PT - JOURNAL ARTICLE AU - Froudist-Walsh, Seán AU - Karolis, Vyacheslav AU - Caldinelli, Chiara AU - Brittain, Philip J. AU - Kroll, Jasmin AU - Rodríguez-Toscano, Elisa AU - Tesse, Marcello AU - Colquhoun, Matthew AU - Howes, Oliver AU - Dell'Acqua, Flavio AU - Thiebaut de Schotten, Michel AU - Murray, Robin M. AU - Williams, Steven C.R. AU - Nosarti, Chiara TI - Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study AID - 10.1523/JNEUROSCI.4769-14.2015 DP - 2015 Dec 02 TA - The Journal of Neuroscience PG - 15787--15799 VI - 35 IP - 48 4099 - http://www.jneurosci.org/content/35/48/15787.short 4100 - http://www.jneurosci.org/content/35/48/15787.full SO - J. Neurosci.2015 Dec 02; 35 AB - The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI.SIGNIFICANCE STATEMENT Here we used the example of perinatal brain injury (PBI) associated with very preterm birth to study the brain's ability to adapt to injury sustained early in life. In adulthood, individuals with PBI did not show significant deficits in working memory, but exhibited less activation in typical frontoparietal working memory areas. They also showed a relative overactivation of nontask-specific brain areas (perisylvian cortex) compared with controls, and such activation was negatively correlated with the size of white matter pathways involved in working memory (dorsal cingulum). Furthermore, this “extra” activation was associated with better working memory performance and could represent a novel compensatory mechanism following PBI. Such information could inform the development of neuroscience-based cognitive interventions following PBI.