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NIH grant 4R00AA031508-03: Developing Functional Connectivity-Guided TMS for Alcohol Use Disorder
Institute: {'code': 'AA', 'abbreviation': 'NIAAA', 'name': 'National Institute on Alcohol Abuse and Alcoholism', 'admin_org_id': '12500001', 'admin_funding_url': ''}. PI: Daniel McCalley. Award: $249000.
Start: 2026-09-05T00:00:00.
Alcohol Use Disorder (AUD) contributes to 88,000 deaths per year in the United States. Although several pharmacological treatments are available, adherence to these
treatments is low and approximately 60% of individuals relapse within 6 months. Further, these treatments modulate the brain in a relatively global fashion.
Neuroimaging studies of AUD patients has shown that elevated cortico-striatal activity in response to alcohol cues predicts relapse. Thus, there is an emerging interest in
developing novel, neural-circuit specific therapeutic tools to enhance AUD treatment outcomes. Transcranial magnetic stimulation (TMS) is one such non-invasive,
neural-circuit specific tool. Through electromagnetic induction, repetitive pulses of TMS can be applied to the cortex to change neural activity within a cortical circuit.
Subsequently, TMS for AUD has been developed as a strategy to reduce brain reactivity to alcohol cues within the prefrontal cortex and its downstream targets in the
striatum. I recently led an analysis of a randomized, double-blind clinical trial applying 10 days of TMS to the medial prefrontal cortex among AUD patients. Relative to
sham, individuals who received real TMS were 3 times more likely to remain sober and experienced a reduction in alcohol cue-reactivity. Despite these results,
approximately 1/3 of individuals who received real TMS relapsed to alcohol and reductions to striatal reactivity to alcohol cues were not uniform. My NIAAA-sponsored
F31 demonstrated that individual patterns of brain response to alcohol cues are highly variable among AUD patients and often occur outside of the prefrontal cortex.
Given this variability, delivering TMS to a fixed point on the scalp leads to a situation in which TMS electrical fields do not always overlap with an individual’s brain
response to alcohol cues. In a proof-of-concept retrospective analysis, I found that patients who had overlap between alcohol cue-reactivity patterns and TMS electrical
fields had the best clinical outcomes. The K99 portion of this award built upon this by developing 1) a fMRI-derived pipeline to identify clinically relevant TMS targets
based on alcohol-cue reactivity and 2) delivered prospective fMRI-guided TMS in a preliminary, pilot sample. First, using an existing fMRI data set (n=99), we found that
individualized TMS targets, defined by maximal alcohol cue-reactivity, can be centered within the dorsomedial prefrontal and occipital cortices and that those with frontal
TMS targets have higher craving scores and relapse more quickly following treatment. Then, we found that, relative to sham, one session of personalized fMRI-guided
TMS acutely reduces striatal reactivity to alcohol cues and alcohol craving, an effect that most pronounced among individuals receiving posterior-parietal stimulation. In
the R00 phase of this award, we intend to develop a double-blind randomized controlled trial to evaluate the influence of 15 sessions of fMRI-guided TMS (3
sessions/day) to reduce striatal reactivity to alcohol cues (Aim 1) and 3-month alcohol relapse rates (Aim 2). In an exploratory analysis, we will evaluate whether acute
change in alcohol cue-reactivity and craving can predict long-term treatment outcome following 15 sessions of fMRI-guided TMS (Aim 3).document fetched 2026-09-13 02:46