Genetic variability in the human cannabinoid receptor 1 is associated with resting state EEG theta power in humans.

It has long been postulated that exogenous cannabinoids have a profound effect on human cognitive functioning. These cannabinoid effects are thought to depend, at least in parts, on alterations of phase-locking of local field potential neuronal firing. The latter can be measured as activity in the theta frequency band (4-7Hz) by electroencephalogram. Theta oscillations are supposed to serve as a mechanism in neural representations of behaviorally relevant information. However, it remains unknown whether variability in endogenous cannabinoid activity is involved in theta rhythms and therefore, may serve as an individual differences index of human cognitive functioning. To clarify this issue, we recorded resting state EEG activity in 164 healthy human subjects and extracted EEG power across frequency bands (δ, θ, α, and ß). To assess variability in the endocannabinoid system, two genetic polymorphisms (rs1049353, rs2180619) within the cannabinoid receptor 1 (CB1) were determined in all participants. As expected, we observed significant effects of rs1049353 on EEG power in the theta band at frontal, central and parietal electrode regions. Crucially, these effects were specific for the theta band, with no effects on activity in the other frequency bands. Rs2180619 showed no significant associations with theta power after Bonferroni correction. Taken together, we provide novel evidence in humans showing that genetic variability in the cannabinoid receptor 1 is associated with resting state EEG power in the theta frequency band. This extends prior findings of exogenous cannabinoid effects on theta power to the endogenous cannabinoid system.

Differences between nicotine-abstinent smokers and non-smokers in terms of visuospatial attention and inhibition before and after single-blind nicotine administration.

The cholinergic system is implicated in visuospatial attention and inhibition, however the exact role is still unclear. Two key mechanisms in visuospatial attention are bias and disengagement. Bias refers to neuronal signals that enhance the sensitivity of the sensory cortex, disengagement is the decoupling of attention. Previous studies suggest that nicotine affects disengagement and (related) inhibition. However the exact relation is still unknown. Furthermore, nicotine-abstinence in 'healthy' smokers may resemble some anomalies of visuospatial attention and inhibition as seen in Attention Deficit/Hyperactivity Disorder (ADHD). Smokers and non-smokers (32 male students) performed in a visuospatial cueing (VSC) task, to assess bias and disengagement, and in a stop-signal task (SST) to assess inhibition. It was expected that nicotine abstinent smokers compared to non-smokers, would show poor disengagement (indicated by an enhanced validity effect) and poor inhibitory control (indicated by an enhanced stop-signal reaction time (SSRT)). It was expected that nicotine would positively affect disengagement and inhibition: hypothesis 1 stated that this effect would be larger in smokers as opposed to non-smokers, in terms of smoking-related deficient inhibitory control. Hypothesis 2 stated the exact opposite, in terms of drug-tolerance. Results indicated no baseline differences. Nicotine enhanced inhibition more in non-smokers relative to smokers. Integrating the results, nicotine-abstinent smokers do not seem to resemble ADHD patients, and do not seem to smoke in order to self-medicate a pre-existing deficit pertaining to mechanisms of visuospatial attention and inhibition. Nicotine may affect inhibition more in non-smokers relative to smokers, consistent with a drug-tolerance account.

The effect of enhancing cholinergic neurotransmission by nicotine on EEG indices of inhibition in the human brain.

The role of the cholinergic system in inhibition remains to be elucidated. Nicotine is a potent tool to augment this system, but most studies investigated its effects solely on behavior. Reference to brain activity is important to specifically identify inhibition-related mechanisms. In the current study the objective was to elucidate the role of the cholinergic system in inhibition. 16 healthy non-smokers performed in a stop task while EEG was recorded. A pre- versus post-treatment, within subjects, placebo controlled, single-blind design was used. It was hypothesized that nicotine would decrease stop-signal reaction time (SSRT) and increase the amplitude of inhibition-related event related potentials, the stop N2 and stop P3. Behavioral measures show nicotine shortened SSRT, but only when pretreatment values were not taken into account. On EEG measures, an enhanced stop P3 under nicotine was found, but only in a subsample sensitive to nicotine based on diastolic blood pressure. The results are indicative of enhanced inhibitory activity possibly reflecting enhanced activation in the superior frontal gyrus.

