Christian Mohr

The anterior cingulate cortex contains distinct areas dissociating external from self-administered painful stimulation: a parametric fMRI study.

&NA; The anterior cingulate cortex (ACC) has a pivotal role in human pain processing by integrating sensory, executive, attentional, emotional, and motivational components of pain. Cognitive modulation of pain‐related ACC activation has been shown by hypnosis, illusion and anticipation. The expectation of a potentially noxious stimulus may not only differ as to when but also how the stimulus is applied. These combined properties led to our hypothesis that ACC is capable of distinguishing external from self‐administered noxious tactile stimulation. Thermal contact stimuli with noxious and non‐noxious temperatures were self‐administered or externally applied at the resting right hand in a randomized order. Two additional conditions without any stimulus‐eliciting movements served as control conditions to account for the certainty and uncertainty of the impending stimulus. Calculating the differences in the activation pattern between self‐administered and externally generated stimuli revealed three distinct areas of activation that graded with perceived stimulus intensity: (i) in the posterior ACC with a linear increase during external but hardly any modulation for the self‐administered stimulation, (ii) in the midcingulate cortex with activation patterns independent of the mode of application and (iii) in the perigenual ACC with increasing activation during self‐administered but decreasing activation during externally applied stimulation. These data support the functional segregation of the human ACC: the posterior ACC may be involved in the prediction of the sensory consequences of pain‐related action, the midcingulate cortex in pain intensity coding and the perigenual ACC is related to the onset uncertainty of the impending stimuli.

Differential cerebellar activation related to perceived pain intensity during noxious thermal stimulation in humans: a functional magnetic resonance imaging study

Little is known about the cerebellar involvement in pain processing in spite of the fact that the cerebellum probably plays a crucial role in pain-related behavior. Using functional magnetic resonance imaging we examined the differential cerebellar activation in 18 healthy subjects in relation to their perceived pain-intensity of noxious and non-noxious thermal stimuli. In contrast to non-noxious (40 degrees C) stimuli, noxious (48.5 degrees C) stimuli revealed activation in the deep cerebellar nuclei, anterior vermis and bilaterally in the cerebellar hemispheric lobule VI. With the same noxious stimulus (48.5 degrees C) there was differential cerebellar activation depending on the perceived pain intensity: high pain intensity ratings were associated with activation in ipsilateral hemispheric lobule III-VI, deep cerebellar nuclei and in the anterior vermis (lobule III). This differential cerebellar activation pattern probably reflects not only somatosensory processing but also perceived pain intensity that may be important for cerebellar modulation of nociceptive circuits.

Structural Changes in the Human Brain following Vestibular Neuritis Indicate Central Vestibular Compensation

Vestibular neuritis (VN) is a sudden unilateral vestibular failure (UVF) with a variable course. Caloric hyporesponsiveness often persists, and it is largely unknown why patients with the same degree of hyporesponsiveness show different functional recovery. As the peripheral vestibular deficit alone does not seem to determine functional recovery, it was the aim of this study to elucidate whether structural (morphological) brain changes (1) contribute to central vestibular compensation, and (2) account for the variability of clinical recovery in VN. Structural global gray‐matter volume (GMV) changes in 15 VN patients were compared with age‐matched controls. Morphometric changes in multisensory vestibular cortices, which may be related to functional disability scores, were hypothesized. Patients were examined with neuro‐otological tests and clinical scores to assess vestibular disability. Using voxel‐based morphometry (VBM, SPM2), categorical comparison revealed GMV increase in patients’ multisensory vestibular cortices [insula, inferior parietal lobe (IPL), superior temporal gyrus (STG)], cerebellum, and motion‐sensitive areas in the middle temporal area (MT). GMV decrease was found in the midline pontomedullary junction. Simple regression analysis revealed (1) GMV increase in insula and retroinsular vestibular cortex and STG with improving clinically assessed vestibular deficits, and (2) GMV increase in insula vestibular cortex and STG with improving self‐assessed vestibular impairment. For the first time, these data suggest structural cortical plasticity in multisensory vestibular‐cortex areas in VN that are related to clinical vestibular function and vertigo. As increase of GMV was related to an improvement of vestibular function, structural alterations may be related to central vestibular compensation.

Central representation of cold-evoked pain relief in capsaicin induced pain: an event-related fMRI study.

