Biomedical subjects

C Büchel

Publications and source records attributed to C Büchel.

At least 19 recordsLinked to original sources

PubMed2006

Detecting fearful and neutral faces: BOLD latency differences in amygdala-hippocampal junction.

Evolutionary survival and procreation are augmented if an individual organism quickly detects environmental threats and rapidly initiates defensive behavioral reactions. Thus, facial emotions signaling a potential threat, e.g., fear or anger, should be perceived rapidly and automatically, possibly through a subcortical processing route which includes the amygdala. Using event-related functional magnetic resonance imaging (fMRI), we investigated the time course of the response in the amygdala to neutral and fearful faces, which appear from dynamically decreasing random visual noise. We aimed to detect differences of the amygdala response between fearful and neutral faces by estimating the latency of the blood oxygenation level-dependent (BOLD) response. We found that bilateral amygdala-hippocampal junction activation occurred earlier for fearful than for neutral faces. Our findings support the theory of a dual route architecture in which the subcortical thalamic-hippocampal-amygdala route serves fast preconscious threat perception.

Amygdala↗

PubMed2005

Mechanisms of placebo analgesia: rACC recruitment of a subcortical antinociceptive network.

Placebo analgesia is one of the most striking examples of the cognitive modulation of pain perception and the underlying mechanisms are finally beginning to be understood. According to pharmacological studies, the endogenous opioid system is essential for placebo analgesia. Recent functional imaging data provides evidence that the rostral anterior cingulate cortex (rACC) represents a crucial cortical area for this type of endogenous pain control. We therefore hypothesized that placebo analgesia recruits other brain areas outside the rACC and that interactions of the rACC with these brain areas mediate opioid-dependent endogenous antinociception as part of a top-down mechanism. Nineteen healthy subjects received and rated painful laser stimuli to the dorsum of both hands, one of them treated with a fake analgesic cream (placebo). Painful stimulation was preceded by an auditory cue, indicating the side of the next laser stimulation. BOLD-responses to the painful laser-stimulation during the placebo and no-placebo condition were assessed using event-related fMRI. After having confirmed placebo related activity in the rACC, a connectivity analysis identified placebo dependent contributions of rACC activity with bilateral amygdalae and the periaqueductal gray (PAG). This finding supports the view that placebo analgesia depends on the enhanced functional connectivity of the rACC with subcortical brain structures that are crucial for conditioned learning and descending inhibition of nociception.

Adolescent↗

PubMed2005

Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism.

Mutations in the Parkin gene are the most common known single cause of early-onset parkinsonism. It has been shown that asymptomatic carriers with a single mutant allele have latent presynaptic dopaminergic dysfunction in the striatum. Here we used functional MRI to map movement-related neuronal activity during internally selected or externally determined finger movements in 12 asymptomatic carriers of a Parkin mutation and 12 healthy non-carriers. Mean response times were 63 ms shorter during internally selected movements than during externally guided movements (P = 0.003). There were no differences in mean response times between groups (P > 0.2). Compared with externally determined movements, the internal selection of movements led to a stronger activation of rostral motor areas, including the rostral cingulate motor area (rCMA), rostral supplementary motor area, medial and dorsolateral prefrontal cortices. The genotype had a significant impact on movement-related activation patterns. Asymptomatic carriers showed a stronger increase in movement-related activity in the right rCMA and left dorsal premotor cortex, but only if movements relied on internal cues. In addition, synaptic activity in the rCMA had a stronger influence on activity in the basal ganglia in the context of internally selected movements in asymptomatic carriers relative to non-carriers. We infer that this reorganization of striatocortical motor loops reflects a compensatory effort to overcome latent nigrostriatal dysfunction.

Adult↗

PubMed2005

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

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.

Adult↗

PubMed2005

The robustness of perception.

