Biomedical subjects

H Flor

Publications and source records attributed to H Flor.

At least 19 recordsLinked to original sources

PubMed2007

Gene-gene effects on central processing of aversive stimuli.

Emotional reactivity and regulation are fundamental to human behavior. As inter-individual behavioral variation is affected by a multitude of different genes, there is intense interest to investigate gene-gene effects. Functional sequence variation at two genes has been associated with response and resiliency to emotionally unpleasant stimuli. These genes are the catechol-O-methyltransferase gene (COMT Val158Met) and the regulatory region (5-HTTLPR) of the serotonin transporter gene. Recently, it has been proposed that 5-HTT expression is not only affected by the common S/L variant of 5-HTTLPR but also by an A to G substitution. Using functional magnetic resonance imaging, we assessed the effects of COMT Val(158)Met and both 5-HTT genotypes on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 48 healthy subjects. Based on previous studies, the analysis of genotype effects was restricted to limbic brain areas. To determine allele-dose effects, the number of COMT Met158 alleles (i.e., lower activity of COMT) and the number of 5-HTT low expressing alleles (S and G) was correlated with the blood oxygen level-dependent (BOLD) response to pleasant or unpleasant stimuli compared to neutral stimuli. We observed an additive effect of COMT and both 5-HTT polymorphisms, accounting for 40% of the inter-individual variance in the averaged BOLD response of amygdala, hippocampal and limbic cortical regions elicited by unpleasant stimuli. Effects of 5-HTT and COMT genotypes did not affect brain processing of pleasant stimuli. These data indicate that functional brain imaging may be used to assess the interaction of multiple genes on the function of neuronal networks.

Adult↗

PubMed2007

Limitations of pharmacotherapy: behavioral approaches to chronic pain.

Pharmacotherapy is most appropriate in acute pain, whereas in chronic pain states behavioral approaches or a combination of behavioral treatment and pharmacotherapy is more appropriate. In this chapter we first describe the role of learning and memory as well as other psychological factors in the development of chronic pain and emphasize that chronic pain must viewed as the result of a learning process with resulting central neuroplastic changes. We then describe operant behavioral and cognitive-behavioral treatments as well as biofeedback and relaxation techniques and present innovative treatment procedures aimed at altering central pain memories. We complete the section with a discussion of combined behavioral and pharmacological approaches and an interdisciplinary view.

Behavior Therapy↗

PubMed2006

Differential cerebral activation during observation of expressive gestures and motor acts.

We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (fMRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Broca's and Wernicke's areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures.

Adult↗

PubMed2006

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

Adolescent↗

PubMed2005

An expanded view of psychological aspects in head pain: the biopsychosocial model.

Traditionally, headache has been viewed from a limited perspective, both medically and psychologically. The authors propose that a more expanded view of headache that considers each perspective as important, as embodied in the biopsychosocial model, will greatly enhance understanding and be more useful in treatment planning. This model views pain as emanating from a complex interaction of biological, psychological and social variables. This paper describes the key behavioural, affective and cognitive influences and provides pertinent supporting examples from the literature.

Affect↗

PubMed2004

[Visualisation of phantom- and backpain using imaging techniques. Implication for treatment].

If patients with chronic low back pain are stimulated in the painful region, an expanded representation of the back in the primary somatosensory cortex becomes visible that increases with chronicity. This "pain memory" might play an important role in the chronicity process. In patients with phantom limb pain, e.g. subsequent to the amputation of an arm or leg, a shift in the representation of neighboring areas into the deafferented area in primary somatosensory cortex has been observed. This reorganization of functional brain maps is not present in congenital amputees or amputees without phantom limb pain. The magnitude of such pain is positively correlated with this reorganization. We present a model of phantom limb pain that assigns an important role to pre-existing chronic pain. The modulation of plasticity and phantom limb pain by anesthesiological manipulation, the use of NMDA receptor antagonists and opioids is presented. Behaviorally relevant stimulation, e.g. by the use of a myoelectric prosthesis or sensory discrimination training can also influence the cortical somatosensory pain memory. More recent studies focus also on brain areas such as the cingulate gyrus believed to be involved in the affective processing of pain.

