Challenge 60 year old with mild cognitive impairment Poor - PowerPoint PPT Presentation

oo oo ot ot oo oo oo oo oo oo oo oo oo oo oo ot oo g oo oo oo oo goo g g g g g ot ot g ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot g g ot g g ot not This is just not good enough g g g g g g g g g ot g g g g g g g g g g g g ot ot g ot g g g ot g ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot ot Disclosures Harnessing Brain Plasticity Akili Interactive Labs Co-founder and Chief Science Advisor Pending patents: Adam Gazzaley, MD PhD “Enhancing Cognition in the Presence of Distraction and/or Interruption” “Method of Suppressing Irrelevant Stimuli” Professor - Neurology, Physiology and Psychiatry Director- Gazzaley Lab, Neuroscape Lab “Methods of Enhancing Performance on a Cognitive Task By Improved Self-Regulation of Internal Distraction and Neuroscience Imaging Center Computer Readable Medium and Devices for Practicing the Same” University of California, San Francisco “Methods of Enhancing Cognition and Systems for Practicing the Same” Current Approach Challenge 60 year old with mild cognitive impairment • Poor characterization Develop an effective approach to enhance cognition • Poor targeting • Non-personalized in both healthy and impaired individuals • Unimodal • Open Loop

Step 1: Understand the target Create a New Approach Create a New Approach targeted fMRI fM fMRI RI EEG EEG TMS personalized multimodal closed-loop Cognitive Control Cognitive Control Early sensory processing modulation mediated by prefrontal cortical networks Our mental abilities that allow us to dynamically interact with our complex environment based on our goals Declines as we age - Gazzaley, et al. Journal of Cognitive Neuroscience (2005) - Gazzaley et al. Nature Neuroscience (2005) - Gazzaley et al. Cerebral Cortex (2007) - Gazzaley et al. Neuropsychology ( 2007 ) - Rutman et al. Journal of Cognitive Neuroscience (2009) - Gazzaley et al. PNAS (2008) Attention Working Memory - Berry et al. Journal of Neurophysiology (2009) - Zanto, et al. Cortex (2010) - Clapp, Rubens and Gazzaley Cerebral Cortex (2010) - Clapp & Gazzaley Neurobiology of Aging (2010) - Zanto & Gazzaley Journal of Neuroscience (2010) - Berry et al. PLoS One (2010) - Zanto, Rubens & Gazzaley Neuroimage (2010) - Clapp, Rubens & Gazzaley PNAS (2011) - Zanto & Gazzaley Neuropsychologia (2010) - Wais et al. Journal of Neuroscience (2010) - Wais, Kim & Gazzaley Cerebral Cortex ( ( 2011 ) - Anguera & Gazzaley Clinical Neurophysiology ( 2011 ) - Zanto et al. Nature Neuroscience (2011) - Wais & Gazzaley Brain Research ( 2012 ) - Chadick & Gazzaley Nature Neuroscience (2011) - Cashdollar et al. Psychology and Aging ( 2013 ) Goal Management - Wais & Gazzaley Psychonomic Bulletin and Review ( 2011 ) - Mishra & Gazzaley Neuropsychologia (2013) - Mishra & Gazzaley Journal of Neuroscience (2012) - Zanto et al. PLoS One (2013) Gazzaley Neuropsychologia (2011) Gazzaley Principles of Frontal Lobe Function (2011)

Step 2: Build an engine Step 2: Build an engine Step 1: Understand the target Create a New Approach Create a New Approach • Targeting • Personalized • Multimodal • Closed Loop Adaptivity / Feedback cognitive exercises and video game training Interference Training Study Enhance cognitive control abilities in healthy older adults 2008-2013 Attention Working Memory Joaquin Anguera Goal Management Anguera, Boccanfuso, Rintoul, Al-Hashimi, Faraji, Janowich, Kong, Larraburo, Rolle, Johnston & Gazzaley Video game training enhances cognitive control in older adults Nature 2013

Funded by Robert Wood Johnson Foundation Decades of Life Anguera et al. Nature 2013 Anguera et al. Nature 2013 Anguera et al. Nature 2013 Training Study Interference Training Multitasking Performance mance Midline Frontal Theta 12 hours 12 hours 12 h 12 h 12 h 12 hours ours ours 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -27% -2 -2 -2 -2 -2 -2 -2 -2 -2 -27% -2 -2 -2 -2 -2 -2 -2 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% 7% -20% -40% Multi-tasking Index -60% -6 -63% -6 -6 -6 -6 -6 -63% -6 -6 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% 3% -80% -100% 1 month 6 months 20s 30s 40s 50s 60s 70s later later A Neural Bridge Transfer of Benefits 12 hours 12 hours Pre & Post Working Memory Pre -Training Post -Training & Transfer of Benefits Sustained Benefits Attention Span Multitasking on Game Attention Span

