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Preclinical evidence implicates several neurotransmitter systems in the extinction of conditioned fear. These results are of great interest, because the reduction of acquired fear associations is critical in therapies for anxiety disorders. We tested whether findings with respect to the N-methyl-D-aspartate (NMDA) and cannabinoid receptor (CB) systems in animals carry over to healthy human subjects. To that end, we administered selected doses of D-cycloserine (partial NMDA receptor agonist, 250 mg), delta-9-tetrahydrocannabinol (THC, CB(1) receptor agonist, 10 mg), or placebo prior to the extinction session of a 3-day conditioning protocol. D-cycloserine did not affect within-session extinction, or the retention of extinction in healthy human participants, in contrast with patient data but in line with previous reports in healthy volunteers. During extinction training, Δ9-THC reduced conditioned skin conductance responses, but not fear-potentiated startle. This effect was not retained at the retention test 2 days later, suggesting it was dependent on acute effects of the drug. Our findings implicate that facilitation of the CB(1) or NMDA system with the substances used in this study does not affect conditioned fear extinction lastingly in healthy humans. The apparent discrepancy between these findings and the results from (pre-)clinical trials is discussed in terms of room for improvement in these systems in healthy volunteers, and the lack of specificity of THC as a CB(1) agonist. [ABSTRACT FROM AUTHOR]

BACKGROUND: A lack of inhibitory control has been suggested to be the core deficit in children with attention deficit hyperactivity disorder (ADHD). This means that a primary deficit in behavioral inhibition mediates a cascade of secondary deficits in other executive functions, such as arousal regulation. Clinical observations have revealed that with increasing age symptoms of hyperactivity and impulsivity decline at a higher rate than those of inattention. This might imply that a deficit in attention rather than a lack of inhibitory control is the major feature in adult ADHD. METHOD: To study whether an attentional or inhibitory deficit predominates, the stop-signal task and the stop-change task were presented to 24 adults with ADHD combined subtype and 24 controls. RESULTS: Relative to controls, the stop-signal reaction time (SSRT) was significantly more prolonged than the go-stimulus reaction time (RT) in patients with ADHD. This disproportionate elongation of the SSRT was comparable across tasks, even though the stop-change task exerted more complex (or at least different) demands on the inhibitory system than the stop-signal task. ADHD patients had a higher proportion of choice errors, possibly reflecting more premature responses. Specifically in the stop-change task, patients had more variable choice responses and made more inappropriate change responses, which may also reflect enhanced impulsivity. CONCLUSIONS: The results support a core deficit in behavioral inhibition in adults with ADHD. We further suggest that there is more evidence for a critical role of deficient inhibitory control in adults than in children with ADHD. [ABSTRACT FROM AUTHOR]

Successful reappraisal modulates the impact of emotion-inducing stimuli through reinterpretation of their meaning and decreases subjective emotional experience. Here the question is addressed how the altered emotional experience is related to altered electro-cortical responses, and about the neural mechanisms underlying regulation itself. To this end, we recorded EEG during a cued emotion-regulation paradigm including negative and neutral pictures. Firstly, based on hypothesis-driven analysis of the Late Positive Potential (LPP), we found that the early fronto-centro-parietal LPP (400-1000 ms) increased when passively viewing negative versus neutral pictures. Reappraisal did not decrease this LPP. Instead, only during reappraisal, the emotion effect on the parietal LPP was sustained until the picture offset. Secondly, we applied a localizer approach to uncover reappraisal effects with other spatiotemporal characteristics than the traditional LPP but did not observe such effects. Despite indications of theta oscillations being associated with cognitive and/or affective control, no significant effects were found on theta activity for emotion processing or reappraisal. Our findings suggest that emotion regulation may affect the LPP in several ways, depending on the task design and including affective as well as more cognitive influences. A potential role for theta in emotion regulation remains to be elucidated., (Copyright © 2024. Published by Elsevier B.V.)

We compared how different levels of cognitive load affect frontal P3 (fP3) Event-Related Potential (ERP) to novel sounds. Previous studies demonstrated the predictive value of the probe-elicited frontal P3 (fP3) ERP for subsequent detection failures. They also demonstrated how fP3 is reduced when performing visual and/or manual and/or cognitively demanding tasks. These results are consistent with fP3 indexing orienting to novels or, more neutrally: susceptibility. Here, we tested how fP3 is affected by a threefold variation of cognitive load induced by the verb (generation) task. Participants heard a noun and either listened to it, repeated it, or generated a semantically related verb. These conditions were manipulated between groups. One group (N = 16) experienced the listen and repeat condition; the other group (N = 16) experienced the listen and generate condition. When fP3 was probed 0 or 200 ms after noun offset, it was reduced (relative to no noun) only while repeating or generating, not while listening. An additional probe-elicited ERP was identified as novelty-related negativity, and its contaminating influence on fP3 estimation accounted for by a novel vector-filter procedure. We conclude that cognitive load does not affect fP3-indexed susceptibility. Instead, fP3-indexed susceptibility is affected by presentation of the stimulus, with the most pronounced effect in conditions where a vocal response is needed (i.e., repeat or generate, but not listen), independent of the complexity of the response., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Impulse control and adequate decision making are vital functions when it comes to detection and adherence to personal goals and societal rules. In the current study we tested the hypothesis that increasing the salience of environmental cues would be most effective in improving impulse control, as assessed by a stop-signal task, in subjects with low environmental susceptibility as indexed by low pre-stimulus EEG alpha power. In addition, we anticipated that an external-reward manipulation improves performance during a Go/No go task, especially in individuals with low task-induced motivation as indexed by low theta/beta power ratios. High salience of stop signals enhanced stopping performance but there was no difference in responsivity to the salience manipulation between participants with high and low EEG alpha power. Individuals with low theta/beta power ratios responded more accurately when rewards were involved. Together these results suggest that increasing the salience of external cues may help impulse control in general, whereas the effectiveness of external-reward manipulations is higher in individuals with low task-induced motivation., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

