Fig. 5: Parcellating the hypothalamus improves predictions of stress.

Sensitivity of whole-hypothalamus as opposed to nuclei-specific hypothalamus connectivity was established using two control analyses: (1) using the original 15 ROIs (left column) and (2) using the original ROIs but replacing 7 amygdala nuclei by one whole amygdala mask (9 ROIs, right column). A Out-of-sample predictions of test group participants using weights estimated on the training group (as in Figs. 3C and 4A, n = 198 and n = 200) were significant based on whole-hypothalamus connectivity both when using amygdala nuclei or whole amygdala connectivity (one-sided correlations to assess positive relationships). B However, regression coefficients were reduced in both cases (bottom row) compared to the equivalent prediction using hypothalamus nuclei-specific functional connectivity (top row), even when correcting for the difference in the number of predictors (one-sided p-values from non-parametric test using permutation null distributions, see Methods). C As in Fig. 4A we generated predictions using increasing numbers of edges (coloured bars): left: whole hypothalamus x ROIs (1 × 15) vs. nuclei version (7 × 15 = 105); right: whole hypothalamus + whole amygdala ROIs (1 × 9) vs. nuclei version (7 × 9 = 63). Peak predictions were higher in both cases when using hypothalamus nuclei and highest overall when subdividing both hypothalamus and amygdala into their component nuclei (left: 22 edges: r = 0.272; right: 36 edges, r = 0.282). D Fingerprints associated with the predictions using all 15 (left) and 9 (right) whole-hypothalamus edges; on the right, the amygdala was also treated as a single structure. The highest contributing edge was hypothalamus coupling with RNMR in both cases. Source data for 5B–D are provided as a Source Data file. rnd randomised, NAc nucleus accumbens, BNST bed nucleus of the stria terminalis, SN substantia nigra, dPAG dorsal periaqueductal grey, vlPAG ventrolateral PAG, RNDR dorsal raphe nuclei, RNMR median raphe nuclei, LC locus coeruleus, Ce central amygdala nucleus, CoN cortical amygdala nuclei, B basal amygdala nucleus, AB/BM auxiliary basal or basomedial amygdala nucleus, LaI lateral intermediate amygdala nuclei, LaD lateral dorsal amygdala nuclei, LaV/BL lateral ventral portion containing portions of basolateral amygdala nucleus.