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Pain can be modulated by several cognitive techniques, typically involving increased cognitive control and decreased sensory processing. Recently, it has been demonstrated that pain can also be attenuated by mindfulness. Here, we investigate the underlying brain mechanisms by which the state of mindfulness reduces pain. Mindfulness practitioners and controls received unpleasant electric stimuli in the functional magnetic resonance imaging scanner during a mindfulness and a control condition. Mindfulness practitioners, but not controls, were able to reduce pain unpleasantness by 22% and anticipatory anxiety by 29% during a mindful state. In the brain, this reduction was associated with decreased activation in the lateral prefrontal cortex and increased activation in the right posterior insula during stimulation and increased rostral anterior cingulate cortex activation during the anticipation of pain. These findings reveal a unique mechanism of pain modulation, comprising increased sensory processing and decreased cognitive control, and are in sharp contrast to established pain modulation mechanisms.

In emotional learning tasks, sex differences, stress effects and an interaction of these two moderators have often been observed. The sex hormones estradiol (E2) and progesterone (P4) vary over the menstrual cycle. We tested groups with different sex hormone status: 39 men, 30 women in the luteal phase (LU, high E2+P4) and 29 women taking oral contraceptives (OC, low E2+P4). They received either 30 mg cortisol or placebo prior to instructed differential fear conditioning consisting of neutral conditioned stimuli (CS) and an electrical stimulation (unconditioned stimulus; UCS). One figure (CS+) was paired with the UCS, the other figure (CS-) never. During extinction, no electrical stimulation was administered. Regarding fear acquisition, results showed higher skin conductance and higher brain responses to the CS+ compared to the CS- in several structures that were not modulated by cortisol or sex hormones. However, OC women exhibited higher CS+/CS- differentiations than men and LU women in the amygdala, thalamus, anterior cingulate and ventromedial prefrontal cortex during extinction. The suppression of endogenous sex hormones by OC seems to alter neuronal correlates of extinction. The observation that extinction is influenced by the current sex hormone availability is relevant for future studies and might also be clinically important.

The "dual klepsydra model" (DKM) of internal time representation successfully models duration reproduction data, but relations between the DKM-based parameter kappa ("loss rate") and procedural variables (presentation modality) or individual characteristics (cognitive indices, age, sex) remained as yet unexplored. For that purpose, were-analyzed data from an earlier time reproduction study (N = 100), using visually or acoustically presented intervals of 1-5 sec. duration. Typical values of parameter kappa were approximately 0.03-0.04 sec.(-1), corresponding to relaxation times of internal "lossy integrators" of approximately 30 sec. Significant effects of presentation modality (smaller kappa values for the visual reproduction task) and of age (greater kappa in acoustic reproduction with increasing age) were observed. Cognitive variables (working memory, general fluid reasoning, attention) and sex of participants were not associated with kappa. Cognitive functions seem to play only a minor, if any, role at the level of time representation addressed by the DKM.

An important feature of the human defense system comprises fear learning, which stress hormones can crucially modulate. However, stress hormones might influence men and women differently, in part because of interactions with sex hormones. In women, distinct stages of the menstrual cycle or the intake of oral contraceptives (OC) affect sex hormone levels. In this study, we used a differential fear conditioning paradigm with electrical stimulation as unconditioned stimulus (UCS) following one neutral stimulus (conditioned stimulus, CS+), but not another (CS-).To investigate implicit fear learning, participants were distracted from detecting the contingencies between CS and UCS. To address interaction effects of sex and stress hormones, 32 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women received either 30 mg cortisol or a placebo. In the contrast CS+ minus CS-, an interaction between cortisol administration and sex hormone status emerged in the anterior parahippocampal gyrus and the hippocampus. Cortisol reduced fear learning in men, FO, and LU women, but enhanced it in OC women. Additionally, cortisol attenuated differential amygdala activation in the entire group. These results demonstrate that OC usage substantially modifies cortisol effects on emotional learning in women, particularly in memory-related medial temporal lobe regions. Further, a high dose of cortisol reduces amygdala differentiation pointing to a lowered learning ability of the defense system under high cortisol concentrations, irrespective of current sex hormone availability.

The unexpected return of mental clarity and memory shortly before death in patients suffering from severe psychiatric and neurologic disorders, which we have called "terminal lucidity", has been reported in the medical literature over the past 250 years, but has received little attention. We review a range of terminal lucidity cases in order to encourage investigation of the mechanisms involved and possible insights into both the neuroscience of memory and cognition at the end of life and treatment of terminal illness. These examples include case reports of patients suffering from brain abscesses, tumors, strokes, meningitis, dementia or Alzheimer's disease, schizophrenia, and affective disorders. Several of these accounts suggest that during terminal lucidity, memory and cognitive abilities may function by neurologic processes different from those of the normal brain. We expect that significant contributions to better understanding the processes involved in memory and cognition processing might be gained through in-depth studies of terminal lucidity. Studying terminal lucidity might also facilitate the development of novel therapies. In addition, increased awareness of unusual end-of-life experiences could help physicians, caregivers, and bereaved family members be prepared for encountering such experiences, and help those individuals cope with them.

