Johan Wikström

Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) with luteal phase related anxiety and mood swings compromise quality of life in around 4% of reproductive women. While anxiety is related to amygdala function, prior studies on amygdala reactivity both in healthy controls and women with PMDD are inconsistent with respect to menstrual cycle effects. Here women with PMDD and healthy controls were exposed to emotional faces during the mid-follicular and late luteal phase, and mean blood-oxygen-level dependence (BOLD) signal changes in the amygdala were determined with functional magnetic resonance imaging (fMRI). Women with PMDD had enhanced bilateral amygdala reactivity in the follicular phase in comparison with healthy controls, but there was no difference between groups during the luteal phase. In contrast, healthy controls displayed higher left amygdala reactivity in the luteal than in their follicular phase. However, among women with PMDD follicular phase progesterone serum concentrations were positively correlated with bilateral amygdala reactivity while depression scores were positively correlated with right amygdala reactivity in the luteal phase. In addition, women with PMDD and high scores on trait anxiety had increased right amygdala reactivity in the luteal as compared to the follicular phase. Finally, amygdala reactivity was more prone to habituation in women with PMDD, as they had enhanced amygdala reactivity in comparison with controls at the first, but not the second scanning session. Thus, while the study failed to indicate increased luteal phase amygdala reactivity in women with PMDD, our findings suggest that anxiety proneness and progesterone levels modulate menstrual cycle related amygdala reactivity in women with PMDD.

Future train traffic control: control by re-planning

Improving train traffic control can be a cost-efficient way to improve train traffic punctuality and increase utilization of existing and future railway infrastructure. However, performance in train traffic control tasks currently involves working on a technical level in order to regulate the traffic flow. Working in a preventive manner is poorly supported and train traffic controllers are usually restricted to just solving problems as they occur. This often results in unnecessarily long delays and decreased timeliness of train traffic. The main objective of this paper is to describe a proposed control strategy and a case study, which evaluates the control strategy and the prototype tool derived from the research. By shifting the control paradigm to a high-level control strategy, many of today’s problems may be avoided, with benefits of the reduction in delays, improved timeliness and better utilization of the infrastructure. Twenty-one train traffic controllers participated in a case study, with a simulated prototype environment. The majority of the participating train traffic controllers were positive to the new concepts and ideas. Many of the important aspects of the proposed control strategy can be investigated with the simulation, but due to the complexity of train traffic some issues must be evaluated in an operative environment.

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

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.

Ankle brachial index <0.9 underestimates the prevalence of peripheral artery occlusive disease assessed with whole-body magnetic resonance angiography in the elderly.

Background: Whole-body magnetic resonance angiography (WBMRA) permits noninvasive vascular assessment, which can be utilized in epidemiological studies. Purpose: To assess the relation between a low ankle brachial index (ABI) and high-grade stenoses in the pelvic and leg arteries in the elderly. Material and Methods: WBMRA was performed in a population sample of 306 subjects aged 70 years. The arteries below the aortic bifurcation were graded after the most severe stenosis according to one of three grades: 0–49% stenosis, 50–99% stenosis, or occlusion. ABI was calculated for each side. Results: There were assessable WBMRA and ABI examinations in 268 (right side), 265 (left side), and 258 cases (both sides). At least one ⩾50% stenosis was found in 19% (right side), 23% (left side), and 28% (on at least one side) of the cases. The corresponding prevalences for ABI <0.9 were 4.5%, 4.2%, and 6.6%. An ABI cut-off value of 0.9 resulted in a sensitivity, specificity, and positive and negative predictive value of 20%, 99%, 83%, and 84% on the right side, and 15%, 99%, 82%, and 80% on the left side, respectively, for the presence of a ⩾50% stenosis in the pelvic or leg arteries. Conclusion: An ABI <0.9 underestimates the prevalence of peripheral arterial occlusive disease in the general elderly population.

The Prevalence and Quantification of Atherosclerosis in an Elderly Population Assessed by Whole-Body Magnetic Resonance Angiography

Objective—The principal aim of the present study was to explore the feasibility of using whole-body magnetic resonance angiography to assess atherosclerosis in different vascular territories in a cohort of elderly. Methods and Results—Three hundred six 70-year-old subjects (145 women, 161 men) recruited from a population-based cohort study (Prospective Investigation of the Vasculature in Uppsala Seniors, ie, the PIVUS study) underwent 1.5-T whole-body magnetic resonance angiography with gadodiamide. The arteries were divided into 26 segments. In total, 7956 vessel segments were evaluated with 7900 segments (99.3%) possible to evaluate. Of these, 7186 segments (91%) were normal. Luminal narrowing of ≥50% was observed in 9 (1.5%) of the renal arteries, 12 (1.8%) of the carotid arteries, in 31 segments (1.1%) of the pelvic/upper leg territories, and in 136 segments (6.2%) of territories in the lower leg. Approximately one-third of the sample had no vascular abnormalities, one-third had stenoses of <50%, and the remainder had stenoses ≥50% or occlusions. Six subjects (2%) had aortic aneurysms. In subjects without evident vascular disease, 26% had significant vascular abnormalities. Conclusions—Whole-body magnetic resonance angiography performed with a clinical scanner can be used for quantifying atherosclerosis in different vascular territories in a single examination in an elderly population.

