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

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

Hospital Central de Asturias Centro Universitario DBS - STN Total implants Bilateral Unilateral Total patients TOTAL Movement Disorders Multidisciplinary Team

Pre - STN DBS OFF medication Good Indication Post - STN DBS ON DBS - OFF Medication Bad results? 6 months N= 32 mA S Hzpole mean s.d min th quar median th quar max

0.3 a 0.4 mm 0.1 a 0.2 mm 1.0 mmMETHODOLOGY

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.

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)

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

Therapeutic tetraelectrode 7.5 mm Intracerebral Extracraneal To the Electromyograph G1 G2

Video 1Video 2 Video 3 Tetraelectrode Stimulation DisKinesiasRigidity Tremor

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 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.

Threshold to evoke motor responses (Sporadic motor responses) pole mean mA s.d Motor evoked potential (Direct motor responses) pole mean mA s.d ( x mA; 100 mS; 3 p.p.s) Stimulation: DBS monopolar - 2 pole Recording: Ext. Dig. Communis rectified EMG ms 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

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 ) <0.001 <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 Therapeutic DBS parameters mA mS Hz Pole Mean S.D. Mean S.D. Set A ( N = 18) Stimulus intensity needed to induce Motor threshold Therapeutic DBS parameters mA mS Hz Pole Mean S.D. Mean S.D. Set B ( N = 14) 5.0 TOTAL Patients Number = 32 Median values = mA x mA 100 S 3 pps TOTAL Number = 32

S.I 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

STN monopolar stimulation Are this cortical recorded components EMG artefacts? Stimulation: DBS monopolar - 2 pole Recording: Ext. Dig. Communis rectified EMG ms 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 Fpz+Fz 25 ms 40 V 5.5ms 7 a 12 ms 75ms Stim.

S.I 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 s.d 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

S.I Fpz Fz Cz Pz Oz P4 C4 F4 Fp 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

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

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

S.I 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

S.I 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