The effect of the augmentation of cholinergic neurotransmission by nicotine on EEG indices of visuospatial attention.

The cholinergic system has been implicated in visuospatial attention but the exact role remains unclear. In visuospatial attention, bias refers to neuronal signals that modulate the sensitivity of sensory cortex, while disengagement refers to the decoupling of attention making reorienting possible. In the current study we investigated the effect of facilitating cholinergic neurotransmission by nicotine (Nicorette Freshmint 2mg, polacrilex chewing gum) on behavioral and electrophysiological indices of bias and disengagement. Sixteen non-smoking participants performed in a Visual Spatial Cueing (VSC) task while EEG was recorded. A randomized, single-blind, crossover design was implemented. Based on the scarce literature, it was expected that nicotine would specifically augment disengagement related processing, especially manifest as an increase of the modulation of the Late Positive Deflection (LPD) by validity of cueing. No effect was expected on bias related components (cue-locked: EDAN, LDAP; target-locked: P1 and N1 modulations). Results show weak indications for a reduction of the reaction time validity effect by nicotine, but only for half of the sample in which the validity effect on the pretest was largest. Nicotine reduced the result of bias as indexed by a reduced P1 modulation by validity, especially in subjects with strong peripheral responses to nicotine. Nicotine did not affect ERP manifestations of the directing of bias (EDAN, LDAP) or disengagement (LPD).

Auditory event-related potentials (P3a, P3b) and genetic variants within the dopamine and serotonin system in healthy females.

The late positive components of the human event-related brain potential comprise electrocortical reflections of stimulus-driven attentional capture (the anteriorly distributed P3a) and top-down control detection of relevant events (the posteriorly distributed P3b). As of yet, the neuropharmacologic and neurogenetic origin of the P3a and P3b is not fully understood. In this study, we address the contribution of dopaminergic and serotoninergic mechanisms. Sixty healthy females completed an active auditory novelty oddball paradigm while EEG was recorded. In all subjects, genetic polymorphisms within the dopamine system (dopamine transporter [DAT1], catecholamine-O-methyltransferase val158met [COMT val158met]) and the serotonin system (serotonin transporter [5HTTLPR]) were assessed. Across genotypes, novels (relative to standards) elicited a fronto-centrally distributed P3a, and targets (relative to standards) a parieto-centrally distributed P3b. Genotypes effects were observed for both P3a (COMT, 5HTTPLR) and P3b (DAT1, COMT, 5HTTLPR) only at prefrontal electrode location (Fz). Specifically, the frontal P3a was enhanced in COMT met/met homozygotes, but not in DAT1 9R. The target-related P3b was enhanced in COMT met/met and DAT1 9R relative to its genetic counterparts, but only at frontal electrodes. This 'anteriorized' enhancement may reflect either an additional frontal component in the target-related P3 dependent on dopamine, or a more subtle shift in the neural ensemble that generates the target-related P3. Results for 5HTTLPR short allele homozygotes mimicked those in COMT met/met homozygotes. In all, the present findings suggest involvement of frontal-cortical dopaminergic and serotoninergic mechanisms in bottom-up attentional capture (COMT val158met, 5HTTLPR), with an additional top-down component sensitive to striatal signals (DAT1).

Genetic polymorphisms of the dopamine and serotonin systems modulate the neurophysiological response to feedback and risk taking in healthy humans.

