The Addictive Brain
Wednesday 22 April 2009
Room 311 10:30-12:30


Dieter Meyerhoff and John D. Port

10:30 429. Altered Resting-State Default Mode Network Connectivity in Adults Prenatally Exposed to Alcohol
    Priya Santhanam1, Zhihao Li1, Mary Ellen Lynch2, Claire D. Coles2, Xiaoping Hu1
Biomedical Engineering, Georgia Institute of Technology/ Emory University, Atlanta, GA, USA; 2Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA
    As the default mode network (DMN) has not been previously examined in a population with prenatal alcohol exposure (PAE), the current study examined resting state connectivity in DMN in two PAE groups versus healthy controls. The time course seed, used for cross-correlation, was taken from anterior cingulate region of deactivation during a cognitive task. Resting state synchrony of DMN was lower in both PAE groups as compared to controls (p=0.019 and p=0.027 for dysmorphic and non-dysmorphic, respectively); however, deactivation during cognition was not significantly different. Results imply PAE may be affecting connectivity at rest (baseline arousal) but not task-related arousal.
10:42 430. Prenatal Cocaine Exposure Alters Ventromedial Prefrontal Activity Associated with Emotion Regulation
    Zhihao Li1, Priya Santhanam1, Claire D. Coles2, Mary Ellen Lynch2, Stephan Hamann3, Xiaoping Hu1
Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, GA, USA; 2Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA; 3Psychology, Emory University, Atlanta, GA, USA
    Prenatal cocaine exposure (PCE) is associated with arousal dysregulation but the neurobiological bases have not been well investigated yet. The present fMRI data showed that PCE subjects could not increase their ventromedial prefrontal activation in excerting emotional suppression, which complemented previous findings about altered amygdala emotional responses in PCE subjects.
10:54 431.

Greater Than Age-Related Decline in Temporal and Occipital Cortices of Methamphetamine Users

