normal

Normal SchizophreniaSZ10s and 10s age groups, accuracy per second

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Supplementary Figure 1

Supplementary Fig 1. Comparative results of SZ10s and 10s age groups. a-d show the accuracy per second of SZ10s and 10s age groups, at the different loads of difficulty with combinations of different learning time and delay span. * : p < 0.05; ** : p < 0.01; *** : p < 0.0001.

Normal SchizophreniaSZ30s and 30s age groups, accuracy per second

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Supplementary Fig 2. Comparative results of SZ30s and 30s age groups. a-d show the accuracy per second of SZ30s and 30s age groups, at the different loads of difficulty with combinations of different learning time and delay span. * : p < 0.05; ** : p < 0.01; *** : p < 0.0001.

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Accuracy per second of control group 　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s

　 load 2 load 3 load 4 load 2 load 3 load 4 load 2 load 3 load 4 load 2 load 3 load 4

10s 0.84±0.04 0.57±0.04 0.31±0.03 0.84±0.05 0.55±0.05 0.27±0.03 0.81±0.05 0.69±0.04 0.44±0.03 0.89±0.04 0.62±0.04 0.40±0.04

20s 0.95±0.04 0.66±0.04 0.43±0.04 1.06±0.03 0.80±0.04 0.44±0.04 1.00±0.03 0.85±0.04 0.66±0.04 1.03±0.04 0.82±0.04 0.59±0.04

30s 0.90±0.04 0.62±0.05 0.36±0.03 0.94±0.04 0.58±0.05 0.35±0.03 0.95±0.03 0.74±0.04 0.53±0.06 0.94±0.03 0.71±0.04 0.47±0.04

40s 0.84±0.04 0.59±0.04 0.37±0.03 0.90±0.03 0.59±0.05 0.31±0.04 0.86±0.03 0.69±0.04 0.41±0.03 0.89±0.03 0.63±0.04 0.39±0.03

50s 0.66±0.05 0.39±0.05 0.24±0.03 0.64±0.05 0.45±0.05 0.22±0.03 0.64±0.05 0.47±0.04 0.34±0.03 0.67±0.05 0.50±0.05 0.32±0.04

Accuracy per second p value of control group　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s


20s vs 10s 0.0604 0.1438 0.0045 0.0002 <0.0001 0.0003 0.0003 0.0044 <0.0001 0.0091 0.0004 0.0004

20s vs 30s 0.4809 0.5579 0.1228 0.0494 0.0006 0.0657 0.2505 0.057 0.007 0.086 0.048 0.024

20s vs 40s 0.0722 0.2915 0.1874 0.0109 0.0011 0.0126 0.0101 0.0067 <0.0001 0.0141 0.0015 0.0003

20s vs 50s <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

Accuracy per second of schizophrenia group 　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s


SZ10s 0.80±0.04 0.55±0.06 0.25±0.04 0.83±0.05 0.56±0.06 0.26±0.04 0.84±0.04 0.61±0.05 0.42±0.04 0.84±0.04 0.65±0.05 0.38±0.04

SZ20s 0.66±0.06 0.48±0.06 0.21±0.03 0.68±0.06 0.48±0.06 0.20±0.04 0.78±0.04 0.62±0.06 0.43±0.05 0.81±0.04 0.54±0.05 0.28±0.03

SZ30s 0.59±0.06 0.43±0.06 0.21±0.04 0.59±0.06 0.43±0.06 0.22±0.04 0.64±0.05 0.49±0.04 0.35±0.04 0.65±0.05 0.46±0.05 0.31±0.04

Accuracy per second p value of schizophrenia group　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s


SZ20s vs SZ10s 0.0693 0.0473 0.4671 0.0688 0.3337 0.3617 0.4105 0.963 0.8381 0.6689 0.1292 0.1171

SZ20s vs SZ30s 0.3097 0.915 0.9315 0.2048 0.5845 0.7611 0.0314 0.0857 0.24 0.0197 0.2604 0.6855

Supplementary Table 1

Supplementary Table 1, Accuracy per second, various groups. Red indicates significant difference.

Supplementary Table 2, Comparison between schizophrenia and control groups, p value. Red indicates significant difference.