The natural environment around us, which is often crowded, cluttered or even foggy, is subject to a dynamically changing composition of objects and events. The human brain is continuously perceiving, recognizing and evaluating this dynamic scene composition. If the perception of degraded visual objects is important, e.g. in the case of potential threat stimuli, the brain needs to be more sensitive in detecting these objects from the natural environment. It is therefore hypothesized that reacting to the dynamically changing environment involves a robust and quick processing of salient information, which can be either with or without conscious awareness. We investigated the dynamics and robustness of perception using pictures of three salience levels, i.e. fearful faces (most salient), neutral faces (salient) and houses (nonsalient), which appear from dynamically decreasing random visual noise. Stimuli were matched for luminance, contrast, brightness and spatial frequency information. Reaction times show a significantly earlier response for faces than for houses. Fearful faces were significantly more quickly detected than neutral faces. The neural correlates sustaining robust perception were investigated with event-related functional magnetic resonance imaging (fMRI). The amygdala showed a significant perception-related response for faces, as compared to houses, that was further enhanced for fearful faces as compared to neutral faces. Our data indicate that emotionally salient information processing is (i) mediated by the amygdala and (ii) more robust than for nonsalient stimuli as it shows a significantly lower perceptual threshold.

Adolescent↗

PubMed2004

Somatotopic representation of nociceptive information in the putamen: an event-related fMRI study.

The ability to locate pain plays a pivotal role in immediate defence and withdrawal behaviour. However, it is unclear to what extent nociceptive information is relayed to and processed in subcortical structures relevant for motor preparation and possibly the generation of withdrawal behaviour. We used single-trial functional magnetic resonance imaging (fMRI) to assess whether nociceptive information is represented in the putamen in a somatotopic manner. We therefore applied thulium-YAG laser-evoked pain stimuli, which had no concomitant tactile component, to the dorsum of the left hand and foot to 15 healthy subjects in a randomized order. In addition, 11 subjects were stimulated on the right body side. Differential representations of hand- and foot-related blood oxygen level dependent (BOLD) responses within the putamen were assessed using a single subject approach. Nociceptive stimuli significantly activated the putamen bilaterally. However, a somatotopic organization for hand- and foot-related responses was only present in the contralateral putamen. Here the foot was located anteriorly and medially to the hand, which parallels results from anatomical and microstimulation studies in monkeys and also human imaging data on the arrangement of movement related activity in the putamen. This result provides evidence for the hypothesis that behaviourally relevant nociceptive information without additional information from the tactile system is represented in the putamen and made available for pain related motor responses.

Adult↗

PubMed2004

White matter asymmetry in the human brain: a diffusion tensor MRI study.

Language ability and handedness are likely to be associated with asymmetry of the cerebral cortex (grey matter) and connectivity (white matter). Grey matter asymmetry, most likely linked to language has been identified with voxel-based morphometry (VBM) using T(1)-weighted images. Differences in white matter obtained with this technique are less consistent, probably due to the relative insensitivity of the T(1) contrast to the ultrastructure of white matter. Furthermore, previous VBM studies failed to find differences related to handedness in either grey or white matter. We revisited these issues and investigated two independent groups of subjects with diffusion-tensor imaging (DTI) for asymmetries in white matter composition. Using voxel-based statistical analyses an asymmetry of the arcuate fascicle was observed, with higher fractional anisotropy in the left hemisphere. In addition, we show differences related to handedness in the white matter underneath the precentral gyrus contralateral to the dominant hand. Remarkably, these findings were very robust, even when investigating small groups of subjects. This highlights the sensitivity of DTI for white matter tissue differences, making it an ideal tool to study small patient populations.

Adult↗

PubMed2004

Somatotopic organization of human somatosensory cortices for pain: a single trial fMRI study.

The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. To investigate the somatotopic organization of the nociceptive system, we applied Thulium-YAG-laser evoked pain stimuli, which have no concomitant tactile component, to the dorsum of the left hand and foot in randomized order. We used single-trial functional magnetic resonance imaging (fMRI) to assess differential hemodynamic responses to hand and foot stimulation for the group and in a single subject approach. The primary somatosensory cortex (SI) shows a clear somatotopic organization ipsi- and contralaterally to painful stimulation. Furthermore, a differential representation of hand and foot stimulation appeared within the contralateral opercular--insular region of the secondary somatosensory cortex (SII). This result provides evidence that both SI and SII encode spatial information of nociceptive stimuli without additional information from the tactile system and highlights the concept of a redundant representation of basic discriminative stimulus features in human somatosensory cortices, which seems adequate in view of the evolutionary importance of pain perception.

