communicating brains: autism and neurodevelopmental...

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Communicating Brains: Autism and Neurodevelopmental Disorders 12/6/12 Elysa Marco, PhD BIOGRAPHY: Dr. Marco is the director of research for the UCSF Autism and Neurodevelopment Program (ANP). In addition to the founding and directing research efforts for the UCSF ANP, Dr. Marco directs the cognitive and behavioral child neurology clinic and participates in the neurology, psychiatry, and genetics multidisciplinary autism clinics at UCSF. Dr. Marco’s research laboratory applies her clinical expertise in cognition and behavior to understanding the neural mechanisms of neurodevelopmental disorders related to autism, agenesis of the corpus callosum, sensory processing disorder (SPD), ADHD, and brain injury. Her laboratory is focuses on how individuals with neurodevelopmental differences process basic sensory information from perception to action. Her NIH funded research investigates how children with autism process sensory information using magnetoencephalographic imaging and her expanding treatment projects are targeting computer training as a tool for augmenting positive brain plasticity. BIBLIOGRAPHY: Marco EJ, Hinkley LB, Hill SS, Nagarajan; Sensory Processing in Autism: A Review of Neurophysiologic Findings. Pediatric Research. 2011 May;69(5 Pt 2):48R54R. Leekam et. al. Describing the Sensory Abnormalities of Children and Adults with Autism. J Autism Dev Disord. 2007 May;37(5):894910. Binder JR et. Al. Human temporal lobe activiation by speech and nonspeech sounds. Cereb Cortex 2000 May; 10(5):51228. Taylor N, Isaac C, Milne E; A Comparison of the Development of Audiovisual Integration in Children with Autism Spectrum Disorders and Typically Developing Children. JADD. 2010 Vol 40(11) p14031411. Guiraud JA, Tomalski P, Kushnerenko E, et al. Atypical Audiovisual Speech Integration in Infants at Risk for Autism. PLos One 2012, 7(5): e36428.Published online 2012 May 15. Nina F. Dronkers, PhD BIOGRAPHY: Nina F. Dronkers is a VA Research Career Scientist and Director of the Center for Aphasia and Related Disorders with the Department of Veterans Affairs Northern California Health Care System. She is also an Adjunct Professor at the University of California, Davis in the Department

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Page 1: Communicating Brains: Autism and Neurodevelopmental ...minimedicalschool.ucsf.edu/syllabus/fall2012/12-6 - Communicating... · Communicating Brains: Autism and Neurodevelopmental

Communicating Brains: Autism and Neurodevelopmental Disorders 12/6/12 

 Elysa Marco, PhD 

  BIOGRAPHY:  Dr. Marco is the director of research for the UCSF Autism and Neurodevelopment Program (ANP). In addition to the founding and directing research efforts for the UCSF ANP, Dr. Marco directs the cognitive and behavioral child neurology clinic and participates in the neurology, psychiatry, and genetics multidisciplinary autism clinics at UCSF. Dr. Marco’s research laboratory applies her clinical expertise in cognition and behavior to understanding the neural mechanisms of neurodevelopmental disorders related to autism, agenesis of the corpus callosum, sensory processing disorder (SPD), ADHD, and brain injury. Her laboratory is focuses on how individuals with neurodevelopmental differences process basic sensory information from perception to action. Her NIH funded research investigates how children with autism process sensory information using magnetoencephalographic imaging and her expanding treatment projects are targeting computer training as a tool for augmenting positive brain plasticity.    BIBLIOGRAPHY:  Marco EJ, Hinkley LB, Hill SS, Nagarajan; Sensory Processing in Autism: A Review of Neurophysiologic Findings. Pediatric Research. 2011 May;69(5 Pt 2):48R‐54R.  Leekam et. al. Describing the Sensory Abnormalities of Children and Adults with Autism. J Autism Dev Disord. 2007 May;37(5):894‐910.  Binder JR et. Al. Human temporal lobe activiation by speech and nonspeech sounds. Cereb Cortex 2000 May; 10(5):512‐28.  Taylor N, Isaac C, Milne E; A Comparison of the Development of Audiovisual Integration in Children with Autism Spectrum Disorders and Typically Developing Children.  JADD. 2010 Vol 40(11) p1403‐1411.  Guiraud JA, Tomalski P, Kushnerenko E, et al. Atypical Audiovisual Speech Integration in Infants at Risk for Autism. PLos One  2012, 7(5): e36428.Published online 2012 May 15.  

