Migraine or any headaches and white matter hyperintensities and their progression in women and men.

BACKGROUND: Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders. METHODS: Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2-3 vs. 0-1) by log-binomial regression, adjusted for confounders. RESULTS: The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454-6880) mm3 in women and 4812 (2842-8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache. CONCLUSIONS: Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research.

Smoking and short-term response to intravitreal anti-Vascular Endothelial Growth Factor injections in neovascular age-related macular degeneration.

PURPOSE: To evaluate the role of smoking status on the response to three monthly intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) injections in treatment-naive neovascular AMD (nAMD) patients. METHODS: We conducted a single-center, retrospective, case-control cohort study in Belgium. RESULTS: Intravitreal treatment (IVT) was performed in 147 eyes of 131 patients, including 92 females (70%). Mean age at the time of the first IVT was 79±9 years. Seventeen patients (13%) were actively smoking at the time of the anti-VEGF IVT. On average, active smokers were 11 years younger than non-smokers when starting IVT treatment. They also showed more frequent subretinal fluid than non-smokers (94% vs. 65%). Mann-Whitney analyses comparing change in central macular thickness and change in logarithm of the minimum angle of resolution visual acuity between active smokers and non-smokers showed no significant difference in treatment response between both groups. Likewise, no significant difference was found when comparing treatment response between patients with less than 10 pack-years (PY) (including never-smokers) and patients with over 10 PY. In a binary logistic regression model, male patients responded worse to anti-VEGF IVT than their female counterparts, with an odds ratio (OR) of 0.27 for good response. This was the only statistically significant predictor of treatment response. CONCLUSION: Our study failed to demonstrate an effect of smoking on the short-term treatment response to anti-VEGF in nAMD.

Cognitive profiles in older males and females.

Males and females are subject to differences in cognitive processing strategies, i.e. the way males and females solve cognitive tasks. So far primarily reported for younger adults, this seems to be especially important in older adults, who also show sex differences in cognitive impairments. Therefore, the aim of the current study was to examine the older adult population with respect to cognitive profiles derived from a large variety of cognitive functions. Using an exploratory component analysis with consecutive confirmatory factor analysis in a sample of 676 older adults, neuropsychological performance data in a variety of cognitive domains was decomposed into cognitive components. A general cognitive profile based on the whole group fits unequally well on the two sexes. Importantly, cognitive profiles based on either males or females differ in terms of their composition of cognitive components, i.e. three components in males versus four components in females, with a generally better model fit in females. Thus, related to the established differences in processing styles between males and females the current study found a rather decomposed (or local) cognitive profile in females while males seem to show a holistic (or global) cognitive profile, with more interrelations between different cognitive functions.

Resting-state networks in the course of aging-differential insights from studies across the lifespan vs. amongst the old.

Resting-state functional connectivity (RSFC) has widely been used to examine reorganization of functional brain networks during normal aging. The extraction of generalizable age trends, however, is hampered by differences in methodological approaches, study designs and sample characteristics. Distinct age ranges of study samples thereby represent an important aspect between studies especially due to the increase in inter-individual variability over the lifespan. The current review focuses on comparing age-related differences in RSFC in the course of the whole adult lifespan versus later decades of life. We summarize and compare studies assessing age-related differences in within- and between-network RSFC of major resting-state brain networks. Differential effects of the factor age on resting-state networks can be identified when comparing studies focusing on younger versus older adults with studies investigating effects within the older adult population. These differential effects pertain to higher order and primary processing resting-state networks to a varying extent. Especially during later decades of life, other factors beyond age might come into play to understand the high inter-individual variability in RSFC.

Age-related decrease of functional connectivity additional to gray matter atrophy in a network for movement initiation.

