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Inconsistent findings from several functional magnetic resonance imaging (fMRI) studies on fear and disgust raise the question which brain regions are relatively specialized and which are general in the processing of these basic emotions. Some of these inconsistencies could partially be due to inter-individual differences in the experience of the applied emotional stimuli. In the present study, we therefore correlated the participants' individual online reports of fear and disgust with their hemodynamic responses towards each of the fear- and disgust-inducing scenes. Sixty six participants (32 females) took part in the fMRI study. In an event-related design, they saw 50 pictures with different emotional impact (10 neutral, 20 disgust-inducing, 20 fear-inducing). Pictures were presented for 4 s and participants rated each picture online - just after the presentation - on the dimensions disgust and fear among others. The results indicate that the processing of disgust- and fear-inducing pictures involves similar as well as distinct brain regions. Both emotional stimulus categories resulted in activations in the extended occipital cortex, in the prefrontal cortex, and in the amygdala. However, insula activations were only significantly correlated with subjective ratings of disgust, pointing to a specific role of this brain structure in the processing of disgust.

Theta increases with workload and is associated with numerous processes including working memory, problem solving, encoding, or self monitoring. These processes, in turn, involve numerous structures of the brain. However, the relationship between regional brain activity and the occurrence of theta remains unclear. In the present study, simultaneous EEG-fMRI recordings were used to investigate the functional topography of theta. EEG-theta was enhanced by mental arithmetic-induced workload. For the EEG-constrained fMRI analysis, theta-reference time-series were extracted from the EEG, reflecting the strength of theta occurrence during the time course of the experiment. Theta occurrence was mainly associated with activation of the insular cortex, hippocampus, superior temporal areas, cingulate cortex, superior parietal, and frontal areas. Though observation of temporal and insular activation is in accord with the theory that theta specifically reflects encoding processes, the involvement of several other brain regions implies that surface-recorded theta represents comprehensive functional brain states rather than specific processes in the brain. The results provide further evidence for the concept that emergent theta band oscillations represent dynamic functional binding of widely distributed cortical assemblies, essential for cognitive processing. This binding process may form the source of surface-recorded EEG theta.

This study investigated differences in brain activation during meditation between meditators and non-meditators. Fifteen Vipassana meditators (mean practice: 7.9 years, 2h daily) and fifteen non-meditators, matched for sex, age, education, and handedness, participated in a block-design fMRI study that included mindfulness of breathing and mental arithmetic conditions. For the meditation condition (contrasted to arithmetic), meditators showed stronger activations in the rostral anterior cingulate cortex and the dorsal medial prefrontal cortex bilaterally, compared to controls. Greater rostral anterior cingulate cortex activation in meditators may reflect stronger processing of distracting events. The increased activation in the medial prefrontal cortex may reflect that meditators are stronger engaged in emotional processing.

Some authors have suggested separate mechanisms for the processing of temporal intervals above versus below 2-3s. Given that the evidence is mixed, the present experiment was carried out as a critical test of the separate-mechanism hypothesis. Subjects reproduced five standard durations of 1-5s presented in the auditory and visual modalities. The Corsi-block test was used to assess effects of working-memory span on different interval lengths. Greater working-memory span was associated with longer reproductions of intervals of 3-5s. A factor analysis run on mean reproduced intervals revealed one modality-unspecific factor for durations of 1-2s and two modality-specific factors for longer intervals. These results are interpreted as further indications that two different processes underlie temporal reproductions of shorter and longer intervals.

