| 1. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 2. |
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| 3. |
- Bengtsson, Johan, et al.
(author)
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Ambulatory Heart Rate Variability in Schizophrenia or Depression : Impact of Anticholinergic Burden and Other Factors
- 2021
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In: Journal of Clinical Psychopharmacology. - 0271-0749 .- 1533-712X. ; 41:2, s. 121-128
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Journal article (peer-reviewed)abstract
- BACKGROUND: Heart rate variability (HRV) has been found reduced in patients with schizophrenia and depression. However, there is a lack of knowledge on how demographic, lifestyle, and pharmacological factors contribute to the reduction in HRV in these patients.METHODS: We recruited 37 patients with schizophrenia, 43 patients with unipolar depression, and 64 healthy controls. A combined chest-worn HRV and accelerometer device was used in an ambulatory measurement. Age, sex, anticholinergic burden of medication, nicotine use, body mass index, and ongoing physical activity were assessed in multiple regression models regarding their influence on HRV, measured as the standard deviation of all the RR intervals (SDNN).RESULTS: In the fully adjusted model, schizophrenia (β = -0.23, P = 0.019), depression (β = -0.18, P = 0.028), age (β = -0.34, P < 0.000), ongoing physical activity (β = -0.23, P = 0.001), and anticholinergic burden (β = -0.19, P = 0.025) influenced SDNN negatively. Sex, nicotine use, and BMI had negligible effects on SDNN.CONCLUSIONS: We show for the first time that a quantified score of anticholinergic burden of medication has a negative relationship to HRV in patients with schizophrenia or depression, but that the diagnoses themselves still exhibit an effect on HRV.
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| 4. |
- Bengtsson, Johan, et al.
(author)
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Autonomic modulation networks in schizophrenia : The relationship between heart rate variability and functional and structural connectivity in the brain
- 2020
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In: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 300
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Journal article (peer-reviewed)abstract
- Heart rate variability (HRV), a measurement of autonomic nervous system (ANS) activity, has been found reduced in schizophrenia. The anterior cingulate cortex (ACC), which is important in regulating the ANS, is structurally and functionally affected in schizophrenia. We investigate the relationship between HRV and functional and structural connectivity of the ACC in patients with schizophrenia and healthy controls. Ten patients with a diagnosis of schizophrenia and ten healthy controls were recruited. Heart rate was monitored in a naturalistic out-of-clinic setting. Magnetic resonance imaging (MRI) was performed, including resting-state functional MRI and diffusion tensor imaging. Patients with schizophrenia had significantly lower HRV compared to controls. A positive correlation between ACC connectivity with the bilateral cerebellum and HRV was found in the patients. HRV was also positively correlated with amplitude of low frequency fluctuations (ALFF) in the cerebellum, and with axial diffusivity in the middle cerebellar peduncle, in the patients. There was a significant negative relationship between antipsychotic medication dosage, HRV and all neuroimaging measures related to HRV. We conclude that ACC connectivity seems to be affected in schizophrenia, both structurally and functionally, and that the ACC-cerebellum connectivity, as well as cerebellar function, is associated with ANS regulation in patients with schizophrenia.
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| 5. |
- Bengtsson, Johan
(author)
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Negative symptoms, repetitive transcranial magnetic stimulation and heart rate variability in schizophrenia and depression
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Negative symptoms comprise anhedonia, avolition, and blunted affect. Although first described in schizophrenia, these symptoms share phenomenology with the depressive state. Pharmacological treatment has not been successful in reducing negative symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological treatment option for moderate to severe depression. There have also been attempts to treat negative symptoms in both schizophrenia and depression with rTMS.Cardiovascular disease is common in schizophrenia and depression. Heart rate variability (HRV) is an established proxy for cardiac autonomic functioning and numerous studies have found lower HRV in patients with schizophrenia and depression. The impact of psychopharmacological treatment on HRV has been extensively studied and anticholinergic compounds have been found to decrease HRV.Lastly, since the most commonly used rTMS depression targets are also the brain regions involved in central autonomic regulation, there is reason to consider a potential effect of rTMS on HRV.The overall aim of this thesis was to investigate negative symptoms, rTMS, and HRV in schizophrenia and depression.Study I was a validation study of a Swedish translation of the Clinical Assessment Interview for Negative Symptoms (CAINS). Thirty-four patients with schizophrenia were interviewed and it was concluded that the Swedish version of the CAINS exhibited acceptable psychometric properties.Study II was a double-blind randomized controlled trial of rTMS for negative symptoms in schizophrenia and depression. There was a significant decrease of negative symptoms in the depression group, but not in the schizophrenia group. There were no effects on overall depressive symptoms in either group.Study III assessed determinants of HRV in schizophrenia, depression, and healthy controls. The results indicated lower HRV in both patient groups, even after controlling for several factors, and also that anticholinergic burden impacted HRV.In Study IV, the relationship between HRV and the functional and structural connectivity of the anterior cingulate cortex was investigated in patients with schizophrenia and compared with that in healthy controls. It was found that connectivity with the cerebellum might play a role in the autonomic modulation network in patients with schizophrenia.Lastly, in Study V, the effect of a treatment course with rTMS on HRV was investigated in patients with depression, as well as HRV’s relationship to symptom change. No effects on HRV were detected, nor any correlations between HRV and symptom change. Further, baseline HRV could not predict treatment response.
