BRRC Weekly Meeting Purpose 1. Cultivate our community 2. Share our science 3. Real time communications

BRRC Weekly MeetingBRRC Weekly Meeting

PurposePurpose1.1. Cultivate our communityCultivate our community2.2. Share our scienceShare our science3.3. Real time communicationsReal time communications

BRRC weekly meeting BRRC weekly meeting specsspecs

• Each Monday from after Labor Day Each Monday from after Labor Day until last Monday before Memorial until last Monday before Memorial Day (except federal holidays) Day (except federal holidays)

• 4:30-5:304:30-5:30• VA-UF Education Building VA-UF Education Building

conference roomconference room

BRRC weekly meeting BRRC weekly meeting agendaagenda

• 4:30-4:454:30-4:45 AnnouncementsAnnouncements• 4:45-5:154:45-5:15 Scientific talkScientific talk• 5:15-5:30 5:15-5:30 Question/AnswerQuestion/Answer

Everyone is expected to:Everyone is expected to:• AttendAttend• Actively listen and contribute to Actively listen and contribute to

discussionsdiscussions• Willingly present once per yearWillingly present once per year

BRRC reviewed

• Purpose = • About veterans-age related disease and war related injuries to the nervous

system• NEUROrehabilitation innovation and evolution

• Problem = neurorehabilitation lags behind other biomedical discovery

• History of nihilism about neurorehablitation• Particularly difficult research to do

• Unique difficulties to participating in rehabilitation research • Dearth of adequate outcome measures for appropriately measuring the

impact of various forms of neurorehabilitation• Limited appreciation for clinical trials methodology

• Focus• The neuroscience of learning, injury and recovery • Use dependent learning-a paradigm shift for neuro rehabilitation

BRRC Purpose = About veterans-age related disease and war related injuries to the nervous system

... ... to bind up the nation’s wounds; to care for him who shall have borne the battle...to bind up the nation’s wounds; to care for him who shall have borne the battle...

...Abraham Lincoln, March 4, 1865...Abraham Lincoln, March 4, 1865

BRRC reviewed

•BRRC-• Purpose =

•About veterans-age related disease and war related injuries to the nervous system

•NEUROrehabilitation innovation and evolution

CORES

TREATMENTINITIATIVES

BRRC: NEUROrehabilitation innovation and evolution

2009to

2014

2004to

2009

1999to

2004MOTOR

COGNITIVE

FUNC

IMAGING

HUMAN

MTR

PERF

Rehabilitation Neuroscience

ResearchINITIATIVE

Our overarching question is how can CNS (brain Our overarching question is how can CNS (brain and spinal cord) structure and function be driven and spinal cord) structure and function be driven

to remodel in the months and years after to remodel in the months and years after damage?damage?

• There is overwhelming evidence to indicate that CNS continuously There is overwhelming evidence to indicate that CNS continuously remodels its neural circuitry across our lifespan in order to encode remodels its neural circuitry across our lifespan in order to encode new experiences (Black et al., 1997; Grossman et al., 2002) and new experiences (Black et al., 1997; Grossman et al., 2002) and our goal is to capitalize upon the way the brain normally learns.our goal is to capitalize upon the way the brain normally learns.

• We believe the endogenous process of functionally appropriate We believe the endogenous process of functionally appropriate

reorganization in healthy brains and spinal cords is key to reorganization in healthy brains and spinal cords is key to promoting reorganization of remaining tissue in the damaged promoting reorganization of remaining tissue in the damaged mature CNS.mature CNS.

• This approach of using learning, alone and in combination with This approach of using learning, alone and in combination with other therapies, to promote adaptive neural plasticity is a growing other therapies, to promote adaptive neural plasticity is a growing focus of research in animal models of CNS damage (Jones et al., focus of research in animal models of CNS damage (Jones et al., 1998; Johansson, 2000; 2003; Jones et al., 2003; Monfils et al., 1998; Johansson, 2000; 2003; Jones et al., 2003; Monfils et al., 2005) and forms the basis of our approach to human 2005) and forms the basis of our approach to human neurorehabilitation clinical trials. neurorehabilitation clinical trials.

BRRC reviewed•Problem = neurorehabilitation lags behind other biomedical discovery•History of nihilism about neurorehablitation

Are functional deficits treatable?Are functional deficits treatable?

Our Professional NihilismOur Professional Nihilism

Finger, 1994, p.15

Aristotle (384-322 B.C.)Aristotle (384-322 B.C.)

