GAMING FOR BRAIN TRAINING - Craig Stark, Ph.D - UCI MIND

G AMING FOR B RAIN T RAINING

 Craig Stark, Ph.D.
 James L. McGaugh Chair in Neurobiology of Learning and Memory

 Department of Neurobiology and Behavior
 School of Biological Sciences, University of California Irvine

 UCI MIND, ADRC, and CNLM

Art by Greg Dunn – www.gregadunn.com

Take Home Messages

1) Our hippocampal memory system declines with age
 and is part of why we lose our memory for details.

2) ”Environmental enrichment” using video games can
be used to improve hippocampal function and memory.

Typical kinds of memory that get worse with age – memory
for details and specifics

 I remember it, but when was it?

 I’ve seen her before and know I met her, but who is she?

 I know I came home and put my keys down, but where are they?

 Extensive research in our lab and others have shown this
 happens because of changes to your hippocampus.

Meet the hippocampus
 Using pattern separation, the
 hippocampus lets us rapidly store
 arbitrary associations to support:
 Episodic memory
 Detail memory
 Recollection
 Source memory
 Associations

Mnemonic Similarity Task (MST) lets us test how
well our hippocampal memory is working

 Encoding Phase Test Phase
 Indoor/Outdoor? Old/Similar/New? … … …

 Repetitions 1
 JRW
 0.6
 **

 Corrected Pattern Separation
 0.5
 0.8 CA

 Corrected Recognition
 RS

 Novel Foils 0.6
 0.4

 0.3
 0.4
 Similar Lures 0.2 CA

 0.2 RS
 0.1
 128 items JRW
 0 0
 2.5 s Patients Controls Patients
 Con
 Controls
 0.5 s ISI
 H Con H
 Kirwan, Hartshorn, Stark, Goodrich-
 Hunsaker, Hopkins, & Stark (2012)

Kirwan & Stark (2007, Learn Mem); Stark, Yassa, Lacy, & Stark (2013, Neuropsychologia); Stark, Kirwan, & Stark (2019, TICS)

Aging leads to impaired memory for details of events
(discrimination) or lower memory “fidelity”
 Pattern Separation
 Discrimination Score
 / Details Recognition / Gist
 Traditional Recognition
 0.5
 MS (Lure p|sim - Foil p|sim)

 … 1.0 … …

 Old(True Rep) - Old(Foil)
 0.4
 0.8

 0.3
 0.6

 0.2 0.4

 0.1 0.2

 0.0 0.0
 I
 9

 9

 4

 9

 I
 9

 9

 4

 9
 C

 C
 -3

 -5

 -7

 -8

 -3

 -5

 -7

 -8
 M

 M
 20

 40

 60

 75
 20

 40

 60

 75

 Age Group Age Group

Stark, Yassa, Lacy, & Stark (2013)

Aging (in rats) leads to a changes in hippocampal
connectivity and function
 Auto-associative
 Amyg. Mossy Fibers
 DG Fibers
 Perforant
 PHC/POR Path
 CA3
 II VTA MS
 (DA) (ACh)
 Neocortical ERC III
 Association Areas Schaffer
 IV-VI Collaterals

 PRC

 PreS ParS CA1
 RSC
 Sub Sub-
 cort.

 Fornix

 MB
Stark and Stark (2015)

Diffusion weighted imaging lets us examine the brain’s
connections and microstructure

Hippocampal connectivity via diffusion imaging
shows age-related changes tied to memory

 Global Diffusivity
 Tract Diffusivity |
 ?

 R2 = 0.29, p < 0.001

 0.04 Young
 Old Age
 Perforant Path Signal

 0.03 Tract FA | Global FA
 0.02
 Bennett, Huffman & Stark (2014, Cerebral Cortex)
 0.01

 0.00
 -5 0 5
 Medial Position Lateral

 Yassa, Muftuler, & Stark (2010, PNAS)

Within hippocampal gray, diffusion metrics of
neurite density (NDI) increase with age

 Hippocampal Grey Matter Hippocampal DG/CA3 Grey Matter

 0.8 ✱✱

 0.6
 NDI

 NDI
 0.4

 0.2

 0.0
 Young Older 0 20 40 60 80 100
 Age

 Ventakesh, Stark, Stark, & Bennet (2020) Radhakrishnan, Stark, & Stark (2020)

The age-related changes in gray matter microstructure
are tied to memory performance as well
 DG/CA3
 0.2
 Globally Regressed NDI

 0.1

 0.0

 -0.1
 Old
 Young " = 0.2647; = 0.0010
 -0.2
 0 5 10 15 20
 RAVLT
 Memory Delay
 Performance

Radhakrishnan, Stark, & Stark (2020)

Take Home Message: Part 1

Our memory gets worse as we age, but in a particular
 way. We keep the gist and lose the details.