Comparative p value of accuracy per second

　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s


10s vs SZ10s 0.5478 0.9218 0.3205 0.8497 0.9192 0.8815 0.6424 0.2113 0.6144 0.3839 0.7112 0.7427

20s vs SZ20s <0.0001 0.0005 <0.0001 <0.0001 <0.0001 <0.0001 0.0003 0.0005 <0.0001 0.0004 <0.0001 <0.0001

30s vs SZ30s <0.0001 0.0032 0.0043 <0.0001 0.0369 0.0148 <0.0001 0.0001 0.0022 <0.0001 0.0001 0.0059



4 9 2

3 5 7

8 1 6

Supplementary Fig 3. The historical Chinese jiugongtu“九宫图” . (a), The jiugongtu map is a Chinese historical artifact developed several centuries before 0 BCE, perhaps first described in I Jing [25,37] . It presents a grid-like arrangement of number-marks. The substitution of numbers for the number of marks (b), shows that the numbers from 1 to 9 are arranged so as to add up to 15 in whatever dimension we proceed to calculate. This magic square is well-known in Chinese culture, making it a friendly and understandable spatial map for subjects. (c), The SWAPS test uses the nine-spaced grid as a background, but fills it with paired symbols.

a b c

Supplementary Fig 4. Comparison of schizophrenic and healthy groups. SWAPS showed the highest percentage of correct choices in the age 20-27 (group 20s) healthy control group but not in schizophrenia patients ages 20-29 (group SZ20s). a-d show the percentage of correct choices in 5 healthy control age groups (10s, 20s, 30s, 40s, 50s), at different difficulty loads and with different combinations of learning time and delay span. (e-h) show the percentage of correct choices for 3 age groups in schizophrenia patients (SZ10s, SZ20s, SZ30s), under the same learning time and delay span conditions as the healthy control groups. Lt, learning time (0.5sec or 2sec); D, delay span (0.5sec or 2 sec).

Correct choice, control (%)

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Reaction time, schizophrenia groups (ms)

b c da

Supplementary Fig 5. Healthy control and schizophrenia groups, showing reaction time. a-d shows the reaction time of 5 healthy control age groups, at different loads of difficulty with different combinations of learning time Lt and delay span D. e-f show the reaction time of 3 age groups in schizophrenia patients, matching the control group’s Lt and D conditions. Lt :Learning time; D: Delay span, error bar shows standard error.

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Normal SchizophreniaComparison of SZ10s and 10s, correct choices (%)

c d

Comparison of SZ10s and 10s, reaction time

Supplementary Fig 6. Comparative results of SZ10s and 10s age groups. Percentage of correct choice is shown in a, b, c, d and reaction time is shown in e, f, g, h. *p < 0.05; **p < 0.01; ***p < 0.0001; error bar shows standard error.

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Supplementary Fig 7. Comparative results of SZ20s and 20s age groups. a-d show the percentage of correct choices of SZ20s and 20s age groups, at the different loads of difficulty with the combination of different learning time and delay span. e-h show the reaction time of SZ20s and 20s age groups, at different loads of difficulty with combinations of different learning time and delay span. * : p < 0.05; ** : p < 0.01; *** : p < 0.0001.

* *****

Normal SchizophreniaSZ20s and 20s age groups, correct choice (%)

SZ20s and 20s age groups, reaction time (ms)

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Normal SchizophreniaComparison of SZ30s and 30s, correct choices (%)

Supplementary Fig 8. Comparative results of SZ30s and 30s age groups. Percentage of correct choice is shown in a, b, c, d and reaction time is shown in e, f, g, h. *p < 0.05; **p < 0.01; ***p < 0.0001; error bar shows standard error.

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Comparison of SZ30s and 30s, reaction time

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Supplementary Fig 9. Various learning times, and delay spans for test design. In designing the test, we examined various learning times, and delay spans for health people group ages 18-24. The first versions of the test needed to determine the most appropriate Lt and D to show differentiation between loads. Fig. 5a shows the variation of correct responses through difficulty loads two, three and four, presenting evidence that the design of the test can discriminate between difficulty loads. We found that D of up to 2 seconds had the same results as D of up to 5 seconds (Fig. 5b). The added time did not increase accuracy in responses, and so we shortened D in our test design to 2 seconds. We found that Lt shows the largest differences between loads when Lt has a value of between 0 and 2 seconds, and when Lt exceeds 2 seconds the test results for all loads of difficulty begin to converge toward higher percentage of correct response (Fig. 5c). Lt :Learning time; D: Delay span. error bar shows standard error.

