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  • 1. Aminoff, Sofie R
    et al.
    Jensen, Jimmy
    University of Oslo & Oslo University Hospital.
    Lagerberg, Trine V
    Andreassen, Ole A
    Melle, Ingrid
    Decreased self-reported arousal in schizophrenia during aversive picture viewing compared to bipolar disorder and healthy controls.2011In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 185, no 3, 309-314 p.Article in journal (Refereed)
    Abstract [en]

    Both schizophrenia (SCZ) and bipolar disorder (BD) are associated with disturbances in emotion processing. Previous studies suggest that patients with SCZ assess unpleasant pictures as less arousing than healthy controls (HC), while patients with BD assess neutral pictures as more arousing than HC. No previous studies have investigated whether there is a difference in emotional response across all three groups. Our aim was to explore whether there was a difference in the evaluation of valence and in arousal between SCZ, BD and HC for aversive and neutral pictures. We showed 72 pictures (neutral, non-socially aversive and socially aversive) from the International Affective Picture System (IAPS) to 347 subjects. There was a clear interaction effect between the diagnostic group and increasing picture aversiveness for both valence and arousal. There were no significant differences in valence ratings between the different groups or in arousal ratings on any type of stimuli between BD patients and HC. However, SCZ patients reported significantly lower arousal for aversive stimuli, particularly with a social content, when compared to BD patients and HC. This was more pronounced in females. The presence of lifetime psychotic symptoms did not influence emotional responses.

  • 2. Aminoff, Sofie Ragnhild
    et al.
    Jensen, Jimmy
    Institute of Clinical Medicine, University of Oslo & Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, Germany.
    Lagerberg, Trine Vik
    Hellvin, Tone
    Sundet, Kjetil
    Andreassen, Ole A
    Melle, Ingrid
    An association between affective lability and executive functioning in bipolar disorder.2012In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 198, no 1, 58-61 p.Article in journal (Refereed)
    Abstract [en]

    Studies suggest altered affect regulation manifested by affective lability in manic/mixed and euthymic states in patients with bipolar disorder (BD). Altered affect regulation may arise from disturbances in interactions between the cognitive and the emotional brain networks. However, the relationship between affective lability and executive function has not previously been studied. Our aim was to investigate affective lability, as measured with the Affective Lability Scale (ALS) in patients with BD (N=32) compared to healthy controls (HC) (N=60), and its relationship to executive functioning. We found significantly higher ALS scores in the BD than in the HC group, indicating a higher degree of affective lability in patients with BD. Sub-sample analysis revealed a significant positive relationship between affective lability and semantic set shifting abilities in BD only. These findings suggest that higher levels of affective lability compared with controls are a trait as well as state dependent in BD, and that disturbed affective lability may arise from an aberrant interaction between cognitive and emotional brain networks.

  • 3.
    Bolstad, Ingeborg
    et al.
    Norge.
    Andreassen, Ole A.
    Norge.
    Groote, Inge R.
    Norge.
    Haatveit, Beathe
    Norge.
    Server, Andres
    Norge.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap. Norge.
    No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol2015In: Frontiers in Human Neuroscience, ISSN 1662-5161, Vol. 9, 296Article in journal (Refereed)
    Abstract [en]

    Background: Aripiprazole is an atypical antipsychotic drug that is characterized by partial dopamine D2 receptor agonism. Its pharmacodynamic profile is proposed to be beneficial in the treatment of cognitive impairment, which is prevalent in psychotic disorders. This study compared brain activation characteristics produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist, during a task targeting executive functioning.

    Methods: Healthy participants received an acute oral dose of haloperidol, aripiprazoleor placebo before performing an executive functioning task while blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out.

    Results: There was a tendency towards reduced performance in the aripiprazole group compared to the two other groups. The image analysis yielded a strong task related BOLD-fMRI response within each group. An uncorrected between-group analysis showed that aripiprazole challenge resulted in stronger activation in the frontal and temporal gyri and the putamen compared with haloperidol challenge, but after correcting for multiple testing there was no significant group difference.

    Conclusion: No significant group differences between aripiprazole and haloperidol infrontal cortical activation were obtained when corrected for multiple comparisons.

  • 4.
    Bolstad, Ingeborg
    et al.
    Norge.
    Andreassen, Ole A
    Norge.
    Groote, Inge
    Norge.
    Server, Andres
    Norge.
    Sjaastad, Ivar
    Norge.
    Kapur, Shitij
    Storbritannien.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: a pharmacological fMRI study2015In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 25, no 12, 2252-2261 p.Article in journal (Refereed)
    Abstract [en]

    The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out. The fMRI task, targeting the mesolimbic motivational system that is thought to be disturbed in psychosis, was based on the conditioned avoidance response (CAR) animal model - a widely used test of therapeutic potential of antipsychotic drugs. In line with the CAR animal model, the present results show that subjects given haloperidol were not able to avoid more aversive than neutral task trials, even though the response times were shorter during aversive events. In the aripiprazole and placebo groups more aversive than neutral events were avoided. Accordingly, the task-related BOLD-fMRI response in the mesolimbic motivational system was diminished in the haloperidol group compared to the placebo group, particularly in the ventral striatum, whereas the aripiprazole group showed task-related activations intermediate of the placebo and haloperidol groups. The current results show differential effects on brain function by aripiprazole and haloperidol, probably related to altered DA transmission. This supports the use of pharmacological fMRI to study antipsychotic properties in humans.

  • 5.
    Bolstad, Ingeborg
    et al.
    KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital.
    Andreassen, Ole A.
    KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital.
    Reckless, Greg E.
    KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital.
    Sigvartsen, Niels P.
    KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital.
    Server, Andres
    Department of Neuroradiology, Oslo University Hospital.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Aversive event anticipation affects connectivity between the ventral striatum and the orbitofrontal cortex in an fMRI avoidance task2013In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 6, e68494- p.Article in journal (Refereed)
    Abstract [en]

    Ability to anticipate aversive events is important for avoiding dangerous or unpleasant situations. The motivation to avoid an event is influenced by the incentive salience of an event-predicting cue. In an avoidance fMRI task we used tone intensities to manipulate salience in order to study the involvement of the orbitofrontal cortex in processing of incentive salience. In the task, cues predicting either aversive or neutral avoidable tones were presented. Ventral striatum, amygdala and anterior insula activations were significantly stronger during presentation of cues for aversive than neutral tones. A psychophysiological interaction analysis showed stronger connectivity between the ventral striatum and the orbitofrontal cortex during aversive than neutral conditions. The present study shows an interaction between the ventral striatum, a structure previously linked to negative incentive salience, and the orbitofrontal cortex supporting a role for this region in processing salience. In addition, this study replicates previous findings suggesting that the task is robust.

