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What are most promising lifestyle and tech options to harness lifelong
neuroplasticity, and what are key roadblocks ahead?
Chaired by: Dr. David Bach,
Founder and President of
the Platypus Institute
Dr. Álvaro Pascual-
Leone, Director of
the Berenson-Allen Center for
Noninvasive Brain Stimulation
at Beth Israel Deaconess
Medical Center
Dr. David Bartrés-Faz,
Principal Investigator of
the Barcelona Brain
Health Initiative (BBHI)
Dr. Simone Schurle,
Assistant Professor for
Responsive Biomedical
Systems at the Swiss Federal
Institute of Technology
Towards a Brain Health Index:
Perturbation-based Biomarkers
Alvaro Pascual-Leone, M.D., Ph.D.
Berenson-Allen Center for Noninvasive Brain Stimulation
Division of Cognitive Neurology • Brain Fit Club
Beth Israel Deaconess Medical Center & Harvard Medical School
Disclosures
• Scientific Advisory Board Member for Neosync,
Starlab, Neuroelectrics, Magstim, Axilum Robotics,
Constant Therapy
• I will talk about off-label applications of noninvasive
brain stimulation
• Listed inventor on various patents on combination of
noninvasive brain stimulation with EEG and fMRI
Alvaro Pascual-Leone, MD, PhD
www.brainfitclub.org
The Brain Fit Club
at BIDMC
1. Measure
2. Personalize Prescription
3. Supervise Interventions
4. Assess Benefit
Brain Health Index
Monitor Progress
Adjust the Plan
Personalized Plan
https://club.bbhi.cat
Barcelona Brain Health Index
Transcranial Magnetic Stimulation
Controlled
Perturbation
Measure Evoked
Responses
1. (Noninvasive) Brain Stimulation offers valuable
translatable perturbation biomarkers to bridge the
model systems to humans
2. Characterization of the dynamics of such circuits can
provide novel insights into the neurobiology of
neuropsychiatric diseases and offer new individualized
therapeutic opportunities
Non-invasive Brain Stimulation
Perturbation Biomarkers
Regional cortical hyperexcitability in
epilepsy
Shafi et al
Ann Neurol 2015
Mo Shafi
TMS: Paired-Pulse
Kobayashi et al Lancet Neurol 03
SICI
GABA-A
ICF
NMDA
Defective ICI
in Pain
Lefaucher et al Neurology 2007
GABA-A
GABA-B
Identifying inhibitory deficits in disease
Farzan 2010 Brain; Frantseva 2014 Cerebral Cortex
Faranak
Farzan
TMS-EEG measures correlate with cognition
Rogasch 2015 Cortex
Repetitive TMS:
Theta Burst Stimulation
Frontiers Synaptic Plasticity 2011; Brain Topography 2011; Eur J
Neurosci 2012
8 s 2 s
200 ms
Bursts of 3 pulses
at 50 Hz
600 pulses
over 192 s
Following iTBSBaseline
LTD-like
Plasticity
LTP-like
Plasticity
Following cTBS
TBS
Frontiers Synaptic Plasticity 2011Brain Topography 2011; Eur J Neurosci 2012
Measuring Plasticity in Humans
Lindsay Obermann
Marine Vernet
The efficacy of the mechanisms of
plasticity decreases over the lifespan
Frontiers in Aging Neuroscience 2011; Brain Topography 2011
Caterina
Freitas
Age [years]20 80
BrainPlasticityIndex
10
50
r = -0.54
p = 0.001
12
10
6
4
0
ADAS-CogScore
2
8
-100 -50 0 50 100 150
T10 MEP Amplitude (% ∆ from baseline)
200
ADAS-Cog score by T10 Plasticity
Peter Fried
NIDDK
NINDS
The Mechanisms of Plasticity Predict
Cognitive Function
Age
Brain
Plasticity
CognitiveCapacity
Genetic Factors
Environmental Factors Individual Differences
Alteration of Mechanisms of Plasticity as
measured by TBS
LTD-like
Plasticity
LTP-like
Plasticity
Oberman et al
Eur J Neurosci 2012
Autism
Spectrum
Disorder
Koch et al
J Alz Dis 2012
Brem et al
Ann Neurol in press
Alzheimer’s
Disease
Fried et al
DM2Translatable
Phenotype
CorticalReactivityandE/IBalance
CorticalPlasticity
TMS in Animal Models
NMDA-
dependent
LTD-like
effect
Mechanisms of cortical reactivity
and plasticity
Brain Health Index
Monitor Progress
Adjust the Plan
Personalized Plan
Barcelona Brain Health Initiative
David Bartrés-Faz
Faculty of Medicine and Health Sciences
University of Barcelona
Alvaro Pascual-Leone
Berenson-Allen Center for Nonivasive Brain Stimulation
BIDMC Harvard Medical School
To better understand lifestyle determinants and their mechanisms leading to optimal
brain function in advanced age.