Healthy aging is accompanied by a decrease in cognitive and motor capacities. In a network associated with movement initiation, we investigated age-related changes of functional connectivity (FC) as well as regional atrophy in a sample of 232 healthy subjects (age range 18-85 years). To this end, voxel-based morphometry and whole-brain resting-state FC were analyzed for the supplementary motor area (SMA), anterior midcingulate cortex (aMCC) and bilateral striatum (Str). To assess the specificity of age-related effects, bilateral primary sensorimotor cortex (S1/M1) closely associated with motor execution was used as control seeds. All regions showed strong reduction of gray matter volume with age. Corrected for this regional atrophy, the FC analysis revealed an age × seed interaction for each of the bilateral Str nodes against S1/M1 with consistent age-related decrease in FC with bilateral caudate nucleus and anterior putamen. Specific age-dependent FC decline of SMA was found in bilateral central insula and the adjacent frontal operculum. aMCC showed exclusive age-related decoupling from the anterior cingulate motor area. The present study demonstrates network as well as node-specific age-dependent FC decline of the SMA and aMCC to highly integrative cortical areas involved in cognitive motor control. FC decrease in addition to gray matter atrophy within the Str may provide a substrate for the declining motor control in elderly. Finally, age-related FC changes in both the network for movement initiation as well as the network for motor execution are not explained by regional atrophy in the healthy aging brain.

Cytoarchitecture, probability maps and functions of the human frontal pole.

The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities.

Differentiated parietal connectivity of frontal regions for "what" and "where" memory.

In a previous meta-analysis across almost 200 neuroimaging experiments, working memory for object location showed significantly stronger convergence on the posterior superior frontal gyrus, whereas working memory for identity showed stronger convergence on the posterior inferior frontal gyrus (dorsal to, but overlapping with Brodmann's area BA 44). As similar locations have been discussed as part of a dorsal frontal-superior parietal reach system and an inferior frontal grasp system, the aim of the present study was to test whether the regions of working-memory related "what" and "where" processing show a similar distinction in parietal connectivity. The regions that were found in the previous meta-analysis were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modelling and task-independent resting state correlations. While the ventral seed showed significantly stronger connectivity with the bilateral intraparietal sulcus (IPS), the dorsal seed showed stronger connectivity with the bilateral posterior inferior parietal and the medial superior parietal lobule. The observed connections of regions involved in memory for object location and identity thus clearly demonstrate a distinction into separate pathways that resemble the parietal connectivity patterns of the dorsal and ventral premotor cortex in non-human primates and humans. It may hence be speculated that memory for a particular location and reaching towards it as well as object memory and finger positioning for manipulation may rely on shared neural systems. Moreover, the ensuing regions, in turn, featured differential connectivity with the bilateral ventral and dorsal extrastriate cortex, suggesting largely segregated bilateral connectivity pathways from the dorsal visual cortex via the superior and inferior parietal lobules to the dorsal posterior frontal cortex and from the ventral visual cortex via the IPS to the ventral posterior frontal cortex that may underlie action and cognition.

Meta-analytical definition and functional connectivity of the human vestibular cortex.

Contrary to most other sensory systems, no consensus has been reached within the scientific community about the exact locations and functions of human cortical areas processing vestibular information. Metaanalytical modelling using activation likelihood estimation (ALE) for the integration of neuroimaging results has already been successfully applied to several distinct tasks, thereby revealing the cortical localization of cognitive functions. We used the same algorithm and technique with all available and suitable PET and fMRI studies employing a vestibular stimulus. Most consistently across 28 experiments vestibular stimuli evoked activity in the right hemispheric parietal opercular area OP 2 implicating it as the core region for vestibular processing. Furthermore, we took our primary results as a seeding point and fed them into a functional connectivity analysis based on resting-state oscillations in 100 healthy subjects. This subsequent calculation confirmed direct connections of the area OP 2 with every other region found in the meta-analysis, in particular temporo-parietal regions, premotor cortex, and the midcingulate gyrus. Thus revealing a joint vestibular network in accordance with a concept from animal literature termed the inner vestibular circle. Moreover, there was also a significant vestibular connectivity overlap with frontal but not parietal cortical centres responsible for the generation of saccadic eye movements, likely to be involved in nystagmus fast phase generation. This was shown in an additional ocular motor meta-analysis. We conclude that the cytoarchitectonic area OP 2 in the parietal operculum, embedded in a joint vestibular network, should be the primary candidate for the human vestibular cortex. This area may represent the human homologue to the vestibular area PIVC as proposed by Guldin and Grüsser in non-human primates.