At least some of this is tied to age-related alterations
 in hippocampal circuitry.

 Can we do anything about this?

Leading an “enriched” life has positive effects on a mouse’s
brain (and the hippocampus in particular)
 Hippocampal Neurogenesis

 Standard “Enriched”

 # New Adult Neurons
 van Praag, Kempermann, & Gage (2000)

 Amount of Exploration
 Freund et al (2013)

Exploration and enrichment help mice, but what about us? Would
environmental enrichment help our hippocampus and memory?

We could try this in people… Baltimore KidsWorks

Castle Rock Epic Sky Tour

Geocaching (REI) Underground city of Derinkuyu (Stuart Jackson-Carter)

Can we use actual videogames to provide enrichment
and improve memory?

Video gamers who play complex 3D games have better
memory for details than non-gamers

 ?

 Non-Gamers Gamers

Clemenson & Stark (2015, J Neurosci)

Starting to play videogames with spatial exploration
improves this hippocampus-based memory for details

 A. Hippocampal-based Memory
 *
 0.6
 *
 Super Mario

 0.4
 No Game + Angry Birds
 ?
 No Game Control 0.2
 Angry Birds
 Super Mario Bros 3D World

 2 weeks 2 weeks
 0.0
Pre-Test Post-Test 1 Post-Test 2
 Before After Delay

Clemenson & Stark (2015, J Neurosci)

This works in older adults too

Clemenson, Stark, Rutledge, & Stark (2020)

This works in older adults too

 ?

 Washout
 Washout
Clemenson, Stark, Rutledge, & Stark (2020)

Across 5 studies and ~300 participants – the more enriching
the experience, the more your memory improves

 Young Older Young Middle Aged Older
 60-80 40-49 65-89
 0.20 0.20 0.20 0.20 0.20

 0.15 0.15 0.15 0.15 0.15

 0.10 0.10 0.10 0.10 0.10

 ? 0.05 0.05 0.05 0.05 0.05

 0.00 0.00 0.00 0.00 0.00

 Minecraft Minecraft Real-world
 -0.05 -0.05 -0.05 -0.05 -0.05

 Directed Building

 Directed Building
 Free Exploration

 Free Exploration

 Scavenger Hunt
 Explore & Build
 Free Building

 Free Building
 Super Mario

 Super Mario
 Angry Birds

 Angry Birds
 No contact

 No contact

 Real-world
 Solitaire

Clemenson & Stark (2015); Clemenson, Stark, Rutledge, & Stark (2020); Clemenson, Henningfield & Stark (2019); Clemenson, Stark, & Stark (in preparation); Kolarik, Stark, Rutledge, & Stark (2020)

Games are great – but no matter what, engage in new things
and be engaged in what you do

Take Home Message: Part 2

 Exploring large, immersive video game worlds
 provides us with a proxy for environmental
 enrichment in humans.

 Like rodents, our memory performance improves
 with enrichment and spatial exploration seems to
 do this very well.

Credits
 Branden
 Kolarik
 Dane
 Clemenson
 Shauna
 Stark

 Jessica
 Lingad Hamsi
 Radhakrishnan

Alysa Ojeda Ham Lizabeth Mayer Kaitlyn Norton Noorhan Rahmatullah Alyssa Harris
Jocelyn Cho Anastasia Cervera Madeleine Duong Emily Castro Lulian Wang
Duran Baja Allyson Chu Shelby Clark Ariana Otero Steven Yang
Kevin Yin Lara Kirandag Nicholas Williams Zeqian Mao Sean Kil
Katrina Hough Ujwal Aluru Ali Karimi Derrick Quach Melisa Anjejo