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

SLIDE 1

Harnessing Brain Plasticity

Adam Gazzaley, MD PhD

Professor - Neurology, Physiology and Psychiatry Director- Gazzaley Lab, Neuroscape Lab Neuroscience Imaging Center University of California, San Francisco

Akili Interactive Labs Co-founder and Chief Science Advisor Pending patents:

“Enhancing Cognition in the Presence of Distraction and/or Interruption” “Method of Suppressing Irrelevant Stimuli” “Methods of Enhancing Performance on a Cognitive Task By Improved Self-Regulation of Internal Distraction and Computer Readable Medium and Devices for Practicing the Same” “Methods of Enhancing Cognition and Systems for Practicing the Same”

Disclosures

Challenge

Develop an effective approach to enhance cognition in both healthy and impaired individuals

Poor characterization
Poor targeting
Non-personalized
Unimodal
Open Loop

60 year old with mild cognitive impairment

This is just not good enough not

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Current Approach

SLIDE 2

Create a New Approach

closed-loop targeted personalized multimodal

fMRI EEG TMS EEG fM fMRI RI

Create a New Approach

Step 1: Understand the target

Our mental abilities that allow us to dynamically interact with our complex environment based on our goals

Cognitive Control

Attention Working Memory Goal Management

Early sensory processing modulation mediated by prefrontal cortical networks Declines as we age

Gazzaley et al. Cerebral Cortex (2007)
Wais et al. Journal of Neuroscience (2010)
Zanto et al. Nature Neuroscience (2011)
Gazzaley, et al. Journal of Cognitive Neuroscience (2005)
Clapp, Rubens and Gazzaley Cerebral Cortex (2010)
Berry et al. Journal of Neurophysiology (2009)
Zanto & Gazzaley Journal of Neuroscience (2010)
Rutman et al. Journal of Cognitive Neuroscience (2009)
Chadick & Gazzaley Nature Neuroscience (2011)
Wais & Gazzaley Psychonomic Bulletin and Review (2011)
Wais, Kim & Gazzaley Cerebral Cortex (

(2011)

Mishra & Gazzaley Journal of Neuroscience (2012)
Zanto, Rubens & Gazzaley Neuroimage (2010)

Gazzaley Neuropsychologia (2011)

Gazzaley Principles of Frontal Lobe Function (2011)

Gazzaley et al. PNAS (2008)
Gazzaley et al. Nature Neuroscience (2005)
Zanto, et al. Cortex (2010)
Clapp & Gazzaley Neurobiology of Aging (2010)
Zanto & Gazzaley Neuropsychologia (2010)
Gazzaley et al. Neuropsychology (2007)
Clapp, Rubens & Gazzaley PNAS (2011)
Wais & Gazzaley Brain Research (2012)
Anguera & Gazzaley Clinical Neurophysiology (2011)
Cashdollar et al. Psychology and Aging (2013)
Berry et al. PLoS One (2010)
Mishra & Gazzaley Neuropsychologia (2013)
Zanto et al. PLoS One (2013)

Cognitive Control

SLIDE 3

Step 2: Build an engine Step 1: Understand the target

Create a New Approach

Step 2: Build an engine

Create a New Approach

Targeting
Personalized
Multimodal
Closed Loop

Adaptivity / Feedback

cognitive exercises and video game training

Enhance cognitive control abilities in healthy older adults

Attention Working Memory Goal Management

Interference Training Study

2008-2013

Anguera, Boccanfuso, Rintoul, Al-Hashimi, Faraji, Janowich, Kong, Larraburo, Rolle, Johnston & Gazzaley Video game training enhances cognitive control in older adults Nature 2013

