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Dirk T Leube

Publications and source records attributed to Dirk T Leube.

14 recordsLinked to original sources

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↗

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↗

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↗

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↗

Visualization and quantification of disease progression in multiple system atrophy.

To visualize and quantify disease progression in multiple system atrophy (MSA) from cerebellar type (MSA-C), we combined two magnetic resonance imaging (MRI) techniques, voxel-based morphometry (VBM) and 3D-based volumetry. Patients suffering from MSA-C (n = 14) were imaged twice with an interval of 2.0 +/- 0.2 years. We first applied VBM to map brain morphology changes between MSA patients and controls and to identify brain areas that showed a significant amount of atrophy. Using 3D-based volumetry, we confirmed that in MSA-C patients, the brainstem including medulla and pons, vermis and cerebellar hemispheres, caudate nucleus and putamen showed significant atrophy compared with controls. Next, we used 3D-based volumetry to analyze the atrophy rates. Atrophy rates in patients with MSA were significantly different from controls for putamen (-11.4% +/- 2.6%/year), vermis (-12.3% +/- 2.9%/year), and cerebellar hemispheres (-6.6% +/- 1.1%/year). The results show that 3D-based MRI volumetry is a tool that allows the disease progression of MSA to be followed over a time period of 2 years and suggest that it may serve as a surrogate marker in clinical trials to measure disease progression.

Aged↗

Disorders of agency in schizophrenia correlate with an inability to compensate for the sensory consequences of actions.

Psychopathological symptoms in schizophrenia patients suggest that the concept of self might be disturbed in these individuals [1]. Delusions of influence make them feel that someone else is guiding their actions, and certain kinds of their hallucinations seem to be misinterpretations of their own inner voice as an external voice, the common denominator being that self-produced information is perceived as if coming from outside. If this interpretation were correct, we might expect that schizophrenia patients might also attribute the sensory consequences of their own eye movements to the environment rather than to themselves, challenging the percept of a stable world. Indeed, this seems to be the case because we found a clear correlation between the strength of delusions of influence and the ability of schizophrenia patients to cancel out such self-induced retinal information in motion perception. This correlation reflects direct experimental evidence supporting the view that delusions of influence in schizophrenia might be due to a specific deficit in the perceptual compensation of the sensory consequences of one's own actions [1, 2, 3, 4, 5 and 6].

Adult↗

Cortical activation during cholinesterase-inhibitor treatment in Alzheimer disease: preliminary findings from a pharmaco-fMRI study.

OBJECTIVE: Cholinesterase inhibitors improve cognitive functioning in Alzheimer disease (AD). The authors studied, with functional magnetic resonance imaging (fMRI), the neural mechanism by which this cholinergic enhancement improves memory encoding in AD over longer time periods. METHODS: Brain activation was measured in 10 patients with AD and 10 healthy elderly comparison subjects with fMRI while they were encoding novel faces. Patients were scanned again after a 10-week open treatment with the cholinesterase-inhibitor donepezil. RESULTS: Neuropsychologically-tested memory performance improved during the treatment phase in the patients. During the encoding of novel faces, elderly comparison subjects showed more activation in the right fusiform gyrus than the group of AD patients. After a 10-week treatment with donepezil, the fusiform gyrus was also activated in patients, similar to the comparison group. CONCLUSIONS: The right fusiform gyrus is associated with the processing of faces. Cholinergic enhancement augments selective attention by increased selectivity of perceptual responses in patients with AD. This mechanism may contribute to a more efficient processing of the attended stimulus and thus be a mechanism underlying clinical improvement of cognitive functioning. These promising preliminary findings need to be confirmed in a larger, controlled trial in which both fMRI and attention measures serve as outcomes.

Aged↗

Neural correlates of metaphor processing.

Metaphoric language is used to express meaning that is otherwise difficult to conceptualize elegantly. Beyond semantic analysis, understanding the figurative meaning of a metaphor requires mental linkage of different category domains normally not related to each other. We investigated processing of metaphoric sentences using event-related functional magnetic resonance imaging (fMRI). Stimuli consisted of 60 novel short German sentence pairs with either metaphoric or literal meaning. The pairs differed only in their last one to three words and were matched for syntax structure, word frequency, connotation and tense. Fifteen healthy subjects (six female, nine male, 19-51 years) read these sentences silently and judged by pressing one of two buttons whether they had a positive or negative connotation. Reading metaphors in contrast to literal sentences revealed signal changes in the left lateral inferior frontal (BA 45/47), inferior temporal (BA 20) and posterior middle/inferior temporal (BA 37) gyri. The activation in the left inferior frontal gyrus may reflect semantic inferencing processes during the understanding of a metaphor. This is in line with the results from other functional imaging studies showing an involvement of the left inferior frontal gyrus in integrating word and sentence meanings. Previous results of a right hemispheric involvement in metaphor processing might reflect understanding of complex sentences.

