Whole-brain connectome analysis for elucidating specific structural neural networks in idiopathic normal-pressure hydrocephalus.

OBJECTIVE

To test the hypothesis that idiopathic normal-pressure hydrocephalus (iNPH) is also associated with reproducible whole-brain structural connectivity reductions detectable by diffusion MRI connectomics, beyond the established clinical triad of gait disturbance, cognitive impairment, and urinary incontinence.

MATERIALS AND

METHODS

Twenty patients with iNPH (71-84 years; Evans index 32.1-43.5) diagnosed according to the Japanese guidelines and 20 age-matched healthy controls (70-88 years) underwent 3.0-T MRI. Distortion-corrected diffusion-weighted imaging (b = 2000s/mm2, 32 directions) was analyzed using constrained spherical deconvolution and anatomically constrained probabilistic tractography. Connectivity matrices were constructed for 84 regions (Desikan-Killiany atlas), yielding 3486 unique edges. Group differences were tested edge wise using the Mann-Whitney U test with Bonferroni-adjusted p-values; statistical significance was defined as adjusted p < 0.01, and effect sizes were quantified using the rank-biserial correlation (large effect: r > 0.5).

RESULTS

iNPH showed significantly reduced connectivity predominantly in interhemispheric edges (adjusted p < 0.01; r = 0.89-0.98). The paracentral lobule exhibited the greatest number of decreased connections (11 edges), followed by the posterior cingulate gyrus (9 edges) and the superior frontal gyrus (8 edges).

CONCLUSIONS

iNPH is associated with robust interhemispheric disconnection and prominent involvement of motor- and midline-related networks, supporting connectome-derived markers for further validation.