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Haatveit, B., Jensen, J., Alnæs, D., Kaufmann, T., Brandt, C. L., Thoresen, C., . . . Westlye, L. T. (2016). Reduced load-dependent default mode network deactivation across executive tasks in schizophrenia spectrum disorders. NeuroImage: Clinical, 12, 389-396
Open this publication in new window or tab >>Reduced load-dependent default mode network deactivation across executive tasks in schizophrenia spectrum disorders
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2016 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 12, p. 389-396Article in journal (Refereed) Published
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.

Keywords
Across tasks, Default mode network, Functional magnetic resonance imaging, Independent component analysis, Schizophrenia spectrum disorder, Task-positive network
National Category
Neurosciences
Identifiers
urn:nbn:se:hkr:diva-16224 (URN)10.1016/j.nicl.2016.08.012 (DOI)000390196400045 ()27622135 (PubMedID)
Available from: 2016-11-01 Created: 2016-11-01 Last updated: 2018-01-13Bibliographically approved
Kruschwitz, J. D., Walter, M., Varikuti, D., Jensen, J., Plichta, M. M., Haddad, L., . . . Walter, H. (2015). 5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus. Brain Structure and Function, 220(4), 2373-2385
Open this publication in new window or tab >>5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus
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2015 (English)In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 220, no 4, p. 2373-2385Article in journal (Refereed) Published
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.

National Category
Psychology
Identifiers
urn:nbn:se:hkr:diva-12054 (URN)10.1007/s00429-014-0782-0 (DOI)000356874700035 ()24874919 (PubMedID)
Available from: 2014-06-02 Created: 2014-06-02 Last updated: 2017-12-05Bibliographically approved
Brandt, C. L., Kaufmann, T., Agartz, I., Hugdahl, K., Jensen, J., Ueland, T., . . . Westlye, L. T. (2015). Cognitive effort and schizophrenia modulate large-scale functional brain connectivity. Schizophrenia Bulletin, 41(6), 1360-1369
Open this publication in new window or tab >>Cognitive effort and schizophrenia modulate large-scale functional brain connectivity
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2015 (English)In: Schizophrenia Bulletin, ISSN 0586-7614, E-ISSN 1745-1701, Vol. 41, no 6, p. 1360-1369Article in journal (Refereed) Published
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.

Keywords
psychotic disorders, cognition, brain networks, independent component analysis
National Category
Psychology
Identifiers
urn:nbn:se:hkr:diva-13699 (URN)10.1093/schbul/sbv013 (DOI)000364774900021 ()25731885 (PubMedID)
Available from: 2015-03-04 Created: 2015-03-04 Last updated: 2017-12-04Bibliographically approved
Bolstad, I., Andreassen, O. A., Groote, I., Server, A., Sjaastad, I., Kapur, S. & Jensen, J. (2015). Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: a pharmacological fMRI study. European Neuropsychopharmacology, 25(12), 2252-2261
Open this publication in new window or tab >>Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: a pharmacological fMRI study
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2015 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 25, no 12, p. 2252-2261Article in journal (Refereed) Published
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.

Keywords
Aripiprazole, dopamine, haloperidol, healthy volunteers, ventral striatum, fMRI
National Category
Neurosciences
Identifiers
urn:nbn:se:hkr:diva-14989 (URN)10.1016/j.euroneuro.2015.09.016 (DOI)26476705 (PubMedID)
Available from: 2015-11-04 Created: 2015-11-04 Last updated: 2018-01-10Bibliographically approved
Reckless, G. E., Andreassen, O. A., Server, A., Østefjells, T. & Jensen, J. (2015). Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task. NeuroImage: Clinical, 8, 290-297
Open this publication in new window or tab >>Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task
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2015 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 8, p. 290-297Article in journal (Refereed) Published
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.

Keywords
Connectivity, fMRI, Motivation, Negative symptoms, Perceptual decision-making, Schizophrenia
National Category
Neurosciences
Identifiers
urn:nbn:se:hkr:diva-13937 (URN)10.1016/j.nicl.2015.04.025 (DOI)000373187100031 ()26106553 (PubMedID)
Available from: 2015-05-25 Created: 2015-05-25 Last updated: 2018-01-11Bibliographically approved
Bolstad, I., Andreassen, O. A., Groote, I. R., Haatveit, B., Server, A. & Jensen, J. (2015). No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol. Frontiers in Human Neuroscience, 9, Article ID 296.
Open this publication in new window or tab >>No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol
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2015 (English)In: Frontiers in Human Neuroscience, ISSN 1662-5161, E-ISSN 1662-5161, Vol. 9, article id 296Article in journal (Refereed) Published
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.

