NEURAL CONTROL OF MOVEMENT: ENGINEERING THE RHYTHMS OF THE BRAIN Madeleine Lowery School of Electrical and Electronic Engineering Centre for Biomedical Engineering University College Dublin
Parkinson s disease 2 nd most common neurological disorder 1-3 % of the population over 65 7 million individuals worldwide
Loss of dopamine in Parkinson s disease Imaging of dopaminergic activity in the Parkinsonian basal ganglia shown by fluorodopa PET. Dunnett and Björklund, Nature 399, 1999.
Deep Brain Stimulation (DBS) Stimulation electrode Subcutaneous extension wire Implanted stimulator Pulse amptlitude DBS waveform V Stimulating pulse Pulse duration Charge-balancing pulse Time
Deep Brain Stimulation (DBS) DBS OFF DBS ON
Modelling deep brain stimulation Macroscopic models System models Neural networks Single neurons Electric field
Electric field effects Scalp Skull Electrode Cerebrospinal fluid Grey and white matter brain tissue Nerves
Volume of neural tissue activated.975 quantile mean.25 quantile Grant and Lowery, IEEE Trans. Biomed. Eng., 21. Schmidt et al., IEEE Trans. Biomed. Eng., 213.
NETWORK EFFECTS White matter fiber architecture of the brain. Measured from diffusion spectral imaging (DSI). www.humanconnectomeproject.org
NETWORK EFFECTS Interneurons Cortex Pyramidal tract neurons Soma Striatum AIS Axon GPe Thalamus Collateral STN GPi DBS LFP GABA Glutamate Electrode
Neural oscillations in Parkinson's disease Simulated STN local field potential.5 1. 1.5 2. Time (s) DBS ON 1 2 3 4 5 Frequency (Hz) Recorded STN local field potential * DBS ON 1 2 3 4 5 Frequency (Hz) *Clinical data recorded by Dr Hayriye Cagnan and Prof. Peter Brown, University of Oxford. DBS off DBS on DBS off DBS on Beta band power (normalised) 1..8.6.4.2.2.4.6.8 1 1.2 DBS amplitude (arbitrary units) Simulated data Experimental data
Suppression of local field potential oscillations with DBS Variation with DBS parameters (pulse amplitude, duration and frequency) 1 Oscillation amplitude 1.4 1.2 1.8.6.4.2 12 1 8 Pulse duration (ms) 6 4 2 4 3 2 Amplitude (ma) 1 Oscillation amplitude 1.5 1.5 2 4 6 8 1 12 Pulse duration (ms) 25 2 15 1 Frequency (Hz) Oscillation amplitude 1.4 1.2 1.8.6.4.2 25 2 Frequency (Hz) 15 1 4 3 2 1 Amplitude (ma).9.8.7.6.5.4.3.2
Suppression of low-frequency oscillations with high-frequency dither
Suppression of low-frequency oscillations with high-frequency dither DBS T.2 DBS on a α T y.1 -.1 -.2 1 sec u 2 y arctan G( s) h ( s b) ks 2 y
Comparison with Clinical Data Comparison with clinical data DBS amplitude for tremor suppression (ma) 1 5 1 5 Patient A Patient B 1 5 1 2 3 1 2 3 Patient C Patient D 1 5 1 2 3 1 2 3 Frequency of Stimulation (Hz) Beta (15-3 Hz) LFP power 1.8.6.4.2 1 2 3 1 Patient #3 R 2 =.783.8.6.4.2 Patient #1 R 2 =.959 1 2 3 1.8.6.4.2 1 2 3 4 5 1 Patient #4 R 2 =.987.8.6.4.2 Amplitude of stimulation (V) Patient #2 R 2 =.687 1 2 3 4 5 Clinical data 1 (measured limb tremor) Model predictions Clinical LFP data (recorded at DBS electrode) Model prediction 1 Clinical patient data from Benabid et al., The Lancet, 337:43 46, 1991. Davidson, et al., IEEE Trans. Biomed. Eng. (214; 215)
Adaptive deep brain stimulation
Adaptive deep brain stimulation Local field potential EMG signal Muscle force and tremor
Adaptive deep brain stimulation Controller Local field potential EMG signal Muscle force and tremor
Conclusions Engineering the rhythms of the brain Understand and modify neural activity DBS suppresses neural oscillations Variation with stimulation parameters Adaptive DBS in near future
Acknowledgements UCD Neuromuscular Systems and Neural Engineering Lab Dr Peadar Grant Dr Guiyeom Kang Dr Clare Davidson Eleanor Dunn Prof. Annraoi de Paor Collaborators Dr Hayriye Cagnan and Prof. Peter Brown, University of Oxford. Dr Christian Schmidt and Prof. Ursula Van Rienen, University of Rostock.
Closed-loop control of DBS Strongly-coupled network Weakly-coupled network Increased synaptic gain to induce stronger oscillations Grant and Lowery, IEEE Trans. Neural Syst & Rehab Eng, 214
Neural oscillations in Parkinson's DBS ON DBS OFF Oscillatory activity recorded from GPi during and after bilateral STN DBS. From Andrea A. Kühn et al. J. Neurosci. 28;28:6165-6173
Suppression of local field potential oscillations with DBS Variation with DBS parameters (pulse amplitude, duration and frequency) Normalised beta oscillation amplitude