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Hippocampal and striatal gray matter volume are associated with a smoking cessation treatment outcome: results of an exploratory voxel-based morphometric analysis

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Abstract

Rationale

Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain structure including reduced gray matter (GM) volume and/or density in areas including frontal and cingulate cortices, thalamus, and insula. However, associations between brain structure and smoking cessation treatment outcomes have not been reported.

Objectives

In the present analysis we sought to identify associations between regional GM volume—as measured by voxel-based morphometry (VBM)—and a smoking cessation treatment outcome (point prevalence abstinence at 4 weeks).

Methods

Adult smokers underwent high-resolution anatomical MRI scanning prior to an open label smoking cessation treatment trial. VBM was conducted in SPM5 using the DARTEL algorithm and relapser vs. quitter groups were compared using independent sample t tests (p < 0.001, uncorrected). Analyses controlled for potentially confounding factors including years smoked, cigarettes per day, total intracranial volume (TIV), and sex.

Results

Of 18 smokers, 8 achieved a 4-week point prevalence abstinence, confirmed by CO level (≤8 ppm). After controlling for all covariates, compared to relapsers, quitters had significantly higher GM volume in the left putamen and right occipital lobe, while also significantly lower GM volume in bilateral hippocampus and right cuneus.

Conclusions

These preliminary results suggest that maintaining smoking abstinence is associated with higher pre-quit brain volume in regions that subserve habit learning and visual processing, and lower brain volume in regions that subserve long-term memory processes and visual information processing. Future, large-scale studies can determine whether brain structure variables can serve as clinically useful predictors of smoking cessation treatment outcome.

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References

  • Almeida OP, Garrido GJ, Lautenschlager NT, Hulse GK, Jamrozik K, Flicker L (2008) Smoking is associated with reduced cortical regional gray matter density in brain regions associated with incipient Alzheimer disease. Am J Geriatr Psychiatry 16(1):92–98

    Article  PubMed  Google Scholar 

  • Ashburner J (2007) A fast diffeomorphic image registration algorithm. Neuroimage 38(1):95–113

    Article  PubMed  Google Scholar 

  • Bartzokis G, Mintz J, Marx P, Osborn D, Gutkind D, Chiang F et al (1993) Reliability of in vivo volume measures of hippocampus and other brain structures using MRI. Magn Reson Imaging 11(7):993–1006

    Article  CAS  PubMed  Google Scholar 

  • Benwell ME, Balfour DJ, Anderson JM (1988) Evidence that tobacco smoking increases the density of (−)-[3H]nicotine binding sites in human brain. J Neurochem 50(4):1243–1247

    Article  CAS  PubMed  Google Scholar 

  • Bergouignan L, Chupin M, Czechowska Y, Kinkingnéhun S, Lemogne C, Le Bastard G et al (2009) Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression? NeuroImage 45(1):29–37

    Article  PubMed  Google Scholar 

  • Bestmann S, Baudewig J, Siebner HR, Rothwell JC, Frahm J (2004) Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits. Eur J Neurosci 19(7):1950–1962

    Article  PubMed  Google Scholar 

  • Brambilla P, Harenski K, Nicoletti MA, Mallinger AG, Frank E, Kupfer DJ et al (2001) Anatomical MRI study of basal ganglia in bipolar disorder patients. Psychiatry Research: Neuroimaging 106(2):65–80

    Article  CAS  PubMed  Google Scholar 

  • Brody AL, Mandelkern MA, Jarvik ME, Lee GS, Smith EC, Huang JC et al (2004) Differences between smokers and nonsmokers in regional gray matter volumes and densities. Biol Psychiatry 55(1):77–84

    Article  PubMed  Google Scholar 

  • Burwell RD, Amaral DG (1998) Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat. J Comp Neurol 398(2):179–205

    Article  CAS  PubMed  Google Scholar 

  • Burwell RD, Saddoris MP, Bucci DJ, Wiig KA (2004) Corticohippocampal contributions to spatial and contextual learning. J Neurosci 24(15):3826–3836

    Article  CAS  PubMed  Google Scholar 

  • Canteras NS, Swanson LW (1992) Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat. J Comp Neurol 324(2):180–194

    Article  CAS  PubMed  Google Scholar 

  • Carter BL, Robinson JD, Lam CY, Wetter DW, Tsan JY, Day SX et al (2006) A psychometric evaluation of cigarette stimuli used in a cue reactivity study. Nicotine Tob Res 8(3):361–369

    Article  PubMed  Google Scholar 

  • Crombag HS, Bossert JM, Koya E, Shaham Y (2008) Review. Context-induced relapse to drug seeking: a review. Philos Trans R Soc Lond B Biol Sci 363(1507):3233–3243

