| 1. |
- Brandt, Christine Lycke, et al.
(författare)
-
Cognitive effort and schizophrenia modulate large-scale functional brain connectivity
- 2015
-
Ingår i: Schizophrenia Bulletin. - 0586-7614 .- 1745-1701. ; 41:6, s. 1360-1369
-
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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| 2. |
- Lycke Brandt, Christine, et al.
(författare)
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Working memory networks and activation patterns in schizophrenia and bipolar disorder : comparison with healthy controls
- 2014
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Ingår i: British Journal of Psychiatry. - 0007-1250 .- 1472-1465. ; 204:4, s. 290-298
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Mørch-Johnsen, Lynn, et al.
(författare)
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The neural correlates of negative symptoms in schizophrenia : examples from MRI literature
- 2018
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Ingår i: Clinical EEG and Neuroscience. - 1550-0594 .- 2169-5202. ; 49:1, s. 12-17
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Tidskriftsartikel (refereegranskat)abstract
- Negative symptoms of schizophrenia have a negative impact on psychosocial functioning and disease outcome. It is therefore important to investigate the pathophysiology underlying negative symptoms as this may aid the development of better treatment. In the current article, examples from studies investigating neural correlates of negative symptoms in schizophrenia are given. Investigations using both structural and functional magnetic resonance imaging are presented at different levels of symptomatology descriptions, from the more heterogenous construct of negative symptoms to more single discrete symptoms. Some methods to improve imaging studies of negative symptoms in schizophrenia are also suggested.
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| 4. |
- Welander-Vatn, Audun, et al.
(författare)
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The neural correlates of cognitive control in bipolar I disorder : an fMRI study of medial frontal cortex activation during a Go/No-go task
- 2013
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Ingår i: Neuroscience Letters. - 0304-3940 .- 1872-7972. ; 549, s. 51-56
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Aminoff, Sofie Ragnhild, et al.
(författare)
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An association between affective lability and executive functioning in bipolar disorder.
- 2012
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Ingår i: Psychiatry Research. - 0165-1781 .- 1872-7123. ; 198:1, s. 58-61
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Aminoff, Sofie R, et al.
(författare)
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Decreased self-reported arousal in schizophrenia during aversive picture viewing compared to bipolar disorder and healthy controls.
- 2011
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Ingår i: Psychiatry Research. - 0165-1781 .- 1872-7123. ; 185:3, s. 309-314
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- 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. - 1932-6203. ; 8:6, s. e68494-
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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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| 8. |
- 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
-
Ingår i: PLoS ONE. - : Public Library of Science. - 1932-6203. ; 8:6
-
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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| 9. |
- Bolstad, Ingeborg, et al.
(författare)
-
Effects of haloperidol and aripiprazole on the human mesolimbic motivational system : a pharmacological fMRI study
- 2015
-
Ingår i: European Neuropsychopharmacology. - 0924-977X .- 1873-7862. ; 25:12, s. 2252-2261
-
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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| 10. |
- 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
-
Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 25:12, s. 2252-2261
-
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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| 11. |
- Bolstad, Ingeborg, et al.
(författare)
-
No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol
- 2015
-
Ingår i: Frontiers in Human Neuroscience. - 1662-5161 .- 1662-5161. ; 9
-
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 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.
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| 12. |
- 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
-
Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media S.A.. - 1662-5161. ; 9
-
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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| 13. |
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| 14. |
- Brandt, Christine Lycke, et al.
(författare)
-
Cognitive effort and schizophrenia modulate large-scale functional brain connectivity
- 2015
-
Ingår i: Schizophrenia Bulletin. - : Oxford University Press. - 0586-7614 .- 1745-1701. ; 41:6, s. 1360-1369
-
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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| 15. |
- Brown, A A, et al.
(författare)
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Genetic variants affecting the neural processing of human facial expressions : evidence using a genome-wide functional imaging approach.
- 2012
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Ingår i: Translational psychiatry. - 2158-3188. ; 2, s. e143-
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 16. |
- Danielsen, A, et al.
(författare)
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Investigating repetition and change in musical rhythm by functional MRI
- 2014
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Ingår i: Neuroscience. - 0306-4522 .- 1873-7544. ; 275, s. 469-476
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 17. |
- Danielsen, A, et al.
(författare)
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Investigating repetition and change in musical rhythm by functional MRI
- 2014
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Ingår i: Neuroscience. - : Elsevier Ltd.. - 0306-4522 .- 1873-7544. ; 275, s. 469-476
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 18. |
- Dehkharghani, A., et al.