  • 6.
    Brandt, Christine Lycke
    et al.
    Norge.
    Kaufmann, Tobias
    Norge.
    Agartz, Ingrid
    Norge.
    Hugdahl, Kenneth
    Norge.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Ueland, Torill
    Norge.
    Haatveit, Beathe
    Norge.
    Skatun, Kristina C.
    Norge.
    Doan, Nhat Trung
    Norge.
    Melle, Ingrid
    Norge.
    Andreassen, Ole A.
    Norge.
    Westlye, Lars T.
    Norge.
    Cognitive effort and schizophrenia modulate large-scale functional brain connectivity2015In: Schizophrenia Bulletin, ISSN 0586-7614, E-ISSN 1745-1701, Vol. 41, no 6, 1360-1369 p.Article in journal (Refereed)
    Abstract [en]

    Schizophrenia (SZ) is characterized by cognitive dysfunction and disorganized thought, in addition to hallucinations and delusions, and is regarded a disorder of brain connectivity. Recent efforts have been made to characterize the underlying brain network organization and interactions. However, to which degree connectivity alterations in SZ vary across different levels of cognitive effort is unknown. Utilizing independent component analysis (ICA) and methods for delineating functional connectivity measures from functional magnetic resonance imaging (fMRI) data, we investigated the effects of cognitive effort, SZ and their interactions on between-network functional connectivity during 2 levels of cognitive load in a large and well-characterized sample of SZ patients (n = 99) and healthy individuals (n = 143). Cognitive load influenced a majority of the functional connections, including but not limited to fronto-parietal and default-mode networks, reflecting both decreases and increases in between-network synchronization. Reduced connectivity in SZ was identified in 2 large-scale functional connections across load conditions, with a particular involvement of an insular network. The results document an important role of interactions between insular, default-mode, and visual networks in SZ pathophysiology. The interplay between brain networks was robustly modulated by cognitive effort, but the reduced functional connectivity in SZ, primarily related to an insular network, was independent of cognitive load, indicating a relatively general brain network-level dysfunction.

  • 7. Brown, A A
    et al.
    Jensen, Jimmy
    University of Oslo & University of Oslo & Charité Universitätsmedizin, Berlin, Germany.
    Nikolova, Y S
    Djurovic, S
    Agartz, I
    Server, A
    Ferrell, R E
    Manuck, S B
    Mattingsdal, M
    Melle, I
    Hariri, A R
    Frigessi, A
    Andreassen, O A
    Genetic variants affecting the neural processing of human facial expressions: evidence using a genome-wide functional imaging approach.2012In: Translational psychiatry, ISSN 2158-3188, Vol. 2, e143- p.Article in journal (Refereed)
    Abstract [en]

    Human faces present crucial visual information for social interaction. Specialized brain regions are involved in the perception of faces, with the fusiform face area (FFA) a key neuronal substrate. Face processing is genetically controlled, but by which specific genes is unknown. A genome-wide approach identified common single nucleotide polymorphisms (SNPs) associated with areas of increased brain activity in response to affective facial expressions, measured with functional magnetic resonance imaging. SNPs in 20 genetic regions were linked with neural responses to negative facial expressions in a Norwegian sample (n=246), which included patients with mental illness. Three genetic regions were linked with FFA activation in a further discovery experiment using positive facial expressions and involving many of the same individuals (n=284). Two of these three regions showed significant association with right FFA activation to negative facial expressions in an independent North American replication sample of healthy Caucasians (n=85, 3q26.31, P=0.004; 20p12.3, P=0.045). The activation patterns were particularly striking for the SNP in 3q26.31, which lies in a gene TMEM212; only the FFA was activated. The specialized function of this brain region suggests that TMEM212 could contribute to the innate architecture of face processing.

  • 8. Danielsen, A
    et al.
    Otnæss, M K
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Williams, S C R
    Østberg, B C
    Investigating repetition and change in musical rhythm by functional MRI2014In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 275, 469-476 p.Article in journal (Refereed)
    Abstract [en]

    Groove-based rhythm is a basic and much appreciated feature of Western popular music. It is commonly associated with dance, movement and pleasure and is characterized by the repetition of a basic rhythmic pattern. At various points in the musical course, drum breaks occur, representing a change compared to the repeated pattern of the groove. In the present experiment, we investigated the brain response to such drum breaks in a repetitive groove. Participants were scanned with functional magnetic resonance imaging (fMRI) while listening to a previously unheard naturalistic groove with drum breaks at uneven intervals. The rhythmic pattern and the timing of its different parts as performed were the only aspects that changed from the repetitive sections to the breaks. Differences in blood oxygen level-dependent activation were analyzed. In contrast to the repetitive parts, the drum breaks activated the left cerebellum, the right inferior frontal gyrus (RIFG), and the superior temporal gyri (STG) bilaterally. A tapping test using the same stimulus showed an increase in the standard deviation of inter-tap-intervals in the breaks versus the repetitive parts, indicating extra challenges for auditory-motor integration in the drum breaks. Both the RIFG and STG have been associated with structural irregularity and increase in musical-syntactical complexity in several earlier studies, whereas the left cerebellum is known to play a part in timing. Together these areas may be recruited in the breaks due to a prediction error process whereby the internal model is being updated. This concurs with previous research suggesting a network for predictive feed-forward control that comprises the cerebellum and the cortical areas that were activated in the breaks.

  • 9. Diaconescu, Andreea Oliviana
    et al.
    Jensen, Jimmy
    Centre for Addiction and Mental Health, Toronto, ON, Canada & Charité Universitätsmedizin, Berlin, Germany.
    Wang, Hongye
    Willeit, Matthäus
    Menon, Mahesh
    Kapur, Shitij
    McIntosh, Anthony R
    Aberrant Effective Connectivity in Schizophrenia Patients during Appetitive Conditioning2011In: Frontiers in human neuroscience, ISSN 1662-5161, Vol. 4, 239- p.Article in journal (Refereed)
    Abstract [en]

    It has recently been suggested that schizophrenia involves dysfunction in brain connectivity at a neural level, and a dysfunction in reward processing at a behavioral level. The purpose of the present study was to link these two levels of analyses by examining effective connectivity patterns between brain regions mediating reward learning in patients with schizophrenia and healthy, age-matched controls. To this aim, we used functional magnetic resonance imaging and galvanic skin recordings (GSR) while patients and controls performed an appetitive conditioning experiment with visual cues as the conditioned (CS) stimuli, and monetary reward as the appetitive unconditioned stimulus (US). Based on explicit stimulus contingency ratings, conditioning occurred in both groups; however, based on implicit, physiological GSR measures, patients failed to show differences between CS+ and CS- conditions. Healthy controls exhibited increased blood-oxygen-level dependent (BOLD) activity across striatal, hippocampal, and prefrontal regions and increased effective connectivity from the ventral striatum to the orbitofrontal cortex (OFC BA 11) in the CS+ compared to the CS- condition. Compared to controls, patients showed increased BOLD activity across a similar network of brain regions, and increased effective connectivity from the striatum to hippocampus and prefrontal regions in the CS- compared to the CS+ condition. The findings of increased BOLD activity and effective connectivity in response to the CS- in patients with schizophrenia offer insight into the aberrant assignment of motivational salience to non-reinforced stimuli during conditioning that is thought to accompany schizophrenia.