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| 6. |
- Bengtsson, Johan, et al.
(author)
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No effects on heart rate variability in depression after treatment with dorsomedial prefrontal intermittent theta burst stimulation
- 2023
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In: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 128:1
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Journal article (peer-reviewed)abstract
- Background: The purpose of this study was to investigate whether treatment of a depressive episode with intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) had any effects on heart rate variability (HRV). We also investigated if changes in HRV covaried with symptom change after iTBS and if HRV could predict symptom change.Methods: We included 49 patients with a current depressive episode. All were randomized to receive a double-blind treatment course with active or sham iTBS over the DMPFC. HRV data were obtained from 1 h of night data before and after the iTBS. The standard deviation of the RR interval (SDNN) was chosen as primary outcome measure. Depressive, negative, and anxiety symptoms as well as self-rated health were assessed by clinicians or by self-report.Results: The group×time linear mixed model revealed no effect of iTBS on SDNN (estimate = −1.8, 95% confidence interval [CI]: −19.9 to 16.2). There were neither correlations between HRV and depressive, negative, or anxiety symptom change after iTBS nor with self-assessed health. No predictive value of HRV was found.Conclusions: Treatment for depression with dorsomedial iTBS had neither negative nor positive effects on the cardiac autonomic nervous system.
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| 7. |
- Bodén, Robert, 1973-, et al.
(author)
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Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression : a randomized controlled trial
- 2021
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 290, s. 308-315
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Journal article (peer-reviewed)abstract
- BackgroundIntermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) has shown promise in open-label trials of depression.MethodsIn this randomized, double-blind, sham controlled trial we evaluate iTBS over the DMPFC for anhedonia, avolition, and blunted affect in patients with schizophrenia or depression. Active iTBS was delivered over the DMPFC with 1200 pulses per session, twice daily over ten weekdays at target intensity with an angled figure-of eight coil. Sham condition comprised the magnetically shielded side of the coil and simultaneous transcutaneous electrical nerve stimulation. Primary outcome was change on the Clinical Assessment Interview for Negative Symptoms (CAINS).ResultsTwenty-eight patients were randomized to active iTBS and 28 to sham. Mean (standard deviation) change in CAINS score from baseline to the day after last treatment was -5.3 (8.1) in active iTBS and -2.1 (7.1) in sham. A linear model showed no significant effect of treatment, accounting for baseline scores p=.088. Sub analyses per diagnostic group showed a significant effect in patients with depression, p=.038, but not in the schizophrenia group, p=.850. However, overall depressive symptoms did not change significantly in patients with depression. There were three serious adverse events, all in the sham group.LimitationsPossibly too short treatment course and few patients with schizophrenia.ConclusionIn this first transdiagnostic randomized controlled trial of iTBS over DMPFC for anhedonia, avolition, and blunted affect it can be concluded that it was generally tolerable and safe but only more effective than sham in the subgroup of patients with depression.
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| 8. |
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| 9. |
- Bodén, Robert, 1973-, et al.
(author)
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Suppressing visual hallucinations in an adolescent by occipital transcranial magnetic stimulation: A single-case experimental research design.
- 2021
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In: Neuropsychological rehabilitation. - : Informa UK Limited. - 1464-0694 .- 0960-2011. ; 33:2, s. 346-55
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Journal article (peer-reviewed)abstract
- Visual hallucinations after central or peripheral impairment, commonly called Charles Bonnet syndrome, are often highly distressing and with few available treatment options. Here we report a case where an adolescent developed severely distressing visual hallucinations after hypoxic damage to the occipital cortex following a suicide attempt. The patient received active and sham occipital continuous theta-burst stimulation (cTBS) in a single-case experimental research design and a subsequent open phase, to evaluate cTBS as a Charles Bonnet treatment. The visual hallucinations seemed to decrease more during active than sham cTBS in the blind phase, and in the following week of repeated five daily treatments they almost disappeared. A normalization of increased activity in the lateral visual network after cTBS was observed on a functional magnetic resonance imaging resting-state analysis compared with 42 healthy controls. Visual evoked potentials stayed largely unchanged both in the sham-controlled blind phase and the subsequent open phase. During the two weeks after the open phase with repeated cTBS sessions, the visual hallucinations gradually reappeared and almost returned to the baseline level. Our findings suggest that active cTBS over the primary visual cortex can reduce visual hallucinations through modulation of downstream visual regions, though the effect is temporally limited.