(författare)
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Quantum magnetism in strongly interacting one-dimensional spinor Bose systems
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Strongly interacting one-dimensional quantum systems often behave in a manner that is distinctly different from their higher-dimensional counterparts. When a particle attempts to move in a one-dimensional environment it will unavoidably have to interact and 'push' other particles in order to execute a pattern of motion, irrespective of whether the particles are fermions or bosons. A present frontier in both theory and experiment are mixed systems of different species and/or particles with multiple internal degrees of freedom. Here we consider trapped two-component bosons with short-range inter-species interactions much larger than their intra-species interactions and show that they have novel energetic and magnetic properties. In the strongly interacting regime, these systems have energies that are fractions of the basic harmonic oscillator trap quantum and have spatially separated ground states with manifestly ferromagnetic wave functions. Furthermore, we predict excited states that have perfect antiferromagnetic ordering. This holds for both balanced and imbalanced systems, and we show that it is a generic feature as one crosses from few-to many-body systems.
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| 19. |
- Delfin, Carl, 1986, et al.
(författare)
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Exploring the Effects of an Acute Dose of Antipsychotic Medication on Motivation-mediated BOLD Activity Using fMRI and a Perceptual Decision-making Task
- 2020
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 440, s. 146-159
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Tidskriftsartikel (refereegranskat)abstract
- The left inferior frontal gyrus and the bilateral ventral striatum are thought to be involved in motivation-mediated decision-making. Antipsychotics may influence this relationship, and atypical antipsychotics improve secondary negative symptoms in schizophrenia, such as loss of motivation, although the acute effects of pharmacological medication on motivation are not fully understood. In this single-blinded, randomized controlled trial, 49 healthy volunteers were randomized into three groups to receive a single dose of haloperidol, aripiprazole or placebo. Between 4.0 and 5.6 h later, participant's brain blood-oxygen-level dependent (BOLD) activity was recorded using functional magnetic resonance imaging (fMRI) while completing a perceptual decision-making fMRI task consisting of one neutral and one motivated condition. Response bias, reflecting the participant's willingness to say that the target stimulus is present, was calculated using signal detection theory. Concurrent with widespread changes in BOLD signal in the motivated vs. neutral condition, a less conservative, mathematically optimal response bias was observed in the motivated condition across the whole sample. Within-group differences in BOLD signal in the left inferior frontal gyrus and bilateral ventral striatum were observed between conditions in the aripiprazole and haloperidol groups, but not in the placebo group. No robust between-group differences in brain activity in the left inferior frontal gyrus or the bilateral ventral striatum were found. Overall, we found no robust evidence for an effect of either aripiprazole or haloperidol on motivationally mediated behavior. An interesting pattern of correlations possibly related to pharmacologically induced alterations in the dopamine system was observed, although findings remain inconclusive and must be replicated in larger samples. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
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| 20. |
- Diaconescu, Andreea Oliviana, et al.
(författare)
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Aberrant Effective Connectivity in Schizophrenia Patients during Appetitive Conditioning
- 2011
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Ingår i: Frontiers in human neuroscience. - 1662-5161. ; 4, s. 239-
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 21. |
- Diaconescu, Andreea Oliviana, et al.
(författare)
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Dopamine-induced changes in neural network patterns supporting aversive conditioning.
- 2010
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Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 1313, s. 143-161
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 22. |
- Forssen, Christian, 1974, et al.
(författare)
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Living on the edge of stability, the limits of the nuclear landscape
- 2013
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Ingår i: Physica Scripta. - : IOP Publishing. - 1402-4896 .- 0031-8949. ; T152:T152, s. 014022-
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Tidskriftsartikel (refereegranskat)abstract
- A first-principles description of nuclear systems along the drip lines presents a substantial theoretical and computational challenge. In this paper, we discuss the nuclear theory roadmap, some of the key theoretical approaches, and present selected results with a focus on long isotopic chains. An important conclusion, which consistently emerges from these theoretical analyses, is that three-nucleon forces are crucial for both global nuclear properties and detailed nuclear structure, and that many-body correlations due to the coupling to the particle continuum are essential as one approaches particle drip lines. In the quest for a comprehensive nuclear theory, high performance computing plays a key role.
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| 23. |
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| 24. |
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| 25. |
- 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. - 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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| 26. |
- Haatveit, Beathe, et al.