 

Nina F. Dronkers, PhD  BIOGRAPHY:  Nina F. Dronkers is a VA Research Career Scientist and Director of the Center for Aphasia and Related Disorders with the Department of Veterans Affairs Northern California Health Care System.  She is also an Adjunct Professor at the University of California, Davis in the Department 

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of Neurology and a consultant to the UCSF Memory and Aging Center.  She received her interdisciplinary Ph.D. degree in Neuropsychology from the University of California, Berkeley in 1985, and has since specialized in the mapping of speech, language, and cognitive disorders that occur after injury to the brain.  Using numerous methodologies, Dr. Dronkers and her colleagues have isolated numerous brain regions  that play critical roles  in  the processing of speech and  language, as well as how these relate to other cognitive skills. Her  latest work  involves analyzing the structural and functional connections that contribute to  language and cognitive processing through advanced work with diffusion and resting state functional neuroimaging.    BIBLIOGRAPHY:  

1. Bates, E., Wilson, S.M., Saygin, A.P., Dick, F., Sereno, M., Knight, R.T. & Dronkers, N.F. Voxel‐based lesion‐symptom mapping. Nature Neuroscience, 2003, 6(5), 448‐450.  

2. Dronkers, N.F. A new brain region for speech: The insula and articulatory planning. Nature, 1996, 384, 159‐161.  

3. Dronkers, N.F. & Ogar, J. Aphasia. In M.J. Aminoff and R.B. Daroff (Eds.), Encyclopedia of the Neurological Sciences, 2nd edition, San Diego, California: Academic Press, in press. 

 

4. Dronkers, N.F., Plaisant, O., Iba‐Zizen, M.T. & Cabanis, E.A. Paul Broca’s historic cases: High resolution MR imaging of the brains of Leborgne and Lelong. Brain, 2007, 130, 1432‐1441. 

 

5. Gorno‐Tempini, M.L., Dronkers, N.F., Rankin, K.P., Ogar, J.M., Phenegrasamy, L., Rosen, H.J., Johnson, J.K., Weiner, M.W., Miller, B.L.  Cognition and anatomy in three variants of primary progressive aphasia.  Annals of Neurology, 2004, 55(3), 335‐346. 

 

6. Turken, A.U. & Dronkers, N.F. The neural architecture of the language comprehension network: converging evidence from lesion and connectivity analyses. Frontiers in Systems Neuroscience, 2011, 5, 1‐20. 

  

Communicating Brains: From Autism and Dyslexia to Progressive Aphasia  

Maya L. Henry, PhD, CCC‐SLP   BIOGRAPHY:  Dr. Henry is an Assistant Adjunct Professor and speech‐language pathologist working with the language team at the Memory and Aging Center at UCSF. She is also an Assistant Professor in the Communicative Disorders Program at San Francisco State University. She received her master’s degree and PhD from the University of Arizona, studying the nature and treatment of 

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acquired neurogenic communication disorders. She has conducted NIH‐funded studies examining the neural bases of spoken and written language in primary progressive aphasia (PPA) and also examining the utility of speech and language treatment in the three variants of this disorder. Her broad research interests include the neural and cognitive bases for speech and language, rehabilitation of speech and language in individuals with aphasia, and ways in which neuroimaging can inform treatment research in individuals with stroke and neurodegenerative disease. Dr. Henry runs a monthly support group for individuals with PPA in the Bay Area.   BIBLIOGRAPHY:  

Beeson PM, King RM, Bonakdarpour B, Henry ML, Cho H, Rapcsak SZ. Positive effects of language treatment for the logopenic variant of primary progressive aphasia. Journal of Molecular Neuroscience. 2011:1‐13.  

