Methodologies and instruments for the characterization of the Parkinson disease

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1 Methodologies and instruments for the characterization of the Parkinson disease Computer Engineering Faculty Author: Alfonso Isola Supervisor Chiar.mo Prof. Ing. P. Arena Co-Supervisors Supervisors: Chiar.mo Prof. P. Mazzone Ing. Adriano Basile Ing. Davide Lombardo Ing. Guido Vagliasindi

Chiar.mo Prof. Ing. P. Arena Co-Supervisors Supervisors: Chiar.mo Prof. P. Mazzone Ing.

2 Introduction Project Cooperation Cooperation among the DIEES of the Università degli Studi di Catania, ania, the STMicroelectronics of Catania and the Orthopedic Surgery Center of the A. Alesini Hospital- Roma. Technology used DBS Activa Therapy and LFP recordings (furnished( by Medtronic) This therapy is a big scientific opportunity Objectives Design a Data-Logger for the mass-storage storage of the neuro celebral signals taken from Basal Ganglia nucleuses by means of DB leads. Possible Applications Medical Research and careful characterization of the Parkinson disease Auto-setting of the neurostimolator s parameters 2/15

Technology used DBS Activa Therapy and LFP recordings (furnished( by Medtronic) This therapy is a big scientific opportunity Objectives Design a Data-Logger

3 The Parkinson disease The Parkinson disease (MP) is an evolution progressive illness with unknown causes (idiopathic), correlated to a neural degeneration of the Substantia Nigra. The main clinical symptoms are: Bradikinesia (slowness of movement) Akinesia (lack of movement) Tremor Rigidity Postural instability Therapy Pharmaceutical (L-DOPA) Loss of effictivenes after 5 years Clinic therapy useless in some patients LTDS (Long( Term Dopa Syndrome) Surgical lesions (Pallidotomy surgery) These lesions are executed in the STN or GPi Invasive Irreversible Therapy Electric stimulation at high frequency (DBS) It succeds in attenuating the symptoms Unknown workings, maybe it forces the neurons of the stimulated zone to work at high freq. 80% 70% 60% 50% 40% 30% 20% 10% 0% 31% 50% 74% 3-5 yrs 5-7 yrs yrs Percentage of patients that suffer of LTDS 3/15

Clinic therapy useless in some patients LTDS (Long( Term Dopa Syndrome) Surgical lesions (Pallidotomy surgery) These lesions are executed in the STN or GPi Invasive Irreversible Therapy Electric

4 The Basal Ganglia nucleuses The Basal Ganglia nucleuses consist of several subcortical structures densely interconnected The main four nucleuses are: the Striated (Putamen & Caudate) the Globus Pallidus (GP) the Substantia Nigra (SN) The Subthalamic nucleus (STN) The Globus Pallidus consist of : Internal Globus Pallidus (GPi) External Blobus Pallidus (GPe) The Substantia Nigra consist of: reticular part (SNr) compact part (SNc) 4/15

Substantia Nigra (SN) The Subthalamic nucleus (STN) The Globus Pallidus consist of : Internal Globus

5 The boxes and arrows Model Physiological activity of the B.G. nucleuses Cortex Pathological activity of the B.G. nucleuses Cortex Indirect Putamen Inib D2 Ec D1 Direct Indirect Putamen Direct SNc SNc GPe Talamo GPe Talamo STN STN GPi SNr GPi SNr The direct and indirect paths The Direct path is positive in the Putamen Talamo action The Indirect path is negative 5/15

nucleuses Cortex Indirect Putamen Inib D2 Ec D1 Direct Indirect Putamen Direct SNc SNc GPe

6 Deep Brain Stimulation The neurostimolator is planted completely under skin; ; the leads are planted inside the GPi or the STN, only later having identified the objective nucleus through MRI. The neurostimolator has two electrodes,, one for each part of the brain We have to tune neurostimulator parameters (Voltage to be applied, Duty Cycle square wave, etc.). Each electrode has 4 terminal contacts 6/15