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Correct choices of different age groups in control (%)　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s


10s 92.4±1.9 75.1±3.3 47.4±3.7 89.4±2.9 70.3±3.7 39.5±3.4 92.7±2.1 85.8±2.8 66.3±3.7 93.3±1.8 80.7±2.9 61.0±3.7

20s 97.6±0.9 91.2±1.4 67.6±3.5 97.6±0.8 90.5±1.9 58.8±3.8 98.3±0.7 94.9±1.5 84.8±2.3 98.6±0.6 93.2±1.7 81.1±2.8

30s 96.6±1.2 78.7±3.7 56.1±4.0 96.0±1.3 73.2±3.7 49.7±3.6 98.5±0.6 88.7±2.2 74.7±3.4 97.6±0.8 87.8±2.4 66.2±4.0

40s 96.1±1.1 77.5±3.0 55.4±2.4 97.1±0.9 78.9±2.6 43.9±3.6 97.1±0.9 87.9±2.2 60.4±3.1 96.4±1.0 84.6±2.3 56.4±3.5

50s 93.8±1.9 67.6±3.4 51.2±3.5 93.8±1.6 71.5±3.4 45.3±3.9 95.7±1.5 84.0±3.0 64.5±3.5 94.9±1.5 79.7±3.8 59.0±3.9

Comparative p value of correct choice between different age groups in control　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s


20s vs 10s 0.0111 0.0002 <0.0001 0.001 <0.0001 0.0002 0.0031 0.0061 <0.0001 0.0022 0.0008 <0.0001

20s vs 30s 0.6298 0.0043 0.0213 0.5191 0.0001 0.075 0.9303 0.065 0.0286 0.5349 0.144 0.0037

20s vs 40s 0.4637 0.0027 0.0185 0.8485 0.0133 0.0054 0.5511 0.0435 <0.0001 0.2239 0.0269 <0.0001

20s vs 50s 0.0764 <0.0001 0.0021 0.142 <0.0001 0.0136 0.1944 0.0024 <0.0001 0.0469 0.0007 <0.0001

Correct choices of different age groups in schizophrenia(%)　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s


SZ10s 93.8±2.4 77.1±4.2 45.3±5.4 91.1±2.5 72.4±4.7 41.1±5.0 97.4±1.3 82.8±3.3 67.2±4.4 96.4±1.6 85.4±3.9 61.5±5.8

SZ20s 87.5±3.8 66.1±6.2 42.2±5.4 86.5±2.7 66.7±5.6 37.0±5.2 93.8±2.1 84.4±3.4 64.6±5.1 93.8±2.3 79.7±4.2 46.9±4.6

SZ30s 89.6±4.2 72.9±4.3 40.1±5.0 85.4±4.0 70.3±5.2 37.5±4.5 93.8±3.2 81.8±3.4 62.0±4.5 91.7±3.1 76.6±3.6 55.2±4.1

Comparative p value of Correct choice between different age groups in schizophrenia　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2s


SZ20s vs SZ10s 0.1395 0.1831 0.8264 0.1317 0.3927 0.6269 0.1683 0.9237 0.6258 0.8308 0.1781 0.0323

SZ20s vs SZ30s 0.8995 0.5295 0.4333 0.7309 0.9855 0.8664 0.8229 0.7008 0.6731 0.1195 0.4594 0.4174


Supplementary Table 1, Correct choice (%), various groups. Red indicates significant difference.


Reaction time of different age groups in control (ms)



10s 1240±76 1735±210 1710±111 1240±89 1638±151 1921±226 1406±128 1440±111 1680±125 1192±86 1473±88 1779±124

20s 1017±38 1234±45 1601±108 960±32 1227±56 1524±91 1013±36 1203±57 1414±68 1019±45 1251±79 1557±92

30s 1175±66 1473±105 1766±155 1092±50 1414±79 1643±108 1098±45 1301±58 1574±88 1085±35 1358±68 1619±99

40s 1227±58 1467±79 1640±82 1129±42 1462±72 1770±135 1195±58 1400±82 1647±106 1149±64 1450±75 1650±100

50s 1800±225 2358±231 2789±258 1887±224 2176±213 2837±274 1934±267 2225±238 2275±178 1806±198 2251±268 2576±236

Comparative p value of reaction time between different age groups in control



20s vs 10s 0.1193 0.0182 0.5961 0.0477 0.0175 0.1067 0.0247 0.1456 0.0965 0.188 0.1982 0.2268

20s vs 30s 0.2757 0.2624 0.4259 0.3498 0.2807 0.631 0.6256 0.5505 0.3222 0.6205 0.54 0.7387

20s vs 40s 0.1638 0.2929 0.859 0.2529 0.1944 0.341 0.3187 0.2494 0.1657 0.3442 0.2726 0.6297

20s vs 50s <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

Reaction time of different age groups in schizophrenia (ms)



SZ10s 1260±69 1566±114 2034±202 1201±74 1501±107 2412±449 1223±62 1543±148 1833±132 1225±36 1463±101 1879±158