Gorno‐Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006‐1014. 

Henry ML, Beeson PM, Rapcsak SZ. Treatment for lexical retrieval in progressive aphasia. Aphasiology. 2008;22(7):826‐838.  

Henry ML, Beeson PM, Alexander GE, Rapcsak SZ. Written language impairments in primary progressive aphasia: A reflection of damage to central semantic and phonological processes. J Cogn Neurosci. 2012;24(2):261‐275.  

Mesulam MM. Primary progressive aphasia. Ann Neurol. 2001;49(4):425‐432.  

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Elysa Marco, MD12.6.12

Asst. Prof, UCSF Depts of Neurology, Pediatrics, and PsychiatryDirector of Research, UCSF Autism and Neurodevelopment

Program

Communicating Brains: Autism and Neurodevelopmental Disorders

Communication begins with sensory perception and processing:

Review basics of sensory processing from a neuroscience perspectiveHow does this differ in children with autism and neurodevelopmentaldisorders?What are we doing at UCSF to help?

The first question is:Are there sensory differences in autism at the bedside?… all you need to do is ask!

Or read…

Emergence (pgs 21 & 28)Even today, sudden loud noises such as a

car backfiring, will make me jump and a panicky feeling overwhelms me. Loud high pitched noises such as a motorcycle’s sound, are still painful to me.

Tactile stimulation for me and many autistic children is a no-win situation. Our bodies cry out for human contact but when the contact is made, we withdraw in pain and confusion.

Grandin, T. Publisher: Warner Books (September 1, 1996) Emergence: Labeled A ti ti

Sensory Processing Disruption is Ubiquitous in Autism Sensory behavioral differences occur in over 90%

of individuals with autism

Children with autism are more likely to have multiple domains affects than controls (70% vs. 13%)

Leekam et. al. (2007) Describing the Sensory Abnormalities of Children and Adults with Autism

Sensory Symptoms in Autism

No sensorydifferences

MultipleDomain

SingleDomain

Children with Developmental Disabilities and Language Impairment also have sensory symptoms

Leekam et. al. (2007) Describing the Sensory Abnormalities of Children and Adults with Autism

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Sensory Processing Disruption has long-term impact Sensory symptoms often persist into adulthood Sensory processing is the basis for all learning and

behavior

Leekam et. al. (2007) Describing the Sensory Abnormalities of Children and Adults with Autism

What do I mean by sensory processing-bringing together neuroscience & behavioral sciences?

The steps of sensory processing:Unimodal Perception (Auditory, Somatosensory,

Visual, Olfactory)Multimodal IntegrationAttaching Meaning (Linguistic & Emotional)Creating ResponsePerforming Response (Verbal/Motor)

Some basic neuroanatomy Early Auditory Processing

CN 8 synapses at ipsilateral cochlear nuclear complex (medulla) Only from one ear & gets spectral and

temporal information

Superior olivary complex Bilateral input Sound localization (delay & intensity)

Inferior colliculus medial geniculate nucleus auditory cortex

All neurons tonotopically organized More frequency specific as you go up Information goes up and down!

http://brainconnection.positscience.com/med/medart/l/anat/990705.jpg

Central Auditory Processing Can we measure auditory processing in the scanner?

EEG

Yes!

MEG

fMRI

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How do neurons talk to each other?How can you measure electrical activity?

Using magnetoencephalographicImaging

Milli-second & milli-meter cortical activity resolution (w/MRI co-registration)

Non-invasive

Well tolerated

Let’s use auditory processing as a example.