Abstract The termination of an unpleasant or painful somatic condition can produce a rewarding sense of relief, even if the stimulus that causes the termination is itself unpleasant or painful under normal circumstances. We aimed to identify central neural mechanisms of pain relief from capsaicin‐elicited heat‐hyperalgesia by administering cold stimuli. We hypothesized that cooling might facilitate endogenous descending inhibitory mechanisms. We compared intraindividual neural responses of 15 healthy male volunteers to cold (20, 0 °C), intermediate (30 °C) and heat stimuli (43 °C) on untreated vs. capsaicin‐treated skin using event‐related fMRI in a 2 × 4 factorial design. Thermal stimuli were applied at the right hand in two separate imaging sessions using a Peltier‐element. Psychophysical ratings of the perceived valence and intensity (VAS: 1–100) were obtained after each stimulus. The 43 °C‐stimulus was perceived as excessively painful on capsaicin‐treated skin as opposed to an unpleasant sensation on normal skin. In contrast, the 0 °C‐stimulus was perceived unpleasant when applied on untreated skin while subjects rated the same stimulus pleasant in the capsaicin‐treated condition. When neural responses to the 0 °C‐stimulus were compared between the untreated and capsaicin‐treated skin condition there were stronger BOLD‐responses in prefrontal cortex (PFC) and periaqueductal grey (PAG) which correlated with increasing perceived pleasantness (VAS). Based on a connectivity analysis which identified cold‐dependent contributions of PFC activity with PAG in heat‐hyperalgesia we propose that cold‐induced pain relief partly results from activation of endogenous descending inhibition of nociception. The data illustrate that perception of nociceptive input may largely be determined by competing aversive‐appetitive motivational states.

Neural activity related to self- versus externally generated painful stimuli reveals distinct differences in the lateral pain system in a parametric fMRI study

Self‐generated sensory stimulation can be distinguished from externally generated stimulation that is otherwise identical. To determine how the brain differentiates external from self‐generated noxious stimulation and which structures of the lateral pain system use neural signals to predict the sensory consequences of self‐generated painful stimulation, we used functional magnetic resonance imaging to examine healthy human subjects who received thermal‐contact stimuli with noxious and non‐noxious temperatures on the resting right hand in random order. These stimuli were internally (self‐generated) or externally generated. Two additional conditions served as control conditions: to account for stimulus onset uncertainty, acoustic stimuli preceding the same thermal stimuli were used with variable or fixed delays but without any stimulus‐eliciting movements. Whereas graded pain‐related activity in the insula and secondary somatosensory cortex (SII) was independent of how the stimulus was generated, it was attenuated in the primary somatosensory cortex (SI) during self‐generated stimulation. These data agree with recent concepts of the parallel processing of nociceptive signals to the primary and secondary somatosensory cortices. They also suggest that brain areas that encode pain intensity do not distinguish between internally or externally applied noxious stimuli, i.e., this adaptive biological mechanism prevents harm to the individual. The attenuated activation of SI during self‐generated painful stimulation might be a result of the predictability of the sensory consequences of the pain‐related action. Hum Brain Mapp, 2006.

Structural brain changes following peripheral vestibulo-cochlear lesion may indicate multisensory compensation

Background Do central mechanisms account for the variability of clinical recovery following peripheral vestibulo-cochlear lesions? Objective To investigate structural (morphological) plasticity in the human brain following unilateral vestibulo-cochlear lesions which might contribute to central vestibular compensation. Methods The authors compared regional grey matter volume (GMV) changes in patients after surgical removal of unilateral acoustic neuroma with age-matched control subjects, and hypothesised morphometric changes in the vestibular and auditory cortices which may be related to functional disability scores. Patients were examined with a battery of neuro-otological tests and clinical scores to assess vestibular and auditory disability. Results Voxel-based morphometry was used for categorical comparison between patients and age- and gender-matched controls. GMV increase was found bilaterally in primary somatosensory cortices and motion-sensitive areas in the medial temporal gyrus (MT). Simple regression analysis revealed a GMV increase (1) in the contralesional superior temporal gyrus/posterior insula to be correlated with decreasing clinically assessed vestibular deficits; (2) in the contralesional inferior parietal lobe with decreasing functional impairment of daily living activities; and (3) in the contralesional auditory cortex (Heschl gyrus) with decreasing hearing impairment. Conclusions These data may suggest structural cortical plasticity in multisensory vestibular cortex areas of patients with unilateral peripheral vestibulo-cochlear lesion after surgical removal of acoustic neuroma. As changes of GMV were related to vestibular function, structural brain changes may reflect central mechanisms of vestibular compensation.