During the COVID-19 pandemic, the use of face masks has become a daily routine. Studies have shown that face masks increase the ambiguity of facial expressions which not only affects (the development of) emotion recognition, but also interferes with social interaction and judgement. To disambiguate facial expressions, we rely on perceptual (stimulus-driven) as well as preconceptual (top-down) processes. However, it is unknown which of these two mechanisms accounts for the misinterpretation of masked expressions. To investigate this, we asked participants (N = 136) to decide whether ambiguous (morphed) facial expressions, with or without a mask, were perceived as friendly or unfriendly. To test for the independent effects of perceptual and preconceptual biases we fitted a drift-diffusion model (DDM) to the behavioral data of each participant. Results show that face masks induce a clear loss of information leading to a slight perceptual bias towards friendly choices, but also a clear preconceptual bias towards unfriendly choices for masked faces. These results suggest that, although face masks can increase the perceptual friendliness of faces, people have the prior preconception to interpret masked faces as unfriendly., (© 2023. Springer Nature Limited.)

Our visual environment is relatively stable over time. An optimized visual system could capitalize on this by devoting less representational resources to objects that are physically present. The vividness of subjective experience, however, suggests that externally available (perceived) information is more strongly represented in neural signals than memorized information. To distinguish between these opposing predictions, we use EEG multivariate pattern analysis to quantify the representational strength of task-relevant features in anticipation of a change-detection task. Perceptual availability was manipulated between experimental blocks by either keeping the stimulus available on the screen during a 2-s delay period (perception) or removing it shortly after its initial presentation (memory). We find that task-relevant (attended) memorized features are more strongly represented than irrelevant (unattended) features. More importantly, we find that task-relevant features evoke significantly weaker representations when they are perceptually available compared with when they are unavailable. These findings demonstrate that, contrary to what subjective experience suggests, vividly perceived stimuli elicit weaker neural representations (in terms of detectable multivariate information) than the same stimuli maintained in visual working memory. We hypothesize that an efficient visual system spends little of its limited resources on the internal representation of information that is externally available anyway., (© The Author(s) 2023. Published by Oxford University Press.)

Stop-signal tasks (SSTs) combined with human electro-cortical recordings (Event-Related Potentials, ERPs) have revealed mechanisms associated with successful stopping (relative to failed), presumably contributing to inhibitory control. The corresponding ERP signatures have been labeled stop N1 (+/- 100-ms latency), stop N2 (200 ms), and stop P3 (160-250 ms), and argued to reflect more sensory-specific (N1) versus more generic (N2, P3) mechanisms. However, stop N1 and stop N2, as well as latencies of stop-P3, appear to be quite inconsistent across studies. The present work addressed the possible influence of stop-signal salience, expecting high salience to induce clear stop N1s but reduced stop N2s, and short-latency stop P3s. Three SST varieties were combined with high-resolution EEG. An imperative visual (go) stimulus was occasionally followed by a subsequent (stop) stimulus that signalled to withhold the just initiated response. Stop-Signal Reaction Times (SSRTs) decreased linearly from visual-low to visual-high-salience to auditory. Auditory Stop N1 was replicated. A C1-like visual evoked potential (latency < 100 ms) was observed only with high salience, but not robustly associated with successful versus failed stops. Using the successful-failed contrast a visual stop-N1 analogue (112-156 ms post-stop-signal) was identified, as was right-frontal stop N2, but neither was sensitive to salience. Stop P3 had shorter latency for high than for low salience, and the extent of the early high-salience stop P3 correlated inversely with SSRT. These results suggest that salience-enhanced inhibitory control as manifest in SSRTs is associated with generic rather than sensory-specific electrocortical mechanisms., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social impairments and restricted, repetitive behaviors. Treatment of ASD is notoriously difficult and might benefit from identification of underlying mechanisms that overlap with those disturbed in other developmental disorders, for which treatment options are more obvious. One example of the latter is attention-deficit hyperactivity disorder (ADHD), given the efficacy of especially stimulants in treatment of ADHD. Deficiencies in catecholaminergic systems [dopamine (DA), norepinephrine (NE)] in ADHD are obvious targets for stimulant treatment. Recent findings suggest that dysfunction in catecholaminergic systems may also be a factor in at least a subgroup of ASD. In this review we scrutinize the evidence for catecholaminergic mechanisms underlying ASD symptoms, and also include in this analysis a third classic ascending arousing system, the acetylcholinergic (ACh) network. We complement this with a comprehensive review of DA-, NE-, and ACh-targeted interventions in ASD, and an exploratory search for potential treatment-response predictors (biomarkers) in ASD, genetically or otherwise. Based on this review and analysis we propose that (1) stimulant treatment may be a viable option for an ASD subcategory, possibly defined by genetic subtyping; (2) cerebellar dysfunction is pronounced for a relatively small ADHD subgroup but much more common in ASD and in both cases may point toward NE- or ACh-directed intervention; (3) deficiency of the cortical salience network is sizable in subgroups of both disorders, and biomarkers such as eye blink rate and pupillometric data may predict the efficacy of targeting this underlying deficiency via DA, NE, or ACh in both ASD and ADHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Koevoet, Deschamps and Kenemans.)