(författare)
-
Reduced load-dependent default mode network deactivation across executive tasks in schizophrenia spectrum disorders
- 2016
-
Ingår i: NeuroImage Clinical. - : Elsevier BV. - 0353-8842 .- 2213-1582. ; 12, s. 389-396
-
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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| 27. |
- Haatveit, Beathe, et al.
(författare)
-
Stability of executive functions in first episode psychosis : one year follow up study
- 2015
-
Ingår i: Psychiatry Research. - 0165-1781 .- 1872-7123. ; 228:3, s. 475-481
-
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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| 28. |
- Haatveit, Beathe, et al.
(författare)
-
Stability of executive functions in first episode psychosis : one year follow up study
- 2015
-
Ingår i: Psychiatry Research. - : Elsevier Ireland Ltd. - 0165-1781 .- 1872-7123. ; 228:3, s. 475-481
-
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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| 29. |
- Heimdal, Jimmy, et al.
(författare)
-
The role of axial ligands for the structure and function of chlorophylls
- 2007
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 1432-1327 .- 0949-8257. ; 12:1, s. 49-61
-
Tidskriftsartikel (refereegranskat)abstract
- We have studied the effect of axial ligation of chlorophyll and bacteriochlorophyll using density functional calculations. Eleven different axial ligands have been considered, including models of histidine, aspartate/glutamate, asparagine/glutamine, serine, tyrosine, methionine, water, the protein backbone, and phosphate. The native chlorophylls, as well as their cation and anion radical states and models of the reaction centres P680 and P700, have been studied and we have compared the geometries, binding energies, reduction potentials, and absorption spectra. Our results clearly show that the chlorophylls strongly prefer to be five-coordinate, in accordance with available crystal structures. The axial ligands decrease the reduction potentials, so they cannot explain the high potential of P680. They also redshift the Q band, but not enough to explain the occurrence of red chlorophylls. However, there is some relation between the axial ligands and their location in the various photosynthetic proteins. In particular, the intrinsic reduction potential of the second molecule in the electron transfer path is always lower than that of the third one, a feature that may prevent back-transfer of the electron.
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| 30. |
- Jensen, Jimmy, et al.
(författare)
-
Direct activation of the ventral striatum in anticipation of aversive stimuli.
- 2003
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Ingår i: Neuron. - 0896-6273 .- 1097-4199. ; 40:6, s. 1251-1257
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 31. |
- Jensen, Jimmy
(författare)
-
Dyslexia among adults : Neuropsychology and personality
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Reading and writing skills are of crucial importance in modern society. Therefore, dyslexia is a significant handicap, not only in respect of lexical skills and processing of language-based information - it appears to have social consequences as well, as evidenced for instance by the high frequency of dyslexics among long-term unemployed people. One major research problem is that the term dyslexia is not well-defined. In consequence, there is no consensus about epidemiology, causal factors and correlates. However, some findings tend to be reported more consistently among dyslexics; phonological deficits, a relatively unresponsive visual magnocellular system and problems with automatization of complex cognitive tasks. Furthermore, impaired memory functioning and low self-esteem are associated with dyslexia. Another research problem is that our knowledge of dyslexia is to a large extent based on studies of children. Lacking direct evidence from studies of adults, we tend to extrapolate our knowledge about children. The aim of the present thesis, which comprises five empirical studies, was to explore neuropsychological and personality correlates of dyslexia among adults. We found a high frequency of dyslexics among prison inmates (41%), who performed more poorly on most of the neuropsychological tasks, and had a deviant personality pattern: higher anxiety and more deviant scores on scales reflecting social interactions, compared to non-dyslexic inmates. Non-criminal dyslexics used an inflexible strategy in a continuous performance test, an attribute that also characterized prison inmates, dyslexic or not. Dyslexics were less prone, or able, to shift from an egocentric perspective when invited to view a statement from another's psychological perspective, compared to non-dyslexics. Furthermore, these dyslexics had more difficulties to understand certain concepts reflecting emotional states and social interactions. Some aspects of the deviant personality pattern described in dyslexics, and corroborated by our own previous findings, were demonstrated to reflect ADHD rather than dyslexia. In contrast, memory dysfunction appears to be a stable correlate of dyslexia. Finally, we evaluated a 20 week educational programme for dyslexics. Reading and writing skills, memory and self-confidence improved compared to dyslexic controls. The findings are discussed in a neo-Darwinian context, favouring the theory that the evolution of language is based on pre-language mental faculties serving skills needed for complex social interactions, rather than a new and specific "language" faculty. Problems and consequences of the lack of consensus about the definition of dyslexia are also discussed, concluding that these differences are of minor importance when we design remediation interventions.