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| 10. |
- Edebol Carlman, Hanna M. T., et al.
(author)
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Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects : A Randomised Clinical Trial and Proof-of-Concept Study
- 2022
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In: Nutrients. - : MDPI. - 2072-6643. ; 14:7
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Journal article (peer-reviewed)abstract
- Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.
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| 11. |
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| 12. |
- Frick, Andreas, Docent, et al.
(author)
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Habitual caffeine consumption moderates the antidepressant effect of dorsomedial intermittent theta-burst transcranial magnetic stimulation
- 2021
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In: Journal of Psychopharmacology. - : Sage Publications. - 0269-8811 .- 1461-7285. ; 35:12, s. 1536-1541
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Journal article (peer-reviewed)abstract
- Background:Potentiating current antidepressant treatment is much needed. Based on animal studies, caffeine may augment the effects of currently available antidepressants.Objective:Here, we tested whether habitual caffeine consumption moderates the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) using intermittent theta-burst stimulation (iTBS).Methods:Forty patients with current depressive episodes were randomized to active iTBS (n = 19) or sham treatment (n = 21; shielded side of the coil and weak transcutaneous electrical stimulation) delivered two times per day for 10–15 weekdays. Neuronavigated stimulation was applied to the dorsomedial prefrontal cortex. Symptom improvement was measured using change in self-reported Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pretreatment habitual caffeine consumption was quantified using self-reports of number of cups of coffee and energy drinks consumed the 2 days before the treatment starts.Results:Habitual caffeine consumption was associated with symptom improvement following active iTBS (r = 0.51, 95% confidence interval (CI): 0.08–0.78, p = 0.025) but not following sham treatment (r = −0.02, 95% CI: −0.45 to 0.42, p = 0.938). A multiple regression analysis corroborated the findings by showing a significant caffeine consumption × treatment group interaction (β = 0.62, p = 0.043), but no main effects of treatment group (β = 0.22, p = 0.140) or caffeine consumption (β = −0.01, p = 0.948). No group differences in pretreatment symptom scores or caffeine consumption were detected (p values > 0.86).Conclusion:Habitual caffeine consumption moderated the antidepressant effect of dorsomedial iTBS, consistent with caffeine improving antidepressant pharmacological treatments in animals. Caffeine is an antagonist of adenosine receptors and may enhance antidepressant effects through downstream dopaminergic targets.
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| 13. |
- Kaboodvand, Neda, et al.
(author)
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Macroscopic resting state model predicts theta burst stimulation response : A randomized trial
- 2023
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In: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 19:3
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Journal article (peer-reviewed)abstract
- Repetitive transcranial magnetic stimulation (rTMS) is a promising alternative therapy for treatment-resistant depression, although its limited remission rate indicates room for improvement. As depression is a phenomenological construction, the biological heterogeneity within this syndrome needs to be considered to improve the existing therapies. Whole-brain modeling provides an integrative multi-modal framework for capturing disease heterogeneity in a holistic manner.Computational modelling combined with a probabilistic nonparametric fitting was applied to the resting-state fMRI data from 42 patients (21 women), to parametrize baseline brain dynamics in depression. All patients were randomly assigned to two treatment groups, namely active (i.e., rTMS, n = 22) or sham (n = 20). The active treatment group received rTMS treatment with an accelerated intermittent theta burst protocol over the dorsomedial prefrontal cortex. The sham treatment group underwent the identical procedure but with the magnetically shielded side of the coil.We stratified the depression sample into distinct covert subtypes based on their baseline attractor dynamics captured by different model parameters. Notably, the two detected depression subtypes exhibited different phenotypic behaviors at baseline. Our stratification could predict the diverse response to the active treatment that could not be explained by the sham treatment. Critically, we further found that one group exhibited more distinct improvement in certain affective and negative symptoms. The subgroup of patients with higher responsiveness to treatment exhibited blunted frequency dynamics for intrinsic activity at baseline, as indexed by lower global metastability and synchrony.Our findings suggested that whole-brain modeling of intrinsic dynamics may constitute a determinant for stratifying patients into treatment groups and bringing us closer towards precision medicine.