Joaquin Anguera

SLIDE 4

Funded by Robert Wood Johnson Foundation

Interference Training

Training Study

1 month later 12 hours

Multitasking Performance mance

100%
80%
60%
40%
20%

0%

20s 30s 40s 50s 60s 70s

Multi-tasking Index

Decades of Life

Anguera et al. Nature 2013

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%

Midline Frontal Theta

27%
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27%

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%

63%
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63%

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%

12 hours 12 h 12 h 12 h 12 hours

urs
urs

6 months later

Transfer of Benefits

& Attention Span Working Memory

12 hours

Anguera et al. Nature 2013

A Neural Bridge

Pre -Training

12 hours Pre & Post

Attention Span Transfer of Benefits Sustained Benefits Multitasking on Game

Post -Training

Anguera et al. Nature 2013

SLIDE 5

★ 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 prefrontal cortex networks.

Move to the Real World

Akili Interactive Labs Co-founder and Chief Science Advisor

Patent-pending: “Enhancing Cognition in the Presence of Distraction and/or Interruption”

Akili Int cti Lab Aki Aki Aki Aki Aki Aki Akili li li li li li li Int Int Int Int Int Int Intera era era era eracti cti cti cti cti cti ctive ve ve ve ve Lab Lab Lab Lab Lab Lab Labs s s s s

World

★ Attention Deficit Disorder (ADD)

Scott Kollins, Duke University / Andrew Cutler, FLCRC
[Shire Pharmaceuticals]

★ Depression

Patricia Arean, UCSF
[NIH]

★ Traumatic Brain Injury (TBI)

Kristine Yaffe, UCSF

★ Alzheimer’s Disease

[Pfizer]

★ Autism

Elysa Marco, UCSF
[Wallace Foundation / James Gates Family Foundation]

Evaluate as Diagnostics & Therapeutics

r,

Famil mily F y Foundat dation ion] ]

Bridging the Gap Between Technology and Neuroscience

Neuroscapelab.com

SLIDE 6

Mobile / Wireless

New Technology

Virtual Reality Motion Capture

New Technology

New Games...

SLIDE 7

Physical Rhythm Meditation Attention

Neuro Crossfit

Step 3: Enhance the effects Step 2: Build the engine Step 1: Understand the target

Create a New Approach

Neuromodulation Neurofeedback

Video Games

Enhance the Effects Real-Time EEG

SLIDE 8

Close the Loop

Behavior Environment Electrical Neural

2015 2020 2015 2015 2020 2015 2015

EEG EEG

targeted / personalized / multimodal / closed-loop

G

Alzheimer’s Disease Anxiety Disorder Attention Deficit Disorder Depression Post Traumatic Stress Disorder Autism Schizophrenia Traumatic Brain Injury Parkinson’s Disease Multiple Sclerosis

Over the Next 10 Years ...

Education

Addiction

Thanks for your attention

SLIDE 9

Many thanks

Omar Alhashimi
Alan Legitt
Benjamin Dorn
Cammie Rolle
Jacki Janowich
Roger Anguera
Rajat Jain

Students Associates Financial Support

David Ziegler
Morgan Hough
WanYu Hsu
Yixuan Ku
Martine Schouwenburg

Fellows

www.gazzlab.com

Game Development

Matt Omernick
Dmitri Ellingson
Eric Johnson
Noah Fahlstein

Faculty

Ted Zanto
Judy Pa
Jyoti Mishra
Peter Wais
Joaquin Anguera

Hardware

Apple
NVIDIA
National Institute on Aging
National Institute of Mental Health
American Federation of Aging Research
Robert Wood Johnson Foundation
Zynga.org Foundation
Center 17 Foundation
Sandler Foundation
Ellison Medical Foundation
James Gates Family Foundation
Rose Family Foundation
Feldman Family Foundation
Grammy Foundation
Biggelsworth Foundation
Laney and Pasha Thornton
UCSF CTSI
Posit Science
Pfizer / Eisai
Tim Ferriss
William Getty
Tully and Elise Friedman
Sara and Evan Williams Foundation

GlassBrain

Tim Mullen
Christian Kothe
Oleg Konigs
John Fesenko
Oculus VR
Ty Clark
Matt Whitman
Mike Gonzales
Mickey Hart
to Gazzlab alumni, collaborators,

research and industry partners ...