SZ20s 1526±118 1845±117 2377±214 1420±103 1688±149 2340±369 1294±92 1580±118 1666±108 1227±58 1723±157 1868±137

SZ30s 1843±152 2175±189 2782±293 1865±218 2103±183 2213±200 1734±149 1875±135 2303±284 1643±128 1919±112 2279±194

Comparative p value of reaction time between different age groups in schizophrenia



SZ20s vs SZ10s 0.0547 0.2565 0.2165 0.1813 0.3601 0.8511 0.6467 0.8258 0.4465 0.9865 0.1015 0.9573

SZ20s vs SZ30s 0.0223 0.1807 0.1453 0.0049 0.0431 0.7403 0.005 0.0766 0.0041 0.0005 0.2181 0.0523

Supplementary Table 4, Reaction time, various groups. Red indicates significant difference.

Supplementary Table 5, Comparison between schizophrenia and control groups, p value. Red indicates significant difference.

Comparative p value of correct choices in compatible age groups between control and schizophrenia



10s vs SZ10s 0.6903 0.7119 0.7422 0.6229 0.7246 0.7817 0.069 0.4542 0.8706 0.2123 0.2785 0.9444

20s vs SZ20s 0.003 <0.0001 0.0001 0.002 <0.0001 0.0003 0.0836 0.0097 0.0005 0.0546 0.0027 <0.0001

30s vs SZ30s 0.0336 0.2993 0.0127 0.0028 0.6231 0.0429 0.0647 0.0786 0.0233 0.0173 0.0101 0.0696

Comparative p value of reaction time in compatible age groups between control and schizophrenia



10s vsSZ10s 0.8707 0.1377 0.1876 0.8328 0.4462 0.1492 0.183 0.4847 0.431 0.7472 0.9421 0.5915

20s vs SZ20s <0.0001 0.0067 0.0024 0.0014 0.0136 0.0203 0.0465 0.0134 0.208 0.0539 0.0012 0.1061

30s vs SZ30s <0.0001 0.0015 <0.0001 <0.0001 0.0002 0.0976 <0.0001 0.0001 0.0003 <0.0001 <0.0001 0.0005



Supplementary Table 6, demographic information of patients and their counterparts.

Demographic information10s 20s 30s SZ10s SZ20s SZ30s

No. of participants 43 37 41 24 24 24Female (%) 46.51% 51.35% 48.78% 54.17% 50.00% 50.00%Male (%) 53.49% 48.65% 51.22% 45.83% 50.00% 50.00%Age 14.2±0.1 23.8±0.2 33.7±0.5 15.8±0.2 25.0±0.5 35.9±0.6Education years 7.2±0.1 16.2±0.1 16.4±0.2 8.3±0.4 12.1±0.5 12.3±0.6Age of onset NA NA NA 14.9±0.3 19.8±0.8 25.9±1.4Course of disease NA NA NA 1.2±0.2 5.3±0.9 10.1±1.5The first onset (%) NA NA NA 70.83% 33.33% 20.80%

P value in comparison of accuracy per second male and female in different age groups

　 Lt 0.5s D 0.5s Lt 0.5s D 2s Lt 2s D 0.5s Lt 2s D 2slevel 2 level 3 level 4 level 2 level 3 level 4 level 2 level 3 level 4 level 2 level 3 level 4

10s 0.0249 0.4143 0.4347 0.6145 0.8617 0.4775 0.2758 0.2516 0.7220 0.0797 0.6655 0.585920s 0.7381 0.7547 0.4556 0.6075 0.9892 0.4107 0.2115 0.5768 0.4865 0.2880 0.8327 0.810330s 0.5595 0.8233 0.4685 0.869 0.9094 0.353 0.2178 0.0901 0.6976 0.7600 0.8365 0.219940s 0.4646 0.8704 0.4900 0.6643 0.1474 0.4869 0.7740 0.3781 0.2884 0.3348 0.8389 0.613550s 0.1344 0.5870 0.6832 0.2722 0.6180 0.2348 0.2737 0.4525 0.9279 0.1450 0.3796 0.6330SZ10s 0.7819 0.9747 0.5996 0.3390 0.3546 0.776 0.8794 0.9940 0.3020 0.2703 0.5002 0.1353SZ20s 0.5246 0.9628 0.9470 0.2205 0.9060 0.9107 0.3194 0.6249 0.4250 0.3893 0.8653 0.6337SZ30s 0.2362 0.5061 0.3944 0.3780 0.3559 0.7123 0.3557 0.0967 0.1543 0.3804 0.2351 0.6364


Supplementary Table 7, Comparison between male and female of all the tested age group, p value. Red indicates significant difference.

normal

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