The neurostimolator has two electrodes,, one for each part of the brain We have to tune

7 Signals Analysis Patients Exercise Protocol used Go-no-go Free movement Spectral Analysis Tecniques used Short Time Fourier analysis (STFT) Power Spectral Density (PSD) Synchronous and asyncronous activities Inside the β band (10 40 Hz) Close the 70 Hz (only( for the STN) The Neuronal Gate Theory in STN 7/15

Spectral Density (PSD) Synchronous and asyncronous activities Inside the β

8 Signals Analysis The effects of the L-Dopa on the PSD of the signal rstn12: 8/15

9 Signals Analysis The movement Effects We have verified that during a patient voluntary movement and without dose of L-Dopa, inside the β band the signal rstn12 PSD reduces its amplitude, while doesn t appear the high-frequency synchronization (typical of the L- Dopa case). 9/15

band the signal rstn12 PSD reduces its amplitude, while doesn t

10 Signals Analysis Degradation of the signals in case of re-quantization of data from 12 to 8 bits: This last analysis is useful in order to reach the aim of this work, or better to design a Data Logger for the mass-storage storage of neurocerebral signals. It consist of one ST7 microcontrollor, which is furnished of a 8 bits ADC. The final results of this study, allow to underline as the reduction of the quantization bits doesn t cause the loss of any signal intrinsic characteristic both in the time domain and the frequency domain. 10/15

It consist of one ST7 microcontrollor, which is furnished of a 8 bits ADC.

11 Limits of the analyzed recordings Measurements executed with different exercise protocols Different Signals amplification and Sampling frequecy Different and bounded measurements duration (Implementation of a DBS signals Data Logger) Need to have DB measurements related to the most varied conditions in which the patient can be during his day. (Future implementation of an adaptive and autonomous DBS Parameters Control System) 11/15

signals Data Logger) Need to have DB measurements related to the most varied conditions in which the patient

12 Data Logger The development card choice in order to implement the Data Logger has been the ST7F265 Mass Storage Evaluation Kit. STVD 7 INDART-STx 12/15

13 The recording Firmware main() Begin Media_check() USER_application() The recording routine Signal_Record() exploits a timer interrupt routine in order to take a signal sample (1 byte) every t seconds (ex. t =125µs if Fs=8KHz). This sample is saved inside one of the 512 bytes recording buffers available. Just one of the buffers is full by means of the DTC (Data Transfer Coprocessor) unit the buffer is downloaded inside a file wave held in a SD-MMC memory. Signal_Record() End 13/15

This sample is saved inside one of the 512 bytes recording buffers available.

14 The Neurocerebral signals Mass-storage storage System Circuit of Signal adaptation ADC 8 bit byte RAM ST7F265 MCU DTC Buffer_0 512 Byte Data Logger The data are saved inside a WAVE file held inside a SD-MMC memory. 14/15

RAM ST7F265 MCU DTC Buffer_0 512 Byte Data Logger The

15 Future developments Implementation of an adaptive and autonomous Control System for the DBS technical parameters. CONTROL 15/15

16 Thanks Supervisor of Università degli Studi di Catania, Prof. P. Arena Co-Supervisors of Univeristà di Catania, Ing. D. Lombardo e Ing. G.Vagliasindi,, and of ST Microelectronics di Catania Ing. Adriano Basile Prof. P. Mazzone (Centro( Traumatologico Ortopedico dell Ospedale A. Alesini - Roma) 16/15

Lombardo e Ing. G.Vagliasindi,, and of ST Microelectronics di Catania Ing.

Motor dysfunction 2: Spinal cord injury and subcortical motor disorders ANATOMY REVIEW: Basal Ganglia

Motor dysfunction 2: Spinal cord injury and subcortical motor disorders ANATOMY REVIEW: Basal Ganglia A group of subcortical nuclei caudate, putamen, globus pallidus Caudate & Putamen = Neostriatum caudate