1. Program for CognitiveProgram for Cognitive
Sciences (PICS)Sciences (PICS)
Dr. Joy Hirsch, DirectorDr. Joy Hirsch, Director
Harry D. Schneider, MD.
Co-Investigator
Debra Schneider
Clinical Coordinator
Autism Research
Program
COLUMBIA UNIVERSITY

2. TODAY’S CHAT…
 The discovery of language-specific
areas and their connections in the
brains of children with low-
functioning autism.
 FMRI-based emerging theories
leading to practical applications
and treatments.

3. Sharing knowledge is a good thing!
• Most of what I know is from parents who
keep me up to date about new biomedical
interventions and behavioral treatments.
• In return, I try to teach them something
about functional MRI – and linguistics.
• Let’s have a go at functional MRI first.

4. I. Principles of Functional Specificity in the BrainI. Principles of Functional Specificity in the Brain
• The Real Estate Principle: a
fundamental notion of brain
organization.
• It suggests the brain’s real
estate is divided into subunits
based on function.

5. To understand MRI we need to
review the atom.
MRI is based on the spinning of protons:

6. • Scanner Environment [1.5] T
• Protons align along an axis
Outside Field Inside Field
Protons in Brain
(scattered)
B. Spinning protons are littleB. Spinning protons are little
magnets: they make electricity.magnets: they make electricity.
[3.0] T
(aligned)
Protons in Brain

7. MAGNETISM MAKES
ELECTRICITY!
• Protons precess around the axis and create
a small electrical current (MRI signal)
RFi
(precess)
(wobble)
• A radio frequency pulse (63.3 mHz on an
“FM radio”) is applied to aligned protons

8. FINDING THE REAL ESTATEFINDING THE REAL ESTATE
These currents have different strengths depending
upon local magnetic field strengths: we use them to
find their location of origin in the brain
This electrical current is emitted by the protons
as they relax into their aligned state.
RFo
Location of
signals are
recorded for
structural MRI
u
n
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f
o
r
m
g
r
a
d
i
e
i
e
l
d
f
i
e
l
d

9. For functional MRI: Blood Oxygen Level
Dependent Signal (BOLD SIGNAL)
Deoxy-HGB is
paramagnetic and distorts
the local magnetic field,
causing signal loss
(Pauling,1936)
Result:
Less distortion of the
magnetic field in local MR
signal increase
Neural activation is
associated with an increase
in blood flow and oxygen
use.
(Roy & Sherrington, 1890)
Result:
Reduction in the proportion
of deoxy-HGB in the local
vasculature.
PhysiologyPhysiology PhysicsPhysics

10. Computations to get a FunctionalComputations to get a Functional
MRI MapMRI Map
FunctionalFunctional
Brain MapBrain Map
Reconstruction
Alignment
Voxel by voxel analysis
Graphical representation

11. Normal Language Areas of the
Cortex

12. With fMRI we use Diffusion Tensor Imaging (DTI)
Wernicke
Broca
Passive listening:
Arcuate Fasciculus
Axial view of functional activity Sagittal view of DTI Connections between
Broca’s and Wernicke’s Areas
DTI: Neural Connections
DTI map of a typical language system.

13. CLINICAL APPLICATIONS OF fMRICLINICAL APPLICATIONS OF fMRI
The science of the mind leads to theThe science of the mind leads to the
treatment of the mind.treatment of the mind.
 Mapping for neurosurgical planning
 Assessment of cognitive function in
non-responsive adults and babies
 Neural reorganization in dyslexia.
 Low-functioning language
Autism!

14. Neurosurgical planning: fMRI Task BatteryNeurosurgical planning: fMRI Task Battery
(active)
Picture
Naming
Listening
to Words
(passive)
Language
GTsGFiGTTGOi
Vision
Reversing
Checkerboard
CaS
(passive)
Motor
Finger Thumb
Tapping
GPrC
(active)
Sensory
Touch
GPoC
(passive)
From Hirsch, J., et al; Neurosurgery 47: 711-722, 2000
Applications of the Real Estate PrincipleApplications of the Real Estate Principle
Hirsch, J., Columbia University.

