Lateralization of language to the left hemisphere is considered a key aspect of human brain organization. We used diffusion tensor MRI to perform in vivo virtual dissection of language pathways to assess the relationship between brain asymmetry and cognitive performance in the normal population. Our findings suggest interhemispheric differences in direct connections between Broca's and Wernicke's territories, with extreme leftward lateralization in more than half of the subjects and bilateral symmetrical distribution in only 17.5% of the subjects. Importantly, individuals with more symmetric patterns of connections are better overall at remembering words using semantic association. Moreover, preliminary analysis suggests females are more likely to have a symmetrical pattern of connections. These findings suggest that the degree of lateralization of perisylvian pathways is heterogeneous in the normal population and, paradoxically, bilateral representation, not extreme lateralization, might ultimately be advantageous for specific cognitive functions.arcuate fasciculus ͉ brain asymmetry ͉ diffusion tensor imaging ͉ language lateralization ͉ verbal memory

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BackgroundWhile current recommendations on exercise type and volume have strong experimental bases, there is no clear evidence from large-sized studies indicating whether increasing training intensity provides additional benefits to subjects with type 2 diabetes.ObjectiveTo compare the effects of moderate-to-high intensity (HI) versus low-to-moderate intensity (LI) training of equal energy cost, i.e. exercise volume, on modifiable cardiovascular risk factors.DesignPre-specified sub-analysis of the Italian Diabetes and Exercise Study (IDES), a randomized multicenter prospective trial comparing a supervised exercise intervention with standard care for 12 months (2005–2006).SettingTwenty-two outpatient diabetes clinics across Italy.PatientsSedentary patients with type 2 diabetes assigned to twice-a-week supervised progressive aerobic and resistance training plus exercise counseling (n = 303).InterventionsSubjects were randomized by center to LI (n = 142, 136 completed) or HI (n = 161, 152 completed) progressive aerobic and resistance training, i.e. at 55% or 70% of predicted maximal oxygen consumption and at 60% or 80% of predicted 1-Repetition Maximum, respectively, of equal volume.Main Outcome Measure(s)Hemoglobin (Hb) A1c and other cardiovascular risk factors; 10-year coronary heart disease (CHD) risk scores.ResultsVolume of physical activity, both supervised and non-supervised, was similar in LI and HI participants. Compared with LI training, HI training produced only clinically marginal, though statistically significant, improvements in HbA1c (mean difference −0.17% [95% confidence interval −0.44,0.10], P = 0.03), triglycerides (−0.12 mmol/l [−0.34,0.10], P = 0.02) and total cholesterol (−0.24 mmol/l [−0.46, −0.01], P = 0.04), but not in other risk factors and CHD risk scores. However, intensity was not an independent predictor of reduction of any of these parameters. Adverse event rate was similar in HI and LI subjects.ConclusionsData from the large IDES cohort indicate that, in low-fitness individuals such as sedentary subjects with type 2 diabetes, increasing exercise intensity is not harmful, but does not provide additional benefits on cardiovascular risk factors.Trial Registration www.ISRCTN.org ISRCTN-04252749.

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