Abstract Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in post-mortem studies of neurodegenerative diseases ...and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in-vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultra-high field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22-80 years. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 out of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in-vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases.
Major depressive disorder (MDD) has been associated with abnormal prefrontal-limbic interactions and altered catecholaminergic neurotransmission. The val158met polymorphism on the ...catechol-O-methyltransferase (COMT) gene has been shown to influence prefrontal cortex (PFC) activation during both emotional processing and working memory (WM). Although COMT-genotype is not directly associated with MDD, it may affect MDD pathology by altering PFC activation, an endophenotype associated with both COMT and MDD. 125 participants, including healthy controls (HC, n=28) and MDD patients were genotyped for the COMT val158met polymorphism and underwent functional magnetic resonance imaging (fMRI-neuroimaging) during emotion processing (viewing of emotional facial expressions) and a WM task (visuospatial planning). Within HC, we observed a positive correlation between the number of met-alleles and right inferior frontal gyrus activation during emotional processing, whereas within patients the number of met-alleles was not correlated with PFC activation. During WM a negative correlation between the number of met-alleles and middle frontal gyrus activation was present in the total sample. In addition, during emotional processing there was an effect of genotype in a cluster including the amygdala and hippocampus. These results demonstrate that COMT genotype is associated with relevant endophenotypes for MDD. In addition, presence of MDD only interacts with genotype during emotional processing and not working memory.
In the context of chronic childhood emotional maltreatment (CEM; emotional abuse and/or neglect), adequately responding to facial expressions is an important skill. Over time, however, this adaptive ...response may lead to a persistent vigilance for emotional facial expressions. The amygdala and the medial prefrontal cortex (mPFC) are key regions in face processing. However, the neurobiological correlates of face processing in adults reporting CEM are yet unknown. We examined amygdala and mPFC reactivity to emotional faces (Angry, Fearful, Sad, Happy, Neutral) vs scrambled faces in healthy controls and unmedicated patients with depression and/or anxiety disorders reporting CEM before the age of 16 years (n = 60), and controls and patients who report no childhood abuse (n = 75). We found that CEM was associated with enhanced bilateral amygdala reactivity to emotional faces in general, and independent of psychiatric status. Furthermore, we found no support for differential mPFC functioning, suggesting that amygdala hyper-responsivity to emotional facial perception in adults reporting CEM may be independent from top-down influences of the mPFC. These findings may be key in understanding the increased emotional sensitivity and interpersonal difficulties, that have been reported in individuals with a history of CEM.
Structural brain changes in migraine Palm-Meinders, Inge H; Koppen, Hille; Terwindt, Gisela M ...
JAMA : the journal of the American Medical Association,
11/2012, Letnik:
308, Številka:
18
Journal Article
Recenzirano
Odprti dostop
A previous cross-sectional study showed an association of migraine with a higher prevalence of magnetic resonance imaging (MRI)-measured ischemic lesions in the brain.
To determine whether women or ...men with migraine (with and without aura) have a higher incidence of brain lesions 9 years after initial MRI, whether migraine frequency was associated with progression of brain lesions, and whether progression of brain lesions was associated with cognitive decline.
In a follow-up of the 2000 Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis cohort, a prospective population-based observational study of Dutch participants with migraine and an age- and sex-matched control group, 203 of the 295 baseline participants in the migraine group and 83 of 140 in the control group underwent MRI scan in 2009 to identify progression of MRI-measured brain lesions. Comparisons were adjusted for age, sex, hypertension, diabetes, and educational level. The participants in the migraine group were a mean 57 years (range, 43-72 years), and 71% were women. Those in the control group were a mean 55 years (range, 44-71 years), and 69% were women. MAIN OUTCOME MEASURES Progression of MRI-measured cerebral deep white matter hyperintensities, infratentorial hyperintensities, and posterior circulation territory infarctlike lesions. Change in cognition was also measured.
Of the 145 women in the migraine group, 112 (77%) vs 33 of 55 women (60%) in the control group had progression of deep white matter hyperintensities (adjusted odds ratio OR, 2.1; 95%CI, 1.0-4.1; P = .04). There were no significant associations of migraine with progression of infratentorial hyperintensities: 21 participants (15%) in the migraine group and 1 of 57 participants (2%) in the control group showed progression (adjusted OR, 7.7; 95% CI, 1.0-59.5; P = .05) or new posterior circulation territory infarctlike lesions: 10 of 203 participants (5%) in the migraine group but none of 83 in the control group (P = .07). There was no association of number or frequency of migraine headaches with progression of lesions. There was no significant association of high vs nonhigh deep white matter hyperintensity load with change in cognitive scores (-3.7 in the migraine group vs 1.4 in the control group; 95% CI, -4.4 to 0.2; adjusted P = .07).
In a community-based cohort followed up after 9 years, women with migraine had a higher incidence of deep white matter hyperintensities but did not have significantly higher progression of other MRI-measured brain changes. There was no association of migraine with progression of any MRI-measured brain lesions in men.
