Fig. 1: Observed similarity of published work using LNM networks from original and randomized lesions.

a,b, Images of LNM-related circuitry maps from recent LNM and sLNM publications (from refs. ^{16,20,25,29,38,41,42,43}). Panel a is reproduced with permission. c, Correlation between sLNM networks for reduced PTSD risk²⁵ and cognitive decline induced by DBS in Parkinson’s disease⁴³ (shown in b). d, Recomputed LNM maps resulting from the application of voxel-wise Lead-DBS⁵⁴ on publicly available lesions for addiction³⁸, migraine²⁰, neurogenic stuttering⁴⁴, neglect syndrome⁵³, insomnia⁵³ and disrupted agency¹⁶. Reconstruction of LNM maps (d, first two images) compared to those reported in the original study (a) is high. e–g, Correlations between reconstructed LNM maps depicted in d are shown. h–j, Results show high similarity between LNM circuits derived from cortical deviations for six psychiatric conditions (BP and OCD are shown) and healthy controls; data taken from ref. ²⁸. k, The most reported regions across 102 LNM networks from a literature survey (Supplementary Tables 1 and 2), highlighting the prevalence of the top 10% highest correlated and anticorrelated voxels. Extensive overlap is evident in the insula, ACC and frontal pole. l–n, LNM networks derived from random lesions also show highly similar LNM outcomes. For example, lesions that disrupted agency¹⁶ and spin-randomized versions of these lesions (middle row) across the brain, as well as completely randomized seed locations (bottom row), result in similar LNM outcomes (shown in n). o,q, Plot of the spatial correlation between the original LNM map (disrupted agency¹⁶) and a typical example from the randomized conditions. p,r, Randomization of lesions was repeated 1,000 times, with almost all occasions resulting in highly similar LNM maps between the original (disrupted agency) and random conditions (box plots show values of n = 1,000 permutations; (p) minima = 0.06, maxima = 0.92, center = (median) 0.75, bounds of box (Q1 25th percentile–Q3 75th percentile) = 0.66–0.81, whiskers = 0.43–0.92; (r) minima = 0.58, maxima = 0.96, center = (median) 0.84, bounds of box (Q1 25th percentile–Q3 75th percentile) = 0.81–0.87, whiskers = 0.72–0.96). s, The application of LNM (Lead-DBS) on lesions associated with addiction remission (top left, lesion masks taken from ref. ³⁸). The panel also shows LNM outputs on the same lesion set but now spin-randomized across the cortex (top right, exemplary spin, r = 0.48), following a random selection of 100 lesions with mixed symptomatology (bottom left, ‘mixed lesions’, r = 0.93), and based on 100 synthetic lesions (bottom right, r = 0.71). All approaches yield very similar LNM maps. t–v, Plots show data (ASD²⁸) from an alternative null analysis, with the connections of the group connectome C binarized and randomized (t, left = original matrix, right = randomized matrix). Once again, LNM analyses resulted in very similar maps. Plot in u shows a representative example (ASD) and v shows a box plot of all randomizations (box plot shows values of n = 1,000 permutations; minima = 0.93, maxima = 0.98, center = (median) 0.96, bounds of box (Q1 25th percentile–Q3 75th percentile) = 0.96–0.96, whiskers = 0.94–0.98). ADHD, attention-deficit/hyperactivity disorder; BP, bipolar disorder; MDD, major depressive disorder; OCD, obsessive-compulsive disorder; PTSD, post-traumatic stress disorder; s subjects; SCZ, schizophrenia.