Prospective on the Catalonia (Barcelona) population 2014
Josefson et al. JAGS 2012•Population is ageing
•Ageing is an important risk factor for major brain diseases
•Brain diseases are #1 leading cause of disability Maintenance of optimal cognitive performance occurs
in around 20% of elders.
Disease DisabilitySymptoms
Diagnoses
Treatment
Health
Brain resilience
Preserved function
Resilience promotionPrevention
Brain health maintenance is best adressed from current brain health
Altered function
Relevance of modifiable lifestyles to maintain brain health at old age
35% of cases with dementia are atributed to a
combination of these 9 risk factors
Removal of APOE effects only reduces risk -7%
Erickson et al. PNAS 2011
Lifestyles and Brain Health: Lifespan & individualized perspective
Previous, reported
Current, intervention
Modulation by genetic background
Wirth et al. J Neurosci 2014
Cognitive activity Physical activity Nutrition Socialization
Sleep Vital plan General health
Lifestyle pillars in BBHI
30
BBHI apprach: combining observational and interventional studies
Longitudinal
prospective
cohort
+ 5,000 participants  Phase I : lifestyle questionnaires / scales
1,000 participants  Phase II: in person assessment
250 control, health education
500 participants  Phase III: Intervention
40-65 years old, no neuropsychiatric diagnosis
PRE-POST: MRI, EEG, TMS, Neuropsychological assessment,
gait analysis, voice recording, blood samples…
ICT-based, mobile Apps, personalized...
250 personalized coaching
31
Phase I: Healthy Habits Monitor
https://club.bbhi.cat
Peers
comparison
• ICT-based intervention
• 500 participants
• Personalized
• Individualized coaching support
• Motivation, adherence
• Smartphones, wearables and Apps
• Tracking and monitoring
• Managing and communication
• Automatic alert systems
Phase III: mHealth for monitoring and adherence
32
In summary…..
• The BBHI combines a follow-up study cohort and a multimodal intervention to
investigate the impact of positive lifestyles on brain health.
• The study is focused on middle-aged healthy individuals and incorporates
biological-based measures for the investigation of the mechanisms through
with such lifestyles exert its effects.
• It provides individual web-based/APP feedback to participants and uses mobile
Health technologies and a personalized coach approaches, aiming to increase
engagement and adherence.
Simone Schürle, PhD
Responsive Biomedical System Lab
ETH Zurich
Department of Health Science and Technology
Institute for Translational Medicine
36
06.10.201
7
37
06.10.201
7
38
06.10.201
7
Nanotechnology for Neurotechnology
39
06.10.201
7
Nanostructures: a platform for brain repair and augmentation
Image source: Vidu et al. Front Syst Neurosci. 2014; 8: 91.
40
06.10.201
7
Human Enhancement
https://toplink.weforum.org/knowledge/insight/a1Gb0000001k1imEAA/explore/summary
Global Future Council on the Future
of Human Enhancement
41
06.10.201
7
Human Enhancement
Body Brain
Human enhancement aims to improve the
quality of life over its course, at any age and
stage, by enhancing our functional capabilities.Performance
Age
42
Human Enhancement
4 main pathways
1) Manipulation and extension of our body and brains
2) Modifications of our genes, our own biological mass
3) Alterations on a molecular and pharmacological level
4) Changes of our environment
43
Call for Code of Ethics
Key Issues
1) Equity and Social Justice
2) Maintaining Humanness and Autonomy
3) Transparency and Access to Information
44
Concluding Notes
▪ Responsible research and tech development
▪ Engagement of the public in this conversation
Need for ethical guidelines and frameworks that
▪ help innovation to foster
▪ benefit individuals and society
▪ and prevent catastrophe
Lunch break
Please be back at 12.30pm US Pacific Time/
3.30pm Eastern Time for a fascinating afternoon!
