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The Boston Retinal Implant Project         Center for Noninvasive Brain Stimulation
Center for Innovative Visual Rehabilitation            Harvard Medical School
        Boston VA Medical Center               Beth Israel Deaconess Medical Center
     www.bostonretinalimplant.org                         www.tmslab.org
Are the Blind Really Better?                                                         Auditory

                              Tactile

                                               1.5
JVP Domes
                                               1.4

                                  Threshold
                                               1.3
                                               1.2
                                               1.1
                                               1.0
                                               0.9                            Gougoux et al. Nature, 2005
                                                     Blind      Sighted

              1.2

              1.1
                                                                               Verbal Memory
  Threshold




               1

              0.9

              0.8

              0.7
                    Reading   Homol           Non-Dom    Non-Dom
                                                        Homologous

               van Boven et al. Neurology 2000
                                                                          Amedi et al. Nat Neurosci 2003; 2004
"we only use about 30% of our brains"…???
TOUCH
           MOTOR              SPATIAL
                             AWARNESS
WORKING
MEMORY




                                       VISION
   SMELL




                   TASTE     HEARING
      SPEECH
TOUCH
                   SPATIAL
                  AWARNESS
WORKING
MEMORY




                            VISION




                  HEARING
Watching the Brain in Action: Functional Neuroimaging
                                           RESTING          TASK




                                             Task        Rest       Difference




                                                     -          =
Generating
  Verbs

             Speaking
              Words

                        Hearing
                        Words

                                  Seeing
                                  Words

                                                         from Posner and Raichle
Activation of Occipital (Visual) Cortex in the Blind


                 Braille                              Sound Localization                          Verbal Memory




 Sadato, Pascual-Leone et al., Nature: 1996; Brain:   Gougoux et al., 2005 PLoS; Nature 2004   Amedi et al. Nat Neurosci 2003; 2004
 1998
Occipital Visual Cortex: Early vs. Late Blind

              EARLY BLIND                LATE BLIND




                                            Burton et al., J. Neurophysiol: 2002
The Blindfold Experiment: Tactile
                                            Day 5 > Day 1
                                      Blindfold vs Non Blindfold




       Pascual-Leone et al., 2003   Merabet et al., PLOS One 2008
The Blindfold Experiment: Tactile


                                               Right Hand (reading)

                                50



                                40
Braille Character Recognition




                                30
          [% errors]




                                20

                                      Blindfolded: Training
                                      Non Blindfolded: Training
                                10




                                0
                                     Day 1                    Day 3   Day 5



                                                                              Kauffman et al., Neuroreport 2002
Braille Alexia Following an Occipital Stroke


Case Report:
 - 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




                                                  From Hamilton et al., 2000; Neuroreport
Transcranial Magnetic Stimulation (TMS): "virtual brain lesions"

 Generated
 Magnetic                     Induced
   Field                       Current


                           TMS Coil




   Low frequency (e.g. 1 Hz)
   = lowered excitability
   High frequency (e.g. 10-20 Hz)
   = increased excitability
Modulating Braille Reading Performance by Modulating Brain Activity




                                                         Low
                                                      frequency




Tactile and linguistic manifestations
of "visual" cortex modulation
                                                                          High
                                                                       frequency




                                          Roy H. Hamilton and Alvaro Pascual-Leone TICS 1998
“Painting is a blind man’s
profession, as blind people have
a clearer vision of reality”
                      - Picasso




“I wish I had been born blind,
because it would have enhanced
my artistic perception of the
world”
                      - Monet
Esref Armagan
www.armagan.com
Drawing vs. Scribbling




                         Amedi et al., 2008
Activation of Occipital (Visual) Cortex in the Blind
                Braille                                        Sound Localization                      Verbal Memory




 Sadato, Pascual-Leone et al., Nature: 1996;   Gougoux et al., 2005 PLoS; Nature 2004   Amedi et al. Nat Neurosci 2003; 2004
 Brain: 1998




Activation of Auditory Cortex in the Deaf
                      Sign Language                                 Motion Perception                  Vibro-tactile

                                                          +




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




                                   Anindya “Bapin”
                                    Bhattacharyya
http://www.bapin.info/index.html
Communicating with Bapin:
Functional Neuroimaging: ASL (word>non word)
    A.B.                                S.W.




