www.tmslab.org

Center for Noninvasive Brain StimulationHarvard Medical School

Beth Israel Deaconess Medical Centerwww.bostonretinalimplant.org

The Boston Retinal Implant ProjectCenter for Innovative Visual Rehabilitation

Boston VA Medical Center

Are the Blind Really Better?

Tactile

Auditory

0.7

0.8

0.9

1

1.1

1.2

Reading Homol Non-Dom Non-DomHomologous

Thre

shold

van Boven et al. Neurology 2000

0.9

1.0

1.1

1.2

1.3

1.4

1.5

Blind Sighted

Thre

shold

JVP Domes

Gougoux et al. Nature, 2005

Verbal Memory

Amedi et al. Nat Neurosci 2003; 2004

"we only use about 30% of our brains"…???

TASTESPEECH

HEARING

VISION

SPATIAL AWARNESS

TOUCHMOTOR

WORKING MEMORY

SMELL

HEARING

VISION

SPATIAL AWARNESS

TOUCH

WORKING MEMORY

Watching the Brain in Action: Functional Neuroimaging

from Posner and Raichle

RESTING TASK

Generating Verbs

SpeakingWords

HearingWords

SeeingWords

Task Rest Difference

- =

Activation of Occipital (Visual) Cortex in the Blind

Sadato, Pascual-Leone et al., Nature: 1996; Brain:1998

Gougoux et al., 2005 PLoS; Nature 2004 Amedi et al. Nat Neurosci 2003; 2004

Braille Sound Localization Verbal Memory

EARLY BLIND LATE BLIND

Burton et al., J. Neurophysiol: 2002

Occipital Visual Cortex: Early vs. Late Blind

Day 5 > Day 1Blindfold vs Non Blindfold

Pascual-Leone et al., 2003 Merabet et al., PLOS One 2008

The Blindfold Experiment: Tactile

The Blindfold Experiment: Tactile

Kauffman et al., Neuroreport 2002

Right Hand (reading)

0

10

20

30

40

50

Bra

ille

Cha

ract

er R

ecog

nitio

n[%

erro

rs]

Day 1 Day 3 Day 5

Blindfolded: Training

Non Blindfolded: Training

Case Report:

From Hamilton et al., 2000; Neuroreport

- 63 y.o. right-handed female- blind at birth (retinopathy of pre-maturity) - Reported VA: No Light Perception OU- normal milestones, Braille at 6 y.o.- proficient reader: 120-150 symbols/min

Complaint: light-headedness, difficulty swallowing, loss of motor coordination, LOC- admitted to emergency - 24 hr coma- “normal physical and neurological exam”- within 24 hrs; alert and interactive

Braille Alexia Following an Occipital Stroke

Transcranial Magnetic Stimulation (TMS): "virtual brain lesions"

TMS Coil

Low frequency (e.g. 1 Hz)= lowered excitability

High frequency (e.g. 10-20 Hz)= increased excitability

Induced Current

GeneratedMagnetic

Field

Modulating Braille Reading Performance by Modulating Brain Activity

Roy H. Hamilton and Alvaro Pascual-Leone TICS 1998

Tactile and linguistic manifestationsof "visual" cortex modulation

Low frequency

Highfrequency

“I wish I had been born blind, because it would have enhanced my artistic perception of the world”

“Painting is a blind man’s profession, as blind people have a clearer vision of reality”

- Picasso

- Monet

Esref Armaganwww.armagan.com

Drawing vs. Scribbling

Amedi et al., 2008

Activation of Auditory Cortex in the Deaf

Nishimura et al., Nature, 1999 Finney et al., Nat Neurosci, 2001 Auer et al., Neuroreport, 2007

Activation of Occipital (Visual) Cortex in the Blind

Sadato, Pascual-Leone et al., Nature: 1996; Brain: 1998

Gougoux et al., 2005 PLoS; Nature 2004 Amedi et al. Nat Neurosci 2003; 2004

Braille Sound Localization Verbal Memory

Sign Language

+

Motion Perception Vibro-tactile

Anindya “Bapin” Bhattacharyya

http://www.bapin.info/index.html

Helen Keller

Communicating with Bapin:

Functional Neuroimaging: ASL (word>non word)

A.B.

Diffusion Tensor Imaging

S.W.

Wayfinding, Navigation and Cognitive Mapping

http://upload.wikimedia.org/wikipedia/en/c/c9/Doom-boxart.jpg�

Jaime Sanchez and CoworkersC5: University of Chile, Santiagohttp://www.c5.cl/audio/pags/softwares/audio_doom/audiodoom_metod.htm

target virtual world reconstruction final representation

player (facing north)

monster

jewel

door

table furniture stairwell exit

First Floor

Second Floor

First Floor

Second Floor

Transfer of Navigation Skills Learned with AbES to Real World

breakdown of path

path taken

statistics

lobbyentrance

classroom10

Virtual World Real World

Quantitative:- time to target- # of mistakes made

Qualitative:-type of errors made- strategies employed-"creativity" and problem solving

Outcome Measures

AbES and Functional Neuroimaging

AbES projectedon a screen

control keys

reflecting mirror

subject wearing

headphones

instructions vs rest

auditorycortex

goal-directed navigation vs rest

frontalcortex

visualcortex

parietalcortex

posteriorhippocampus

Audio-Haptic Doom and crossmodal interfacing

Other Software: University of Chile, Department of Computer Science

Artist Bernardo Strozzi (Italian, Genoese, 1581–1644)Title Tobias Curing His Father's Blindness

Case Report: Subject M.M.- monocular, and at age 3 blinded in fellow eye from a chemical burn. Undergoes corneal transplant at childhood; unsuccessful.- some light perception, no experience of form or contrast perception. Reports no visual memories or imagery.- at 43 y.o., undergoes corneal/limbal stem cell transplant.- highly motivated, intelligent individual.

courtesy the Discovery Channel

CHOROIDRPE

PHOTORECEPTORS

GANGLION CELLS

VITREOUS

BIPOLAR CELLS

NFL

SUB RETINAL

The Retinal Approach

Video courtesy of Second Sightwww.2-sight.com

maximal visualfunction

maximal cross-modaladaptation

?? ?

Cross-modal AdaptedOccipital cortex

Visual Occipital cortex

Factors:Onset

DurationType of Vision LossPrior Experience

Rehabilitation Strategy

Merabet et al., 2006

…Corollaries and Lessons Learned…

Nishimura et al., Nature, 1999

Lee et al., 2001 Nature

Nature

Auditory Cortex

correlation between degree of hypometabolism and successwith a CI. imaging is prognosticother regressors:-duration of deafness,-duration of CI use

*resting hypometabolism and notcross-modal activation* pre-lingual deaf children

…Corollaries and Lessons Learned…

www.cyberkineticsinc.com

Brain Machine Interfaces

Ersland et al., NeuroReport 8, 207–210 (1996)

left (intact) right (amputated)

TOUCH

HEARING

TASTE

SMELL

VISION

TOUCH

HEARING

TASTE

SMELL

Jaime Sanchez, PhDUniversity of Chile

Alvaro Pascual-Leone, MD PhDEla Bhatt, PhD

Mark Halko, PhDSouzana Obretenova

Center for Noninvasive Brain Stimulation

Joseph Rizzo, MDBoston Retinal Implant Project

Carroll Center for the Blind

Boston University Center for Biomedical Imaging

Our patients…