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This study investigated whether bulimia nervosa (BN) and binge-eating disorder (BED) are associated with structural brain abnormalities. Both disorders share the main symptom binge-eating, but are considered differential diagnoses. We attempted to identify alterations in grey matter volume (GMV) that are present in both psychopathologies as well as disorder-specific GMV characteristics. Such information can help to improve neurobiological models of eating disorders and their classification. A total of 50 participants (patients suffering from BN (purge type), BED, and normal-weight controls) underwent structural MRI scanning. GMV for specific brain regions involved in food/reinforcement processing was analyzed by means of voxel-based morphometry. Both patient groups were characterized by greater volumes of the medial orbitofrontal cortex (OFC) compared to healthy controls. In BN patients, who had increased ventral striatum volumes, body mass index and purging severity were correlated with striatal grey matter volume. Altogether, our data implicate a crucial role of the medial OFC in the studied eating disorders. The structural abnormality might be associated with dysfunctions in food reward processing and/or self-regulation. The bulimia-specific volume enlargement of the ventral striatum is discussed in the framework of negative reinforcement through purging and associated weight regulation.

Drug-associated stimuli (cues) have a prominent role in addiction research because they are able to provoke craving and relapses. Generally, drug cues are seen as conditioned excitatory stimuli, which elicit drug seeking and usage. However, newer data suggest differential effects for smoking stimuli depending on their stage in the smoking ritual. Specifically, stimuli associated with the terminal stage of smoke consumption (END-stimuli) may evoke reactivity opposite to the reactivity evoked by stimuli associated with the beginning of smoke consumption (BEGIN-stimuli). This fMRI study compared 20 nondeprived smokers with 20 nonsmokers to unravel the influence of smoking-related pictures displaying the beginning (BEGIN-stimuli) and termination (END-stimuli) of the smoking ritual on neural activity in the addiction network. In addition, 20 deprived smokers (12 h deprivation) were investigated to explore the effects of deprivation on the processing of these stimuli. In nondeprived smokers, BEGIN-stimuli reliably activated the addiction network (for example, the ventral striatum, orbitofrontal cortex, and anterior cingulate cortex (ACC)). In contrast, END-stimuli triggered a differential pattern of activations as well as deactivations; deactivations were found in the ventral striatum and the ACC. Deprivation had no clear effect on the responses triggered by BEGIN-stimuli, but affected the reactivity to END-stimuli. Our data clearly suggest that stimuli associated with different stages of the smoking ritual trigger differential neuronal responses. While BEGIN-stimuli generally seem to activate the addiction network, END-stimuli presumably have some inhibitory properties. This new finding might add to a more differentiated understanding of cue reactivity and addiction.

A Concealed Information Test (CIT) investigates differential physiological responses to deed-related (probe) vs. irrelevant items. The present study focused on the detection of concealed information using simultaneous recordings of autonomic and brain electrical measures. As a secondary issue, verbal and pictorial presentations were compared with respect to their influence on the recorded measures. Thirty-one participants underwent a mock-crime scenario with a combined verbal and pictorial presentation of nine items. The subsequent CIT, designed with respect to event-related potential (ERP) measurement, used a 3-3.5s interstimulus interval. The item presentation modality, i.e. pictures or written words, was varied between subjects; no response was required from the participants. In addition to electroencephalogram (EEG), electrodermal activity (EDA), electrocardiogram (ECG), respiratory activity, and finger plethysmogram were recorded. A significant probe-vs.-irrelevant effect was found for each of the measures. Compared to sole ERP measurement, the combination of ERP and EDA yielded incremental information for detecting concealed information. Although, EDA per se did not reach the predictive value known from studies primarily designed for peripheral physiological measurement. Presentation modality neither influenced the detection accuracy for autonomic measures nor EEG measures; this underpins the equivalence of verbal and pictorial item presentation in a CIT, regardless of the physiological measures recorded. Future studies should further clarify whether the incremental validity observed in the present study reflects a differential sensitivity of ERP and EDA to different sub-processes in a CIT.