Adult↗

Brain regions sensitive to the face inversion effect: a functional magnetic resonance imaging study in humans.

Perception of upright faces relies on configural processing. Therefore recognition of inverted, compared to upright faces is impaired. In a functional magnetic resonance imaging experiment we investigated the neural correlate of a face inversion task. Thirteen healthy subjects were presented with a equal number of upright and inverted faces alternating with a low level baseline with an upright and inverted picture of an abstract symbol. Brain activation was calculated for upright minus inverted faces. For this differential contrast, we found a signal change in the right superior temporal sulcus and right insula. Configural properties are processed in a network comprising right superior temporal and insular cortex.

Adult↗

Successful episodic memory retrieval of newly learned faces activates a left fronto-parietal network.

It is easier to recognize a familiar face than a newly learned face. The neural basis of familiar face recognition has been elucidated in functional imaging and lesion studies. Behavioural and neuropsychological data indicate, however, that brain systems involved in episodic retrieval of familiar and newly learned faces are distinct. In our study, 12 subjects viewed 30 novel faces in an encoding session. In the study condition, event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation during correct recognition of the recently learned faces to that observed during correct rejection of unknown control faces. Differences were present in the left inferior parietal (BA 40) and left medial frontal/anterior cingulate (BA 32/9) cortex. These two regions may be part of a pathway in the dorsal visual stream, responsible for a "feeling of familiarity" in contrast to the ventral pathway in the temporal lobes, which is mainly involved in the recognition of personal identity.

Adult↗

The neural correlates of perceiving one's own movements.

Feedforward mechanisms are important for movement control. They may also contribute to the identification of self-produced actions by attenuating the sensory consequences of self-produced movements. In our study, subjects opened and closed their hand slowly and continuously (0.5 Hz). This movement was filmed with an MRI compatible video camera and projected online onto a screen, viewed by the subject while BOLD contrast was measured with fMRI. The temporal delay between movement and feedback was parametrically varied (0-200 ms). In each trial, subjects judged whether there was a delay or not. There was a positive correlation between the extent of the temporal delay and activation in the right posterior superior temporal cortex (pSTS) and a negative correlation in the left putamen. A second analysis addressed the neural correlates of subjective judgement under conditions of uncertainty. This contrast showed a differential activation in the cerebellum. These results support the assumption of a forward model implying that predictions generated in motor areas attenuate sensory areas. They also suggest that efference copy mechanisms are not located within specific brain areas but are implemented as a specific form of interaction between perceptual and motor areas depending on the modalities and the type of actions involved. Further, conscious detection of small temporal deviations might be based on signals generated in the cerebellum which provide fine-grained temporal information. These results might be useful to refine theories about the role of forward mechanisms in the emergence of disorders of the self, such as in schizophrenia.

Adult↗

Self-consciousness, self-agency, and schizophrenia.

Empirical approaches on topics such as consciousness, self-awareness, or introspective perspective, need a conceptual framework so that the emerging, still unconnected findings can be integrated and put into perspective. We introduce a model of self-consciousness derived from phenomenology, philosophy, the cognitive, and neurosciences. We will then give an overview of research data on one particular aspect of our model, self-agency, trying to link findings from cognitive psychology and neuroscience. Finally, we will expand on pathological aspects of self-agency, and in particular on psychosis in schizophrenia. We show, that a deficient self-monitoring system underlies, in part, hallucinations and formal thought (language) disorder in schizophrenia. We argue, that self-consciousness is a valid construct and can be studied with the instruments of cognitive and neuroscience.

Awareness↗

Observing one's hand become anarchic: an fMRI study of action identification.

The self seems to be a unitary entity remaining stable across time. Nevertheless, current theorizing conceptualizes the self as a number of interacting sub-systems involving perception, intention and action (self-model). One important function of such a self-model is to distinguish between events occurring as a result of one's own actions and events occurring as the result of somebody else's actions. We conducted an fMRI experiment that compared brain activation after an abrupt mismatch between one's own movement and its visual consequences with an abrupt mismatch between one's own movement and somebody else's visually perceived hand movement. A right fronto-parietal network was selectively active during a sudden mismatch between one's own observed and performed hand action.

Awareness↗