Objective: We experimentally test the effect of cognitive load on auditory susceptibility during automated driving., Background: In automated vehicles, auditory alerts are frequently used to request human intervention. To ensure safe operation, human drivers need to be susceptible to auditory information. Previous work found reduced susceptibility during manual driving and in a lesser amount during automated driving. However, in practice, drivers also perform nondriving tasks during automated driving, of which the associated cognitive load may further reduce susceptibility to auditory information. We therefore study the effect of cognitive load during automated driving on auditory susceptibility., Method: Twenty-four participants were driven in a simulated automated car. Concurrently, they performed a task with two levels of cognitive load: repeat a noun or generate a verb that expresses the use of this noun. Every noun was followed by a probe stimulus to elicit a neurophysiological response: the frontal P3 (fP3), which is a known indicator for the level of auditory susceptibility., Results: The fP3 was significantly lower during automated driving with cognitive load compared with without. The difficulty level of the cognitive task (repeat or generate) showed no effect., Conclusion: Engaging in other tasks during automated driving decreases auditory susceptibility as indicated by a reduced fP3., Application: Nondriving task can create additional cognitive load. Our study shows that performing such tasks during automated driving reduces the susceptibility for auditory alerts. This can inform designers of semi-automated vehicles (SAE levels 3 and 4), where human intervention might be needed.

Humans can flexibly transfer information between different memory systems. Information in visual working memory (VWM) can for instance be stored in long-term memory (LTM). Conversely, information can be retrieved from LTM and temporarily held in WM when needed. It has previously been suggested that a neural transition from parietal- to midfrontal activity during repeated visual search reflects transfer of information from WM to LTM. Whether this neural transition indeed reflects consolidation and is also observed when memorizing a rich visual scene (rather than responding to a single target), is not known. To investigate this, we employed an EEG paradigm, in which abstract six-item colour-arrays were repeatedly memorized and explicitly visualized, or merely attended to. Importantly, we tested the functional significance of a potential neural shift for longer-term consolidation in a subsequent recognition task. Our results show a gradually enhanced- and sustained modulation of the midfrontal P170 component and a decline in parietal CDA, during repeated WM maintenance. Improved recollection/visualization of memoranda upon WM-cueing, was associated with contralateral parietal- and right temporal activity. Importantly, only colour-arrays previously held in WM, induced a greater midfrontal P170-response, together with left temporal- and late centro-parietal activity, upon re-exposure. These findings provide evidence for recruitment of an LTM-supporting neural network which facilitates visual WM maintenance., (© 2022. The Author(s).)

Neuro-Cardiac-Guided Transcranial Magnetic Stimulation (NCG-TMS) was studied for its potential to specifically target the frontal-vagal network. Previous research demonstrated that prefrontal stimulation led to significant heartrate slowing. We aimed to replicate these results in a larger sample and extend the findings to investigate dose-response relationships, reproducibility and stimulation frequency (10 Hz and intermittent theta burst (iTBS)). Data of forty-five healthy controls were analyzed, of which 28 received 10 Hz TMS (NCG-TMS) and 27 iTBS (NCG-iTBS; 10 received both protocols) at different stimulation sites according to the 10-20-EEG system. NCG-TMS yielded a relative heartrate deceleration at the F3/4 coil position replicating earlier studies. Both internal consistency and dose-response relationships were found. For NCG-iTBS adverse events were reported and topography for frontal-vagal activation was more lateralised relative to NCG-TMS. These results indicate that we were able to transsynaptically stimulate the frontal-vagal network and that excitability thresholds for the prefrontal cortex may differ relative to motor cortex., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Emotional facial expressions are important visual communication signals that indicate a sender's intent and emotional state to an observer. As such, it is not surprising that reactions to different expressions are thought to be automatic and independent of awareness. What is surprising, is that studies show inconsistent results concerning such automatic reactions, particularly when using different face stimuli. We argue that automatic reactions to facial expressions can be better explained, and better understood, in terms of quantitative descriptions of their low-level image features rather than in terms of the emotional content (e.g. angry) of the expressions. Here, we focused on overall spatial frequency (SF) and localized Histograms of Oriented Gradients (HOG) features. We used machine learning classification to reveal the SF and HOG features that are sufficient for classification of the initial eye movement towards one out of two simultaneously presented faces. Interestingly, the identified features serve as better predictors than the emotional content of the expressions. We therefore propose that our modelling approach can further specify which visual features drive these and other behavioural effects related to emotional expressions, which can help solve the inconsistencies found in this line of research.

