Are we there yet? Progress toward
an intervention for impairments in
spatial and temporal cognition
MIND INSTITUTE
Tony J. Simon Ph.D.
MIND Institute
University of California, Davis
tjsimon@ucdavis.edu
Twitter: @22qUCDMIND
Bottom Line - At the Top!
❖
Goal: create a truly evidence-based digital
neurotherapeutic intervention indicated for several
disorder populations
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Planned Deliverables: scientifically-validated, marketready intervention & efficacy data
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Value: real health, not consumer/entertainment,
product backed by expert clinician-scientist lab & data
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What is the Problem?
Some brains incompletely represent spatial/temporal information
Characteristic of several neurodevelopmental disorders (NDDs):
~2 million US individuals (genetically defined NDDs)
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Chromosome 22q11.2 Deletion syndrome
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Fragile X syndrome and “premutation carriers”
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Turner syndrome
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Williams syndrome
Commonly reported within phenotype of
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Non-Verbal Learning Disorder - less clearly defined disorder
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What is the Problem?
Some brains incompletely represent spatial/temporal information
As a consequence of:
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Healthy aging of the neurocognitive system
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Brain injury or insult to parietal lobes/hippocampus
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Open heart surgery repairs for congenital heart defects
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or possibly, cardiac defect’s effect on brain development?
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What Is The Solution?
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Fastbrain*, a “Digital Drug” neurotherapeutic
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Convergence of video game technology and
two cognitive neuroscience evidence bases
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Targeted to specific neurocognitive functions
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Novel proprietary algorithms adaptively
titrate neurocognitive stimulation solely to
individual’s spatiotemporal ability
*Patent pending
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Spatial /
Temporal
Resolution
in NDDs
Fastbrain*
Action Video
Game
Cognitive
Effects
What is the Problem?
Fix your eyes on the cross on left. Count the bars on the right without moving eyes
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Brain incompletely represents spatial/temporal information
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as in photo from 4 megapixel vs. 16 megapixel camera
Features of individual units merge into others = “crowding”
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Hypergranularity hypothesis for NDDs - Simon, 2008
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loss of higher spatial and temporal frequency detection?
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Primary Patient Group
Indication: Impaired ability to mentally represent and
process information about space and time.
Leads to significant functional impairments in:
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ability to understand quantity, learn numbers, do math,
make change, tell time, learn to drive, navigate ….
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creates lifelong stress and anxiety, reduces employment
opportunities and earnings, if not independent living
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individuals become lifelong consumers of, not
contributors to, societal resources
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What is the Evidence?
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Children with 22q11.2DS much less able than typically
developing peers to use attention to accurately detect objects
beyond center of visual focus
Each ring is 10º
more “eccentric”
from center
What is the Evidence?
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When comparing a test magnitude to a fixed reference
magnitude, children with 22q11.2DS require a significantly
greater difference to perform as accurately as typically
developing children.
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most TD children 80% correct at 93% vs. 87% ratio for children
with 22q11.2DS, who show even
greater impairment for time
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What is the Evidence?
Children with 22q11.2DS much less able than typically
developing peers to accurately identify out-of-phase
Flicker
flickering target
Phas
Flicker Phase all groups
100
TD=39
22q=58
SCA=27
90
100
TD
22q
SCA
90
80
Accuracy (%)
80
Accuracy (%)
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70
70
60
60
50
50
40
2
4
6
Hz
8
10
40
P difficulty
, 0.003) and,
expected, this
emerged
numbers
above them
of asprocessing
a difference
second only
target
that for
comes
200–500
subitizing
range
of NVGPs.
Errorfirst
bars one.
denoteSecond
s.e.m. (*Pis,the
0.05,cost
**P ,
after the
onset
of the
of 0.01).
switchin
tasks between the first and second target (from identification
detection);
unlike the
attentional
blinkover
per the
se, this
effect
mo
enhanced
allocation
of spatial
attention
visual
field,is even
pronounced
when the
targets are temporally adjacent and th
locations,
intwo
VGPs.
Figure 2 Enumeration performance. When asked to report the number of squares briefly untrained
as the time
between
targetsthat
increases.
Th
flashed, VGPs were able to apprehend more items at once than were NVGPs (4.9 versus decreases
The threeslowly
experiments
described
sothe
fartwo
indicated
video-ga
attentional
bottleneck
is not specific
to vision
but rather
3.3). Overall, VGPs were significantly more accurate than NVGPs (78% versus 65%,
playing
enhances
the capacity
of visual
attention
and itsappea
spa
21,23,24
.