Back Pain↗

PubMed2004

The influence of the 5-HT3 receptor antagonist tropisetron on pain in fibromyalgia: a functional magnetic resonance imaging pilot study.

OBJECTIVE: Central pain processing is altered in patients with fibromyalgia syndrome (FMS). The serotonin metabolism, especially the 5-HT3 receptor, seems to play an important role. METHODS: We investigated the effect of the local injection of the 5-HT3 receptor antagonist tropisetron on the perception and central processing of pain in FMS patients using painful mechanical stimulation and functional magnetic resonance imaging (fMRI) within the framework of a pre-/posttreatment double-blind design. RESULTS: In the contralateral primary somatosensory cortex, contralateral posterior insula, and anterior cingulate cortex, we found that the activation was significantly reduced after treatment. On average, patients rated the stimulation-induced pain intensity as stronger in the session after treatment compared to before treatment, although the individual data revealed a heterogeneous pattern. All patients showed sensitisation during the painful stimulation, which was not influenced by the treatment. CONCLUSIONS: Both the sensory-discriminative and motivational-affective components of pain as measured by fMRI were altered by tropisetron.

Brain↗

PubMed2003

Remote activation of referred phantom sensation and cortical reorganization in human upper extremity amputees.

Phantom limb sensation, whether painful or not, frequently occurs after peripheral nerve lesions. It can be elicited by stimulating body parts adjacent to the amputation site (referred to as phantom sensation) and it is often similar in quality to the stimulation at the remote site. The present study induced referred phantom sensations in two upper limb amputees. Neuroelectric source imaging (ESI) as well as functional magnetic resonance imaging (fMRI) was used to assess reorganization in primary somatosensory cortex (SI). Whereas recent studies found mislocalization of sensation related to stimulation mainly in regions adjacent and ipsilateral to the amputation site, we report here the elicitation of phantom sensation in the arm by stimulation in the lower body part both ipsi- and contralateral to the amputation in two arm amputees. The fMRI evaluation of one patient showed no shift in the location of the foot whereas ESI revealed major reorganization of the mouth region in primary somatosensory cortex in both patients. These data suggest that cortical structures other than SI might be contributing to the phenomenon of referred sensation. Candidate structures are the thalamus, secondary somatosensory cortex, posterior parietal cortex and prefrontal cortex.

Adult↗

PubMed2003

[Phantom limb pain: aspects of neuroplasticity and intervention].

Phantom-limb pain is a common sequel of amputation, occurring in up to 80 % of the amputee population. It must be differentiated from non-painful phantom phenomena, residual-limb pain, and non-painful residual-limb phenomena. A comprehensive model of phantom-limb pain is presented that assigns a major role to pain occurring before the amputation and to central as well as peripheral changes related to it. Special emphasis is put on the role of cortical reorganization in the development of phantom limb pain. Finally, new approaches to the prevention and treatment of phantom limb pain are presented that have a positive influence on phantom limb pain by preventing or reversing cortical reorganization.

Clinical Trials as Topic↗

PubMed2002

Stimulus-induced craving and startle potentiation in abstinent alcoholics and controls.

Abstinent alcoholics often deny craving for alcohol but still show a high level of relapse. The eyeblink response to startling noise was used as an indicator of the emotional response to alcohol-related, positive, negative and neutral visual stimuli in abstinent alcoholics, social drinkers and rarely drinking controls. The cognitive evaluation of the stimuli was assessed by ratings of subjective craving, valence and arousal. The startle response of the alcoholics to alcohol-related stimuli was significantly inhibited despite an aversive overt stimulus-evaluation. These findings indicate that alcohol-related stimuli may have appetitive incentive salience for alcoholics in spite of verbal reports of craving and valence to the opposite.

Acoustic Stimulation↗

PubMed2002

Development of alcohol-associated cues and cue-induced brain activation in alcoholics.

