CORTICAL DEVELOPMENT, PLASTICITY AND RE-ORGANIZATION IN CHILDREN

WITH HEARING IMPAIRMENT.

Anu Sharma, Ph.D.

University of Colorado at Boulder

Funded by: National Institutes of Health

Keck Foundation

National Organization of Hearing Research

American Hearing Research Foundation

Peter Roland, M.D. Paul Bauer, M.D.Bob Peters, M.D

Kathryn Martin, M.S., CCC-A

Ross Roeser, Ph.D.

Emily Tobey, Ph.D.

,Sandra Gabbard,Ph.D., Herman Jenkins M.D., Allison Biever, AuD, David Kelsall, M.D.

Deborah Hayes

Dallas, Texas

Leif Hergils and Hans Lindehammer

Linkoping Hospital, Sweden

Denver, Colorado

Andrej Kral, M.D., Ph.D.

Institute for Neurophysiologie, Hamburg, Germany

Michael Dorman

Julia Campbell, AuD, Garrett Cardon, Au.D, Phillip Gilley,

Ph.D.University of Colorado at Boulder

To elucidate some of the

principles of neuroplasticity

which underlie early intervention.

AIM

1) Refining and ‘pruning’ of neural

pathways are necessary for learning.

2) There are optimal windows of

opportunity or ‘sensitive periods’ in

developmental neuroplasticity.

3) Cortical re-organization occurs

when sensory stimulation is not

provided in a timely fashion.

Plasticity

The brain’s ability to change in

structure and function in response to

input from the environment.

Early in life, neurons begin to form

connections or synapses. Proper

connections are essential for

learning.

More synapses in the human brain

in a millimeter cubed than stars

in the milky way.

Many factors underlie plasticityNeurogenesis

Cell Death

Inhibition

Excitation

Synaptogenisis

Increased dendritic branches/spines

Receptor trafficking

Connection strength

Long term potentiation (LTP)

Long term depression (LTD)

BDNF

NGF NGF

NGF

NGF

BDNF

BDNF

BDNF

Tt

Time

•Newborn baby’s brain grows to 3

times it’s initial size in the 1st year of life.

Are there sensitive periods for central auditory development?

A sensitive period is a window within

which the potential for neuroplasticity

reaches a maximum.

Nobel Prize in Physiology/Medicine 1981

….for discoveries concerning information processing in the visual system, including critical

periods…

Hubel and Wiesel

Since 1997, our research has explored Since 1997, our research has explored the deterioration, development and the deterioration, development and

plasticity of the human central auditory plasticity of the human central auditory pathway.pathway.

P1 has input from primary auditory cortex and recip rocal cortico-cortical loops.

(Liegeois-Chuvel et al.,1994; Eggermont and Ponton 2002; Sharma et al., 2007; Kral and Eggermont 2008; Gilley et al., 2009)

-100 0 100 200 300 400 500 600

Latency (msec)

-100 0 100 200 300 400 500 600

4 uV

P1

Cortical Auditory Evoked Responses

High density EEG

y = -34.56*LN(x) + 161.49R2 = 0.846 p<0.0001

Normal Hearing Children (N=190)

Sharma et al., 2002

Cochlear Implant SubjectsCochlear Implant Subjects

•• 245 congenitally deaf pediatric cochlear 245 congenitally deaf pediatric cochlear implant usersimplant users

Age at implantation ranged from 7 months Age at implantation ranged from 7 months to 15 yearsto 15 years

•• Experience with implant ranged from 6 Experience with implant ranged from 6 months to 10 yearsmonths to 10 years

Cochlear Implanted Children (N = 245)

-100 0 100 200 300 400 500 600 Latency (msec)

-100 0 100 200 300 400 500 600

4 uV

P1

Sharma et al., (2002; 2006)

There is a sensitive period of 3.5 There is a sensitive period of 3.5 years during which implantation years during which implantation

occurs into a highly plastic central occurs into a highly plastic central auditory system.auditory system.

Implantation after 7 years Implantation after 7 years occurs into a central auditory occurs into a central auditory system which shows reduced system which shows reduced

plasticity.plasticity.

Children implanted under ages 3-4 years show significantly better speech

perception and language skills compared to children implanted after

ages 6-7 years.

(Niparko, CDaCI 2009; Kirk et al., 2002; Summerfield, 2002, Manrique 2002, Waltzman and Cohen, 1998,

Gantz et al., 1999)

Synaptic Density in Auditory Cortex

Huttenlocher and Dhabolkar (1997)

3.5 years

Evidence for a Sensitive Period from Brain Imaging Studies

0 2 4 6 8 10 12 14 16 18 20 22 32 340

50

100

150

200

250

300 > 7 years 3.5 - 6.5 years < 3.5 years

P1

late

ncy

(ms)

Age (years)

Age of Implantation

From Lee et al. (2003)Sharma et al., 2002

Spearman’s rho=-0.659p=0.001Spearman’s rho=-0.659p=0.001

Children who performed well with the implant showed a hypometabolic auditory cortex.

