Autism: New research, evidence-

based intervention

Martha S. Burns, Ph.D.

Joint Appointment Professor
Northwestern University
.

Selected New References

• Bolkan,S and Gordon J (2016) Untangling Autism. Nature, Volume 532. April 7,
45-46.
• Bourgeron, Thomas (2015) From the genetic architecture to synaptic plasticity in
autism spectrum disorder. NATURE REVIEWS NEUROSCIENCE, VOLUME 16,
SEPTEMBER 2015, 551-563
• Cupolillo, D. (2016) Autistic-Like Traits and Cerebellar Dysfunction in Purkinje
Cell PTEN Knock-Out Mice. Neuropsychopharmacology. Volume 41, Issue 6,
1457-1466
• e la Torre-Ubieta, L.. Won, H., Stein, J.L. and Geschwind, G.H. (2016)
Advancing the understanding of autism disease mechanisms though genetics.
Nature Medicine April ; 22(4): 345–361. doi:10.1038/nm.4071.
• Foxe, J. et al. (2013) Severe Multisensory Speech Integration Deficits in High-
Functioning School-Aged Children with Autism Spectrum Disorder (ASD) and
Their Resolution During Early Adolescence. Cerebral Cortex Advance Access
published August 28, 2013
• Herbert, Martha (2014) Autism Brain Origins-Environment and Physiology Really
Matter. Blog post July 2014 and summarized on Autism Speaks Website
• Jeste & Geschwind (2014) From Genes to Behaviour- a conceptual framework.
Nature Reviews Neurology Volume: 10, Pages:74–81
• Krumm, N. et al., (2014) A de novo convergence of autism genetics and
molecular neuroscience. Trends Neurosci. 2014 February ; 37(2): 95–105.
• Stoner, R., Chow, M. and Boyle, M. et al (2014) Patches of Disorganization in
the Neocortex of Children with Autism. New England Journal of Medicine,
370(13): 1209-1219
• Wells et al (2016) Thalamic reticular impairment underlies attention deficit
in Ptchd1Y/− mice. Nature Volume 532, April 7.
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DSM 5

• (DSM-5) defines ASD by deficits in two core

domains—
– social interaction and communication,
– repetitive, restrictive behaviors—
– with onset during early development.
• ASD unifies three previously separate but highly
related diagnoses: autistic disorder, Asperger’s
disorder and pervasive developmental
disorder–not otherwise specified (PDD-NOS).

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 Autism Prevalence
CDC, March 2016

1 in 68 in US
No change from 2012

Other statistics – CDC 2016

• ASD is about 4.5 times more common
among boys (1 in 42) than among girls
(1 in 189).
• ASD is reported to occur in all racial,
ethnic, and socioeconomic groups.
• About 1 in 6 children in the United
States have a developmental disability
– From mild (such as speech and language
impairments) to serious developmental
disabilities
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 So what is going on?
6 known issues
ASD’s are neurodevelopmental disorders
1. Patches of disrupted cortical
tissue
2. Problems with brain
connectivity

ASD’s are Neurodevelopmental

3. An imbalance in neural
excitation and inhibition
4. Pruning deficits (over and
under pruning)

ASD’s are Neurodevelopmental

5. There may be core brain

regions that get problems started
• This is important because drugs
can be developed to alter the
affects of a disrupted protein –
see e.g. Wells et al April 2016
6. There are genetically based
metabolic problems
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What else do we know?

• ASD’s are polygenetic –

– There are complex inherited and
mutant genetic changes
associated with ASD (and other
neurodevelopmental disorders
like seizure disorders, ID, and
perhaps learning disabilities)

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Reminder – How Synapses Work

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Reminder - Neurons that fire together

wire together in networks

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 Neuropathology #1
Patches of disrupted tissue, seen post-mortem

Stoner et al, 2014 findings : patches of disorganization in many areas of the

neocortex (the outer layer of gray matter in the brain), though not the same
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from one person to the next.

#1 Neuropathology (continued) –
Seen on MRI (Herbert 2014)

Herbert and colleagues have seen similar patches of cortical thinning and
thickening on MRI images of children with ASD distributed all over
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the cortex
(2014)

Neuropathology #2
FIGURE 3.
Problems with connectivity
Trajectories of Mean Fractional Anisotropy for High-Risk Groups, Projection Fiber Tracts
(Wolff, et al 2012)

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5
 Novel technique shows how autism
affects social brain
Published: Wednesday 14 October 2015
Medical News Today
• An observed lack of connectivity by Kay
Jann et al. in a network important for social
skills implies that information cannot flow as
it should between distant areas of the brain
• Helps explain why people with ASD have
difficulty in social responsiveness.

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Neuropathology #3:
Excitation/inhibition
• We have known about problems with
excitation and inhibition for over a decade
• J. L. R. Rubensteinand M. M. Merzenich
(2003) Model of autism: increased ratio of
excitation/inhibition in key neural systems.
Genes and Behavior.