Myers Sound

Move to the Real World

Akili Interactive Labs Co-founder and Chief Science Advisor

Patent-pending: “Enhancing Cognition in the Presence of Distraction and/or Interruption”

Aki Aki Aki Aki Aki Aki Aki Aki Aki Akili li li li li li li li li li Int Int Int Int Int Int Int Int Int Intera era era era eracti cti cti cti cti cti cti cti cti ctive ve ve ve ve Lab Lab Lab Lab Lab Lab Lab Lab Lab Labs s s s s

World

SLIDE 10

Physical / Cognitive

Body-Brain Trainer

Collaborators: Anthony Luke & Christian Thompson Game Developer Leads: Ty Clark & Roger Anguera

Rhythm

Rhythmicity

Collaborator: Mickey Hart Game Developer Lead: Studio Bee

SLIDE 11

Distributed Attention

Virtual Attention

Internal Attention

Meditrain

Collaborator: Jack Kornfield Game Developer Lead: Zynga

SLIDE 12

100%
80%
60%
40%
20%

0%

20s 30s 40s 50s 60s 70s

% % %

Multi-tasking Index d’

27%

No Cost

63%

Decades of Life

Anguera et al. Nature 2013

Interference Training

12 hours

100%
80%
60%
40%
20%

0%

20s 30s 40s 50s 60s 70s

% % %

Multi-tasking Index d’ No Cost

63%

Decades of Life

Training Study

13%

Pre 1 mo. 6 mo.

27%

Single-task train Multi-task train No-contact control

Anguera et al. Nature 2013

Interference Training

100%
80%
60%
40%
20%

0%

20s 30s 40s 50s 60s 70s

% %

Multi-tasking Index d’ No Cost

Decades of Life

Training Study

Pre 1 mo. 6 mo.

Single-task train Multi-task train No-contact control

40%
20

%

40%
20
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20%

% %

Anguera et al. Nature 2013

Interference Training

SLIDE 13

Frontal Theta Power

0 - 600 ms

Before Training After Training

12 hours

Anguera et al. Nature 2013

Interference Training

†

Initial

*

Older Adults Younger Adults

Older Adults Post-Training

Single-Task Training Si le le-T k Multi-Task Training

†

No Contact Control de de de der r r

Older Adults Post-Training ng ng ng

Frontal Theta Power

12 hours

Interference Training

†

Initial

*

Older Adults Younger Adults

Older Adults Post-Training

Single-Task Training Si le le-T k Multi-Task Training

†

No Contact Control de de de der r r

Old Older Adults Post-Training ng ng ng Initial

Long-Range Theta Coherence

12 hours

†

Interference Training

Multi-task training Single-task training No-contact control

150
75

75 150

Pre-Post RT (msec)

* †

Working Memory

Delayed-Recognition Task Tests of Variables of Attention (TOVA)

a)

5

6 18 29 40

Pre-Post RT (msec)

Sustained Attention

* †

Anguera et al. Nature 2013

12 hours

Interference Training

SLIDE 14

22.5

22.5 45 67.5 90

1.25

1.25 2.5 3.75 5

R² = 0.3163

Pre-Post TOVA RT

Post-Pre mf Theta

Magnitude of Theta Enhancement Correlates with Gains in Sustained Attention (TOVA)

Pre-Train Post-Train

12 hours

Interference Training

1.75
1.5
1.25
1
0.75
0.5
0.25
1

1 2 3 4 5

R² = 0.5738

Post-Pre mf Theta

Magnitude of Theta Enhancement Correlates with Sustained Performance Gains at 6 months

6 month - Post Train Multi-tasking cost

12 hours

Pre-Train Post-Train