Thus,
by
using
an
identification/detection
attention
amodal
P , 0.003) and, as expected, this difference only emerged for numbers above the
distribution. We next examined the temporal characteristics
blink attention
task, we could
test whether
aft
subitizing range of NVGPs. Error bars denote s.e.m. (*P , 0.05, **P , 0.01).
visual
and asked
whether the
the enhanced
pressure tocapacities
act rapidly
video-game
not only
applied to
purely
visualgames,
bottlene
several
visual training
items, which
is inherent
to amost
action
al
but
also
generalized
to
an
amodal
one.
enhanced allocation of spatial attention over the visual field, even at
untrained locations, in VGPs.
The three experiments described so far indicated that video-game
playing enhances the capacity of visual attention and its spatial
distribution. We next examined the temporal characteristics of
visual attention and asked whether the pressure to act rapidly on
several visual items, which is inherent to most action games, alters
What Is The Solution?
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Fastbrain is a digital neurotherapeutic
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Uniquely translates action video gaming
“active compound” into treatment
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Many studies show enhanced spatial/
temporal resolution in serious action
gamers (VGP) and trained non-gamers
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No such change results from non action
game types (e.g. Tetris)
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Figure 3 Measure of attention over space. a, Sequence of displays in the useful fie
& Bavelier.
Nature,
2003(triangle within c
view task. Participants indicatedGreen
the spoke
on which the
small target
Figure
4
Measure
of
attention
over
time.
a,
Attentional
blink
task.
Blackaffords
letters an
were
appeared. By presenting the target at different eccentricities, this task
Digital Neurotherapeutics - Better Targeted?
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Medications alter levels of
target across entire brain
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Targets need instead to be
specific circuits & functions
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Cannot train whole brain
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Most “brain training” creates
non-transferrable practice
Digital vs Pharma Neurotherapeutics
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Behavior change is target outcome, possible with digital
alone
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Pharma alone may well be only half the intervention
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e.g. failed trials of FXS drugs like mGluR inhibitors
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not solely due to differential responders
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“what fires together wires together” won’t happen
without targeted behavioral intervention
Better outcome measured derivable from source paradigms
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Why Not Off-The-Shelf Games?
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Many AVGs not great for cognitively impaired kids
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Commercial game algorithms respond to many factors
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Instead, convert AVG active compound to health product
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adaptivity not targeted to spatiotemporal ability
disguised as game with commercial-level production
values to ensure motivation & compliance
Must be “medicine that children want to take”!
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Fastbrain Functional Prototype
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Met our criteria for a scalable prototype
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Filed patent for proprietary algorithms
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Completed basic play testing/focus grouping
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played by 2 kids (7 & 8 years) from target populations
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both challenged but showed progress
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very motivated to play more
Now cacheing data with IRB approval & iterating design
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Considerable work put into decisions on optimal
appropriate platform and input device to best
translate science and accommodate target populations
So, Does Fastbrain Work?
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Current prototype only
Spatial Extent
intended as proof of concept
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We limited the “range” &
accelerated the adaptation
Space
Space
6 year-old
impaired child
Young
adult unimpaired
“gamer”
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Yet, prototype is sensitive to
competence & generates
Temporal Rate
change in the impaired!
Shows the algorithms can
achieve their stated goals!
Time
Time
Does Fastbrain Induce Change?
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To try to extend training, we
changed “consistency”
parameter
requires 14 of 20 correct for
FOV change (from 7 of 10)
AB returned 4 months later
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FB20 games 1 & 2 improvement
slower, asymptotes similarly,
increased duration
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possible enhanced initial
ability? Does achieve longer
play (i.e. training) time
Spatial Extent
Temporal Rate
What’s Next?
•Pilot efficacy trial - “unfunded” project underway
• Implement functionality for larger trials/experiments
•Will require significant investment of resources
• License IP to existing entity & develop in
partnership
• create start-up, raise funds, hire staff ……
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Thank you for your time!
MIND INSTITUTE
What’s The Expected Exit?
A. Initiate start-up, raise $$, develop full Fastbrain product
B. License IP to existing entity & develop in partnership
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“Brain health” company seeking new/more evidencebased neurotherapeutics
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Akili, Lumosity, LearningRx, HappyNeuron, Posit
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