The objective of this study was to develop new standardized alcohol-associated cues and assess their effects on brain activation with functional magnetic resonance imaging (fMRI). Pictures of alcoholic and neutral beverages and affectively neutral pictures were presented to 44 abstinent alcoholics and 37 age-matched healthy control subjects. We assessed the skin conductance response, and the elicited arousal and valence. Alcoholics and control subjects did not differ in arousal, valence or skin conductance response evoked by alcohol-associated and affectively neutral stimuli, while nonalcoholic beverages were rated as more unpleasant and arousing by alcoholics compared with control subjects. In the fMRI pilot study, alcohol and abstract pictures were presented to six abstinent alcoholics and induced a significant activation of brain areas associated with visual emotional processes such as the fusiform gyrus, parts of the brain reward system (basal ganglia and orbitofrontal gyrus) and further brain regions in the frontal and parietal cortices associated with the attention network. These observations suggest that standardized pictures of alcoholic beverages can be used to assess brain circuits involved in the processing and evaluation of alcohol cues.

Adult↗

PubMed2001

Early activation of the primary somatosensory cortex without conscious awareness of somatosensory stimuli in tumor patients.

The primary sensory cortex has usually been regarded as a necessary step in the information processing stream leading to conscious awareness. Recently, it has been proposed that that higher order associative areas rather than the primary sensory areas are the neural basis of conscious perception. In two patients with tumors near the central region we recorded magnetic somatosensory evoked fields. Magnetic source imaging revealed early (40 ms) neural activation in primary somatosensory cortex and absence of later (>60 ms) neural activation in the primary and associative areas in these patients. None of the patients showed conscious awareness of somatosensory stimuli applied to the corresponding body site although the first component of the evoked field was within normal limits. The time course of the magnetic responses and additional evidence on intensity ratings of somatosensory stimuli suggest that early activity in the primary somatosensory cortex is not sufficient for conscious experience to emerge.

Adult↗

PubMed2001

Effect of sensory discrimination training on cortical reorganisation and phantom limb pain.

Phantom limb pain is a frequent consequence of the amputation of a body part. Based on the finding that phantom limb pain is closely associated with plastic changes in the primary somatosensory cortex and animal data showing that behaviourally relevant training alters the cortical map, we devised a sensory discrimination training programme for patients with intractable phantom limb pain. Compared with a control group of medically treated patients, the training group had significant reductions in phantom limb pain (p=0.002) and cortical reorganisation (p=0.05) that were positively associated with improved sensory discrimination ability.

Adult↗

PubMed2001

Reorganization of motor and somatosensory cortex in upper extremity amputees with phantom limb pain.

Phantom limb pain (PLP) in amputees is associated with reorganizational changes in the somatosensory system. To investigate the relationship between somatosensory and motor reorganization and phantom limb pain, we used focal transcranial magnetic stimulation (TMS) of the motor cortex and neuroelectric source imaging of the somatosensory cortex (SI) in patients with and without phantom limb pain. For transcranial magnetic stimulation, recordings were made bilaterally from the biceps brachii, zygomaticus, and depressor labii inferioris muscles. Neuroelectric source imaging of the EEG was obtained after somatosensory stimulation of the skin overlying face and hand. Patients with phantom limb pain had larger motor-evoked potentials from the biceps brachii, and the map of outputs was larger for muscles on the amputated side compared with the intact side. The optimal scalp positions for stimulation of the zygomaticus and depressor labii inferioris muscles were displaced significantly more medially (toward the missing hand representation) in patients with phantom limb pain only. Neuroelectric source imaging revealed a similar medial displacement of the dipole center for face stimulation in patients with phantom limb pain. There was a high correlation between the magnitude of the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortex and phantom limb pain. These results show enhanced plasticity in both the motor and somatosensory domains in amputees with phantom limb pain.

Adult↗

PubMed2001

Perceptual phenomena after unilateral arm amputation: a pre-post-surgical comparison.

