Dissociation between the Activity of the Right Middle Frontal Gyrus and the Middle Temporal Gyrus in Processing Semantic Priming

The aim of this event-related functional magnetic resonance imaging (fMRI) study was to test whether the right middle frontal gyrus (MFG) and middle temporal gyrus (MTG) would show differential sensitivity to the effect of prime-target association strength on repetition priming. In the experimental condition (RP), the target occurred after repetitive presentation of the prime within an oddball design. In the control condition (CTR), the target followed a single presentation of the prime with equal probability of the target as in RP. To manipulate semantic overlap between the prime and the target both conditions (RP and CTR) employed either the onomatopoeia “oink” as the prime and the referent “pig” as the target (OP) or vice-versa (PO) since semantic overlap was previously shown to be greater in OP. The results showed that the left MTG was sensitive to release of adaptation while both the right MTG and MFG were sensitive to sequence regularity extraction and its verification. However, dissociated activity between OP and PO was revealed in RP only in the right MFG. Specifically, target “pig” (OP) and the physically equivalent target in CTR elicited comparable deactivations whereas target “oink” (PO) elicited less inhibited response in RP than in CTR. This interaction in the right MFG was explained by integrating these effects into a competition model between perceptual and conceptual effects in priming processing

Neonatal Brain Injury and Neuroanatomy of Memory Processing following Very Preterm Birth in Adulthood: An fMRI Study

Altered functional neuroanatomy of high-order cognitive processing has been described in very preterm individuals (born before 33 weeks of gestation; VPT) compared to controls in childhood and adolescence. However, VPT birth may be accompanied by different types of adverse neonatal events and associated brain injury, the severity of which may have differential effects on brain development and subsequent neurodevelopmental outcome. We conducted a functional magnetic resonance imaging (fMRI) study to investigate how differing degrees of neonatal brain injury, detected by neonatal ultrasounds, affect the functional neuroanatomy of memory processing in VPT young adults. We used a verbal paired associates learning task, consisting of four encoding, four cued-recall and four baseline condition blocks. To further investigate whether differences in neural activation between the groups were modulated by structural brain changes, structural MRI data were also collected. We studied 12 VPT young adults with a history of periventricular haemorrhage with associated ventricular dilatation, 17 VPT individuals with a history of uncomplicated periventricular haemorrhage, 12 individuals with normal ultrasonographic findings, and 17 controls. Results of a linear trend analysis demonstrated that during completion of the paired associates learning task right frontal and right parietal brain activation decreased as the severity of neonatal brain injury increased. There were no statistically significant between-group differences in on-line task performance and participants' intelligence quotient (IQ) at assessment. This pattern of differential activation across the groups was observed particularly in the right middle frontal gyrus during encoding and in the right posterior cingulate gyrus during recall. Structural MRI data analysis revealed that grey matter volume in the right superior temporal gyrus, right cerebellum, left middle temporal gyrus, right globus pallidus and right medial frontal gyrus decreased with increasing severity of neonatal brain injury. However, the significant between-group functional neuroanatomical differences were not directly attributable to the detected structural regional differences

Histone Deacetylase Activity Modulates Alternative Splicing

There is increasing evidence to suggest that splicing decisions are largely made when the nascent RNA is still associated with chromatin. Here we demonstrate that activity of histone deacetylases (HDACs) influences splice site selection. Using splicing-sensitive microarrays, we identified ∼700 genes whose splicing was altered after HDAC inhibition. We provided evidence that HDAC inhibition induced histone H4 acetylation and increased RNA Polymerase II (Pol II) processivity along an alternatively spliced element. In addition, HDAC inhibition reduced co-transcriptional association of the splicing regulator SRp40 with the target fibronectin exon. We further showed that the depletion of HDAC1 had similar effect on fibronectin alternative splicing as global HDAC inhibition. Importantly, this effect was reversed upon expression of mouse HDAC1 but not a catalytically inactive mutant. These results provide a molecular insight into a complex modulation of splicing by HDACs and chromatin modifications