  • 10. Diaconescu, Andreea Oliviana
    et al.
    Menon, Mahesh
    Jensen, Jimmy
    Department of Psychiatry, University of Oslo and Oslo University Hospital, Ullevål, Oslo, Norway.
    Kapur, Shitij
    McIntosh, Anthony Randal
    Dopamine-induced changes in neural network patterns supporting aversive conditioning.2010In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1313, 143-161 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the present paper is to assess the effects of altered dopamine (DA) transmission on the functional connectivity among brain regions mediating aversive conditioning in humans. To this aim, we analyzed a previous published data set from a double-blind design combined with functional magnetic resonance imaging (fMRI) recordings in which healthy volunteers were randomly assigned to one of three drug groups: amphetamine (an indirect DA agonist), haloperidol (DA D2 receptor antagonist), and placebo. Participants were exposed to an aversive classical conditioning paradigm using cutaneous electrical stimulation as the unconditioned stimulus (US), and visual cues as the conditioned stimuli (CS) where one colour (CS+) was followed by the US in 33% of the trials and another colour (CS-) had no consequences. All participants reported awareness of stimulus contingencies. Group analysis of fMRI data revealed that the left ventral striatum (VS) and amygdala activated in response to the CS+ in all the three groups. Because of their activation patterns and documented involvement in aversive conditioning, both regions were used as seeds in the functional connectivity analysis. To constrain the functional networks obtained to relate to the conditioned response, we also correlated seed activity with the Galvanic Skin Response (GSR). In the placebo group, the right ventral tegmental area/substantia nigra (VTA/SN), bilateral caudate, right parahippocampal gyrus, left inferior parietal lobule (IPL), bilateral postcentral gyrus, bilateral middle frontal (BA 46), orbitofrontal, and ventromedial prefrontal cortices (PFC, BA 10/11) correlated with the VS and amygdala seeds in response to the CS+ compared to the CS-. Enhancing dopamine transmission via amphetamine was associated with reduced task differences and significant functional connectivity for both CS+ and CS- conditions between the left VS seed and regions modulated by DA, such as the left VTA/SN, right caudate, left amygdala, left middle frontal gyrus (BA 46), and bilateral ventromedial PFC (BA 10). Blocking dopamine transmission via haloperidol was associated with significant functional connectivity across an alternate network of regions including the left amygdala seed and the right insula, the left ACC (BA 24/32), bilateral IPL (BA 40), precuneus (BA 7), post-central gyrus, middle frontal gyrus (BA 46), and supplementary motor area (SMA, BA 6) to the CS+ versus the CS-. These data provide insight into the distinct effects of DA agents on the functional connectivity between striatal, limbic, and prefrontal areas.

  • 11.
    Haatveit, Beathe
    et al.
    Norge.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Psykologi. Kristianstad University, Research environment Man & Biosphere Health (MABH).
    Alnæs, Dag
    Norge.
    Kaufmann, Tobias
    Norge.
    Brandt, Christine L.
    Norge.
    Thoresen, Christian
    Norge.
    Andreassen, Ole A.
    Norge.
    Melle, Ingrid
    Norge.
    Ueland, Torill
    Norge.
    Westlye, Lars T.
    Norge.
    Reduced load-dependent default mode network deactivation across executive tasks in schizophrenia spectrum disorders2016In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 12, 389-396 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Schizophrenia is associated with cognitive impairment and brain network dysconnectivity. Recent efforts have explored brain circuits underlying cognitive dysfunction in schizophrenia and documented altered activation of large-scale brain networks, including the task-positive network (TPN) and the task-negative default mode network (DMN) in response to cognitive demands. However, to what extent TPN and DMN dysfunction reflect overlapping mechanisms and are dependent on cognitive state remain to be determined.

    METHODS: In the current study, we investigated the recruitment of TPN and DMN using independent component analysis in patients with schizophrenia spectrum disorders (n = 29) and healthy controls (n = 21) during two different executive tasks probing planning/problem-solving and spatial working memory.

    RESULTS: We found reduced load-dependent DMN deactivation across tasks in patients compared to controls. Furthermore, we observed only moderate associations between the TPN and DMN activation across groups, implying that the two networks reflect partly independent mechanisms. Additionally, whereas TPN activation was associated with task performance in both tasks, no such associations were found for DMN.

    CONCLUSION: These results support a general load-dependent DMN dysfunction in schizophrenia spectrum disorder across two demanding executive tasks that is not merely an epiphenomenon of cognitive dysfunction.

  • 12.
    Haatveit, Beathe
    et al.
    Oslo University Hospital.
    Melle, Ingrid
    Oslo University Hospital.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Sundet, Kjetil
    University of Oslo.
    Vaskinn, Anja
    University of Oslo.
    Simonsen, Carmen
    Oslo University Hospital.
    Andreassen, Ole
    Oslo University Hospital.
    Ueland, Torill
    Oslo University Hospital.
    Are executive functions stable in first episode patients?: one year follow-up study2014In: Early Intervention in Psychiatry, ISSN 1751-7885, E-ISSN 1751-7893, Vol. 8, 75- p.Article in journal (Refereed)
  • 13.
    Haatveit, Beathe
    et al.
    University of Oslo.
    Vaskinn, Anja
    University of Oslo.
    Sundet, Kjetil S
    University of Oslo.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap. University of Oslo.
    Andreassen, Ole A
    University of Oslo.
    Melle, Ingrid
    University of Oslo.
    Ueland, Torill
    University of Oslo.
    Stability of executive functions in first episode psychosis: one year follow up study2015In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 228, no 3, 475-481 p.Article in journal (Refereed)
    Abstract [en]

    Executive functioning is a multi-dimensional construct covering several sub-processes. The aim of this study was to determine whether executive functions, indexed by a broad range of executive measures remain stable in first episode psychosis (FEP) over time. Eighty-two patients and 107 age and gender matched healthy controls were assessed on five subdomains of executive functioning; working memory, fluency, flexibility, and inhibitory control at baseline and at 1 year follow-up. Results showed that patients performed significantly poorer than controls on all executive measures at both assessment points. In general executive functions remained stable from baseline to follow-up, although both groups improved on measures of inhibitory control and flexibility. In phonemic fluency, controls showed a slight improvement while patients showed a slight decline. Investigation of individual trajectories revealed some fluctuations in both groups over time, but mainly supports the group level findings. The implications of these results are discussed.

  • 14.
    Jensen, Jimmy
    et al.
    University of Oslo & Ullevaal University Hospital, Oslo.
    Kapur, S.
    Salience and psychosis: moving from theory to practise2009In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 39, no 2, 197-198 p.Article in journal (Other academic)
  • 15.
    Jensen, Jimmy
    et al.
    PET Centre, Centre for Addiction and Mental Health, Baycrest Geriatric Centre, Toronto, Ontario, Canada.
    McIntosh, Anthony R
    Crawley, Adrian P
    Mikulis, David J
    Remington, Gary
    Kapur, Shitij
    Direct activation of the ventral striatum in anticipation of aversive stimuli.2003In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 40, no 6, 1251-1257 p.Article in journal (Refereed)
    Abstract [en]

    The brain "reward" system, centered on the limbic ventral striatum, plays a critical role in the response to pleasure and pain. The ventral striatum is activated in animal and human studies during anticipation of appetitive/pleasurable events, but its role in aversive/painful events is less clear. Here we present data from three human fMRI studies based on aversive conditioning using unpleasant cutaneous electrical stimulation and show that the ventral striatum is reliably activated. This activation is observed during anticipation and is not a consequence of relief after the aversive event. Further, the ventral striatum is activated in anticipation regardless of whether there is an opportunity to avoid the aversive stimulus or not. Our data suggest that the ventral striatum, a crucial element of the brain "reward" system, is directly activated in anticipation of aversive stimuli.

