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.