Edited by Marcus E. Raichle, Washington University in St. Louis, St. Louis, MO, and approved April 7, 2015 (received for review December 10, 2014)
We investigated the way in which the human thalamus and cortex are functionally connected at the time of normal birth. We found the functional parcellation of the thalamus to be a good facsimile of that found in adult studies. However, although primary cortical regions were almost entirely connected to specific thalamic regions, heteromodal cortex was more widely connected to multiple thalamic regions, giving the potential for an integrative role for these circuits. Development seemed to have been modulated by the experience of premature extrauterine life, with an increase in connectivity to primary sensory cortex, but reduced connectivity between areas of the thalamus and heteromodal cortex known to support higher cognitive functions.
Connections between the thalamus and cortex develop rapidly before birth, and aberrant cerebral maturation during this period may underlie a number of neurodevelopmental disorders. To define functional thalamocortical connectivity at the normal time of birth, we used functional MRI (fMRI) to measure blood oxygen level-dependent (BOLD) signals in 66 infants, 47 of whom were at high risk of neurocognitive impairment because of birth before 33 wk of gestation and 19 of whom were term infants. We segmented the thalamus based on correlation with functionally defined cortical components using independent component analysis (ICA) and seed-based correlations. After parcellating the cortex using ICA and segmenting the thalamus based on dominant connections with cortical parcellations, we observed a near-facsimile of the adult functional parcellation. Additional analysis revealed that BOLD signal in heteromodal association cortex typically had more widespread and overlapping thalamic representations than primary sensory cortex. Notably, more extreme prematurity was associated with increased functional connectivity between thalamus and lateral primary sensory cortex but reduced connectivity between thalamus and cortex in the prefrontal, insular and anterior cingulate regions. This work suggests that, in early infancy, functional integration through thalamocortical connections depends on significant functional overlap in the topographic organization of the thalamus and that the experience of premature extrauterine life modulates network development, altering the maturation of networks thought to support salience, executive, integrative, and cognitive functions.
Author contributions: H.T., C.F.B., S.J.C., and A.D.E. designed research; H.T., C.F.B., P.N., A.E., S.J.C., N.K., T.A., N.T., M.A.R., D.A., N.G.-C., and J.V.H. performed research; H.T., C.F.B., A.M., and J.V.H. contributed new reagents/analytic tools; H.T., J.O., and A.M. analyzed data; and H.T., C.F.B., J.O., G.B., P.N., A.M., A.E., S.J.C., N.K., T.A., N.T., M.A.R., D.A., N.G.-C., J.V.H., and A.D.E. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
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