Adult↗

PubMed2003

Single trial fMRI reveals significant contralateral bias in responses to laser pain within thalamus and somatosensory cortices.

Pain is processed in multiple brain areas, indicating the complexity of pain perception. The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. We used single-trial functional magnetic resonance imaging (fMRI) to assess hemodynamic responses to right and left painful stimulation. Thulium-YAG-(yttrium-aluminium-granate)-laser-evoked pain stimuli, without concomitant tactile component, were applied to either hand in a randomized order. A contralateral bias of the BOLD response was investigated to determine areas involved in the coding of the side of stimulation, which we observed in primary (SI) and secondary (SII) somatosensory cortex, insula, and the thalamus. This suggests that these structures provide spatial information of selective nociceptive stimuli. More importantly, this contralateral bias of activation allowed functionally segregated activations within the SII complex, the insula, and the thalamus. Only distinct subregions of the SII complex, the posterior insula and the lateral thalamus, but not the remaining SII complex, the anterior insula and the medial thalamus, showed a contralaterally biased representation of painful stimuli. This result supports the hypothesis that sensory-discriminative attributes of painful stimuli, such as those related to body side, are topospecifically represented within the forebrain projections of the nociceptive system and highlights the concept of functional segregation and specialization within these structures.

Adult↗

PubMed2003

Differential modulation of subcortical target and cortex during deep brain stimulation.

The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit.

Aged↗

PubMed2003

Pharmacologically modulated fMRI--cortical responsiveness to levodopa in drug-naive hemiparkinsonian patients.

According to the basal ganglia-thalamocortical circuit model, dopamine depletion in the nigrostriatal system leads to hypoactivation in the supplementary motor area (SMA) and the primary motor cortex (M1) in Parkinson's disease. This functional cortical deafferentation and its reversibility by levodopa (L-dopa) treatment has been established in previous studies for SMA but remains controversial for M1. We used functional MRI (fMRI) and a simple finger opposition task to correlate blood oxygenation level-dependent (BOLD) signal changes with motor performance, assessed separately for each hand between fMRI scanning sessions. Eight drug-naive patients with an akinetic idiopathic hemiparkinsonian syndrome (Hoehn and Yahr stage 1-1.5) and 10 healthy controls were studied. Patients performed a simple, auditory-paced random finger- opposition task every 3 s before and repeatedly every 20 min after intake of 300 mg of fast-release L-dopa. M1 contralateral to the affected hand and SMA, predominantly of the contralateral side, showed a BOLD signal increase after L-dopa intake. Furthermore, comparing BOLD responses of M1 and SMA between the patients and controls revealed that these areas were hypoactive before L-dopa treatment. Signal changes in M1 and SMA were highly correlated with motor performance, which increased after L-dopa intake. This result is not confounded by a performance effect because the motor task employed during scanning was identical throughout all sessions. In contrast to previous imaging studies in which cortical reorganization in Parkinson's disease was thought to have caused M1 hyperactivation, our data are in accordance with the hypothesis that, in de novo idiopathic hemiparkinsonian syndrome, motor cortex hypoactivation in contralateral M1 and bilateral SMA is caused by a decreased input from the subcortical motor loop, which is reversible by L-dopa.

Adult↗

PubMed2003

Contralateral coding of imagined body parts in the superior parietal lobe.

In monkeys, neurons in the superior parietal lobe (area 5) code for spatial position of contralateral body parts by combining visual and somatosensory signals. Using a modified version of the classical mental rotation task, we were able to demonstrate that in humans activation in the contralateral superior parietal lobe could be evoked when mental rotation was combined with motor imagery of hands. These findings show that even in the absence of visual and somatosensory input, information provided by motor imagery suffices to induce contralateral superior parietal lobe monitoring of the imagined limb configuration. This constitutes an important prerequisite for effective imagined motor practice that can be used to improve actual motor performance.