15. fMRI TO DIAGNOSE AND INFORM TREATMENT OF
ALTERNATIVE AND ATYPICAL NEUROCIRCUITRY OF BRAIN
Shaywitz, et
al. 1998
Howard &
Hirsch, 2004
Dyslexia Non-impaired
Dyslexia occurs in 15% of the U.S. population
Diagnoses Based On Variations in NeurocircuitryDiagnoses Based On Variations in Neurocircuitry
Program for Imaging and Cognitive Sciences J. Hirsch, Columbia University

16. Anxiety
Disorders,
PTSD
Neural
Reorganization
Eating
Disorders, AN,
Obesity
Deception
NeuroGenetics
Neural Surgical
Planning
Seizure
Localization
Autism
Disorders of
Consciousness
Decision
Sciences
NeuroLaw
Language
Acquisition
Pain
IV.FUTURE DIRECTIONS FOR BRAIN
MAPPING IN CLINICAL
NEUROSCIENCE

17. Now on to even more boring stuff!
LINGUISTICS


18. HOW DID YOU LEARN YOUR
(FIRST) LANGUAGE?
• No one really taught it to you!
• There were no verbs to conjugate.
• There were no behavioral interventions.
• You just looked, listened and one day you
began speaking!

19. What about language development
in a neurotypical child?
• Because languages are infinite and a childhood is only
finite, children can not just memorize language, they
must leap into the linguistic unknown and generalize to
an infinite world of as-yet unspoken sentences. (Pinker,
1994)
• This is done by acquiring grammar. The child is a
‘naturalist’, passively observing the speech of other‘s.
The child picks up grammar “implicitly” (unconsciously).
• Chomsky: “Language is innate” (we are born “hard-
wired” to learn a language.

20. Neurotypical grammar (cont’d):
• Although some children might say
“Mommy gived the book”
• A child never learns to say:
“Mommy the gives book”
• The unconscious grammar machine
does not allow for too much error!

21. OUR BRAINS HAVE TWO (2)
memory systems
• 1) The Explicit System – also called the
“declarative” system and the conscious
memory systems.
Conscious vs. Unconscious!
• 2) The Implicit System – also called the
“procedural” and unconscious systems”

22. OUR BRAINS HAVE TWO (2)
memory systems
• 1) The Explicit System – also called the
“declarative” system and the conscious
memory systems.
• REMEMBER THE 2 MEMORY
SYSTEMS!
• 2) The Implicit System – also called the
“procedural” and unconscious systems”

23. Implicit and Explicit Memory: an
important distinction!
• Implicit memory: our previous experiences aid
in the performance of tasks without conscious
awareness of these previous experiences
(Schacter, 1987). “déjà vu”: “If you give me the
first letter, I will remember the word.”
 In daily life, people rely on implicit memory
(procedural memory) that allows us to
remember how to tie our shoes or ride a bicycle
without consciously thinking about these
activities

24. On the other hand, Explicit Memory
• Explicit memory is the conscious, intentional
recollection of previous experiences and
information.
• In daily life, people rely on explicit memory
(declarative memory), that stores facts:
memories that can be consciously discussed,
textbook learning, knowledge, memories of
personal events, and learning new vocabulary.

25. A good example: How do we drive
a car?
• Implicitly ? (automatic and unconscious)
• Explicitly? (thinking about what we learned
in driving school)?
• Or both ways? e.g. “Did you ever drive
home…”

26. A BRAIN MODEL of LANGUAGE
 Our mental grammar (SVO) depends on a
neural system composed of a network of basal-
ganglia connected to frontal, parietal and
cerebellar structures: this is implicit,
unconscious memory or procedural memory.
 Learning words depends on a different brain
system- the temporal-lobe and hippocampus:
this is (conscious, explicit or) declarative
memory which stores facts and events you can
recall.

27. Normal Language Areas of the
Cortex: explicit learning

28. The Procedural Brain (“Reptile”
Brain)- for the infant’s language!

29. What are the parts of the
Procedural Memory Machine:
• Basal Ganglia (Parkinson's disease).
• Cerebellum (balance, movement)
• Substantia Nigra (dopamine)
• Thalamus (a translator for brain)
• Superior temporal cortex (comprehension
areas)
• pre-SMA : motor planning areas.