Previous studies have not clearly demonstrated whether motivational tendencies during reward feedback are mainly characterized by appetitive responses to a gain or mainly by aversive consequences of reward omission. In the current study this issue was addressed employing a passive head or tails game and using the startle reflex as an index of the appetitive-aversive continuum. A second aim of the current study was to use startle-reflex modulation as a means to compare the subjective value of monetary rewards of varying magnitude. Startle responses after receiving feedback that a potential reward was won or not won were compared with a baseline condition without a potential gain. Furthermore, startle responses during anticipation of no versus potential gain were compared. Consistent with previous studies, startle-reflex magnitudes were significantly potentiated when participants anticipated a reward compared to no reward, which may reflect anticipatory arousal. Specifically for the largest reward (20-cents) startle magnitudes were potentiated when a reward was at stake but not won, compared to a neutral baseline without potential gain. In contrast, startle was not inhibited relative to baseline when a reward was won. This suggests that startle modulation during feedback is better characterized in terms of potentiation when missing out on reward rather than in terms of inhibition as a result of winning. However, neither of these effects were replicated in a more targeted second experiment. The discrepancy between these experiments may be due to differences in motivation to obtain rewards or differences in task engagement. From these experiments it may be concluded that the nature of the processing of reward feedback and reward cues is very sensitive to experimental parameters and settings. These studies show how apparently modest changes in these parameters and settings may lead to quite different modulations of appetitive/aversive motivation. A future experiment may shed more light on the question whether startle-reflex modulation after feedback is indeed mainly characterized by the aversive consequences of reward omission for relatively large rewards.

Prevalence rates of attention-deficit/hyperactivity disorder (ADHD) differ with geographical areas varying in sunlight intensity. Sun- or daylight reaching the retina establishes entrainment of the circadian clock to daylight. Changes herein, hence, alterations in clock alignment, could be reflected indirectly in inattention via sleep duration. We here studied (1) annual variation in inattention at treatment initiation; (2) annual variation in response to ADHD treatment [methylphenidate (MPH)] by day of treatment initiation; and (3) dose dependence. We predicted least baseline inattention during a period of high sunlight intensity implying more room for improvement (i.e., a better treatment response) when sunlight intensity is low. These hypotheses were not confirmed. High-dose treated patients, however, had significantly better attention after treatment than low-dosed treated patients, only when treated in the period from winter to summer solstice. Change in solar irradiance (SI) during low-dosed treatment period was negatively related to attentional improvement. The above described findings were primarily found in inattention ratings and replicated in omission errors on a continuous performance task. Daylight and inattention have been proposed to be related via mediation of the circadian system. One mechanism of MPH may be to enhance sensitivity to the diurnal entrainment to sunlight and the question can be raised whether appropriate lighting could potentiate the effects of stimulants.

Predicting what will happen in the future in terms of potential reward is essential in daily life. The aim of the current study was to investigate the neurotransmitter systems involved in the anticipation of reward value and probability. We hypothesized that dopaminergic and noradrenergic antagonism would affect anticipation of reward value and probability, respectively. Twenty-three healthy participants were included in a haloperidol (2 mg) × clonidine (0.150 mg) × placebo cross-over design and subjected to a Go/NoGo experimental task during which cues signaled the probability of subsequent target appearance. Reward value (amount of money that could be won for correct and fast responding to the target) as well as probability of target appearance was orthogonally manipulated across four task blocks. Cue-elicited EEG event-related potentials were recorded to assess anticipation of value and probability, respectively. The processing of reward value was affected by dopaminergic antagonism (haloperidol), as evidenced by reduction of the reward-related positivity and P300 to reward cues. This reduction was specifically significant for subjects with high baseline dopamine levels for the P300 and most pronounced for these subjects for the reward-related positivity. In contrast, the processing of reward probability was affected by noradrenergic antagonism (clonidine). In addition, both drugs reduced overall performance (omission rate, response speed variability). We conclude that at least anticipation of reward value and probability, respectively, is specifically affected by dopaminergic versus noradrenergic antagonism.