  • 16.
    Jensen, Jimmy
    et al.
    Malmö högskola.
    Nilsson, Lise-Lotte
    Malmö högskola.
    Levander, Sten
    Malmö högskola.
    Neurocognitive and psychopathological correlates of self-monitoring ability in schizophrenia.2004In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491, Vol. 254, no 5, 312-317 p.Article in journal (Refereed)
    Abstract [en]

    In a previous study reported by our group one salient finding was that many patients with schizophrenia appeared to be unable to judge their own quality of life (QoL) and that this inability was associated with negative symptoms. The association between negative symptoms, poor self-monitoring capacity and lack of insight might be explained by a common underlying factor, i.e. neurocognitive impairment. Fifty schizophrenic patients were examined by symptom ratings and a comprehensive neuropsychological test battery. The cognitive performance of the patients was very poor. The major findings of the present study were the association between clinically rated Lack of judgement (PANSS G12) and 1) a set of standard performance and executive indices of the computerised tests, and 2) difference scores between objective performance/strategies and self-ratings of the same attributes. There appears to be a substantial contribution of cognitive and executive problems to the poor judgement and lack of insight of schizophrenic patients, and these problems can to some extent be assessed objectively.

  • 17.
    Jensen, Jimmy
    et al.
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, Canada.
    Smith, Andrew J
    Willeit, Matthäus
    Crawley, Adrian P
    Mikulis, David J
    Vitcu, Irina
    Kapur, Shitij
    Separate brain regions code for salience vs. valence during reward prediction in humans.2007In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 28, no 4, 294-302 p.Article in journal (Refereed)
    Abstract [en]

    Predicting rewards and avoiding aversive conditions is essential for survival. Recent studies using computational models of reward prediction implicate the ventral striatum in appetitive rewards. Whether the same system mediates an organism's response to aversive conditions is unclear. We examined the question using fMRI blood oxygen level-dependent measurements while healthy volunteers were conditioned using appetitive and aversive stimuli. The temporal difference learning algorithm was used to estimate reward prediction error. Activations in the ventral striatum were robustly correlated with prediction error, regardless of the valence of the stimuli, suggesting that the ventral striatum processes salience prediction error. In contrast, the orbitofrontal cortex and anterior insula coded for the differential valence of appetitive/aversive stimuli. Given its location at the interface of limbic and motor regions, the ventral striatum may be critical in learning about motivationally salient stimuli, regardless of valence, and using that information to bias selection of actions.

  • 18.
    Jensen, Jimmy
    et al.
    Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin.
    Walter, Henrik
    Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin.
    Incentive motivational salience and the human brain2014In: Restorative Neurology and Neuroscience, ISSN 1878-3627, Vol. 32, no 1, 141-147 p.Article in journal (Refereed)
    Abstract [en]

    In this paper the concept of incentive motivational salience is briefly described, pioneering studies on the subject of the mesolimbic motivational system are reviewed, and studies we have been involved in conducting which elaborate on this subject are discussed. In particular, we aim to show that the mesolimbic motivational system is recruited as a reaction to primary and secondary reinforcers as a function of salience, that is independent of valence. Furthermore, studies showing that both psychological and pharmacological interventions can affect the function of the mesolimbic motivational system and how its' dysfunction is related to psychopathological phenomena with an emphasis on psychosis are discussed.

  • 19.
    Jensen, Jimmy
    et al.
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada & Department of Psychiatry, Ullevål University Hospital and Oslo University, Oslo, Norway.
    Willeit, Matthäus
    Zipursky, Robert B
    Savina, Ioulia
    Smith, Andrew J
    Menon, Mahesh
    Crawley, Adrian P
    Kapur, Shitij
    The formation of abnormal associations in schizophrenia: neural and behavioral evidence.2008In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1470-634X, Vol. 33, no 3, 473-479 p.Article in journal (Refereed)
    Abstract [en]

    It is hypothesized that due to an abnormal functioning of the reward system patients with schizophrenia form context-inappropriate associations. It has been shown that the dopamine target regions, especially the ventral striatum, are critical in the formation of reward associations. We wanted to examine how the ventral striatum responds as patients learn reward-related associations and how this neural response is linked to objective and subjective behavioral measures. Functional magnetic resonance imaging (fMRI) Blood oxygen level dependent (BOLD) responses were examined using aversive Pavlovian learning in 13 medicated patients with schizophrenia and 13 matched healthy controls. Colored circles served as conditioned stimulus (CS+) while a loud, individually adjusted, noise served as the unconditioned stimulus. Circles of another color served as neutral comparators (CS-). Subjective indices were assessed by a post-scan self-report, and galvanic skin responses (GSR) were used as objective measures of associative learning. fMRI data were analyzed using a random effects model in SPM2. Patients showed inappropriately strong activations in the ventral striatum in response to the neutral stimulus (CS-) as compared to the healthy controls. Consistent with this neural evidence of aberrant learning, patients also showed evidence of abnormal learning by self-report and as indexed by GSR. The main finding here is that patients with schizophrenia, when exposed to neutral stimuli in a threatening situation, show an abnormal pattern of learning. The aberrant activations and response are consistent with the idea that patients aberrantly assign motivational salience to neutral stimuli, and this process may be one of the aberrations that predisposes them to psychosis.

  • 20.
    Kruschwitz, J. D.
    et al.
    Charité, Berlin.
    Walter, M.
    University Hospital of Magdeburg.
    Varikuti, D.
    University Hospital of Magdeburg.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Plichta, M. M.
    University of Heidelberg.
    Haddad, L.
    University of Heidelberg.
    Grimm, O.
    University of Heidelberg.
    Mohnke, S.
    Charité, Berlin.
    Pöhland, L.
    Charité, Berlin.
    Schott, B.
    Charité, Berlin.
    Wold, A.
    Charité, Berlin.
    Mühleisen, T. W.
    University of Bonn.
    Heinz, A.
    Charité, Berlin.
    Erk, S.
    Charité, Berlin.
    Romanczuk-Seiferth, N.
    Charité, Berlin.
    Witt, S. H.
    University of Heidelberg.
    Nöthen, M. M.
    University of Bonn.
    Rietschel, M.
    University of Heidelberg.
    Meyer-Lindenberg, A.
    University of Heidelberg.
    Walter, H.
    Charité, Berlin.
    5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus2015In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 220, no 4, 2373-2385 p.Article in journal (Refereed)
    Abstract [en]

    The s/s-genotype of the 5-HTTLPR polymorphism and the personality trait of neuroticism have both been associated with experiences of negative affect, anxiety and mood disorders, as well as an emotional processing bias towards negative facial emotions. On a neural level, this bias can be characterized by altered amygdala and fusiform gyrus (FFG) activity during perception of negative facial expressions. Using resting-state functional magnetic resonance imaging in a multi-center-sample of 178 healthy subjects of European descent, this study investigated the association of 5-HTTLPR (short s- and long l-allele) including the genotype of the single nucleotide polymorphism (SNP) rs25531 (A/G) within this region polymorphism, and trait neuroticism on resting-state functional connectivity (rs-FC) between amygdala and the FFG. Moreover, we aimed to identify additional brain regions with associations of 5-HTTLPR/rs25531 (combined according to its expression; low: s/s; high: lA/lA; intermediate: s/lA, s/lG, lG/lG, lA/lG) and trait neuroticism to amygdala rs-FC. Separate analyses for 5-HTTLPR/rs25531 and neuroticism (controlling for age, gender, handedness, and research site) revealed that s/s-homozygotes and individuals high in neuroticism obtained altered amygdala rs-FC in the right occipital face area, which is considered to be a "core component" of the face processing system. Importantly, effects of neuroticism were replicated across three independent research sites. Additionally, associations of 5-HTTLPR/rs25531 genotype and amygdala rs-FC were observed in the anterior and posterior cingulate cortex, whereas neuroticism was not related to rs-FC in these areas. The presented data implies that 5-HTTLPR/rs25531 variants and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus and suggests that variants of 5-HTTLPR/rs25531 genotype and different levels of neuroticism may partly account for altered processing of negative facial emotions.

