Fig. 7. Pulsatile GnRH improves patient brain connectivity, cognition.

(A-F) Biochemical profile at baseline (BL, blue dots, n=7) and after 6-month pulsatile GnRH therapy (6M, blue triangles, n=7), compared to healthy age- and sex-matched controls (C, open circles, n=5 for inhibin-B and n=6 for all the other parameters). (G-L) Results of cognitive tests in male Down syndrome patients (n=7) at BL (blue dots) and after 6M of GnRH therapy (blue triangles): MoCA total score, visuo-spatial index, executive index, attention index, memory index and Token test score. (M) 3D-drawings representing a cube and a bed, part of visuospatial index score of the MoCA at BL and 6M for each subject (S1-S7). S2, S3, S5 and S7 improved at 6M. (N) Statistical parametric maps of brain anatomy differences between DS patients (n=8) and age-matched male controls (n=44) after p_FWE<0.05 correction for multiple comparisons at the whole-brain level. Voxel-based quantification of magnetization transfer (MT) saturation maps reveal volume loss in the cerebellum, anterior cingulate cortex, supplementary motor cortex, substantia nigra, thalamus, insula and primary motor cortex M1, and loss of myelin content in the thalamus, primary sensorimotor cortex S1/M1, angular gyrus, insula, and superior frontal and temporal gyri bilaterally. (O) Resting-state functional MRI comparison of functional connectivity in DS (n=7) at BL and after 6MGnRH therapy in the visual (including all occipital regions, the lingual gyrus and the cuneus) and sensorimotor (pre- and post-central gyri, middle frontal gyrus) default-mode network (DMN), connected to the superior parietal lobule, the superior temporal gyrus, some prefrontal areas and part of the anterior DMN (increased; FDR-corrected p<0.0005); as well as within the hippocampal regions of the ventral DMN linked to the amygdala (reduced; FDR-corrected p<0.0005). *p<0.05, **p<0.01. MoCA: Montreal cognitive assessment; FDR: false discovery rate; FWE: family-wise error; GM: grey matter; WM: white matter.