Gunther Ladurner

A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans

Obesity is the most common nutritional disorder in Western society. Uncoupling protein-2 (UCP2) is a recently identified member of the mitochondrial transporter superfamily that is expressed in many tissues, including adipose tissue. Like its close relatives UCP1 and UCP3, UCP2 uncouples proton entry in the mitochondrial matrix from ATP synthesis and is therefore a candidate gene for obesity. We show here that a common G/A polymorphism in the UCP2 promoter region is associated with enhanced adipose tissue mRNA expression in vivo and results in increased transcription of a reporter gene in the human adipocyte cell line PAZ-6. In analyzing 340 obese and 256 never-obese middle-aged subjects, we found a modest but significant reduction in obesity prevalence associated with the less-common allele. We confirmed this association in a population-based sample of 791 middle-aged subjects from the same geographic area. Despite its modest effect, but because of its high frequency (∼63%), the more-common risk allele conferred a relatively large population-attributable risk accounting for 15% of the obesity in the population studied.

The visual word form area and the frequency with which words are encountered: evidence from a parametric fMRI study.

Cohen and Dehaene et al. proposed that the Visual Word Form Area (VWFA) in the left midfusiform gyrus, contrary to its name, is limited to the extraction of an abstract letter string and not involved in proper visual word recognition. We examined this prelexical function of the VWFA by a parametric block design with five levels of written word frequency. The lowest level was represented by pseudowords and the highest level by words of very high frequency. Contrary to the assumed prelexical function of the VWFA, increasing frequency was associated with decreasing brain activation in a large posterior cluster of the left hemisphere including middle and posterior fusiform regions. The same negative relation between frequency and activation was found in several left frontal clusters. The relation of increasing frequency and decreasing activation in occipitotemporal regions corresponds to a similar relation in the same brain regions found by studies which experimentally manipulated object or face familiarity. This convergence suggests that fusiform regions are specialized for extracting and storing abstract patterns when processing visual objects and these patterns serve as recognition units in subsequent encounters with the same objects.

Thinking of mental and other representations: The roles of left and right temporo-parietal junction

Abstract Adopting new versions of the false belief and “false” photo vignettes used by Saxe & Kanwisher (2003) we were able to show activation in all five areas previously reported. Activations by added false sign and temporal change control vignettes in these areas showed that the right temporo-parietal junction (TPJ-R) is specifically associated with processing mental states like belief. In contrast, TPJ-L was also activated by false signs suggesting an association with processing perspective differences for mental and non-mental objects in line with work on visual perspective tasks. A similar, but less clearly interpretable pattern of activations was also found in the middle temporal gyrus, precuneus and in the MPFC. These results are discussed in relation to findings in normal development where false belief and false sign tasks associate more strongly with each other than does each of them with the “false” photo task.

The Metabolic Syndrome Is a Stronger Risk Factor for Early Carotid Atherosclerosis in Women Than in Men

Background and Purpose— The metabolic syndrome (MetS) is associated with an increased risk for subsequent development of type 2 diabetes mellitus, cardiovascular disease, and stroke. Type 2 diabetes increases the risk of stroke and coronary heart disease in women to a greater extent than in men, and thus the question arises whether there are sex differences in the association of early atherosclerosis and MetS. Methods— 1588 middle-aged Austrian subjects (1001 males, 587 females) were included in the present study. MetS was defined by the criteria of the National Cholesterol Education Program Adult Treatment Panel III. Early atherosclerosis was assessed by intima-media thickness (IMT) and extent of plaques (B-score) of the carotid arteries. Results— B-score and carotid artery IMT parameters were significantly higher in subjects with the MetS. After adjustment for established risk factors, the difference in B-score remained significant only in women. Computed common carotid artery IMT values using general linear model equations with age, body mass index, and low-density lipoprotein cholesterol as covariates displayed the highest values for men with MetS (811.8±9.5 &mgr;m). Women with MetS (797.6±15 &mgr;m) and men without the syndrome (788.8±5 &mgr;m) showed similar IMTs, whereas women without the MetS presented significantly lower values (735.6±7 &mgr;m). Among the subcomponents of the MetS, high-density lipoprotein cholesterol showed the strongest impact on IMT in men, whereas blood glucose ranked first in women. Conclusions— The effect of MetS on early atherosclerosis is more pronounced in females. The impact of the components of MetS on carotid IMT differs between men and women.

Temporo-parietal junction activity in theory-of-mind tasks: Falseness, beliefs, or attention

By combining the false belief (FB) and photo (PH) vignettes to identify theory-of-mind areas with the false sign (FS) vignettes, we re-establish the functional asymmetry between the left and right temporo-parietal junction (TPJ). The right TPJ (TPJ-R) is specially sensitive to processing belief information, whereas the left TPJ (TPJ-L) is equally responsible for FBs as well as FSs. Measuring BOLD at two time points in each vignette, at the time the FB-inducing information (or lack of information) is presented and at the time the test question is processed, made clear that the FB is processed spontaneously as soon as the relevant information is presented and not on demand for answering the question in contrast to extant behavioral data. Finally, a fourth, true belief vignette (TB) required teleological reasoning, that is, prediction of a rational action without any doubts being raised about the adequacy of the actors information about reality. Activation by this vignette supported claims that the TPJ-R is activated by TBs as well as FBs.