  • 21.
    Lycke Brandt, Christine
    et al.
    K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo.
    Eichele, Tom
    Department of Biological and Medical Psychology, University of Bergen.
    Melle, Ingrid
    K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo.
    Sundet, Kjetil
    Department of Psychology, University of Oslo.
    Server, Andrés
    Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo University Hospital.
    Agartz, Ingrid
    K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo.
    Hugdahl, Kenneth
    Department of Biological and Medical Psychology, University of Bergen.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Andreassen, Ole A.
    K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo.
    Working memory networks and activation patterns in schizophrenia and bipolar disorder: comparison with healthy controls2014In: British Journal of Psychiatry, ISSN 0007-1250, E-ISSN 1472-1465, Vol. 204, no 4, 290-298 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Schizophrenia and bipolar disorder are severe mental disorders with overlapping genetic and clinical characteristics, including cognitive impairments. An important question is whether these disorders also have overlapping neuronal deficits.

    AIMS: To determine whether large-scale brain networks associated with working memory, as measured with functional magnetic resonance imaging (fMRI), are the same in both schizophrenia and bipolar disorder, and how they differ from those in healthy individuals.

    METHOD: Patients with schizophrenia (n = 100) and bipolar disorder (n = 100) and a healthy control group (n = 100) performed a 2-back working memory task while fMRI data were acquired. The imaging data were analysed using independent component analysis to extract large-scale networks of task-related activations.

    RESULTS: Similar working memory networks were activated in all groups. However, in three out of nine networks related to the experimental task there was a graded response difference in fMRI signal amplitudes, where patients with schizophrenia showed greater activation than those with bipolar disorder, who in turn showed more activation than healthy controls. Secondary analysis of the patient groups showed that these activation patterns were associated with history of psychosis and current elevated mood in bipolar disorder.

    CONCLUSIONS: The same brain networks were related to working memory in schizophrenia, bipolar disorder and controls. However, some key networks showed a graded hyperactivation in the two patient groups, in line with a continuum of neuronal abnormalities across psychotic disorders.

  • 22. 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, 143-149 p.Article 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.

  • 23. Menon, Mahesh
    et al.
    Jensen, Jimmy
    Schizophrenia Program and PET Centre, Centre for Addiction and Mental Health, Toronto, Canada & Department of Psychiatry, Ullevål University Hospital, Oslo University, Oslo, Norway.
    Vitcu, Irina
    Graff-Guerrero, Ariel
    Crawley, Adrian
    Smith, Mark A
    Kapur, Shitij
    Temporal difference modeling of the blood-oxygen level dependent response during aversive conditioning in humans: effects of dopaminergic modulation.2007In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 62, no 7, 765-772 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The prediction error (PE) hypothesized by the temporal difference model has been shown to correlate with the phasic activity of dopamine neurons during reward learning and the blood-oxygen level dependent (BOLD) response during reward and aversive conditioning tasks. We hypothesized that dopamine would modulate the PE related signal in aversive conditioning and that haloperidol would reduce PE related activity, while an acute dose of amphetamine would increase PE related activity in the ventral striatum.

    METHODS: Healthy participants took an acute dose of amphetamine, haloperidol, or placebo. We used functional magnetic resonance imaging (fMRI) to measure the BOLD signal while they carried out an aversive conditioning task, using cutaneous electrical stimulation as the unconditioned stimulus (US) and yellow and blue circles as conditioned stimulus (CS+ and CS-, respectively).

    RESULTS: Prediction error related BOLD activity was seen only in the ventral striatum in the placebo subjects. The subjects given amphetamine showed a wider network of PE related BOLD activity, including the ventral striatum, globus pallidus, putamen, insula, anterior cingulate, and substantia nigra/ventral tegmental area. Haloperidol subjects did not show PE related activity in any of these regions.

    CONCLUSIONS: Our results provide the first demonstration that the modulation of dopamine transmission affects both the physiological correlates and PE related BOLD activity during aversive learning.

  • 24.
    Mohnke, Sebastian
    et al.
    Charité Universitätsmedizin Berlin.
    Erk, Susanne
    Charité Universitätsmedizin Berlin.
    Schnell, Knut
    University of Heidelberg.
    Schütz, Claudia
    University of Bonn.
    Romanczuk-Seiferth, Nina
    Charité Universitätsmedizin Berlin.
    Grimm, Oliver
    Central Institute of Mental Health, Mannheim.
    Haddad, Leila
    Central Institute of Mental Health, Mannheim.
    Pöhland, Lydia
    Charité Universitätsmedizin Berlin.
    Garbusow, Maria
    Charité Universitätsmedizin Berlin.
    Schmitgen, Mike M.
    University of Heidelberg.
    Kirsch, Peter
    Central Institute of Mental Health, Mannheim.
    Esslinger, Christine
    Otto-von-Guericke University, Magdeburg.
    Rietschel, Marcella
    University of Heidelberg, Mannheim.
    Witt, Stephanie H.
    University of Heidelberg, Mannheim.
    Nöthen, Markus M.
    University of Bonn, Bonn.
    Cichon, Sven
    University of Bonn.
    Mattheisen, Manuel
    University of Heidelberg.
    Mühleisen, Thomas
    Research Centre Jülich.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Schott, Björn H.
    Charité Universitätsmedizin Berlin.
    Maier, Wolfgang
    University of Bonn.
    Heinz, Andreas
    Charité Universitätsmedizin Berlin.
    Meyer-Lindenberg, Andreas
    Central Institute of Mental Health, Mannheim.
    Walter, Henrik
    Charité Universitätsmedizin Berlin.
    Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind network2014In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 39, no 5, 1196-1205 p.Article in journal (Refereed)
    Abstract [en]

    The single-nucleotide polymorphism (SNP) rs1344706 in ZNF804A is one of the best-supported risk variants for psychosis. We hypothesized that this SNP contributes to the development of schizophrenia by affecting the ability to understand other people's mental states. This skill, commonly referred to as Theory of Mind (ToM), has consistently been found to be impaired in schizophrenia. Using functional magnetic resonance imaging, we previously showed that in healthy individuals rs1344706 impacted on activity and connectivity of key areas of the ToM network, including the dorsomedial prefrontal cortex, temporo-parietal junction, and the posterior cingulate cortex, which show aberrant activity in schizophrenia patients, too. We aimed to replicate these results in an independent sample of 188 healthy German volunteers. In order to assess the reliability of brain activity elicited by the ToM task, 25 participants performed the task twice with an interval of 14 days showing excellent accordance in recruitment of key ToM areas. Confirming our previous results, we observed decreasing activity of the left temporo-parietal junction, dorsomedial prefrontal cortex, and the posterior cingulate cortex with increasing number of risk alleles during ToM. Complementing our replication sample with the discovery sample, analyzed in a previous report (total N=297), further revealed negative genotype effects in the left dorsomedial prefrontal cortex as well as in the temporal and parietal regions. In addition, as shown previously, rs1344706 risk allele dose positively predicted increased frontal-temporo-parietal connectivity. These findings confirm the effects of the psychosis risk variant in ZNF804A on the dysfunction of the ToM network.