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| 14. |
- Kesarimangalam, Sriram, 1983, et al.
(author)
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Fluorescence Microscopy of Nanochannel-Confined DNA
- 2024
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In: Methods in Molecular Biology. - 1940-6029 .- 1064-3745. - 9781071633762 - 9781071633779 ; , s. 175-202
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Book chapter (other academic/artistic)abstract
- Stretching of DNA in nanoscale confinement allows for several important studies. The genetic contents of the DNA can be visualized on the single DNA molecule level, and the polymer physics of confined DNA and also DNA/protein and other DNA/DNA-binding molecule interactions can be explored. This chapter describes the basic steps to fabricate the nanostructures, perform the experiments, and analyze the data.
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| 15. |
- Malm, Erika, et al.
(author)
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Pain trajectories of dorsomedial prefrontal intermittent theta burst stimulation versus sham treatment in depression
- 2020
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In: BMC Neurology. - : BMC. - 1471-2377. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Prefrontal repetitive transcranial magnetic stimulation is an established add-on treatment for major depressive disorder and is increasingly feasible with protocols of short duration, such as intermittent theta burst stimulation (iTBS). The most common and limiting side effect is pain at the site of application. Our objective was to investigate how pain develops over time in patients with depression receiving iTBS compared to sham stimulation. Methods: This is a subsample from a randomized clinical trial. Patients received daily sessions of 2400 pulses of dorsomedial prefrontal iTBS or sham stimulation with transcutaneous electric stimulation during 2 to 3 weeks. After unmasking of treatment allocation, patients receiving sham treatment were offered active iTBS in an open phase. Patients rated pain on a scale from 0 to 10 after the last train of stimulation on the first, fifth and final treatment day. A Mann-Whitney U-test was conducted to test for group differences and related-samples Friedman's tests to analyze changes in pain ratings over time. Results: The scalp pain in the group receiving iTBS was rated higher than sham treatment on the first (U = 263.5,p = 0.035) and fifth day (U = 271.0,p = 0.020) but not on the final day (U = 210.5,p = 0.121). The pain decreased mainly during the first 5 days of treatment (chi(2) = 0.875,p = 0.040). In the open phase the pain decreased from the first day to the final day (chi(2) = 1.194,p = 0.001). Conclusions: The subjective pain perception of active dorsomedial iTBS was higher than sham treatment but decreased over time, indicating an analgesic effect, or habituation. The result from this study can be used to inform patients about what to expect regarding pain during an iTBS treatment course. Trial registration: Clinicaltrials.gov, NCT02905604. Registered 19 September 2016.
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| 16. |
- Nordin, Kristin, et al.
(author)
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Structural whole-brain covariance of the anterior and posterior hippocampus : Associations with age and memory
- 2018
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In: Hippocampus. - : John Wiley & Sons. - 1050-9631 .- 1098-1063. ; 28:2, s. 151-163
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Journal article (peer-reviewed)abstract
- The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations.
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| 17. |
- Persson, Jonas, 1983-, et al.
(author)
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Inhibitory and excitatory neurotransmitter systems in depressed and healthy : A positron emission tomography and magnetic resonance spectroscopy study
- 2021
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In: Psychiatry Research. - : Elsevier. - 0925-4927 .- 1872-7506. ; 315
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Journal article (peer-reviewed)abstract
- The Gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems are implicated in depression. While previous studies found reduced GABA levels, and a tendency towards reduced Glu, using proton (H-1) magnetic resonance spectroscopy (H-1-MRS), little is known about GABA(A) receptor availability in depression. Here, the aim was to characterize GABA and Glu-levels in dorsal anterior cingulate cortex (dACC), whole-brain GABA(A) availability, and their relationship in patients with depression compared to healthy controls. Forty-two patients and 45 controls underwent H-1-MRS using a MEGA-PRESS sequence to quantify dACC GABA+ and Glu (contrasted against creatine [Cr]). Immediately preceding the H-1-MRS, a subsample of 28 patients and 15 controls underwent positron emission tomography (PET) with [C-11]Flumazenil to assess whole-brain GABA(A) receptor availability. There were no differences in dACC GABA+/Cr or Glu/Cr ratios between patients and controls. The same was true for whole-brain GABA(A) receptor availability. However, there was a significant negative relationship between GABA+/Cr ratio and receptor availability in ACC, in a whole-brain voxel-wise analysis across patients and controls, controlling for group or depressive symptoms. This relatively large study did not support the GABA-deficit hypothesis in depression, but shed light on GABA-system functioning, suggesting a balance between neurotransmitter concentration and receptor availability in dACC.
