Cognitive Training. Adam Gazzaley, MD PhD

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1 Cognitive Training Adam Gazzaley, MD PhD Director, Neuroscience Imaging Center Neurology, Physiology and Psychiatry University of California, San Francisco Akili Interactive Labs Co-founder and Chief Science Advisor

2 Goal Develop an effective approach to enhance and maintain cognition throughout the lifespan

Cognition Brain processes used to organize information Attention: Selecting information Perception: Interpreting information Emotion: Extracting salience of

3 Cognition Brain processes used to organize information Attention: Selecting information Perception: Interpreting information Emotion: Extracting salience of information Memory: Retaining and retrieving information Decision Making: Reasoning based on information Motor/Language Output: Actions based on information

4 Cognitive Enhancement Optimizing our brain s information processing systems

5 Cognitive Control Mental abilities that allow us to interact with our complex world based on our goals Selective Attention Sustained Attention Distraction Resistance Working Memory Multitasking Task switching

6 Cognitive Control Early top-down modulation of sensory processing mediated by dynamic prefrontal cortical networks Declines as we age fmri EEG TES Gazzaley Neuropsychologia (2011) Gazzaley Principles of Frontal Lobe Function (2011)

7 Can we develop a custom-designed video game to enhance cognitive control in older adults?

8 Interference Training

9 Multi-tasking Index d Interference Training No Cost 0% -20% -27% -40% -60% -80% -63% -100% 20s 30s 40s 50s 60s 70s Decades of Life Anguera et al. Nature 2013

10 Multi-tasking Index d Interference Training 12 hours No Cost 0% -13% -20% -27% -40% -60% -80% -63% -100% 20s 30s 40s 50s 60s 70s Decades of Life Anguera et al. Nature 2013 Pre 1 mo. 6 mo. Training Study Multi-task train Single-task train No-contact control

11 Multi-tasking Index d Interference Training Frontal Theta Power 12 hours 0% -20% -40% -60% -80% -100% 20s 30s 40s 50s 60s 70s Decades of Life Anguera et al. Nature 2013 Pre 1 mo. 6 mo. Training Study Multi-task train Single-task train No-contact control

12 Interference Training Frontal Theta Power 12 hours ms Before Training After Training Anguera et al. Nature 2013

13 Neural Changes Frontal Theta Power Initial 12 hours * Older Adults Younger Adults Older Adults Post-Training Multi-Task Training Single-Task Training No Contact Control

14 Neural Changes Long-Range Theta Coherence Initial * Older Adults Younger Adults Older Adults Post-Training PLV % Change Multi-Task Training Single-Task Training No Contact Control 12 hours

15 Pre-Post RT (msec) Pre-Post RT (msec) Transfer of Benefits 12 hours Working Memory Sustained Attention 150 * 40 a) * Delayed-Recognition Task Tests of Variables of Attention (TOVA) Multi-task training Single-task training No-contact control Anguera et al. Nature 2013

16 Theta & Transfer Magnitude of Theta Enhancement Correlates with Gains in Sustained Attention (TOVA) 12 hours 90 Pre-Post TOVA RT R² = Post-Pre mf Theta Pre-Train Post-Train Anguera et al. Nature 2013

17 Theta & Sustainability Magnitude of Theta Enhancement Correlates with Sustained Performance Gains at 6 months 0 12 hours 6 month - Post Train Multi-tasking cost R² = Post-Pre mf Theta Pre-Train Post-Train Anguera et al. Nature 2013

18 Conclusions Adaptive training of information processing drives generalized enhancements in cognitive control. Task improvements are associated with changes in engagement of prefrontal cortical networks.

19 Recommendations Develop adaptive, immersive, interactive software targeting core cognitive deficits of older adults. Validate in placebo-controlled studies using outcome measures and neural recordings directed at the goal of feasibility, proof-of-principle and mechanism. Extend with mobile studies to directly compare to other approaches and understand transfer and sustainability. Enhance by combining with other approaches - e.g., physical exercise, neuromodulation, neurofeedback. Translate through critical interactions with industry.

on Aging National Institute of Mental Health Faculty Ted Zanto

Arean Elysa Marco Fellows David Ziegler Morgan Hough Bradley

Support Research Associates Jacki Janowich Cammie Rolle Roger

Omernick Dmitri Ellingson Eric Johnson Noah Fahlstein UCSF CTSI

Mike Gonzales Mickey Hart thanks to the many Gazzlab alumni and

Alhashimi Alan Legitt Benjamin Dorn WanYu Hsu Jamie Gates

20 Many thanks Hardware Support Apple Oculus VR NVIDIA National Institute on Aging National Institute of Mental Health Faculty Ted Zanto Judy Pa American Federation of Aging Research Robert Wood Johnson Foundation Zynga.org Foundation Jyoti Mishra Peter Wais Research Partners Pat Arean Elysa Marco Fellows David Ziegler Morgan Hough Bradley Voytek Joaquin Anguera Yixuan Ku Martine Schouwenburg Financial Support Research Associates Jacki Janowich Cammie Rolle Roger Anguera Rajat Jain Anirudh Wodeyar Game Development Matt Omernick Dmitri Ellingson Eric Johnson Noah Fahlstein UCSF CTSI Posit Science Pfizer / Eisai Tim Ferriss Ty Clark Matt Whitman Mike Gonzales Mickey Hart thanks to the many Gazzlab alumni and past partners Sandler Foundation Students Zack Chadick Omar Alhashimi Alan Legitt Benjamin Dorn WanYu Hsu Jamie Gates Family Foundation Rose Family Foundation Feldman Family Foundation Grammy Foundation GlassBrain Partners Tim Mullen Christian Kothe Oleg Konigs John Fesenko Matt Omernick

CAMARIN E. ROLLE 675 Nelson Rising Lane San Francisco, CA Phone: (415)

Camarin Rolle 1 of 6 CAMARIN E. ROLLE 675 Nelson Rising Lane San Francisco, CA. 94158 Phone: (415) 502-7322 Email: cammie.rolle@gmail.com Education B.A. Psychology, University of California, Davis, September