In this study we evaluate how cognitive load affects susceptibility to auditory signals. Previous research has used the frontal P3 (fP3) event related potential response to auditory novel stimuli as an index for susceptibility to auditory signals. This work demonstrated that tasks that induce cognitive load such as visual and manual tasks, reduced susceptibility. It is however unknown whether cognitive load without visual or manual components also reduces susceptibility. To investigate this, we induced cognitive load by means of the verb generation task, in which participants need to think about a verb that matches a noun. The susceptibility to auditory signals was measured by recording the event related potential in response to a successively presented oddball probe stimulus at 3 different inter-stimulus intervals, 0 ms, 200 ms or 400 ms after the offset of the noun from the verb generation task. An additional control baseline condition, in which oddball response was probed without a verb generation task, was also included. Results show that the cognitive load associated with the verb task reduces fP3 response (and associated auditory signal susceptibility) compared to baseline, independent of presentation interval. This suggests that not only visual and motor processing, but also cognitive load without visual or manual components, can reduce susceptibility to auditory signals and alerts., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Major Depressive Disorder (MDD) is a psychiatric disorder characterized by high comorbidity with cardiovascular disease. Furthermore, a combination of high heart rate (HR) and low heart rate variability (HRV) has been frequently reported in depressed patients. The present review proposes a frontal-vagal (brain-heart) network that overlaps with functional nodes of the depression network. Moreover, we summarize neuromodulation studies that have targeted key nodes in this depression network, with subsequent impact on heart rate (HR) or heart-rate-variability (HRV), such as the dorsolateral prefrontal cortex (DLPFC), subgenual anterior cingulate cortex (sgACC), and the vagus nerve (VN). Based on the interplay of this frontal-vagal network, we emphasize the importance of including HR and HRV measurements in human depression studies, in particular those that conduct neuromodulation, in order to obtain a better understanding of the pathways that are affected, and we explore the possibilities of using this frontal-vagal interplay as a method for target engagement in neuromodulation treatments. This frontal-vagal network theory opens-up the possibility for individualizing neuromodulation treatments such as rTMS. A recent development called Neuro-Cardiac-Guided TMS (NCG-TMS), was developed based on this theory, and an individual-participant meta-analysis is presented. Four studies provide consistent and replicable support for NCG-TMS as a target engagement method, with consistent HR deceleration during frontal TMS and HR acceleration during motor strip TMS., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Optimal decision-making requires humans to predict the value and probability of prospective (rewarding) outcomes. The aim of the present study was to evaluate and dissociate the cortical mechanisms activated by information on an upcoming potentially rewarded target stimulus with varying probabilities. Electro-cortical activity was recorded during a cued Go/NoGo experiment, during which cue letters signaled upcoming target letters to which participants had to respond. The probability of target letter appearance after the cue letter and the amount of money that could be won for correct and fast responses were orthogonally manipulated across four task blocks. As expected, reward availability affected a prefrontally distributed reward-related positivity, and a centrally distributed P300-like event-related potential (ERP). Moreover, a late prefrontally distributed ERP was affected by probability information. These results show that information on value and probability, respectively, activates separate mechanisms in the cortex. These results contribute to a further understanding of the neural underpinnings of normal and abnormal reward processing., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide 12 easy-to-implement consensus recommendations and point out the problems that can arise when they are not followed. Furthermore, we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis., Competing Interests: FV, GB, PB, AB, JB, CC, HC, LC, BC, JC, AD, DE, HG, IG, AH, RH, SJ, JK, IL, CL, GL, DM, SM, AM, MP, RP, KR, MR, JS, AS, KT, Mv, LV, MV, JW, RW, BZ, CB No competing interests declared, AA, NS Reviewing editor, eLife, CB has received payment for consulting and speaker's honoraria from GlaxoSmithKline, Novartis, Genzyme, and Teva. He has recent research grants with Novartis and Genzyme, SC consults for Shire, Ieso Digital Health, Cambridge Cognition, and Promentis. Dr Chamberlain's research is funded by Wellcome Trust (110049/Z/15/Z), TR consults for Cambridge Cognition, Mundipharma and Unilever. He receives royalties from Cambridge Cognition (CANTAB) and has recent research grants with Shionogi and SmallPharma, KR has received speaker's honoraria and grants for other projects from Eli Lilly and Shire, RS has consulted to Highland Therapeutics, Eli Lilly and Co., and Purdue Pharma. He has commercial interest in a cognitive rehabilitation software company, eHave, (© 2019, Verbruggen et al.)

Alcohol use disorder (AUD) is characterized by excessive and persistent alcohol use, despite adverse consequences. AUD often originates during adolescence, as do other substance use disorders. However, despite periods of excessive alcohol intake, many adolescents reduce their alcohol use by early adulthood. Brain development, social context, personality traits, and genetic makeup are thought to play an important role in these age-dependent fluctuations in alcohol use. However, studies that directly investigate age-related differences in the effects of alcohol exposure on brain and behavior are sparse. Therefore, to better understand the relationship between adolescent alcohol consumption and AUD-like behavior, this study compared the degree of control over alcohol seeking in rats that differed in terms of age of onset of alcohol drinking and in their level of alcohol consumption. We hypothesized that control over alcohol seeking is more prominent in adolescent-onset rats than in adult-onset rats, and that control over alcohol seeking is related to the consumed amount of alcohol. To test this hypothesis, alcohol seeking in the presence of a conditioned aversive stimulus was assessed after 2 months of intermittent alcohol access (IAA) in rats that consumed alcohol from postnatal day 42 (adolescence) or day 77 (adulthood). The rats were subdivided into low (LD), medium (MD), or high (HD) alcohol drinking rats, in order to assess the impact of the extent of alcohol intake on control over alcohol seeking. The adolescent-onset animals consumed slightly, but significantly less alcohol compared to the adult-onset rats. In adult-onset rats, we found that conditioned suppression of alcohol seeking, i.e., reduction of alcohol seeking by presentation of a conditioned aversive stimulus, was most pronounced in LD. By contrast, in the adolescent-onset rats, MD and HD showed increased alcohol seeking compared to LD, which was suppressed by conditioned aversive stimuli. Taken together, these findings reveal a complex relationship between the age of onset and level of alcohol intake with control over alcohol seeking, whereby adolescent rats consume less alcohol than adults. In adult rats, control over alcohol seeking is negatively related to preceding levels of alcohol intake. By contrast, adolescent rats appear to retain control over alcohol seeking, even after a history of high levels of alcohol intake.

