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Biomedical subjects

Herta Flor

Publications and source records attributed to Herta Flor.

At least 37 records · Page 2Linked to original sources

Altered cortisol awakening response in posttraumatic stress disorder.

An altered function of the hypothalamic-pituitary-adrenal axis is assumed to be characteristic for Posttraumatic Stress Disorder (PTSD), although there is inconsistent empirical evidence. Only few studies examined the awakening cortisol response and a daytime profile in PTSD. Salivary cortisol levels were measured at seven intervals from awakening until 8 PM in trauma-exposed subjects with (N=29) and without PTSD (N=19) and in 15 non-exposed controls. While the three groups did not differ with respect to their first cortisol level immediately after awakening, the expected cortisol increase to awakening 15-60 min later was significantly lower in PTSD patients compared to non-PTSD subjects and healthy controls. This effect remained stable when trauma-exposed subjects with comorbid major depression were excluded from the analysis. A significant negative correlation between the overall cortisol secretion (AUC(G)) and overall PTSD symptomatology and hyper-arousal symptoms was found. The findings are discussed in light of the hypothesis of a counterregulation of hyper-arousal symptoms and chronic stress in PTSD.

Adult↗

Dynamic modulation of the primary somatosensory cortex during seeing and feeling a touched hand.

Previous work has demonstrated cross-modal links between vision and somatosensation at an early stage of sensory processing. Furthermore, recent behavioral studies have shown that viewing the stimulated body part can enhance tactile discrimination ability at the stimulated site. This study aims to investigate the role of the primary somatosensory cortex (SI) during visuotactile integration processes. Subjects looked at a hand in a video being touched on the first digit (D1) in synchrony with felt touches on their real hidden hand as compared with watching a video with asynchronous touches. During synchronous stimulation, subjects reported to feel the tactile sensation on the video hand, thus indicating that in this condition the subjects regarded the video hand as their own touched hand. This feeling disappeared in the asynchronous condition. Using neuromagnetic source imaging, we assessed the topography of the functional organization of SI related to tactile stimulation of D1. The cortical representation of D1 moved to a more inferior location during synchronous in comparison to asynchronous stimulation and rest. This modulation of the map in SI was significantly positively correlated with the feeling that the seen touch in the video represented the touch on the real hand. Thus, only if the seen touch is attributed to the own body, SI seems to be modulated.

Adolescent↗

Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions.

Altered glucocorticoid receptor (GR) signaling is a postulated mechanism for the pathogenesis of major depression. To mimic the human situation of altered GR function claimed for depression, we generated mouse strains that underexpress or overexpress GR, but maintain the regulatory genetic context controlling the GR gene. To achieve this goal, we used the following: (1) GR-heterozygous mutant mice (GR+/-) with a 50% GR gene dose reduction, and (2) mice overexpressing GR by a yeast artificial chromosome resulting in a twofold gene dose elevation. GR+/- mice exhibit normal baseline behaviors but demonstrate increased helplessness after stress exposure, a behavioral correlate of depression in mice. Similar to depressed patients, GR+/- mice have a disinhibited hypothalamic-pituitary-adrenal (HPA) system and a pathological dexamethasone/corticotropin-releasing hormone test. Thus, they represent a murine depression model with good face and construct validity. Overexpression of GR in mice evokes reduced helplessness after stress exposure, and an enhanced HPA system feedback regulation. Therefore, they may represent a model for a stress-resistant strain. These mouse models can now be used to study biological changes underlying the pathogenesis of depressive disorders. As a first potential molecular correlate for such changes, we identified a downregulation of BDNF protein content in the hippocampus of GR+/- mice, which is in agreement with the so-called neurotrophin hypothesis of depression.

Animals↗

Predictors of pain behaviors in fibromyalgia syndrome.

