Biomedical subjects

Michael Erb

Publications and source records attributed to Michael Erb.

At least 19 recordsLinked to original sources

PubMed2007

Regulation of emotional responses elicited by threat-related stimuli.

The capacity to voluntarily regulate emotions is critical for mental health, especially when coping with aversive events. Several neuroimaging studies of emotion regulation found the amygdala to be a target for downregulation and prefrontal regions to be associated with downregulation. To characterize the role of prefrontal regions in bidirectional emotion regulation and to investigate regulatory influences on amygdala activity and peripheral physiological measures, a functional magnetic resonance imaging (fMRI) study with simultaneous recording of self-report, startle eyeblink, and skin conductance responses was carried out. Subjects viewed threat-related pictures and were asked to up- and downregulate their emotional responses using reappraisal strategies. While startle eyeblink responses (in successful regulators) and skin conductance responses were amplified during upregulation, but showed no consistent effect during downregulation, amygdala activity was increased and decreased according to the regulation instructions. Trial-by-trial ratings of regulation success correlated positively with activity in amygdala during upregulation and orbitofrontal cortex during downregulation. Downregulation was characterized by left-hemispheric activation peaks in anterior cingulate cortex, dorsolateral prefrontal cortex, and orbitofrontal cortex and upregulation was characterized by a pattern of prefrontal activation not restricted to the left hemisphere. Further analyses showed significant overlap of prefrontal activation across both regulation conditions, possibly reflecting cognitive processes underlying both up- and downregulation, but also showed distinct activations in each condition. The present study demonstrates that amygdala responses to threat-related stimuli can be controlled through the use of cognitive strategies depending on recruitment of prefrontal areas, thereby changing the subject's affective state.

Adolescent↗

PubMed2006

Neural correlates of metaphor processing in schizophrenia.

OBJECTIVE: A main feature of schizophrenic thought and language disturbance is concretism, the inability to understand the figurative meaning of proverbs and metaphors. Although this is routinely tested during clinical interview, its neural basis is unknown. METHOD: We investigated processing of metaphoric sentences with functional magnetic resonance imaging (fMRI) in 12 patients with schizophrenia and 12 control subjects. Stimuli consisted of 60 novel short sentences with either metaphoric or literal meaning presented visually, intersparsed by a low level baseline (grey background). Subjects read these sentences silently and judged by button press whether they had a positive or negative connotation. RESULTS: Reading metaphors in contrast to literal sentences revealed signal changes in the left inferior frontal gyrus in the control subjects (BA 45/47) and an area 3 cm dorsal to that in the patients (BA 45). Only activation in this area was negatively correlated with the severity of concretism rated with the PANSS. Comparison between groups for the contrast metaphors vs. low level baseline revealed stronger signal changes in the control group in the right superior/middle temporal gyrus (BA 39) and the left inferior frontal gyrus (BA 45) in the patients. CONCLUSIONS: The results in the control subjects are in line with studies showing an involvement of the left inferior frontal and right lateral temporal cortex during context processing. Failure to recruit these areas in the patients may underlie schizophrenic concretism.

Brain↗

PubMed2006

Successful verbal retrieval in elderly subjects is related to concurrent hippocampal and posterior cingulate activation.

OBJECTIVE: Memory decline and hippocampal atrophy are two major aspects of Alzheimer's disease. Using a response-related fMRI design, we investigated the relationship between successful verbal retrieval and concurrent cerebral activation in elderly subjects in different stages of cognitive decline. We chose a correlational over the more traditional categorical approach to increase the power of detecting relevant activations. METHODS: Eleven subjects with Alzheimer's disease, 21 elderly subjects with mild cognitive impairment, and 29 age-matched cognitively unimpaired subjects learned 180 nouns. While measuring brain activation with fMRI, the subjects had to classify these 180 learned plus 180 new distractor words as known or new. Response-related fMRI analysis was used to identify cerebral activation by correctly remembered words (hits) that correlated with retrieval success in the whole group. RESULTS: Successful verbal retrieval was significantly correlated with concurrent activation of the left hippocampus and posterior cingulate gyrus. CONCLUSION: The study confirms the importance of adequate hippocampal function for successful verbal retrieval in the elderly. In addition, our study supports connectivity studies indicating a functional relationship between the hippocampus and the posterior cingulate gyrus during successful verbal retrieval in the elderly in different stages of cognitive decline.

