# Neural Mechanisms Connecting Deficient Sleep and Smoking Relapse: An RCT of CBT for Insomnia in Adults who Smoke

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $468,440

## Abstract

Abstract
Deficient sleep aggravates negative mood and reduces self-control and represents a primary withdrawal
symptom and robust predictor of relapse in adults who smoke. We propose to investigate how cognitive
behavioral therapy for insomnia (CBT-I) ameliorates negative emotions, improves self-control, and promotes
cessation and to identify the neural markers of the effects of CBT-I among individuals who smoke.
 Nicotine influences the brain through its action on cholinergic systems. Cholinergic innervations of the
cerebral cortex arise primarily from the basal nucleus of Meynert (BNM) in the forebrain. With reciprocal
connection with the medial frontal cortex (MFC), the BNM respond vigorously to salient stimuli, e.g., drug cues,
to obtain reward and MFC inhibition of the BNM interrupts the impulsive response. As a hub that regulates
sleep-wake cycle and motivated behavior, the hypothalamus is heavily connected with the BNM as well as
hippocampal limbic circuits. Thus, hypothalamus dysfunction may associate sleep deficiency with negative
emotion and impaired control in adults who smoke. Our over-arching hypothesis is that CBT-I ameliorates
negative emotions, improves self-control, and promotes smoking cessation by remediating hypothalamus and
BNM circuit dysfunction.
 We build on our preliminary findings of CBT-I and imaging studies and propose to recruit a cohort of 114
treatment-seeking adults who smoke to test this hypothesis. Participants will be stratified to a CBT group
receiving standard care (i.e., counseling + varenicline) + CBT-I or a standard care (SC) group with SC only.
Treatment will start 4 weeks (lead-in period) prior to a scheduled quit date. All participants will undergo MRI at
baseline and at week 4 to probe attentional bias and response inhibition during exposure to smoking vs.
neutral cues and to probe negative emotion processing. Participants then continue to receive their assigned
treatment for 4 more weeks (quit period) and attend follow-ups at week 8, 12, and 26. Our aims are 1) to
examine baseline associations among clinical measures of sleep deficiency, task performance (attentional bias
and response inhibition to smoking cues, reaction time in negative emotion processing), and neural metrics
(BNM and hypothalamus circuit activities and connectivities); 2) to examine the effects of CBT-I on clinical,
task, and neural outcomes; and 3) to examine whether CBT vs. SC results in superior cessation outcomes,
including higher biochemically-verified 7-day point prevalence quit rates at week 8, and how self-control and
emotion processing at week 4 quit date predict week 8 cessation outcomes.
 By investigating the effects of CBT-I on impulse control and emotion processing as well as how the under-
studied basal forebrain and hypothalamic circuit mechanisms may support the benefits of CBT-I in adults who
smoke, the study will advance both the neuroscience and treatment of tobacco use disorders.

## Key facts

- **NIH application ID:** 10985196
- **Project number:** 1R01DA061285-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** LISA M FUCITO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $468,440
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985196

## Citation

> US National Institutes of Health, RePORTER application 10985196, Neural Mechanisms Connecting Deficient Sleep and Smoking Relapse: An RCT of CBT for Insomnia in Adults who Smoke (1R01DA061285-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10985196. Licensed CC0.

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