1. Hospital Central de Asturias Centro Universitario Unidad Multidisciplinar de los Trastornos del Movimiento Scalp evoked potentials induced by Therapeutic DBS of Subthalamic nucleus F. Fernández-González, F. Seijo, C. Vallés, B. Lozano, L. Guisasola, C. Salvador, A. Galindo

2. -Fz+Cz -Cz-+Pz -Pz+Oz -Fpz+Fz 50 ms Scalp evoked potentials Therapeutic DBS-STN stimulation RL

3. Hospital Central de Asturias Centro Universitario DBS - STN19981999200020012002 Total implants Bilateral 3 4 12 25 11 90 Unilateral 6 0 6 5 2 19 Total patients 9 4 18 30 13+ TOTAL 9 13 31 61 74+ 109 Movement Disorders Multidisciplinary Team

4. Pre - STN DBS OFF medication Good Indication Post - STN DBS ON DBS - OFF Medication Bad results? 6 months N= 32 mA S Hzpole mean 2.975.0156.5 1.9 s.d. 0.620.4 25.60.7 min. 1.060.0130.00.0 1th quar. 2.560.0135.02.0 median 2.960.0135.02.0 3th quar. 3.290.0185.02.0 max. 4.0120.0185.03.0

5. 0.3 a 0.4 mm 0.1 a 0.2 mm 1.0 mmMETHODOLOGY

6. Monopolar G2 recording G1 G2 Unitary Recording Trigger threshold From STN we can record neurons with single and bursting pattern, From rostro-dorso-lateral Subthalamus we can record kinestethic unitary activities (32%). The kinesthetic neurons are somatotopically organized.

7. Bipolar G1-G2 recording G1 G2 Multiunitary Recording 1 Second - 2 mm from AC-PC plane - 3 mm from AC-PC plane - 4 mm from AC-PC plane - 5 mm from AC-PC plane From rostro-dorso-lateral STN we can record a kinesthetic related multiunitary activity with a 4Hz pattern ( - 3 mm AC-PC plane), descending 1 mm into the STN, the multiunitary recording show different values ( an irregular pattern at 7-9 Hz)

8. Bipolar G1-G2 recording G1 G2 Multiunitary Recording 1 Second - 2 mm from AC-PC plane - 3 mm from AC-PC plane - 4 mm from AC-PC plane - 5 mm from AC-PC plane From Cortex (Cx) to Substantia Nigra pars reticulata (SNr) two seconds of multiunitary neuronal activity (bipolar recording) are recorded and stored in steps of 1 mm of the recording track, starting at cortex. From the 2 sec. recording of multiunitary neuronal activity the on line process calculates the integral of the multiunitary one, and is plotted against the distance to the target in a graphic that shows the stereotactic angle of the electrode trajectory in the sagital plane. Right HemisphereLeft Hemisphere Cx STR CI STN SNr

9. Therapeutic tetraelectrode 7.5 mm Intracerebral Extracraneal To the Electromyograph G1 G2

10. Video 1Video 2 Video 3 Tetraelectrode Stimulation DisKinesiasRigidity Tremor

11. 0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 25.0 27.5 30.0 32.5 35.0 10.0 7.5 5.0 2.5 0.0 -2.5 -5.0 -7.5 -10.0 -12.5 -15.0 -17.5 -20.0 0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 25.0 27.5 30.0 32.5 35.0 Fp. 3 (-3 IPC) AC-PC Plane Simulation of the electrical current diffusion by DBS monopolar stimulus. Stimulus: 2mA, 100 sec Current density = 0.02 mA/mm 2 2.5 mm 5.0 mm Stimulus: 5mA, 100 sec Current density = 0.01 mA/mm 2 Is necesary a CD = 0.04 mA/mm2 to excite large axons and a CD = 0.3 mA/mm2 to excite small ones.

12. 0 1 2 3 Threshold to evoke motor responses (Sporadic motor responses) pole mean mA 3.0 3.5 4.3 5.3 s.d. 1.2 1.2 1.6 1.8 Motor evoked potential (Direct motor responses) pole mean mA 4.9 5.6 6.6 7.6 s.d. 1.8 1.6 1.7 1.8 3210 3210 ( x mA; 100 mS; 3 p.p.s) Stimulation: DBS monopolar - 2 pole Recording: Ext. Dig. Communis rectified EMG -40 -20 0.0 +20 +40 +60 +80 +100 +120 +140ms 60 V 58.8ms 12.6ms 1.7mA 1.9mA 2.1mA 2.3mA 2.5mA Subthreshol 2.9mA 3.4mA 3.8mA Motor threshold 4.1mA 4.3mA 4.4mA 4.5mA 4.6mA Motor response 4.7mA 4.9mA 5.0mA Data from 64 implants

