| 1. |
- Nelander, Maria, et al.
(author)
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Assessment of cerebral perfusion and edema in preeclampsia with intravoxel incoherent motion MRI
- 2018
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:10, s. 1212-1218
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Journal article (peer-reviewed)abstract
- BackgroundCerebral complications are the main reasons for morbidity and mortality in preeclampsia and eclampsia. Still we do not know if the pathophysiology entails hypo- or hyperperfusion of the brain, or how and when edema emerges, due to the difficulty to examine the cerebral circulation.Material and methodsWe have used a non-invasive diffusion weighted magnetic resonance imaging (MRI) technique, intravoxel incoherent motion, to study cerebral perfusion on the capillary level and cerebral edema in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant women (n=16). Estimates of cerebral blood volume, blood flow and edema were measured in five different regions. These points were chosen to represent blood supply areas of both the carotid and vertebrobasilar arteries, and to include both white and grey matter.ResultsExcept for the caudate nucleus, we did not detect any differences in cerebral perfusion measures on a group level. In the caudate nucleus we found lower cerebral blood volume and lower blood flow in preeclampsia compared to both normal pregnancy (p=0.01 and p=0.03, respectively) and non-pregnant women (both p=0.02). No differences in edema were detected between study groups.ConclusionThe cerebral perfusion measures were comparable between the study groups, except for a portion of the basal ganglia where hypoperfusion was detected in preeclampsia compared to normal pregnancy and non-pregnant women.
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| 2. |
- Nelander, Maria, 1974-, et al.
(author)
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Cerebral osmolytes and plasma osmolality in pregnancy and preeclampsia : a proton magnetic resonance spectroscopy study
- 2018
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In: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 31:7, s. 847-853
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Journal article (peer-reviewed)abstract
- Background: Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia.Method: We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant controls (n=16). Cerebral levels organic osmolytes were further correlated to plasma osmolality, and plasma levels of glutamate and sodium.Results: Compared to non-pregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes myo-inositol, choline and creatine (p=0.001 or less), and all these metabolites correlated with each other (p<0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (p<0.008), and cerebral myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (p<0.05).Conclusion: Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia.
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| 3. |
- Nelander, Maria, 1974-
(author)
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Preeclampsia and the Brain : Epidemiological and Magnetic Resonance Studies
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Preeclampsia is a pregnancy specific syndrome that causes substantial maternal and fetal morbidity and mortality. One major contributor to maternal deaths is eclampsia, i.e. when seizures arise in the context of preeclampsia. The pathophysiology of eclampsia is still incompletely chartered and the long-term cerebral consequences of preeclampsia are also largely unknown.This thesis consists of a register based cohort study (n=3232, study I), and a cross-sectional neuroimaging study of pregnant women with and without preeclampsia (n=78, studies II-IV).In paper I, we compared the incidence of dementia and cardiovascular disease (CVD) between women ≥65 years with a self-reported history of hypertensive pregnancy, and women with a normotensive pregnancy. No difference was found regarding dementia, but an increased risk of CVD persisted among these elderly women.In paper II, we used phosphorus magnetic resonance spectroscopy to measure cerebral magnesium levels (Mg2+). We found lower levels of Mg2+ in women with preeclampsia than in women with normal pregnancy and non-pregnant women. Further, which was novel, we showed that lower cerebral Mg2+levels correlated with visual disturbances. The findings are interesting, since magnesium sulfate is the most effective treatment and prophylaxis for eclampsia, but with a largely unknown mechanism of action.In paper III, we measured cerebral organic osmolytes with proton magnetic resonance spectroscopy and found lower levels of osmolytes in pregnancy. Cerebral osmolytes were positively correlated with a decreased plasma osmolality, indicating that there is a joint biological mechanism. The only osmolyte that differed between women with preeclampsia and healthy pregnant women was glutamate. Glutamate is an excitatory neurotransmitter, which also functions as an osmolyte. Thus, lower cerebral glutamate levels could have implications on the pathophysiology of seizures.In paper IV, cerebral perfusion and edema were assessed with magnetic resonance imaging using intravoxel incoherent motion technique. A reduced perfusion fraction was found in a part of the basal ganglia in women with preeclampsia. No difference in edema was detected.Our findings indicate Mg2+ metabolism, plasma hypoosmolality and possibly cerebral hypoperfusion to be involved in the pathophysiology of cerebral affection in preeclampsia.
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| 4. |
- Bannbers, Elin, 1984-, et al.
(author)
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Prefrontal activity during response inhibition decreases over time in the postpartum period
- 2013
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In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 241, s. 132-138
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Journal article (peer-reviewed)abstract
- The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, during the postpartum period and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48 h of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in performance on the Go/NoGo task were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted. (C) 2012 Elsevier B.V. All rights reserved.
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| 5. |
- Dubol, Manon, et al.