Neuroscapelab.com Patent-pending: “Enhancing Cognition in the Presence of Distraction and/or Interruption” Move to the Real World World ★ Adaptivity / feedback video game training of interference processing drives enhancements of cognitive control abilities in older adults. ★ Task improvements are associated with changes in engagement of Akili Interactive Labs Akili Int Aki Aki Aki Aki Aki Aki Akili li Int li li li li li Int Int Int Int Int Intera eracti era era era cti cti cti cti cti cti ctive ve Lab ve ve ve Lab Lab Labs Lab Lab Lab Lab s s s s Co-founder and Chief Science Advisor prefrontal cortex networks. Evaluate as Diagnostics & Therapeutics ★ Attention Deficit Disorder (ADD) Scott Kollins, Duke University / Andrew Cutler, FLCRC r, • • [Shire Pharmaceuticals] ★ Depression Patricia Arean, UCSF • [NIH] • ★ Traumatic Brain Injury (TBI) Kristine Yaffe, UCSF • Bridging the Gap Between Technology and Neuroscience ★ Alzheimer’s Disease [Pfizer] • ★ Autism Elysa Marco, UCSF • • [Wallace Foundation / James Gates Family Foundation] Famil mily F y Foundat dation ion] ]

New Technology Mobile / Wireless New Technology Virtual Reality Motion Capture New Games...

Step 2: Build the engine Step 3: Enhance the effects Step 1: Understand the target Neuro Crossfit Create a New Approach Meditation Physical Rhythm Attention Real-Time EEG Enhance the Effects Neuromodulation Neurofeedback Video Games

Close the Loop 2015 2020 2015 2015 2020 2015 2015 0 Behavior Neural EEG G EEG Electrical Environment targeted / personalized / multimodal / closed-loop Over the Next 10 Years ... Addiction Parkinson’s Disease Anxiety Disorder Schizophrenia Alzheimer’s Disease Multiple Sclerosis Thanks for your attention Depression Education Autism Attention Deficit Disorder Traumatic Brain Injury Post Traumatic Stress Disorder

Patent-pending: “Enhancing Cognition in the Presence of Distraction and/or Interruption” Faculty Fellows Associates Students Many thanks • Ted Zanto • David Ziegler • Cammie Rolle • Omar Alhashimi • Judy Pa • Morgan Hough • Jacki Janowich • Alan Legitt • Jyoti Mishra • WanYu Hsu • Roger Anguera • Benjamin Dorn • Peter Wais • Rajat Jain • Yixuan Ku • Joaquin Anguera • Martine Schouwenburg Game Development GlassBrain Hardware • Apple • NVIDIA • Oculus VR • Matt Omernick • Ty Clark • Tim Mullen • Myers Sound • Dmitri Ellingson • Matt Whitman • Christian Kothe • Eric Johnson • Mike Gonzales • to Gazzlab alumni, collaborators, • Oleg Konigs • Noah Fahlstein • Mickey Hart www.gazzlab.com • John Fesenko research and industry partners ... Financial Support • National Institute on Aging • Ellison Medical Foundation • UCSF CTSI • National Institute of Mental Health • James Gates Family Foundation • Posit Science • American Federation of Aging Research • Rose Family Foundation • Pfizer / Eisai • Robert Wood Johnson Foundation • Feldman Family Foundation • Tim Ferriss • Zynga.org Foundation • Grammy Foundation • William Getty • Center 17 Foundation • Biggelsworth Foundation • Tully and Elise Friedman • Sandler Foundation • Laney and Pasha Thornton • Sara and Evan Williams Foundation Move to the Real World World Aki Aki Aki Aki Aki Aki Aki Aki Aki Akili Akili Interactive Labs li li Int li li li li li li li Int Int Int Int Int Int Int Int Intera eracti era era era cti cti cti cti cti cti cti cti ctive ve ve Lab ve ve Lab Lab Lab Lab Lab Lab Lab Lab Labs s s s s Co-founder and Chief Science Advisor

Physical / Cognitive Body-Brain Trainer Game Developer Leads: Ty Clark & Roger Anguera Collaborators: Anthony Luke & Christian Thompson Rhythm Rhythmicity Game Developer Lead: Studio Bee Collaborator: Mickey Hart

Distributed Attention Virtual Attention Internal Attention Meditrain Game Developer Lead: Zynga Collaborator: Jack Kornfield