for Neuro-Therapeutics Dr Christopher Brown Pain and cognitive - - PowerPoint PPT Presentation

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

Update November 2017

Detection of pathophysiology Real-time monitoring of brain states and treatment efficacy

Detecting and treating brain mechanisms of chronic pain and mental ill-health

Delivery of targeted neuro-therapies

Vision: A Neuro-therapeutics Platform

Chronic pain Mental health

Reduces pain perception and pain processing in insular cortex

Increase in alpha power Decrease in pain processing

Example neuro-therapy: Alpha entrainment

Ecsy, Jones and Brown, European Journal of Pain, 2016, 2017

• Alpha entrainment: Visual

, auditory, tactile, electrical

• Patient eligibility, perceptions

and preferences

• Changes in brain physiology in response to

sensory stimulation - to o ptimise stimulation protocols

• EEG electrode

designs

• Patient preferences
• Technical development

t

• wards

quantitative testing

• Identify methods for

real

• time analysis
• Patient views on design / capability
• Patient
• inputted data over 3 months (max)

NewMind Plus Stage 1 funding: Aims

• 1. To gather patient views on new

technology in healthcare

• 2. To obtain pilot data for larger

projects / funding opportunities

Theme 1: Brain stimulation therapy Theme 2: Personalised brain monitoring Theme 3: Smartphone symptom tracking

Work Packages: Overview

Work package Description Progress

• 1. Stimulation technology

Apps for neural entrainment, tACS modifications Started: July 2017 Completion date: Dec 2017

• 2. Patient workshops

4 workshops of 4hrs duration involving 24 patients Started: Aug 2017 Completion: Dec 2017 (analysis 2018)

• 3. Smartphone pain diary

Longitudinal observation over 3 months in 24 patients Started: Aug 2017 Completion date: March 2018

• 4. EEG personalisation

Technical development towards adaptability to each patient Started: July 2017 Completion date: Oct 2017

• 5. Review real-time EEG

data modelling

Literature review and expert consultation Started: Nov 2017 Completion date: Dec 2018

• 6. Experimental study

Proof-of-concept quantitative EEG during sensory stimulation Started: Oct 2017 Completion date: April 2018

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

Transcranial Alternating Current Stimulation

• Alternating current applied at the same frequency as alpha waves
• 1. Stimulation technology

Tactile Stimulation

• App produces vibrotactile stimulation at alpha frequency
• Electrical stimulation for lab studies

• 2. Patient workshops: Topics

Topics

i. Introduction to the project ii. Smartphone pain diary apps

• iii. Customising EEG for neuro-therapy
• iv. Visual/auditory/tactile/tACS

demonstration and try-out

Participants

TOTAL: 23 Workshop 1: 5 Workshop 2: 6 Workshop 3: 9 (2 returning) Workshop 4: 11 (6 returning)

• 2. Patient workshops: Findings

Progress/projections

• July 2017: Student intern for 10 weeks
• Aug 2017: First patient workshop
• Oct 2017: MSc student in Clinical and Health

Psychology recruited

% Patients passing screening per stimulation Not intere sted Intere sted Very intere sted Interest in using apps to monitor chronic pain 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.” “Wouldn’t choose to use it” “I became hyper after a while and disorientated”

• Dec 2017: Final patient workshop
• Jan 2018: Qualitative analysis of audio transcripts
• Jun 2018: Anticipated completion

• 3. Smartphone pain diary

Progress/projections:

• Aug 2017: First patients started use
• March 2018: Last patients will end use

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

• 3. Smartphone pain diary

• 4. EEG personalisation

11

Starting state-of-the-art Now

• Ag/AgCl for better sensing
• Flexible
• Many more shapes
• User comfort testing

(central leg important)

• Controlled test setup

• 5. Brain state (EEG) modelling
• Building on EPSRC fellowship

research of Dr Nelson Trujillo- Barreto

• Accurate models of brain state

changes are required for close- loop interventions.

• 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

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

• 6. Experimental study

Visual stimulation Entrainment of alpha oscillations ERP measures of neural plasticity

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

P300

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