Analysis of Variance↗

PubMed2002

A fully automated method for tissue segmentation and CSF-correction of proton MRSI metabolites corroborates abnormal hippocampal NAA in schizophrenia.

In this report, we describe the implementation and application of a fully automated segmentation routine using SPM99 algorithms and MATLAB for clinical Magnetic Resonance Spectroscopic Imaging (MRSI) studies. By segmenting high-resolution 3-D image data and coregistering the results to the spatial localizer slices of a spectroscopy examination, the program offers the possibility to easily calculate segmentation maps for a large variety of MRSI experiments. The segmented data are corrected for the individual point-spread function, slice and VOI profiles for measurement sequences with selective pulses as well as for the chemical shifts of different metabolites. The new method was applied to investigate discrete hippocampal metabolite abnormalities in a small sample of schizophrenic patients in comparison to healthy controls (15 patients, 15 controls). Only after correction was the N-acetyl-aspartate (NAA) signal significantly lower in patients compared to controls. No differences were found for the corrected signals from the creatine/phosphocreatine (Cr) or choline-containing compounds (Ch). These results are in good agreement with neuropathological and previous MR spectroscopy studies of the hippocampus in schizophrenic patients.

Adult↗

PubMed2002

Event-related fMRI reveals cortical sites involved in contextual sentence integration.

We examined the effects of difficulty of sentential integration on blood oxygenation level-dependent contrast changes. Difficulty of integration was operationalized as the degree to which sentence-final nouns matched the expectations generated by preceding context. Nine young adults read short sentence fragments (e.g., "The pilot flies.") which were completed by highly expected nouns (e.g., "the plane"), unexpected yet semantically legal nouns (e.g., "the kite"), nouns that violated the verbs' selection restriction rules (e.g., "the book"), and pseudowords (e.g., "the foop") and made quick lexical decisions on the sentence-final item. Overall, word completions resulted in higher changes in activation than pseudoword completions. The largest of those changes were observed in left angular and posterior middle temporal gyri, suggesting that despite the lexical nature of the task, word stimuli embedded in sentence contexts triggered integrative-semantic processes beyond a lexical level. A region-of-interest analysis in left inferior frontal and left posterior middle temporal areas revealed activation for both unexpected and anomalous completions when compared to expected completions. Thus, while the underlying processing mechanisms may differ, sentential integration appears similarly effortful for these two types of completions. Our findings are consistent with previous reports of local increases in activation as a function of (syntactic) complexity, while extending the findings to processing demands of semantic integration. Because of its sensitivity to changes in semantic congruence and the implicit nature of the task involved, we argue that the present paradigm is well suited to study patients with potential semantic deficits after brain damage.

Adult↗

PubMed2002

Distortion-free diffusion tensor imaging of cranial nerves and of inferior temporal and orbitofrontal white matter.

The main impact of functional neuroimaging has been its ability to locate neuronal activity either directly (EEG, MEG) or through the hemodynamic response caused by neuronal activity (PET, fMRI). In the past decade functional neuroimaging has been extended to investigate how brain regions interact, using the concepts of functional and effective connectivity. These concepts are further strengthened by estimates of anatomical connectivity of the same subject. A tool to determine anatomical connectivity in vivo may be provided by diffusion tensor imaging (DTI) methods. These can be used to determine the orientation of fiber bundles in white matter on the basis of the diffusion characteristics of water. Commonly, DTI data are acquired using echo planar imaging which suffers from susceptibility artifacts in orbitofrontal and inferior temporal cortex. Here we demonstrate the use of an alternative pulse sequence, diffusion-weighted single-shot STEAM, for assessing fiber orientation in orbitofrontal cortex and the cranial nerves. The scope of DTI needs to be extended to these structures to investigate psychiatric disorders in which orbitofrontal pathology or temporo-frontal disconnection have been postulated.

Adult↗

PubMed2002

Subcortical structures involved in pain processing: evidence from single-trial fMRI.