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New research points to the genetics

that contribute to that disruption
• Bourgeron, 2015 • Figure 4 | Main
Complex genetic synaptic functions
mechanisms associated with
ASD.
contribute to the
disruption of
synaptic
homeostasis

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 Neuropathology # 4.
Pruning deficits
(over and under pruning)

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Synaptic pruning fine-tunes local circuitry – over or

under pruning would alter network development and
function

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Multisensory integration problems

• Identified by OT’s as • Seen in speech
sensory integration integration with visual
disorder processing as well
(Foxe et al, 2013)

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 Neuropathology #5
There may be core brain areas that get the
abnormal developmental process started

(Bolken & Jordon, 2016) a. Gene mutation associated with Thalamic

Reticular Nucleus

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Brief Primer on Genetics

• Genetic risk of autism increases with family
history – prevalence of ASD-risk genes
• There are also more rare genetic mutations
seen in individuals on the autism spectrum
• And, this is where it gets complicated – some
genetic mutations may cause problems with
neural connectivity by affecting synaptic
plasticity

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Neuropathology #5
There may be core brain areas that get
the abnormal developmental process
started (Cupolillo, et al. 2016; Cerebellar Purkinje Cells)
We have know since Margaret Bauman’s seminal research on aberrant
Purkinje cells in ASD that this may represent a key area of dysfunction

Cupolillo et al (2016) have identified a key gene that leads to the Purkinje
Cell dysfunction – and perhaps an underlying cause of social problems
Figure 5 Repetitive behavior and impaired sociability in PTEN-KO
mice. PTEN-KO mice

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 Understanding the Genetic Risk
of Autism is important

Bourgeron,
Bourgeron2015
2015 25

DeNovo mutations proliferate in

ASD’s
– DeNovo (anew) mutations in
maternal (egg) or paternal
cells (sperm), in stem cells, or
during brain development, are
seen in DNA samples of
children with ASD

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https://gene.sfari.org/autdb/Welcome.
do as of 3.30.17
Latest Statistics (Updated December, 2015)
# of Genes: 859
# of Curated References: 1521
# of Additional Non-curated References: 1366

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 What can be done with such a
complex condition?

• Behavioral treatments must be

individualized to the child’s
specific problems
• Exercises must be very
repetitive to compete with non-
adaptive networks

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The ASD Research

• 34 professionals across the country

• 100 children
– must have worked with Fast ForWord for at least
20 days
– must have been diagnosed within the Autism
Spectrum by a medical professional

• Two types of information

– Age equivalent test scores before and after
treatment
– Results of a functional skills checklist

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Changes in Attention After Fast ForWord Training

(73% response rate)

Attention
81 % Increase • for testing
1%
• for computer activities
Decrea • for structured therapy
se
activities
• for listening to stories
18 % • for group activities
No
Change

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 Changes in Language After Fast ForWord Training
(86% response rate)

Language
• response time
• following directions
83 % Improvement • understanding humor
1% • overall comprehension
Regression
• imitation skills for words &
phrases
16 %
• use of new vocabulary
No • length in utterance
Change
• answering questions - Y / N
• answering questions - WH
• verbal fluency - flow of speech
• overall expression
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Changes in Social Skills After Fast ForWord Training

(88% response rate)

Social/Communication skills
76 % Improvement
• eye contact
• addressing people by name
1%
Regression• topic maintenance
• appropriate attention-getting
• greetings / closures
• appropriate protesting / refusal
• ability to verbally negotiate
23 %
No Change • initiation of communication

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Russo, Hornickel, Nicol, Zecker, & Kraus, 2010

Improved pitch tracking

Pre Post

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 Typical 7 year old Struggling Reader
reader
Six weeks - 90
min/day – five
days a week
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The Economist: April 16-22, 2016

Special Section on “How to Deal with Autism”
– In America, less than ½ of those with
ASD graduate from High School
– Autism imposes hefty economic costs
– Costs could be as high as 2% of GDP –
but “this need not be the case”
“Beautiful or otherwise, an autistic mind is a
terrible thing to waste.” page 9

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1. Starts in the brain: builds “superhighways” in

language and reading areas.

2. Cross-trains memory, attention, processing, literacy

skills in a highly personalized and intense way than
other approaches.

Results: improvements in
attention, language, social skills, reading.

“My son is 11 with high functioning autism…He has finished one segment and
the results are great! He is able to sound out words better, spell better and
work with more focus.” – 2016 parent comment on Facebook

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 After the Webinar

The slides, a certificate of attendance, and a link to the

recording will be emailed within a few days. Thank you!

Request a personalized demo:

www.scientificlearning.com

Email additional questions: webinars@scilearn.com

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