Homozygous LAMC3 mutation links to structural and functional changes in visual attention networks.

The occipital lobe contains a substantial part of the neural machinery involved in visual perception. Mutations in the LAMC3 gene have recently been shown to cause complex bilateral occipital cortical gyration abnormalities. However, to what extent these structural changes impact visual behavior is not known. We recorded responses for two screening test batteries targeting visual function (Leuven - Perceptual Organization Screening Test, Cortical Vision Screening Test) and measured eye fixation performance in a visual attention experiment from a patient with homozygous LAMC3 gene mutation. Using voxel-based morphometry (VBM) we quantitatively assessed the extent of structural changes brought on by the genetic mutation by comparing mean cortical curvature, cortical thickness, and gray matter volume in 34 cortical areas between patient and an age-, sex-, and education-matched control group. Anatomical connectivity between these cortical areas was investigated by a structural covariance analysis. Visual screening-, and behavioral results revealed that the patient's impairments were predominantly in visuo-spatial attention. Consistent with this, VBM and structural connectivity results revealed significant structural changes in cortical regions subserving attentional functions. We conclude that the LAMC3 gene mutation affects cortical areas beyond the occipital lobe and primarily those visual functions that involve heavily distributed networks - such as visuo-spatial attention.

Cortical connectivity in the face of congenital structural changes-A case of homozygous LAMC3 mutation.

The homozygous LAMC3 gene mutation is associated with severe bilateral smoothening and thickening of the lateral occipital cortex . Despite this and further significant changes in gray matter structure, a patient harboring this mutation exhibited a range of remarkably intact perceptual abilities . One possible explanation of this perceptual sparing could be that the white matter structural integrity and functional connectivity in relevant pathways remained intact. To test this idea, we used diffusion tensor and functional magnetic resonance imaging to investigate functional connectivity in resting-state networks in major structural pathways involved in object perception and visual attention and corresponding microstructural integrity in a patient with homozygous LAMC3 mutation and sex, age, education, and socioeconomically matched healthy control group. White matter microstructural integrity results indicated widespread disruptions in both intra- and interhemispheric structural connections except inferior longitudinal fasciculus. With a few exceptions, the functional connectivity between the patient's adjacent gray matter regions of major white matter tracts of interest was conserved. In addition, functional localizers for face, object, and place areas showed similar results with a representative control, providing an explanation for the patient's intact face, place, and object recognition abilities. To generalize this finding, we also compared functional connectivity between early visual areas and face, place, and object category-selective areas, and we found that the functional connectivity of the patient was not different from the control group. Overall, our results provided complementary information about the effects of LAMC3 gene mutation on the human brain including intact temporo-occipital structural and functional connectivity that are compatible with preserved perceptual abilities.