We investigate how susceptible human drivers are to auditory signals in three situations: when stationary, when driving, or when being driven by an autonomous vehicle. Previous research has shown that human susceptibility is reduced when driving compared to when being stationary. However, it is not known how susceptible humans are under autonomous driving conditions. At the same time, good susceptibility is crucial under autonomous driving conditions, as such systems might use auditory signals to communicate a transition of control from the automated vehicle to the human driver. We measured susceptibility using a three-stimulus auditory oddball paradigm while participants experienced three driving conditions: stationary, autonomous, or driving. We studied susceptibility through the frontal P3 (fP3) Electroencephalography Event-Related Potential response (EEG ERP response). Results show that the fP3 component is reduced in autonomous compared to stationary conditions, but not as strongly as when participants drove themselves. In addition, the fP3 component is further reduced when the oddball task does not require a response (i.e., in a passive condition, versus active). The implication is that, even in a relatively simple autonomous driving scenario, people's susceptibility of auditory signals is not as high as would be beneficial for responding to auditory stimuli., Competing Interests: The authors have declared that no competing interests exist.

Background: Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During EMDR, patients make horizontal eye movements (EMs) while simultaneously recalling a traumatic memory, which renders the memory less vivid and emotional when it is later recalled again. Recalling highly emotional autobiographical memories enhances noradrenergic neurotransmission. Noradrenaline (NA) strengthens memory (re)consolidation. However, memories become less vivid after recall+EMs. Therefore, NA might either play no significant role or serve to strengthen memories that are degraded by EMs. The present study was designed to test the latter hypothesis. We predicted that blocking NA would abolish the memory degrading effects of EMs., Methods: Fifty-six healthy participants selected three negative autobiographical memories. One was then recalled while making EMs, one was recalled without EMs, and one was not recalled. Vividness and emotionality of the memories as well as heart rate and skin conductance level during memory retrieval were measured before, directly after, and 24 hours after the EM task. Before the task, participants received a placebo or the noradrenergic β-receptor blocker propranolol (40 mg)., Results: There were no effects of EMs on memory emotionality or psychophysiological measures in the propranolol and placebo groups. However, in the placebo group, but not in the propranolol group, memory vividness significantly decreased from pretest to posttest and follow-up after recall+EMs relative to the control conditions., Conclusions: Blocking NA abolished the effects of EMs on the vividness of emotional memories, indicating that NA is crucial for EMDR effectiveness and possibly strengthens the reconsolidation of the degraded memory., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Prior research has shown that the ratio between resting-state theta (4-7 Hz)-beta (13-30 Hz) oscillations in the electroencephalogram (EEG) is associated with reward- and punishment-related feedback learning and risky decision making. However, it remains unclear whether the theta/beta EEG ratio is also an electrophysiological index for poorer behavioral adaptation when reward and punishment contingencies change over time. The aim of the present study was to investigate whether resting-state theta (4-7 Hz)-beta (13-30 Hz) EEG ratio correlated with reversal learning. A 4-min resting-state EEG was recorded and a gambling task with changing reward-punishment contingencies was administered in 128 healthy volunteers. Results showed an inverse relationship between theta/beta EEG ratio and reversal learning. Our findings replicate and extend previous findings by showing that higher midfrontal theta/beta EEG ratios are associated with poorer reversal learning and behavioral adaptive responses under changing environmental demands.

Reinforcement learning tasks are often used to assess participants' tendency to learn more from the positive or more from the negative consequences of one's action. However, this assessment often requires comparison in learning performance across different task conditions, which may differ in the relative salience or discriminability of the stimuli associated with more and less rewarding outcomes, respectively. To address this issue, in a first set of studies, participants were subjected to two versions of a common probabilistic learning task. The two versions differed with respect to the stimulus (Hiragana) characters associated with reward probability. The assignment of character to reward probability was fixed within version but reversed between versions. We found that performance was highly influenced by task version, which could be explained by the relative perceptual discriminability of characters assigned to high or low reward probabilities, as assessed by a separate discrimination experiment. Participants were more reliable in selecting rewarding characters that were more discriminable, leading to differences in learning curves and their sensitivity to reward probability. This difference in experienced reinforcement history was accompanied by performance biases in a test phase assessing ability to learn from positive vs. negative outcomes. In a subsequent large-scale web-based experiment, this impact of task version on learning and test measures was replicated and extended. Collectively, these findings imply a key role for perceptual factors in guiding reward learning and underscore the need to control stimulus discriminability when making inferences about individual differences in reinforcement learning.

Antidepressant medication is the most common treatment for major depressive disorder (MDD), however, the precise working mechanism underlying these treatments remains unclear. Recent neuromodulation treatments demonstrate that direct stimulation of the dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and subgenual anterior cingulate (sgACC) relate to clinical improvement, suggesting connectivity alterations of the DLPFC-DMPFC-sgACC network to mediate antidepressant response. The international Study to Predict Optimized Treatment in Depression (iSPOT-D) is an international multicentre study that collected EEG data for 1008 MDD patients, randomized to 3 different antidepressant medications (N=447 MDD with complete pre- and post-treatment data and N=336 non-MDD). Treatment response was defined by a decline of >50% on the Hamilton Rating Score for Depression (HRSD 17 ). We investigated whether connectivity in alpha and theta frequencies of the DLPFC-DMPFC-sgACC network changed from pre- to post-treatment between: (i) patients and controls, and (ii) responders (R) and non-responders (NR). Women exhibited higher alpha and theta connectivity compared to males, both pre- and post-treatment. Furthermore, theta, but not alpha, hypo-connectivity was found for MDD patients. A decreased alpha connectivity after treatment was found only for male responders, while non-responders and females exhibited no changes in alpha connectivity. Decreasing alpha connectivity could potentially serve as a treatment emergent biomarker, in males only. Furthermore, it could be useful to a priori stratify by gender for future MDD studies., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

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.