We find early primary auditory cortex processing differences

But, it depends on who you ask…Faster Slower

Ferri (1000 hz, 100ms tone)

Martineau (1000 hz, 4ms tone)

Marco et. al. (1000 hz, 80ms)

Bruneau (750khz, 200ms)

Oram Cardy (1000hz, 300ms)

Roberts (delay RH, 200, 300, 500, 1000 hz 300ms)

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Nath A R et al. J. Neurosci. 2011;31:13963-13971

©2011 by Society for Neuroscience

Audiovisual Integration-McGurkEffect

What about Auditory and Visual Integration? McGurk (multisensory)

Posterior Parietal Cortex

Whole-brain regression of fMRI responses and McGurksusceptibility–

The more your integrate, the more activity you show in the yellow region below

Nath A R et al. J. Neurosci. 2011;31:13963-13971

Do children with autism show a McGurk effect?

Taylor et. al. 2010. Comparison of the develoment of audiovisual integration in children with autism spectrum disorders and typically developing children. JADD.

High Risk Infants may not process AV mismatch

Guiraud, et. al. (2012) Atypical audiovisual speech integration in infants at risk for autism. PLoS One.

What about other neurodevelopmentaldisorders?

Absent

Images courtesy of Dr. Elliott Sherr

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Atypical Auditory Behavior in AgCC: What does brain activity look like

during communication in AgCC?

How are we planning on helping: Our goal is to build both areas of strength and areas of challenge

Kids and video games:if you can’t beat em, join em…

NeuroRacer:What happens when Neuroscience meets Video Gaming in the bay area

Adam GazzaleyDirector of “The NIC”

Eric JohnstonLucas Arts

a)

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Autism and SPD kids have trouble staying in the center of the road

Gazzaley Lab Unpublished data

Decades of Life

% of time at road center

Sensory Processing Disorder (n=14)

Autistic Children (n=9)

Drive w/ Irrelevant signs

Autism and SPD kids take longer to shoot:with visual distraction

Gazzaley Lab Unpublished data

Decades of Life

RT (m

sec)

Sensory Processing Disorder (n=14)

Autistic Children (n=9)

Sign with Road

Training Study

12 hours

‐13%‐13%

PreTrainPreTrain

1 mo.Later1 mo.Later

6 mo.later6 mo.later

Can we improve accuracy with practice?

Single‐task trainMulti‐task train

No‐contact controlGazzaley Lab Unpublished data

Decades of Life

Sensory Processing Disorder (n=14)

Autistic Children (n=9)

Multi‐tasking In

dex (d

’)

Many Hands with thanks to Lucy Miller & the Wallace Research Foundation:

MEG/DTI Team

SrikantanNagarajan

PratikMukherjee

Elliott Sherr

Leighton Hinkley

Shivani Desai*Ashley Antovich

Julia Harris*

Susannah Hill

Richard Hill

Angelina Jocson

Kasra Khatibi

Anne Bernard

Monica Arroyo

Heidi Kirsch

Anne Findlay

Suzanne Homna

Julia Owens

NeuroracerTeamAdam Gazzaley

Joaquin Anguera

Cammie Rolle

Johno Gibbons

Annie Aiken

MAC

Bruce Miller

Joel Kramer

John Neuhaus

Sensory Processing Foundation

Lucy Miller

Sarah Schoen

UCSF Autism and Neurodevelopment center

Bryna Siegel

Robert Hendren

Lauren Weiss

The kids and their parents!

This research effort has been supported by an NSADA NINDS (K12 NS01692–07) award and UL RR024131-01 from the NCRR a component of NIH and the NIH Roadmap for Medical Research. Ongoing work is supported by the Wallace Research Foundation. No conflicts of interest.

Thank you!

Speech and Language DeficitsAfter Injury to the Adult Brain

Nina F. Dronkers, Ph.D.VA Northern California Health Care System

University of California, Davis

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Why do we study communication abilities in the

injured brain?

