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Objective  To determine the impact of Zika virus ( ZIKV ) infection on brain structure and functional organization of severely affected adult patients with neurological complications that extend beyond Guillain–Barré Syndrome ( GBS )‐like manifestations and include symptoms of the central nervous system ( CNS ).    Methods  In this first case–control neuroimaging study, we obtained structural and functional magnetic resonance images in nine rare adult patients in the subacute phase, and healthy age‐ and sex‐matched controls.  ZIKV  patients showed atypical descending and rapidly progressing peripheral nervous system ( PNS ) manifestations, and importantly, additional  CNS  presentations such as perceptual deficits. Voxel‐based morphometry was utilized to evaluate gray matter volume, and resting state functional connectivity and Network Based Statistics were applied to assess the functional organization of the brain.    Results  Gray matter volume was decreased bilaterally in motor areas (supplementary motor cortex, specifically Frontal Eye Fields) and beyond (left inferior frontal sulcus). Additionally, gray matter volume increased in right middle frontal gyrus. Functional connectivity increased in a widespread network within and across temporal lobes.    Interpretation  We provide preliminary evidence for a link between  ZIKV  neurological complications and changes in adult human brain structure and functional organization, comprising both motor‐related regions potentially secondary to prolonged  PNS  weakness, and nonsomatomotor regions indicative of  PNS ‐independent alternations. The latter included the temporal lobes, particularly vulnerable in a range of neurological conditions. While future studies into the  ZIKV ‐related neuroinflammatory mechanisms in adults are urgently needed, this study indicates that  ZIKV  infection can lead to an impact on the brain.

Impact of Zika Virus on adult human brain structure and functional organization