# Brain Function and Connectivity in Methamphetamine Dependence: The Link to Neuroinflammation and the Effects of Ibudilast

> **NIH VA IK2** · PORTLAND VA MEDICAL CENTER · 2021 · —

## Abstract

Candidate: I have had extensive training in fields of neuroimaging and the neurobiology of drug abuse. My
work has focused on investigating the effects of dopamine signaling in neural circuits with a focus on risky
decision-making and addiction-related phenotypes. This work has led to 12 publications in top-tier journals with
6 as first-author, multiple speaking engagements and 6 NIH fellowship awards. With a long-standing
commitment to contribute to the health of veterans, I am dedicated to developing an independent research
career at the VA focused on using multi-modal imaging to understand the pathophysiology of addiction but with
a focus on treatment and interventions.
Environment: I am pursuing this line of work at the VA Portland Health Care System and Oregon Health &
Science University, which are physically connected by an indoor sky bridge and allows complete access to a
multitude of collaborative laboratories and seminars. Through joint appointments I will have access to a full
range of technical and computing resources along with scientific/consultative support services. The activities of
the proposed project will occur with shared resources and facilities, including advanced imaging equipment
such as the Siemens 3T PRISMA MAGNETOM Trio and positron emission tomography (PET).
Research Methamphetamine (MA) use disorder is a major health problem facing our veterans. As veterans
with MA-use disorder are more likely to experience a disruption in care, an integrated approach combining
traditional treatment options and pharmacological interventions are essential in developing a comprehensive
treatment program. Although both inflammation and MA use dysregulate dopamine function, the mechanistic
link between MA-induced neuroinflammation and dopaminergic brain deficits has not been studied. This study
will therefore test a model whereby MA-induced neuroinflammation and its reduction with ibudilast influences
brain function and behavior in veterans with MA-use disorder.
 The first aim of the project will compare veterans with and without MA-use disorder to determine whether
MA-induced neuroinflammation is associated with impairments in cognitive control and abnormalities in
functional connectivity of neural networks and brain activation in response to reward in the mesocorticolimbic
system. Neuroimaging measures will include PET to quantify neuroinflammation; resting-state functional
magnetic resonance imaging (fMRI) to assess functional connectivity of neural networks and fMRI paired with
the Monetary Incentive Delay Task (MID) to measure brain activation in response to reward. We will then
assess whether a 6-week treatment of ibudilast, an anti-inflammatory reduces neuroinflammation and improves
brain function and behavior in a randomized placebo-controlled study in veterans with MA-use disorder. If
inflammation is associated with functional brain deficits and ibudilast is proven effective in restoring function
and connectivity of neural networ...

## Key facts

- **NIH application ID:** 10291802
- **Project number:** 5IK2CX001790-04
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** Milky Kohno
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291802

## Citation

> US National Institutes of Health, RePORTER application 10291802, Brain Function and Connectivity in Methamphetamine Dependence: The Link to Neuroinflammation and the Effects of Ibudilast (5IK2CX001790-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10291802. Licensed CC0.

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