• The more we understand about the injured brain, the more we

can help patients toward a more rapid and effective recovery.

• Individuals with brain-injuries teach us a great deal about how

the normal brain processes language; understanding how

language breaks down tells us a lot about it normally

functions.

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Research at our Aphasia Center• We conduct extensive speech, language, and

neuropsychological evaluations of aphasic stroke patients to determine the specific deficits they are experiencing.

• We also scan participants in an MRI scanner to see which part of the brain was affected by the stroke.

Research at our Aphasia Center

We then use these data to test brain-behavior relationships

– Identify patients with the same specific deficits and computer-overlap their lesions to determine if a common area of injury can be found

– Apply new voxel-based lesion symptom mapping techniques that statistically examine brain-behavior relationships at the 1 mm voxel level

– Evaluate the role of fiber pathways in the brain that also support language functions.

Fluency Comprehension

Broca’s aphasia

arcuate fasciculus Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Some Causes of Brain Injury in Adults

• Stroke• Tumor• Head Trauma• Severe Epilepsy• Neurodegenerative disease (e.g., Alzheimer’s

Disease)• Anoxia• Infectious disease• Toxicity

Blood Clot Lodged in Artery

What is a Stroke?

© National Stroke Association

Bleeding into the Brain

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Strokes and Aphasia

• Strokes can lead to speech and language

disorders that severely disrupt one’s

ability to communicate.

• A disruption of core language functions as

a result of injury to the brain is called

“aphasia”.

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Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Strokes Can Affect Language in Different Ways

Strokes in the front regions of the brain can lead to non-fluent speech

(video of individualwith Broca’s aphasia -

not available for distribution)

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Broca’s Aphasia

• Halting, telegraphic, agrammatic speech with reliance on content words and a paucity of function words

• Impaired comprehension for complex grammatical structures

• Repetition of sentences reflects agrammatic style• Word finding difficulty• Almost always accompanied by dysarthria and/or

apraxia of speech• Reading and writing also impaired

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Written Picture Description: Moderate Broca’s Aphasia

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

3-D MRI of an Individual with Broca’s Aphasia

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Lesion Overlapping of 36 Patients with Broca’s Aphasia

The injuries tend to involve more anterior areas.

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Strokes Can Affect Language in Different Ways

Strokes in posterior regions of the brain leave the person with fluent speech, but which is hard to understand.

(video of individualwith Wernicke’s aphasia -

not available for distribution)

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Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Severe Wernicke’s Aphasia

• Reflects extreme disruption of language

system without encumbrance of motor speech

deficits

• Chronic Wernicke’s aphasia occurs very rarely

• Acute Wernicke’s aphasia typically evolves

into milder forms of aphasia

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Lesion Overlapping of Patients with Wernicke’s Aphasia

The injuries tend to involve more posterior areas.

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Strokes Can Affect Language in Different Ways

Larger strokes can leave patients with only automatic sounds, words or phrases with which to communicate

(video of individualwith severe Broca’s aphasia -not available for distribution)

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Tips for Communicatingwith Individuals with Aphasia

• Keep the sentences simple, but avoid talking down.

• Reduce your rate of speech; emphasize key words.

• Make sure you have the person’s attention.

• Try writing, drawing, or gestures in addition to speech.

• Give them time to talk.

• Ask yes/no questions if the aphasia is severe.

• Provide practice trials and give positive feedback.

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Things to Remember• On the other hand, individuals with aphasia have not lost

their intelligence.

• They may find it more difficult to process incoming

information or to solve difficult problems; they may have

lost some of the language that would normally help them.

• Though they may have difficulty expressing their thoughts

with words, their thoughts and ideas are not typically

affected.

What has research with aphasic

individuals taught us about language

processing in the normal brain?

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Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

What Have We Learned?

The areas of the brain that support

language are far more extensive than

previously thought.

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Language Areas in Older Models

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Examples of Additional Language Areas from Recent Research

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

What Have We Learned?

