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  • 1. Mattingsdal, Morten
    et al.
    Brown, Andrew Anand
    Djurovic, Srdjan
    Sønderby, Ida Elken
    Server, Andres
    Melle, Ingrid
    Agartz, Ingrid
    Hovig, Eivind
    Jensen, Jimmy
    Institute of Clinical Medicine, University of Oslo.
    Andreassen, Ole A.
    Pathway analysis of genetic markers associated with a functional MRI faces paradigm implicates polymorphisms in calcium responsive pathways2013In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 70, p. 143-149Article in journal (Refereed)
    Abstract [en]

    Several lines of evidence suggest that common polygenic variation influences brain function in humans. Combining high-density genetic markers with brain imaging techniques is constricted by the practicalities of collecting sufficiently large brain imaging samples. Pathway analysis promises to leverage knowledge on function of genes to detect recurring signals of moderate effect. We adapt this approach, exploiting the deep information collected on brain function by fMRI methods, to identify molecular pathways containing genetic variants which influence brain activation during a commonly applied experiment based on a face matching task (n=246) which was developed to study neural processing of faces displaying negative emotions. Genetic markers moderately associated (p<10(-4)) with whole brain activation phenotypes constructed by applying principal components to contrast maps, were tested for pathway enrichment using permutation based methods. The most significant pathways are related to post NMDA receptor activation events, driven by genetic variants in calcium/calmodulin-dependent protein kinase II (CAMK2G, CAMK2D) and a calcium-regulated nucleotide exchange factor (RASGRF2) in which all are activated by intracellular calcium/calmodulin. The most significant effect of the combined polygenic model were localized to the left inferior frontal gyrus (p=1.03 × 10(-9)), a region primarily involved in semantic processing but also involved in processing negative emotions. These findings suggest that pathway analysis of GWAS results derived from principal component analysis of fMRI data is a promising method, to our knowledge, not previously described.

  • 2. Ousdal, Olga Therese
    et al.
    Reckless, Greg E
    Server, Andres
    Andreassen, Ole A
    Jensen, Jimmy
    Oslo University Hospital, Oslo, Norway & University of Oslo, Oslo, Norway & Charité Universitätsmedizin, Berlin, Germany.
    Effect of relevance on amygdala activation and association with the ventral striatum.2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 62, no 1, p. 95-101Article in journal (Refereed)
    Abstract [en]

    While the amygdala historically has been implicated in emotional stimuli processing, recent data suggest a general role in parceling out the relevance of stimuli, regardless of their emotional properties. Using functional magnetic resonance imaging, we tested the relevance hypothesis by investigating human amygdala responses to emotionally neutral stimuli while manipulating their relevance. The task was operationalized as highly relevant if a subsequent opportunity to respond for a reward depended on response accuracy of the task, and less relevant if the reward opportunity was independent of task performance. A region of interest analysis revealed bilateral amygdala activations in response to the high relevance condition compared to the low relevance condition. An exploratory whole-brain analysis yielded robust similar results in bilateral ventral striatum. A subsequent functional connectivity analysis demonstrated increased connectivity between amygdala and ventral striatum for the highly relevant stimuli compared to the less relevant stimuli. These findings suggest that the amygdala's processing profile goes beyond detection of emotions per se, and directly support the proposed role in relevance detection. In addition, the findings suggest a close relationship between amygdala and ventral striatal activity when processing relevant stimuli. Thus, the results may indicate that human amygdala modulates ventral striatum activity and subsequent behaviors beyond that observed for emotional cues, to encompass a broader range of relevant stimuli.

  • 3.
    Ousdal, Olga Therese
    et al.
    Oslo University Hospital.
    Specht, Karsten
    University of Bergen.
    Server, Andres
    Oslo University Hospital.
    Andreassen, Ole A.
    Oslo University Hospital.
    Dolan, Ray J.
    University College London.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    The human amygdala encodes value and space during decision making2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 101, p. 712-719Article in journal (Refereed)
    Abstract [en]

    Valuable stimuli are invariably localized in space. While our knowledge regarding the neural networks supporting value assignment and comparisons is considerable, we lack a basic understanding of how the human brain integrates motivational and spatial information. The amygdala is a key structure for learning and maintaining the value of sensory stimuli and a recent non-human primate study provided initial evidence that it also acts to integrate value with spatial location, a question we address here in a human setting. We measured hemodynamic responses (fMRI) in amygdala while manipulating the value and spatial configuration of stimuli in a simple stimulus-reward task. Subjects responded significantly faster and showed greater amygdala activation when a reward was dependent on a spatial specific response, compared to when a reward required less spatial specificity. Supplemental analysis supported this spatial specificity by demonstrating that the pattern of amygdala activity varied based on whether subjects responded to a motivational target presented in the ipsilateral or contralateral visual space. Our data show that the human amygdala integrates information about space and value, an integration of likely importance for assigning cognitive resources towards highly valuable stimuli in our environment.

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