RATIONALE: Biased processing of drug-associated stimuli is believed to be a crucial feature of addiction. Particularly, an attentional bias seems to contribute to the disorder's maintenance. Recent studies suggest differential effects for stimuli associated with the beginning (BEGIN-smoking-stimuli) or the terminal stage of the smoking ritual (END-smoking-stimuli), with the former but not the later evoking high cue-reactivity. OBJECTIVE: The current study investigated the neuronal network underlying an attentional bias to BEGIN-smoking-stimuli and END-smoking-stimuli in smokers and tested the hypothesis that the attentional bias is greater for BEGIN-smoking-stimuli. METHODS: Sixteen non-deprived smokers and 16 non-smoking controls participated in an fMRI study. Drug pictures (BEGIN-smoking-stimuli, END-smoking-stimuli) and control pictures were overlaid with geometrical figures and presented for 300 ms. Subjects had to identify picture content (identification-task) or figure orientation (distraction-task). The distraction-task was intended to demonstrate attentional bias. RESULTS: Behavioral data revealed an attentional bias to BEGIN-smoking-stimuli but not to END-smoking-stimuli in both groups. However, only smokers showed mesocorticolimbic deactivations in the distraction-task with BEGIN-smoking-stimuli. Importantly, these deactivations were significantly stronger for BEGIN- than for END-smoking-stimuli and correlated with the attentional bias score. CONCLUSIONS: Several explanations may account for missing group differences in behavioral data. Brain data suggest smokers using regulatory strategies in response to BEGIN-smoking-stimuli to prevent the elicitation of motivational responses interfering with distraction-task performance. These strategies could be reflected in the observed deactivations and might lead to a performance level in smokers that is similar to that of non-smokers.

BACKGROUND: Gene by environment (G×E) interaction between genetic variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) and stressful life events (SLEs) has been extensively studied in the context of depression. Recent findings suggest increased neural and endocrine stress sensitivity as a possible mechanism conveying elevated vulnerability to psychopathology. Furthermore, these G×E mediated alterations very likely reflect interrelated biological processes. METHODS: In the present functional magnetic resonance imaging study, amygdala reactivity to fearful stimuli was assessed in healthy male adults (n = 44), who were previously found to differ with regard to endocrine stress reactivity as a function of 5-HTTLPR × SLEs. Furthermore, functional connectivity between the amygdala and the hypothalamus was measured as a potential mechanism linking elevated neural and endocrine responses during stressful/threatening situations. The study sample was carefully preselected regarding 5-HTTLPR genotype and SLEs. RESULTS: We report significant G×E interaction on neural response patterns and functional amygdala-hypothalamus connectivity. Specifically, homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs (S'S'/high SLEs group) displayed elevated bilateral amygdala activation in response to fearful faces. Within the same sample, a comparable G×E interaction effect has previously been demonstrated regarding increased cortisol reactivity, indicating a cross-validation of heightened biological stress sensitivity. Furthermore, S'S'/high SLEs subjects were characterized by an increased functional coupling between the right amygdala and the hypothalamus, thus indicating a potential link between neural and endocrine hyperreactivity. CONCLUSIONS: The present findings contribute to the ongoing debate on 5-HTTLPR × SLEs interaction and are discussed with respect to clinical implications.

The perception of action is influenced by the observer's familiarity with its movement. However, how does motor familiarity with own movement patterns modulate the visual perception of action effects? Cortical activation was examined with fMRI while 20 observers were watching videotaped point-light displays of markers on the shoulders, the right elbow, and wrist of an opposing table tennis player. The racket and ball were not displayed. Participants were asked to predict the invisible effect of the stroke, that is, the ball flight direction. Different table tennis models were used without the observers knowing and being informed in advance that some of the presented videos displayed their own movements from earlier training sessions. Prediction had to be made irrespective of the identity of the player represented by the four moving markers. Results showed that participants performed better when observing their "own" strokes. Using a region-of-interest approach, fMRI data showed that observing own videos was accompanied by stronger activation (compared to other videos) in the left angular gyrus of the inferior parietal lobe and the anterior rostral medial frontal cortex. Other videos elicited stronger activation than own videos in the left intraparietal sulcus and right supramarginal gyrus. We suggest that during action observation of motorically familiar movements, the compatibility between the observed action and the observers' motor representation is already coded in the parietal angular gyrus--in addition to the paracingulate gyrus. The activation in angular gyrus is presumably part of an action-specific effect retrieval that accompanies actor-specific prefrontal processing. The intraparietal sulcus seems to be sensitive to incongruence between observed kinematics and internal model representations, and this also influences processing in the supramarginal gyrus.

