Decreased functional connectivity in dorsolateral prefrontal cortical networks in adult macaques with neonatal hippocampal lesions: Relations to visual working memory deficits.

Neonatal hippocampal lesions in monkeys impairs normal performance on both relational and working memory tasks, suggesting that the early lesions have impacted the normal development of prefrontal-hippocampal functional interactions necessary for normal performance on these tasks. Given that working memory processes engage distributed neuronal networks associated with the prefrontal cortex, it is critical to explore the integrity of distributed neural networks of dorsolateral prefrontal cortex (dlPFC) following neonatal hippocampal lesions in monkeys. We used resting-state functional MRI to assess functional connectivity of dlPFC networks in monkeys with neonatal neurotoxic hippocampal lesion (Neo-Hibo, n=4) and sham-operated control animals (Neo-C, n=4). Significant differences in the patterns of dlPFC functional networks were found between Groups Neo-Hibo and Neo-C. The within-group maps and the between-group comparisons yielded a highly coherent picture showing altered interactions of core regions of the working memory network (medial prefrontal cortex and posterior parietal cortex) as well as the dorsal (fundus of superior temporal area and superior temporal cortex) and ventral (V4 and infero-temporal cortex) visual processing areas in animals with Neo-Hibo lesions. Correlations between functional connectivity changes and working memory impairment in the same animals were found only between the dlPFC and visual cortical areas (V4 and infero-temporal cortex). Thus, the impact of the neonatal hippocampal lesions extends to multiple cortical areas interconnected with the dlPFC.