Towards a Next Generation Platform for Neuro-Therapeutics

Transcription

1 Update November 2017 Towards a Next Generation Platform for Neuro-Therapeutics Dr Christopher Brown Pain and cognitive neuroscience Dr Alex Casson EPS researcher Prof Anthony Jones Neuro-rheumatologist Dr Nelson Trujillo-Barreto EPSRC research fellow Val Derbyshire Patient user representative Katrina Delargy TIYGA Health Marie Shorrock MSc student (Neuroscience) Sabirah Chowdhury MSc student (Clinical and Health Psychology) Dr Joanna Brooks Psychology and Mental Health

2 Vision: A Neuro-therapeutics Platform Chronic pain Mental health Detection of pathophysiology Real-time monitoring of brain states and treatment efficacy Delivery of targeted neuro-therapies Detecting and treating brain mechanisms of chronic pain and mental ill-health

3 Example neuro-therapy: Alpha entrainment Ecsy, Jones and Brown, European Journal of Pain, 2016, 2017 Increase in alpha power Decrease in pain processing Reduces pain perception and pain processing in insular cortex

4 NewMind Plus Stage 1 funding: Aims 1. To gather patient views on new technology in healthcare Theme 1: Brain stimulation therapy Alpha entrainment: Visual, auditory, tactile, electrical Patient eligibility, perceptions and preferences Theme 2: Personalised brain monitoring EEG electrode designs Patient preferences Theme 3: Smartphone symptom tracking Patient views on design / capability 2. To obtain pilot data for larger projects / funding opportunities Changes in brain physiology in response to sensory stimulation - to o ptimise stimulation protocols Technical development t owards quantitative testing Identify methods for real - time analysis Patient - inputted data over 3 months (max)

5 Work Packages: Overview Work package Description Progress 1. Stimulation technology Apps for neural entrainment, tacs modifications 2. Patient workshops 4 workshops of 4hrs duration involving 24 patients 3. Smartphone pain diary Longitudinal observation over 3 months in 24 patients 4. EEG personalisation Technical development towards adaptability to each patient 5. Review real-time EEG data modelling Literature review and expert consultation 6. Experimental study Proof-of-concept quantitative EEG during sensory stimulation Started: July 2017 Completion date: Dec 2017 Started: Aug 2017 Completion: Dec 2017 (analysis 2018) Started: Aug 2017 Completion date: March 2018 Started: July 2017 Completion date: Oct 2017 Started: Nov 2017 Completion date: Dec 2018 Started: Oct 2017 Completion date: April 2018

6 1. Stimulation technology Visual Stimulation App displays rapidly flashing light, applied via a VR headset Auditory Stimulation App plays binaural beats at the same frequency as alpha waves Tactile Stimulation App produces vibrotactile stimulation at alpha frequency Electrical stimulation for lab studies Transcranial Alternating Current Stimulation Alternating current applied at the same frequency as alpha waves

7 2. Patient workshops: Topics Topics i. Introduction to the project Participants TOTAL: 23 ii. iii. iv. Smartphone pain diary apps Customising EEG for neuro-therapy Visual/auditory/tactile/tACS demonstration and try-out Workshop 1: 5 Workshop 2: 6 Workshop 3: 9 (2 returning) Workshop 4: 11 (6 returning)

8 2. Patient workshops: Findings Interest in using apps to monitor chronic pain Not intere sted Intere sted % Patients passing screening per stimulation Selected patients comments upon trying visual stimulation: Took away my awareness of a particularly nasty ache. Stimulating and relaxing helped to take my mind off the pain. Very intere sted Progress/projections July 2017: Student intern for 10 weeks Aug 2017: First patient workshop Oct 2017: MSc student in Clinical and Health Psychology recruited Wouldn t choose to use it Dec 2017: Final patient workshop I became hyper after a while and disorientated Jan 2018: Qualitative analysis of audio transcripts Jun 2018: Anticipated completion

9 3. Smartphone pain diary Patient use: 13 patients began using the apps 9 patients are still using the apps Tracking e.g. pain, mood, activity, sleep (patient choice) Max 3 months use per patient Progress/projections: Aug 2017: First patients started use March 2018: Last patients will end use

10 3. Smartphone pain diary

11 4. EEG personalisation Starting state-of-the-art Now Ag/AgCl for better sensing Flexible Many more shapes User comfort testing (central leg important) Controlled test setup 11

12 5. Brain state (EEG) modelling Building on EPSRC fellowship research of Dr Nelson Trujillo- Barreto Accurate models of brain state changes are required for closeloop interventions. Progress/projections: Nov 2017: Discussions on real-time implementation May 2018: Toolboxes applied to NewMind project data Dec 2018: Matlab toolboxes publicised; technical papers published; companion review article published Brain states are assumed to have characteristics of switching dynamics: 1. Discrete and differentiable 2. Causally-related 3. Dynamical: changing over time Switching dynamics models (widely used in robotics), are now being applied to infer brain networks dynamics from EEG

13 6. Experimental study Visual stimulation Entrainment of alpha oscillations ERP measures of neural plasticity P300 Progress/projections: Sept 2017: MSc Neuroscience student started on project Oct 2017: Pilots started in healthy volunteers (N=5, protocol development) Dec 2017: Patient study to begin (N=24) April 2018: Anticipated end date

14 Further funding Current funding (beyond NewMind) Clinical studies: MRC CiC (Jan 2018 Oct 2018), 68,000 Funding a post-doctoral researcher Extension of experimental studies in chronic pain patients to N=50 in total Pilot trial of neural entrainment and EEG in patients homes Near-term funding needs Technology development: NewMind Stage 2 / EPSRC? DSTL? InnovateUK? Further validation of electrodes 3D and inkjet printed Computational acceleration for real-time brain modelling Tactile stimulation: repurposing existing TENS machines Automated analysis of numerical and text inputs to apps