  • 25. Ousdal, O T
    et al.
    Jensen, Jimmy
    University of Oslo.
    Server, A
    Hariri, A R
    Nakstad, P H
    Andreassen, O A
    The human amygdala is involved in general behavioral relevance detection: evidence from an event-related functional magnetic resonance imaging Go-NoGo task.2008In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 156, no 3, 450-455 p.Article in journal (Refereed)
    Abstract [en]

    The amygdala is classically regarded as a detector of potential threat and as a critical component of the neural circuitry mediating conditioned fear responses. However, it has been reported that the human amygdala responds to multiple expressions of emotions as well as emotionally neutral stimuli of a novel, uncertain or ambiguous nature. Thus, it has been proposed that the function of the amygdala may be of a more general art, i.e. as a detector of behaviorally relevant stimuli [Sander D, Grafman J, Zalla T (2003) The human amygdala: an evolved system for relevance detection. Rev Neurosci 14:303-316]. To investigate this putative function of the amygdala, we used event related functional magnetic resonance imaging (fMRI) and a modified Go-NoGo task composed of behaviorally relevant and irrelevant letter and number stimuli. Analyses revealed bilateral amygdala activation in response to letter stimuli that were behaviorally relevant as compared with letters with less behavioral relevance. Similar results were obtained for relatively infrequent NoGo relevant stimuli as compared with more frequent Go stimuli. Our findings support a role for the human amygdala in general detection of behaviorally relevant stimuli.

  • 26.
    Ousdal, Olga T.
    et al.
    Oslo University Hospital.
    Andreassen, Ole A.
    Oslo University Hospital.
    Server, Andres
    Oslo University Hospital.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Increased amygdala and visual cortex activity and functional connectivity towards stimulus novelty is associated with state anxiety2014In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 4, e96146- p.Article in journal (Refereed)
    Abstract [en]

    Novel stimuli often require a rapid reallocation of sensory processing resources to determine the significance of the event, and the appropriate behavioral response. Both the amygdala and the visual cortex are central elements of the neural circuitry responding to novelty, demonstrating increased activity to new as compared to highly familiarized stimuli. Further, these brain areas are intimately connected, and thus the amygdala may be a key region for directing sensory processing resources to novel events. Although knowledge regarding the neurocircuit of novelty detection is gradually increasing, we still lack a basic understanding of the conditions that are necessary and sufficient for novelty-specific responses in human amygdala and the visual cortices, and if these brain areas interact during detection of novelty. In the present study, we investigated the response of amygdala and the visual cortex to novelty, by comparing functional MRI activity between 1st and 2nd time presentation of a series of emotional faces in an event-related task. We observed a significant decrease in amygdala and visual cortex activity already after a single stimulus exposure. Interestingly, this decrease in responsiveness was less for subjects with a high score on state anxiety. Further, novel faces stimuli were associated with a relative increase in the functional coupling between the amygdala and the inferior occipital gyrus (BA 18). Thus, we suggest that amygdala is involved in fast sensory boosting that may be important for attention reallocation to novel events, and that the strength of this response depends on individual state anxiety.

  • 27. Ousdal, Olga Therese
    et al.
    Anand Brown, Andrew
    Jensen, Jimmy
    Oslo University Hospital, Oslo, Norway & University of Oslo, Oslo, Norway & Charité Universitätsmedizin, Berlin, Germany.
    Nakstad, Per H
    Melle, Ingrid
    Agartz, Ingrid
    Djurovic, Srdjan
    Bogdan, Ryan
    Hariri, Ahmad R
    Andreassen, Ole A
    Associations between variants near a monoaminergic pathways gene (PHOX2B) and amygdala reactivity: a genome-wide functional imaging study.2012In: Twin Research and Human Genetics, ISSN 1832-4274, Vol. 15, no 3, 273-285 p.Article in journal (Refereed)
    Abstract [en]

    As the amygdala is part of the phylogenetic old brain, and its anatomical and functional properties are conserved across species, it is reasonable to assume genetic influence on its activity. A large corpus of candidate gene studies indicate that individual differences in amygdala activity may be caused by genetic variants within monoaminergic signaling pathways such as dopamine, serotonin, and norepinephrine. However, to our knowledge, the use of genome-wide data to discover genetic variants underlying individual differences in adult amygdala activity is novel. In the present study, the combination of genome-wide data and functional imaging phenotypes from an emotional faces task yielded a significant association between rs10014254 and the amygdala using a region of interest approach. This single nucleotide polymorphism is located in a regulatory region upstream of the Paired-like homeobox 2b (PHOX2B) gene; therefore it could affect the expression of this gene. PHOX2B regulates the expression of enzymes necessary for the synthesis of several monoamines and is essential for the development of the autonomic nervous system. However, an attempt to replicate the finding in an independent sample from North America did not succeed. The synthesis of functional magnetic resonance imaging (fMRI) and genome-wide data takes a hypothesis-free approach as to which genetic variants are of interest. Therefore, we believe that an undirected finding within such a plausible region is of interest, and that our results add further support to the hypothesis that monoaminergic signaling pathways play a central role in regulating amygdala activity.

  • 28. 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, 95-101 p.Article 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.

  • 29.
    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, 712-719 p.Article 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.

  • 30. Reckless, Greg E.
    et al.
    Bolstad, Ingeborg
    Nakstad, Per H.
    Andreassen, Ole A.
    Jensen, Jimmy
    Division of Mental Health and Addiction, Oslo University Hospital.
    Motivation alters response bias and neural activation patterns in a perceptual decision-making task.2013In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 238, 135-147 p.Article in journal (Refereed)
    Abstract [en]

    Motivation has been demonstrated to affect individuals' response strategies in economic decision-making, however, little is known about how motivation influences perceptual decision-making behavior or its related neural activity. Given the important role motivation plays in shaping our behavior, a better understanding of this relationship is needed. A block-design, continuous performance, perceptual decision-making task where participants were asked to detect a picture of an animal among distractors was used during functional magnetic resonance imaging (fMRI). The effect of positive and negative motivation on sustained activity within regions of the brain thought to underlie decision-making was examined by altering the monetary contingency associated with the task. In addition, signal detection theory was used to investigate the effect of motivation on detection sensitivity, response bias and response time. While both positive and negative motivation resulted in increased sustained activation in the ventral striatum, fusiform gyrus, left dorsolateral prefrontal cortex (DLPFC) and ventromedial prefrontal cortex, only negative motivation resulted in the adoption of a more liberal, closer to optimal response bias. This shift toward a liberal response bias correlated with increased activation in the left DLPFC, but did not result in improved task performance. The present findings suggest that motivation alters aspects of the way perceptual decisions are made. Further, this altered response behavior is reflected in a change in left DLPFC activation, a region involved in the computation of perceptual decisions.

