for 115,899 of 125,751 (92%) eligible women. Overtreatment was observed in the see-and-treat approach (immediate treatment) for women with low-grade referral cytology (4%; hospital range, 0%-25%), CIN ≤ 1 treatment specimens (26%; hospital range, 10%-55%), and follow-up cervix cytology ≥2 months before the guideline recommendation after treatment for CIN 2 (2%; hospital range, 0%-9%) or CIN 3 (5%; hospital range, 0%-19%). By contrast, undertreatment was observed for treatment within 3 months after a CIN 3 biopsy result (90%; hospital range 59%-100%) and follow-up ≥2 months beyond the guideline recommendation after treatments for CIN 2 (21%, hospital range 7%-48%) and CIN 3 (20%, hospital range 7%-90%). In conclusion, we found evidence of CIN overtreatment and undertreatment in all measured domains at the hospital level. Guideline adherence could be improved by implementing the developed indicators in an audit and feedback instrument for use by healthcare professionals in routine practice.

Genotype scores predict drug efficacy in subtypes of female sexual interest/arousal disorder: A double-blind, randomized, placebo-controlled cross-over trial.

Attempts to develop a drug treatment for female sexual interest/arousal disorder have so far been guided by the principle of 'one size fits all', and have failed to acknowledge the complexity of female sexuality. Guided by personalized medicine, we designed two on-demand drugs targeting two distinct hypothesized causal mechanisms for this sexual disorder. The objective of this study was to design and test a novel procedure, based on genotyping, that predicts which of the two on-demand drugs will yield a positive treatment response. In a double-blind, randomized, placebo-controlled cross-over experiment, 139 women with female sexual interest/arousal disorder received three different on-demand drug-combination treatments during three 2-week periods: testosterone 0.5 mg + sildenafil 50 mg, testosterone 0.5 mg + buspirone 10 mg, and matching placebo. The primary endpoint was change in satisfactory sexual events. Subjects' genetic profile was assessed using a microarray chip that measures 300,000 single-nucleotide polymorphisms. A preselection of single-nucleotide polymorphisms associated with genes that are shown to be involved in sexual behaviour were combined into a Phenotype Prediction Score. The Phenotype Prediction Score demarcation formula was developed and subsequently validated on separate data sets. Prediction of drug-responders with the Phenotype Prediction Score demarcation formula gave large effect sizes (d = 0.66 through 1.06) in the true drug-responders, and medium effect sizes (d = 0.51 and d = 0.47) in all patients (including identified double, and non-responders). Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the Phenotype Prediction Score demarcation formula were all between 0.78 and 0.79, and thus sufficient. The resulting Phenotype Prediction Score was validated and shown to effectively and reliably predict which women would benefit from which on-demand drug, and could therefore also be useful in clinical practice, as a companion diagnostic establishing the way to a true personalized medicine approach.

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.

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.

Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: a double-blind randomized controlled clinical trial.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help in maintaining FSHD muscle function. Our primary objective was to test whether oral administration of vitamin C, vitamin E, zinc gluconate, and selenomethionine could improve the physical performance of patients with FSHD. Adult patients with FSHD (n=53) were enrolled at Montpellier University Hospital (France) in a randomized, double-blind, placebo-controlled pilot clinical trial. Patients were randomly assigned to receive 500 mg vitamin C, 400mg vitamin E, 25mg zinc gluconate and 200 µg selenomethionine (n=26), or matching placebo (n=27) once a day for 17 weeks. Primary outcomes were changes in the two-minute walking test (2-MWT), maximal voluntary contraction, and endurance limit time of the dominant and nondominant quadriceps (MVCQD, MVCQND, TlimQD, and TlimQND, respectively) after 17 weeks of treatment. Secondary outcomes were changes in the antioxidant status and oxidative stress markers. Although 2-MWT, MVCQ, and TlimQ were all significantly improved in the supplemented group at the end of the treatment compared to baseline, only MVCQ and TlimQ variations were significantly different between groups (MVCQD: P=0.011; MVCQND: P=0.004; TlimQD: P=0.028; TlimQND: P=0.011). Similarly, the vitamin C (P<0.001), vitamin E as α-tocopherol (P<0.001), vitamin C/vitamin E ratio (P=0.017), vitamin E γ/α ratio (P=0.022) and lipid peroxides (P<0.001) variations were significantly different between groups. In conclusion, vitamin E, vitamin C, zinc, and selenium supplementation has no significant effect on the 2-MWT, but improves MVCQ and TlimQ of both quadriceps by enhancing the antioxidant defenses and reducing oxidative stress. This trial was registered at clinicaltrials.gov (number: NCT01596803).

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 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.

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.

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.

Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9-tetrahydrocannabinol (THC).

