Brain Substrates of Early (4 hour) Cigarette Abstinence: Identification of Treatment Targets

Smoking vs. Abstinence
Axial . Saggital . Coronal

Correlation between the Change in Craving and the Change in CBF
Axial . Saggital . Coronal

Post-Hoc Analysis: Correlation with focus and abstinence-inducced reductions in CBF
Axial . Saggital . Coronal
The images shown here are displayed at a reduced threshhold (p<0.005 k=100) to show all regions of differential brain blood flow Back to Home Back to Abstract
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Abstract AUTHORS: Teresa R Franklin; Kanchana Jagannathan; Nathan Hager; Zhuo Fang; Joyce Wong; Anna Rose Childress; John A Detre; Hengyi Rao; Reagan Wetherill

Introduction: Research indicates that overnight nicotine abstinence disrupts neural activity in the mesocorticolimbic reward network; however, less is known about the time course of abstinence induced brain changes. To examine the potential neural effects of early abstinence we used arterial spin labeling perfusion fMRI, to measure regional cerebral blood flow (rCBF) changes in the resting brain induced by 4 hours of nicotine abstinence.

Methods: In a repeated measures design, 5 minutes of resting perfusion fMRI data were acquired in awake nicotine-dependent individuals (eyes open) during 'smoking as usual' (SMK) and following 4 hours of monitored nicotine abstinence (ABS) conditions (N=20). Conditions were compared using a paired t test in SPM8. Craving was assessed prior to each condition.

Results: Compared to SMK, ABS significantly increased craving and reduced rCBF in select regions, including the hippocampus and ventral striatum (cluster corr, =0.01, 943 contiguous voxels). The magnitude of the abstinence-induced change in rCBF correlated with the magnitude of the change in craving across conditions in select regions including the medial and lateral orbitofrontal cortices and the anterior ventral insula (r values ranging from 0.59-0.74).

Conclusions: Results show that as few as 4 hours of abstinence can reduce resting rCBF in multiple nodes of the brain's mesocorticolimbic network, disrupting neural processing. Identifying early withdrawal treatment targets has far-reaching implications, which include thwarting relapse proclivities. Results parallel those of the extant human literature and are in agreement with an extensive preclinical literature showing compromised mesolimbic dopaminergic function and impairments in reward function during nicotine withdrawal.

Keywords:Cigarette smoking, nicotine abstinence, withdrawal, striatum, fMRI

Department of Psychiatry
University of Pennsylvania, Philadelphia, PA USA

Support: This work was supported by the National Institutes of Health, National Institute for Drug Abuse (P60DA005186; K01DA015426; R21DA025882; R21DA032022; R01DA029845 and R01DA030394). The funding organizations had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Contact Information:
Reagan R. Wetherill, Ph.D.
Department of Psychiatry
University of Pennsylvania
Treatment Research Center
3900 Chestnut Street
Philadelphia, PA 19104

Phone: (215) 222-3200 ext. 141
Fax: (215) 386-6770
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