Genetic differences in the dopamine and serotonin systems have been suggested as potential factors underlying interindividual variability in risk taking and in brain activation during the processing of feedback. Here, we studied the effects of dopaminergic (dopamine transporter [DAT1], catecholamine-O-methyltransferase val158met [COMT]) and serotonergic (serotonin transporter [5HTTLPR]) polymorphisms on risk taking and brain responses following feedback in 60 healthy female subjects. The subjects completed a well-established experimental gambling paradigm while an electroencephalogram was recorded. During the task, risk-taking behavior and prefrontal brain responses (feedback-related negativity [FRN]) following monetary gains and losses were assessed. FRN amplitudes were enhanced for nine-repeat-allele carriers of the DAT1 and short-allele carriers of 5HTTLPR, which are both presumably linked to less transporter activity and higher neurotransmitter levels. Moreover, nine-repeat DAT1 carriers displayed a trend toward increased risk taking in general, whereas 5HTTLPR short-allele carriers showed decreased risk taking following gains. COMT val158met genotype was unrelated to FRN amplitude and average risk taking. However, COMT met/met carriers showed a pronounced feedback P3 amplitude independent of valence, and a gradual increase in risk taking during the gambling task. In sum, the present findings underline the importance of genetic variability in the dopamine and serotonin systems regarding the neurophysiology of feedback processing.

Cannabis with high δ9-THC contents affects perception and visual selective attention acutely: an event-related potential study.

OBJECTIVE: Cannabis intake has been reported to affect cognitive functions such as selective attention. This study addressed the effects of exposure to cannabis with up to 69.4mg Delta(9)-tetrahydrocannabinol (THC) on Event-Related Potentials (ERPs) recorded during a visual selective attention task. METHODS: Twenty-four participants smoked cannabis cigarettes with four doses of THC on four test days in a randomized, double blind, placebo-controlled, crossover study. Two hours after THC exposure the participants performed a visual selective attention task and concomitant ERPs were recorded. RESULTS: Accuracy decreased linearly and reaction times increased linearly with THC dose. However, performance measures and most of the ERP components related specifically to selective attention did not show significant dose effects. Only in relatively light cannabis users the Occipital Selection Negativity decreased linearly with dose. Furthermore, ERP components reflecting perceptual processing, as well as the P300 component, decreased in amplitude after THC exposure. Only the former effect showed a linear dose-response relation. CONCLUSIONS: The decrements in performance and ERP amplitudes induced by exposure to cannabis with high THC content resulted from a non-selective decrease in attentional or processing resources. SIGNIFICANCE: Performance requiring attentional resources, such as vehicle control, may be compromised several hours after smoking cannabis cigarettes containing high doses of THC, as presently available in Europe and Northern America.

Heart rate and skin conductance in four-year-old children with aggressive behavior.

Autonomic underarousal, indicated by low heart rate (HR) and skin conductance level (SCL), is related to childhood aggression. However, results are inconsistent in preschoolers. We assessed HR, SCL, heart rate reactivity and skin conductance reactivity in four-year-old children. Comparisons were made between children with a high level and with a low level of aggressive behavior according to the Child Behavior Checklist 1 1/2-5 as well as between children who were diagnosed with Oppositional Defiant Disorder or Conduct Disorder (ODD/CD) and children with a low level of aggression. Preschool children with a high level of aggressive behavior showed lower SCL and SCR and children with ODD/CD showed lower SCL. In contrast, we did not find lower HR and HRR in preschool children with a high level of aggressive behavior or ODD/CD. Thus, results suggest that decreased SCL, but not HR, is a characteristic of preschool children with aggressive behavior or ODD/CD.

Activation of the septohippocampal system differentiates anxiety from fear in startle paradigms.