Aged↗

PubMed2006

Exploring the visual world: the neural substrate of spatial orienting.

Inspecting the visual environment, humans typically direct their attention across space by means of voluntary saccadic eye movements. Neuroimaging studies in healthy subjects have identified the superior parietal cortex and intraparietal sulcus as important structures involved in visual search. However, in apparent contrast, spatial disturbance of free exploration typically is observed after damage of brain structures located far more ventrally. Lesion studies in such patients disclosed the inferior parietal lobule (IPL) and temporo-parietal junction (TPJ), the superior temporal gyrus (STG) and insula, as well as the inferior frontal gyrus (IFG) of the right hemisphere. Here we used functional magnetic resonance imaging to investigate the involvement of these areas in active visual exploration in the intact brain. We conducted a region of interest analysis comparing free visual exploration of a dense stimulus array with the execution of stepwise horizontal and vertical saccades. The comparison of BOLD responses revealed significant signal increases during exploration in TPJ, STG, and IFG. This result calls for a reappraisal of the previous thinking on the function of these areas in visual search processes. In agreement with lesion studies, the data suggest that these areas are part of the network involved in human spatial orienting and exploration. The IPL dorsally of TPJ seem to be of minor importance for free visual exploration as these areas appear to be equally involved in the execution of spatially predetermined saccades.

Adult↗

PubMed2006

Laterality in metaphor processing: lack of evidence from functional magnetic resonance imaging for the right hemisphere theory.

We investigated processing of metaphoric sentences using event-related functional magnetic resonance imaging (fMRI). Seventeen healthy subjects (6 female, 11 male) read 60 novel short German sentence pairs with either metaphoric or literal meaning and performed two different tasks: judging the metaphoric content and judging whether the sentence has a positive or negative connotation. Laterality indices for 8 regions of interest were calculated: Inferior frontal gyrus (opercular part and triangular part), superior, middle, and inferior temporal gyrus, precuneus, temporal pole, and hippocampus. A left lateralised network was activated with no significant differences in laterality between the two tasks. The lowest degree of laterality was found in the temporal pole. Other factors than metaphoricity per se might trigger right hemisphere recruitment. Results are discussed in the context of lesion and hemifield studies.

Adult↗

PubMed2006

Mild cognitive impairment (MCI) and actual retrieval performance affect cerebral activation in the elderly.

Cerebral activation in the elderly may depend on general cognitive decline as well as actual retrieval performance. Consequently, activation between subjects with and without Mild Cognitive Impairment (MCI), and between remembered and non-remembered words was compared. Twenty-one MCI and 29 healthy control subjects learned 180 nouns. During retrieval, subjects had to discriminate these and 180 distractor words. fMRI identified response-related activation. Most retrieval-related activation was comparable in both groups. However, MCI subjects showed more activation in the prefrontal cortex than controls during processing of hits and correct rejections. Hits showed increased activation than misses in the precuneus and left lateral parieto-occipital cortex; misses showed more activation than correct rejections in the precuneus to cuneus. Verbal retrieval activated a large common network in the elderly independently of MCI. Increased activation in MCI subjects in prefrontal cortex depends on response category. Activation differences between response categories might reflect success (hits) and effort (misses). Increased retrieval-related activation may be used as early marker in subjects at risk of Alzheimer's disease.

Aged↗

PubMed2006

Effects of prosodic emotional intensity on activation of associative auditory cortex.