Background: Excessive anticipatory reactions to potential future adversity are observed across a range of anxiety disorders, but the neurogenetic mechanisms driving interindividual differences are largely unknown. We aimed to discover and validate a gene-brain-behavior pathway by linking presumed genetic risk for anxiety-related psychopathology, key neural activity involved in anxious anticipation, and resulting aversive emotional states., Methods: The functional neuroanatomy of aversive anticipation was probed through functional magnetic resonance imaging in two independent samples of healthy subjects (n = 99 and n = 69), and we studied the influence of genetic variance in the serotonin transporter linked polymorphic region (5-HTTLPR). Skin conductance and startle data served as objective psychophysiological indices of the intensity of individuals' anticipatory responses to potential threat., Results: Threat cues signaling risk of future electrical shock activated the dorsomedial prefrontal cortex (dmPFC), anterior insula, bed nucleus of the stria terminalis, thalamus, and midbrain consistently across both samples. Threat-related dmPFC activation was enhanced in 5-HTTLPR short allele carriers in sample 1 and this effect was validated in sample 2. Critically, we show that this region mediates the increase in anticipatory psychophysiological reactions in short allele carriers indexed by skin conductance (experiment 1) and startle reactions (experiment 2)., Conclusions: The converging results from these experiments demonstrate that innate 5-HTTLPR linked variation in dmPFC activity predicts psychophysiological responsivity to pending threats. Our results reveal a neurogenetic pathway mediating interindividual variability in anticipatory responses to threat and yield a novel mechanistic account for previously reported associations between genetic variability in serotonin transporter function and stress-related psychopathology., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Inhibition concerns the capacity to suppress on-going response tendencies. Patient data and results from neuro-imaging and magnetic-stimulation studies point to a proactive mechanism involving top-down control signals that potentiate inhibitory sensory-motor connections, depending on whether possibly necessary inhibition is anticipated or not. The proactive mechanism is manifest in stronger sensory-cortex responses to stop signals yielding successful inhibition, observed as a modulation of short-latency human evoked potentials (N1) which may overlap with generic mechanisms for infrequent-event detection. A second, reactive, mechanism would be much more independent of the specific inhibition context, and generalize to situations in which behavioral interrupt is not dictated by task demands but invoked by the salience of task-irrelevant but potentially distracting events. The reactive mechanism is visible in a longer-latency human event-related potential termed frontal P3 (fP3) which is elicited by (successful) stop stimuli and most likely originates from dorsal-medial prefrontal cortex (preSMA), and is dissociated from the proactive mechanism pharmacologically and by individual differences. Implications may arise for more personalized treatments of disorders such as ADHD., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Preparation for an action, such as grasping an object, is accompanied by an enhanced perception of the object's action-relevant features, such as orientation and size. Cortical feedback from motor planning areas to early visual areas may drive this enhanced perception. To examine whether action preparation modulates activity in early human visual cortex, subjects grasped or pointed to oriented objects while high-resolution fMRI data were acquired. Using multivoxel pattern analysis techniques, we could decode with >70% accuracy whether a grasping or pointing action was prepared from signals in visual cortex as early as V1. These signals in early visual cortex were observed even when actions were only prepared but not executed. Anterior parietal cortex, on the other hand, showed clearest modulation for actual movements. This demonstrates that preparation of actions, even without execution, modulates relevant neuronal populations in early visual areas., (Copyright © 2015 the authors 0270-6474/15/356472-09$15.00/0.)

This study aimed to examine facial mimicry in 6-7 year old children with autism spectrum disorder (ASD) and to explore whether facial mimicry was related to the severity of impairment in social responsiveness. Facial electromyographic activity in response to angry, fearful, sad and happy facial expressions was recorded in twenty 6-7 year old children with ASD and twenty-seven typically developing children. Even though results did not show differences in facial mimicry between children with ASD and typically developing children, impairment in social responsiveness was significantly associated with reduced fear mimicry in children with ASD. These findings demonstrate normal mimicry in children with ASD as compared to healthy controls, but that in children with ASD the degree of impairments in social responsiveness may be associated with reduced sensitivity to distress signals.

Empathy has been associated with decreased antisocial and increased prosocial behavior. This study examined empathy and prosocial behavior in response to sadness and distress in disruptive behavior disorder (DBD) and attention-deficit hyperactivity disorder (ADHD). Six- and 7-year-old children with DBD (with and without ADHD) (n = 67) and with ADHD only (n = 27) were compared to typically developing children (TD) (n = 37). Parents and teachers rated affective empathy in response to sadness and distress on the Griffith Empathy Measure. Children reported affective empathic ability in response to sad story vignettes. Empathy-induced prosocial behavior in response to sadness and distress was assessed with a computer task, the Interpersonal Response Task (IRT). Compared to TD, children with DBD (with and without ADHD) and those with ADHD only were rated as less empathic by their teachers, but not by their parents. No differences between groups were observed in children who reported affect correspondence. Children with DBD (with and without ADHD) showed less prosocial behavior in response to sadness and distress compared to TD. Children with ADHD only did not differ from TD. An additional analysis comparing all children with a diagnosis to the TD group revealed that the difference in prosocial behavior remained after controlling for ADHD symptoms, but not after controlling for DBD symptoms. These findings of impaired empathy-induced prosocial behavior in response to sadness and distress in young children with DBD suggest that interventions to ameliorate peer relationships may benefit from targeting on increasing prosocial behavior in these children.

