Program for Cognitive Sciences (PICS)
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Program for Cognitive Sciences (PICS)
Dr. Joy Hirsch, Director
Harry D. Schneider, MD.
Co-Investigator Clinical Coordinator Autism Research Program
Debra Schneider
COLUMBIA UNIVERSITY
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 for restoring language. Our mathematicians calculated that…
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.
Combining Existing Science with Innovative Research
• We can restore language to stroke victims, because they have neurotypical anatomy. • To restore language to ASD children without neurotypical anatomy, we used fMRI to discover how their brains functioned for language. • We developed a map of the autistic brain and existing treatment technology for language. • We had the beginnings of a treatment plan!
I. 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.
To understand MRI we need to review the atom.
MRI is based on the spinning of protons:
B. Spinning protons are little magnets: they make electricity.
• Scanner Environment [1.5] T [3.0] T • Protons align along an axis
Protons in Brain Outside Field Protons in Brain Inside Field
(scattered)
(aligned)
MAGNETISM MAKES ELECTRICITY!
• A radio frequency pulse (63.3 mHz on an “FM radio”) is applied to aligned protons RFi
• Protons precess around the axis and create a small electrical current (MRI signal)
(precess)
(wobble)
This electrical current is emitted by the protons as they relax into their aligned state.
f i e l d
u n i f o r m
FINDING THE REAL ESTATE
RFo
These currents have different strengths depending upon local magnetic field strengths: we use them to find their location of origin in the brain
g r a d i e i e l d
Location of signals are recorded for structural MRI
For functional MRI: Blood Oxygen Level Dependent Signal (BOLD SIGNAL)
Physiology Physics
Neural activation is associated with an increase in blood flow and oxygen use. (Roy & Sherrington, 1890) Result: Reduction in the proportion of deoxyHGB in the local vasculature.
DeoxyHGB 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
Computations to get a Functional MRI Map
Reconstruction Alignment Voxel by voxel analysis Graphical representation
Functional Brain Map
Functional MRI
• • • • Is safe! No x-rays are used. No contrast agents are injected. It has been used on infants and pregnant women without complications. • But…it is noisy, so it is not always patient friendly, especially to kids on the spectrum.
A one-minute review of Brains and Blobs.
• Gross anatomy.
• Brain activations (called “blobs”).
• Brain connectivity.
Normal Language Areas of the Cortex
With fMRI we use Diffusion Tensor Imaging (DTI)
Passive listening: DTI: Neural Connections
Broca
Arcuate Fasciculus
Wernicke
Axial view of functional activity
Sagittal view of DTI Connections between Broca’s and Wernicke’s Areas
DTI map of a typical language system.
Neurosurgical planning: fMRI Task Battery Sensory
Touch (passive)
Applications of the Real Estate Principle
Motor
Finger Thumb Tapping
Language
Picture Naming (active) Listening to Words (passive)
Vision
Reversing Checkerboard
(active)
(passive)
GPoC
GPrC
GOi GTT GFi GTs
CaS
From Hirsch, J., et al; Neurosurgery 47: 711-722, 2000
Hirsch, J., Columbia University.
CLINICAL APPLICATIONS OF fMRI The science of the mind leads to the treatment of the mind.
Mapping for neurosurgical planning Assessment of cognitive function in nonresponsive adults and babies Neural reorganization in dyslexia.
Lowfunctioning language Autism!
Diagnoses Based On Variations in Neurocircuitry
fMRI TO DIAGNOSE AND INFORM TREATMENT OF ALTERNATIVE AND ATYPICAL NEUROCIRCUITRY OF BRAIN
Dyslexia
Nonimpaired
Shaywitz, et al. 1998
Howard & Hirsch, 2004
Dyslexia occurs in 15% of the U.S. population
Program for Imaging and Cognitive Sciences J. Hirsch, Columbia
Anxiety Disorders, PTSD
Eating Disorders, AN, Obesity Deception
Neural Surgical Planning
Autism
NeuroLaw Language Acquisition
Decision Sciences
Neural Reorganization
Seizure Localization Pain
Disorders of Consciousness
NeuroGenetics
I. FUTURE DIRECTIONS FOR BRAIN MAPPING IN CLINICAL NEUROSCIENCE
Now on to even more boring stuff!