It has been suggested that different brain areas are involved in the modulation and expression of fear and anxiety. In the present study we investigated these potential differences by using the fear-potentiated-startle (FPS) and light-enhanced-startle (LES) paradigms to differentiate between fear and anxiety, respectively. Male Wistar rats were tested in the FPS and LES paradigm and perfused 1 h after the test session. Fos immunoreactivity (IR) was quantified in 21 brain areas and compared between FPS, LES and four control conditions. Both FPS and LES procedures significantly enhanced the acoustic startle response. A principal component analysis of Fos-IR-data showed that 70% of the changes in Fos-IR could be explained by three independent components: an arousal-component, identifying brain areas known to be activated under conditions of vigilance, arousal and stress, a LES- and an FPS-component. The LES component comprised the septohippocampal system and functionally interrelated areas including nucleus accumbens, anterior cingulate cortex, lateral habenula and supramammillary areas, but not the dorsolateral part of the bed nucleus of the stria terminalis. The central amygdaloid nucleus and the dorsolateral part of the bed nucleus of the stria terminalis loaded exclusively on the FPS component. Analysis of the separate brain areas revealed significantly higher Fos-IR in LES relative to FPS in the anterior cingulate cortex, nucleus accumbens shell, lateral septum, lateral habenula and area postrema. We conclude that the neural circuitry activated during FPS and LES shows clear differences. In anxiety as induced by LES, activation of the septohippocampal system and related areas seems to play a major role. In fear as induced by FPS, the central amygdaloid nucleus and the dorsolateral part of the bed nucleus of the stria terminalis loaded on the same component, but Fos-IR observed in these brain regions did not differentiate between anxiety and fear. Furthermore, principal-component analysis appears a useful tool in detecting and describing correlated changes in patterns of neuronal activity.

Event-related potentials and secondary task performance during simulated driving.

Inattention and distraction account for a substantial number of traffic accidents. Therefore, we examined the impact of secondary task performance (an auditory oddball task) on a primary driving task (lane keeping). Twenty healthy participants performed two 20-min tests in the Divided Attention Steering Simulator (DASS). The visual secondary task of the DASS was replaced by an auditory oddball task to allow recording of brain activity. The driving task and the secondary (distracting) oddball task were presented in isolation and simultaneously, to assess their mutual interference. In addition to performance measures (lane keeping in the primary driving task and reaction speed in the secondary oddball task), brain activity, i.e. event-related potentials (ERPs), was recorded. Performance parameters on the driving test and the secondary oddball task did not differ between performance in isolation and simultaneous performance. However, when both tasks were performed simultaneously, reaction time variability increased in the secondary oddball task. Analysis of brain activity indicated that ERP amplitude (P3a amplitude) related to the secondary task, was significantly reduced when the task was performed simultaneously with the driving test. This study shows that when performing a simple secondary task during driving, performance of the driving task and this secondary task are both unaffected. However, analysis of brain activity shows reduced cortical processing of irrelevant, potentially distracting stimuli from the secondary task during driving.

Acute effects of nicotine on attention and response inhibition.

Smoking is highly prevalent among patients with Attention Deficit Hyperactivity Disorder (ADHD). Previous studies using the reversed continuous performance task (R-CPT) have suggested that nicotine reduces inattention. Since especially adults with ADHD have been claimed to suffer from a core deficit in inhibitory control, this study aimed at determining whether nicotine improves response inhibition in addition to attention. Sixteen healthy regular smokers participated in a pre/post treatment design in which transdermal patches containing 7 and 21 mg nicotine per day were administered in a counterbalanced, double-blind manner. In a second study, patches containing 0 mg (placebo) and 21 mg per day were administered to a different group of regular smokers. For replication purposes, the R-CPT and the profile of mood states (POMS) were administered. Furthermore, a different version of the continuous performance task (CPT-AX) and the stop-signal task, traditionally used to measure response inhibition, were presented. The high dose of nicotine was found to relieve self-reported Depression in Study 1 and Fatigue in Study 2. Performance data indicated acute effects of nicotine on attention-related, but not on inhibition-related measures. Especially the comparison with placebo revealed decreases in reaction time and variability of responding. The results imply that patients with ADHD smoke to reduce inattention.

Simulation of a nitrification control concept considering influent ammonium load.