Functional magnetic resonance imaging was used to investigate hemodynamic responses to adjectives pronounced in happy and angry intonations of varying emotional intensity. In separate sessions, participants judged the emotional valence of either intonation or semantics. To disentangle effects of emotional prosodic intensity from confounding acoustic parameters, mean and variability of volume and fundamental frequency of each stimulus were included as nuisance variables in the statistical models. A linear dependency between hemodynamic responses and emotional intensity of happy and angry intonations was found in the bilateral superior temporal sulcus during both tasks, indicating that increases of hemodynamic responses in this region are elicited by both positive and negative prosody independent of low-level acoustic properties and task instructions.

Acoustic Stimulation↗

PubMed2006

Unraveling the differential expression of the two isoforms of myelin-associated glycoprotein in a mouse expressing GFP-tagged S-MAG specifically regulated and targeted into the different myelin compartments.

The two myelin-associated glycoprotein (MAG) isoforms are cell adhesion molecules that differ only in their cytoplasmic domains, but their specific roles are not well understood. In this study, we present a transgenic mouse line that specifically expresses GFP-tagged S-MAG correctly regulated and targeted into the myelin sheath allowing the specific discrimination of L- and S-MAG on the subcellular level. Here, we describe the differential expression pattern and spatial distribution of L- and S-MAG during development as well as in the adult central and peripheral nervous system. In peripheral nerves, where S-MAG is the sole isoform, we observed S-MAG concentrated in different ring-like structures such as periaxonal and abaxonal rings, and discs spanning through the compact myelin sheath perpendicular to the axon. In summary, our data provide new insight in the subcellular distribution of the two isoforms fundamental for the understanding of their specific functions in myelin formation and maintenance.

Animals↗

PubMed2006

Impact of voice on emotional judgment of faces: an event-related fMRI study.

Emotional information can be conveyed by various means of communication, such as propositional content, speech intonation, facial expression, and gestures. Prior studies have demonstrated that inputs from one modality can alter perception in another modality. To evaluate the impact of emotional intonation on ratings of emotional faces, a behavioral study first was carried out. Second, functional magnetic resonance (fMRI) was used to identify brain regions that mediate crossmodal effects of emotional prosody on judgments of facial expressions. In the behavioral study, subjects rated fearful and neutral facial expressions as being more fearful when accompanied by a fearful voice as compared to the same facial expressions without concomitant auditory stimulus, whereas no such influence on rating of faces was found for happy voices. In the fMRI experiment, this shift in rating of facial expressions in presence of a fearfully spoken sentence was correlated with the hemodynamic response in the left amygdala extending into the periamygdaloid cortex, which suggests that crossmodal effects on cognitive judgments of emotional information are mediated via these neuronal structures. Furthermore, significantly stronger activations were found in the mid-portion of the right fusiform gyrus during judgment of facial expressions in presence of fearful as compared to happy intonations, indicating that enhanced processing of faces within this region can be induced by the presence of threat-related information perceived via the auditory modality. Presumably, these increased extrastriate activations correspond to enhanced alertness, whereas responses within the left amygdala modulate cognitive evaluation of emotional facial expressions.

Acoustic Stimulation↗

PubMed2006

Deactivation of brain areas during self-regulation of slow cortical potentials in seizure patients.

This study investigates the neurophysiological basis of EEG feedback for patients with epilepsy. Brain areas are identified that become hemodynamically deactivated when epilepsy patients, trained in EEG self-regulation, generate positive slow cortical potentials (SCPs). Five patients were trained in producing positive SCPs, using a training protocol previously established to reduce seizure frequency in patients with drug refractory epilepsy. Patients attempted to produce positive SCP shifts in a functional magnetic resonance imaging (fMRI) scanner. Two patients were able to reliably produce positive SCP shifts. When these successful regulators were prompted to produce positive SCPs, blood oxygen level-dependent (BOLD) response indicated deactivation, in comparison to a control state, around the recording electrode, frontal lobe, and thalamus. Unsuccessful regulators' BOLD response indicated no deactivation in cortical areas proximal to the active electrode. No thalamic deactivation was found in poor regulators. Decreased seizure frequency from SCP training may be the result of positively reinforced inhibition in cortical areas proximal to active electrode placement, the frontal cortex, and the thalamus.