LINGUISTICS
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!
How can children do what every second language learner dreams about - learn grammar without even thinking about it? • Children all know more about the language than they could reasonably have learned if they had to depend entirely on the input they were exposed to. • This is the “ poverty of stimulus theory” – the fact that grammar is unlearnable given the linguistic data available to children. Conclusion: grammar cannot be learnt but is rather an innate knowledge of the possibilities and impossibilities for any human language.
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 “hardwired” to learn a language.
Neurotypical grammar (cont’d):
• Although some children might say “Mommy gived the book” • A child never says: “Mommy the gives book” or “Mommy gives book the” • The unconscious grammar machine does not allow for too much error!
How do we become fluent?
• To achieve fluency in our native or a foreign language, two things should be combined: the words and their use. in other words, Grammar and pragmatics of language.
The Grammar is Universal
• The evidence includes:
the spontaneous production of language that children can learn to speak on a basis of minimal linguistic experience the fact that language choices need to be constrained in order to make learning quick and efficient the ability to change from one structure to another easily
What is changing from one structure? Structure Dependency
• All languages are “structure dependant”. This relationship between different elements of a sentence is learnt by children through Universal Grammar. • If every structure had a rule, our language systems would be too complicated and could not be adopted by adults, let alone infants. • Rearranging structures of a sentence is not just a matter of recognizing phrases and then moving them around: It is moving the correct element within the right phrase
An example of “moving things around correctly !
A child’s learns how to move things around to ask a question.
The boy who is sitting on the rug is hungry. Q. Is the boy who is sitting on the rug hungry? Is the boy sitting on the rug that is being vacuumed by his mother? Q. The boy is sitting on the rug that is being vacuumed by his mother.
What about Pragmatics ?
• Pragmatics is concerned with how communication is achieved in a given instance of language use. • It is the study of how the meaning of a sentence (or other linguistic unit) changes depending on how and where it is expressed. • It is concerned with transmission of meaning based on the context of an utterance, knowledge about the status of those speaking, the inferred intent of the speaker and the way in which we reach our goals in communication. • E.g. : “We could say: no eating in this lecture room”. • or “Somebody’s pizza is making me hungry and I can’t concentrate”.
What do we need to know about grammar?
• Grammar is not learned, it is implicitly acquired! • Acquired means learning something: • • • • unconsciously almost inadvertently becoming automatic in its use. not quite knowing how we do it!
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”
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”
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.
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.
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? home…” e.g. “Did you ever drive
Implicit Learning: New Frontiers
Implicit learning is what happens when people are just going about their daily life activitie not on memorizing or on learning per se,” It is involved in learning new motor skills such as bike riding, and learning new languages, picking up new cognitive skills such as chess playing, and in developing intuitions about how other people will act. A child’s learning its first languge from birth to age 3 is IMPLICIT This style of learning is subtle, occurring without intention or conscious awareness that the learning is taking place. It is also not easy to explain. Often people can’t fully articulate what they’ve learned, even though they may have absorbed and retained significant amounts of information. We think it is much more important for adapting to new places and people than more conscious forms of learning
The 2 memory systems use 2 different brain areas!
Our mental grammar (SVO), relies on implicit, unconscious and procedural memory uses a primitive network of areas deep in the brain Learning words relies on conscious, explicit declarative memory, which also stores facts and events you can recall and depends on a different brain network: surface brain areas and the hippocampus
The Procedural Brain (“Reptile” Brain)- for the infant’s language!
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) SMA : motor planning areas. Parts of Wernicke’s and Broca’s area
Language Areas of the Cortex: explicit learning
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!
For the Purposes of this talk, Let’s keep it simple:
• Implicit = Unconscious = Procedural
MEMORY • Explicit = Conscious = Declarative
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, or 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.
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)
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! • People with anterograde amnesia can not remember what was just learned: “each day is a new day” – but they can be taught to drive! They can be taught implicit stuff!