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| 18. |
- Persson, Jonas, 1983-, et al.
(author)
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Intermittent theta burst stimulation over the dorsomedial prefrontal cortex modulates resting-state connectivity in depressive patients : A sham-controlled study
- 2020
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In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 394
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Journal article (peer-reviewed)abstract
- The mechanisms underlying repetitive transcranial magnetic stimulation (rTMS) treatment are largely unknown. Although there is a general lack of sham controlled studies, findings show altered functional connectivity to the stimulated region following treatment. When targeting the dorsolateral prefrontal cortex (dlPFC), connectivity with the subgenual anterior cingulate cortex (sgACC) is predictive of response, but less is known about the effects on functional connectivity of targeting the dorsomedial PFC (dmPFC). Here, 30 patients with an ongoing depressive episode were recruited and randomized to 20 sessions at target intensity of either active or sham intermittent theta burst stimulation (iTBS) over dmPFC. Those receiving sham were offered active treatment in a subsequent open phase. A seven minute resting-state scan and depressive symptom assessment was performed before and after treatment. After exclusions due to attrition and excessive head movements 23 patients remained for analysis. Seed-based resting-state connectivity was calculated using two seeds for the dmPFC target as well as the sgACC. A symptom related increase in dmPFC connectivity after active treatment, compared to sham treatment, was found. The effect was observed in a region overlapping the precuneus and the posterior cingulate cortex (PCC), suggesting an increase in the connectivity between the targeted salience network and the default mode network mediating improvement in depressive symptoms. Connectivity between the precuneus and both the sgACC and the treatment target was predictive of symptom improvement following active treatment. The findings have implications for understanding the mechanisms behind iTBS and may inform future efforts to individualize the treatment.
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| 19. |
- Persson, Jonas, 1983-
(author)
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Making Head or Tail of the Hippocampus : A Long-Axis Account of Episodic and Spatial Memory
- 2015
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Doctoral thesis (other academic/artistic)abstract
- While episodic and spatial memory both depend on the hippocampus, opposite gender differences in these functions suggest they are partly separate, with different neural underpinnings. The anterior and posterior hippocampus differ in structure and whole-brain connectivity, and studies point to the posterior hippocampus being more involved in spatial memory while the anterior hippocampus’ role in episodic memory is less clear. This thesis aims to explore the role of the anterior and posterior hippocampus, and associated brain regions, in episodic and spatial memory. Paper I studied gender differences in hippocampal activation underlying differences in spatial memory performance. Better performance in men was accompanied by greater right-lateralization of hippocampal activation compared to women. Paper II investigated regions of gray matter that covaried in volume with the anterior and posterior hippocampus, and whether these covariance patterns depended on gender and were related to behavior. The anterior and posterior hippocampus showed different patterns of covariance, with the anterior hippocampus covariance pattern observed in women and the posterior hippocampus covariance pattern primarily in men. Paper III considered whether the location of hippocampal recruitment in episodic memory depends on memory content. Verbal stimuli were associated with more anterior, and left-lateralized, encoding activations than pictorial stimuli, which in turn were associated with more posterior and bilateral encoding activations. This was not observed during retrieval. Paper IV investigated whether resting-state connectivity associated with the anterior and posterior hippocampus predicts episodic and spatial memory performance, respectively. Resting-state connectivity associated with the anterior, not posterior, hippocampus predicted episodic memory performance, while resting-state connectivity associated with the posterior, not anterior, hippocampus predicted spatial memory performance. This thesis lends further support to differences in function and structure between the anterior and posterior hippocampus suggesting that these two sub–segments play different roles in episodic and spatial memory. Further, it suggests that gender differences in anterior and posterior hippocampus function underlies gender differences in episodic and spatial memory, respectively. Considering the anterior and posterior hippocampus, as well as men and women, separately, is hence important when studying the effect of age and pathology on the hippocampus and associated memory functions.
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| 20. |
- Persson, Jonas, 1983-, et al.
(author)
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Phosphodiesterase 10A levels are related to striatal function in schizophrenia : a combined positron emission tomography and functional magnetic resonance imaging study
- 2020
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In: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 270:4, s. 451-459
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Journal article (peer-reviewed)abstract
- Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.
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| 21. |
- Persson, Jonas, 1983-, et al.