  • 31.
    Reckless, Greg E.
    et al.
    Norge.
    Andreassen, Ole A.
    Norge.
    Server, Andres
    Norge.
    Østefjells, Tiril
    Norge.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task2015In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 8, 290-297 p.Article in journal (Refereed)
    Abstract [en]

    Background

    Negative symptoms in schizophrenia have been associated with structural and functional changes in the prefrontal cortex. They often persist after treatment with antipsychotic medication which targets, in particular, the ventral striatum (VS). As schizophrenia has been suggested to arise from dysfunctional connectivity between neural networks, it is possible that residual aberrant striato-cortical connectivity in medicated patients plays a role in enduring negative symptomology. The present study examined the relationship between striato-cortical connectivity and negative symptoms in medicated schizophrenia patients.

    Methods

    We manipulated motivation in a perceptual decision-making task during functional magnetic resonance imaging. Comparing healthy controls (n = 21) and medicated patients with schizophrenia (n = 18) we investigated how motivation-mediated changes in VS activation affected functional connectivity with the frontal cortex, and how changes in connectivity strength from the neutral to motivated condition related to negative symptom severity.

    Results

    A pattern of aberrant striato-cortical connectivity was observed in the presence of intact VS, but altered left inferior frontal gyrus (IFG) motivation-mediated activation in patients. The more severe the patient's negative symptoms, the less the connectivity strength between the right VS and left IFG changed from the neutral to the motivated condition. Despite aberrant striato-cortical connectivity and altered recruitment of the left IFG among patients, both patients and healthy controls adopted a more liberal response strategy in the motivated compared to the neutral condition.

    Conclusions

    The present findings suggest that there is a link between dysfunctional striato-cortical connectivity and negative symptom severity, and offer a possible explanation as to why negative symptoms persist after treatment with antipsychotics.

  • 32.
    Reckless, Greg E.
    et al.
    University of Oslo.
    Ousdal, Olga T.
    University of Oslo.
    Server, Andres
    Oslo University Hospital.
    Walter, Henrik
    Charité Universitätsmedizin, Berlin.
    Andreassen, Ole A.
    University of Oslo.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    The left inferior frontal gyrus is involved in adjusting response bias during a perceptual decision-making task2014In: Brain and Behavior, ISSN 2162-3279, Vol. 4, no 3, 398-407 p.Article in journal (Refereed)
    Abstract [en]

    Introduction

    Changing the way we make decisions from one environment to another allows us to maintain optimal decision-making. One way decision-making may change is how biased one is toward one option or another. Identifying the regions of the brain that underlie the change in bias will allow for a better understanding of flexible decision-making.

    Methods

    An event-related, perceptual decision-making task where participants had to detect a picture of an animal amongst distractors was used during functional magnetic resonance imaging. Positive and negative financial motivation were used to affect a change in response bias, and changes in decision-making behavior were quantified using signal detection theory.

    Results

    Response bias became relatively more liberal during both positive and negative motivated trials compared to neutral trials. For both motivational conditions, the larger the liberal shift in bias, the greater the left inferior frontal gyrus (IFG) activity. There was no relationship between individuals' belief that they used a different strategy and their actual change in response bias.

    Conclusions

    The present findings suggest that the left IFG plays a role in adjusting response bias across different decision environments. This suggests a potential role for the left IFG in flexible decision-making.

  • 33.
    Sigvartsen, Niels Petter
    et al.
    University of Oslo, Norway.
    Jensen, Jimmy
    University of Oslo, Oslo University Hospital, Norway.
    Temporal difference modelling of aversive conditioning and extinction: An fMRI study2009In: Front. Neur. Conference Abstract: Neuroinformatics 2009, 2009Conference paper (Other academic)
    Abstract [en]

    The prediction error (PE) signal from temporal difference (TD) models have been shown to correlate with activity in specific brain regions in both human and animals during conditioning tasks. One of the key regions involved is the ventral striatum (VS). The purpose of this study was to investigate how the TD model predicted VS activations during aversive conditioning and extinction. Functional Magnetic Resonance Imaging (fMRI) Blood-Oxygen Level Dependent (BOLD) data were acquired on a 1.5 T GE Signa scanner. Thirty-three healthy subjects completed a 33% partially reinforced classical conditioning paradigm using coloured circles as the conditioned stimulus (CS) and aversive cutaneous electrical stimulation (CES) as the unconditioned stimulus (US). After a short break a second scanning session was performed where the subjects were divided into three groups (N=11 in each group): 1) a control group that repeated the paradigm; 2) an extinction group that repeated the paradigm with the CES turned off without their knowledge; and 3) an intervention group that were told that the CES would be turned off before they repeated the paradigm. Thus, in the second session the extinction and intervention groups saw the CS but without US. A modified TD algorithm was used to generate a salience PE signal vector which was used as a regressor in the fMRI analyses. Pre-processing and analyses of data were done using SPM5. Final analysis of the first session and preliminary analysis of the control and extinction groups from the second session are reported here. Analysis of the first session included all 33 subjects and PE activations bilaterally in the VS, anterior insula and anterior cingulate were obtained. Analyses from the second session showed that activations were predicted by salience PE bilaterally in the VS and the anterior insula in the control group while the extinction group recruited the VS and the ventro-medial PFC. The findings from the first session and the control group in the second session replicated previous studies. However, the results of the second session in the extinction group extend that fMRI BOLD behave according to salience PE to a more general level in aversive learning ranging from acquisition to maintenance to extinction of associations.

  • 34. Tesli, Martin
    et al.
    Skatun, Kristina C.
    Ousdal, Olga Therese
    Brown, Andrew Anand
    Thoresen, Christian
    Agartz, Ingrid
    Melle, Ingrid
    Djurovic, Srdjan
    Jensen, Jimmy
    Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin.
    Andreassen, Ole A.
    CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls2013In: PloS one, ISSN 1932-6203, Vol. 8, no 2, e56970- p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Several genetic studies have implicated the CACNA1C SNP rs1006737 in bipolar disorder (BD) and schizophrenia (SZ) pathology. This polymorphism was recently found associated with increased amygdala activity in healthy controls and patients with BD. We performed a functional Magnetic Resonance Imaging (fMRI) study in a sample of BD and SZ cases and healthy controls to test for altered amygdala activity in carriers of the rs1006737 risk allele (AA/AG), and to investigate if there were differences across the diagnostic groups.

    METHODS: Rs1006737 was genotyped in 250 individuals (N = 66 BD, 61 SZ and 123 healthy controls), all of Northern European origin, who underwent an fMRI negative faces matching task. Statistical tests were performed with a model correcting for sex, age, diagnostic category and medication status in the total sample, and then in each diagnostic group.

    RESULTS: In the total sample, carriers of the risk allele had increased activation in the left amygdala. Group-wise analyses showed that this effect was significant in the BD group, but not in the other diagnostic groups. However, there was no significant interaction effect for the risk allele between BD and the other groups.

    CONCLUSIONS: These results indicate that CACNA1C SNP rs1006737 affects amygdala activity during emotional processing across all diagnostic groups. The current findings add to the growing body of knowledge of the pleiotropic effect of this polymorphism, and further support that ion channel dysregulation is involved in the underlying mechanisms of BD and SZ.