Adult↗

PubMed2006

Cerebrocerebellar circuits for the perceptual cancellation of eye-movement-induced retinal image motion.

Despite smooth pursuit eye movements, we are unaware of resultant retinal image motion. This example of perceptual invariance is achieved by comparing retinal image slip with an internal reference signal predicting the sensory consequences of the eye movement. This prediction can be manipulated experimentally, allowing one to vary the amount of self-induced image motion for which the reference signal compensates and, accordingly, the resulting percept of motion. Here we were able to map regions in CRUS I within the lateral cerebellar hemispheres that exhibited a significant correlation between functional magnetic resonance imaging signal amplitudes and the amount of motion predicted by the reference signal. The fact that these cerebellar regions were found to be functionally coupled with the left parieto-insular cortex and the supplementary eye fields points to these cortical areas as the sites of interaction between predicted and experienced sensory events, ultimately giving rise to the perception of a stable world despite self-induced retinal motion.

Brain Mapping↗

PubMed2006

BMP2/4 and BMP5-8 in jellyfish development and transdifferentiation.

Bone morphogenetic proteins (BMPs) have key roles in gastrulation, mesoderm induction and axial patterning. The multitude of bilaterian BMPs employed in these morphogenetic processes contrasts starkly with the scarcity of BMPs in Cnidaria, the most basal eumetazoan phylum. In coral, sea anemone and hydra species, BMPs have been found to be associated with larval and polyp axial patterning. In the hydrozoan jellyfish Podocoryne (Hydractinia) carnea the BMP2/4 and BMP5-8 genes are expressed unilaterally in the larva, corroborating a possible role in larval axial development. With the focal area of BMP expression in the anterior region, however, the jellyfish larva may have a developmental reversal of spatial polarity compared to the anthozoan larva. In medusa development, BMP genes are expressed in divergent expression territories within the presumptive radial canals and in various parts of the endoderm, indicative of an involvement in mesoderm patterning and gastrovascular system formation reminiscent of bilaterian BMP functions. In addition, the BMP2/4 and BMP5-8 genes may play roles in wound response and dedifferentiation or S-phase re-entry, respectively, as the former is expressed in striated muscle cells immediately after excision from the bell and the latter in the initial phase of muscle cell transdifferentiation.

Amino Acid Sequence↗

PubMed2005

Cerebral pathways in processing of affective prosody: a dynamic causal modeling study.

This study was conducted to investigate the connectivity architecture of neural structures involved in processing of emotional speech melody (prosody). 24 subjects underwent event-related functional magnetic resonance imaging (fMRI) while rating the emotional valence of either prosody or semantics of binaurally presented adjectives. Conventional analysis of fMRI data revealed activation within the right posterior middle temporal gyrus and bilateral inferior frontal cortex during evaluation of affective prosody and left temporal pole, orbitofrontal, and medial superior frontal cortex during judgment of affective semantics. Dynamic causal modeling (DCM) in combination with Bayes factors was used to compare competing neurophysiological models with different intrinsic connectivity structures and input regions within the network of brain regions underlying comprehension of affective prosody. Comparison on group level revealed superiority of a model in which the right temporal cortex serves as input region as compared to models in which one of the frontal areas is assumed to receive external inputs. Moreover, models with parallel information conductance from the right temporal cortex were superior to models in which the two frontal lobes accomplish serial processing steps. In conclusion, connectivity analysis supports the view that evaluation of affective prosody requires prior analysis of acoustic features within the temporal and that transfer of information from the temporal cortex to the frontal lobes occurs via parallel pathways.

Adult↗

PubMed2005

Novel cell-penetrating alpha-keto-amide calpain inhibitors as potential treatment for muscular dystrophy.