    Article  PubMed  Google Scholar 

  • Dickerson BC, Fenstermacher E, Salat DH, Wolk DA, Maguire RP, Desikan R et al (2008) Detection of cortical thickness correlates of cognitive performance: Reliability across MRI scan sessions, scanners, and field strengths. Neuroimage 39(1):10–18

    Article  CAS  PubMed  Google Scholar 

  • Domino EF, Ni L, Xu Y, Koeppe RA, Guthrie S, Zubieta JK (2004) Regional cerebral blood flow and plasma nicotine after smoking tobacco cigarettes. Prog Neuropsychopharmacol Biol Psychiatry 28(2):319–327

    Article  CAS  PubMed  Google Scholar 

  • Durazzo TC, Gazdzinski S, Yeh PH, Meyerhoff DJ (2008) Combined neuroimaging, neurocognitive and psychiatric factors to predict alcohol consumption following treatment for alcohol dependence. Alcohol Alcohol 43(6):683–691

    PubMed  Google Scholar 

  • Emdad R, Bonekamp D, Sondergaard HP, Bjorklund T, Agartz I, Ingvar M et al (2006) Morphometric and psychometric comparisons between non-substance-abusing patients with posttraumatic stress disorder and normal controls. Psychother Psychosom 75(2):122–132

    Article  PubMed  Google Scholar 

  • Ernst M, Matochik JA, Heishman SJ, Van Horn JD, Jons PH, Henningfield JE et al (2001) Effect of nicotine on brain activation during performance of a working memory task. Proc Natl Acad Sci 98(8):4728–4733

    Article  CAS  PubMed  Google Scholar 

  • Fuchs RA, Evans KA, Ledford CC, Parker MP, Case JM, Mehta RH et al (2004) The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats. Neuropsychopharmacology 30(2):296–309

    Article  Google Scholar 

  • Fuchs RA, Evans KA, Ledford CC, Parker MP, Case JM, Mehta RH et al (2005) The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats. Neuropsychopharmacology 30(2):296–309

    Article  CAS  PubMed  Google Scholar 

  • Gallinat J, Meisenzahl E, Jacobsen LK, Kalus P, Bierbrauer J, Kienast T et al (2006) Smoking and structural brain deficits: a volumetric MR investigation. Eur J Neurosci 24(6):1744–1750

    Article  PubMed  Google Scholar 

  • Gilbert AR, Mataix-Cols D, Almeida JR, Lawrence N, Nutche J, Diwadkar V et al (2008) Brain structure and symptom dimension relationships in obsessive-compulsive disorder: a voxel-based morphometry study. J Affect Disord 109(1–2):117–126

    Article  PubMed  Google Scholar 

  • Gould TJ (2006) Nicotine and hippocampus-dependent learning: implications for addiction. Mol Neurobiol 34(2):93–107

    Article  CAS  PubMed  Google Scholar 

  • Gray R, Rajan AS, Radcliffe KA, Yakehiro M, Dani JA (1996) Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 383(6602):713–716

    Article  CAS  PubMed  Google Scholar 

  • Grusser SM, Wrase J, Klein S, Hermann D, Smolka MN, Ruf M et al (2004) Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology (Berl) 175(3):296–302

    Article  Google Scholar 

  • Hyman BT, Van Hoesen GW, Damasio AR (1990) Memory-related neural systems in Alzheimer's disease: an anatomic study. Neurology 40(11):1721–1730

    CAS  PubMed  Google Scholar 

  • Jacobsen LK, Krystal JH, Mencl WE, Westerveld M, Frost SJ, Pugh KR (2005) Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biol Psychiatry 57(1):56–66

    Article  PubMed  Google Scholar 

  • Klein A, Andersson J, Ardekani BA, Ashburner J, Avants B, Chiang MC et al (2009) Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration. Neuroimage 46(3):786–802

    Article  PubMed  Google Scholar 

  • Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology 35(1):217–238

    Article  PubMed  Google Scholar 

  • Koolschijn PC, van Haren NE, Lensvelt-Mulders GJ, Hulshoff Pol HE, Kahn RS (2009) Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 30(11):3719–3735

    Google Scholar 

  • Kosten TR, Scanley BE, Tucker KA, Oliveto A, Prince C, Sinha R et al (2006) Cue-induced brain activity changes and relapse in cocaine-dependent patients. Neuropsychopharmacology 31(3):644–650

    Article  CAS  PubMed  Google Scholar 

  • Levin ED, McClernon FJ, Rezvani AH (2006) Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology (Berl) 184(3–4):523–539