Consolidation of nihilism about Consolidation of nihilism about the potential of the potential of

neurorehabilitationneurorehabilitation Santiago Ramon y CajalSantiago Ramon y Cajal

“Once development was ended, the founts of growth and regeneration of axons and dendrites dried up irrevocably. In adult centres, the nerve paths are something fixed and immutable; everything may die, nothing may be regenerated” (p.750) Finger, 1994, p47

BRRC reviewed

• BRRC-• Purpose =

• About veterans-age related disease and war related injuries to the nervous system

• NEUROrehabilitation innovation and evolution• Problem = neurorehabilitation lags behind other biomedical

discovery• History of nihilism about neurorehablitation• Particularly difficult research to do

• Unique difficulties to participating in rehabilitation research - length of participation- exquisite selection criteria

• Dearth of adequate outcome measures for appropriately measuring the impact of various forms of neurorehabilitation

BRRC reviewed


• About veterans-age related disease and war related injuries to the nervous system• NEUROrehabilitation innovation and evolution

• Problem = neurorehabilitation lags behind other biomedical discovery• History of nihilism about neurorehablitation• Particularly difficult research to do

• Unique difficulties to participating in rehabilitation research • Dearth of adequate outcome measures for appropriately measuring

the impact of various forms of neurorehabilitation• Limited appreciation for clinical trials methodology;

• Phases• Translations• Maturation

““The popular belief that only The popular belief that only randomized, controlled trials produce randomized, controlled trials produce trustworthy results and that all trustworthy results and that all observational studies are misleading observational studies are misleading does a disservice to … clinical does a disservice to … clinical investigation….” (Concato et al, 2000)investigation….” (Concato et al, 2000)

““A major fault with evidence-based A major fault with evidence-based medicine is its emphasis on medicine is its emphasis on randomized controlled trials” (Iggo, randomized controlled trials” (Iggo, 1995).1995).

Rehabilitation and Neural Repair:The Maturation of Treatments

from Discovery at the Bench to Changing Care for AllConceptConcept ApplicationApplicationInnovationInnovation EvolutionEvolution

Basic scienceBasic science Phase 1 Clinical Trial Phase 1 Clinical Trial Phase 2 Clinical Phase 2 Clinical TrialTrial

Phase 3 Clinical TrialPhase 3 Clinical Trial Health Services Health Services ResearchResearch



Clinical trials: a process of Clinical trials: a process of evolutionevolution

• Each phase asks an important but Each phase asks an important but different questiondifferent question

• Each phase may involve revision of the Each phase may involve revision of the treatment method based upon what was treatment method based upon what was learnedlearned

• Each subsequent phase is reliant on Each subsequent phase is reliant on successful resolution and completion of successful resolution and completion of the prior phase question.the prior phase question.

Basic science Translational rehabilitation neuroscience

research

Exploratory Clinical Study

Phase 1 Clinical Trial



Health Services Research

Purpose Basic Discovery Translation from animal to human application; normal human to pathology

Treatment Innovation

Treatment Evolution/Formalization

Treatment Efficacy

Treatment Effectiveness

Delivery Method/Societal Impact




• Each phase asks an important but different Each phase asks an important but different questionquestion

• Each phase may involve revision of the Each phase may involve revision of the treatment method based upon what was treatment method based upon what was learnedlearned

• Each subsequent phase is reliant on successful Each subsequent phase is reliant on successful resolution and completion of the prior phase resolution and completion of the prior phase question.question.

• Each phase requires rigorous but different Each phase requires rigorous but different scientific methods using sophisticated scientific methods using sophisticated experimental designs specifically tailored experimental designs specifically tailored to answer the specific questions askedto answer the specific questions asked


research









Treatment Efficacy



ParticipantModel

Animal or human

Animal to human, normal to pathology

Human individuals

Replications of individuals

Human groupings

Human populations

Populations and Institutions

Research Methodology

Within subject and group comparisons


Individual, small group. Within subject experimental designs

Small N Group.Within subject experimental designs, repeated across subjects

Medium N Group. Randomized group designs

Large N Group, population.Multisite randomized clinical trial

Large group, population, institutional system. Group designs




• Each phase asks an important but different questionEach phase asks an important but different question• Each phase may involve revision of the treatment Each phase may involve revision of the treatment

method based upon what was learnedmethod based upon what was learned• Each subsequent phase is reliant on successful Each subsequent phase is reliant on successful

resolution and completion of the prior phase resolution and completion of the prior phase question.question.