Pain is processed in multiple cortical and subcortical brain areas. Subcortical structures are substantially involved in different processes that are closely linked to pain processing, e.g. motor preparation, autonomic responses, affective components and learning. However, it is unclear to which extent nociceptive information is relayed to and processed in subcortical structures. We used single-trial functional magnetic resonance imaging (fMRI) to identify subcortical regions displaying hemodynamic responses to painful stimulation. Thulium-YAG (yttrium-aluminum-granate) laser evoked pain stimuli, which have no concomitant tactile component, were applied to either hand of healthy volunteers in a randomized order. This procedure allowed identification of areas displaying differential fMRI responses to right- and left-sided stimuli. Hippocampal complex, amygdala, red nucleus, brainstem and cerebellum were activated in response to painful stimuli. Structures related to the affective processing of pain showed bilateral activation, whereas structures involved in the generation of withdrawal behavior, namely red nucleus, putamen and cerebellum displayed differential (i.e. asymmetric) responses according to the side of stimulation. This suggests that spatial information about the nociceptive stimulus is made available in these structures for the guidance of defensive and withdrawal behavior.

Adult↗

PubMed2002

Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study.

Only recently have neuroimaging studies moved away from describing regions activated by noxious stimuli and started to disentangle subprocesses within the nociceptive system. One approach to characterizing the role of individual regions is to record brain responses evoked by different stimulus intensities. We used such a parametric single-trial functional MRI design in combination with a thulium:yttrium-aluminium-granate infrared laser and investigated pain, stimulus intensity and stimulus awareness (i.e. pain-unrelated) responses in nine healthy volunteers. Four stimulus intensities, ranging from warm to painful (300-600 mJ), were applied in a randomized order and rated by the subjects on a five-point scale (P0-4). Regions in the dorsolateral prefrontal cortex and the intraparietal sulcus differentiated between P0 (not perceived) and P1 but exhibited no further signal increase with P2, and were related to stimulus perception and subsequent cognitive processing. Signal changes in the primary somatosensory cortex discriminated between non-painful trials (P0 and P1), linking this region to basic sensory processing. Pain-related regions in the secondary somatosensory cortex and insular cortex showed a response that did not distinguish between innocuous trials (P0 and P1) but showed a positive linear relationship with signal changes for painful trials (P2-4). This was also true for the amygdala, with the exception that, in P0 trials in which the stimulus was not perceived (i.e. 'uncertain' trials), the evoked signal changes were as great as in P3 trials, indicating that the amygdala is involved in coding 'uncertainty', as has been suggested previously in relation to classical conditioning.

Adult↗

PubMed2001

Localisation of the PsbH subunit in photosystem II: a new approach using labelling of His-tags with a Ni(2+)-NTA gold cluster and single particle analysis.

Photosystem II core dimers were isolated from the green alga Chlamydomonas reinhardtii by Ni(2+)-affinity chromatography exploiting a 6 x His tag located at the N terminus of the PsbH protein. This protein is predicted to have a single transmembrane helix. In order to identify the location of PsbH within the photosystem II complex, the His-tagged core dimers were labelled using a Ni(2+)-NTA gold cluster and subjected to electron microscopy and image analysis. This new method enabled us to identify the location of the labelled His tag by statistical analysis of electron micrographs of the gold-labelled photosystem II complex. Comparison of these data with electron and X-ray crystallographic analysis of photosystem II indicates that the N terminus of PsbH is close to the two transmembrane helices of cytochrome b(559). Our analysis suggests that this approach is a powerful method to locate specific proteins within multisubunit complexes like photosystem II when crystallographic analysis is of insufficient resolution to directly identify amino acid side-chains. Moreover, it can be combined with cross-linking studies, and here we demonstrate that PsbH is a near neighbour of PsbX, which is consistent with the latter subunit being located close to the alpha and beta-subunits of cytochrome b(559). However, cross-linking between PsbH and PsbW was not detected despite the fact that the latter cross-linked with the alpha-subunit of cytochrome b(559).

Animals↗