    Article  CAS  Google Scholar 

  • Maguire EA, Frackowiak RSJ, Frith CD (1996) Learning to find your way: a role for the human hippocampal formation. Proc R Soc Lond, B Biol Sci 263(1377):1745–1750

    Article  CAS  Google Scholar 

  • Marks MJ, Burch JB, Collins AC (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. J Pharmacol Exp Ther 226(3):817–825

    CAS  PubMed  Google Scholar 

  • Matsuyama S, Matsumoto A, Enomoto T, Nishizaki T (2000) Activation of nicotinic acetylcholine receptors induces long-term potentiation in vivo in the intact mouse dentate gyrus. Eur J Neurosci 12(10):3741–3747

    Article  CAS  PubMed  Google Scholar 

  • McClernon FJ, Hiott FB, Liu J, Salley AN, Behm FM, Rose JE (2007) Selectively reduced responses to smoking cues in amygdala following extinction-based smoking cessation: results of a preliminary functional magnetic resonance imaging study. Addict Biol 12(3–4):503–512

    Article  CAS  PubMed  Google Scholar 

  • McClernon FJ, Kozink RV, Rose JE (2008) Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues. Neuropsychopharmacology 33(9):2148–2157

    Article  CAS  PubMed  Google Scholar 

  • McClernon FJ, Kozink RV, Lutz AM, Rose JE (2009) 24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum. Psychopharmacology (Berl) 204(1):25–35

    Article  CAS  Google Scholar 

  • Mishkin M, Petri HL (1984) Memories and habits: some implications for the analysis of learning and retention. In: Squire L, Butters N (eds) Neuropsychology of memory. Guilford, New York, pp 287–296

    Google Scholar 

  • Morgane PJ, Galler JR, Mokler DJ (2005) A review of systems and networks of the limbic forebrain/limbic midbrain. Prog Neurobiol 75(2):143–160

    Article  PubMed  Google Scholar 

  • Morra JH, Tu Z, Apostolova LG, Green AE, Avedissian C, Madsen SK et al (2009) Automated mapping of hippocampal atrophy in 1-year repeat MRI data from 490 subjects with Alzheimer's disease, mild cognitive impairment, and elderly controls. NeuroImage 45(1, Supplement 1): S3–S15

  • Munafo MR, Zetteler JI, Clark TG (2007) Personality and smoking status: a meta-analysis. Nicotine Tob Res 9(3):405–413

    Article  PubMed  Google Scholar 

  • Packard MG, McGaugh JL (1996) Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning. Neurobiol Learn Mem 65(1):65–72

    Article  CAS  PubMed  Google Scholar 

  • Packard MG, Hirsh R, White NM (1989) Differential effects of fornix and caudate nucleus lesions on two radial maze tasks: evidence for multiple memory systems. J Neurosci 9(5):1465–1472

    CAS  PubMed  Google Scholar 

  • Robbins TW, Ersche KD, Everitt BJ (2008) Drug addiction and the memory systems of the brain. Ann N Y Acad Sci 1141:1–21

    Article  CAS  PubMed  Google Scholar 

  • Rose JE, Behm FM, Salley AN, Bates JE, Coleman RE, Hawk TC et al (2007) Regional brain activity correlates of nicotine dependence 32(12):2441–2452

    Google Scholar 

  • Schwartz RD, Kellar KJ (1983) Nicotinic cholinergic receptor binding sites in the brain: regulation in vivo. Science 220(4593):214–216

    Article  CAS  PubMed  Google Scholar 

  • See RE (2002) Neural substrates of conditioned-cued relapse to drug-seeking behavior. Pharmacol Biochem Behav 71(3):517–529

    Article  CAS  PubMed  Google Scholar 

  • See RE, Elliott JC, Feltenstein MW (2007) The role of dorsal vs ventral striatal pathways in cocaine-seeking behavior after prolonged abstinence in rats. Psychopharmacology (Berl) 194(3):321–331

    Article  CAS  Google Scholar 

  • Shiffman S, Paty JA, Gnys M, Kassel JA, Hickcox M (1996) First lapses to smoking: within-subjects analysis of real-time reports. J Consult Clin Psychol 64(2):366–379

    Article  CAS  PubMed  Google Scholar 

  • Smolka MN, Buhler M, Klein S, Zimmermann U, Mann K, Heinz A et al (2006) Severity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery. Psychopharmacology (Berl) 184(3–4):577–588

    Article  CAS  Google Scholar 

  • Spinella M (2002) Correlations between orbitofrontal dysfunction and tobacco smoking. Addict Biol 7(4):381–384