30. How do children “learn to speak”?
• The do not “learn” it, they “acquire” it.
• ALL CHILDREN FROM BIRTH TO
ABOUT AGE TWO (2) USE THE
IMPLICIT SYSTEM FOR LANGUAGE.
• IT IS AN UNCONSCIOUS PROCESS
THAT DOES NOT INVOLVE TEACHING!

31. For the Purposes of this talk,
Let’s keep it simple:
• Implicit = Unconscious = Procedural
MEMORY
• Explicit = Conscious = Declarative

32. Do the two systems work together?
• NO ! But, teaching explicitly face to face
can “help” implicit learning indirectly:
• It can help the brain focus on relevant
items, such as sounds, parts of words.
• It can make these relevant language
features stand out more, such as
concentrating on the ends of words or
what happens between words.

33. Is Grammar just another skill, like
driving a car?
• YES!
• It is no coincidence that the
beginnings of grammar follow
closely on the heels of a baby –
the ability to walk and talk both
appear around fifteen months!
(Pinker, 1994)

34. THINK OF AMNESIA
• A person with amnesia (retrograde) can
not remember what happened in the past
– but they can remember how to drive a
car! They do NOT forget implicit stuff!
• A person with anterograde amnesia can
not remember what the just learned: “each
day is a new day” – but they can be taught
to drive! They can be taught implicit stuff!

35. A NEUROTYPICAL CHILD’S
LANGUAGE

36. What about an ‘autistic’ child’s
language acquisition?
Language Production
• No words by 12 to 14 months.
• Less than one dozen words by age 18 months.
• No two-word phrases by age two years or sentences by
age three years
• Inability to use language conversationally, "talking to
talk" .
• Inability to recount an event or tell a coherent story.
Language Comprehension:
• How much do they really understand?
• Have they acquired the procedural grammar “blueprint”.?
• If they can understand: “ the boy hugs the girl”,
can they also understand “the girl is hugged by the boy’?

37. Do LFA autism children use implicit
or explicit processes ?
• Low-functioning children with autism (generally)
have to MEMORIZE almost of the language they
can produce ! This is explicit or declarative
memory and it takes up a lot of space on the
brain’s “hard drive”.
• This is a huge mental process, using up a lot of
brain energy and by itself may not lead to full
language recovery.

38. SYNTAX DEPENDS ON
PROCEDURAL MEMORY
• Faulty procedural learning may complicate
the simultaneous application of different
elements of verbal communication.
• Verbal “intonation” of children with ASD is
better in repetition tasks (declarative
memory)
• Than in spontaneous speech (procedural
memory)

39. Faulty procedural memory
a child with ASD will not able to memorize:
• prepositions, adjectives, adverbs
• pronouns: I, you, he, she, my, your, etc.),
• things (this, that, these, those),
• places (here, there, above, below, etc.),
• times (now, tomorrow, yesterday);
• ungrammatical sentences
• Word meaning (frequently used words)

40. The Infant Needs Procedural
memory
• Learning of categories requires procedural
memory: difficult in ASD children
• If some categories are learned, many ASD kids
might not be able to understand them within the
meaning of WHOLE sentences, which the
procedural system needs to reconstruct in the
brain actions described by another speaker.
• The absence of imaginative activity might also
occur, because of the problems surrounding the
learning of concepts and categories, which also
requires procedural memory.

41. What does the LFA brain have to
do with this?
• There is often limited, implicit “innate” grammar usable in
autism, because deep brain structures have been
partially damaged. The language-learning template was
most likely NOT blueprinted in many kids!
• The ability to speak requires being able to retrieve
the grammar template from other brain areas – in
ASD the connections to these areas are not intact.
• Our goal is to stimulate these brain areas to acquire
the template – i.e., to give them back a basic
language blueprint – and then to help them restore
neural connections to retrieve it!

42. Autism is a “Spectrum Disorder”
• Autistic brains are different from
neurotypical brains and low-functioning
autistic brains are different from high-
functioning autistic brains.
• There is more pathology in the grey
matter, the white matter fibers, specific
brain areas (e.g. the cerebellum) and the
connections between these areas.