(author)
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Acute nicotine exposure blocks aromatase in the limbic brain of healthy women : A [11C]cetrozole PET study
- 2023
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In: Comprehensive Psychiatry. - : Elsevier. - 0010-440X .- 1532-8384. ; 123
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Journal article (peer-reviewed)abstract
- Background: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain.Methods: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [11C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI -based approach was employed to assess changes in [11C]cetrozole non-displaceable binding potential.Results: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [11C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d =-0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend.Conclusions: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction.
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| 6. |
- Dubol, Manon, et al.
(author)
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Differential grey matter structure in women with premenstrual dysphoric disorder : evidence from brain morphometry and data-driven classification
- 2022
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In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
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Journal article (peer-reviewed)abstract
- Premenstrual dysphoric disorder (PMDD) is a female-specific condition classified in the Diagnostic and Statical Manual—5th edition under depressive disorders. Alterations in grey matter volume, cortical thickness and folding metrics have been associated with a number of mood disorders, though little is known regarding brain morphological alterations in PMDD. Here, women with PMDD and healthy controls underwent magnetic resonance imaging (MRI) during the luteal phase of the menstrual cycle. Differences in grey matter structure between the groups were investigated by use of voxel- and surface-based morphometry. Machine learning and multivariate pattern analysis were performed to test whether MRI data could distinguish women with PMDD from healthy controls. Compared to controls, women with PMDD had smaller grey matter volume in ventral posterior cortices and the cerebellum (Cohen’s d = 0.45–0.76). Region-of-interest analyses further indicated smaller volume in the right amygdala and putamen of women with PMDD (Cohen’s d = 0.34–0.55). Likewise, thinner cortex was observed in women with PMDD compared to controls, particularly in the left hemisphere (Cohen’s d = 0.20–0.74). Classification analyses showed that women with PMDD can be distinguished from controls based on grey matter morphology, with an accuracy up to 74%. In line with the hypothesis of an impaired top-down inhibitory circuit involving limbic structures in PMDD, the present findings point to PMDD-specific grey matter anatomy in regions of corticolimbic networks. Furthermore, the results include widespread cortical and cerebellar regions, suggesting the involvement of distinct networks in PMDD pathophysiology.
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| 7. |
- Dubol, Manon, et al.
(author)
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Grey matter correlates of affective and somatic symptoms of premenstrual dysphoric disorder
- 2022
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- Ovarian hormones fluctuations across the menstrual cycle are experienced by about 58% of women in their fertile age. Maladaptive brain sensitivity to these changes likely leads to the severe psychological, cognitive, and physical symptoms repeatedly experienced by women with Premenstrual Dysphoric Disorder (PMDD) during the late luteal phase of the menstrual cycle. However, the neuroanatomical correlates of these symptoms are unknown. The relationship between grey matter structure and PMDD symptom severity was delineated using structural magnetic resonance imaging during the late luteal phase of fifty-one women diagnosed with PMDD, combined with Voxel- and Surface-Based Morphometry, as well as subcortical volumetric analyses. A negative correlation was found between depression-related symptoms and grey matter volume of the bilateral amygdala. Moreover, the severity of affective and somatic PMDD symptoms correlated with cortical thickness, gyrification, sulcal depth, and complexity metrics, particularly in the prefrontal, cingulate, and parahippocampal gyri. The present findings provide the first evidence of grey matter morphological characteristics associated with PMDD symptomatology in brain regions expressing ovarian hormone receptors and of relevance to cognitive-affective functions, thus potentially having important implications for understanding how structural brain characteristics relate to PMDD symptomatology.
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| 8. |
- Engman, Jonas, et al.
(author)
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Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.
- 2018
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In: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 43:3, s. 555-563
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Journal article (peer-reviewed)abstract
- The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.
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| 9. |
- Gingnell, Malin, 1982-, et al.
(author)
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Emotional anticipation after delivery - a longitudinal neuroimaging study of the postpartum period
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Journal article (peer-reviewed)abstract
- Neuroimaging research has begun to unveil the mechanisms behind emotion processing during the postpartum period, which, in turn, may be of relevance for the development of postpartum depression. The present study sought to longitudinally investigate the neural correlates of emotion anticipation during the postpartum period in healthy women. Functional magnetic resonance imaging was employed to measure the blood oxygen level-dependent signal in the brain in response to anticipation of negative emotional stimuli and during processing of images with positive or negative valence. The participating women were scanned twice: the first scan occurred during the first 48 hours after delivery, and the second was performed 4-6 weeks after delivery. The early postpartum period was characterized by higher anterior cingulate cortex reactivity during anticipation of negative emotional stimuli than the late postpartum period. This was accompanied by a negative relationship with insular reactivity during the early postpartum period and a trend towards an increase in insular reactivity in the late postpartum period. Thus, during the first four weeks of the postpartum period, a diminished top-down regulatory feedback on emotion-related areas of the brain was noted. This finding suggests a physiologically important adaptation during the healthy postpartum period.
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| 10. |
- Gingnell, Malin, et al.
(author)
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Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill : A double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive
- 2013
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 38:7, s. 1133-1144
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Journal article (peer-reviewed)abstract
- OBJECTIVE:Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing.METHODS:Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale.RESULTS:During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala.CONCLUSION:COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives.
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