Dipeptide-derived alpha-keto-amide compounds with potent calpain inhibitory activity have been identified. These reversible covalent inhibitors have IC(50) values down to 25nM and exhibit greatly improved activity in muscle cells compared to the reference compound MDL28170. Several novel calpain inhibitors have shown positive effects on histological parameters in an animal model of Duchenne muscular dystrophy demonstrating their potential as a treatment option for this fatal disease.

Amides↗

PubMed2005

Processing of auditory spatial cues in human cortex: an fMRI study.

The issue of where in the human cortex coding of sound location is represented still is a matter of debate. It is unclear whether there are cortical areas that are specifically activated depending on the location of sound. Are identical or distinct cortical areas in one hemisphere involved in processing of sounds from the left and right? Also, the possibility has not been investigated so far that distinct areas have a preference for processing of central and eccentric sound locations. The present study focussed on these issues by using functional magnetic resonance imaging (fMRI). Activations evoked by left, right and central sounds were analysed separately, and contrasts were computed between these conditions. We did not find areas, which were involved in the processing of exclusively left, right or central sound positions. Large overlapping areas rather were observed for the three sound stimuli, located in the temporal, parietal and frontal cortices of both hemispheres. This result argues for the idea of a widely distributed bilateral network accessing an internal representation of the body to encode stimulus position in relation to the body median plane. However, two areas (right BA 40 and left BA 37) also were found to have preferences for sound position. In particular, BA 40 turned out to be significantly more activated by processing central positions, compared to eccentric stimuli. In line with previous findings on visual perception, the latter observation supports the assumption that the right inferior parietal cortex may be preferentially involved in the perception of central stimulus positions in relation to the body.

Acoustic Stimulation↗

PubMed2005

Impact of task difficulty on lateralization of pitch and duration discrimination.

To investigate lateralization of duration and pitch discrimination processing with emphasis on the influences of task difficulty, we used event-related functional magnetic resonance imaging. Seventeen healthy volunteers performed paired auditory discrimination tasks at varying levels of difficulty. Analysis of lateralization effects revealed leftward lateralization within the insular and the temporal cortex under both conditions. Moreover, parametric analysis of haemodynamic responses showed increasing activation within the right temporal cortex correlated to increasing accuracy of stimulus discrimination. Thus, highly differential acoustic stimuli seem to be predominantly processed within the right hemisphere, whereas the detection of slight signal differences might be linked to the left hemisphere. In conclusion, we found evidence for preferential involvement of the right hemisphere in holistic feature processing within the auditory domain.

Acoustic Stimulation↗

PubMed2005

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↗

PubMed2005

Transcranial magnetic stimulation in the visual system. II. Characterization of induced phosphenes and scotomas.

Transcranial magnetic stimulation (TMS) induces phosphenes and disrupts visual perception when applied over the occipital pole. Both the underlying mechanisms and the brain structures involved are still unclear. In the first part of this study we show that the masking effect of TMS differs to masking by light in terms of the psychometric function. Here we investigate the emergence of phosphenes in relation to perimetric measurements. The coil positions were measured with a stereotactic positioning device, and stimulation sites were characterized in four subjects on the basis of individual retinotopic maps measured by with functional magnetic resonance imaging. Phosphene thresholds were found to lie a factor of 0.59 below the stimulation intensities required to induce visual masking. They covered the segments in the visual field where visual suppression occurred with higher stimulation intensity. Both phosphenes and transient scotomas were found in the lower visual field in the quadrant contralateral to the stimulated hemisphere. They could be evoked from a large area over the occipital pole. Phosphene contours and texture remained quite stable with different coil positions over one hemisphere and did not change with the retinotopy of the different visual areas on which the coil was focused. They cannot be related exclusively to a certain functionally defined visual area. It is most likely that both the optic radiation close to its termination in the dorsal parts of V1 and back-projecting fibers from V2 and V3 back to V1 generate phosphenes and scotomas.

Adult↗