OBJECTIVE: To evaluate the contributions of physical, pain-related, cognitive, stress-related, affective, and spouse-related variables to differences in pain behaviors in subgroups of patients with fibromyalgia syndrome (FMS). METHODS: One hundred forty FMS patients underwent medical, physical, and psychological evaluation. Patients and 30 pain-free controls performed a routine physical activity (window-washing task) to elicit pain behaviors with or without the presence of their spouses. The behaviors and spouses' responses during this task were videotaped and subsequently rated. Patients were classified as dysfunctional (DYS), interpersonally distressed (ID), or adaptive copers (AC) based on responses to the Multidimensional Pain Inventory. Hierarchical regression analyses were used to identify predictors of pain behaviors for the total group and subgroups of patients. RESULTS: Patients classified as DYS demonstrated the highest number of pain behaviors compared with those classified as ID or AC. This difference was observable when the spouse was present. Spouse responses and physical variables were significantly related to pain behaviors in the DYS and ID groups with the model accounting for 77.1% and 41.9% of the variance, respectively. In contrast, for the AC group, stress factors were the most significant predictor of pain behaviors, accounting for 22.8% of the variance. CONCLUSION: The results indicate that different variables account for the presence of pain behaviors in different subgroups of patients. The data provide support for the heterogeneity of the diagnosis of FMS and have implications for treatment of subgroups of patients.

Behavior↗

Localization of the human female breast in primary somatosensory cortex.

RATIONALE: Despite an extensive body of research on the topography of the primary somatosensory cortex (S1) little is known about the representation of the trunk. AIM: The aim of this study was to determine the representation of the breast in S1 in human females. RESULTS: The representation of the human breast in primary somatosensory cortex was determined in ten healthy female subjects. Non-painful electrical stimulation of the mammilla (Th4 dermatome), groin (L1 dermatome) and the first digit of both sides of the body activated cutaneous receptors and thus elicited somatosensory evoked potentials. The representation of these body parts in primary somatosensory cortex (S1) was determined using neuroelectric source imaging. Equivalent current dipole localizations were overlaid with individual structural magnetic resonance images to account for individual cortical differences. The breast representation was localized between the representation of the groin and the first digit. In the medial-lateral direction the representation of the breast was approximately 15 mm lateral of the longitudinal fissure in the contralateral hemisphere. Source localizations were stable across subjects. However, one subject showed ipsilateral representation of the breast, which might be related to bilateral receptive fields of the ventral body midline representation. This study confirms the Penfield and Rasmussen (1950) invasive data by use of noninvasive source imaging.

Adolescent↗

Dynamic shifts in the organization of primary somatosensory cortex induced by bimanual spatial coupling of motor activity.

Previous work has shown that training and learning can induce powerful changes in the homuncular organization of the primary somatosensory cortex (SI). Moreover, a number of studies suggest the existence of short-term adaptation of representational maps in SI. Recently, motor activity has been shown to induce rapid modulation of somatosensory cortical maps. It is hypothesized that there is a task-related influence of motor and premotor areas upon the organization of somatosensory cortex. In order to test this hypothesis, we studied the functional organization of somatosensory cortex by examining coupling effects in a bimanual movement task. Bimanual coupling is known to be related to an activation of the premotor cortex and the supplementary motor area. The functional organization of the somatosensory cortex for known bimanual coupling effects was compared to the organization of the somatosensory cortex during the same movements but with only a small effort in coupling. Topography of the functional organization of the somatosensory cortex was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digit (D5). We could show that the cortical representations of D1 and D5 moved further apart during the bimanual coupling task in comparison to the same task without coupling and rest. Our data suggest that somatosensory cortical maps undergo fast and dynamic modulation as a result of a task-related influence of motor or premotor areas.

Adult↗

Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex.

Catechol-O-methyltransferase (COMT) degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A functional polymorphism in the COMT gene (val158met) accounts for a fourfold variation in enzyme activity. The low-activity met158 allele has been associated with improved working memory but with higher risk for anxiety-related behaviors. Using functional magnetic resonance imaging, we assessed the effects of COMT genotype on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 35 healthy subjects. The analysis of genotype effects was restricted to brain areas with robust activation by the task. To determine genedose effects, the number of met158 alleles (0, 1, or 2) was correlated with the blood oxygen level-dependent (BOLD) response elicited by pleasant or unpleasant stimuli compared with neutral stimuli. COMT genotype had no significant impact on brain activation by pleasant stimuli but was related to the neural response to unpleasant stimuli: reactivity to unpleasant stimuli was significantly positively correlated with the number of met158 alleles in the limbic system (left hippocampus, right amygdala, right thalamus), connected prefrontal areas (bilateral ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex), and the visuospatial attention system (bilateral fusiform gyrus, left inferior parietal lobule). Genotype explained up to 38% of interindividual variance in BOLD response elicited by unpleasant stimuli. We conclude that (1) genetic variations can account for a substantial part of interindividual variance in task-related brain activation and that (2) increased limbic and prefrontal activation elicited by unpleasant stimuli in subjects with more met158 alleles might contribute to the observed lower emotional resilience against negative mood states.