A NEUROTYPICAL CHILD’S LANGUAGE
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 initiate and maintain language conversationally using colloquial conversation. • 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’?
Do “LFA” 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.
SYNTAX DEPENDS ON PROCEDURAL MEMORY
• Faulty procedural learning is due to those deep brain areas that were partially damaged both in utero and after birth • This is the cause of ASD kids having no grammar and having to memorize everything! • Without the grammar machine a child can not become fluent nor verbally communicate!
Faulty procedural memory
A child with ASD will have difficulty with: • 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); • Recognizing ungrammatical sentences • Word meaning (frequently used words)
Faulty Procedural Memory II
• Faulty procedural acquisition may complicate the simultaneous application of elements of verbal communication. Difficulty in inferring appropriate words: prepositions, adjectives, adverbs. deictic terms for person (I, you, he, she, my, your, etc.), things (this ,that, these, those), places (here, there, above, below, etc.), times (now, tomorrow, yesterday) • Verbal intonation of children with ASD is better in repetition tasks (declarative memory) than in spontaneous speech (procedural memory)
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, in which the procedural system tries to reconstruct in its brain the 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.
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!
Autism is a “Spectrum Disorder”
• Low-functioning ASD brains are different from high-functioning ASD 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.
DORSAL AND VENTRAL STREAMS FOR LANGUAGE: both begin at Wernicke’s area.
THE DORSAL STREAM
• Begins in STG and goes from the inferior parietal cortex to the posterior frontal lobe via motor and supplementary motor areas. • Functions: maps phonemic representations onto motor representations for articulations. repetition of speech intact.
DORSAL SYSTEM (cont’d)
• Processing of complex grammatical structures (e.g., computing hierarchical dependency relations)
• Involves Broca’s area (BA 44,45)
VENTRAL SYSTEM
• Middle and inferior temporal gyrus to the ventrolateral prefrontal cortex. • Serves as a “sound-to-meaning” interface: maps sound-based speech to distributed cortical representations. • Associated with sentence comprehension.
VENTRAL SYSTEM (cont’d)
• The VS has an iterative exchange with the pre-frontal cortex: executive aspects of semantic processing. • VS involved in semantically-based analysis of grammatical structures • Processes simple grammatical structures (the STG -> frontal operculum) • THE VS IS SEEN TO BE USED IN LFA KIDS!
Linguistics of Ventral and Dorsal Streams
• When sound images of words are lost, children would not be able to understand words because sounds would mean nothing to them without the sound images of words. (like listening to a foreign language). • When motor images of words are impaired, then the LFA child would not be able to REPEAT words – but comprehension and expression are OK.
Integration of the two streams
• The dorsal stream is involved in auditory-motor integration by mapping acoustic speech sounds to articulatory representations. The prototype task targeting this dorsal stream is repetition of speech. • The ventral stream serves as a sound-tomeaning interface by mapping sound-based representations of speech to widely distributed conceptual representations. The prototype task targeting this ventral stream is listening to meaningful speech.
DORSAL AND VENTRAL STREAMS REPRESENTNG THE LINGUISTICS.
NEUROTYPICAL CHILD 7
Diffusion Tensor Imaging (DTI): LF autism
Broca
Arcuate Fasciculus
Wernicke
DTI map: Wernicke’s Area does NOT reach
Broca’s Area.
AUTISTIC 6 YEAR OLD
AUTISTIC 7 YEAR OLD
TITLE
Language “Real Estate”
Normal Autistic 6 yr. old Autistic 7 yr. old
Language Connectivity
Alternative Neurocircuitry in Autism Spectrum Disorder
Autism occurs in as many as 1 child in 150 in the U.S.
What do the activations show?
• We do not always find typical language areas, such as Broca’s and Wernicke’s areas, becoming activated to passive language listening – when they should! • 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).
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.
Some initial thoughts.
• DTI connectivity 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.
BACK TO THE FIRST SLIDE
What about practical applications and treatments? What are some “Emerging Theories” in treating autism? • (hint: the brain is “plastic”)
Novel Treatments for Autism
1. Novel language rehabilitations. 2. Application of musicology to linguistics. 3. Virtual movement: cerebellar stimulation. 4. Neuromodulation.
