| 1. |
- Bolstad, Ingeborg, et al.
(författare)
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Aversive event anticipation affects connectivity between the ventral striatum and the orbitofrontal cortex in an fMRI avoidance task
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science. - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Bolstad, Ingeborg, et al.
(författare)
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Effects of haloperidol and aripiprazole on the human mesolimbic motivational system : a pharmacological fMRI study
- 2015
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 25:12, s. 2252-2261
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Bolstad, Ingeborg, et al.
(författare)
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No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol
- 2015
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media S.A.. - 1662-5161. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- 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 frontaland 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.
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| 4. |
- Brandt, Christine Lycke, et al.
(författare)
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Cognitive effort and schizophrenia modulate large-scale functional brain connectivity
- 2015
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Ingår i: Schizophrenia Bulletin. - : Oxford University Press. - 0586-7614 .- 1745-1701. ; 41:6, s. 1360-1369
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Haatveit, Beathe, et al.
(författare)
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Reduced load-dependent default mode network deactivation across executive tasks in schizophrenia spectrum disorders
- 2016
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Ingår i: NeuroImage Clinical. - : Elsevier BV. - 0353-8842 .- 2213-1582. ; 12, s. 389-396
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Haatveit, Beathe, et al.
(författare)
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Stability of executive functions in first episode psychosis : one year follow up study
- 2015
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Ingår i: Psychiatry Research. - : Elsevier Ireland Ltd. - 0165-1781 .- 1872-7123. ; 228:3, s. 475-481
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Ousdal, Olga T., et al.
(författare)
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Increased amygdala and visual cortex activity and functional connectivity towards stimulus novelty is associated with state anxiety
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science. - 1932-6203. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Ousdal, Olga Therese, et al.
(författare)
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The human amygdala encodes value and space during decision making
- 2014
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Ingår i: NeuroImage. - : Academic Press Inc.. - 1053-8119 .- 1095-9572. ; 101, s. 712-719
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Tidskriftsartikel (refereegranskat)abstract
- Valuable stimuli are invariably localized in space. While our knowledge regarding the neural networks supporting value assignment and comparisons is considerable, we lack a basic understanding of how the human brain integrates motivational and spatial information. The amygdala is a key structure for learning and maintaining the value of sensory stimuli and a recent non-human primate study provided initial evidence that it also acts to integrate value with spatial location, a question we address here in a human setting. We measured hemodynamic responses (fMRI) in amygdala while manipulating the value and spatial configuration of stimuli in a simple stimulus-reward task. Subjects responded significantly faster and showed greater amygdala activation when a reward was dependent on a spatial specific response, compared to when a reward required less spatial specificity. Supplemental analysis supported this spatial specificity by demonstrating that the pattern of amygdala activity varied based on whether subjects responded to a motivational target presented in the ipsilateral or contralateral visual space. Our data show that the human amygdala integrates information about space and value, an integration of likely importance for assigning cognitive resources towards highly valuable stimuli in our environment.
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| 9. |
- Reckless, Greg E., et al.
(författare)
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Negative symptoms in schizophrenia are associated with aberrant striato-cortical connectivity in a rewarded perceptual decision-making task
- 2015
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Ingår i: NeuroImage Clinical. - : Elsevier BV. - 0353-8842 .- 2213-1582. ; 8, s. 290-297
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Reckless, Greg E., et al.
(författare)
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The left inferior frontal gyrus is involved in adjusting response bias during a perceptual decision-making task
- 2014
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Ingår i: Brain and Behavior. - : John Wiley and Sons Inc.. - 2162-3279. ; 4:3, s. 398-407
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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