Cerebellar neural responses related to actively and passively applied noxious thermal stimulation in human subjects: a parametric fMRI study ☆

Cerebellar activation is consistently found during noxious stimulation but little is known about its pain-related specificity. Under natural circumstances noxious stimuli are actively or passively delivered with concomitant tactile sensory stimulation. Using fMRI we therefore studied pain-related cerebellar activation with innocuous and noxious thermal stimuli in a parametric design taking motor execution as confounding factor into account. With respect to psychophysical pain ratings anterior vermal and ipsilateral hemispheric lobule VI activation was parametrically modulated for stimulus intensity in actively but not in passively elicited thermal stimulation. The cerebellum seems to be capable of distinguishing active from passive painful stimuli.

Effects of perceived and exerted pain control on neural activity during pain relief in experimental heat hyperalgesia: A fMRI study

Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain control and emotional reappraisal irrespective of whether this control is exerted or only perceived. Self‐initiated termination of pain elicits different expectations of subsequent pain relief as compared to perceived pain control. It is unknown whether and how this perceived vs. exerted control on pain differs and affects subsequent pain relief. Using fMRI, we studied two factors of pain control on pain relief: the (i) sense of control (perceived control but no execution) and (ii) the execution of control (exerted control). To account for the impact of factual execution of pain control on pain relief we applied bearable short and hardly bearable long contact‐heat stimuli which were applied either controllable or not. Using controllability as factor, there was dissociable neural activity during pain relief: following the perceived control condition neural activity was found in the orbitofrontal and mediofrontal cortex and, following the exerted control condition, in the anterolateral and dorsolateral prefrontal cortex and posterior parietal cortex.

Common neural systems for contact heat and laser pain stimulation reveal higher-level pain processing.

Our current knowledge of pain‐related neuronal responses is largely based on experimental pain studies using contact heat or nontactile laser painful stimulation. Both stimuli evoke pain, yet they differ considerably in their physical and perceptual properties. In sensory cortex, cerebral responses to either stimulus should therefore substantially differ. However, given that both stimuli evoke pain, we hypothesized that at a certain subset of cortical regions the different physical properties of the stimuli become less important and are therefore activated by both stimuli. In contrast, regions with clearly dissociable activity may belong to “lower‐level” pain processing mechanisms depending on the physical properties of the administered stimuli. We used functional magnetic resonance (fMRI) to intraindividually compare pain‐related activation patterns between laser and contact heat stimulation using four different intensities of laser and contact heat stimuli. Common and dissociable neural responses were identified by correlating perceived pain intensities with blood oxygenation level dependent (BOLD) signal changes. Only neuronal responses to stimuli that were perceived as painful were analyzed. Pain‐related BOLD signal increases independent of stimulus modality were detected in the anterior insula, anterior cingulate cortex, medial secondary somatosensory cortex, and the prefrontal cortex. These similarities are likely to reflect higher‐level pain processing, which is largely independent of the single physical parameters that determine the painful nature of the stimuli. Hum Brain Mapp 2008.

Grading system for the selection of patients with congenital aural atresia for active middle ear implants

IntroductionActive middle ear implants (aMEI) are being increasingly used for hearing restoration in congenital aural atresia. The existing gradings used for CT findings do not meet the requirements for these implants. Some items are expendable, whereas other important imaging factors are missing. We aimed to create a new grading system that could describe the extent of the malformation and predict the viability and challenges of implanting an aMEI.MethodsOne hundred three malformed ears were evaluated using HRCT of the temporal bone. The qualitative items middle ear and mastoid pneumatization, oval window, stapes, round window, tegmen mastoideum displacement and facial nerve displacement were included. An anterior- and posterior round window corridor, oval window and stapes corridor were quantified and novelly included. They describe the size of the surgical field and the sight towards the windows.ResultsThe ears were graded on a 16-point scale (16–13 easy, 12–9 moderate, 8–5 difficult, 4–0 high risk). The strength of agreement between the calculated score and the performed implantations was good. The comparison of the new 16-point scale with the Jahrsdoerfer score showed that both were able to conclusively detect the high-risk group; however, the new 16-point scale was able to further determine which malformed ears were favorable for aMEI, which the Jahrsdoerfer score could not do.ConclusionThe Active Middle Ear Implant Score for aural atresia (aMEI score) allows more precise risk stratification and decision making regarding the implantation. The use of operative corridors seems to have significantly better prognostic accuracy than the Jahrsdoerfer score.