(author)
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Predicting episodic and spatial memory performance from hippocampal resting-state functional connectivity : Evidence for an anterior-posterior division of function
- 2018
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In: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 28:1, s. 53-66
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Journal article (peer-reviewed)abstract
- fMRI studies have identified distinct resting-state functional connectivity (RSFC) networks associated with the anterior and posterior hippocampus. However, the functional relevance of these two networks is still largely unknown. Hippocampal lesion studies and task-related fMRI point to a role for the anterior hippocampus in non-spatial episodic memory and the posterior hippocampus in spatial memory. We used Relevance Vector Regression (RVR), a machine-learning method that enables predictions of continuous outcome measures from multivariate patterns of brain imaging data, to test the hypothesis that patterns of whole-brain RSFC associated with the anterior hippocampus predict episodic memory performance, while patterns of whole-brain RSFC associated with the posterior hippocampus predict spatial memory performance. Magnetic resonance imaging (MRI) and memory assessment took place at two separate occasions. The anterior and posterior RSFC largely corresponded with previous findings, and showed no effect of laterality. Supporting the hypothesis, RVR produced accurate predictions of episodic performance from anterior, but not posterior, RSFC, and accurate predictions of spatial performance from posterior, but not anterior, RSFC. In contrast, a univariate approach could not predict performance from resting-state connectivity. This supports a functional dissociation between the anterior and posterior hippocampus, and indicates a multivariate relationship between intrinsic functional networks and cognitive performance within specific domains, that is relatively stable over time.
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| 22. |
- Persson, Sofia, et al.
(author)
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Hyperandrogenic symptoms are a persistent suffering in midlife women with pcos; a prospective cohort study in sweden
- 2023
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In: Biomedicines. - : MDPI. - 2227-9059. ; 11:1
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Journal article (peer-reviewed)abstract
- Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women, and the majority suffers from hyperandrogenism. Hyperandrogenism causes psychological morbidity and impaired quality of life in women with PCOS during the reproductive years, but data on prevalence and impact during midlife are lacking. Thus, this study aimed to address whether hyperandrogenism persists into midlife and, if so, what impact it has on quality of life. In order to answer this question, we performed a multicenter prospective cohort study, where we included women already diagnosed with PCOS who had reached the age of 45 years or more and age-matched controls. All participants underwent a physical exam, structured medical interview, biochemical testing and filled out self-assessment questionnaires. More than 40% of the women with PCOS and 82% of those who presented with the hyperandrogenic phenotype at the diagnostic work-up still suffered from hirsutism. Circulating testosterone levels were similar between women with PCOS and controls while free androgen index was higher in women with PCOS, independent of weight. Women with hyperandrogenic PCOS expressed persisting concerns regarding hirsutism at the follow-up assessment. In conclusion, women with PCOS who present with hyperandrogenic symptoms at the time they are diagnosed with PCOS have a higher risk of persistent androgenic symptoms and impaired quality of life in midlife.
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| 23. |
- Pudas, Sara, 1983-
(author)
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Brain characteristics of memory decline and stability in aging : Contributions from longitudinal observations
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Aging is typically associated with declining mental abilities, most prominent for some forms of memory. There are, however, large inter-individual differences within the older population. Some people experience rapid decline whereas others seem almost spared from any adverse effects of aging. This thesis examined the neural underpinnings of such individual differences by using longitudinal observations of episodic memory change across 15-20 years, combined with structural and functional magnetic resonance imaging of the brain. Study I found significant correlations between volume and activity of the hippocampus (HC), and memory change over a 6-year period. That is, individuals with decline in HC function also had declining memory. In contrast, Study II showed that successfully aged individuals, who maintained high memory scores over 15-20 years, had preserved HC function compared to age-matched elderly with average memory change. The successful agers had HC activity levels comparable to those of young individuals, as well as higher frontal activity. Study III revealed that individual differences in memory ability and brain activity of elderly reflect both differential age-related changes, and individual differences in memory ability that are present already in midlife, when age effects are minimal. Specifically, memory scores obtained 15-20 years earlier reliably predicted brain activity in memory-relevant regions such as the frontal cortex and HC. This observation challenges results from previous cross-sectional aging studies that did not consider individual differences in cognitive ability from youth. Collectively the three studies implicate HC and frontal cortex function behind heterogeneity in cognitive aging, both substantiating and qualifying previous results from cross-sectional studies. More generally, the findings highlight the importance of longitudinal estimates of cognitive change for fully understanding the mechanisms of neurocognitive aging.
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| 24. |
- Pudas, Sara, 1983-, et al.