Thank you, Speakers & Participants!
Thank you, Summit Sponsors!
Thank you, Summit Partners!
To learn more, visit sharpbrains.com

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What are most promising lifestyle and tech options to harness lifelong neuroplasticity, and what are key roadblocks ahead?

  • 1.
  • 2.
  • 3. What are most promising lifestyle and tech options to harness lifelong neuroplasticity, and what are key roadblocks ahead? Chaired by: Dr. David Bach, Founder and President of the Platypus Institute Dr. Álvaro Pascual- Leone, Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center Dr. David Bartrés-Faz, Principal Investigator of the Barcelona Brain Health Initiative (BBHI) Dr. Simone Schurle, Assistant Professor for Responsive Biomedical Systems at the Swiss Federal Institute of Technology
  • 4. Towards a Brain Health Index: Perturbation-based Biomarkers Alvaro Pascual-Leone, M.D., Ph.D. Berenson-Allen Center for Noninvasive Brain Stimulation Division of Cognitive Neurology • Brain Fit Club Beth Israel Deaconess Medical Center & Harvard Medical School
  • 5. Disclosures • Scientific Advisory Board Member for Neosync, Starlab, Neuroelectrics, Magstim, Axilum Robotics, Constant Therapy • I will talk about off-label applications of noninvasive brain stimulation • Listed inventor on various patents on combination of noninvasive brain stimulation with EEG and fMRI Alvaro Pascual-Leone, MD, PhD
  • 6. www.brainfitclub.org The Brain Fit Club at BIDMC 1. Measure 2. Personalize Prescription 3. Supervise Interventions 4. Assess Benefit
  • 7. Brain Health Index Monitor Progress Adjust the Plan Personalized Plan
  • 10. 1. (Noninvasive) Brain Stimulation offers valuable translatable perturbation biomarkers to bridge the model systems to humans 2. Characterization of the dynamics of such circuits can provide novel insights into the neurobiology of neuropsychiatric diseases and offer new individualized therapeutic opportunities Non-invasive Brain Stimulation Perturbation Biomarkers
  • 11. Regional cortical hyperexcitability in epilepsy Shafi et al Ann Neurol 2015 Mo Shafi
  • 12. TMS: Paired-Pulse Kobayashi et al Lancet Neurol 03 SICI GABA-A ICF NMDA
  • 13. Defective ICI in Pain Lefaucher et al Neurology 2007 GABA-A GABA-B
  • 14. Identifying inhibitory deficits in disease Farzan 2010 Brain; Frantseva 2014 Cerebral Cortex Faranak Farzan
  • 15. TMS-EEG measures correlate with cognition Rogasch 2015 Cortex
  • 16. Repetitive TMS: Theta Burst Stimulation Frontiers Synaptic Plasticity 2011; Brain Topography 2011; Eur J Neurosci 2012 8 s 2 s 200 ms Bursts of 3 pulses at 50 Hz 600 pulses over 192 s Following iTBSBaseline LTD-like Plasticity LTP-like Plasticity Following cTBS
  • 17. TBS Frontiers Synaptic Plasticity 2011Brain Topography 2011; Eur J Neurosci 2012 Measuring Plasticity in Humans Lindsay Obermann Marine Vernet
  • 18. The efficacy of the mechanisms of plasticity decreases over the lifespan Frontiers in Aging Neuroscience 2011; Brain Topography 2011 Caterina Freitas Age [years]20 80 BrainPlasticityIndex 10 50
  • 19. r = -0.54 p = 0.001 12 10 6 4 0 ADAS-CogScore 2 8 -100 -50 0 50 100 150 T10 MEP Amplitude (% ∆ from baseline) 200 ADAS-Cog score by T10 Plasticity Peter Fried NIDDK NINDS The Mechanisms of Plasticity Predict Cognitive Function
  • 21. Alteration of Mechanisms of Plasticity as measured by TBS LTD-like Plasticity LTP-like Plasticity Oberman et al Eur J Neurosci 2012 Autism Spectrum Disorder Koch et al J Alz Dis 2012 Brem et al Ann Neurol in press Alzheimer’s Disease Fried et al DM2Translatable Phenotype
  • 22. CorticalReactivityandE/IBalance CorticalPlasticity TMS in Animal Models NMDA- dependent LTD-like effect Mechanisms of cortical reactivity and plasticity
  • 23. Brain Health Index Monitor Progress Adjust the Plan Personalized Plan
  • 24. Barcelona Brain Health Initiative David Bartrés-Faz Faculty of Medicine and Health Sciences University of Barcelona Alvaro Pascual-Leone Berenson-Allen Center for Nonivasive Brain Stimulation BIDMC Harvard Medical School
  • 25. To better understand lifestyle determinants and their mechanisms leading to optimal brain function in advanced age. Prospective on the Catalonia (Barcelona) population 2014 Josefson et al. JAGS 2012•Population is ageing •Ageing is an important risk factor for major brain diseases •Brain diseases are #1 leading cause of disability Maintenance of optimal cognitive performance occurs in around 20% of elders.