43. Alternative Neurocircuitry in Autism Spectrum DisorderAlternative Neurocircuitry in Autism Spectrum Disorder
Autism occurs in as many as 1 child in 150 in the U.S.

44. NEUROTYPICAL CHILD 7

45. Diffusion Tensor Imaging (DTI): LF autism
Wernicke
Broca
Arcuate Fasciculus
DTI map: Wernicke’s Area does NOT reach
Broca’s Area.

46. AUTISTIC 6 YEAR OLD

47. AUTISTIC 7 YEAR OLD

48. Language “Real Estate”
Language Connectivity
Normal Autistic 6 yr. old Autistic 7 yr. old
TITLE

49. What do the activations show?
• We do not always find typical language
areas, such as Broca’s and Wernicke’s
areas, become activated to passive
language listening.
• Broca’s area sometimes responds to
music without responding to language!
• The “language activations” are often
pushed towards the posterior parts of the
brain (sensory integration areas).

50. What else do we see in the
connections?
• The connections from Wernicke’s area, when
present, do not make it to Broca’s area, which
they should via the Arcuate Fasciculus.
• Sometimes these connections are incomplete,
sometimes they are very meager in appearance,
and sometimes they go the wrong way: to the
back of the brain instead of the front.
• Sometimes they take a “southern route” towards
the front of the brain, instead of a northern one –
which they should take.

51. Some initial thoughts.
• DTI confirms the notion that not only abnormal
areas for language are activated, but the neural
circuitry that is established deviates from those
seen in a neurotypical brain.
• There are other known language pathways that
we have yet to confirm with DTI. These are the
ones that go to the deep structures in the cortex.
• We have reason to believe, based on
neuropsychological evaluations, that there may
be some connectivity to these areas.

52. BACK TO THE FIRST SLIDE
 What about practical
applications and
treatments?
 What are some “Emerging
Theories” in autism?

53. Novel Treatments for Autism
1. Novel language rehabilitations.
2. Application of musicology to
linguistics.
3. Virtual movement: cerebellar
stimulation.
4. Neuromodulation.

54. What’s available: excellent evidence-
based communication interventions.
• ABA - from BF Skinner to (Lovaas et
al, 1966): strengthening effects of
reinforcement during teaching
• Stimulus-stimulus pairing: e.g.
phoneme + reward.
• Milieu-based interventions: time
delay, milieu teaching, natural
language paradigms.

55. What do we have that’s novel?
1) A “Language-Template”
Rehabilitation Program.
• Language is innate! (Chomsky, 1965): we
are born with a “blueprint” for grammar”.
• Our brains depend on primitive brain
systems (e.g. the basal ganglia) to acquire
this grammar “blueprint.
• Emerging Theory: implicit (procedural)
grammar training can create a (new)
language template: the brain areas for
grammar-learning are ‘plastic’!

56. “Back to the Future”
• We need to activate the innate “brain
module” in children with autism.
• Some of this IMPLCIT training involves
“unconsciously, inadvertently, ‘learning’ to
speak a language for the first time all over
again” !

57. An emerging theory (cont’d)
We can modulate the successful acquisition of this
grammar template: “dopamine”.
(substantia nigra, Parkinson’s D, basal ganglia)
1. with the use of “language-specific motivations”.
(integrative motivation)
2. with novel implicit training techniques geared
to stimulate the basal ganglia via dopaminergic
brain pathways (it is imitation, joint attention -
but it’s more than that)

58. DOPAMINE PATHWAYS

59. DOPAMINERGIC PATHWAYS
TOP: BASAL GANGLIA
BOTTOM: DOPAMINE, EMOTIONS
Caudate Putamen
Substantia Nigra Amygdala

60. PROXIMITY OF BASAL GANGLIA
AND SUBSTANTIA NIGRA
.

61. 2) What about the application of
“musicology” to language
 Music therapy is useful with autistic children: non
threatening, socially interactive, uses musical
games with eye contact (it has the “right stuff”).
 Emerging Theory: the evolution of language,
gesture (hand movements) and music use
cerebral networks that are functionally linked.
 Our neuroimaging findings indicate a strong
“overlap of neural resources” involved in the
processing of language and music.

