1. Effects of cognitive training by video game on schizophrenia patients Ryuta KAWASHIMA, Kunio IZUKA IDAC, Tohoku University, Sendai Japan Katsuki NAKAMURA Primate Research Institute, Kyoto University, Kyoto Japan Masato TAIRA Tokyo Medical and Dental University, Tokyo Japan

2. Introduction Cognitive impairment is one of the major symptoms of schizophrenia. Broad cognitive impairment is observed across most cognitive domains. We have been investigating beneficial effects on wide range of cognitive functions by cognitive training using a video game (Brain age, Nintendo, Kyoto, Japan, 2005) on both healthy elders and young subjects (Nouchi et al., 2012, 2013). We found both subjects could improve working memory, executive functions and processing speed in short term (15 minutes per day, 4 weeks) training. The purpose of this preliminary study was to investigate whether cognitive training by video game can be used for one of the cognitive rehabilitation methods on patients with schizophrenia. Nouchi et al., PLoS One 2012, 2013

3. Participants (40 schizophrenic patients will be invited) Outpatients of Tohoku Univ. Hospital and outpatients who were referred from other hospitals Aged 18-39, right-handed schizophrenic patients (DSM-IV) Clinically stable (no admission to hospital within the last 8 weeks/ no plan to change anti- psychotic drugs) 【 Exclusion criteria 】 Estimated IQ by JART ＜ 80, brain injury, neurological disorder, substance abuse Design We have been conducting a randomized controlled study using following design. However, in this preliminary report, we only present results from 4 patients (aged 23 to 36, two females) who were treated as same as intervention group at pre and post. Methods cognitive assessment / MRI cognitive assessment / MRI ＜intervention group＞ cognitive training : Brain Age （30min. 4times /week） treatment as usual ＜control group＞ play videogames （30min. 4times /week） treatment as usual 8 weeks cognitive assessment / MRI 3 months pre follow uppost

4. Methods 2 Outcome measures ・ IQ JART (Japanese adult reading test) ・ Cognitive functions BACSverbal learning, working memory motor speed, verbal fluency process speed, executive function WAIS- Ⅲ arithmetic WMS-Rvisual learning, visual working memory Stroop testexecutive function Trail Making Test A/Bprocessing speed, executive function Raven’s progressive matrices testreasoning ・ Clinical symptoms PANSS (Positive and Negative Syndrome Scale) ・ Self-efficacy, social function, cognitive style GAF(Global Assessment of Functioning), Rosenberg Self-Esteem Scale Social Functioning Scale-J, Schizophrenia Cognition Rating Scale QOL26, BCIS(Beck Cognitive Insight Scale), BCSS(Brief Core Schema Scale) ・ Neuroimaging MRI (structure, DTI, rCBF, functional connectivity) We report those results.

5. Results our preliminary intervention Reference data: previous study ‘treatment as usual’ group (Ikezawa, 2012) (Z score, mean±S.E.) BACS PrePost PrePostPrePost PrePostPrePostPrePost

6. Results 2 pre post TMT-A (sec.)28.8±2.928.0±4.4 TMT-B (sec.)67.8±10.664.5±11.9 Stroop color naming39.5±3.045.8±11.4 Stroop interference (%)21.9%±6.7 26.2 %±8.3 Raven's Matrices test11.3±4.313.8±5.0 WAIS-III arithemetic11.5±1.912.0±2.6 WMS-R spatial working memory18.0±0.819.3±1.7 WMS-R visual learning5.8±0.66.3±1.3 other cognitive measures (n=4, mean±S.E.)

7. Conclusion This preliminary study demonstrates the transfer effect of the cognitive training by commercially available video game on the improvement of working memory, executive functions and processing speeds in the schizophrenia patients. The results are consistent with our previous study on healthy subjects. These results suggest that there is a possibility that cognitive training by video game can use as one of the cognitive rehabilitation methods for schizophrenia patients. We, then, are going to start randomized controlled study in large samples to confirm our preliminary results, and to show long-term effects and relevance for every-day functioning in the near future.

8. What is “Brain Age” In addition, Nintendo DS is handy hardware, and has hand-written letters and voice recognition capabilities so that it can be used for smooth training for every one at anywhere without stresses. Brain Age is one of the popular brain training games. It was developed based on the previous findings of a cognitive training program for the elderly (Uchida & Kawashima, 2008). The previous study used reading aloud and simple arithmetic calculations as training tasks. The reasons why these tasks were selected were that 1) these tasks activated the dorsolateral prefrontal cortex activated in comparison to the resting state (Kawashima et al., 2004, Miura et al., 2003), 2) these task were very simple. Most games in Brain Age contain the elements of these reading aloud and simple arithmetic calculations.