Buchenhofen wastewater treatment plant of Wupperverband (650,000 p.e.) is currently being expanded for targeted nitrogen elimination. In view of the limited space available for extension, an optimized control concept is to be used in order to minimize the number of additional tanks required. This concept was investigated by dynamic simulation based on Activated Sludge Model No. 1. The investigations included a pure feedback control configuration and a configuration combining feedback und feedforward control, considering the influent ammonium load, for aeration. The results show that combined feedforward/feedback control has significant advantages over pure feedback control. In particular, this configuration allows a reduction in the effluent NH4-N peaks, which is especially important because of the low NH4-N limit of 5 mg NH4-N/L in a grab sample.

Threat-induced cortical processing and startle potentiation.

This paper presents cortical responses as reflected in event-related potentials (ERP) in an instructed fear paradigm. Safe cues and threat cues that predict shock were presented at an unprecedented fast rate (mean SOA of 2.1 s). Startle and subjective measures confirmed that threat relative to safe cues elicited fear. Several ERP correlates of fear processing were predicted and confirmed: modulation of exogenous sensory components, frontal selection positivity, and increase of P3. Furthermore, a frontal negative slow wave was observed. These results are discussed in relation to attentional selection models and emotional processing.

Stimulus-preceding negativity induced by fear: a manifestation of affective anticipation.

The Stimulus-Preceding Negativity (SPN), a slow cortical potential, has been studied in relation to anticipatory attention. A review of the literature suggests that most instances of SPN are observed in anticipation of motivational stimuli, such as aversive stimuli and stimuli that provide Knowledge of Results. In the present study, SPN was recorded in 12 subjects in a threat-of-shock experiment. This manipulation induced fear, as shown by subjective ratings and potentiation of the eyeblink startle. The fear-induced SPN showed a frontocentral maximum and coarse source analysis suggested that it was generated in midline frontal areas, possibly by the anterior cingulate cortex. It is concluded that the fear-induced SPN is a manifestation of affective anticipation. Possible thalamocortical and amygdalocortical contributions to its generation are discussed.

Hallucinatory predisposition and vividness of auditory imagery: self-report and behavioral indices.

This study examined the relation between a subjective and a behavioral measure of the vividness of auditory imagery as well as the disposition towards hallucination in normal subjects. In addition to the Launay-Slade Hallucination Scale, subjects (57 university students) completed the Betts questionnaire in which they rated the vividness of their experienced mental images and performed a behavioral task aimed at measuring auditory imagery. The task consisted of a perception and an imagery condition in which subjects had to indicate the odd one of three everyday sounds. Performance on the behavioral task did not correlate with the auditory or scores on the Visual subscale of the Betts. In addition, neither scores on the behavioral measure nor the Auditory subscale of the Betts correlated significantly with hallucinatory predisposition as rated on the Launay-Slade Hallucination Scale. In contrast, the Visual subscale of the Betts did correlate with scores on the Launay-Slade Hallucination Scale, consistent with previous research. We conclude that there is no straightforward relationship between imagery vividness and hallucinatory experiences and that subjective and objective indices of imagery vividness measure different aspects of mental function.

Event-related desynchronization during anticipatory attention for an upcoming stimulus: a comparative EEG/MEG study.

OBJECTIVES: Our neurophysiological model of anticipatory behaviour (e.g. Acta Psychol 101 (1999) 213; Bastiaansen et al., 1999a) predicts an activation of (primary) sensory cortex during anticipatory attention for an upcoming stimulus. In this paper we attempt to demonstrate this by means of event-related desynchronization (ERD). METHODS: Five subjects performed a time estimation task, and were informed about the quality of their time estimation by either visual or auditory stimuli providing Knowledge of Results (KR). EEG and MEG were recorded in separate sessions, and ERD was computed in the 8-10 and 10-12 Hz frequency bands for both datasets. RESULTS: Both in the EEG and the MEG we found an occipitally maximal ERD preceding the visual KR for all subjects. Preceding the auditory KR, no ERD was present in the EEG, whereas in the MEG we found an ERD over the temporal cortex in two of the 5 subjects. These subjects were also found to have higher levels of absolute power over temporal recording sites in the MEG than the other subjects, which we consider to be an indication of the presence of a 'tau' rhythm (e.g. Neurosci Lett 222 (1997) 111). CONCLUSIONS: It is concluded that the results are in line with the predictions of our neurophysiological model.