What’s available: excellent evidencebased 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.
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 implicit grammar-learning are ‘plastic’!
“Back to the Future”
• We need to re-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” !
An emerging theory (cont’d)
We can modulate the successful acquisition of this grammar template: “dopamine”. (substantia nigra, Parkinson’s D, basal ganglia) 4. with the use of “language-specific motivations”. (integrative motivation) 6. with novel implicit training techniques geared to stimulate the basal ganglia via dopaminergic brain pathways (it includes imitation and joint attention - but it’s more than that)
DOPAMINE PATHWAYS
DOPAMINERGIC PATHWAYS TOP: BASAL GANGLIA BOTTOM: DOPAMINE, EMOTIONS
Caudate
Putamen
Substantia Nigra
Amygdala
PROXIMITY OF BASAL GANGLIA AND SUBSTANTIA NIGRA
.
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, gestures (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.
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
.
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. • 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. • 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”). • Mozart: many of the children whose Broca’s area did not respond to language responded to Mozart.
3. Language acquisition and Body Movement: The cerebellum:
• 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.
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.
Gross (Grey’s) Anatomy 101
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.
Cerebellar “therapy” and implicit language acquisition
• Emerging Theory: stimulating the cerebellum by virtual or real 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 real or virtual movement technology –the “Top Gun” effect or simply bouncing on a ball - with implicit language-learning techniques is being developed to modulate language acquisition in children with autism.
4) NEUROMODULATION • Transcranial Magnetic Stimulation. • Transcranial Direct Current Stimulation.
Transcranial Magnetic Stimulation
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.
Can TMS be used in ASD? SO FAR THE DATA HAVE NOT BEEN VERY GOOD WITH TMS, BUT, WE HAVE SUCCESS WITH TDCS !!
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.
Transcranial Direct Current Stimulation (tDCS)
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 language learning techniques !
This is tDCS & implicit learning !
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…..
We need your help to figure this all out !!!
Program for Cognitive Sciences (PICS)
Dr. Joy Hirsch, Director
Harry D. Schneider, MD.
Co-Investigator Clinical Coordinator Autism Research Program
Debra Schneider
COLUMBIA UNIVERSITY
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 for restoring language. Our mathematicians calculated that…
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.
Combining Existing Science with Innovative Research
• We can restore language to stroke victims, because they have neurotypical anatomy. • To restore language to ASD children without neurotypical anatomy, we used fMRI to discover how their brains functioned for language. • We developed a map of the autistic brain and existing treatment technology for language. • We had the beginnings of a treatment plan!
I. 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.
To understand MRI we need to review the atom.
MRI is based on the spinning of protons:
B. Spinning protons are little magnets: they make electricity.
• Scanner Environment [1.5] T [3.0] T • Protons align along an axis
Protons in Brain Outside Field Protons in Brain Inside Field
(scattered)
(aligned)
MAGNETISM MAKES ELECTRICITY!
• A radio frequency pulse (63.3 mHz on an “FM radio”) is applied to aligned protons RFi
• Protons precess around the axis and create a small electrical current (MRI signal)
(precess)
(wobble)
This electrical current is emitted by the protons as they relax into their aligned state.
f i e l d
u n i f o r m
FINDING THE REAL ESTATE
RFo
These currents have different strengths depending upon local magnetic field strengths: we use them to find their location of origin in the brain
g r a d i e i e l d
Location of signals are recorded for structural MRI
For functional MRI: Blood Oxygen Level Dependent Signal (BOLD SIGNAL)
Physiology Physics
Neural activation is associated with an increase in blood flow and oxygen use. (Roy & Sherrington, 1890) Result: Reduction in the proportion of deoxyHGB in the local vasculature.
DeoxyHGB 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
Computations to get a Functional MRI Map
Reconstruction Alignment Voxel by voxel analysis Graphical representation
Functional Brain Map
Functional MRI
• • • • Is safe! No x-rays are used. No contrast agents are injected. It has been used on infants and pregnant women without complications. • But…it is noisy, so it is not always patient friendly, especially to kids on the spectrum.