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| 32. |
- Jensen, Jimmy, et al.
(författare)
-
Effect of emotional content on brain activation patterns in a reality monitoring task
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Every day we take in large amounts of information from the external world, and we also synthesize representations of things or situations that we have not perceived through our senses. The ability to distinguish between a memory that contains representations from external world and a memory representing an imagined picture is necessary to make sense of the surroundings. This process is called reality monitoring. In the present study we aimed to confirm the existence of the reality monitoring network as reported by previous studies. Further, we wanted to extend these findings by investigating the effect of stimuli aversiveness on the reality monitoring processes and its neural correlates. Twenty-five subjects were included in the study after passing a somatic and psychiatric health screening. The subjects first completed an encoding task of 80 trials outside the scanner. Small descriptions of either an object or a situation (two or three word sentences) were presented on a computer screen. Immediately after the description was shown, a frame that was either empty or containing a picture related to the description was shown for three seconds. The subjects were instructed to look at the picture in the frame or imagine a relevant picture when the frame was empty. The subjects were then instructed to consider whether the pictures were “Unpleasant” or “Not unpleasant” by choosing between the two alternatives on the computer screen. A retrieval task was carried out as Blood-Oxygen Level Dependent (BOLD) fMRI data was collected. During this task the participants were presented with small descriptions that were either presented during the encoding task or they were new. The subjects were to decide whether they previously had viewed a picture associated with the description (a V trial), whether they had imagined a picture associated with the description (an I trial) or whether the description was entirely new (an N trial). The subjects completed a total of 140 randomly presented trials during two runs (20 trials of each category and 20 baseline trials). T2*-weighted functional MRI images were collected on a 3T General Electrics Signa HDx scanner. Data were analysed using SPM8.Overall, most of the trials were considered neutral, and this was true within both the I and the V conditions. Fewer I trials than V trials were considered aversive. The response times were longer in I compared to the V for the aversive trials, and there was a trend for the same effect for the neutral trials. There were no significant differences in response time between neutral and aversive trial. The analysis of the retrieval task behavioural data revealed a higher accuracy rate for aversive trials in the I than the V, while there was no effect for neutral trials. An ANOVA for the corresponding response times showed a main effect of source of encoding where responses were shorter in V than I trials. In paired tests this difference was significant for neutral trials. Paired tests of emotional content within source showed a difference between aversive and neutral trials for I. Successful retrieval and discrimination between sources of encoding generated activations in the left posterior precuneus. Activations of the anterior cingulate were also present. An effect of stimuli aversiveness on brain activation was present in mediolateral prefrontal cortex and the precuneus, indicating a stronger effort of these regions during retrieval of source memory linked to aversive stimuli.In summary, activation patterns in reality monitoring networks were replicated from earlier studies. Further, the results suggest that activations in overlapping networks are increased for aversive stimuli compared to neutral stimuli.
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| 33. |
- Jensen, Jimmy, et al.