Current models of attention describe attention not as a homogenous entity but as a set of neural networks whose measurement yields a set of three endophenotypes-alerting, orienting, and executive control. Previous findings revealed different neuroanatomical regions for these subsystems, and data from twin studies indicate differences in their heritability. The present study investigated the molecular genetic basis of attention in a sample of 100 healthy subjects. Attention performance was assessed with the attention network test that distinguishes alerting, orienting, and executive control (conflict) using a simple reaction time paradigm with different cues and congruent and incongruent flankers. Two gene loci on candidate genes for cognitive functioning, the functional catechol-O-methyltransferase (COMT) VAL158MET and the tryptophan hydroxylase 2 (TPH2) -703 G/T promoter polymorphism, were tested for possible associations with attention. COMT is involved in the catabolism of dopamine, and TPH is the rate-limiting enzyme for serotonin synthesis. Results showed no effect of the COMT polymorphism on attention performance. However, the TT genotype of TPH2 -03 G/T was significantly associated with more errors (a possible indicator of impaired impulse control; p = .001) and with decreased performance in executive control (p = .001). This single-nucleotide polymorphism on the TPH2 gene explained more than 10% of the variance in both indicators of attention stressing the role of the serotonergic system for cognitive functions.

Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.

OBJECTIVE: The experience of time is strongly related to our momentary mood states. Patients with a life-threatening illness experience an extreme change in mood and suffer from psychological distress that can develop into clinically relevant psychiatric disorders, like anxiety and depression. The aim of this study was to investigate the associations among the subjective perception of time, psychological distress, and quality of life in patients with hematological malignancies. METHODS: Eighty-eight inpatients with hematological malignancies rated how fast time passes subjectively on a visual analog scale and prospectively estimated a time span of 13 min. The Hospital Anxiety and Depression Scale (HADS) self-report measures of health-related quality of life (FACT-G) and spiritual well-being (FACIT-Sp) were employed to assess psychological distress and quality of life. RESULTS: Those patients who reported a lower quality of life, less spiritual well-being, and more anxiety experienced a slower passage of subjective time and overestimated the 13-min time interval. SIGNIFICANCE OF RESULTS: Our interpretation of the results is that patients with a life-threatening illness who show symptoms of psychological distress draw attention away from meaningful thoughts and actions and, thus, experience time as passing more slowly. An altered sense of time can be a sign of mental suffering, which should be addressed within psycho-oncological interventions. As this is the first study to demonstrate this relation in cancer patients, further research is needed to investigate the experience of time and its relation to meaning as an issue in clinical diagnostics.

Cognitive disturbances are common in Parkinson's disease (PD). Examination of cognitive function often reveals deficits in executive functions, including maintenance and inhibition of attention, flexibility in thinking, and planning. The involvement of the dopaminergic system in cognitive executive functions has been suggested by numerous studies. The aim of the present study was to analyze the effect of cognitive training on cognitive performance of PD-patients (N=26). Half of the patients participated in a cognitive training regimen, while the other patients only received standard treatment. The outcome showed improved performance of the group with cognitive treatment in two executive tasks after the training period, while no improvement was seen in the standard-treatment group. The results indicate that specific training is required for improvement of executive functions, while general rehabilitation is not sufficient. Thus, PD-patients might benefit from a short-term cognitive executive function training program that is tailored to the individual patient's needs.

Dopamine is known as the main neurotransmitter modulating the activation of the reward system of the brain. The DRD2 TaqIA polymorphism is associated with dopamine D2 receptor density which plays an important role in the context of reward. Persons carrying an A1 allele have a lower D2 receptor density and a higher risk to show substance abuse. The present study was designed to investigate the influence of the DRD2 TaqIA polymorphism and the selective D2 receptor agonist bromociptine on the activation of the reward system by means of functional magnetic resonance imaging (fMRI). In a double-blind crossover study with 24 participants we found an increase of reward system activation from placebo to bromocriptine only in subjects carrying the A1 allele. Furthermore, only A1 carrier showed an increase of performance under bromocriptine. The results are interpreted as reflecting a specific sensitivity for dopamine agonists in persons carrying an A1 allele and may complement actual data and theories of the development of addiction disorders postulating a higher genetic risk for substance abuse in carrier of the A1 allele.