Adult↗

Deficient fear conditioning in psychopathy: a functional magnetic resonance imaging study.

CONTEXT: Psychopaths belong to a larger group of persons with antisocial personality disorder and are characterized by an inability to have emotional involvement and by the repeated violation of the rights of others. It was hypothesized that this behavior might be the consequence of deficient fear conditioning. OBJECTIVE: To study the cerebral, peripheral, and subjective correlates of fear conditioning in criminal psychopaths and healthy control subjects. DESIGN: An aversive differential pavlovian delay conditioning paradigm with slides of neutral faces serving as conditioned and painful pressure as unconditioned stimuli. SETTING: The Department of Medical Psychology at the University of Tübingen, Tübingen, Germany. PARTICIPANTS: Ten male psychopaths as defined by the Hare Psychopathy Checklist-Revised and 10 age- and education-matched healthy male controls. The psychopaths were criminal offenders on bail and waiting for their trial or were on parole. The healthy controls were recruited from the community. MAIN OUTCOME MEASURES: Brain activation based on functional magnetic resonance imaging, electrodermal responses, emotional valence, arousal, and contingency ratings. RESULTS: The healthy controls showed enhanced differential activation in the limbic-prefrontal circuit (amygdala, orbitofrontal cortex, insula, and anterior cingulate) during the acquisition of fear and successful verbal and autonomic conditioning. The psychopaths displayed no significant activity in this circuit and failed to show conditioned skin conductance and emotional valence ratings, although contingency and arousal ratings were normal. CONCLUSION: This dissociation of emotional and cognitive processing may be the neural basis of the lack of anticipation of aversive events in criminal psychopaths.

Adult↗

Activation of naloxone-sensitive and -insensitive inhibitory systems in a human pain model.

UNLABELLED: We investigated naloxone effects in a model of electrically induced pain and hyperalgesia. In a double-blind, placebo-controlled, cross-over study, 15 volunteers underwent four 150-minute sessions of high-current-density electrical stimulation of their forearms. After 60 minutes, naloxone or placebo was given intravenously (increasing plasma concentrations of 0.1, 1, and 10 ng/mL; 30 minutes each) in 3 of the 4 sessions. Pain ratings and areas of mechanical hyperalgesia were assessed at regular intervals during all sessions. The low doses of naloxone did not cause any significant change of pain rating of areas of hyperalgesia. In terms of intrasession effects, pain ratings and areas of hyperalgesia significantly decreased during the sessions to 62% (pain rating), 70% (area of punctuate hyperalgesia), and 82% (area of allodynia) of the initial values. Naloxone (10 ng/ml) reversed these decreases. In terms of between-session effects, the time course of pain ratings remained constant from session to session. In contrast, the areas of punctate hyperalgesia successively decreased to 60% of initial value at the fourth repetition. The session effect was not reversed by naloxone. High-current-density electrical stimulation provokes central sensitization, but in addition inhibitory systems are activated that are only partly naloxone-sensitive. PERSPECTIVE: Endogenous inhibitory systems are of major importance for clinical pain conditions, but are not reflected in traditional human pain models. Here we show activation of a naloxone-sensitive short-term and a naloxone-insensitive long-term inhibitory system in a new model of electrically induced pain and hyperalgesia.

Adult↗

The assessment of craving: psychometric properties, factor structure and a revised version of the Alcohol Craving Questionnaire (ACQ).