Painful and non-painful phantom phenomena occur frequently after amputations but are rarely investigated in the perioperative stage. The goal of the present study was the assessment of phantom phenomena, pain and changes in primary somatosensory cortex prior to and after upper limb amputation. Two patients who suffered from metastatic carcinoma were examined 2 days prior to and 7 days after the amputation of an arm using comprehensive psychometric assessments and neuroelectric source imaging. Both patients reported phantom limb pain that was similar to their pre-amputation pain. In one patient, reorganization of the mouth area into the deafferented hand area took place immediately after the amputation. In the other patient reorganization had occurred prior to the amputation possibly related to non-use of the arm several years prior to the amputation.

Aged↗

PubMed2001

The effect of opioids on phantom limb pain and cortical reorganization.

The efficacy of oral retarded morphine sulphate (MST) was tested against placebo in a double-blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation. Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST or Placebo. The titration phase was 2 weeks. The dose of MST was titrated to at least 70 mg/day and at highest 300 mg/day. Pain intensity was assessed hourly on visual analog scales during a 4-week treatment-free phase, both treatment phases and at two follow-ups (6 and 12 months). Reorganization of somatosensory cortex, electric perception and pain thresholds as well as selective attention were measured pre- and post-treatment. A significant pain reduction was found during MST but not during placebo. A clinically relevant response to MST (pain reduction of more than 50%) was evident in 42%, a partial response (pain reduction of 25-50%) in 8% of the patients. Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST concurrent with the reduction in pain intensity. Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST. Thus, opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization. These data need to be replicated in larger patient samples.

Adult↗

PubMed2001

[The phantom and stump phenomena interview (PSPI)].

RESEARCH QUESTION: A structured German-language interview was developed for the assessment of painful and non-painful phantom and stump phenomena after amputation. The aim was a thorough assessment of the quality, quantity and time course of these phenomena, which is of scientific as well as therapeutic relevance. METHODS: Each phenomenon was assessed using visual analogue scales as well as qualitative descriptors adapted from the McGill Pain Inventory and from literature reports. The factor structure and psychometric properties of the interview were evaluated in a sample of 139 upper and lower limb amputees. Test-retest coefficients were obtained in a subset of 20 amputees. RESULTS: As expected, all pain-related scales showed a two-dimensional internal structure with the factors "affective pain" and "sensory pain". For the non-painful phantom sensations, three factors "general/kinesthetic phantom sensations", "phantom movements" and "paresthesias" were obtained, while for non-painful stump sensations only one general factor emerged. The internal consistency was high with respect to the pain-related scales and was still satisfying for the scales that cover nonpainful phantom and stump phenomena. All scales have sufficient validity. Test-retest coefficients suggest a satisfactory stability of all scales that assess present phenomena, while the stability of the retrospective scales is markedly lower and in some cases insufficient. CONCLUSIONS: The phantom and stump phenomena interview is a highly reliable and valid instrument to assess present perceptual phenomena after amputation. Only the included retrospective scales apparently show low stability scores over time. This raises the more general question of the validity of retrospective pain reports.

Adult↗

PubMed2001

[Cortical reorganization and pain. Empirical findings and therapeutic implication using the example of phantom pain].

The neuroscientific research of the past years has shown that extensive plastic change occurs in the adult human brain. The functional reorganization of the somatosensory and motor maps related to phantom limb pain is described. Subsequent to deafferentation amputees with phantom limb pain show a shift of neighbouring representation zones into the deafferented zone of the somatosensory and motor cortex that can be detected with noninvasive neuroimaging methods. This reorganization of the sensory and motor maps is not found in painfree amputees and persons with congenital loss of a limb. We discuss a model of the development of phantom limb pain that incorporates both peripheral and central factors and assigns an important role to chronic pain before the amputation. The modulation of plasticity and phantom limb pain by anesthesiological interventions is described and the results of preemptive analgesia for the prevention of phantom limb pain are discussed. Opioid treatment and behaviorally relevant stimulation are effective means to eliminate phantom limb pain and cortical somatosensory pain memories.

Humans↗