A simultaneous EEG-fMRI study of painful electric stimulation

Together with a detailed behavioral analysis, simultaneous measurement of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) permits a better elucidation of cortical pain processing. We applied painful electrical stimulation to 6 healthy subjects and acquired fMRI simultaneously with an EEG measurement. The subjects rated various stimulus properties and the individual affective state. Stimulus-correlated BOLD effects were found in the primary and secondary somatosensory areas (SI and SII), the operculum, the insula, the supplementary motor area (SMA proper), the cerebellum, and posterior parts of the anterior cingulate gyrus (ACC). Perceived pain intensity was positively correlated with activation in these areas. Higher unpleasantness rating was associated with suppression of activity in areas known to be involved in stimulus categorization and representation (ventral premotor cortex, PCC, parietal operculum, insula) and enhanced activation in areas initiating, propagating, and executing motor reactions (ACC, SMA proper, cerebellum, primary motor cortex). Concordant dipole localizations in SI and ACC were modeled. Using the dipole strength in SI, the network was restricted to SI. The BOLD signal change in ACC was positively correlated to the individual dipole strength of the source in ACC thus revealing a close relationship of BOLD signal and possibly underlying neuronal electrical activity in SI and the ACC. The BOLD signal change decreased in SI over time. Dipole strength of the ACC source decreased over the experiment and increased during the stimulation block suggesting sensitization and habituation effects in these areas.     

The impact of chronic pain in children and adolescents: Development and initial validation of a child and parent version of the Pain Experience Questionnaire

Psychosocial factors are crucial for understanding and treating chronic pain in adults, but also in children. For children, very few questionnaires for a multidimensional pain assessment exist. In adults, the Multidimensional Pain Inventory (MPI; [Kerns RD, Turk DC, Rudy TE. The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain 1985;23:345-56]) has been widely used to determine patients' adjustment to chronic pain. Using one section of the MPI as a model, we developed and evaluated the Pain Experience Questionnaire (PEQ) - child and parent version - that assesses the psychosocial impact of chronic pain in children and adolescents. As substantiated by confirmatory factor analysis in a sample of 111 children and adolescents (7-18 years) with chronic pain, the child PEQ entails the subscales pain severity, pain-related interference, affective distress and perceived social support. The parent version contains the subscales severity of the child's pain, interference and parental affective distress. Child and parent PEQ subscales were internally consistent. Age was unrelated to PEQ subscale scores. Girls and their mothers endorsed significantly greater pain severity, interference and affective distress. Validity analyses yielded a pattern of correlations with measures of depression, trait anxiety, pain activity, child behaviors, pain-related cognitions, and parenting behavior that is consistent with psychometric data of the adult MPI and previous findings on psychosocial aspects of chronic pediatric pain. Significant differences between children depending on patient status (participants in experimental or treatment studies, outpatients, inpatients) suggest external validity of the PEQ. Despite the preliminary nature of the psychometric evaluation, the child and parent PEQ seem promising for a comprehensive assessment of pediatric pain.     

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.     

A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression

Major depressive disorder (MDD) is characterized by altered emotional and cognitive functioning. We performed a voxel-based whole-brain meta-analysis of functional neuroimaging data on altered emotion and cognition in MDD. Forty peer-reviewed studies in English-language published between 1998 and 2010 were included, which used functional neuroimaging during cognitive-emotional challenge in adult individuals with MDD and healthy controls. All studies reported between-groups differences for whole-brain analyses in standardized neuroanatomical space and were subjected to Activation Likelihood Estimation (ALE) of brain cluster showing altered responsivity in MDD. ALE resulted in thresholded and false discovery rate corrected hypo- and hyperactive brain regions. Against the background of a complex neural activation pattern, studies converged in predominantly hypoactive cluster in the anterior insular and rostral anterior cingulate cortex linked to affectively biased information processing and poor cognitive control. Frontal areas showed not only similar under- but also over-activation during cognitive-emotional challenge. On the subcortical level, we identified activation alterations in the thalamus and striatum which were involved in biased valence processing of emotional stimuli in MDD. These results for active conditions extend findings from ALE meta-analyses of resting state and antidepressant treatment studies and emphasize the key role of the anterior insular and rostral anterior cingulate cortex for altered emotion and cognition in MDD.     

Topology of pulmonary arterioles,capillaries, and venules in the cat

It is shown in this paper that each alveolus is not a unit of microcirculation: It is not supplied by one arteriole and one venule; each arteriole supplies several alveoli, which are connected to other alveoli before draining into venules. The spatial relationship among the arterioles, venules, and capillaries in the lung is not clear in the literature. To clarify the topology, we developed a special method of particulate polymer casting of the vascular tree, and four criteria to decide whether a noncapillary vessel is arterial or venous. Then on each histological cross section of the lung parenchyma, we marked all arteries with white dots, and all veins with red dots, and covered the area of white dots with one color, and the area of red dots with another. A two-colored map emerged. A two-colored cartographic map can only show islands in an ocean. Our histological maps of the cat lung show that the arterial zones are islands, and the venous zone is the ocean. From these maps quantitative information about the arterial and venous zones in the lung is obtained by stereological methods, and the data for the cat are presented. A morphological definition of the average length of capillary blood vessels connecting arterioles and venules is proposed. The average morphological length of capillary blood vessels in cat lung was found to be 556 ± 286 (SD) μm when the transpulmonary pressure was 10 cm H₂O. The average length of capillaries (L) is an important determinant of pulmonary blood flow: for given arterial and venous pressures, the flow rate is inversely proportional to L², the square of the average length; the transit time (time available for diffusion and oxygenation) varies directly with L²; the regional difference of blood flow also depends on L.     

Labeled Lectin Studies of Renal Tubular Dysgenesis and Renal Tubular Atrophy of Postnatal Renal Ischemia and end-Stage Kidney Disease

Renal tubular dysgenesis (RTD), with hypoplasia especially of renal proximal convoluted tubules and clinical neonatal anuria or oliguria, has been reported as a congenital familial (autosomal recessive) disease, variably with features of oligohydramnios, Potter syndrome, or pulmonary hypoplasia. A similar tubular lesion due to antenatal tubular atrophy has been reported for conjoined twins with twin-twin transfusion syndrome or acardia and in infants of mothers given antihypertensive agents, including angiotensin-converting enzyme (ACE) inhibitors, during pregnancy, and it has been seen as a unilateral lesion in young infants with renal artery stenosis due to arteritis or medial arterial calcinosis. The renal tubular changes in RTD are very like those of the “endocrine kidney” in experimental animals and resemble those of the renal tubular atrophy of end-stage kidney diseases such as glomerulonephritis, tubulointerstitial kidney disease, obstructive uropathy/pyelonephritis, graft rejection of transplanted kidneys, or the renal parenchymal changes seen with protracted dialysis therapy. Labeled lectins that differentially mark proximal convoluted, distal convoluted and connecting, and collecting tubules showed no distinctive differences in stainingpatterns of the hypoplastic renal tubules of infants and children with RTD, postnatal renal artery obstruction, or the various types of end-stage renal disease with the lectins used (PNA, GSL1, UEA, and LTA). The findings suggest that the renal tubular changes in some if not all the conditions studied are the result of renal ischemia. The reported familial RTD with hypernephronic nephromegaly may be a specific disorder, but other forms could reflect renal ischemia acquired in utero or in early or later postnatal life.