RATIONALE: Delta(9)-Tetrahydrocannabinol (THC) is the main active constituent of cannabis. In recent years, the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette (20% THC cigarettes). Acute cognitive and psychomotor effects of THC among recreational users after smoking cannabis cigarettes containing such high doses are unknown. OBJECTIVES: The objective of this study was to study the dose-effect relationship between the THC dose contained in cannabis cigarettes and cognitive and psychomotor effects for THC doses up to 69.4 mg (23%). MATERIALS AND METHODS: This double-blind, placebo-controlled, randomised, four-way cross-over study included 24 non-daily male cannabis users (two to nine cannabis cigarettes per month). Participants smoked four cannabis cigarettes containing 0, 29.3, 49.1 and 69.4 mg THC on four exposure days. RESULTS: The THC dose in smoked cannabis was linearly associated with a slower response time in all tasks (simple reaction time, visuo-spatial selective attention, sustained attention, divided attention and short-term memory tasks) and motor control impairment in the motor control task. The number of errors increased significantly with increasing doses in the short-term memory and the sustained attention tasks. Some participants showed no impairment in motor control even at THC serum concentrations higher than 40 ng/mL. High feeling and drowsiness differed significantly between treatments. CONCLUSIONS: Response time slowed down and motor control worsened, both linearly, with increasing THC doses. Consequently, cannabis with high THC concentrations may be a concern for public health and safety if cannabis smokers are unable to titrate to a high feeling corresponding to a desired plasma THC level.

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.

Effects of chronic drinking on verb generation: an event related potential study.

In alcohol dependent individuals, abnormalities in brain functioning have been revealed using event-related potential (ERP) methods. In the present study, we investigated whether in non-alcohol dependent drinkers functioning of the brain is also compromised as a function of recent and lifetime drinking history (LDH). An ERP verb generation task consisting of two conditions (generating verbs describing the use of visually presented nouns versus reading nouns aloud) was used; subtracting ERPs in the latter condition from those in the former should reveal the sequence of brain processes involved in verb generation. Four groups were included, consisting of individuals drinking either lightly, moderately, heavily, or excessively (overall mean age 46.6 years). Participants were sober at the time of testing. Although the excessive group had the highest per cent retrieval errors, there was no continuous relationship between this score and amount of alcohol consumption. However, number of glasses per week affected differential ERPs associated with verb generation both at short (120-220 ms, mid-frontal sites) and at longer latencies (from 700 ms on),left-temporal and right-frontal electrode sites (T7, F6). It is concluded that moderate, heavy, and excessive drinkers, compared to light drinkers, show abnormal brain potentials associated with verb generation over frontal and temporal areas. Moderate to excessive drinking alters some but not all brain processes involved in verb generation. In particular the frontal and temporal brain areas appear to be vulnerable for the effects of chronic lifetime drinking.

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.

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.

Hypothesis testing in distributed source models for EEG and MEG data.

Hypothesis testing in distributed source models for the electro- or magnetoencephalogram is generally performed for each voxel separately. Derived from the analysis of functional magnetic resonance imaging data, such a statistical parametric map (SPM) ignores the spatial smoothing in hypothesis testing with distributed source models. For example, when intending to test a single voxel, actually an entire region of voxels is tested simultaneously. Because there are more parameters than observations, typically constraints are employed to arrive at a solution which spatially smooths the solution. If ignored, it can be concluded from the hypothesis test that there is activity at some location where there is none. In addition, an SPM on distributed source models gives the illusion of very high resolution. As an alternative, a multivariate approach is suggested in which a region of interest is tested that is spatially smooth. In simulations with MEG and EEG it is shown that clear hypothesis testing in distributed source models is possible, provided that there is high correspondence between what is intended to be tested and what is actually tested. The approach is also illustrated by an application to data from an experiment measuring visual evoked fields when presenting checkerboard patterns.

Effects of chronic alcohol consumption in a visual attention task and an auditory oddball task: an event-related potential study.

BACKGROUND: In alcohol-dependent individuals changes in brain functioning, as measured with Event Related Potentials (ERP) have been reported. METHODS: In the present study a visual attention and an auditory oddball task were used to investigate possible differences between light, moderate, and heavy social drinkers and excessive drinkers. It was hypothesized that with increasing alcohol intake an increasing number of ERP components elicited in the visual attention task and the auditory oddball task would show diminished amplitudes. RESULTS: No differences were found between light, moderate, and heavy social drinkers. A trend for a smaller P3 amplitude in the visual attention task was found when comparing the alcohol-dependent participants with the light social drinkers. It is argued that this difference might be an effect of alcohol dependence and/or a reflection of possible unknown or undetected family history of alcohol-related disturbances. CONCLUSIONS: In the current study, even at rather large amounts of regular alcohol intake, no evidence was found for any toxic effect of social alcohol use neither in a visual attention task nor in an auditory oddball task.