Music training and mental imagery ability.

Neuroimaging studies have suggested that the auditory cortex is involved in music processing as well as in auditory imagery. We hypothesized that music training may be associated with improved auditory imagery ability. In this study, performance of musically trained and musically naive subjects was compared on: (1) a musical mental imagery task (in which subjects had to mentally compare pitches of notes corresponding to lyrics taken from familiar songs); (2) a non-musical auditory imagery task (in which subjects had to mentally compare the acoustic characteristics of everyday sounds); and (3) a comparable measure of visual imagery (in which subjects had to mentally compare visual forms of objects). The musically trained group did not only perform better on the musical imagery task, but also outperformed musically naive subjects on the non-musical auditory imagery task. In contrast, the two groups did not differ on the visual imagery task. This finding is discussed in relation to theoretical proposals about music processing and brain activity.

Perception, mental imagery and reality discrimination in hallucinating and non-hallucinating schizophrenic patients.

OBJECTIVES: In this study the hypothesis was tested that hallucinations result from confusing external and internal stimulus sources, i.e., perception and imagery, respectively. DESIGN AND METHODS: Thirteen hallucinating and 19 non-hallucinating schizophrenic patients, as well as 14 control participants performed multiple tests of perception, vividness of mental imagery and the ability to discriminate between them (reality discrimination). These functions were tested in both the auditory and the visual modalities. RESULTS: There were no group differences on perceptual acuity. The results on one imagery task indicated that for the hallucinating patients, the relative, but not the absolute, level of vividness of mental images might be higher in the auditory modality, which was the modality in which 12 of the patients also experienced hallucinations, than in the visual modality. Finally, there was a positive relationship between severity of (auditory) hallucinations and reality discrimination problems. CONCLUSIONS: Hallucinations may result from increased vividness of mental imagery, and their severity increases with larger impairments in reality discrimination. It is recommended that research into, and cognitive behavioural therapy for, hallucinations should also focus on their sensory qualities.

Mental imagery and perception in hallucination-prone individuals.

College students screened for hallucination-proneness using the Launay-Slade Hallucination Scale (LSHS) were compared on measures of self-report vividness of imagery and on behavioral measures of imagery and perception (visual and auditory). Specifically, we tested the hypothesis whether hallucination-prone individuals would show smaller differences between imagery and perception performance, which may be indicative of increased sensory characteristics of mental images. We replicated earlier findings of higher self-report imagery ratings in the high hallucination-prone group. However, the two groups did not differ on five of six behavioral imagery-perception comparisons. On one visual task, hallucination-proneness was associated with larger imagery-perception differences. Our results reveal a dissociation between the level of subjective experience and the information processing level. Although vividness of mental images may be subjectively associated with mild hallucinatory experiences, we suggest that cognitive processes associated with reality discrimination rather than increased perceptual characteristics of mental images may play a role at the information processing level.

An ERP correlate of metrical stress in spoken word recognition.

Rhythmic properties of spoken language such as metrical stress, that is, the alternation of strong and weak syllables, are important in speech recognition of stress-timed languages such as Dutch and English. Nineteen subjects listened passively to or discriminated actively between sequences of bisyllabic Dutch words, which started with either a weak or a strong syllable. Weak-initial words, which constitute 12% of the Dutch lexicon, evoked more negativity than strong-initial words in the interval between P2 and N400 components of the auditory event-related potential. This negativity was denoted as N325. The N325 was larger during stress discrimination than during passive listening. N325 was also larger when a weak-initial word followed a sequence of strong-initial words than when it followed words with the same stress pattern. The latter difference was larger for listeners who performed well on stress discrimination. It was concluded that the N325 is probably a manifestation of the extraction of metrical stress from the acoustic signal and its transformation into task requirements.