Report from the Clinical Neuroscience and Behavioral

Research Work Group

NIDA CouncilMay 6, 2015

Charge to the Work Group

• Convened in November 2014 by Dr. Nora Volkow

• Review DCNBR programs and activities in the context of– Opportunities and challenges presented by scientific and

technological advances and cross-cutting NIH initiatives– Overlapping science and missions of other NIDA Divisions

(including the ABCD Study)– Overall NIDA strategic planning process

• Provide recommendations to NIDA regarding the structure, function and overall strategic direction to maximize the impact of clinical neuroscience and neurobehavioral interventions research without constraining considerations to a narrow focus on DCNBR per se

Work Group Membership and Staff

John Rotrosen, MD (Chair) F. Xavier Castellanos, MDHans Breiter, MD Harriet de Wit, PhDKathleen Carroll, PhD Terry L. Jernigan, PhDBetty (BJ) Casey, PhD Lisa Marsch, PhD

Ericka Boone, PhD Susan HolbrookRobert J. Katt, PhD Patrice Pettinato

Work Group Meetings

• November conference call with Dr. Volkow• December, January conference calls (2)• February 4-6 meeting at NIDA

– Drs. Volkow and Compton– DCNBR and Branch Leadership– DBNBR, DESPR, DPMCDA, CCTN, IRP, ARP, DER, ODHD– Drs. Volkow and Compton

• February, March, April conference calls (8) • E-mail

NIDA Leadership and Staff

Will Aklin Lisa OnkenAlbert Avila Joni RutterAntonello Bonci Phil SkolnickCheryl Anne Boyce Jack SteinMaureen Boyle Geetha SubramaniamRedonna Chandler Betty TaiUsha Charya Dave ThomasWilson Compton Nora Volkow Joseph Frascella Susan WeissSteven Grant Cora Lee WetheringtonTessa Hall Caitlin Dudevoir (SEI)Jacques Normand

Division of Clinical Neuroscience and Behavioral Research

• Created in 2004• Critical role in NIDA’s overall organization

– Development– Clinical Neuroscience– Treatment– DCNBR also houses the Women & Sex/Gender Research

Program and NIDA leadership for NIDA/NIH Pain Consortium

• Collaboration with DBNBR, DESPR, CCTN, AIDS Research Program and trans-NIH

Three Take-Home Messages

The past decade has witnessed advances in addiction neuroscience, pathophysiology, and pharmacologic and behavioral interventions that have outpaced or rivaled those achieved for any other brain disease

No small part of the credit for this is owed to work that DCNBR has led and funded

Translational neuroscience and neurobehavioral interventions research must remain amongst NIDA’s highest priorities

Opportunities and Challenges

• Rapid advances in genetics, molecular biology, functional imaging, circuitry

• NIH BRAIN Initiative• NIH Blueprint for Neuroscience Research • Precision medicine• Big Data (BD2K)

All of these create exceptional opportunities to expand translational neuroscience and neurobehavioral interventions in addictions. There is great urgency to capitalize on these.

The Work Group views translational neuroscience and neurobehavioral interventions research to be central to NIDA’s capacity to address theses challenges.

DCNBR Accomplishments(Just a Few of Many)

• Circuitry associated with addiction continuum• Neuroeconomic approaches to decision-making, impulsivity, risk-taking• NIH Stage Model for behavioral treatment research• Widely adopted behavioral interventions (MI, CM, CBT) • Foundational work enabling ABCD Study

– Pediatric imaging / technology development– NIH MRI normal brain development study– Human connectome project– Imaging supplements for large adolescent cohorts

• Centers of Excellence for Pain Education• Technology-based interventions• Combined behavioral / medication interventions• Research training – stellar outcomes

Basic ScienceClinical

NeuroscienceImagingGenetics

Medications &Behavioral

TrialsTreatment &

Criminal JusticeSettings

Public HealthPreventionEconomics

Policy

Scaling Up / Dissemination / Implementation / Sustainability

Population Health

Pathophysiology /Treatment Development / Efficacy /

Safety

Translation in Addiction

DCNBR

Basic ScienceClinical

NeuroscienceImagingGenetics

Medications &Behavioral

TrialsTreatment &

Criminal JusticeSettings

Public HealthPreventionEconomics

Policy

Scaling Up / Dissemination / Implementation / Sustainability

Population Health

Pathophysiology /Treatment Development / Efficacy /

Safety

Translation in Addiction

DBNBR

CCTN

DESPR

DPMCDA

DCNBR

DCNBR Collaborative Initiatives(Just a Few of Many)

• Child and Adolescent Workgroup (NIDA CAWG)• Human Placenta Project• Pediatric Imaging, Neurocognition, Genetics (PING)• National Consortium on Alcohol and Neurodevelopment in

Adolescence (NCANDA)• NIDA Prescription Opioids and Pain Workgroup / NIH Pain

Consortium / Interagency Pain Research Coordinating Committee• Women & Sex/Gender and AI/AN activities (CCTN)• Brain Imaging Drug Use Prevention Messages (DESPR) • Population Assessment of Tobacco and Health (PATH) Study (DESPR)• STTR Data Harmonization (DESPR, ARP)• SBIRT Primary Care (13+ projects) (DESPR)

National Institute of Neurologic Disorders and Stroke

Multidimensional Conceptual ModelEtiology, Progression, Interventions, Outcomes

• Addiction continuum – Vulnerability, exposure, use, craving, tolerance,

dependence, withdrawal, abstinence, relapse, recovery, etc.

