Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study

Abstract

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.Key words: fMRI; perinatal brain injury; plasticity; spherical deconvolution; tractography; working memory Significance StatementHere 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.

A multimodal imaging study of recognition memory in very preterm born adults

“…Specifically, increased activation in the LOC in the very preterm group was associated with worse task performance, which may reflect weaker sensory prediction, and with structural integrity of memory‐related white matter tracts. These findings are inconsistent with our previous study, which indicated that increased activation in a perisylvian region was associated with functional adaptation to successfully perform a working memory task (Froudist‐Walsh et al, ). These contrasting results may suggest that altered patterns of activation may not always be compensatory, but they may also be maladaptive (Turkeltauba et al, ).…”

“…This study complements and extends our previous work, which focused on working memory (Froudist‐Walsh et al, ), to assess different types of memory. It has been suggested that working memory may be a more promising target for cognitive training than recognition memory in very preterm individuals, as core working memory regions are not fully developed until adulthood and have more potential for compensatory functional adaptation, whereas core recognition memory regions reach maturity during childhood, therefore recognition memory impairments may be permanent and less amenable to improvement (Nosarti and Froudist‐Walsh, ).…”

“…Based on the evidence assigning a critical role to the hippocampi in recognition memory processing, and reporting structural hippocampal alterations following very preterm birth, we predicted that adults born very preterm would show decreased neural activation in hippocampi during on-line task performance. In addition, based on results of our recent multimodal neuroimaging study of working memory using the same cohort, which found significant associations in very preterm born adults between neural activation and volume of task-specific white matter tracts (Froudist-Walsh et al, 2015), we predicted that differential neural responses in the preterm group would be associated with white matter alterations of the fornix and the cingulum. Finally, we expected white matter connectivity to underlie the changes of local brain activations and volumetric characteristics.…”

A machine learning investigation of volumetric and functional MRI abnormalities in adults born preterm

“…individuals, which partly overlap with structural changes (Baldoli et al, 2015;Bauml et al, 2014;Froudist-Walsh et al, 2015;Meng et al, 2015). These abnormalities have been linked to pathophysiological cascades that begin at birth and radiate from subcortical injuries, such as hypoxic-ischemic damage to the periventricular white matter (de Vries, Benders, & Groenendaal, 2015;Thompson et al, 2014;Tsimis et al, 2015).…”

“…For example, a common hypothesis is that periventricular white matter injury impacts the development of premyelinating oligodendrocytes and subplate neurons resulting in an impaired development of thalamo-cortical connectivity (Grothe et al, 2017;Hoerder-Suabedissen & Molnar, 2015;Thompson et al, 2014), which then leads to the reduced thalamus gray matter volume (GMV) and related widely distributed white matter changes seen in adulthood Joseph J. Volpe, 2009). Structural damage and downstream abnormalities are also thought to be linked to functional changes, as evident in univariate task-based and resting-state MRI studies (Baldoli et al, 2015;Bauml et al, 2014;Froudist-Walsh et al, 2015;Meng et al, 2015;Shang et al, 2018).…”