Diffusion Tensor Imaging
Wayfinding, Navigation and Cognitive
             Mapping
target virtual world                        reconstruction        final representation




Jaime Sanchez and Coworkers
C5: University of Chile, Santiago
http://www.c5.cl/audio/pags/softwares/audio_doom/audiodoom_metod.htm
stairwell      exit
                                      table furniture

                                                                              door
                    First Floor    monster
      First Floor




                                         player
                                      (facing north)
                                                                    jewel




Second Floor        Second Floor
Transfer of Navigation Skills Learned with AbES to Real World

              Virtual World                            Real World




   Outcome Measures
   Quantitative:                                                            classroom
                                                                                10
   - time to target
   - # of mistakes made                               path
                                                      taken

   Qualitative:                                    lobby
   -type of errors made                           entrance

   - strategies employed                                        breakdown
                                                statistics        of path
   -"creativity" and problem solving
AbES and Functional Neuroimaging
                                                         instructions vs rest




                            AbES projected                                 auditory
               reflecting    on a screen
                 mirror                                                    cortex


                                                 goal-directed navigation vs rest
                                              parietal
                                               cortex                           frontal
                                                                                 cortex
                                subject      visual
     control keys               wearing      cortex
                              headphones




                                                            posterior
                                                          hippocampus
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
The Retinal Approach




                                     VITREOUS

                                     NFL

                                     GANGLION CELLS



                                     BIPOLAR CELLS




                                     PHOTORECEPTORS
                       SUB RETINAL
                                     RPE
                                     CHOROID
Video courtesy of Second Sight
www.2-sight.com
?                ?               ?

                     Cross-modal Adapted
                          Occipital cortex
        Visual
        Occipital cortex




maximal visual                       maximal cross-modal
  function                               adaptation
                        Factors:
                         Onset
                        Duration
                  Type of Vision Loss
                   Prior Experience
                 Rehabilitation Strategy


                                           Merabet et al., 2006
correlation between degree of
                                    hypometabolism and success
…Corollaries and Lessons Learned…   with a CI. imaging is prognostic
                                    other regressors:
                                    -duration of deafness,
                                    -duration of CI use
                        Auditory
                         Cortex     *resting hypometabolism and not
                                    cross-modal activation
                                    * pre-lingual deaf children




   Nishimura et al., Nature, 1999




 Nature




    Lee et al., 2001 Nature
…Corollaries and Lessons Learned…
                                                             Brain Machine Interfaces




                                                            www.cyberkineticsinc.com
left (intact)                           right (amputated)

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



TOUCH                  VISION




  HEARING           SMELL
TASTE



TOUCH




  HEARING           SMELL
Jaime Sanchez, PhD
          University of Chile

      Alvaro Pascual-Leone, MD PhD
              Ela Bhatt, PhD
             Mark Halko, PhD
           Souzana Obretenova
     Center for Noninvasive Brain
               Stimulation

           Joseph Rizzo, MD
    Boston Retinal Implant Project

      Carroll Center for the Blind

Boston University Center for Biomedical
               Imaging


            Our patients…

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Neuroplasticity Following Sensory Loss