The stress hormone cortisol is known to influence declarative memory and associative learning. In animals, stress has often been reported to have opposing effects on memory and learning in males and females. In humans, the effects of cortisol have mainly been studied at the behavioral level. The aim of the present experiment was to characterize the effects of a single cortisol dose (30 mg) on the hemodynamic correlates of fear conditioning. In a double-blind group comparison study subjects (17 females and 17 males) received 30 mg cortisol or placebo orally before participating in a discriminative fear conditioning paradigm. Results revealed that cortisol impaired electrodermal signs of learning (the first interval response) in males, while no conditioned SCRs emerged for the females independent of treatment. fMRI results showed that cortisol reduced activity for the CS+ > CS- comparison in the anterior cingulate, the lateral orbitofrontal cortex and the medial prefrontal cortex in males. Opposite findings (increase in these regions under cortisol) were detected in females. In addition, cortisol reduced the habituation in the CS+ > CS- contrast in the dorsolateral prefrontal cortex independent of sex. Finally, cortisol also modified the response to the electric shock (the UCS) by enhancing the activity of the anterior as well as the posterior cingulate. In sum, these findings demonstrate that in humans cortisol mostly influences prefrontal brain activation during fear conditioning and that these effects appear to be modulated by sex.

This study investigates the effect of awareness of stimulus contingencies on BOLD responses within the amygdala, the orbitofrontal, and the occipital cortex, and on differential skin conductance responses (SCRs) during fear conditioning. Of two geometric figures, the paired conditioned stimulus (CS+) predicted an electrical stimulus (unconditioned stimulus = UCS), whereas the unpaired conditioned stimulus (CS-) was not followed by the UCS. Awareness of stimulus contingencies was manipulated experimentally, creating an aware and an unaware group: a distracter figure and a working memory task were introduced to conceal the stimulus contingencies of the conditioning paradigm, hence preventing contingency detection in the unaware group. The aware group was informed beforehand about the relation between CS+, CS-, and UCS. Differential SCRs were only obtained in the aware but not in the unaware group. Conversely, we observed enhanced responses of the amygdala, the orbitofrontal, and the occipital cortex to the CS+ in the unaware group only. Thus, we found a dissociation of SCR differentiation and the activation of a neural fear network depending on the presence or absence of awareness. These results support a model of fear conditioning that distinguishes between a more cognitive level of learning, reflected in contingency awareness and differential SCRs, and the awareness independent activation of a fear network.

Standard diagnostic procedures for assessing temporal-processing abilities of adult patients with aphasia have so far not been developed. In our study, temporal-order measurements were conducted using two different experimental procedures to identify a suitable measure for clinical studies. Additionally, phoneme-discrimination abilities were tested on the word, as well as on the sentence level, as a relationship between temporal processing and phoneme-discrimination abilities is assumed. Patients with aphasia displayed significantly higher temporal-order thresholds than control subjects. The detection of an association between temporal processing and speech processing, however, depended on the stimuli and the phoneme-discrimination tasks used. Our results also suggest top-down feedback on phonemic processing.

Two correlates of outcome processing in the orbitofrontal cortex (OFC) have been proposed in the literature: One hypothesis suggests that the lateral/medial division relates to representation of outcome valence (negative vs. positive), and the other suggests that the medial OFC maintains steady stimulus-outcome associations, whereas the lateral OFC represents changing (unsteady) outcomes to prepare for response shifts. These two hypotheses were contrasted by comparing the original with the inverted version of the Iowa Gambling Task in an event-related functional magnetic resonance imaging experiment. Results showed (1) that (caudo) lateral OFC was indeed sensitive to the steadiness of the outcomes and not merely to outcome valence and (2) that the original and the inverted tasks, although both designed to measure sensitivity for future outcomes, were not equivalent as they enacted different behaviors and brain activation patterns. Results are interpreted in terms of Kahneman and Tversky's prospect theory suggesting that cognitions and decisions are biased differentially when probabilistic future rewards are weighed against consistent punishments relative to the opposite scenario [Kahneman, D., & Tversky, A. Choices, values, and frames. American Psychologist, 39, 341-350, 1984]. Specialized processing of unsteady rewards (involving caudolateral OFC) may have developed during evolution in support of goal-related thinking, prospective planning, and problem solving.