• Each phase requires rigorous but different scientific Each phase requires rigorous but different scientific methods using sophisticated experimental designs methods using sophisticated experimental designs specifically tailored to answer the specific specifically tailored to answer the specific questions askedquestions asked

• Because the questions asked vary across phases, Because the questions asked vary across phases, outcome measures should differ by phase.outcome measures should differ by phase.


research









Treatment Efficacy



ParticipantModel

Animal or human


Human individuals


Human groupings

Human populations










Outcomes Individual, tx specific probe, performance basedQuantification of TX effect

Individual, tx specific probe, performance basedQuantification of TX effect



Individual, tx specific probe, performance basedQuantification of TX effect, personal imp act

Health Status and Societal impact

Institutional and Societal impact



Basic science Translational

rehabilitation

neuroscience research









Treatment Efficacy



Barriers Questions not guided by the human experience; complain that the clinical perspective is impenetrable

Few researchers interested in this phase.

Unfunded. Un-appreciated. Not published. Considered unscientific (inappro-priately referred to as “case studies”)

Published in select journals only. Considered less rigorous and unscientific (Inappro-priately referred to as “series of case studies”)

Problems with identifying appropriate outcomes; fear of publishing negative results & the potential use of this data (payers)

Experimentally cumbersome. Problems with identifying appropriate outcomes; fear of publishing neg results & the potential use of this data (payers)

Where the rubber meets the road…vulnerable to political climates; fear of the potential use of this data (payers)

Barriers Barriers to evolution of rehabilitation clinical trials

ConceptConcept ApplicationApplicationInnovationInnovation EvolutionEvolution


• Each phase asks an important but different questionEach phase asks an important but different question• Each phase may involve revision of the treatment Each phase may involve revision of the treatment

method based upon what was learnedmethod based upon what was learned• Each subsequent phase is reliant on successful Each subsequent phase is reliant on successful

resolution and completion of the prior phase resolution and completion of the prior phase question.question.

• Each phase requires rigorous but different scientific Each phase requires rigorous but different scientific methods using sophisticated experimental designs methods using sophisticated experimental designs specifically tailored to answer the specific specifically tailored to answer the specific questions askedquestions asked

• Because the questions asked vary across phases, Because the questions asked vary across phases, outcome measures should differ by phase.outcome measures should differ by phase.

Basic science Translational research






Purpose Basic Discovery

Translation from animal to human application; normal human to pathology



Treatment Efficacy



ParticipantModel

Animal or human


Human individuals


Human groupings

Human populations










Outcomes Individual, tx specific probe, performance basedQuantification of TX effect




Individual, tx specific probe, performance basedQuantification of TX effect, personal imp act

Health Status and Societal impact

Institutional and Societal impact

Barriers Questions not guided by the

human experience;

complain that the clinical

perspective is impenetrable

Few researchers interested in this

phase.

Unfunded. Unappreciated. Not published.

Considered unscientific (ex inappropriately referred to as

“case studies”)

Published in select journals

only. Considered less rigorous and unscientific (ex. Inappropriately referred to as “series of case

studies”)

Problems with identifying appropriate

outcomes; fear of publishing neg results & the potential use of this

data (payers)

Experimentally cumbersome. Problems with

identifying appropriate

outcomes; fear of publishing neg results & the

potential use of this data (payers)

Where the rubber meets

the road…vulnerable to

political climates; fear of

the potential use of this data

(payers)

Rehabilitation and Neural Repair: The Maturation of Treatments from Discovery at the Bench to Changing Care for All

Rothi, LJG. Cognitive rehabilitation: The role of theoretical rationales and respect for the maturational process needed of our evidence. J of Head Trauma Res., 2006, 21:194-197

ConceptConcept ApplicationApplicationInnovationInnovation EvolutionEvolution

BRRC reviewed


• About veterans-age related disease and war related injuries to the nervous system• NEUROrehabilitation innovation and evolution

• Problem = neurorehabilitation lags behind other biomedical discovery

• History of nihilism about neurorehablitation• Particularly difficult research to do

• Unique difficulties to participating in rehabilitation research • Dearth of adequate outcome measures for appropriately measuring

the impact of various forms of neurorehabilitation• Limited appreciation for clinical trials methodology;

• Phases• Translations• Maturation

• Focus• The neuroscience of learning, injury and recovery • Use dependent learning-a paradigm shift for neuro rehabilitation

Copyright ©2006 American Physiological Society

Adkins, D. L. et al. J Appl Physiol 101: 1776-1782 2006;doi:10.1152/japplphysiol.00515.2006

Fig. 1. Time course of molecular, anatomic, and physiological plasticity within rat motor cortex during motor skill reach training

Documents

BRRC Weekly Meeting Purpose 1. Cultivate our community 2. Share our science 3. Real time communications