    Article  PubMed  Google Scholar 

  • Squire LR, Knowlton B, Musen G (1993) The structure and organization of memory. Annu Rev Psychol 44:453–495

    Article  CAS  PubMed  Google Scholar 

  • Strafella AP, Paus T, Barrett J, Dagher A (2001) Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci 21(15):RC157

    CAS  PubMed  Google Scholar 

  • Strafella AP, Paus T, Fraraccio M, Dagher A (2003) Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 126(Pt 12):2609–2615

    Article  PubMed  Google Scholar 

  • Swan GE, Lessov-Schlaggar CN (2007) The effects of tobacco smoke and nicotine on cognition and the brain. Neuropsychol Rev 17(3):259–273

    Article  PubMed  Google Scholar 

  • Terribilli D, Schaufelberger MS, Duran FL, Zanetti MV, Curiati PK, Menezes PR et al (in press) Age-related gray matter volume changes in the brain during non-elderly adulthood. Neurobiol Aging PMID: 19282066

  • Tiffany ST (1990) A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes. Psychol Rev 97(2):147–168

    Article  CAS  PubMed  Google Scholar 

  • Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE et al (2008) Molecular genetics of successful smoking cessation: convergent genome-wide association study results. Arch Gen Psychiatry 65(6):683–693

    Article  CAS  PubMed  Google Scholar 

  • Valente AA Jr, Miguel EC, Castro CC, Amaro E Jr, Duran FL, Buchpiguel CA et al (2005) Regional gray matter abnormalities in obsessive–compulsive disorder: a voxel-based morphometry study. Biol Psychiatry 58(6):479–487

    Article  PubMed  Google Scholar 

  • Venkatasubramanian G, Jayakumar PN, Gangadhar BN, Keshavan MS (2008) Neuroanatomical correlates of neurological soft signs in antipsychotic-naive schizophrenia. Psychiatry Research: Neuroimaging 164(3):215–222

    Article  PubMed  Google Scholar 

  • Volkow ND, Wang G-J, Telang F, Fowler JS, Logan J, Childress A-R et al (2006) Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci 26(24):6583–6588

    Article  CAS  PubMed  Google Scholar 

  • Walhovd KB, Fjell AM, Dale AM, McEvoy LK, Brewer J, Karow DS et al (2008) Multi-modal imaging predicts memory performance in normal aging and cognitive decline. Neurobiology of Aging, In Press, Corrected Proof

  • Wrase J, Makris N, Braus DF, Mann K, Smolka MN, Kennedy DN et al (2008) Amygdala volume associated with alcohol abuse relapse and craving. Am J Psychiatry 165(9):1179–1184

    Article  PubMed  Google Scholar 

  • Yakir A, Rigbi A, Kanyas K, Pollak Y, Kahana G, Karni O et al (2007) Why do young women smoke? III. Attention and impulsivity as neurocognitive predisposing factors. Eur Neuropsychopharmacol 17(5):339–351

    Article  CAS  PubMed  Google Scholar 

  • Yoo HK, Kim MJ, Kim SJ, Sung YH, Sim ME, Lee YS et al (2005) Putaminal gray matter volume decrease in panic disorder: an optimized voxel-based morphometry study. Eur J Neurosci 22(8):2089–2094

    Article  PubMed  Google Scholar 

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Acknowledgements

This research was supported by an unrestricted donation from Vector Tobacco Co. to Dr. Rose and by NIDA grant K23DA017261 to Dr. McClernon. We thank Susan Music and Natalie Goutkin for their assistance with MRI scanning.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 2701, Durham, NC, 27708, USA

    Brett Froeliger, Rachel V. Kozink, Jed E. Rose, Frederique M. Behm, Alfred N. Salley & F. Joseph McClernon

  2. Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, USA

    F. Joseph McClernon

  3. Durham Veterans Affairs Medical Center, and VISN 6 Mental Illness Research, Education, and Clinical Center, Durham, NC, USA

    F. Joseph McClernon

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  1. Brett Froeliger
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  2. Rachel V. Kozink
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  3. Jed E. Rose
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  4. Frederique M. Behm
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  5. Alfred N. Salley
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  6. F. Joseph McClernon
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Correspondence to F. Joseph McClernon.

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Froeliger, B., Kozink, R.V., Rose, J.E. et al. Hippocampal and striatal gray matter volume are associated with a smoking cessation treatment outcome: results of an exploratory voxel-based morphometric analysis. Psychopharmacology 210, 577–583 (2010). https://doi.org/10.1007/s00213-010-1862-3

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  • DOI: https://doi.org/10.1007/s00213-010-1862-3

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