SUPPLEMENTARy MATERIAL

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Supplementary material Computerized Cognitive Training

The computerized cognitive training program comprised 14 tasks. The names of the cognitive tasks and the cognitive domains targeted in each task are presented in Supplementary Table 1 (in the online-only Data Supplement). Each task is explained in detail below. In the ‘word finding’ task, the participants had to find the words that included a syllable presented in advance from among multiple choices within a certain time limit (Supplementary Fig. 1A in the online-only Data Supplement). In the ‘selecting cards’ task, the participants had to select the cards with specific numbers that met the requirements specified a priori, such as the smallest number from among multiple choices (Supplementary Fig. 1B in the online-only Data Supplement). The task difficulty was increased by changing the size or location of cards. In the ‘remembering cards’ task (derived from the Korean “hwatu” gambling card game), the participants had to select the card that was briefly presented in advance from among multiple choices (Supplementary Fig. 1C in the online-only Data Supplement). The task difficulty was increased by presenting more cards simultaneously. In the ‘making a hamburger’ task, the process for making a hamburger was presented to the participants, and then they had to select the appropriate food ingredients in the correct sequence from among multiple choices (Supplementary Fig. 1D in the online-only Data Supplement). In ‘comparing sums of money’, the participants were given instructions associated with several market items and their corresponding costs. After a set of items was presented to the participants, they had to calculate the total cost and compare this with simultaneously presented sums of money (Supplementary Fig. 1E in the online-only Data Supplement). In the ‘finding coins’ task, the locations of coins were briefly presented in the background of images of Korean traditional houses. The coins then disappeared and the participants had to identify the locations of the hidden coins (Supplementary Fig. 1F in the online-only Data Supplement). In the ‘mirror maze’ task, the participants had to move objects between the walls of a maze to get to the final destination (Supplementary Fig. 1G in the online-only Data Supplement). They had to refer to mirror images to determine the exact location of the moving objects. In the ‘counting in the number of cubes’ task, the participants had to count the number of cubes of particular colors in three-dimensional models (Supplementary Fig. 1H in the online-only Data Supplement). In the ‘remembering locations’ task, the participants were asked to remember the locations of items that were displayed to them for a few seconds at the beginning of training (Supplementary Fig. 1I in the online-only Data Supplement). They had a certain time limit to find the locations of all the items in the background grid, which they were given in advance. The ‘matching game’ task was almost same as the n-back test, which is a traditional neuropsychological test (Supplementary Fig. 1J in the online-only Data Supplement). The participants were asked to determine whether the current image is the same as the object presented two stages earlier, within a certain time limit. The Stroop task is a computerized version of the Stroop test used in formal neuropsychological tests (Supplementary Fig. 1K in the online-only Data Supplement). The ‘creating 10, 20, 30 each by adding numbers’ task required trained calculation and attention. The participants were asked to provide several numbers that totaled to 10, 20, or 30 within a certain time limit (Supplementary Fig. 1L in the online-only Data Supplement). The ‘roulette’ task involved presenting numbers or fruit icons (Supplementary Fig. 1M in the online-only Data Supplement), and the participants were asked to move each roulette column and row to match the images given in advance. In the ‘backward numeral reading’ task, the participants were asked to read the given numerals backward in the exact order, within a certain time limit (Supplementary Fig. 1N in the online-only Data Supplement).

Neuroimaging analysis Magnetic resonance data acquisition protocol A 1.5-tesla magnetic resonance imaging (MRI) scanner (Achieva, Philips Healthcare, Eindhoven, the Netherlands) was used in this study. The MRI protocols consisted of diffusion-tensor imaging (DTI), axial T1- and T2-weighted spin echo imaging, and three-dimensional spoiled gradient recalled (3D-SPGR) imaging. The acquisition parameters for 3D-SPGR imaging were as follows: 128 contiguous images in the coronal plane with a thickness of 1.0 mm; matrix, 256×256; field of view, 210 mm; repetition time, 22 ms; echo time, 6 ms; flip angle, 30 degrees; and number of excitations, 1. DTI was performed using an echo-planar imaging spin echo sequence. The acquisition parameters for DTI were as follows: repetition time, 5,000 ms; echo time, 50 ms; diffusion b value, 1000; slice thickness, 5 mm; intersection gap, 1 mm; matrix, 256×256; and flip angle, 90 degrees.

Volumetric MRI: surface-based morphometry Any significant changes in cortical thickness were detected using surface-based morphometry with Freesurfer software (version 5.1.0, MGH, Martinos Center, Harvard University, Boston, MA, USA).1 Each analysis was adjusted for age and education level, and the threshold for statistical significance was set at p0.2 was then applied to eliminate non-white-matter tissues and misalignment issues. Voxel-wise statistical analyses were performed for all skeletonized DTI measures across subjects using a general linear model with threshold-free cluster enhancement methods and 10,000 permutations.4 A significance threshold for group comparisons was set at p