(författare)
-
Effect of emotional content on brain activation patterns in a reality monitoring task
- 2018
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Every day we take in large amounts of information from the external world, and we also synthesize representations of things or situations that we have not perceived through our senses. The ability to distinguish between a memory that contains representations from external world and a memory representing an imagined picture is necessary to make sense of the surroundings. This process is called reality monitoring. In the present study we aimed to confirm the existence of the reality monitoring network as reported by previous studies. Further, we wanted to extend these findings by investigating the effect of stimuli aversiveness on the reality monitoring processes and its neural correlates. Twenty-five subjects were included in the study after passing a somatic and psychiatric health screening. The subjects first completed an encoding task of 80 trials outside the scanner. Small descriptions of either an object or a situation (two or three word sentences) were presented on a computer screen. Immediately after the description was shown, a frame that was either empty or containing a picture related to the description was shown for three seconds. The subjects were instructed to look at the picture in the frame or imagine a relevant picture when the frame was empty. The subjects were then instructed to consider whether the pictures were “Unpleasant” or “Not unpleasant” by choosing between the two alternatives on the computer screen. A retrieval task was carried out as Blood-Oxygen Level Dependent (BOLD) fMRI data was collected. During this task the participants were presented with small descriptions that were either presented during the encoding task or they were new. The subjects were to decide whether they previously had viewed a picture associated with the description (a V trial), whether they had imagined a picture associated with the description (an I trial) or whether the description was entirely new (an N trial). The subjects completed a total of 140 randomly presented trials during two runs (20 trials of each category and 20 baseline trials). T2*-weighted functional MRI images were collected on a 3T General Electrics Signa HDx scanner. Data were analysed using SPM8. Overall, most of the trials were considered neutral, and this was true within both the I and the V conditions. Fewer I trials than V trials were considered aversive. The response times were longer in I compared to the V for the aversive trials, and there was a trend for the same effect for the neutral trials. There were no significant differences in response time between neutral and aversive trial. The analysis of the retrieval task behavioural data revealed a higher accuracy rate for aversive trials in the I than the V, while there was no effect for neutral trials. An ANOVA for the corresponding response times showed a main effect of source of encoding where responses were shorter in V than I trials. In paired tests this difference was significant for neutral trials. Paired tests of emotional content within source showed a difference between aversiveand neutral trials for I. Successful retrieval and discrimination between sources of encoding generated activations in the left posterior precuneus. Activations of the anterior cingulate were also present. An effect of stimuli aversiveness on brain activation was present in mediolateral prefrontal cortex and the precuneus, indicating a stronger effort of these regions during retrieval of source memory linked to aversive stimuli. In summary, activation patterns in reality monitoring networks were replicated from earlier studies. Further, the results suggest that activations in overlapping networks are increased for aversive stimuli compared to neutral stimuli.
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| 34. |
- Jensen, Jimmy, et al.
(författare)
-
Incentive motivational salience and the human brain
- 2014
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Ingår i: Restorative Neurology and Neuroscience. - 1878-3627. ; 32:1, s. 141-147
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 35. |
- Jensen, Jimmy, et al.
(författare)
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Neurocognitive and psychopathological correlates of self-monitoring ability in schizophrenia.
- 2004
-
Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer. - 0940-1334 .- 1433-8491. ; 254:5, s. 312-317
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 36. |
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| 37. |
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| 38. |
- Jensen, Jimmy, et al.
(författare)
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Separate brain regions code for salience vs. valence during reward prediction in humans.
- 2007
-
Ingår i: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 28:4, s. 294-302
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 39. |
- Jensen, Jimmy, et al.
(författare)
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The formation of abnormal associations in schizophrenia : neural and behavioral evidence.
- 2008
-
Ingår i: Neuropsychopharmacology. - 0893-133X .- 1740-634X. ; 33:3, s. 473-479
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 40. |
- Jensen, Kasper P., et al.
(författare)
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A comparison of the tetrapyrrole cofactors in nature and their tuning by axial ligands
- 2008
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Ingår i: Computational modeling for homogeneous and enzymatic catalysis. - 9783527318438 ; , s. 27-56
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter illustrates how quantum chemical calculations can be used to elucidate structural and functional aspects of tetrapyrrole cofactors, focusing on porphyrins, cobalamins, coenzyme F430, and chlorophyll. A particular emphasis is put on the biochemical significance of axial ligands, which can tune the function of the tetrapyrroles. With the use of quantum chemical calculations, it is possible to draw important conclusions regarding aspects of tetrapyrroles that could not otherwise be accessed. The results show that the general reactivity is mainly determined by the metal and the tetrapyrrole ring system, whereas the electronic structure and reactivity are tuned by the choice of axial ligands, providing a unique insight into the design of cofactors in nature.
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| 41. |
- Johnson, Calvin W., et al.
(författare)
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White paper: From bound states to the continuum
- 2020
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:12
-
Forskningsöversikt (refereegranskat)abstract
- This white paper reports on the discussions of the 2018 Facility for Rare Isotope Beams Theory Alliance (FRIB-TA) topical program ‘From bound states to the continuum: Connecting bound state calculations with scattering and reaction theory’. One of the biggest and most important frontiers in nuclear theory today is to construct better and stronger bridges between bound state calculations and calculations in the continuum, especially scattering and reaction theory, as well as teasing out the influence of the continuum on states near threshold. This is particularly challenging as many-body structure calculations typically use a bound state basis, while reaction calculations more commonly utilize few-body continuum approaches. The many-body bound state and few-body continuum methods use different language and emphasize different properties. To build better foundations for these bridges, we present an overview of several bound state and continuum methods and, where possible, point to current and possible future connections.