  • 35. Thoresen, Christian
    et al.
    Endestad, Tor
    Sigvartsen, Niels Petter B.
    Server, Andres
    Bolstad, Ingeborg
    Johansson, Mikael
    Andreassen, Ole A.
    Jensen, Jimmy
    Division of Mental Health and Addiction, Oslo University.
    Frontotemporal hypoactivity during a reality monitoring paradigm is associated with delusions in patients with schizophrenia spectrum disorders2014In: Cognitive Neuropsychiatry, ISSN 1354-6805, E-ISSN 1464-0619, Vol. 19, no 2, 97-115 p.Article in journal (Refereed)
    Abstract [en]

    Introduction Impaired monitoring of internally generated information has been proposed to be one component in the development and maintenance of delusions. The present study investigated the neural correlates underlying the monitoring processes and whether they were associated with delusions. Methods Twenty healthy controls and 19 patients with schizophrenia spectrum disorders were administrated a reality monitoring paradigm during functional magnetic resonance imaging. During encoding participants were instructed to associate a statement with either a presented (viewed condition) or an imagined picture (imagined condition). During the monitoring session in the scanner, participants were presented with old and new statements and their task was to identify whether a given statement was associated with the viewed condition, imagined condition, or if it was new. Results Patients showed significantly reduced accuracy in the imagined condition with performance negatively associated with degree of delusions. This was accompanied with reduced activity in the left dorsolateral prefrontal cortex and left hippocampus in the patient group. The severity of delusions was negatively correlated with the blood-oxygenation-level dependent response in the left hippocampus. Conclusions The results suggest that weakened monitoring is associated with delusions in patients with schizophrenia spectrum disorder, and that this may be mediated by a frontotemporal dysfunction.

  • 36. Thoresen, Christian
    et al.
    Jensen, Jimmy
    Oslo University Hospital & University of Oslo & Charité Universitätsmedizin, Berlin, Germany.
    Sigvartsen, Niels Petter B
    Bolstad, Ingeborg
    Server, Andres
    Nakstad, Per H
    Andreassen, Ole A
    Endestad, Tor
    Arousal Modulates Activity in the Medial Temporal Lobe during a Short-Term Relational Memory Task.2011In: Frontiers in human neuroscience, ISSN 1662-5161, Vol. 5, 177- p.Article in journal (Refereed)
    Abstract [en]

    This study investigated the effect of arousal on short-term relational memory and its underlying cortical network. Seventeen healthy participants performed a picture by location, short-term relational memory task using emotional pictures. Functional magnetic resonance imaging was used to measure the blood-oxygenation-level dependent signal relative to task. Subjects' own ratings of the pictures were used to obtain subjective arousal ratings. Subjective arousal was found to have a dose-dependent effect on activations in the prefrontal cortex, amygdala, hippocampus, and in higher order visual areas. Serial position analyses showed that high arousal trials produced a stronger primacy and recency effect than low arousal trials. The results indicate that short-term relational memory may be facilitated by arousal and that this may be modulated by a dose-response function in arousal-driven neuronal regions.

  • 37. Thormodsen, Rune
    et al.
    Jensen, Jimmy
    Oslo University Hospital & University of Oslo, Norway & Charité Universitätsmedizin, Berlin, Germany.
    Holmèn, Aina
    Juuhl-Langseth, Monica
    Emblem, Kyrre Eeg
    Andreassen, Ole Andreas
    Rund, Bjørn Rishovd
    Prefrontal hyperactivation during a working memory task in early-onset schizophrenia spectrum disorders: an fMRI study.2011In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 194, no 3, 257-262 p.Article in journal (Refereed)
    Abstract [en]

    Working memory (WM) dysfunction is increasingly recognized as a core feature of schizophrenia, but few studies have investigated prefrontal activation during WM tasks in early-onset schizophrenia spectrum disorder (EOS). Our aim was to explore prefrontal activation during a WM-task in EOS patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Fifteen patients with EOS and 15 matched healthy controls performed a 0-back and a 2-back task while fMRI data were acquired. Results indicated that even though performance between patients and controls was comparable on both tasks, there was a hyperactivation in patients' ventrolateral prefrontal cortex (VLPFC) during the 2-back task compared to healthy controls. This pattern of activation suggests that, in patients with EOS, the VLPFC compensated in order to match performance of the controls. The activations in the EOS group may reflect the use of a compensatory, cognitive strategy while solving WM-tasks.

  • 38.
    Welander-Vatn, Audun
    et al.
    Institute of Clinical Medicine, Section of Psychiatry, University of Oslo.
    Jensen, Jimmy
    Kristianstad University, School of Education and Environment, Avdelningen för Humanvetenskap.
    Otnaess, Mona K
    Institute of Clinical Medicine, Section of Psychiatry, University of Oslo.
    Agartz, Ingrid
    Institute of Clinical Medicine, Section of Psychiatry, University of Oslo.
    Server, Andres
    Department of Radiology and Nuclear Medicine, Section of Neuroradiology, Oslo University Hospital.
    Melle, Ingrid
    Institute of Clinical Medicine, Section of Psychiatry, University of Oslo.
    Andreassen, Ole A
    Institute of Clinical Medicine, Section of Psychiatry, University of Oslo.
    The neural correlates of cognitive control in bipolar I disorder: an fMRI study of medial frontal cortex activation during a Go/No-go task2013In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 549, 51-56 p.Article in journal (Refereed)
    Abstract [en]

    In addition to dysregulation of mood, bipolar I disorder (BD I) is characterized by abnormalities in the execution of cognitive control. Hypoactivation of a specific sub-region in the cognitive control network, located in the medial frontal cortex, has been described among BD I patients. The aim of this study was to investigate whether patients with BD I showed decreased activation in this brain region as compared to healthy controls when performing a cognitive control task. Twenty-four BD I patients and 24 healthy controls performed a Go/No-go task during a functional magnetic resonance imaging (fMRI) session. Performance and response times were recorded. The BD I subjects had significantly slower response times and more patients made errors of omission compared to the healthy controls during the task. Both BD I subjects and healthy controls demonstrated activations in the brain region of interest during the task, but analyses revealed no statistically significant differences between groups. Although the patients display some deviances in behavioural measures, this study reveals no significant differences between BD I subjects and healthy controls in recruitment of the medial frontal cortex during a Go/No-go task.

  • 39. Welander-Vatn, Audun S
    et al.
    Jensen, Jimmy
    Institute of Psychiatry, University of Oslo & Department of Psychiatry, Ulleval University Hospital, Oslo.
    Lycke, Christine
    Agartz, Ingrid
    Server, Andres
    Gadmar, Øystein Bech
    Melle, Ingrid
    Nakstad, Per Hjalmar
    Andreassen, Ole A
    No altered dorsal anterior cingulate activation in bipolar II disorder patients during a Go/No-go task: an fMRI study.2009In: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 11, no 3, 270-279 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: It has been reported that one of the core features in patients with bipolar disorder II (BD II) is increased impulsivity. The aim of this study was to investigate whether patients with BD II showed decreased activation in the dorsal anterior cingulate cortex (dACC) as compared to healthy controls when performing a task sensitive to impulsivity.

    METHODS: Twenty-seven BD II patients and 28 healthy controls performed a Go/No-go task during a functional magnetic resonance imaging (fMRI) session. Eleven of the patients were unmedicated, and possible group differences between medicated and unmedicated patients were also assessed. Results: The groups did not differ in behavioral performance on the Go/No-go task. Both BD II subjects and healthy controls demonstrated dACC activity during the task, and analyses revealed no statistically significant group differences. Medicated and unmedicated patients also did not differ in the degree of fMRI activation.

    CONCLUSIONS: These findings do not support the hypothesis of abnormal dACC activity during a Go/No-go task in BD II patients.

1 - 39 of 39
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