Executive working memory operations are related to prefrontal regions in the healthy brain. Moreover, neuroimaging data provide evidence for a functional dissociation of ventrolateral and dorsolateral prefrontal cortex. Most authors either suggest a modality-specific or a function-specific prefrontal cortex organization. In the present study we particularly aimed at the identification of different prefrontal cerebral areas that are involved in executive inhibitory processes during spatial working memory encoding. In an fMRI study (functional magnetic resonance imaging) we examined the neural correlates of spatial working memory processing by varying the amount of executive demands of the task. Twenty healthy volunteers performed the Corsi Block-Tapping test (CBT) during fMRI. The CBT requires the storage and reproduction of spatial target sequences. In a second condition, we presented an adapted version of the Block-Suppression-Test (BST). The BST is based on the original CBT but additionally requires the active suppression of visual distraction within the target sequences. In comparison to the CBT performance, particularly the left dorsolateral prefrontal cortex (BA 9) showed more activity during the BST condition. Our results show that the left dorsolateral prefrontal cortex plays a crucial role for executive controlled inhibition of spatial distraction. Furthermore, our findings are in line with the processing model of a functional dorsolateral-ventrolateral prefrontal cortex organization.

Analyses of neural mechanisms of duration processing are essential for the understanding of psychological phenomena which evolve in time. Different mechanisms are presumably responsible for the processing of shorter (below 500 ms) and longer (above 500 ms) events but have not yet been a subject of an investigation with functional magnetic resonance imaging (fMRI). In the present study, we show a greater involvement of several brain regions - including right-hemispheric midline structures and left-hemispheric lateral regions - in the processing of visual stimuli of shorter as compared to longer duration. We propose a greater involvement of lower-level cognitive mechanisms in the processing of shorter events as opposed to higher-level mechanisms of cognitive control involved in longer events.

Fear conditioning is influenced by stress but opposing effects in males and females have often been reported. In a previous human functional magnetic resonance imaging (fMRI) study, we observed acute effects of the stress hormone cortisol on prefrontal structures. Men showed evidence for impaired fear conditioning after cortisol treatment, while the opposite pattern was found for women. In the current experiment, we tested whether similar sex-dependent effects would occur on the neural level if contingency awareness was prevented experimentally to investigate implicit learning processes. A differential fear conditioning experiment with transcutaneous electrical stimulation as unconditioned stimulus and geometric figures as conditioned stimuli (CS) was conducted. One figure was always paired (CS+), whereas the other (CS-) was never paired with the UCS. Thirty-nine (19 female) subjects participated in this fMRI study, receiving either placebo or 30 mg cortisol (hydrocortisone) before conditioning. Dependent variables were skin conductance responses (SCRs) and neural activity (BOLD signal). In line with prior findings in unaware participants, no differential learning could be observed for the SCRs. However, a sex x cortisol interaction was detected with a reduced mean response to the CS after cortisol treatment in men, while the opposite pattern was observed in women (enhanced mean SCR under cortisol). In the contrast CS+ minus CS-, neural activity showed a sex x cortisol interaction in the insula and further trends in the hippocampus and the thalamus. In these regions, cortisol reduced the CS+/CS- differentiation in men but enhanced it in women. In contrast to these sex specific effects, differential amygdala activation was found in the placebo group but not in the cortisol group, irrespective of sex. Further, differential neural activity in the amygdala and thalamus were positively correlated with the SCRs in the placebo group only. The present study in contingency unaware participants illustrates that cortisol has in some brain regions sex specific effects on neural correlates of emotional learning. These effects might translate into a different vulnerability of the two sexes for anxiety disorders.