ALE meta-analysis on facial judgments of trustworthiness and attractiveness.

Faces convey a multitude of information in social interaction, among which are trustworthiness and attractiveness. Humans process and evaluate these two dimensions very quickly due to their great adaptive importance. Trustworthiness evaluation is crucial for modulating behavior toward strangers; attractiveness evaluation is a crucial factor for mate selection, possibly providing cues for reproductive success. As both dimensions rapidly guide social behavior, this study tests the hypothesis that both judgments may be subserved by overlapping brain networks. To this end, we conducted an activation likelihood estimation meta-analysis on 16 functional magnetic resonance imaging studies pertaining to facial judgments of trustworthiness and attractiveness. Throughout combined, individual, and conjunction analyses on those two facial judgments, we observed consistent maxima in the amygdala which corroborates our initial hypothesis. This finding supports the contemporary paradigm shift extending the amygdala's role from dominantly processing negative emotional stimuli to processing socially relevant ones. We speculate that the amygdala filters sensory information with evolutionarily conserved relevance. Our data suggest that such a role includes not only "fight-or-flight" decisions but also social behaviors with longer term pay-off schedules, e.g., trustworthiness and attractiveness evaluation.

Functional heterogeneity of inferior parietal cortex during mathematical cognition assessed with cytoarchitectonic probability maps.

Although the inferior parietal cortex (IPC) has been consistently implicated in mathematical cognition, the functional roles of its subdivisions are poorly understood. We address this problem using probabilistic cytoarchitectonic maps of IPC subdivisions intraparietal sulcus (IPS), angular gyrus (AG), and supramarginal gyrus. We quantified IPC responses relative to task difficulty and individual differences in task proficiency during mental arithmetic (MA) tasks performed with Arabic (MA-A) and Roman (MA-R) numerals. The 2 tasks showed similar levels of activation in 3 distinct IPS areas, hIP1, hIP2, and hIP3, suggesting their obligatory role in MA. Both AG areas, PGa and PGp, were strongly deactivated in both tasks, with stronger deactivations in posterior area PGp. Compared with the more difficult MA-R task, the MA-A task showed greater responses in both AG areas, but this effect was driven by less deactivation in the MA-A task. AG deactivations showed prominent overlap with lateral parietal nodes of the default mode network, suggesting a nonspecific role in MA. In both tasks, greater bilateral AG deactivation was associated with poorer performance. Our findings suggest a close link between IPC structure and function and they provide new evidence for behaviorally salient functional heterogeneity within the IPC during mathematical cognition.

[Foreign body reaction after lens implantation. Correlation between visual acuity and density of giant cells]. / Fremdkörperreaktion nach Linsenimplantation. Beziehung zwischen Visus und Dichte der Riesenzellen.

In the early postoperative stage giant cells often appear on IOLs. Independent of this, a foreign-body reaction may start about 3 months after surgery from posterior synechia. Foreign-body reaction occur more frequently in diabetic patients or patients with glaucoma. In a prospective trial, we examined the surface of the IOLs from 115 patients with diabetes or glaucoma using specular microscopy. We compared the maximal density of the cells to visual acuity. One week and 1 month after surgery, the maximal density of giant cells was between 0 und 20/mm2; vision (median) was independent of the giant cell density in all groups between 20/25 and 20/30. Three months after surgery, the maximal density of giant cells was between 0 und 35/mm2; vision (median) was 20/25 in patients with no giant cells or cell densities up to 15/mm2. Seven patients had cell densities between 16 and 35/mm2; visual acuity (median) was 20/125. The difference was significance was (P < or = 0.05). Six months and 1 year later after surgery, the maximal density of giant cells was between 0 and 41/mm2; the vision (median) in patients with giant cell densities up to 15/mm2 was between 20/20 and 20/25. In five examinations the cell densities were found to be in the range of 16 to 40/mm2; visual acuity (median) was 20/80 in these cases. The difference is not significant (P < or = 0.05). A foreign-body reaction with more than 15 giant cells/mm2 is a rare complication of cataract surgery with lens implantation. Three months after surgery, this complication correlates with poor vision.