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| 42. |
- Kruschwitz, J. D., et al.
(författare)
-
5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus
- 2015
-
Ingår i: Brain Structure and Function. - 1863-2653 .- 1863-2661. ; 220:4, s. 2373-2385
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 43. |
- Kruschwitz, J. D., et al.
(författare)
-
5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus
- 2015
-
Ingår i: Brain Structure and Function. - : Springer Verlag. - 1863-2653 .- 1863-2661. ; 220:4, s. 2373-2385
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 44. |
- Lindahl, Jesper, et al.
(författare)
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Add-on pramipexole for anhedonic depression : study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden
- 2023
-
Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 13:11, s. 9
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed before it could become ready for clinical prime time. Given its mechanism of action, pramipexole might be a useful treatment for a depression subtype characterised by significant anhedonia and lack of motivation-symptoms associated with dopaminergic hypofunction. We recently showed, in an open-label pilot study, that add-on pramipexole is a feasible treatment for depression with significant anhedonia, and that pramipexole increases reward-related activity in the ventral striatum. We will now confirm or refute these preliminary results in a randomised controlled trial (RCT) and an open-label follow-up study. METHODS AND ANALYSIS: Eighty patients with major depression (bipolar or unipolar) or dysthymia and significant anhedonia according to the Snaith Hamilton Pleasure Scale (SHAPS) are randomised to either add-on pramipexole or placebo for 9 weeks. Change in anhedonia symptoms per the SHAPS is the primary outcome, and secondary outcomes include change in core depressive symptoms, apathy, sleep problems, life quality, anxiety and side effects. Accelerometers are used to assess treatment-associated changes in physical activity and sleep patterns. Blood and brain biomarkers are investigated as treatment predictors and to establish target engagement. After the RCT phase, patients continue with open-label treatment in a 6-month follow-up study aiming to assess long-term efficacy and tolerability of pramipexole. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. The study is externally monitored according to Good Clinical Practice guidelines. Results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05355337 and NCT05825235.
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| 45. |
- Mattingsdal, Morten, et al.
(författare)
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Pathway analysis of genetic markers associated with a functional MRI faces paradigm implicates polymorphisms in calcium responsive pathways
- 2013
-
Ingår i: NeuroImage. - 1053-8119 .- 1095-9572. ; 70, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 46. |
- Menon, Mahesh, et al.
(författare)
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Temporal difference modeling of the blood-oxygen level dependent response during aversive conditioning in humans : effects of dopaminergic modulation.
- 2007
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 62:7, s. 765-772
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 47. |
- Mohnke, Sebastian, et al.
(författare)
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Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind network
- 2014
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Ingår i: Neuropsychopharmacology. - 0893-133X .- 1740-634X. ; 39:5, s. 1196-1205
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 48. |
- Mohnke, Sebastian, et al.
(författare)
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Further evidence for the impact of a genome-wide-supported psychosis risk variant in ZNF804A on the Theory of Mind network
- 2014
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Ingår i: Neuropsychopharmacology. - : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 39:5, s. 1196-1205
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 49. |
- Mørch-Johnsen, Lynn, et al.
(författare)
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The neural correlates of negative symptoms in schizophrenia : examples from MRI literature
- 2018
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Ingår i: Clinical EEG and Neuroscience. - : SAGE Publications Inc.. - 1550-0594 .- 2169-5202. ; 49:1, s. 12-17
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Tidskriftsartikel (refereegranskat)abstract
- Negative symptoms of schizophrenia have a negative impact on psychosocial functioning and disease outcome. It is therefore important to investigate the pathophysiology underlying negative symptoms as this may aid the development of better treatment. In the current article, examples from studies investigating neural correlates of negative symptoms in schizophrenia are given. Investigations using both structural and functional magnetic resonance imaging are presented at different levels of symptomatology descriptions, from the more heterogenous construct of negative symptoms to more single discrete symptoms. Some methods to improve imaging studies of negative symptoms in schizophrenia are also suggested.
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| 50. |
- Ousdal, Olga Therese, et al.
(författare)
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Associations between variants near a monoaminergic pathways gene (PHOX2B) and amygdala reactivity : a genome-wide functional imaging study.
- 2012
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Ingår i: Twin Research and Human Genetics. - 1832-4274 .- 1839-2628. ; 15:3, s. 273-285
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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