Priming tasks are used for investigating the deficits of selective attention in schizophrenia, which are thought to be related to the psychotic symptoms. Priming was assessed in acutely psychotic unmedicated (n = 22) and medicated (n = 36) schizophrenia patients and in control subjects (n = 42). The subjects had to indicate the location of a target stimulus in two consecutive stimulus displays (prime and probe). Each stimulus appeared together with a distractor on a screen. Negative Priming is characterized by an increase in reaction time, whenever a probe target is presented at a prime distractor location. Positive Priming is characterized by a decrease in reaction time, when the probe target is presented at the prime target location. Schizophrenia patients altogether showed no abnormalities in priming effects, neither in the acute phase of illness (medicated and unmedicated) nor in partial remission (one month later, medicated). In unmedicated patients however Negative Priming was inversely correlated with the severity of positive symptoms. This indicates a priming deficit in a small subgroup of severely ill patients. The data support the notion that automatic (implicit) mechanisms of learning are unimpaired in schizophrenia patients unless symptoms exceed a certain critical level.

Cognitive deficits affecting memory, attention and speed of information processing are common in multiple sclerosis (MS). The mechanisms of cognitive impairment remain unclear. Here, we examined the association between neuropsychological test performance and brain atrophy in a group of mildly disabled patients with relapsing-remitting MS. We applied voxel-based morphometry (SPM2) to investigate the distribution of brain atrophy in relation to cognitive performance. Patients had lower scores than control subjects on tests of memory and executive function, including the PASAT, Digit Span Backward and a test of short-term verbal memory (Memo). Among patients, but not healthy controls, performance on the PASAT, a comprehensive measure of cognitive function and reference task for the cognitive evaluation of MS-patients, correlated with global grey matter volume as well as with grey matter volume in regions associated with working memory and executive function, including bilateral prefrontal cortex, precentral gyrus and superior parietal cortex as well as right cerebellum. Compared to healthy subjects, patients showed a volume reduction in left temporal and prefrontal cortex, recently identified as areas predominantly affected by diffuse brain atrophy in MS. A comparison of low performers in the patient group with their matched control subjects showed more extensive and bilateral temporal and frontal volume reductions as well as bilateral parietal volume loss, compatible with the progression of atrophy found in more advanced MS-patients. These findings indicate that MS-related deficits in cognition are closely associated with cortical atrophy.

Humans show large differences in the preferred timing of their sleep and activity. This so-called "chronotype" is largely regulated by the circadian clock. Both genetic variations in clock genes and environmental influences contribute to the distribution of chronotypes in a given population, ranging from extreme early types to extreme late types with the majority falling between these extremes. Social (e.g., school and work) schedules interfere considerably with individual sleep preferences in the majority of the population. Late chronotypes show the largest differences in sleep timing between work and free days leading to a considerable sleep debt on work days, for which they compensate on free days. The discrepancy between work and free days, between social and biological time, can be described as 'social jetlag.' Here, we explore how sleep quality and psychological wellbeing are associated with individual chronotype and/or social jetlag. A total of 501 volunteers filled out the Munich ChronoType Questionnaire (MCTQ) as well as additional questionnaires on: (i) sleep quality (SF-A), (ii) current psychological wellbeing (Basler Befindlichkeitsbogen), (iii) retrospective psychological wellbeing over the past week (POMS), and (iv) consumption of stimulants (e.g., caffeine, nicotine, and alcohol). Associations of chronotype, wellbeing, and stimulant consumption are strongest in teenagers and young adults up to age 25 yrs. The most striking correlation exists between chronotype and smoking, which is significantly higher in late chronotypes of all ages (except for those in retirement). We show these correlations are most probably a consequence of social jetlag, i.e., the discrepancies between social and biological timing rather than a simple association to different chronotypes. Our results strongly suggest that work (and school) schedules should be adapted to chronotype whenever possible.