Keywords
dopamine, aripiprazole, haloperidol, executive function, healthy volunteers, fMRI
National Category
Neurology
Identifiers
urn:nbn:se:hkr:diva-13997 (URN)10.3389/fnhum.2015.00296 (DOI)000356072000001 ()26074803 (PubMedID)
Available from: 2015-06-04 Created: 2015-06-04 Last updated: 2017-12-04Bibliographically approved
Haatveit, B., Vaskinn, A., Sundet, K. S., Jensen, J., Andreassen, O. A., Melle, I. & Ueland, T. (2015). Stability of executive functions in first episode psychosis: one year follow up study. Psychiatry Research, 228(3), 475-481
Open this publication in new window or tab >>Stability of executive functions in first episode psychosis: one year follow up study
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2015 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 228, no 3, p. 475-481Article in journal (Refereed) Published
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.

Keywords
cognition. longitudinal study, reliable change, schizophrenia spectrum disorders
National Category
Psychiatry
Identifiers
urn:nbn:se:hkr:diva-14424 (URN)10.1016/j.psychres.2015.05.060 (DOI)000360251400036 ()26165960 (PubMedID)
Available from: 2015-08-07 Created: 2015-08-07 Last updated: 2017-12-04Bibliographically approved
Haatveit, B., Melle, I., Jensen, J., Sundet, K., Vaskinn, A., Simonsen, C., . . . Ueland, T. (2014). Are executive functions stable in first episode patients?: one year follow-up study. Paper presented at 9th International Conference on Early Psychosis – To the New Horizon, 17 November 2014, Tokyo Japan. Early Intervention in Psychiatry, 8, 75
Open this publication in new window or tab >>Are executive functions stable in first episode patients?: one year follow-up study
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2014 (English)In: Early Intervention in Psychiatry, ISSN 1751-7885, E-ISSN 1751-7893, Vol. 8, p. 75-Article in journal, Meeting abstract (Refereed) Published
National Category
Psychiatry
Identifiers
urn:nbn:se:hkr:diva-13289 (URN)10.1111/eip.12199 (DOI)000344785700274 ()
Conference
9th International Conference on Early Psychosis – To the New Horizon, 17 November 2014, Tokyo Japan
Available from: 2014-12-11 Created: 2014-12-11 Last updated: 2017-12-05Bibliographically approved
Thoresen, C., Endestad, T., Sigvartsen, N. P., Server, A., Bolstad, I., Johansson, M., . . . Jensen, J. (2014). Frontotemporal hypoactivity during a reality monitoring paradigm is associated with delusions in patients with schizophrenia spectrum disorders. Cognitive Neuropsychiatry, 19(2), 97-115
Open this publication in new window or tab >>Frontotemporal hypoactivity during a reality monitoring paradigm is associated with delusions in patients with schizophrenia spectrum disorders
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2014 (English)In: Cognitive Neuropsychiatry, ISSN 1354-6805, E-ISSN 1464-0619, Vol. 19, no 2, p. 97-115Article in journal (Refereed) Published
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.

Keywords
delusions, functional magnetic resonance imaging, hippocampus, reality monitoring, schizophrenia
National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:hkr:diva-11634 (URN)10.1080/13546805.2013.776495 (DOI)23756081 (PubMedID)
Available from: 2014-01-14 Created: 2014-01-14 Last updated: 2017-12-06Bibliographically approved
Mohnke, S., Erk, S., Schnell, K., Schütz, C., Romanczuk-Seiferth, N., Grimm, O., . . . Walter, H. (2014). Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind network. Neuropsychopharmacology, 39(5), 1196-1205
Open this publication in new window or tab >>Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind network
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2014 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 39, no 5, p. 1196-1205Article in journal (Refereed) Published
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.

Keywords
Theory of Mind; mentalizing; schizophrenia; imaging genetics; ZNF804A; rs1344706
National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:hkr:diva-11635 (URN)10.1038/npp.2013.321 (DOI)000332918100016 ()24247043 (PubMedID)
Available from: 2014-01-14 Created: 2014-01-14 Last updated: 2018-06-26Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6841-1808

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