• Brain areas do not work in isolation.

• The fibers that connect them help these

regions to interact with each other to

support complex functions such as

language.

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Fiber Bundles in Dissection

brainmind.com

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Visualization of Fiber Tract Data with Diffusion MRI

Visualization by Betty Lee

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Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Visualization of Language Tracts with Diffusion MRI

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Visualization of the Arcuate Fasciculus with Constrained Spherical Deconvolution Tractography

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Visualization of Language Tracts in Stroke

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

What Have We Learned?

• These techniques have taught us a lot about how the brain

processes language and what happens when the brain suffers

an injury.

• With this information, clinicians know that strokes affecting

certain brain structures will cause a loss of specific functions,

and that these will require special training.

• At the same time, brain structures that were spared can be

recruited to help take over the functions that were lost, or,

develop new strategies to compensate for the dysfunction.

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Summary• A complex system such as language requires an

extensive and interactive network of brain regions.

• Understanding this network provides us with the

tools for assisting our patients in their recovery

from brain injury, and, for understanding how

language is processed in the normal brain.

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Thank You

Image by Yoshihito Yagi

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Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

Supported by:

• VA Clinical Science Research and Development Program

• National Institute on Deafness and other Communication Disorders

• National Institute of Neurological Disorders and Stroke

• National Science Foundation

Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA

With special thanks to:

• And Turken, Ph.D.

• Juliana Baldo, Ph.D.

• Our patients and research participants who taught us all we know

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PROGRESSIVE  IMPAIRMENTS  OF  SPEECH  AND  LANGUAGE:  WHEN  APHASIA  ISN’T  CAUSED  BY  A  STROKE  

Maya  L.  Henry,  Ph.D,  CCC-­‐SLP  Memory  and  Aging  Center,  UC  San  Francisco  Communicative  Disorders  Program,  San  Francisco  State  University  

Language  and  normal  aging  §  Most  common  complaint:  “I  just  can’t  remember  the  name….”  (especially  proper  names)  

§  Word-­‐finding  does  decline  with  age  ú  Difficulty  with  access  rather  than  a  deterioration  of  knowledge     Older  adults  outperform  younger  adults  on  vocabulary  tests    

   Semantic  memory  (conceptual  knowledge)  is  preserved  into  old  age  (Burke  &  Shafto,  2008)  

When  is  language  decline  not  normal?  §  When  the  decline  is  more  rapid  than  would  be  expected  and  changes  are  observed  at  ages  <60  years  

§  When  cognitive  processes  not  typically  affected  by  age  are  noticeably  impaired  ú  Motor  control  for  speech  ú  Ability  to  speak  in  complete  sentences  ú  Conceptual  knowledge,  word  meaning  ú  Ability  to  “hold  on  to”  heard  information  (e.g.,  a  phone  number)  

Primary  progressive  aphasia  (PPA)  

§  Slowly  progressive  aphasia  caused  by  neurodegenerative  disease    

§  Language  processes  are  affected  first  and  foremost    (Mesulam,  2008;  Gorno-­‐Tempini  et  al.,  2011)  

§  There  must  be  no  focal  lesion  (e.g.,  stroke)  

Regional cortical atrophy Primary Progressive Aphasia (PPA)

Normal

L L

PPA  affects  core  speech-­‐language  processes  

§  Like  aphasia  resulting  from  stroke,  progressive  aphasia  may  involve  ú  Syntax  (grammar)  ú  Motor  speech  (articulation/voice)  ú  Semantics  (meaning)  ú  Phonology  (sound  system)  ú  Orthography  (written  language)  

 

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Deficits  tend  to  arise  in  patterns:  3  variants  of  PPA  (Gorno-­‐Tempini  et  al.,  2011)  

§  Nonfluent  variant  ú  Impaired  syntax  (sentence  processing)  and/or  motor  speech  (articulation/voice)  

§  Semantic  variant  ú  Impaired  semantic  processing  (conceptual  knowledge)  

§  Logopenic  variant  ú  Impaired  phonological  processing  (sound  system  for  language)  

 

These variants linked to underlying patterns of atrophy caused by different diseases

Nonfluent variant

Semantic variant

Logopenic variant

Wilson et al., 2010

HOW  CAN  PPA  PATIENTS  CONTRIBUTE  TO  OUR  UNDERSTANDING  OF  BRAIN-­‐BEHAVIOR  RELATIONS  FOR  LANGUAGE?  