13. N = 18 Set A : < 2.5 mA N = 14 Set B : > 2.5 mA Stimulus intensity needed to induce Motor threshold on Ext.Dig.Comm. Linear correlation (Motor threshold ) - 0.9 0.7 0.5 0.9 - 0.7 0.6 0.7 0.7 - 0.9 0.5 0.6 0.9 - <0.001 <0.001 <0.001 <0.001 Therapeutic DBS parameters mA mS Hz Pole 0.05 pppp Mean differences Set A versus Set B Stimulus intensity needed to induce Motor threshold 2.0 2.5 3.4 4.3 0.5 0.7 1.0 1.7 Therapeutic DBS parameters mA mS Hz Pole 2.7 58.8 143.3 1.9 0.6 14.3 20.3 0.6 Mean S.D. Mean S.D. Set A ( N = 18) Stimulus intensity needed to induce Motor threshold 3.7 4.1 4.9 5.9 1.1 0.9 1.6 1.5 Therapeutic DBS parameters mA mS Hz Pole 3.1 82.1 166.1 1.7 0.4 30.4 26.4 0.7 Mean S.D. Mean S.D. Set B ( N = 14) 5.0 TOTAL Patients Number = 32 Median values = 3.83.02.5 mA x mA 100 S 3 pps TOTAL Number = 32

14. S.I. 10-20 Fpz Fz Cz Pz Oz P4 C4 F4 Fp2 -Fz+Cz -Cz-+Pz -Fpz+Fz -Pz+Oz 100 ms -Fz+Cz -Cz-+Pz -Pz+Oz -Fpz+Fz 50 ms -Fpz+Fz 25 ms 40uV 5.5 ms 7 a 12 ms 75 ms 0 1 2 3

15. STN monopolar stimulation Are this cortical recorded components EMG artefacts? Stimulation: DBS monopolar - 2 pole Recording: Ext. Dig. Communis rectified EMG -40 -20 0.0 +20 +40 +60 +80 +100 +120 +140ms 60 V 58.8ms 12.6ms 1.7mA 1.9mA 2.1mA 2.3mA 2.5mA Subthreshol 2.9mA 3.4mA 3.8mA Motor threshold 4.1mA 4.3mA 4.4mA 4.5mA 4.6mA Motor response 4.7mA 4.9mA 5.0mA 5.3 mSec Masseter 8.4 mSec Borla mentonniana 13.2 mSec Ext. Dig. Comm. 0 1 2 3 -Fpz+Fz 25 ms 40 V 5.5ms 7 a 12 ms 75ms Stim.

16. 0 1 2 3 S.I. 10-20 Fpz Fz Cz Pz Oz P4 C4 F4 Fp2 Mínimal 1.1 mA STIMULATION: Monopolar DBS-STN Tetraelectrode: 2 Subminimal 0.6 mA RECORDING: A) Ext.Dig.Comm. Integrated EMG B) Scalp evoked potentials Subthreshold 2.3 mA Motor threshold 4.6 mA Direct motor responsesSporadic motor responsesNO motor responses N= 32 mA S Hzpole mean 2.975.0156.5 1.9 s.d. 0.620.4 25.60.7 Remember: therapeutic values 40uV 20 ms Fpz - Fz Fz - Cz Cz - Pz Pz - Oz NO scalp responsesScalp evoked responses Fpz - Fz Fz - Cz Cz - Pz Pz - Oz Fpz - Fz Fz - Cz Cz - Pz Pz - Oz

17. S.I. 10-20 Fpz Fz Cz Pz Oz P4 C4 F4 Fp2 +4 +0 -2 -4 -6 +6 20 ms +2 Stimulation: Bipolar 500 A; 100 s 0.3 a 0.4 mm 0.1 a 0.2 mm 1.0 mm Trajectory Target

18. Based in Parent (1998) 2 a 3 Ramón y Cajal (1906) Capsula interna (2 a 3 ) Lenticular fasciculus or Forels field H2) (2 a 3 ) Subthalamic fasciculus (2 a 3 ) Ansa lenticilaris, Thalamic fasciculus or Forel H1. (2 a 3 ) Zona Incerta Subthalamic nucleus Cerebral peduncule

19. Hospital Central de Asturias Centro Universitario Unidad Multidisciplinar de los Trastornos del Movimiento

20. S.I. 10-20 Fpz Fz Cz Pz Oz P4 C4 F4 Fp2 Ejemplo mapping: N. Mediano dcho. Mapping de la activación cortical inducida por el estimulo umbral motor (3.5 mA) del núcleo Subtalámico derecho, aplicado como estimulación bipolar con cátodo en el polo 2 del tetraelectrodo implantado Umbral motor 20ms 40uV

21. S.I. 10-20 Fpz Fz Cz Pz Oz P4 C4 F4 Fp2 Ejemplo mapping por estimulación a nivel del núcleo Subtalámico Izdo, por estimulo bipolar con cátodo en el polo 2 del tetraelectrodo implantado 0 a 40 ms252 a 292 ms336 a 502 ms Ejemplo mapping: Estimulo N. Mediano derecho Ejemplo mapping: Estimulo n. Subtalámico izquierdo