A one-minute review of Brains and Blobs.
• Gross anatomy.
• Brain activations (called “blobs”).
• Brain connectivity.
Normal Language Areas of the Cortex
With fMRI we use Diffusion Tensor Imaging (DTI)
Passive listening: DTI: Neural Connections
Broca
Arcuate Fasciculus
Wernicke
Axial view of functional activity
Sagittal view of DTI Connections between Broca’s and Wernicke’s Areas
DTI map of a typical language system.
Neurosurgical planning: fMRI Task Battery Sensory
Touch (passive)
Applications of the Real Estate Principle
Motor
Finger Thumb Tapping
Language
Picture Naming (active) Listening to Words (passive)
Vision
Reversing Checkerboard
(active)
(passive)
GPoC
GPrC
GOi GTT GFi GTs
CaS
From Hirsch, J., et al; Neurosurgery 47: 711-722, 2000
Hirsch, J., Columbia University.
CLINICAL APPLICATIONS OF fMRI The science of the mind leads to the treatment of the mind.
Mapping for neurosurgical planning Assessment of cognitive function in nonresponsive adults and babies Neural reorganization in dyslexia.
Lowfunctioning language Autism!
Diagnoses Based On Variations in Neurocircuitry
fMRI TO DIAGNOSE AND INFORM TREATMENT OF ALTERNATIVE AND ATYPICAL NEUROCIRCUITRY OF BRAIN
Dyslexia
Nonimpaired
Shaywitz, et al. 1998
Howard & Hirsch, 2004
Dyslexia occurs in 15% of the U.S. population
Program for Imaging and Cognitive Sciences J. Hirsch, Columbia
Anxiety Disorders, PTSD
Eating Disorders, AN, Obesity Deception
Neural Surgical Planning
Autism
NeuroLaw Language Acquisition
Decision Sciences
Neural Reorganization
Seizure Localization Pain
Disorders of Consciousness
NeuroGenetics
I. FUTURE DIRECTIONS FOR BRAIN MAPPING IN CLINICAL NEUROSCIENCE
Now on to even more boring stuff!
LINGUISTICS
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!
How can children do what every second language learner dreams about - learn grammar without even thinking about it? • Children all know more about the language than they could reasonably have learned if they had to depend entirely on the input they were exposed to. • This is the “ poverty of stimulus theory” – the fact that grammar is unlearnable given the linguistic data available to children. Conclusion: grammar cannot be learnt but is rather an innate knowledge of the possibilities and impossibilities for any human language.
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 “hardwired” to learn a language.
Neurotypical grammar (cont’d):
• Although some children might say “Mommy gived the book” • A child never says: “Mommy the gives book” or “Mommy gives book the” • The unconscious grammar machine does not allow for too much error!
How do we become fluent?
• To achieve fluency in our native or a foreign language, two things should be combined: the words and their use. in other words, Grammar and pragmatics of language.
The Grammar is Universal
• The evidence includes:
the spontaneous production of language that children can learn to speak on a basis of minimal linguistic experience the fact that language choices need to be constrained in order to make learning quick and efficient the ability to change from one structure to another easily
What is changing from one structure? Structure Dependency
• All languages are “structure dependant”. This relationship between different elements of a sentence is learnt by children through Universal Grammar. • If every structure had a rule, our language systems would be too complicated and could not be adopted by adults, let alone infants. • Rearranging structures of a sentence is not just a matter of recognizing phrases and then moving them around: It is moving the correct element within the right phrase
An example of “moving things around correctly !
A child’s learns how to move things around to ask a question.
The boy who is sitting on the rug is hungry. Q. Is the boy who is sitting on the rug hungry? Is the boy sitting on the rug that is being vacuumed by his mother? Q. The boy is sitting on the rug that is being vacuumed by his mother.
What about Pragmatics ?
