This document summarizes a panel discussion on harnessing lifelong neuroplasticity through lifestyle and technology options, and the challenges ahead. The panel was chaired by experts in neuroplasticity and brain health. Panelists discussed using noninvasive brain stimulation techniques like TMS to measure biomarkers of brain circuit dynamics and plasticity. They described ongoing studies measuring lifestyle factors' impacts on brain health through the Barcelona Brain Health Initiative. Another panelist discussed opportunities for brain augmentation through nanotechnology but called for responsible development and public engagement and ethics guidelines to ensure benefits for individuals and society.

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

8. https://club.bbhi.cat
Barcelona Brain Health Index

9. Transcranial Magnetic Stimulation
Controlled
Perturbation
Measure Evoked
Responses

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

20. Age
Brain
Plasticity
CognitiveCapacity
Genetic Factors
Environmental Factors Individual Differences

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

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Nanotechnology for Neurotechnology

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Nanostructures: a platform for brain repair and augmentation
Image source: Vidu et al. Front Syst Neurosci. 2014; 8: 91.

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Human Enhancement
https://toplink.weforum.org/knowledge/insight/a1Gb0000001k1imEAA/explore/summary
Global Future Council on the Future
of Human Enhancement

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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