Recent studies suggest a role for sleep and sleep problems in the etiology of attention deficit hyperactivity disorder (ADHD) and a recent model about the working mechanism of sensori-motor rhythm (SMR) neurofeedback, proposed that this intervention normalizes sleep and thus improves ADHD symptoms such as inattention and hyperactivity/impulsivity. In this study we compared adult ADHD patients (N = 19) to a control group (N = 28) and investigated if differences existed in sleep parameters such as Sleep Onset Latency (SOL), Sleep Duration (DUR) and overall reported sleep problems (PSQI) and if there is an association between sleep-parameters and ADHD symptoms. Secondly, in 37 ADHD patients we investigated the effects of SMR and Theta/Beta (TBR) neurofeedback on ADHD symptoms and sleep parameters and if these sleep parameters may mediate treatment outcome to SMR and TBR neurofeedback. In this study we found a clear continuous relationship between self-reported sleep problems (PSQI) and inattention in adults with- and without-ADHD. TBR neurofeedback resulted in a small reduction of SOL, this change in SOL did not correlate with the change in ADHD symptoms and the reduction in SOL only happened in the last half of treatment, suggesting this is an effect of symptom improvement not specifically related to TBR neurofeedback. SMR neurofeedback specifically reduced the SOL and PSQI score, and the change in SOL and change in PSQI correlated strongly with the change in inattention, and the reduction in SOL was achieved in the first half of treatment, suggesting the reduction in SOL mediated treatment response to SMR neurofeedback. Clinically, TBR and SMR neurofeedback had similar effects on symptom reduction in ADHD (inattention and hyperactivity/impulsivity). These results suggest differential effects and different working mechanisms for TBR and SMR neurofeedback in the treatment of ADHD.

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.

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 β). 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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this review article an overview of the history and current status of neurofeedback for the treatment of ADHD and insomnia is provided. Recent insights suggest a central role of circadian phase delay, resulting in sleep onset insomnia (SOI) in a sub-group of ADHD patients. Chronobiological treatments, such as melatonin and early morning bright light, affect the suprachiasmatic nucleus. This nucleus has been shown to project to the noradrenergic locus coeruleus (LC) thereby explaining the vigilance stabilizing effects of such treatments in ADHD. It is hypothesized that both Sensori-Motor Rhythm (SMR) and Slow-Cortical Potential (SCP) neurofeedback impact on the sleep spindle circuitry resulting in increased sleep spindle density, normalization of SOI and thereby affect the noradrenergic LC, resulting in vigilance stabilization. After SOI is normalized, improvements on ADHD symptoms will occur with a delayed onset of effect. Therefore, clinical trials investigating new treatments in ADHD should include assessments at follow-up as their primary endpoint rather than assessments at outtake. Furthermore, an implication requiring further study is that neurofeedback could be stopped when SOI is normalized, which might result in fewer sessions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Increased theta (4-7 Hz)-beta (13-30 Hz) power ratio in resting state electroencephalography (EEG) has been associated with risky disadvantageous decision making and with impaired reinforcement learning. However, the specific contributions of theta and beta power in risky decision making remain unclear. The first aim of the present study was to replicate the earlier found relationship and examine the specific contributions of theta and beta power in risky decision making using the Iowa Gambling Task. The second aim of the study was to examine whether the relation were associated with differences in reward or punishment sensitivity. We replicated the earlier found relationship by showing a positive association between theta/beta ratio and risky decision making. This correlation was mainly driven by theta oscillations. Furthermore, theta power correlated with reward motivated learning, but not with punishment learning. The present results replicate and extend earlier findings by providing novel insights into the relation between thetabeta ratios and risky decision making. Specifically, findings show that resting-state theta activity is correlated with reinforcement learning, and that this association may be explained by differences in reward sensitivity., (© 2013.)

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)., (Copyright © 2013 Elsevier B.V. All rights reserved.)

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.

Background: Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder of childhood, with average worldwide prevalence of 5.3%, varying by region., Methods: We assessed the relationship between the prevalence of ADHD and solar intensity (SI) (kilowatt hours/square meters/day) on the basis of multinational and cross-state studies. Prevalence data for the U.S. were based on self-report of professional diagnoses; prevalence data for the other countries were based on diagnostic assessment. The SI data were obtained from national institutes., Results: In three datasets (across 49 U.S. states for 2003 and 2007, and across 9 non-U.S. countries) a relationship between SI and the prevalence of ADHD was found, explaining 34%-57% of the variance in ADHD prevalence, with high SI having an apparent preventative effect. Controlling for low birth weight, infant mortality, average income (socioeconomic status), latitude, and other relevant factors did not change these findings. Furthermore, these findings were specific to ADHD, not found for the prevalence of autism spectrum disorders or major depressive disorder., Conclusions: In this study we found a lower prevalence of ADHD in areas with high SI for both U.S. and non-U.S. data. This association has not been reported before in the literature. The preventative effect of high SI might be related to an improvement of circadian clock disturbances, which have recently been associated with ADHD. These findings likely apply to a substantial subgroup of ADHD patients and have major implications in our understanding of the etiology and possibly prevention of ADHD by medical professionals, schools, parents, and manufacturers of mobile devices., (Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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)., (Copyright © 2013 Elsevier Inc. All rights reserved.)