Lee et al., Acta Otolaryngol 2003;123:148-153

N=22

Cochlear Implanted Children: Individual Developmental Trajectories n=(231)

Sharma et al., 2007

Right ITGBilateral STS

Right ITGContralateral STS

Gilley, Sharma, Dorman, 2008

Contralateral Parieto Temporal

PrimaryAssociation

or

‘Higher-order’

Kral, 2007

Partial or Complete Decoupling between Primary & Higher Order Cortex

If proper auditory stimulation is not

provided in a timely fashon then

there may be a disconnection

between areas of the brain which

connect sound with meaning.

These children will have difficulty

learning language through the

auditory modality.

Compensatory plasticity: Cross

Modal Re-organization

Sharma et al., 2007

CROSS-MODAL PLASTICITY: SOMATOSENSORY-AUDITORY

Finney et al., 2001

fMRI activity in deaf adults in response to visual stimuli

Visual activity in temporal cortex at STS

CROSS-MODAL PLASTICITY: VISUAL-AUDITORY

If auditory stimulation is not

delivered in a timely fashion, then

areas of the auditory cortex will re-

organize to process stimuli from

other sensory modalities.

Cross-modal re-organization in deaf cats

Visual abilities in congenitally deaf cats

Lomber et al., 2010, Nature Neuroscience

Visual abilities in congenitally deaf cats

Deaf cats show enhanced localization ability in the periphery

Lomber et al., 2010, Nature Neuroscience

Cortical Cooling (temporary deactivation of certain cortical areas)

When Posterior Auditory Field (PAF) was deactivated, deaf cats lost their enhanced visual ability.

Movement detection in deaf cats

Deaf cats showed enhanced visual localization in the periphery and enhanced thresholds for motion

detection compared to hearing cats.

When areas of the auditory cortex (PAF and DZ) were disabled, deaf cats lost these enhanced

abilities.

Certain higher order auditory areas perform visual functions in long term deafness.

Certain areas of the auditory cortex perform visual functions in

congenital deafness.

Does cross-modal plasticity affect outcome?

Visual Stimuli

128 channel high density EEG net

Photo courtesy EGI

100904/18:45:46.440 Category 1 [Average: <multiple subjects>]

CORTICAL ACTIVATION TO VISUAL STIMULINORMAL HEARING CHILDREN

CORTICAL ACTIVATION TO VISUAL STIMULI

GOOD IMPLANT USER96% SPEECH PERCEPTION (LNT)-8 YEARS OLD

CORTICAL ACTIVATION TO VISUAL STIMULATION

AVERAGE/POOR IMPLANT USER

76% SPEECH PERCEPTION (LNT)-11 YEARS OLD

Cross-modal plasticity appears to be correlated

to speech perception outcome.

Are there certain cognitive circuits activated in deafness which are beneficial for oral

language learning?

Lee et al. (2007) in Cerebral Cortex

n=22 prelingually deaf children

PET in ‘quiet waiting room’ pre implant

Correlate resting metabolic activity with

sentence scores three years after implant

Effect of age was statistically factored out.

Reasoning, attentionalcontrol, working memory,executive functionphonological and semantic Processing.

Decreased activation of temporal areas (Hypometabolism)

Good Outcomes

Increased activation of Dorsolateral

Prefrontal (DLPF)

Complex acoustic signals,voice recognition.

Poor Outcomes

Increased metabolic activity in large ventral regions, including fusiform and lower occipital regions.

Strongest negative correlation with CI outcome was located in the depth of the right STS (area associated with complex auditory pattern recognition).

Results suggest that auditory networks become associated with other cognitive circuits, i.e., re-organization of functional specialization has taken place.

Lee et al. (2007)

How does cross modal re-organization affect integration

across auditory and visual modalities?

McGurk EffectAuditory-Visual Fusion

e.g., hear /pa/, see /ka/

perceive /ta/

Responses of individual subjects to the incongruent auditory-visual/pa/ka/stimulus (McGurk test). “ta” responses indicate audiovisual fusion, “ pa” responses indicate auditory

dominance, and “ka” responses indicate visual domina nce.

Schorr E A et al. PNAS 2005;102:18748-18750

©2005 by National Academy of Sciences

Copyright ©2005 by the National Academy of SciencesSchorr, Efrat A. et al. (2005) Proc. Natl. Acad. Sc i. USA 102, 18748-18750

Late-implanted children show deficits in auditory-visual integration

Conclusions

Early intervention is important for formation of synaptic connections necessary for learning.

There are sensitive periods of optimal neuroplasticity in congenital deafness during which early intervention should be delivered

.

Deafness that continues beyond these sensitive periods results in cross-modal

cortical re-organization which may influence outcomes.

Brain and Behavior Laboratoryhttp://www.colorado.edu/slhs/eeglab

anu.sharma@colorado.edu

Julia Campbell

Garrett Cardon

Phillip Gilley

Amy Nash

Megan Loehman

Katy Brooks

Tim Beneke

Jehan Alsalmi

Amanda Syzmanski

Tracy White

Erin Castioni

Nils Penard

Laura Veazy

Elizabeth Parks

Tony Spahr

Katrina Agung