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ResearchTalks
      Université catholique de Louvain


Neural stimulation, challenges and success
   Stimulation neurale, succès et défis
          Jean DELBEKE, MD, PhD
                 10/10/2011
               Louvain-la-Neuve
From Prometheus to Cyborg fiction

• The pacemaker has opened
  the gate towards functional
  electrical stimulation.

• Cochlear prosthesis, sphincter
  control, drop foot system, pain
  stimulators, vagus nerve
  stimulation, the visual
  prosthesis and many others
  including deep brain stimulation
Apprentissage de la reconnaissance de patterns
             100



              80
 Score (%)




              60



              40



              20



               0
                   1   2   3   4    5     6     7   8    9     10
                                   Evaluation
                                                        57 s
Virtual perception experiment
                          Frequency (Hz) 9 p
mA 0             100            200           300                400
-0,5
                                                     9 p; 106.5 µs
-0,4                                                 F Model

                                               100 µs pulse trains
-0,3                                                80 Hz;106.5 µs
                                                    N Model
-0,2

-0,1

0,0
       0        10            20         30              40
                       Number of pulses (N) 80 Hz
Rhéobase for the perception of pulse trains

           µA

1998                                 2008


  N                             F    F (Hz)
   1                                   10
   2                                   20
   4                                   40
   8                                   80
  16         N                        160
  32                                  320
Wrong assumptions are still the rule

      And yet results
      are being obtained




                           The visual prosthesis
Moi, personne consciente,
libre de penser, vouloir et créer
Phosphene position
                                    90°   180°

 Optic nerve
                                    0°    270°

  Axons:
  0.6 µm
  0.9 µm
  1.2 µm




Visual field
Empedocles (490-430 BC) put forward the
   idea that we see objects because light
streams out of our eyes and touches them.
                                                        (Wikipedia)


           Control
CNS         of eye
          movements

                                                          Extraocular
                                                             muscles
                Efference Copy




                                  Motor Command


                                 Extraocular proprioception


                                      Retinal signal
                                                                        Eye
   Visual
localization                                           Optic nerve
               Comparator
Perception threshold of optic nerve stimuli
  at different phases of the hearth beat
350.00                       Threshold (µA)

300.00

250.00

200.00

150.00
                0°
                90°
100.00
                180°
 50.00          270°
                            % ECG cycle
  0.00
         0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95
Sensors
          Microfluidics   NEUROPROBES
Biofilm Cell migration Growth Differentiation Matrix secretion
         seconds minutes         hours     days           weeks

                                     Platelets,
 Implant          Protein
                                     Monocytes       Neovascularisation
                  Adsorption
                                     Granulocytes
Gold,       Co, Cr, Ni                                    NO, VEGF
silver                         Fibrin clotting
                                erythrocytes
                Complement                       Acute inflammation
 Toxicity       pathway          Bacteria
                                                 TNFα,     Fibroblasts,
                    Infection,                     TGFβ    Macrophages
                    biofouling
 Allergy,                      Large particles,     Wound healing, scar
                                                    Prosthesis integration
 anaphylaxis         Granuloma frustrated
                               phagocytosis         Fibrous capsule
DEEP (Drug-releasing Electrode with Enhanced Properties)




                  x+                                     0
                                 +x e-
                        A-                                    + x A-
                             x
            N                    -x e-             N     n
                  n

            H                                      H
    PPy oxidized form                    PPy neutral (reduced) form
    Conducting form                      Insulating form
    Stores anions                        Releases anions
Typical model in bioengineering
When the other discipline is supposed to know why
            project
Or about the importance to convey the unknown


                      Limited knowledge
    Users need                             Design & Fabrication


                      Empiricism



          Basic research               Applied research



                             Economy
   Available device                         Certifiable product
Neurotech ADNS-300




Nerve




              -
        Amp
                  Stimulation
              +
Contributors to the optic nerve prosthesis
•   Nos volontaires anonymes
•   Université catholique de Louvain, Louvain-la-Neuve, Belgique
     – Laboratoire de Microélectronique (DICE)
     – Génie de la réhabilitation neurale (GREN)
     – Clinique Universitaires St Luc
          • Service d’ophtalmologie, de neurochirurgie, d ’ORL
     – Commission d ’Ethique Hospitalo-Facultaire
•   Matra Electronique, La Croix Saint Ouen, France
•   NeuroTech S.A., Louvain-la-Neuve, Belgium
•   CEA Leti, Grenoble, France
•   ANCL, Case Western Reserve University, Cleveland, Ohio, USA
•   Centro Nacional de Microelectronica, Barcelona, Spain
•   Centre Suisse d’Electronique et de Microtechnique, Neuchâtel, Swisse
•   Empirica GmbH, Bonn, Allemagne
•   Norton-Desmarquest S.A., Saint-Gobin, Vincennes, France
•   BiomeTech S.A., Lyon, France
•   Service d ’Ophtalmologie de l ’Université de Gand, Belgique
•   La Commission Européenne (Projets MIVIP et OPTIVIP), la région Wallonne de
    Belgique, la fondation Alexandre VISION, le Lions club et un donateur anonyme
And later projects …
• Ecole Polytechnique de Louvain
    – PCPM
    – POLY
    – ICTM
•   Faculté de Médecine/MOEX
•   UCLondon
•   UGent
•   UBath
•   CNRS Lille
•   AML
•   It4ip