62. MUSIC IN OUR HEADS!
. Research has found that songs get stuck in our heads because
they create a "brain itch" that can only be scratched by
repeating the tune over and over.

63. Application of musicology to
language (cont’d)
Investigations: We are still discovering which aspects of
music are best suited to facilitate unconscious
acquisition of the rules of grammar.
• 1. Rhythm: “It’s hard to stay still”: an evolutionary
primitive response. - can produce unaware body
movement resulting from processing the beat by motor
areas of the brain – the same areas that process
language acquisition functions.
2. Syntax: Broca’s Area has been shown to be involved
in the detection of music structural irregularities (and
tones) as well detecting as grammar structure
irregularities. (“off key” is the same thing as “bad
grammar”).

64. 3)The cerebellum: Language and
Body Movement
• The cerebellum plays an important role in
the integration of sensory perception and
motor control, providing proprioceptive
(internal) feedback on the position of the
body in space.
• The cerebellum works with many neural
pathways receiving constant feedback on
body position to fine-tune motor our body
movements.

65. Cerebellar connections
• The cerebellum connects to frontal brain areas
to help generate “inner speech” (speech motor
planning”
• It also connects to primitive language areas
used to acquire our first language.
• Common real estate: “Sung” (explicit) language
and spoken language share many common
features and overlap in the posterior
cerebellum, a region known to represent the lips
and tongue.

66. Gross (Grey’s) Anatomy 101

67. The cerebellum in Autism
• Cerebellar dysfunction (pathology) is high
in ASD: but, we have seen activations!
• The cerebellar areas that are damaged
are often areas that receive auditory and
visual input: some implicit language areas
may be partially spared.
• Initiation of speech may be altered or
halted by cerebellar injury in autism.

68. 4) Cerebellar “therapy” and implicit
language acquisition
• Emerging Theory: stimulating the cerebellum by virtual
movement (e.g. spinning) may stimulate growth of new
neural connections from the cerebellum to implicit
language areas (Broca’s area, basal ganglia: the “reptile
brain”)
• Practical Application: Combining virtual movement
technology (“Top Gun”) – or simply bouncing on a ball -
with implicit language-learning techniques is being
developed to modulate language acquisition in children
with autism.

69. 5) NEUROMODULATION
• Transcranial Magnetic
Stimulation.
• Transcranial Direct Current
Stimulation.

70. Transcranial Magnetic Stimulation

71. How do we think TMS works?
• To perform TMS experiments, a stimulator (i.e.,
pulse generator) is needed to which different
stimulation coils can be connected to apply brief
magnetic pulses. These induce flows of
electrical current within brain cells.
• It has been hypothesized that these currents
enhance cortical synapses and modulate
important neurotransmitters.

72. Can TMS be used in ASD?
SO FAR THE DATA HAVE
NOT BEEN VERY GOOD
WITH TMS,
BUT, WE HAVE SUCCESS
WITH TDCS !!

73. Transcranial Direct Current
Stimulation (tDCS)

74. tDCS is SAFE !
 tDCS supplies a weak constant direct current to
the scalp to depolarize neurons below.
 tDCS gives between 0.5 and 4 mA of direct
current delivered through two sponge electrodes
soaked in saline solution.
 The saline-soaked sponges keep current
densities low and safe.
 Anodal (+) tDCS enhances excitability, whereas
cathodal (-) tDCS reduces it.

75. How best to use tDCS?
• Stimulate speech areas of robust activation seen on
individual child’s functional MRI (e.g. Wernicke’s Area)
that are not connected to other speech areas.
• Stimulate areas of no activation, but known to be
important to speech: areas of speech motor planning an
execution:
- Wernicke’s Area: drive it to Broca’s area
- Broca’s; supplementary motor area
- basal ganglia and cerebellum
- frontolimbic system (motivation)
• Use tDCS with implicit learning techniques !

76. This is tDCS & implicit learning !

77. What do some “smart people” at
Columbia think?
 We can use functional MRI to inquire about
abnormalities in brain activations and
connectivity.
 We can use these to guide very early
interventions to improve the language outcome
of children with autism.
 But…..

78. We need your help to figure this all
out !!!