The aim of this fMRI study was to explore brain structures that are involved in the processing of erotic and disgust-inducing pictures. The stimuli were chosen to trigger approach and withdrawal tendencies, respectively. By adding sadomasochistic (SM) scenes to the design and examining 12 subjects with and 12 subjects without sadomasochistic preferences, we introduced a picture category that induced erotic pleasure in one sample and disgust in the other sample. Since we also presented neutral pictures, all subjects viewed pictures of four different categories: neutral, disgust-inducing, erotic, and SM erotic pictures. The analysis indicated that several brain structures are commonly involved in the processing of disgust-inducing and erotic pictures (occipital cortex, hippocampus, thalamus, and the amygdala). The ventral striatum was specifically activated when subjects saw highly sexually arousing pictures. This indicates the involvement of the human reward system during the processing of visual erotica.

Absorption represents a disposition to experience altered states of consciousness characterized by intensively focused attention. It is correlated with hypnotic susceptibility and includes phenomena ranging from vivid perceptions and imaginations to mystical experiences. Based on the assumption that drug-induced and naturally occurring mystical experiences share common neural mechanisms, we hypothesized that Absorption is influenced by the T102C polymorphism affecting the 5-HT2a receptor, which is known to be an important target site of hallucinogens like LSD. Based on the pivotal role ascribed to the prefrontal executive control network for absorbed attention and positive symptoms in schizophrenia, it was further hypothesized that Absorption is associated with the VAL158MET polymorphism of the catechol-O-methyltransferase (COMT) gene affecting the dopaminergic neurotransmitter system. The Tellegen Absorption Scale was administered to 336 subjects (95 male, 241 female). Statistical analysis revealed that the group with the T/T genotype of the T102C polymorphism, implying a stronger binding potential of the 5-HT2a receptor, indeed had significantly higher Absorption scores (F = 10.00, P = 0.002), while no main effect was found for the COMT polymorphism. However, the interaction between T102C and COMT genotypes yielded significance (F = 3.89; P = 0.049), underlining the known functional interaction between the 5-HT and the dopaminergic system. These findings point to biological foundations of the personality trait of Absorption.

The question to what extent emotion-related brain activation depends upon the presentation design (block design vs. event-related design) and the stimulus type (scene pictures vs. pictures with facial mimic) has hardly been addressed in previous functional magnetic resonance imaging (fMRI) research. In the present fMRI experiment, 40 right-handed subjects viewed pictures with fear-inducing and disgust-inducing content as well as facial expressions of fear and disgust. Pictures of neutral objects and neutral facial mimic were used as control stimuli. The pictures were presented in a block design for half of the subjects; the other half viewed the same stimuli as singular events in randomized sequence. The participants had been instructed to passively view the pictures. Disgust-evoking scenes provoked activation in the amygdala, the insula and the orbitofrontal cortex (OFC). This applied to the blocked as well as to the event-related design. Fear-relevant scenes were associated with activity in the insula, the OFC and the middle temporal gyri in the event-related design. The presentation in a block design only led to activation in the middle temporal gyri. Facial expressions of disgust and fear did not trigger significant activation neither in the blocked nor event-related design. This surprising outcome may be a result of context and task effects. The face stimuli which were presented together with the more complex scenes in a passive viewing paradigm possibly were not salient enough to trigger emotional processing.

This functional magnetic resonance imaging study investigated the disgust- and fear-reactivity of patients suffering from obsessive-compulsive disorder (OCD). Ten OCD patients were scanned while viewing blocks of pictures showing OCD triggers from their personal environment and OCD-irrelevant disgust-inducing, fear-inducing and neutral scenes. Afterwards, the patients rated the intensity of the induced disgust, fear and OCD symptoms. The responses were compared with those of 10 healthy control subjects. The disorder-relevant pictures provoked intense OCD symptoms in the clinical group associated with increased activation in the bilateral prefrontal cortex, the left insula, the right supramarginal gyrus, the left caudate nucleus and the right thalamus. The patients gave higher disgust and fear ratings than the controls for all aversive picture categories. Neural responses towards the disorder-irrelevant disgusting and fear-inducing material included more pronounced insula activation in patients than controls. Summarizing, photos of individual OCD-triggers are an effective means of symptom provocation and activation of the fronto-striato-thalamo-parietal network. The increased insular reactivity of OCD patients during all aversive picture conditions might mirror their susceptibility to experience negative somatic states.