Developmental dyslexia: Gray matter abnormalities in the occipitotemporal cortex

Functional neuroimaging studies have consistently demonstrated less activation of the left occipitotemporal cortex in dyslexic readers. This region is considered critical for skilled reading and damage to it in adult readers leads to severe deficits in reading ability. In contrast to these findings, structural abnormalities in the occipitotemporal cortex were not consistently found to date. We used optimized Voxel Based Morphometry with T1 weighted MR images to investigate gray matter volume in 13 dyslexic and 15 nonimpaired reading adolescents (age 14–16). Less gray matter volume for dyslexic readers was found in the left and right fusiform gyrus, the bilateral anterior cerebellum and in the right supramarginal gyrus. Decreased gray matter volume in the left and right fusiform gyrus of dyslexic readers highlights the importance of this brain region for developmental dyslexia. The structural abnormalities in the right occipitotemporal cortex suggest that dyslexia may be such a persistent disorder because an occipitotemporal reading area, critical for skilled reading, cannot develop in any hemisphere. The extended areas of reduced gray matter volume in dyslexic readers in the cerebellum suggest that structural abnormalities in the cerebellum are also strongly associated with dyslexia and warrant further investigation. Hum Brain Mapp, 2008.

Taxi vs. Taksi: On Orthographic Word Recognition in the Left Ventral Occipitotemporal Cortex

The importance of the left occipitotemporal cortex for visual word processing is highlighted by numerous functional neuroimaging studies, but the precise function of the visual word form area (VWFA) in this brain region is still under debate. The present functional magnetic resonance imaging study varied orthographic familiarity independent from phonological-semantic familiarity by presenting orthographically familiar and orthographically unfamiliar forms (pseudohomophones) of the same words in a phonological lexical decision task. Consistent with orthographic word recognition in the VWFA, we found lower activation for familiar compared with unfamiliar forms, but no difference between pseudohomophones and pseudowords. This orthographic familiarity effect in the VWFA differed from the phonological familiarity effect in left frontal regions, where phonologically unfamiliar pseudowords led to higher activation than phonologically familiar pseudohomophones. We suggest that the VWFA not only computes letter string representations but also hosts word-specific orthographic representations. These representations function as recognition units with the effect that letter strings that readily match with stored representations lead to less activation than letter strings that do not.

Evidence for a dysfunction of left posterior reading areas in German dyslexic readers.

The brain activity during a sentence reading task and a visual control task was examined with fMRI in 13 German dyslexic readers and 15 age-matched fluent readers (age: 14-16 years). These participants came from a longitudinal study and the dyslexic readers exhibited a persistent reading fluency deficit from early on. For the first time with German dyslexic readers, and in correspondence with the majority of functional imaging studies, we found reduced dyslexic activation in the left occipitotemporal cortex and in a small region of the left supramarginal gyrus. Enhanced activation was found in left inferior frontal and subcortical regions.

Plasma Adiponectin Levels and Sonographic Phenotypes of Subclinical Carotid Artery Atherosclerosis. Data From the SAPHIR Study

Background and Purpose— Adipose tissue produces and secretes a number of bioactive molecules, conceptualized as adipocytokines. Adiponectin has been identified as one of the adipocytokines, and hypoadiponectinemia was demonstrated in patients with obesity, diabetes mellitus, and coronary artery disease. Whether decreased adiponectin levels are cause or consequence is an important issue in the discussion on the association between adiponectin and atherosclerosis. In the present study, we investigated the association of plasma adiponectin levels with sonographic phenotypes of subclinical atherosclerosis, which may represent different stages of disease as well as common and distinct determinants. Methods— A total of 1515 middle-aged healthy white subjects (940 males and 575 females) were included. Common carotid artery intima-media thickness (CIMT) and presence of atherosclerotic plaques were assessed by B-mode ultrasound. Results— After adjustment for established risk factors, per 1 &mgr;g/mL decrease in adiponectin CIMT increased on the average by 3.48 &mgr;m in males (95% CI, 1.23 to 5.73 &mgr;m) and by 2.39 &mgr;m in females (95% CI, 0.50 to 4.27 &mgr;m). After dichotomizing adiponectin levels at the median and adjustment for established risk factors, the mean difference of CIMT between subjects with low and high adiponectin levels was 20.42 &mgr;m in men (95% CI, 6.80 to 34.04; P=0.003) and 20.75 &mgr;m in women (95% CI, 1.08 to 40.42; P=0.039). No significant relationship was found between adiponectin levels and presence of atherosclerotic plaques. Conclusion— Our results demonstrate an independent negative association of adiponectin levels and CIMT, whereas no relationship with presence of atherosclerotic plaques was found, thus suggesting hypoadiponectinemia as a risk factor in the development of early atherosclerosis.

Menstrual cycle and hormonal contraceptive use modulate human brain structure.

Sex differences in human brain structure have repeatedly been described, but results are inconsistent. However, these studies hardly controlled for cycle phase of women or the use of hormonal contraceptives. Our study shows that these factors are not negligible, but have a considerable influence on human brain structure. We acquired high-resolution structural images from the brains of 14 men, 14 women, who did not use, and 14 women, who did use hormonal contraceptives. Women, who did not use hormonal contraceptives, were scanned twice, once during their early follicular and once during their mid-luteal cycle-phase. Regional gray matter volumes were compared by voxel-based morphometry. Men had larger hippocampi, parahippocampal and fusiform gyri, amygdalae and basal ganglia than women. Women showed larger gray matter volumes in the prefrontal cortex, pre- and postcentral gyri. These sex-dependent effects were modulated by menstrual cycle phases and hormonal contraceptives. We found larger volumes in the right fusiform/parahippocampal gyrus during early follicular compared to mid-luteal cycle phase. Women using hormonal contraceptives showed significantly larger prefrontal cortices, pre- and postcentral gyri, parahippocampal and fusiform gyri and temporal regions, compared to women not using contraceptives.