Remembering our origin: Gender differences in spatial memory are reflected in gender differences in hippocampal lateralization

Gender differences in spatial memory favoring men are frequently reported, and the involvement of the hippocampus in these functions is well-established. However, little is known of whether this behavioral gender difference is mirrored in a gender difference in hippocampal function. Here we assessed hippocampal activity, using functional MRI, while 24 men and women moved through three-dimensional virtual mazes (navigation phase) of varying length, and at the end-point estimated the direction of the starting-point (pointing phase). Men were indeed more accurate than women at estimating direction, and this was especially true in longer mazes. Both genders activated the posterior hippocampus throughout the whole task. During the navigation phase, men showed a larger activation in the right hippocampus than women, while in the pointing phase, women showed a larger activation in the left hippocampus than men. Right-lateralized activation during the navigation phase was associated with greater task performance, and may reflect a spatial strategy that is beneficial in this task. Left-sided activation during the pointing phase might reflect a less efficient post hoc verbal recapitulation of the route. This study is the first to identify neural correlates of the commonly observed male advantage in recalling ones original position, and points to hippocampal lateralization as a possible explanation for this behavioral gender difference.

The effect of premenstrual dysphoric disorder and menstrual cycle phase on brain activity during response inhibition

BACKGROUND Premenstrual dysphoric disorder (PMDD) has generally not been associated with impulsive behavior. However, some studies suggest that women with PMDD have higher impulsivity scores than healthy controls and that brain activity during response inhibition may vary across the menstrual cycle. Therefore, our aim was to unravel potentially important cognitive aspects of PMDD by investigating brain activity during response inhibition in women with PMDD and healthy controls in relation to menstrual cycle phase. METHODS Fourteen PMDD patients and 13 healthy controls performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging. RESULTS Women with PMDD displayed decreased activity during both menstrual cycle phases compared to healthy controls in several task-related parietal areas. A significant group by phase interactions was found in the left insula, driven by enhanced activity among healthy controls in the follicular phase and by enhanced insula activity during the luteal phase among PMDD patients. LIMITATIONS The limitations of the present study are the relatively limited sample size, the relatively small number of NoGo trials and the lack of a baseline contrast for the NoGo trials. CONCLUSIONS During response inhibition women with PMDD have reduced activity in areas associated with attention and motor function which is unrelated to menstrual cycle phase. Insular cortex activity, involved in both affective and cognitive processing, was significantly activated during the luteal phase among PMDD women. These findings are relevant for the understanding of how ovarian steroids influence mood symptoms in women.

Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population

OBJECTIVE The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.

Placental perfusion in normal pregnancy and early and late preeclampsia: a magnetic resonance imaging study.

OBJECTIVE Our primary aim was to investigate if women with early or late preeclampsia have different placental perfusion compared with normal pregnancies. A secondary aim was to investigate if placental perfusion changes with increasing gestational age in normal pregnancy. METHODS The study population included thirteen women with preeclampsia (five with early and eight with late preeclampsia) and nineteen women with normal pregnancy (ten with early and nine with late pregnancy). Early was defined as <34 weeks and late as ≥ 34 weeks gestation. All women underwent a magnetic resonance imaging (MRI) examination including a diffusion weighted sequence at 1.5 T. The perfusion fraction was calculated. RESULTS Women with early preeclampsia had a smaller placental perfusion fraction (p = 0.001) and women with late preeclampsia had a larger placental perfusion fraction (p = 0.011), compared to women with normal pregnancies at the corresponding gestational age. The placental perfusion fraction decreased with increasing gestational age in normal pregnancies (p = 0.001). CONCLUSION Both early and late preeclampsia differ in placental perfusion from normal pregnant women. Observed differences are however in the opposite direction, suggesting differences in pathophysiology. Placental perfusion decreases with increasing gestational age in normal pregnancy.

Sex differences in volume and structural covariance of the anterior and posterior hippocampus

Sex differences in episodic and spatial memory are frequently observed, suggesting that there may be sex-related structural differences in the hippocampus (HC). Earlier findings are inconsistent, possibly due to a known variability along the hippocampal longitudinal axis. Here, we assessed potential sex differences in hippocampal volume and structural covariance with the rest of the brain in young men and women (N=76), considering the anterior (aHC) and posterior (pHC) hippocampus separately. Women exhibited a larger pHC than men adjusted for brain size. Using partial least squares, we identified two significant patterns of structural covariance of the aHC and pHC. The first included brain areas that covaried positively and negatively in volume with both the aHC and pHC in men, but showed greater covariance with the aHC than pHC in women. The second pattern revealed distinct structural covariance of the aHC and pHC that showed a clear difference between men and women: in men the pHC showed reliable structural covariance with the medial and lateral parietal lobes and the prefrontal cortex, whereas in women the aHC showed reliable structural covariance with the anterior temporal lobe bilaterally. This pattern converges with resting state functional connectivity of the aHC and pHC and suggests that these hippocampal sections interact with different brain regions, consistent with a division of labor with regards to episodic and spatial memory. Our findings lend support to a division of the HC into an anterior and posterior part and identify sex as a potential moderating factor when investigating hippocampal structure and connectivity.