AIMS: The goal of the present study was to examine the psychometric properties and factor structure of the Alcohol Craving Questionnaire (ACQ). DESIGN AND PARTICIPANTS: The German version of the ACQ was administered to a sample of 243 alcohol-dependent or alcohol-abusing subjects. A subgroup of the sample (n = 46) completed the German translation of the Obsessive Compulsive Drinking Scale (OCDS) and the ACQ a second time. MEASUREMENTS: To validate the factor models, confirmatory factor analyses (CFA) were carried out. Examination of the psychometric properties of the ACQ included the analysis of the item characteristics to exclude non-sensitive items, an exploratory factor analysis of the remaining items and calculation of internal consistency, test-retest reliability and convergent validity. FINDINGS: Neither of the two models showed a satisfactory correspondence. An exploratory factor analysis of a revised version of the ACQ (ACQ-R), based on the psychometric properties of the items, revealed two stable factors ('urge and intention to drink alcohol' and 'reinforcement') with high internal consistency, test-retest reliability and convergent validity. The model fit was also excellent in the CFA. CONCLUSIONS: The ACQ-R is a reliable and valid instrument to assess alcohol craving. However, the ACQ-R lacks items related to loss of control. Therefore a multi-dimensional assessment, e.g. the combination of the ACQ-R and the OCDS, is recommended.

Adult↗

Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter.

Major depression is conditionally linked to a polymorphism of the human serotonin transporter gene (SLC6A4). During the presentation of aversive, but not pleasant, pictures, healthy carriers of the SLC6A4 short (s) allele showed stronger activation of the amygdala on functional magnetic resonance imaging. s carriers also showed greater coupling between the amygdala and the ventromedial prefrontal cortex, which may contribute to the abnormally high activity in the amygdala and medial prefrontal cortex seen in major depression.

Aged↗

Peripheral and electrocortical responses to painful and non-painful stimulation in chronic pain patients, tension headache patients and healthy controls.

Sixteen chronic back pain (CBP) patients, 16 tension headache (THA) patients and 16 healthy controls (HC) were exposed to four series of ten electric stimuli at perception threshold, pain threshold and 10% below pain tolerance. The EEG was recorded from three sites, in addition, the EMG from the m. frontalis and m. erector spinae, heart rate and skin conductance were assessed. The CBP patients showed significantly lower pain threshold and pain tolerance values than the HC and the THA patients whereas the THA patients displayed a higher pain tolerance. Habituation was reduced in the CBP group. N150, P260, P300 and N500 were not significantly different between the groups nor were there significant group differences in the peripheral measures. However, since the stimulation intensity was significantly lower in the CBP patients, these data are indicative of both enhanced central and peripheral reactivity. The observed lack of habituation may contribute to the persistence of chronic pain.

Adult↗

Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics.

RATIONALE: Animal experiments have provided evidence that the striatum and medial prefrontal cortex play a predominant role in the acquisition and maintenance of drug-seeking behavior. OBJECTIVES: Alcohol-associated stimuli that were regularly paired with alcohol intake may become conditioned cues and elicit a motivational response that triggers relapse in alcohol-dependent patients. METHODS: We used functional magnetic resonance imaging and visual alcohol-associated and control cues to assess brain activation in ten abstinent alcoholics and control subjects. Patients were followed for 3 months, and alcohol intake was recorded. RESULTS: Alcohol-related versus neutral visual stimuli activated the putamen, anterior cingulate and adjacent medial prefrontal cortex in alcoholics compared with healthy controls. Cue-induced activation of these brain areas was pronounced in the five alcoholics who subsequently relapsed during the observation period. A multiple regression analysis showed that, in alcoholics, the amount of subsequent alcohol intake was associated with the intensity of cue-induced brain activation but not the severity of alcohol craving, amount of previous alcohol intake or duration of abstinence before scanning. CONCLUSIONS: This pilot study showed that cue-induced activation of the anterior cingulate, medial prefrontal cortex and striatum may play a role in the attribution of incentive salience to alcohol-associated stimuli, thus increasing the motivational value and attentional processing of alcohol cues. Functional brain imaging may help to identify a group of alcoholics with an otherwise undetected high risk of relapse.

Adult↗

Phantom phenomena in mastectomized patients and their relation to chronic and acute pre-mastectomy pain.

Chronic and acute pre-mastectomy pain as well as prevalence and characteristics of phantom phenomena following mastectomy were investigated by interview in a sample of 39 women who had undergone unilateral breast amputation. Twenty of 39 participants reported phantom sensations in the breast. Nine of the participants with phantom sensations experienced phantom pain and 11 non-painful phantom sensations. Although some features of phantom breast phenomena appear to be similar to characteristics of phantom phenomena in limb amputees, phantom breast phenomena seem to differ in a variety of ways such as time of onset or localization. This difference may be explained by the absence of kinesthesis and the small representation of the human breast. Seven of the 39 participants experienced chronic and six acute breast pain prior to the amputation. The amount of chronic pre-mastectomy breast pain weighted by the amount of involved tissue was significantly higher among participants with non-painful phantom sensations, compared to women with painful phantoms and those without phantom phenomena.