• Pragmatics is concerned with how communication is achieved in a given instance of language use. • It is the study of how the meaning of a sentence (or other linguistic unit) changes depending on how and where it is expressed. • It is concerned with transmission of meaning based on the context of an utterance, knowledge about the status of those speaking, the inferred intent of the speaker and the way in which we reach our goals in communication. • E.g. : “We could say: no eating in this lecture room”. • or “Somebody’s pizza is making me hungry and I can’t concentrate”.
What do we need to know about grammar?
• Grammar is not learned, it is implicitly acquired! • Acquired means learning something: • • • • unconsciously almost inadvertently becoming automatic in its use. not quite knowing how we do it!
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”
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”
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.
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.
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? home…” e.g. “Did you ever drive
Implicit Learning: New Frontiers
Implicit learning is what happens when people are just going about their daily life activitie not on memorizing or on learning per se,” It is involved in learning new motor skills such as bike riding, and learning new languages, picking up new cognitive skills such as chess playing, and in developing intuitions about how other people will act. A child’s learning its first languge from birth to age 3 is IMPLICIT This style of learning is subtle, occurring without intention or conscious awareness that the learning is taking place. It is also not easy to explain. Often people can’t fully articulate what they’ve learned, even though they may have absorbed and retained significant amounts of information. We think it is much more important for adapting to new places and people than more conscious forms of learning
The 2 memory systems use 2 different brain areas!
Our mental grammar (SVO), relies on implicit, unconscious and procedural memory uses a primitive network of areas deep in the brain Learning words relies on conscious, explicit declarative memory, which also stores facts and events you can recall and depends on a different brain network: surface brain areas and the hippocampus
The Procedural Brain (“Reptile” Brain)- for the infant’s language!
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) SMA : motor planning areas. Parts of Wernicke’s and Broca’s area
Language Areas of the Cortex: explicit learning
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!
For the Purposes of this talk, Let’s keep it simple:
• Implicit = Unconscious = Procedural
MEMORY • Explicit = Conscious = Declarative
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, or 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.
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)
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! • People with anterograde amnesia can not remember what was just learned: “each day is a new day” – but they can be taught to drive! They can be taught implicit stuff!
A NEUROTYPICAL CHILD’S LANGUAGE
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 initiate and maintain language conversationally using colloquial conversation. • 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’?
Do “LFA” 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.
SYNTAX DEPENDS ON PROCEDURAL MEMORY
• Faulty procedural learning is due to those deep brain areas that were partially damaged both in utero and after birth • This is the cause of ASD kids having no grammar and having to memorize everything! • Without the grammar machine a child can not become fluent nor verbally communicate!
Faulty procedural memory
A child with ASD will have difficulty with: • 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); • Recognizing ungrammatical sentences • Word meaning (frequently used words)
Faulty Procedural Memory II
• Faulty procedural acquisition may complicate the simultaneous application of elements of verbal communication. Difficulty in inferring appropriate words: prepositions, adjectives, adverbs. deictic terms for person (I, you, he, she, my, your, etc.), things (this ,that, these, those), places (here, there, above, below, etc.), times (now, tomorrow, yesterday) • Verbal intonation of children with ASD is better in repetition tasks (declarative memory) than in spontaneous speech (procedural memory)
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, in which the procedural system tries to reconstruct in its brain the 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.
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!
Autism is a “Spectrum Disorder”
• Low-functioning ASD brains are different from high-functioning ASD 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.
DORSAL AND VENTRAL STREAMS FOR LANGUAGE: both begin at Wernicke’s area.
THE DORSAL STREAM
• Begins in STG and goes from the inferior parietal cortex to the posterior frontal lobe via motor and supplementary motor areas. • Functions: maps phonemic representations onto motor representations for articulations. repetition of speech intact.
DORSAL SYSTEM (cont’d)
• Processing of complex grammatical structures (e.g., computing hierarchical dependency relations)
• Involves Broca’s area (BA 44,45)
VENTRAL SYSTEM
• Middle and inferior temporal gyrus to the ventrolateral prefrontal cortex. • Serves as a “sound-to-meaning” interface: maps sound-based speech to distributed cortical representations. • Associated with sentence comprehension.
