Basal ganglia volume predicts speed processing performance in obese adolescents

La obesidad se ha relacionado con cambios estructurales en los ganglios basales y alteraciones en dominios transversales como la velocidad de procesamiento. El objetivo del presente estudio es investigar la relación entre velocidad de procesamiento y volumen de los ganglios basales en adolescentes con y sin obesidad. Treinta y tres participantes obesos y treinta y tres con peso normal fueron resonados (Siemens 3T Trio) y evaluados neuropsicológicamente. Se compararon los resultados de un índice de velocidad y la ratio de los ganglios basales controlando por edad, sexo y tamaño de la cabeza. Se realizaron regresiones lineales con las estructuras relacionadas con este índice. Se encontraron diferencias en el índice de velocidad, pero no en la ratio de los ganglios basales. El grupo con obesidad mostró una correlación positiva entre velocidad y ratio del globo pálido derecho (r= .41; p= .021). No hallamos relaciones significativas en el grupo normopeso. La ratio del globo pálido derecho predijo parte del rendimiento en velocidad en adolescentes obesos. Las diferencias en velocidad de procesamiento entre adolescentes con y sin obesidad podrían estar moderadas por el tamaño de estructuras subcorticales como el globo pálido.Obesity is related to structural changes in basal ganglia and alterations among transversal domains such as speed processing. The aim of the study is to address the relationship between speed processing and basal ganglia volumes in adolescents with and without obesity. Thirty-three obese and 33 normal-weight participants underwent MRI acquisition (Siemens 3T Trio) and neuropsychological assessment to obtain an index of speed processing. Speed processing index and basal ganglia ratios (VolBrain software) were compared controlling for age, sex and head size. Linear regressions were conducted in the structures related to such index. Groups differed for speed processing index, but did not differ for basal ganglia ratios. The obese group showed positive correlations between speed processing index and the right globus pallidum ratio (r= .41; p= .021). None relationship was found among normal-weight adolescents. Concretely, the right globus pallidum ratio predicted part of the performance in speed in obese participants. The differences in speed processing between adolescents with and without obesity might be mediated by the size of subcortical structures such as the globus pallidum

Hypoxia Disruption of Vertebrate CNS Pathfinding through EphrinB2 Is Rescued by Magnesium

The mechanisms of hypoxic injury to the developing human brain are poorly understood, despite being a major cause of chronic neurodevelopmental impairments. Recent work in the invertebrate Caenorhabditis elegans has shown that hypoxia causes discrete axon pathfinding errors in certain interneurons and motorneurons. However, it is unknown whether developmental hypoxia would have similar effects in a vertebrate nervous system. We have found that developmental hypoxic injury disrupts pathfinding of forebrain neurons in zebrafish (Danio rerio), leading to errors in which commissural axons fail to cross the midline. The pathfinding defects result from activation of the hypoxia-inducible transcription factor (hif1) pathway and are mimicked by chemical inducers of the hif1 pathway or by expression of constitutively active hif1α. Further, we found that blocking transcriptional activation by hif1α helped prevent the guidance defects. We identified ephrinB2a as a target of hif1 pathway activation, showed that knock-down of ephrinB2a rescued the guidance errors, and showed that the receptor ephA4a is expressed in a pattern complementary to the misrouting axons. By targeting a constitutively active form of ephrinB2a to specific neurons, we found that ephrinB2a mediates the pathfinding errors via a reverse-signaling mechanism. Finally, magnesium sulfate, used to improve neurodevelopmental outcomes in preterm births, protects against pathfinding errors by preventing upregulation of ephrinB2a. These results demonstrate that evolutionarily conserved genetic pathways regulate connectivity changes in the CNS in response to hypoxia, and they support a potential neuroprotective role for magnesium

Genetic modulation of neural response during working memory in healthy individuals: interaction of glucocorticoid receptor and dopaminergic genes

Suboptimal performance in working memory (WM) tasks and inefficient prefrontal cortex functioning are related to dysregulation of dopaminergic (DA) and hypothalamic-pituitary-adrenal systems. The aim of the present study was to investigate the joint effect of genetic polymorphisms coding for DA catabolism and glucocorticoid receptor (GR, NR3C1) on brain functioning. The study group (90 right-handed white Caucasian healthy individuals) underwent functional magnetic resonance imaging experiments to examine blood oxygenation level dependent (BOLD) response during a WM task with varying cognitive load (1-, 2- and 3-back). We have also examined skin conductance response (SCR) during the WM task and resting-state cerebral blood flow with continuous arterial spin labelling. The genetic markers of interest included Catechol-O-Methyl-Transferase (COMT) (Met158Val) and NR3C1 single-nucleotide polymorphisms (BclI C/G rs41423247, 9β A/G rs6198 and rs1866388 A/G). Haplotype-based analyses showed (i) a significant effect of COMT polymorphism on left anterior cingulate cortex, with greater deactivation in Met carriers than in Val/Val homozygotes; (ii) a significant effect of BclI polymorphism on right dorsolateral prefrontal cortex (DLPFC), with greater activation in G/G carriers than in C carriers and (iii) an interactive effect of BclI (G/G) and COMT (Met/Met) polymorphisms, which was associated with greater activation in right DLPFC. These effects remained significant after controlling for whole-brain resting-state blood flow. SCR amplitude was positively correlated with right DLPFC activation during WM. This study demonstrated that GR and COMT markers exert their separate, as well as interactive, effects on DLPFC function. Epistasis of COMT and BclI minor alleles is associated with higher activation, suggesting lower efficiency, of DLPFC during WM