In a previous study, migraine cases from the general population were found to be at significantly increased risk of silent infarct-like lesions in the posterior circulation (PC) territory of the ...brain, notably in the cerebellum. In this study we describe the clinical and neuroimaging characteristics of migraine cases with and without aura and controls with PC lesions. In total, 39 PC infarct-like lesions represented the majority (65%) of all 60 identified brain infarct-like lesions in the study sample (n = 435 subjects with and without migraine). Most lesions (n = 33) were located in the cerebellum, often multiple, and were round or oval-shaped, with a mean size of 7 mm. The majority (88%) of infratentorial infarct-like lesions had a vascular border zone location in the cerebellum. Prevalence of these border zone lesions differed between controls (0.7%), cases with migraine without aura (2.2%) and cases with migraine with aura (7.5%). Besides higher age, cardiovascular risk factors were not more prevalent in cases with migraine with PC lesions. Presence of these lesions was not associated with supratentorial brain changes, such as white matter lesions. The combination of vascular distribution, deep border zone location, shape, size and imaging characteristics on MRI makes it likely that the lesions have an infarct origin. Previous investigators attributed cases of similar ‘very small’ cerebellar infarcts in non-migraine patients to a number of different infarct mechanisms. The relevance and likelihood of the aetiological options are placed in the context of known migraine pathophysiology. In addition, the specific involvement of the cerebellum in migraine is discussed. The results suggest that a combination of (possibly migraine attack-related) hypoperfusion and embolism is the likeliest mechanism for PC infarction in migraine, and not atherosclerosis or small-vessel disease.
Aim
The aim of this study was to determine whether tractography of white‐matter tracts can independently predict neurodevelopmental outcome in very preterm infants.
Method
Out of 84 very preterm ...infants admitted to a neonatal intensive care unit, 64 (41 males, 23 females; median gestational age 29.1 weeks range 25.6–31.9; birthweight 1163g range 585–1960) underwent follow‐up at 2 years. Diffusion tensor imaging (DTI) values obtained around term were associated with a neurological examination and mental and psychomotor developmental index scores at 2 years based on the Bayley Scales of Infant Development (version 3). Univariate and logistic regression analyses tested for associations between DTI values and follow‐up parameters. Cut‐off values predicting motor delay and cerebral palsy (CP) were determined for fractional anisotropy, apparent diffusion coefficient (ADC), and fibre lengths.
Results
Infants with psychomotor delay and CP had significantly lower fractional anisotropy values (p=0.002, p=0.04 respectively) and shorter fibre lengths (p=0.02, p=0.02 respectively) of the posterior limb of the internal capsule. Infants with psychomotor delay also had significantly higher ADC values (p=0.03) and shorter fibre lengths (p=0.002) of the callosal splenium. Fractional anisotropy values of the posterior limb of the internal capsule independently predicted motor delay and CP, with sensitivity between 80 and 100% and specificity between 66 and 69%. ADC values of the splenium independently predicted motor delay with sensitivity of 100% and specificity of 65%.
Interpretation
Diffusion tensor imaging tractography at term‐equivalent age independently predicts psychomotor delay at 2 years of age in preterm infants.
This article is commented on by Mirmiran on pages 398–399 of this issue.
Background: The brain is crucial for the control of food intake, reward, and energy homeostasis.Objective: We hypothesized that 1) brain circuits involved in energy homeostasis and reward show ...different functional connectivity patterns between obese and lean individuals and 2) food intake affects functional connectivity differentially in obese and lean individuals. Therefore, we compared the connectivity of the hypothalamus, amygdala, and posterior cingulate cortex, each probing a distinct network related to energy homeostasis and reward, between obese subjects and lean subjects in the fasting state and after meal ingestion.Design: We acquired 3 Tesla resting-state functional magnetic resonance imaging scans after an overnight fast and after ingestion of a liquid mixed meal in 46 obese female participants 19 with normal glucose tolerance and 27 with type 2 diabetes mellitus (T2DM) and 12 lean subjects. Functional connectivity of our regions of interest was assessed by using a seed-based correlation approach.Results: No significant differences between normal-glucose-tolerant and T2DM subjects were observed. In the fasting state, the total obese group had stronger hypothalamic connectivity with the medial prefrontal cortex and the dorsal striatum than did the lean subjects. The amygdala was differentially connected to the right insula in obese compared with lean subjects. Food intake dampened hypothalamic connectivity with the frontal regions in lean subjects, whereas these connections were barely affected in obese subjects.Conclusions: Our results indicate that functional connectivity in several brain networks, particularly the homeostatic and cognitive control network and the reward network, was different between obese and lean subjects. In the fasting state, obesity appears to be associated with stronger functional connectivity between brain areas involved in cognitive control, motivation, and reward, whereas these connections are largely unaffected by food intake in obese compared with lean subjects. This trial was registered at clinicaltrials.gov as NCT01167959.
Background
Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated ...the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies.
Methods
Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations.
Results
We identified 31 cohorts (n = 20,368): 19 ischemic stroke/TIA (n = 7672), 4 memory clinic (n = 1957), 3 high risk elderly (n = 1458) and 5 population-based cohorts (n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity.
Conclusions
Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.
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