(author)
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Midlife memory ability accounts for brain activity differences in healthy aging
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Other publication (other academic/artistic)abstract
- Cross-sectional neuroimaging studies suggest that hippocampal and prefrontal cortex (PFC) functions underlie individual differences in memory ability in elderly individuals, but it is unclear how individual differences in cognitive ability in youth contribute to cognitive and neuroimaging measures in older age. Here, a sample from a longitudinal population-based study (N = 201, aged 55-80) was used to investigate the relative influence of midlife memory ability and age-related memory change on memory-related BOLD-signal variability in healthy elderly. Hierarchical regression analyses showed that midlife memory ability, assessed 15-20 years earlier, explained at least as much variance as memory change in clusters in the left inferior PFC and the bilateral hippocampus, during memory encoding. Memory change estimates, however, were found to be more sensitive in detecting bilateral frontal regions specifically diagnostic of age-related memory change. These finding highlight challenges in interpreting individual differences in neurocognitive measures as age-related changes in the absence of longitudinal data, and also demonstrates the improved sensitivity of longitudinal measures.
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| 25. |
- Rode, Julia, 1992-, et al.
(author)
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Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects : An RCT
- 2022
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In: Cells. - : MDPI. - 2073-4409. ; 11:18
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Journal article (peer-reviewed)abstract
- Probiotics can alter brain function via the gut-brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p < 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR < 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut-brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut-brain communication and hence brain function.
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| 26. |
- Rode, Julia, 1992-, et al.
(author)
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Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects : A Randomized Clinical Trial
- 2022
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In: Frontiers in nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
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Journal article (peer-reviewed)abstract
- Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited.Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task.Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed.Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention.Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest.Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].
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| 27. |
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| 28. |
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| 29. |
- Steinholtz, Linda, et al.
(author)
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GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy : A Positron Emission Tomography and Transcranial Magnetic Stimulation Study.
- 2024
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In: Neuropsychobiology. - : S. Karger. - 0302-282X .- 1423-0224. ; 83:1, s. 17-27
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls.METHODS: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability.RESULTS: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT.CONCLUSION: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.
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| 30. |
- Steinholtz, Linda, et al.
(author)
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Response rate and subjective memory after electroconvulsive therapy in depressive disorders with psychiatric comorbidity
- 2021
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 292, s. 276-283
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Journal article (peer-reviewed)abstract
- Background: Response rates after and tolerability of electroconvulsive therapy (ECT) in depressive disorders with psychiatric comorbidity are uncertain.Methods: Data on patients with a depressive episode and a first course of ECT were collected from the Swedish National Quality Register for ECT. Logistic regression analyses, adjusted for gender, age, and depressive episode severity, were used to compare patients with and without comorbidity. The clinical response assessment Clinical Global Impression - Improvement Scale was used in 4413 patients and the memory item from the Comprehensive Psychiatric Rating Scale was used for subjective memory impairment rating after ECT in 3497 patients.Results: In patients with depressive disorder and comorbid personality disorder or anxiety disorder, 62.7% and 73.5%, respectively, responded after ECT compared with 84.9% in patients without comorbidity [adjusted odds ratio (aOR) 0.43, 95% confidence interval (CI) 0.34-0.55, and aOR 0.61, 95% CI 0.51-0.73, respectively]. The proportion of responding patients with comorbid alcohol use disorder was 77.1%, which was not significantly different from that in patients without comorbidity (aOR 0.75, 95% CI 0.57-1.01). The impact of comorbidity decreased with higher age and depressive episode severity. Subjective ratings of memory impairment did not differ between patients with and without comorbidity.Limitations: Observational non-validated clinical data.Conclusions: The response rate after ECT in depression may be lower with concurrent personality disorder and anxiety disorder; however, the majority still respond to ECT. This implies that psychiatric comorbidity should not exclude patients from ECT.
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| 31. |
- Stening, Eva, et al.
(author)
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Specific patterns of whole-brain structural covariance of the anterior and posterior hippocampus in young APOE ε4 carriers.
- 2017
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In: Behavioural brain research. - : Elsevier BV. - 1872-7549 .- 0166-4328. ; 326, s. 256-264
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Journal article (peer-reviewed)abstract
- Apolipoprotein E (APOE) ε4 has been associated with smaller hippocampal volumes in healthy aging, while findings in young adults are inconclusive. Previous studies have mostly used univariate methods, and without considering potential anterior/posterior differences. Here, we used a multivariate method, partial least squares, and assessed whole-brain structural covariance of the anterior (aHC) and posterior (pHC) hippocampus in young adults (n=97) as a function of APOE ε4 status and sex. Two significant patterns emerged: (1) specific structural covariance of the aHC with frontal regions, temporal and occipital areas in APOE ε4 women, whereas the volume of both the aHC and pHC in all other groups co-varied with frontal, parietal and cerebellar areas; and (2) opposite structural covariance of the pHC in ε4 carriers compared to the aHC in non-carriers, with the pHC of ε4 carriers covarying with parietal and frontal areas, and the aHC of ε4 non-carriers covarying with motor areas and the middle frontal gyrus. APOE ε4 has in young adults been associated with better episodic and spatial memory, functions involving the aHC and pHC, respectively. We found no associations between structural covariance and performance, suggesting that other factors underlie the performance differences seen between carriers and non-carriers. Our findings indicate that APOE ε4 carriers and non-carriers differ in hippocampal organization and that there are differences as a function of sex and hippocampal segment. They stress the need to consider the hippocampus as a heterogeneous structure, and highlight the benefits of multivariate methods in assessing group differences in the brain.
