Laboratory of Molecular Neuroimaging

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Active Studies

Early Methamphetamine Abstinence: fMRI and Cognition

Methamphetamine (MA) abuse is a national public health concern. People who are dependent on MA have problems with mental functions (e.g., learning, remembering, focusing attention, solving problems). Such problems can interfere with their treatment for MA abuse, and thereby may promote continued drug use. While the effects of MA have been studied in rodents and non-human primates, its effects on the human brain have not been well characterized.

This project aims to identify the brain regions and pathways that show dysfunction contributing to the problems of MA abusers in performing mental tasks. We are using functional magnetic resonance imaging (fMRI), a noninvasive brain imaging procedure, to study brain function while research participants perform tests of memory and concentration. We are comparing brain activity in regular users of MA with activity in a comparison group of participants who do not use MA.

MA abusers must abstain from illicit drugs during the study. We use fMRI to measure their brain activity at 4 - 7 days after they stop MA use, and again at about one month later. Knowledge of the pattern of cerebral deficits in MA abusers during drug abstinence can guide development of treatments aimed at reversing or compensating for those deficits.

Our first results, published in the Archives of General Psychiatry (link to paper), showed that, compared to normal non drug-using controls, methamphetamine abusers show regional cerebral metabolic rate (rCMRglc) deficiencies in several executive functioning regions of their brains, namely the medial orbitofrontal cortex, anterior cingulate, etc.

Effects of Methamphetamine Abuse on Cerebral Glucose Metabolism

PET Methamphetamine Scan Abuse of the psychomotor stimulant methamphetamine (METH) is a national public health concern. Although the effects of METH have been extensively studied in animal models, long-term effects of METH on the human brain have not been well characterized. The rate at which a brain area uses glucose, the primary source of energy for the brain, is proportional to the functional activity of that region. Positron emission tomography (PET), a nuclear medicine procedure, will be used with 2-deoxy-2[F-18]fluoro-D-glucose (FDG), a radioactive tracer, to measure the rates at which glucose is used in different regions of the brain. This study has shown that local rates at which the brain uses glucose are abnormal in humans after prolonged METH use and abstinence.

Nicotine Withdrawal, Smoking, and Cognition: An fMRI Study

This study evaluates the effects of smoking nicotine cigarettes on memory, concentration, and brain function during performance of cognitive tasks. The study has two parts: part A involves memory and concentration tests, and part B involves brain scanning with functional magnetic resonance imaging (fMRI). The fMRI procedure can takes pictures of the brain at work by measuring blood flow to different regions of brain as indicated by increases or decreases in local signal intensity resulting from changes in blood oxygen levels.

Genetics of Alcohol Effects on Brain Functioning

Nearly half of Americans over 12 years of age drink alcohol, yet only 5.6% drink heavily. It is important to know why only some people become alcohol-dependent. Alcoholism has a genetic component. The D2 dopamine receptor gene (DRD2) exists in two forms (alleles): A1 and A2. Carriers of the A1 allele are more susceptible to alcoholism. In this study of social drinkers, we will compare carriers and non-carriers of the DRD2 A1 allele, with respect to the effect of alcohol challenge on mood and associated regional brain function. Positron emission tomography (PET), a nuclear medicine procedure, will be used with 2-deoxy-2[F-18]fluoro-D-glucose (FDG), a radioactive tracer, to measure the rates at which glucose is used in different regions of the brain.

