Fig. 5: Phenotypic consequences arising from a deleterious missense mutation in DISC1 (p.Arg517Trp).

a Schematic diagram of spatial working memory test using the Wisconsin General Test Apparatus (WGTA), where the macaque was allowed to choose food (e.g., peanut) from one of the two covered wells with various time delays. Macaque drawings by Mu-Ru Zhou; full painting by Hong-Di Huang. b Performance (percentage of correct choice) of Trp-bearing macaques (n = 3, red) and Arg controls (n = 3, blue) across six tested delays (0 s, 6 s, 12 s, 18 s, 24 s, 30 s). Data here and below are presented as the mean ± SEM. c Inhibition of working memory (ratio of errors score) caused by restraint stress between the Trp-bearing macaques (n = 3) and Arg controls (n = 3). P-value in working memory examinations was estimated by two-tailed t-test. d Neurological function scores performed for 3 adults of homozygous carriers (Trp) vs 19 non-carriers (Arg). P-value were estimated by two-tailed unpaired t-test. e Quantification of brain structure differences in macaques with 3 Trp carriers compared to 3 Arg controls that involved in working memory examinations. Left: gray matter surface area of four lobes in Trp-bearing macaques and Arg controls. Right: visualization of frontal brain regions showing significant differences between Trp-bearing macaques and Arg controls on the mid-gray surfaces of the macaque template. Red indicates the surface area of Trp-bearing macaques is larger than Arg controls, blue is the opposite. Fro, frontal lobe; Par, parietal lobe; Tem, temporal lobe; Occ, occipital lobe. f White matter volume of the four lobes (left) and visualization of temporal brain regions showing significant differences (right) between the 3 Trp carriers and 3 Arg controls. g Ventricle volume of the whole-brain between the Trp carriers (n = 3) and Arg controls (n = 3). e–g Quantitative data in Arg and Trp groups are presented as means ± SEM, with data collected from the two hemispheres of each monkey. Generalized linear mixed models (GLMMs) were used to estimate the statistical significance. Number of pairs of brain areas exhibiting increased (h) and decreased (i) functional connectivity within and across lobes and subcortical area at the median threshold (t = 3.2), respectively, in Trp macaques compared to Arg controls. Detailed information is presented in the right panels adjacent to the matrices. Red, yellow, green, blue and purple dots represent regions of frontal (Fro), parietal (Par), temporal (Tem), occipital lobe (Occ) and subcortical (Sub) regions, respectively. *, p < 0.05; **, p < 0.01; ****, p < 0.0001.