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Use of magnetic resonance imaging in pharmacogenomics.

ABSTRACT: Because of the large variation in the response to psychoactive medication, many studies have attempted to uncover genetic factors that determine response. While considerable knowledge exists on the large effects of genetic polymorphisms on pharmacokinetics and plasma concentrations of drugs, effects of the concentration at the target site and pharmacodynamic effects on brain functions in disease are much less known. This article reviews the role of magnetic resonance imaging (MRI) to visualize response to medication in brain behaviour circuits in vivo in humans and assess the influence of pharmacogenetic factors. Two types of studies have been used to characterize effects of medication and genetic variation. In task-related activation studies the focus is on changes in the activity of a neural circuit associated with a specific psychological process. The second type of study investigates resting state perfusion. These studies provide an assessment of vascular changes associated with bioavailability of drugs in the brain, but may also assess changes in neural activity after binding of centrally active agents. Task-related pharmacogenetic studies of cognitive function have characterized the effects in the prefrontal cortex of genetic polymorphisms of dopamine receptors (DRD2), metabolic enzymes (COMT) and in the post-synaptic signalling cascade under the administration of dopamine agonists and antagonists. In contrast, pharmacogenetic imaging with resting state perfusion is still in its infancy. However, the quantitative nature of perfusion imaging, its non-invasive character and its repeatability might be crucial assets in visualizing the effects of medication in vivo in man during therapy.

SUBMITTER: Viviani R

PROVIDER: S-EPMC3971984 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Use of magnetic resonance imaging in pharmacogenomics.

Viviani Roberto R Lehmann Marie-Louise ML Stingl Julia C JC

British journal of clinical pharmacology 20140401 4

Because of the large variation in the response to psychoactive medication, many studies have attempted to uncover genetic factors that determine response. While considerable knowledge exists on the large effects of genetic polymorphisms on pharmacokinetics and plasma concentrations of drugs, effects of the concentration at the target site and pharmacodynamic effects on brain functions in disease are much less known. This article reviews the role of magnetic resonance imaging (MRI) to visualize r ...[more]

PMID: 23802603

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Project description:BackgroundTool use in humans requires that multisensory information is integrated across different locations, from objects seen to be distant from the hand, but felt indirectly at the hand via the tool. We tested the hypothesis that using a simple tool to perceive vibrotactile stimuli results in the enhanced processing of visual stimuli presented at the distal, functional part of the tool. Such a finding would be consistent with a shift of spatial attention to the location where the tool is used.Methodology/principal findingsWe tested this hypothesis by scanning healthy human participants' brains using functional magnetic resonance imaging, while they used a simple tool to discriminate between target vibrations, accompanied by congruent or incongruent visual distractors, on the same or opposite side to the tool. The attentional hypothesis was supported: BOLD response in occipital cortex, particularly in the right hemisphere lingual gyrus, varied significantly as a function of tool position, increasing contralaterally, and decreasing ipsilaterally to the tool. Furthermore, these modulations occurred despite the fact that participants were repeatedly instructed to ignore the visual stimuli, to respond only to the vibrotactile stimuli, and to maintain visual fixation centrally. In addition, the magnitude of multisensory (visual-vibrotactile) interactions in participants' behavioural responses significantly predicted the BOLD response in occipital cortical areas that were also modulated as a function of both visual stimulus position and tool position.Conclusions/significanceThese results show that using a simple tool to locate and to perceive vibrotactile stimuli is accompanied by a shift of spatial attention to the location where the functional part of the tool is used, resulting in enhanced processing of visual stimuli at that location, and decreased processing at other locations. This was most clearly observed in the right hemisphere lingual gyrus. Such modulations of visual processing may reflect the functional importance of visuospatial information during human tool use.

Dataset Information

Use of magnetic resonance imaging in pharmacogenomics.

Publications

Use of magnetic resonance imaging in pharmacogenomics.

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