Patients suffering from obsessive-compulsive disorder (OCD) are characterized by dysregulated neuronal processing of disorder-specific and also unspecific affective stimuli. In the present study, we investigated whether generic fear-inducing, disgust-inducing, and neutral stimuli can be decoded from brain patterns of single fMRI time samples of individual OCD patients and healthy controls. Furthermore, we tested whether differences in the underlying encoding provide information to classify subjects into groups (OCD patients or healthy controls). Two pattern classification analyses were conducted. In analysis 1, we used a classifier to decode the category of a currently viewed picture from extended fMRI patterns of single time samples (TR=3s) in individual subjects for several pairs of categories. In analysis 2, we used a searchlight approach to predict subjects' diagnostic status based on local brain patterns. In analysis 1, we obtained significant accuracies for the separation of fear-eliciting from neutral pictures in OCD patients and healthy controls. Separation of disgust-inducing from neutral pictures was significant in healthy controls. In analysis 2, we identified diagnostic information for the presence of OCD in the orbitofrontal cortex, and in the caudate nucleus. Accuracy obtained in these regions was 100% (p<10(-6)). To summarize our findings, by using multivariate pattern classification techniques we were able to identify neurobiological markers providing reliable diagnostic information about OCD. The classifier-based fMRI paradigms proposed here might be integrated in future diagnostic procedures and treatment concepts.

The understanding of individual differences in responses to disgusting stimuli is important to gain more insight into the development of certain psychiatric disorders. The aim of this study was to investigate conditioned disgust responses, its potential overlap with conditioned fear responses (CRs) and the influence of disgust sensitivity on blood oxygen level-dependent responses. Yet even though current studies report evidence that disgust sensitivity is a vulnerability factor, the knowledge about the underlying neural mechanisms remains very limited. Two groups were exposed either to a disgust- or a fear-conditioning paradigm. Using functional magnetic resonance imaging, we identified a conjoint activated network including the cingulate cortex, the nucleus accumbens, the orbitofrontal cortex, and the occipital cortex within the disgust- and the fear-conditioning group. Moreover, we report evidence of increased insula activation in the disgust-conditioning group. In addition, functional connectivity analysis revealed increased interconnections, most pronounced within the insula in the high disgust sensitivity group compared with the low disgust sensitivity group. The conjunction results suggest that the conditioned responses in disgust and fear conditioning recruit the same neural network, implicating that different conditioned responses of aversive learning depend on a common neural network. Increased insula activation within the disgust-conditioning group might be attributable to heightened interoceptive processes, which might be more pronounced in disgust. Finally, the findings regarding disgust sensitivity are discussed with respect to vulnerability factors for certain psychiatric disorders.

Abstract-In traditional astrological frameworks of interpretation, resonances between positions of astrological planets in the birth charts of friends (called "candidates" and their "partners") are assumed to play a decisive role. In the study presented here, this general claim is investigated at diff erent levels of sophistication. For this purpose, fi ve main hypotheses are formulated, all of which are diff erent versions of the general assumption that there are more resonances between birth charts of friends than can be expected randomly. The material on which the study is based is taken from a questionnaire concerning the dates of birth of candidates to whom the questionnaire was distributed, as well as those of their partners. Having gained interesting results with partially supporting evidence, but also with elements that did not support the hypotheses, the experiment was repeated with a second sample. It failed to replicate the results of the fi rst experiment.

Attentional, intentional, and motivational factors are known to influence the physiological responses in a Concealed Information Test (CIT). Although concealing information is essentially a social action closely related to motivation, CIT studies typically rely on testing participants in an environment lacking of social stimuli: subjects interact with a computer while sitting alone in an experimental room. To address this gap, we examined the influence of social stimuli on the physiological responses in a CIT. Seventy-one participants underwent a mock-crime experiment with a modified CIT. In a between-subjects design, subjects were either questioned acoustically by a pre-recorded male voice presented together with a virtual male experimenter's uniform face or by a text field on the screen, which displayed the question devoid of face and voice. Electrodermal activity (EDA), respiration line length (RLL), phasic heart rate (pHR), and finger pulse waveform length (FPWL) were registered. The Psychopathic Personality Inventory - Revised (PPI-R) was administered in addition. The differential responses of RLL, pHR, and FPWL to probe vs. irrelevant items were greater in the condition with social stimuli than in the text condition; interestingly, the differential responses of EDA did not differ between conditions. No modulatory influence of the PPI-R sum or subscale scores was found. The results emphasize the relevance of social aspects in the process of concealing information and in its detection. Attentional demands as well as the participants' motivation to avoid detection might be the important links between social stimuli and physiological responses in the CIT.