Individuals are different 'chronotypes' with early 'larks' and late 'owls' forming the limits of a normal distribution in the population. We recently described that late chronotypes who suffer from a conflict between internal and external time ('social jetlag') suffer from more mental distress and are more likely to smoke than early chronotypes (Wittmann, Dinich, Merrow, and Roenneberg, 2006 . Social jetlag: mis-alignment of biological and social time. Chronobiology International, 23:497-509.). We performed a detailed analysis of the same database collected in 2002 comprising 134 daily smokers and 366 nonsmokers, scrutinizing the relationships between chronotype, smoking, and alcohol consumption as well as psychological well-being using a multiple mediation analysis. On average, smokers tend to be later chronotypes, report more sleep-associated psychosomatic symptoms, are more depressed, less balanced, and less vigilant. The mediation analysis suggests that only those late chronotypes who smoke and those who drink more suffer from increased psychological distress. We suggest that 'chronotype' is introduced as an additional factor in substance use, that is, when considering motives for smoking and drinking.

The ability to detect and learn contingencies between fearful stimuli and their predictive cues is an important capacity to cope with the environment. Contingency awareness refers to the ability to verbalize the relationships between conditioned and unconditioned stimuli. Although there is a heated debate about the influence of contingency awareness on conditioned fear responses, neural correlates behind the formation process of contingency awareness have gained only little attention in human fear conditioning. Recent animal studies indicate that the ventral striatum (VS) could be involved in this process, but in human studies the VS is mostly associated with positive emotions. To examine this question, we reanalyzed four recently published classical fear conditioning studies (n = 117) with respect to the VS at three distinct levels of contingency awareness: subjects, who did not learn the contingencies (unaware), subjects, who learned the contingencies during the experiment (learned aware) and subjects, who were informed about the contingencies in advance (instructed aware). The results showed significantly increased activations in the left and right VS in learned aware compared to unaware subjects. Interestingly, this activation pattern was only found in learned but not in instructed aware subjects. We assume that the VS is not involved when contingency awareness does not develop during conditioning or when contingency awareness is unambiguously induced already prior to conditioning. VS involvement seems to be important for the transition from a contingency unaware to a contingency aware state. Implications for fear conditioning models as well as for the contingency awareness debate are discussed.

In experimental studies using flight simulations subjects' duration estimates have shown to be an effective indicator of cognitive task demands. In this study we wanted to find out whether subjective time perception could serve as a measure of cognitive workload during simulated car driving. Participants drove on a round course of a driving simulator consisting of three different environments with different levels of task demands. Drivers were required to perform a time-production task while driving the vehicle. Electrodermal activity and subjective ratings of mental workload (SWAT) were recorded simultaneously. The length of produced intervals increased significantly in more complex driving situations, as did electrodermal activity and subjective ratings of mental workload. Thus, time production is a valid indicator of cognitive involvement in simulated driving and could become a valid method to measure the current mental workload of car drivers in various traffic situations.

Facilitated detection of threatening visual cues is thought to be adaptive. In theory, detection of threat cues should activate the amygdala independently from allocation of attention. However, previous studies using emotional facial expressions as well as phobic cues yielded contradictory results. We used fMRI to examine whether the allocation of attention to components of superimposed spider and bird displays modulates amygdala activation. Nineteen spider-phobic women were instructed to identify either a moving or a stationary animal in briefly presented double-exposure displays. Amygdala activation followed a dose-response relationship: Compared to congruent neutral displays (two birds), amygdala activation was most pronounced in response to congruent phobic displays (two spiders) and less but still significant in response to mixed displays (spider and bird) when attention was focused on the phobic component. When attention was focused on the neutral component, mixed displays did not result in significant amygdala activation. This was confirmed in a significant parametric graduation of the amygdala activation in the order of congruent phobic displays, mixed displays with attention focus on the spider, mixed displays with focus on the bird and congruent neutral displays. These results challenge the notion that amygdala activation in response to briefly presented phobic cues is independent from attention.

