Structural correlates of semantic and phonemic fluency ability in first and second languages

Category and letter fluency tasks are commonly used clinically to investigate the semantic and phonological processes central to speech production, but the neural correlates of these processes are difficult to establish with functional neuroimaging because of the relatively unconstrained nature of the tasks. This study investigated whether differential performance on semantic (category) and phonemic (letter) fluency in neurologically normal participants was reflected in regional gray matter density. The participants were 59 highly proficient speakers of 2 languages. Our findings corroborate the importance of the left inferior temporal cortex in semantic relative to phonemic fluency and show this effect to be the same in a first language (L1) and second language (L2). Additionally, we show that the pre-supplementary motor area (pre-SMA) and head of caudate bilaterally are associated with phonemic more than semantic fluency, and this effect is stronger for L2 than L1 in the caudate nuclei. To further validate these structural results, we reanalyzed previously reported functional data and found that pre-SMA and left caudate activation was higher for phonemic than semantic fluency. On the basis of our findings, we also predict that lesions to the pre-SMA and caudate nuclei may have a greater impact on phonemic than semantic fluency, particularly in L2 speakers

11β-Hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics

In aging humans and rodents, inter-individual differences in cognitive function have been ascribed to variations in long-term glucocorticoid exposure. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates the active glucocorticoid cortisol from circulating inert cortisone, thus amplifying intracellular glucocorticoid levels in some tissues. We show that 11β-HSD1, but not 11β-HSD2, mRNA is expressed in the human hippocampus, frontal cortex, and cerebellum. In two randomized, double-blind, placebo-controlled crossover studies, administration of the 11β-HSD inhibitor carbenoxolone (100 mg three times per day) improved verbal fluency (P < 0.01) after 4 weeks in 10 healthy elderly men (aged 55-75 y) and improved verbal memory (P < 0.01) after 6 weeks in 12 patients with type 2 diabetes (52-70 y). Although carbenoxolone has been reported to enhance hepatic insulin sensitivity in short-term studies, there were no changes in glycemic control or serum lipid profile, nor was plasma cortisol altered. 11β-HSD1 inhibition may be a new approach to prevent/ameliorate cognitive decline

Famous faces activate contextual associations in the parahippocampal cortex

The parahippocampal cortex (PHC) has been traditionally implicated both in place processing and in episodic memory. How could the same cortical region mediate these cognitive functions that seem quite different? We have recently proposed that the PHC should be seen as more generally mediating contextual associative processing, which is required for both navigation and memory. We therefore predicted that any associative objects should activate the PHC. To test this generalization, we investigated the extent to which common stimuli that are nonspatial by nature, namely faces, activate the PHC, although their perception is typically associated with other cortical structures. Specifically, we compared the activation elicited by famous faces, which are highly associated with rich pictorial and contextual information (e.g., Tom Cruise) and are not associated with a specific place, with activation elicited by unfamiliar faces. Consistent with our prediction, contrasting famous with unfamiliar faces revealed significant activation within the PHC. Taken collectively, these findings indicate that the PHC should be regarded as mediating contextual associations in general and not necessarily spatial or episodic information