Thalamo-cortical circuitry in PVL

Project Summary/Abstract
Infants born prematurely are predisposed to hypoxic-ischemic (HI) injury such as periventricular leukomalacia
(PVL), resulting in developmental disturbances to the thalamus, white matter, and cerebral cortex. As a
consequence, survivors of PVL frequently demonstrate visual impairments to varying degrees. Because the
thalamus is critical to visual processing, visual dysfunctions may be more severe if the thalamus is affected as
a consequence of the HI insult. Yet, the effects of PVL on the developing thalamo-cortical network are unclear.
In particular, it is currently not known how aberrant thalamo-cortical connectivity or altered volume of thalamic
nuclei contribute to the deficits in visual processing that are commonly observed in individuals with PVL. To
this end, the overall goal of the current study is to address the hypothesis that visual perceptual processing
deficits may be more severe in individuals with PVL who have decreased volume of visual thalamic nuclei,
distinct changes in myelination of thalamo-cortical networks, or atypical thalamo-cortical connectivity. We have
developed a cutting-edge multimodal MRI approach consisting of morphometric analysis of individual thalamic
nuclei, diffusion kurtosis imaging (DKI), high angular resolution diffusion imaging (HARDI), myelin water
fraction maps, and network connectivity analyses that will be used in conjunction with a battery of tests of
visual perceptual functions to determine the link between thalamic neuronal loss, thalamo-cortical connectivity,
and visual perceptual processing abilities. A total of 36 individuals with PVL will be recruited, along with a
cohort of 36 typically-developing controls. A rigorous statistical plan will use multiple levels of analysis to
investigate the differences in behavioral and neuroimaging variables between individuals with PVL and
controls, as well as the correlation between outcome measures. A series of regression analyses will evaluate
the associations of neuroimaging variables with PVL and functional vision. Models will also consider the effects
of age and gender on neuroimaging and behavioral outcomes. The unique combination of neuroimaging
modalities utilized in this proposed study will provide complementary insight regarding the complex interplay
between preterm HI damage in PVL and the resulting changes in thalamic development, and ultimately relate
these findings to visual perceptual deficits. This study will contribute to our understanding of the impact of PVL
on the establishment and myelination of the thalamo-cortical networks involved with visual perceptual
processes, providing evidence-based biomarkers that can be used to evaluate future therapeutic approaches.

Grant Number: 5R01EY030877-06
NIH Institute/Center: NIH
Principal Investigator: Corinna Bauer