This functional magnetic resonance imaging study investigated long-term effects of cognitive behavior therapy (CBT) in individuals suffering from spider phobia. Ten female patients who had shown positive immediate CBT effects were invited to take part in a 6-month follow-up investigation. Here, the patients, along with eight non-phobic females, were presented with the same pictures depicting spiders, generally disgust-inducing, generally fear-inducing and neutral content, which they had viewed 6 months earlier. Patients' self-report and overt behavior indicated a positive long-term clinical improvement. Related hemodynamic changes included an increase in medial orbitofrontal cortex (OFC) activity. As the medial OFC is involved in emotion-related learning, especially in the representation of positive stimulus-outcome associations, we conclude that the medial OFC effect constitutes the neuronal basis of the lasting positive CBT outcome. Activity to disorder-irrelevant pictures decreased across the sessions in the lateral OFC and in the insula, which most likely reflects general habituation.

BACKGROUND: The underlying neurobiological mechanisms that account for the onset and maintenance of binge-eating disorder (BED) are not sufficiently understood. This functional magnetic resonance imaging (fMRI) study explored the neural correlates of visually induced food reward and loathing. METHOD: Sixty-seven female participants assigned to one of four groups (overweight BED patients, overweight healthy control subjects, normal-weight healthy control subjects, and normal-weight patients with bulimia nervosa) participated in the experiment. After an overnight fast, the participants' brain activation was recorded during each of the following three conditions: visual exposure to high-caloric food, to disgust-inducing pictures, and to affectively neutral pictures. After the fMRI experiment, the participants rated the affective value of the pictures. RESULTS: Each of the groups experienced the food pictures as very pleasant. Relative to the neutral pictures, the visual food stimuli provoked increased activation in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and insula across all participants. The BED patients reported enhanced reward sensitivity and showed stronger medial OFC responses while viewing food pictures than all other groups. The bulimic patients displayed greater arousal, ACC activation, and insula activation than the other groups. Neural responses to the disgust-inducing pictures as well as trait disgust did not differ between the groups. CONCLUSIONS: This study provides first evidence of differential brain activation to visual food stimuli in patients suffering from BED and bulimia nervosa.

The present paper investigates the effects of age, sex, and cognitive factors on temporal-order perception. Nine temporal-order tasks were employed using two and four stimuli presented in the auditory and visual modalities. Significantly increased temporal-order thresholds (TOT) in the elderly were found for almost all tasks, while sex differences were only observed for two tasks. Multiple regression analyses show that the performance on most temporal-order tasks can be predicted by cognitive factors, such as speed of fluid reasoning, short-term memory, and attention. However, age was a significant predictor of TOT in three tasks using visual stimuli. We conclude (1) that age-related differences can often be attributed to cognitive factors involved in temporal-order perception, and (2) that the concept of temporal-order perception is more complex than implied by the current models.

During prolonged observation of an ambiguous figure sudden perceptual reversals occur, while the stimulus itself stays unchanged. There is a vivid debate about whether bottom-up or top-down mechanisms underlie this phenomenon. In the present study, we investigated the interrelation of two experimental factors: volitional control and discontinuous stimulus presentation. Both factors strongly modulate the rate of perceptual reversals and each is attributed either as top-down or bottom-up. We found that participants can apply specific strategies to volitionally increase and/or decrease the stability duration of each of the possible percepts according to the experimental instructions. When attempts of volitional control are combined with discontinuous stimulus presentation the effects are fully additive. Our results indicate that perceptual reversals can originate from different neural mechanisms on different time scales.

Although our eyes receive incomplete and ambiguous information, our perceptual system is usually able to successfully construct a stable representation of the world. In the case of ambiguous figures, however, perception is unstable, spontaneously alternating between equally possible outcomes. The present study compared EEG responses to ambiguous figures and their unambiguous variants. We found that slight figural changes, which turn ambiguous figures into unambiguous ones, lead to a dramatic difference in an ERP ("event-related potential") component at around 400 ms. This result was obtained across two different categories of figures, namely the geometric Necker cube stimulus and the semantic Old/Young Woman face stimulus. Our results fit well into the Bayesian inference concept, which models the evaluation of a perceptual interpretation's reliability for subsequent action planning. This process seems to be unconscious and the late EEG signature may be a correlate of the outcome.