Adolescent↗

P300-amplitudes in upper limb amputees with and without phantom limb pain in a visual oddball paradigm.

The aim of the study was to investigate to what extent cortical hyper-reactivity to visual stimuli is present in upper limb amputees. Five amputees with phantom limb pain (PLP), five amputees without PLP (Non-PLP) and 10 healthy controls (HC) were investigated using a visual oddball paradigm. Two hundred visual stimuli were presented with target stimuli occurring at a probability of 25% and standard stimuli at a probability of 75%. Event-related potentials were recorded from nine scalp positions (F3, F4, Fz, C3, C4, Cz, P3, P4, Pz). The PLP-patients had significantly higher P300-amplitudes to both types of stimuli compared to the non-PLP-patients. The HC were not significantly different from both amputee groups. P300-amplitude to targets at frontal sites in the hemisphere contralateral to the amputation was higher in the PLP patients. P300-latencies to target stimuli differed only at frontal sites with PLP-patients showing significantly longer latencies than non-PLP-patients. To standard stimuli, however, they showed significantly shorter latencies at central and parietal scalp positions. The HC had significantly shorter latencies than both amputee groups. The size of the P300-amplitude was positively correlated with the intensity of PLP. These findings suggest a higher magnitude of non-specific cortical excitability in amputees with PLP and a reduced excitability in amputees without PLP. This extends previous findings of differences in cortical excitability in PLP and non-PLP patients in the sensorimotor domain.

Adult↗

Neuroelectric source imaging of steady-state movement-related cortical potentials in human upper extremity amputees with and without phantom limb pain.

Whereas several studies reported a close relationship between changes in the somatotopic organization of primary somatosensory cortex and phantom limb pain, the relationship between alterations in the motor cortex and amputation-related phenomena has not yet been explored in detail. This study used steady-state movement-related cortical potentials (MRCPs) combined with neuroelectric source imaging to assess the relationship of changes in motor cortex and amputation-related phenomena such as painful and non-painful phantom and residual limb sensations, telescoping, and prosthesis use. Eight upper limb amputees were investigated. A significant positive relationship between reorganization of the motor cortex (distance of the MRCP source location from the mirrored source for hand movement) and phantom limb pain was found. Non-painful phantom sensations as well as painful and non-painful residual limb sensations were unrelated to motor cortical reorganization. A higher amount of motor reorganization was associated with less daily prosthesis use, which also tended to be related to more severe phantom limb pain. These results extend previous findings of a positive relationship between somatosensory reorganization and phantom limb pain to the motor domain and suggest a potential positive effect of prosthesis use on phantom limb pain and cortical reorganization.

Adult↗

Pavlovian conditioning of muscular responses in chronic pain patients: central and peripheral correlates.

A differential conditioning design using an aversive slide as conditioned stimulus (CS(+)) that was followed by an intracutaneous electric stimulus to the left index finger as unconditioned stimulus (US) and a pleasant slide that was not followed by shock (CS(-)) were used to test the hypothesis of enhanced aversive conditioning of muscular responses in chronic back pain patients (CBP). Heart rate, skin conductance levels, and integrated surface electromyograms (EMG) from the left and right m. flexor digitorum, the right m. trapezius, and bilaterally from the m. orbicularis oculi were recorded. The electroencephalogram (EEG) was measured from nine electrode positions. The CBP patients showed an enhanced muscular response of the left forearm (where the US was applied) to the CS(+) already in the preconditioning phase. During acquisition both the left forearm and the right trapezius of the patients but not the controls displayed enhanced muscular responding to the CS(+). During extinction the CBP patients' muscular responses to both CS(+) and CS(-) were elevated. The contingent negative variation of the EEG differentiated between CS(+) and CS(-) in the healthy controls but not the chronic pain patients. These data confirm the hypothesis of enhanced muscular responding in chronic pain patients and suggest a dissociation of muscular and central processes during aversive conditioning in the patients that might contribute to the chronicity problem.

Adult↗