  • 1. The Boston Retinal Implant Project Center for Noninvasive Brain Stimulation Center for Innovative Visual Rehabilitation Harvard Medical School Boston VA Medical Center Beth Israel Deaconess Medical Center www.bostonretinalimplant.org www.tmslab.org
  • 2.
  • 3. Are the Blind Really Better? Auditory Tactile 1.5 JVP Domes 1.4 Threshold 1.3 1.2 1.1 1.0 0.9 Gougoux et al. Nature, 2005 Blind Sighted 1.2 1.1 Verbal Memory Threshold 1 0.9 0.8 0.7 Reading Homol Non-Dom Non-Dom Homologous van Boven et al. Neurology 2000 Amedi et al. Nat Neurosci 2003; 2004
  • 4. "we only use about 30% of our brains"…???
  • 5. TOUCH MOTOR SPATIAL AWARNESS WORKING MEMORY VISION SMELL TASTE HEARING SPEECH
  • 6. TOUCH SPATIAL AWARNESS WORKING MEMORY VISION HEARING
  • 7. Watching the Brain in Action: Functional Neuroimaging RESTING TASK Task Rest Difference - = Generating Verbs Speaking Words Hearing Words Seeing Words from Posner and Raichle
  • 8. Activation of Occipital (Visual) Cortex in the Blind Braille Sound Localization Verbal Memory Sadato, Pascual-Leone et al., Nature: 1996; Brain: Gougoux et al., 2005 PLoS; Nature 2004 Amedi et al. Nat Neurosci 2003; 2004 1998
  • 9. Occipital Visual Cortex: Early vs. Late Blind EARLY BLIND LATE BLIND Burton et al., J. Neurophysiol: 2002
  • 10. The Blindfold Experiment: Tactile Day 5 > Day 1 Blindfold vs Non Blindfold Pascual-Leone et al., 2003 Merabet et al., PLOS One 2008
  • 11. The Blindfold Experiment: Tactile Right Hand (reading) 50 40 Braille Character Recognition 30 [% errors] 20 Blindfolded: Training Non Blindfolded: Training 10 0 Day 1 Day 3 Day 5 Kauffman et al., Neuroreport 2002
  • 12. Braille Alexia Following an Occipital Stroke Case Report: - 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 From Hamilton et al., 2000; Neuroreport
  • 13. Transcranial Magnetic Stimulation (TMS): "virtual brain lesions" Generated Magnetic Induced Field Current TMS Coil Low frequency (e.g. 1 Hz) = lowered excitability High frequency (e.g. 10-20 Hz) = increased excitability
  • 14. Modulating Braille Reading Performance by Modulating Brain Activity Low frequency Tactile and linguistic manifestations of "visual" cortex modulation High frequency Roy H. Hamilton and Alvaro Pascual-Leone TICS 1998
  • 15. “Painting is a blind man’s profession, as blind people have a clearer vision of reality” - Picasso “I wish I had been born blind, because it would have enhanced my artistic perception of the world” - Monet
  • 17. Drawing vs. Scribbling Amedi et al., 2008
  • 18. Activation of Occipital (Visual) Cortex in the Blind Braille Sound Localization Verbal Memory Sadato, Pascual-Leone et al., Nature: 1996; Gougoux et al., 2005 PLoS; Nature 2004 Amedi et al. Nat Neurosci 2003; 2004 Brain: 1998 Activation of Auditory Cortex in the Deaf Sign Language Motion Perception Vibro-tactile + Nishimura et al., Nature, 1999 Finney et al., Nat Neurosci, 2001 Auer et al., Neuroreport, 2007
  • 19. Helen Keller Anindya “Bapin” Bhattacharyya http://www.bapin.info/index.html
  • 21. Functional Neuroimaging: ASL (word>non word) A.B. S.W. Diffusion Tensor Imaging
  • 22. Wayfinding, Navigation and Cognitive Mapping
  • 23.
  • 24. target virtual world reconstruction final representation Jaime Sanchez and Coworkers C5: University of Chile, Santiago http://www.c5.cl/audio/pags/softwares/audio_doom/audiodoom_metod.htm
  • 25. stairwell exit table furniture door First Floor monster First Floor player (facing north) jewel Second Floor Second Floor
  • 26. Transfer of Navigation Skills Learned with AbES to Real World Virtual World Real World Outcome Measures Quantitative: classroom 10 - time to target - # of mistakes made path taken Qualitative: lobby -type of errors made entrance - strategies employed breakdown statistics of path -"creativity" and problem solving
  • 27. AbES and Functional Neuroimaging instructions vs rest AbES projected auditory reflecting on a screen mirror cortex goal-directed navigation vs rest parietal cortex frontal cortex subject visual control keys wearing cortex headphones posterior hippocampus
  • 28. Audio-Haptic Doom and crossmodal interfacing
  • 29. Other Software: University of Chile, Department of Computer Science
  • 30. Artist Bernardo Strozzi (Italian, Genoese, 1581–1644) Title Tobias Curing His Father's Blindness
  • 31. 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
  • 32. The Retinal Approach VITREOUS NFL GANGLION CELLS BIPOLAR CELLS PHOTORECEPTORS SUB RETINAL RPE CHOROID
  • 33. Video courtesy of Second Sight www.2-sight.com
  • 34. ? ? ? Cross-modal Adapted Occipital cortex Visual Occipital cortex maximal visual maximal cross-modal function adaptation Factors: Onset Duration Type of Vision Loss Prior Experience Rehabilitation Strategy Merabet et al., 2006
  • 35. correlation between degree of hypometabolism and success …Corollaries and Lessons Learned… with a CI. imaging is prognostic other regressors: -duration of deafness, -duration of CI use Auditory Cortex *resting hypometabolism and not cross-modal activation * pre-lingual deaf children Nishimura et al., Nature, 1999 Nature Lee et al., 2001 Nature
  • 36. …Corollaries and Lessons Learned… Brain Machine Interfaces www.cyberkineticsinc.com left (intact) right (amputated) Ersland et al., NeuroReport 8, 207–210 (1996)
  • 37. TASTE TOUCH VISION HEARING SMELL
  • 39. Jaime Sanchez, PhD University of Chile Alvaro Pascual-Leone, MD PhD Ela Bhatt, PhD Mark Halko, PhD Souzana Obretenova Center for Noninvasive Brain Stimulation Joseph Rizzo, MD Boston Retinal Implant Project Carroll Center for the Blind Boston University Center for Biomedical Imaging Our patients…