The Concealed Information Test (CIT) requires the examinee to deceptively deny recognition of known stimuli and to truthfully deny recognition of unknown stimuli. Because deception and orienting are typically coupled, it is unclear how exactly these sub-processes affect the physiological responses measured in the CIT. The present study aimed at separating the effects of deception from those of orienting. In a mock-crime study, using a modified CIT, thirty-six of seventy-two subjects answered truthfully ('truth group'), whereas the other thirty-six concealed their knowledge ('lie group'). Answering was delayed for 4 s after item presentation. Electrodermal activity (EDA), respiration (RLL), and phasic heart rate (HR) were recorded. A decomposition of EDA responses revealed two response components; the response in the first interval was expected to indicate orienting, stimulus evaluation, and answer preparation, whereas the response in the second interval was assumed to reflect answer-related processes. Inconclusively, both EDA components differentiated between 'probe' and 'irrelevant' items in both groups. Phasic HR and RLL differed between item classes only in the 'lie' group, thus reflecting answer-related processes, possibly deception, rather than merely orienting responses. The findings further support the notion that psychophysiological measures elicited by a modified CIT may reflect different mental processes involved in orienting and deception.

The simulation concept suggested by Jeannerod (Neuroimage 14:S103-S109, 2001) defines the S-states of action observation and mental simulation of action as action-related mental states lacking overt execution. Within this framework, similarities and neural overlap between S-states and overt execution are interpreted as providing the common basis for the motor representations implemented within the motor system. The present brain imaging study compared activation overlap and differential activation during mental simulation (motor imagery) with that while observing gymnastic movements. The fMRI conjunction analysis revealed overlapping activation for both S-states in primary motor cortex, premotor cortex, and the supplementary motor area as well as in the intraparietal sulcus, cerebellar hemispheres, and parts of the basal ganglia. A direct contrast between the motor imagery and observation conditions revealed stronger activation for imagery in the posterior insula and the anterior cingulate gyrus. The hippocampus, the superior parietal lobe, and the cerebellar areas were differentially activated in the observation condition. In general, these data corroborate the concept of action-related S-states because of the high overlap in core motor as well as in motor-related areas. We argue that differential activity between S-states relates to task-specific and modal information processing.

Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual klepsydra' model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates kappa were in the same order of magnitude as in earlier studies. In both experiments, kappa was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

Following the idea that response inhibition processes play a central role in concealing information, the present study investigated the influence of a Go/No-go task as an interfering mental activity, performed parallel to the Concealed Information Test (CIT), on the detectability of concealed information. 40 undergraduate students participated in a mock-crime experiment and simultaneously performed a CIT and a Go/No-go task. Electrodermal activity (EDA), respiration line length (RLL), heart rate (HR) and finger pulse waveform length (FPWL) were registered. Reaction times were recorded as behavioral measures in the Go/No-go task as well as in the CIT. As a within-subject control condition, the CIT was also applied without an additional task. The parallel task did not influence the mean differences of the physiological measures of the mock-crime-related probe and the irrelevant items. This finding might possibly be due to the fact that the applied parallel task induced a tonic rather than a phasic mental activity, which did not influence differential responding to CIT items. No physiological evidence for an interaction between the parallel task and sub-processes of deception (e.g. inhibition) was found. Subjects' performance in the Go/No-go parallel task did not contribute to the detection of concealed information. Generalizability needs further investigations of different variations of the parallel task.

Functional magnetic resonance imaging studies have examined neural correlates of disgust imagery, but have never taken into account the moderating effects of personality traits. Twenty-four women first viewed and subsequently visualized pictures with disgust-inducing and happiness-inducing content. Relative to the picture perception, disgust, and happiness imagery provoked activation of the insula, anterior cingulate cortex, and parietal cortex. Trait disgust was negatively correlated with localized brain activation (e.g. insula, amygdala, parietal cortex, anterior cingulate cortex) during disgust imagery. This study provides first evidence that disgust propensity is associated with brain activation during imagery of repulsive scenes.