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| 32. |
- Struckmann, Wiebke, et al.
(author)
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Modulation of dorsolateral prefrontal cortex functional connectivity after intermittent theta-burst stimulation in depression : combining findings from fNIRS and fMRI
- 2022
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In: NeuroImage. - : Elsevier. - 2213-1582. ; 34
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Journal article (peer-reviewed)abstract
- Background: Resting-state functional magnetic resonance imaging (fMRI) can assess modulation of functional connectivity networks following repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. Functional near-infrared spectroscopy (fNIRS) is well suited for the concurrent application during rTMS treatment sessions to capture immediate blood oxygenation (oxy-Hb) effects, however limited in spatial resolution.Objective: To understand the network effects behind such a prefrontal fNIRS response during rTMS, and to test whether the fNIRS signal may be predictive of treatment response, we linked data from fNIRS and fMRI within a clinical intervention study.Methods: 42 patients with ongoing depression were recruited and randomized to receive active or sham intermittent theta-burst stimulation (iTBS) over the dorsomedial prefrontal cortex (dmPFC) twice daily for ten days at target intensity. Oxy-Hb was recorded with fNIRS during the first, fifth, and final day of iTBS, with the probe holders located laterally to the TMS coil over regions corresponding to the left and right dorsolateral prefrontal cortex (dlPFC). Resting-state fMRI scanning was performed before and after the whole iTBS treatment course. Functional connectivity analyses were then performed using dlPFC seeds from parcels of a brain atlas showing most overlap with the fNIRS probe locations during treatment.Results: After active iTBS, left dlPFC-connectivity to the right insula/operculum was reduced compared to sham. The left insula showed a connectivity reduction to the left dlPFC that correlated with an improvement in symptoms. In addition, the posterior parietal cortex showed a connectivity reduction to the left dlPFC that correlated with the fNIRS signal following active iTBS. Finally, the fNIRS oxy-Hb signal from the left dlPFC-seed during the first treatment day was predictive of dlPFC-connectivity change to precentral and temporal cortex regions.Conclusion: By linking findings from these two different methods, this study suggests that changes within both the salience network and the central executive network affect the fNIRS response to iTBS.
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| 33. |
- Struckmann, Wiebke, et al.
(author)
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Modulation of the prefrontal blood oxygenation response to intermittent theta-burst stimulation in depression : A sham-controlled study with functional near-infrared spectroscopy
- 2021
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In: World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 22:4, s. 247-256
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To better understand the neural mechanisms behind the effect of intermittent theta-burst stimulation (iTBS), we investigated how the prefrontal blood oxygenation response measured by changes in oxygenated haemoglobin (oxy-Hb) was modulated during a sham-controlled iTBS treatment course, and whether this was related to depressive symptom change.METHODS: In this randomised, double-blind study, patients with ongoing treatment-resistant depression received either active (n = 18) or sham (n = 21) iTBS over the dorsomedial prefrontal cortex for ten to fifteen days with two sessions daily. Event-related functional near-infrared spectroscopy (fNIRS) was measured during each iTBS train, and resting-state oxy-Hb was compared before and after each iTBS session at the first, fifth, and last treatment day.RESULTS: Patients receiving active iTBS had an increase of the event-related oxy-Hb response compared to the sham group on the fifth (bilateral prefrontal cortices p < .001) and last (left prefrontal p = .007, right prefrontal p = .025) treatment day. Resting-state analysis showed suppressed oxy-Hb change in active iTBS compared to sham iTBS on the last treatment day (p = .024). Oxy-Hb change was unrelated to depressive symptom change (p = .474).CONCLUSIONS: This study describes a modulation of the blood oxygenation response over the prefrontal cortex that was built up during the course of active iTBS treatment in depression.
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| 34. |
- Weis, Jan, 1956-, et al.
(author)
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GABA quantification in human anterior cingulate cortex
- 2021
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In: PLOS ONE. - : PLOS. - 1932-6203. ; 16:1
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Journal article (peer-reviewed)abstract
- γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B0 drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation.
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