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ResearchTalks Vol. 2 - Neural stimulation, challenges and success

  • 1. ResearchTalks Université catholique de Louvain Neural stimulation, challenges and success Stimulation neurale, succès et défis Jean DELBEKE, MD, PhD 10/10/2011 Louvain-la-Neuve
  • 2. From Prometheus to Cyborg fiction • The pacemaker has opened the gate towards functional electrical stimulation. • Cochlear prosthesis, sphincter control, drop foot system, pain stimulators, vagus nerve stimulation, the visual prosthesis and many others including deep brain stimulation
  • 3.
  • 4. Apprentissage de la reconnaissance de patterns 100 80 Score (%) 60 40 20 0 1 2 3 4 5 6 7 8 9 10 Evaluation 57 s
  • 5. Virtual perception experiment Frequency (Hz) 9 p mA 0 100 200 300 400 -0,5 9 p; 106.5 µs -0,4 F Model 100 µs pulse trains -0,3 80 Hz;106.5 µs N Model -0,2 -0,1 0,0 0 10 20 30 40 Number of pulses (N) 80 Hz
  • 6. Rhéobase for the perception of pulse trains µA 1998 2008 N F F (Hz) 1 10 2 20 4 40 8 80 16 N 160 32 320
  • 7. Wrong assumptions are still the rule And yet results are being obtained The visual prosthesis
  • 8. Moi, personne consciente, libre de penser, vouloir et créer
  • 9. Phosphene position 90° 180° Optic nerve 0° 270° Axons: 0.6 µm 0.9 µm 1.2 µm Visual field
  • 10. Empedocles (490-430 BC) put forward the idea that we see objects because light streams out of our eyes and touches them. (Wikipedia) Control CNS of eye movements Extraocular muscles Efference Copy Motor Command Extraocular proprioception Retinal signal Eye Visual localization Optic nerve Comparator
  • 11. Perception threshold of optic nerve stimuli at different phases of the hearth beat 350.00 Threshold (µA) 300.00 250.00 200.00 150.00 0° 90° 100.00 180° 50.00 270° % ECG cycle 0.00 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95
  • 12. Sensors Microfluidics NEUROPROBES
  • 13. Biofilm Cell migration Growth Differentiation Matrix secretion seconds minutes hours days weeks Platelets, Implant Protein Monocytes Neovascularisation Adsorption Granulocytes Gold, Co, Cr, Ni NO, VEGF silver Fibrin clotting erythrocytes Complement Acute inflammation Toxicity pathway Bacteria TNFα, Fibroblasts, Infection, TGFβ Macrophages biofouling Allergy, Large particles, Wound healing, scar Prosthesis integration anaphylaxis Granuloma frustrated phagocytosis Fibrous capsule
  • 14. DEEP (Drug-releasing Electrode with Enhanced Properties) x+ 0 +x e- A- + x A- x N -x e- N n n H H PPy oxidized form PPy neutral (reduced) form Conducting form Insulating form Stores anions Releases anions
  • 15. Typical model in bioengineering When the other discipline is supposed to know why project Or about the importance to convey the unknown Limited knowledge Users need Design & Fabrication Empiricism Basic research Applied research Economy Available device Certifiable product
  • 16. Neurotech ADNS-300 Nerve - Amp Stimulation +
  • 17. Contributors to the optic nerve prosthesis • Nos volontaires anonymes • Université catholique de Louvain, Louvain-la-Neuve, Belgique – Laboratoire de Microélectronique (DICE) – Génie de la réhabilitation neurale (GREN) – Clinique Universitaires St Luc • Service d’ophtalmologie, de neurochirurgie, d ’ORL – Commission d ’Ethique Hospitalo-Facultaire • Matra Electronique, La Croix Saint Ouen, France • NeuroTech S.A., Louvain-la-Neuve, Belgium • CEA Leti, Grenoble, France • ANCL, Case Western Reserve University, Cleveland, Ohio, USA • Centro Nacional de Microelectronica, Barcelona, Spain • Centre Suisse d’Electronique et de Microtechnique, Neuchâtel, Swisse • Empirica GmbH, Bonn, Allemagne • Norton-Desmarquest S.A., Saint-Gobin, Vincennes, France • BiomeTech S.A., Lyon, France • Service d ’Ophtalmologie de l ’Université de Gand, Belgique • La Commission Européenne (Projets MIVIP et OPTIVIP), la région Wallonne de Belgique, la fondation Alexandre VISION, le Lions club et un donateur anonyme
  • 18. And later projects … • Ecole Polytechnique de Louvain – PCPM – POLY – ICTM • Faculté de Médecine/MOEX • UCLondon • UGent • UBath • CNRS Lille • AML • It4ip