Remembering something that has not in fact been experienced is commonly referred to as false memory. The Deese-Roediger-McDermott (DRM) paradigm is a well-elaborated approach to this phenomenon. This study attempts to investigate the peripheral physiology of false memories induced in a visual DRM paradigm. The main research question is whether false recognition is different from true recognition in terms of accompanying physiological responses.Sixty subjects participated in the experiment, which included a study phase with visual scenes each showing a group of interrelated items in social contexts. Subjects were divided into an experimental group undergoing a classical DRM design and a control group without DRM manipulation. The control group was implemented in order to statistically control for possible biases produced by memorability differences between stimulus types. After a short retention interval, a pictorial recognition phase was conducted in the manner of a Concealed Information Test. Simultaneous recordings of electrodermal activity, respiration line length, phasic heart rate, and finger pulse waveform length were used. Results yielded a significant Group by Item Type interaction, showing that true recognition is accompanied by greater electrodermal activity than false recognition.Results are discussed in the light of Sokolov's Orienting Reflex, the Preliminary Process Theory and the Concealed Information Test. Implications and restrictions of the introduced design features are critically discussed. This study demonstrates the applicability of measures of peripheral physiology to the field of false memory research.

Fear acquisition and extinction are crucial mechanisms in the etiology and maintenance of anxiety disorders. Moreover, they might play a pivotal role in conveying the influence of genetic and environmental factors on the development of a (more or less) stronger proneness for, or resilience against psychopathology. There are only few insights in the neurobiology of genetically and environmentally based individual differences in fear learning and extinction. In this functional magnetic resonance imaging study, 74 healthy subjects were investigated. These were invited according to 5-HTTLPR/rs25531 (S+ vs. L(A)L(A); triallelic classification) and TPH2 (G(-703)T) (T+ vs. T-) genotype. The aim was to investigate the influence of genetic factors and traumatic life events on skin conductance responses (SCRs) and neural responses (amygdala, insula, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC)) during acquisition and extinction learning in a differential fear conditioning paradigm. Fear acquisition was characterized by stronger late conditioned and unconditioned responses in the right insula in 5-HTTLPR S-allele carriers. During extinction traumatic life events were associated with reduced amygdala activation in S-allele carriers vs. non-carriers. Beyond that, T-allele carriers of the TPH2 (G(-703)T) polymorphism with a higher number of traumatic life events showed enhanced responsiveness in the amygdala during acquisition and in the vmPFC during extinction learning compared with non-carriers. Finally, a combined effect of the two polymorphisms with higher responses in S- and T-allele carriers was found in the dACC during extinction. The results indicate an increased expression of conditioned, but also unconditioned fear responses in the insula in 5-HTTLPR S-allele carriers. A combined effect of the two polymorphisms on dACC activation during extinction might be associated with prolonged fear expression. Gene-by-environment interactions in amygdala and vmPFC activation may reflect a neural endophenotype translating genetic and adverse environmental influences into vulnerability for or resilience against developing affective psychopathology.

During observation of ambiguous figures our perception reverses spontaneously although the visual information stays unchanged. Research on this phenomenon so far suffered from the difficulty to determine the instant of the endogenous reversals with sufficient temporal precision. A novel experimental paradigm with discontinuous stimulus presentation improved on previous temporal estimates of the reversal event by a factor of three. It revealed that disambiguation of ambiguous visual information takes roughly 50 ms or two loops of recurrent neural activity. Further, the decision about the perceptual outcome has taken place at least 340 ms before the observer is able to indicate the consciously perceived reversal manually. We provide a short review about physiological studies on multistable perception with a focus on electrophysiological data. We further present a new perspective on multistable perception that can easily integrate previous apparently contradicting explanatory approaches. Finally we propose possible extensions toward other research fields where ambiguous figure perception may be useful as an investigative tool.

Repeated learning improves memory. Temporally distributed ("spaced") learning can be twice as efficient than massed learning. Importantly, learning success is a non-monotonic maximum function of the spacing interval between learning units. Further optimal spacing intervals seem to exist at different time scales from seconds to days. We briefly review the current state of knowledge about this "spacing effect" and then discuss very similar but so far little noticed spacing patterns during a form of synaptic plasticity at the cellular level, called long term potentiation (LTP). The optimization of learning is highly relevant for all of us. It may be realized easily with appropriate spacing. In our view, the generality of the spacing effect points to basic mechanisms worth for coordinated research on the different levels of complexity.