  • 26. Disease DisabilitySymptoms Diagnoses Treatment Health Brain resilience Preserved function Resilience promotionPrevention Brain health maintenance is best adressed from current brain health Altered function
  • 27. Relevance of modifiable lifestyles to maintain brain health at old age 35% of cases with dementia are atributed to a combination of these 9 risk factors Removal of APOE effects only reduces risk -7%
  • 28. Erickson et al. PNAS 2011 Lifestyles and Brain Health: Lifespan & individualized perspective Previous, reported Current, intervention Modulation by genetic background Wirth et al. J Neurosci 2014
  • 29. Cognitive activity Physical activity Nutrition Socialization Sleep Vital plan General health Lifestyle pillars in BBHI
  • 30. 30 BBHI apprach: combining observational and interventional studies Longitudinal prospective cohort + 5,000 participants  Phase I : lifestyle questionnaires / scales 1,000 participants  Phase II: in person assessment 250 control, health education 500 participants  Phase III: Intervention 40-65 years old, no neuropsychiatric diagnosis PRE-POST: MRI, EEG, TMS, Neuropsychological assessment, gait analysis, voice recording, blood samples… ICT-based, mobile Apps, personalized... 250 personalized coaching
  • 31. 31 Phase I: Healthy Habits Monitor https://club.bbhi.cat Peers comparison
  • 32. • ICT-based intervention • 500 participants • Personalized • Individualized coaching support • Motivation, adherence • Smartphones, wearables and Apps • Tracking and monitoring • Managing and communication • Automatic alert systems Phase III: mHealth for monitoring and adherence 32
  • 33. In summary….. • The BBHI combines a follow-up study cohort and a multimodal intervention to investigate the impact of positive lifestyles on brain health. • The study is focused on middle-aged healthy individuals and incorporates biological-based measures for the investigation of the mechanisms through with such lifestyles exert its effects. • It provides individual web-based/APP feedback to participants and uses mobile Health technologies and a personalized coach approaches, aiming to increase engagement and adherence.
  • 34. Simone Schürle, PhD Responsive Biomedical System Lab ETH Zurich Department of Health Science and Technology Institute for Translational Medicine
  • 35.
  • 39. 39 06.10.201 7 Nanostructures: a platform for brain repair and augmentation Image source: Vidu et al. Front Syst Neurosci. 2014; 8: 91.
  • 41. 41 06.10.201 7 Human Enhancement Body Brain Human enhancement aims to improve the quality of life over its course, at any age and stage, by enhancing our functional capabilities.Performance Age
  • 42. 42 Human Enhancement 4 main pathways 1) Manipulation and extension of our body and brains 2) Modifications of our genes, our own biological mass 3) Alterations on a molecular and pharmacological level 4) Changes of our environment
  • 43. 43 Call for Code of Ethics Key Issues 1) Equity and Social Justice 2) Maintaining Humanness and Autonomy 3) Transparency and Access to Information
  • 44. 44 Concluding Notes ▪ Responsible research and tech development ▪ Engagement of the public in this conversation Need for ethical guidelines and frameworks that ▪ help innovation to foster ▪ benefit individuals and society ▪ and prevent catastrophe
  • 45. Lunch break Please be back at 12.30pm US Pacific Time/ 3.30pm Eastern Time for a fascinating afternoon!
  • 46. Thank you, Speakers & Participants!
  • 47. Thank you, Summit Sponsors!
  • 48. Thank you, Summit Partners!
  • 49. To learn more, visit sharpbrains.com