VENTRAL SYSTEM (cont’d)
• The VS has an iterative exchange with the pre-frontal cortex: executive aspects of semantic processing. • VS involved in semantically-based analysis of grammatical structures • Processes simple grammatical structures (the STG -> frontal operculum) • THE VS IS SEEN TO BE USED IN LFA KIDS!
Linguistics of Ventral and Dorsal Streams
• When sound images of words are lost, children would not be able to understand words because sounds would mean nothing to them without the sound images of words. (like listening to a foreign language). • When motor images of words are impaired, then the LFA child would not be able to REPEAT words – but comprehension and expression are OK.
Integration of the two streams
• The dorsal stream is involved in auditory-motor integration by mapping acoustic speech sounds to articulatory representations. The prototype task targeting this dorsal stream is repetition of speech. • The ventral stream serves as a sound-tomeaning interface by mapping sound-based representations of speech to widely distributed conceptual representations. The prototype task targeting this ventral stream is listening to meaningful speech.
DORSAL AND VENTRAL STREAMS REPRESENTNG THE LINGUISTICS.
NEUROTYPICAL CHILD 7
Diffusion Tensor Imaging (DTI): LF autism
Broca
Arcuate Fasciculus
Wernicke
DTI map: Wernicke’s Area does NOT reach
Broca’s Area.
AUTISTIC 6 YEAR OLD
AUTISTIC 7 YEAR OLD
TITLE
Language “Real Estate”
Normal Autistic 6 yr. old Autistic 7 yr. old
Language Connectivity
Alternative Neurocircuitry in Autism Spectrum Disorder
Autism occurs in as many as 1 child in 150 in the U.S.
What do the activations show?
• We do not always find typical language areas, such as Broca’s and Wernicke’s areas, becoming activated to passive language listening – when they should! • 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).
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.
Some initial thoughts.
• DTI connectivity 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.
BACK TO THE FIRST SLIDE
What about practical applications and treatments? What are some “Emerging Theories” in treating autism? • (hint: the brain is “plastic”)
Novel Treatments for Autism
1. Novel language rehabilitations. 2. Application of musicology to linguistics. 3. Virtual movement: cerebellar stimulation. 4. Neuromodulation.
What’s available: excellent evidencebased 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.
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 implicit grammar-learning are ‘plastic’!
“Back to the Future”
• We need to re-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” !
An emerging theory (cont’d)
We can modulate the successful acquisition of this grammar template: “dopamine”. (substantia nigra, Parkinson’s D, basal ganglia) 4. with the use of “language-specific motivations”. (integrative motivation) 6. with novel implicit training techniques geared to stimulate the basal ganglia via dopaminergic brain pathways (it includes imitation and joint attention - but it’s more than that)
DOPAMINE PATHWAYS
DOPAMINERGIC PATHWAYS TOP: BASAL GANGLIA BOTTOM: DOPAMINE, EMOTIONS
Caudate
Putamen
Substantia Nigra
Amygdala
PROXIMITY OF BASAL GANGLIA AND SUBSTANTIA NIGRA
.
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, gestures (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.
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
.
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. • 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. • 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”). • Mozart: many of the children whose Broca’s area did not respond to language responded to Mozart.
3. Language acquisition and Body Movement: The cerebellum:
• 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.
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.
Gross (Grey’s) Anatomy 101
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.
Cerebellar “therapy” and implicit language acquisition
• Emerging Theory: stimulating the cerebellum by virtual or real 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 real or virtual movement technology –the “Top Gun” effect or simply bouncing on a ball - with implicit language-learning techniques is being developed to modulate language acquisition in children with autism.
4) NEUROMODULATION • Transcranial Magnetic Stimulation. • Transcranial Direct Current Stimulation.
Transcranial Magnetic Stimulation
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.
Can TMS be used in ASD? SO FAR THE DATA HAVE NOT BEEN VERY GOOD WITH TMS, BUT, WE HAVE SUCCESS WITH TDCS !!
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.
Transcranial Direct Current Stimulation (tDCS)
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 language learning techniques !
This is tDCS & implicit learning !
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…..
We need your help to figure this all out !!!