• Brain and behavioral development– Prenatal, infancy, childhood, adolescence, adulthood,

senescence

• Spatial scales of biological function– Genome, epigenome, molecular biology, cells, local

circuits, distributed circuits, organisms, social networks

Challenges and Opportunities

• Recent loss of developmental imaging expertise (Jim Bjork)• Human behavioral-, imaging-, statistical- genetics not

sufficiently covered• Leadership and staff gaps in BITB (Lisa Onken, others)• Gaps in translating between animal and human• Need for more granularity to understand behavior, particularly

growing out of neuroeconomics• Opportunities around complementarity of behavioral-,

pharmacologic-, and physiologic- interventions• Opportunities for more collaboration with other NIDA

Divisions

WG Recommendations1. Apply the multidimensional model of substance abuse across NIDA

including consideration of individual differences in each dimension2. Ensure that the NIDA team has broad expertise across these dimensions

and enthusiasm to collaborate across organizational lines3. Strengthen functional integration across and within NIDA Divisions,

focusing on this multidimensional model4. Take advantage of the ABCD Study to implement functional integration,

with a focus on development, throughout NIDA and across other NIH ICs5. Encourage multimodal integration of imaging studies across both humans

and animal studies6. Encourage data-sharing, repositories, and Big Data analytics7. Ensure that data from previously funded RFAs are collated and reviewed to

monitor success and ensure that findings are integrated into NIDA’s strategic plans and FOAs

Implementation IssuesImplementation may require NIDA to re-examine its overall structure in the context of pragmatic and policy-based constraints and opportunities beyond the Work Group’s purview. To aid NIDA leadership the report concludes with a perspective on four major issues, potential options to address these, and advantages and disadvantages for each option. The options are intended to inform but neither to prescribe nor circumscribe the ways NIDA leadership might address each issue. Similarly, the set of advantages and disadvantages are offered only as a starting point for deliberation.

• Issue 1: What is the best home for NIDA translational neuroscience and neurobehavioral research?

• Issue 2: How should NIDA foster a robust neurobehavioral interventions program?• Issue 3: What is the best way to incorporate developmental science throughout

NIDA?• Issue 4: How should genetics and modern molecular biology be incorporated

across NIDA’s organizational structure?

A key implementation issue is that existing DCNBR staff and leadership vacancies need to be filled at a time when NIDA is comparatively overstaffed.

Issue 1: What is the Best Home for NIDA Translational Neuroscience and Neurobehavioral Research?

Option 1.1: Preserve current DCNBR structure and strengthen the key areas for translational neurobehavioral research by re-engineering DCNBR, perhaps renaming it the Division of Translational Neuroscience and Neurobehavioral Research.

Option 1.2: Merge DCNBR and DBNBR to create a new translational division.

For both options, leadership and staff should have the skill sets required to bridge and integrate the key areas of translational neuroscience, integrated neurobehavioral interventions, and developmental science.

Issue 2: How Should NIDA Foster a Robust Neurobehavioral Interventions Program?

Option 2.1: Within the division housing translational neuroscience and neurobehavioral research strategically strengthen and re-engineer BITB into a new Neurobehavioral Interventions Research Branch (NBIRB).

Option 2.2: Redistribute the current BITB portfolio. Retain neurobehavioral neuroscience and mechanistic research within a re-engineered NBIRB but transfer neurobehavioral implementation and services research to DESPR and CCTN.

In both cases, recruit an NBIRB Branch Chief with key leadership skills and fill vacant positions in line with the areas of responsibility of a re-engineered branch.

Issue 3: What is the Best Way to Incorporate Developmental Science throughout NIDA?

Option 3.1: Establish an Office, Program or Center for Developmental Research reporting directly to the NIDA Director or housed in DER, and assign to it the responsibilities of coordinating developmental research across NIDA and administering the ABCD Study. For both functions draw on scientific and content expertise from across NIDA (and to some extent from the CRAN institutes). Reassign the current BBDB portfolio to other Branches throughout NIDA as appropriate.

Option 3.2: Administer the ABCD Study from within the Office of the NIDA Director or DER but maintain a branch-level unit (BBDB or equivalent), either in the translational neuroscience division or elsewhere, to focus on a portfolio of developmental science.

Issue 4: How Should Genetics and Modern Molecular Biology Be Incorporated across NIDA’s Organizational Structure?

Option 4.1: Create within the division housing translational neuroscience a new branch focused on genetics and molecular research in humans. This branch would manage human genetics-related projects including integrated neurobehavioral interventions research, medications development work, and imaging genetics.

Option 4.2: Instead of creating a new branch, ensure that the division housing translational neuroscience has sufficient staff expertise in human genetics and molecular biology in key areas of clinical neuroscience.

Translational neuroscience, development and neurobehavioral interventions research is at the heart of NIDA’s mission and – regardless of how it’s structured – must be strongly supported