Inter-hemispheric synchronicity and symmetry: The functional connectivity consequences of stroke and neurodegenerative disease

Stroke and neurodegenerative diseases differ along several dimensions, including their temporal trajectories -abrupt onset versus slow disease progression. Despite these differences, they can give rise to very similar cognitive impairments, such as specific forms of aphasia. What has been scarcely investigated, however, is the extent to which the underlying functional neuroplastic consequences are similar or different for these diseases. Here, for the first time, we directly compare changes in the brain’s functional network connectivity, measured with resting-state fMRI, in stroke and progressive neurological disease. Specifically, we examined two groups of individuals with chronic post-stroke aphasia or non-fluent primary progressive aphasia, matched for their behavioral profiles and distribution of left-hemisphere damage. Using previous proposals regarding the neural functional connectivity (FC) phenotype of stroke as a starting point, we compared the two diseases in terms of homotopic FC, intra-hemispheric FC changes and also the symmetry of the FC patterns between the two hemispheres. We found, first, that progressive disease showed significantly higher levels of homotopic connectivity than neurotypical controls and, further, that stroke showed the reverse pattern. For both groups these effects were found to be behaviorally relevant. In addition, within the directly impacted left hemisphere, FC changes for the two diseases were significantly correlated. In contrast, in the right hemisphere, the FC changes differed markedly between the two groups, with the progressive disease group exhibiting rather symmetrical FC changes across the hemispheres whereas the post-stroke group showed asymmetrical FC changes across the hemispheres. These findings constitute novel evidence that the functional connectivity consequences of stroke and neurodegenerative disease can be very different despite similar behavioral outcomes and damage foci. Specifically, stroke may lead to greater independence of hemispheric responses, while neurodegenerative disease may produce more symmetrical changes across the hemispheres and more synchronized activity between the two hemispheres.