Problems identified with home infusion pumps.

A variety of infusion pumps and devices are available on the market today. In this article, the authors examine these products based on questionnaires sent out to typical consumers, including hospitals and caregivers. Using the results of this questionnaire, the authors identify whether or not users of home infusion pumps and devices find them difficult to operate.

Urinary arginine-vasopressin (AVP) excretion in cystic fibrosis (CF).

Free water handling is impaired in chronic obstructive lung disease (COLD). We studied the role of AVP in this mechanism with a sensitive urinary AVP radioimmunoassay (RIA) in 13 patients with CF. The mean age was 14.7 +/- 1.27 SE years. The control group was age and sex matched. While the 24-hour urine volume was not significant different in both groups, urine osmolality was higher in CF (788 mosmol/kg +/- 182 SE vs. 622 mosmol/kg +/- 218 SE; p = 0.05). The 24-hour urinary AVP excretion in CF patients was found to be significantly elevated (174 ng/day +/- 99 SE vs. 74 ng/day +/- 48 SE; p = 0.01). This difference becomes even greater if these values are corrected for body weight (4.4 ng/(kg X day) +/- 2.1 SE vs. 1.5 ng/(kg X day) +/- 0.9 SE; p = 0.005). Lung function studies were available in 8 patients. We used a body plethysmograph to measure FEV1 (1 sec forced expiratory volume) and MEF25 (forced expiratory flow at 25% of vital capacity) as sensitive indices of airway obstruction. There was a significant negative correlation between urinary AVP excretion and MEF25 (r = .76) and FEV1 (r = .65): the more pronounced the airway obstruction the higher the AVP excretion. We conclude that AVP plays a major role in the impaired water handling in COLD. Increased AVP secretion is already present under clinically stable conditions and is dependent on the degree of airway obstruction. In treating those patients one has to be aware of the possibility of water intoxication.

[Presentation of the cooperative study COALL-80 on treatment of childhood ALL (author's transl)]. / Vorstellung der kooperativen Studie COALL-80 zur Behandlung der akuten lymphoblastischen Leukämie (ALL) im Kindesalter.

The cooperative study COALL-80 is derived from the BFM-78-study. The aim of the study is a reduction of the initial therapy-morbidity and -mortality without loss of efficacy by omitting asparaginase from the four drug-induction regimen and interposing it between induction- and CNS-therapy phase. The expected two years disease free survival rate of a pilot study will be 82%. This finding is hitherto comparable with the BFM-study results.

[ALL-study series of Hamburg (author's transl)]. / Hamburger ALL-Studien.

From 1971 through 1979 145 newly diagnosed patients with ALL have been treated within a series of consecutive studies. Study I corresponds to branch A of the 1972 DAL study. In the following studies the induction therapy has been escalated stepwise with the continuation therapy remaining mostly unchanged. Thereby the disease free survival rates increased from 75 to 94% after one year and from 32 to 60% after 4 years respectively. CNS-relapse mainly occurred during the second year of treatment. Their incidence rose from 5% to more than 10% in connection with a change in the radiation portal. Since another correction of the portals with special consideration of the paramedian lower border of the skull base no more CNS-relapses have been observed until now. The actual cooperative ALL-study follows a modified BFM-protocol with postponed asparaginase in hoping to achieve reduced initial morbidity and at least equal good survival times.