Recent Journal Articles

Horti A, Chefer S, Mukhin A, Koren A, Gündisch D, Links J, Kurian V, Dannals R, London E. 6-[18F]fluoro-A 85380, a novel radioligand for in vivo imaging of central nicotinic ACh receptors. Life Sci 2000; 667:463-69.
Bartzokis G, Lu PH, Beckson M, Rapoport R, Grant S, Wiseman EJ, London ED. Abstinence from cocaine reduces high-risk responses on a gambling task. Neuropsychopharmacology 2000;22:102-103.
Grant S, Contoreggi C, London ED. Drug abusers show impaired performance in a laboratory test of decision making. Neuropsychologia 2000;38:1180-1187.
Mukhin AG, Gündisch D, Horti AG, Koren AO, Tamagnan G, Kimes AS, Chambers J, Vaupel DB, King SI, Picciotto MR, Innis RB, London ED. 5-Iodo-A-85380, an 4 2 subtype-selective ligand for nicotinic acetylcholine receptors. Mol Pharmacol 2000;57:642-649.
Koren AO, Horti AG, Mukhin AG, Gündisch E, Dannals RF, London ED. Synthesis and initial in vitro characterization of 6-[18F]fluoro-3-(2(s)-azetidinylmethoxy)-pyridine, a high-affinity radioligand for central nicotinic acetylcholine receptors. J Labelled Compounds & Radiopharmaceuticals 2000;43:413-423.
Ernst M, Matochik J, Heishman S, Van Horn J, Jons P, Henningfield J, London E. Acute and chronic nicotine effects on brain activation during performance of a working memory task. Proc Natl Acad Sci USA 2001;98:4728-4733.
Ernst M, Heishman SJ, Spurgeon L, London ED. Smoking history and nicotine effects on cognitive performance. Neuropsychopharmacology 2001;25:313-319.
Mintzer MZ, Griffiths RR, Contoreggi C, Kimes AS, London ED, Ernst M. Effects of triazolam on brain activity during episodic memory encoding: a PET study. Neuropsychopharmacology 2001;25:744-756.
Ernst M, Bolla K, Mouratidis M, Contoreggi C, Matochik JA, Kurian V, Cadet JL, Kimes AS, London ED. Decision-making in a risk-taking task: A PET study. Neuropsychopharmacology 2002;26:682-691.
Bonson KR, Grant SJ, Contoreggi CS, Links JM, Metcalfe J, Weyl HL, Kurian V, Ernst M, London ED. Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 2002;26:376-386.
Brody A, Mandelkern m, London E, Childress AR, Lee GS, Bota R, Ho M, Saxena S, Baxter L, Madsen D, Jarvik M. Brain metabolic changes during cigarette craving. Arch Gen Psychiatry 2002;59:1162-1172.
Rose JE, Behm FM, Westman EC, Mathew RJ, London ED, Hawk TC, Turkington TG, Coleman RE. Nicotinic influences on neural systems: PET studies in cigarette smokers. Am J Psychiatry 2003; 60:323-33.
Bolla KI, Eldreth DA, London ED et al. Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task: NeuroImage 2003;19:1085-1094.
Chefer S, London E, Koren A, Pavlova OA, Kurian V, Kimes AS, Horti AG, Mukhin AG. Graphical analysis of 2-[18F]FA binding to nicotinic acetylcholine receptors in rhesus monkey brain. Synapse 2003; 48:25-34.
Kimes AS, Horti AG, London ED et al. 2-[18F]F-A85380: PET imaging brain nicotinic acetylcholine receptors and whole body distribution in humans: FASEB J 2003;10:1331-1333.
London E, Simon S, Berman S et al. Regional cerebral dysfunction associated with mood disturbances in abstinent methamphetamine abusers. Arch Gen Psychiatry 2004;61:73-84.
Brody A, Mandelkern M, Jarvik M, Lee G, Smith E, Huang J, Bota R, Bartzokis G, London E. Differences between smokers & non-smokers in regional gray matter volumes & densities. Biol Psych 2004;55:77-84.
Bolla K, Ernst M, Kiehl K, Mouratidis M, Eldreth D, Contoreggi C, Matochik J, Kurian V, Cadet J, Kimes A, Funderburk F, London E. Prefrontal cortical dysfunction in abstinent cocaine abusers. Neuropsych Clin Neurosci, 2004; 16:4.
Brody A, Olmstead R, London E, Farahi J, Meyer J, Grossman P, Lee GS, Huang J, Hahn E, Mandelkern, MA. Smoking-induced ventral striatal dopamine release. Am J Psychiatry 2004;161:1211-1218.
Brody A, Mandelkern M, Lee G, Smith E, Sadeghi M, Saxena S, Jarvik M, London E. Attenuated cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study. Psych Res Neuroimaging, 2004;130:269-281.
Thompson P, Hayashi K, Simon S, Geaga J, Hong M, Sui Y, Lee J, Toga AW, Ling W, London ED. Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci 2004; 24:6028-6036.
JR. Monterosso, AR. Aron, Xl Cordova, J Xu, ED London, (in press) Impaired Response Inhibition Associated With Chronic Methamphetamine Abuse Drug and Alcohol Dependence Drug and Alcohol Dependence.
J Xu, A Mendrek, MS Cohen, J Monterosso, P Rodriquez, SL Simon, A Brody, M Jarvik, CP Domier, R Olmstead, M Ernst, ED London (in press). Brain activity in cigarette smokers performing a working memory task: Effects of smoking. Biol. Psychiatry
B Voytek, SM. Berman, BD Hassid, SL. Simon, MA Mandelkern, AL. Brody, J Monterosso, W Ling, ED. London (in press). Differences in regional brain metabolism associated with marijuana abuse in methamphetamine abusers. Synapse.