§  Converging  and  complementary  evidence  regarding  brain-­‐behavior  relations  for  language  ú  PPA  involves  some  areas  rarely  damaged  in  stroke  

   Anterior  temporal  regions  implicated  in  semantic  processing  

semantic dementia normal

What  can  PPA  tell  us  about  core  language  domains?  

ú  Semantics  ú  Phonology  ú  Orthography  (written  language)  

Language  tasks  

§  Semantic  tasks  

What is this?

Which item goes with the picture on top?

Pyramids and Palm Trees Test (Howard and Patterson, 1992)

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§  Phonological  tasks    

ú  Blend  these  sounds  together                      /b/  /oi/  /l/  à  “boil”    ú  Say  “fat”...now  take  away  “f” à  “at”    ú  Say  “mouth”...now  change  “th”  to  “s” à  “mouse”  

Language  tasks  

Arizona Phonological Battery (Beeson & Rapcsak, unpublished)

§  Written  language  tasks  n  Different word types require different types of

processing

yacht circuit doubt choir sword island debt

Irregular Words

flig hoach snite glope boak cheed merber

Nonwords

Semantically-derived Phonologically-derived

Spoken  language  

Phonology (sounds)

N=15 PPA Henry et al., JoCN, 2011

Semantics (meaning)

Written  language  

N=15 PPA Henry et al., JoCN, 2011

Phonology (sounds)

Semantics (meaning)

Neural  bases  of  semantic  vs.  phonologic  processing  

Spoken language Written language

Treatment  for  speech  and  language  impairments  in  PPA  §  Treatments  similar  to  those  applied  in  stroke  aphasia  appear  promising  (Henry  et  al.,  2008  Beeson  et  al.,  2011;  Newhart  et  al.,  2009)  

§  Treatment  effects  can  be  substantial  and  lasting  

§  Behavioral  therapy  can  result  in  changes  in  language  behaviors  and  also  in  imaging  findings  

 

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Treatment results in PPA"

§  Semantic PPA: impaired meaning system (semantics)"

§  Therapy for naming: take advantage of spared sound system"

atrophy increased activity

Wilson et al., 2009

0  

10  

20  

30  

40  

50  

60  

70  

80  

90  

100  

Pre-­‐Tx   Post-­‐Tx   3  mos.  Post   6  mos  

Trained  spoken  

Trained  written  

Treatment results in PPA"

§  Logopenic PPA: impaired sound system (phonology)"§  Therapy for naming: take advantage of spared meaning

system"

atrophy increased activity

Beeson et al., 2011

Beeson et al., 2011

Treatment results in PPA"

§  Nonfluent PPA: impaired speech!§  Therapy: take advantage of spared language

(reading)"

0.00  

0.05  

0.10  

0.15  

0.20  

Pre-­‐Tx   Post-­‐Tx   3.  mos.  post   6.  mos.  post   I  yr.  post  

Prop

or6o

n  of  to

tal  m

ul6syllabic  words  

Speech  Errors   catastrophe

ca/tas/tro/phe

“catastrophe”

“The meeting was a catastrophe”

In  sum  

§  PPA is a slow decline in speech and language caused by neurodegenerative disease"

§  Semantic, phonologic, and motor systems can be selectively impaired"

§  Treatment for speech-language can have lasting benefits, taking advantage of spared cognitive and neural systems ""

QUESTIONS?