    Helenna Nakama1, Ryan Shimotsu2, Thomas Ernst3, George Fein2, Linda Chang3
Department of Psychiatry, University of Hawaii at Manoa, Honolulu, Hi, USA; 2Neurobehavioral Research, Inc., Honolulu, Hi, USA; 3John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hi, USA
    Methamphetamine (METH) use can lead to brain gray matter deficits. However, the effect of aging on gray matter volumes has not been studied. Structural MRI was performed in 44 METH users and 34 controls subjects. METH users had a 5 to 8-fold greater age-related decline in temporal and occipital lobe gray matter volumes than healthy non-drug users. These findings suggest that METH users may be more vulnerable to age-related atrophic changes, which might contribute to greater age-related cognitive decline, including dementia.
11:06 432. Disrupted Midbrain-Thalamus Functional Connectivity in Cocaine Abusers
    Dardo Tomasi1, Nora D. Volkow2, Ruiliang L. Wang1, Jean H. Carrillo1,3, Thomas Maloney1, Nelly Alia-Klein1, Patricia A. Woicik1, Frank Telang1, Rita Z. Goldstein1
Medical Department, Brookhaven National Laboratory, Upton, NY, USA; 2National Institute on Drug Abuse, National Institute on Health, Bethesda, MD, USA; 3Department of Computer Science, SUNY , Stony Brook, NY, USA
    Chronic cocaine use decreases brain dopamine activity. However the functional effects of this disruption are largely unknown. We used fMRI and seed-voxel correlation analyses to study brain activation to a cognitive-emotional (drug Stroop-like; DS) task and the functional connectivity (fcMRI) between midbrain and forebrain. Cocaine abusers had lower DS activation in the thalamus and lower fcMRI between the thalamus and midbrain than controls, consistently with dopaminergic neuroadaptations resulting from repeated cocaine use. These findings suggest that lower subcortical recruitment and larger cortical recruitment is mediated by abnormal fcMRI of catecholamine (dopamine and noradrenaline) pathways in cocaine abusers.
11:18 433. Acute Ethanol Alters GABA and MyoInositol in Human Brain
    Graeme F. Mason1, June Watzl2, Stuart Weinzimer3, Gerard Sanacora, Elizabeth Guidone, Ismene L. Petrakis, Douglas L. Rothman4, John H. Krystal
1Diagnostic Radiology and Psychiatry, Yale University, School of Medicine, New Haven, CT, USA; 2Diagnostic Radiology, Yale University, School of Medicine, New Haven, CT, USA; 3Pediatrics, Yale University, School of Medicine, New Haven, CT, USA; 4Diagnostic Radiology & Biomedical Engineering, Yale University, School of Medicine, New Haven, CT, USA
    Ethanol is known to potentiate GABA receptors and inhibit glutamate receptors in the brain. We hypothesized that ethanol would alter brain GABA and possibly glutamate levels in a time-dependent manner. Intravenous infusions of ethanol were performed during J-edited MRS measurements of GABA and other compounds in the occipital lobe. GABA and myoinositol were reduced significantly during the infusion, glutamate rose transiently and returned to starting levels, and no changes were seen in tissue water, total creatine, choline, or other metabolites. Brain ethanol closely tracked the breath alcohol, while venous ethanol lagged.
11:30 434. Glutamate Alterations in Alcohol Dependent Patients During Early Detoxification
    Gabriele Ende1, Nuran Tunc-Skarka1, Wolfgang Weber-Fahr1, Mareen Hoerst1, Matthias Ruf1, Monika Uhrig1, Derik Hermann2, Karl Mann2
Neuroimaging, Central Institute of Mental Health, Mannheim, Germany; 2Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health
    The purpose of this study is to determine whether there are significant changes in glutamate concentrations in the anterior cingulate gyrus and frontal white matter in alcohol dependent patients during early detoxification in comparison to healthy controls and whether these changes parallel deficits in NAA and tCho concentrations. Alcoholic patients during early detoxification show reduced levels of Glu in fWM in addition to reduced tNAA and tCho. A rather weak correlation of Glu values acquired at TE = 30 and TE =80 ms gives rise to the suspicion that the separation of Glu from Gln and GABA is not reliable.
11:42 435. Negative Correlation Between Medial Frontal Activity During Inhibitory Control and Impulsiveness in Abstinent Heroin Dependents: An FMRI Study
    Li-ping FU1,2, Zhi-tong ZOU3, Shi-jiang LI4, Guo-hua BI1, Yan WANG3, En-mao YE1, Lin MA3, Zheng Yang1
Beijing Institute of Basic Medical Science, Beijing, China; 2Radiology, Peking University Shougang Hospital , Beijing, China; 3Radiology, General Hospital of People's Liberation Army of China; 4Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA
    Impulsiveness is a hallmark of addiction. In this study, we combined the neurobiological method (fMRI) and laboratory performance (BIS-11) to explore the rapid-response impulsivity in abstinent heroin dependents. A significant negative correlation between the non-planning score of BIS-11 and the activation of bilateral cingulated cortex (CC) and medial frontal gyrus (mFG) was detected, which indicates that the CC and mFG may be the most sensitive brain areas to the neurotoxicity of heroin and the lack of self-control and intolerance of cognitive complexity reflected by the high BIS-scores contributes, at least partly, to the persistent neural dysfunction.
11:54 436. [1-13C] Acetate MRS to Study Glial Glutamate Dysfunction in Methamphetamine Users
    Napapon Sailasuta1, Kent Harris1, Osama Abulseoud2, Brian Ross1
HMRI, Pasadena, CA, USA; 2U of Southern California, Los Angeles, CA, USA
    13C MRS studies of glial glutamate metabolism in abstinent methaphetamine users via C1-acetate infusion.
12:06 437. Brain Reactivity to Smoking-Related Cues During Tobacco Abstinence: An FMRI Study
    Amy C. Janes1, Blaise deB Frederick1, Sarah Richardt1, Caitlin Burbridge1, Emilio Merlo-Pich2, Perry F. Renshaw1, A. Eden Evins3, Maurizio Fava3, Marc J. Kaufman1
Brain Imaging Center, McLean Hospital, Belmont, MA, USA; 2Psychiatry-CEDD, GlaxoSmithKline, Verona, Italy; 3Massachusetts General Hospital, Boston, MA, USA
    Nicotine replacement therapies (NRT) reduce smoking withdrawal symptoms but not cue-induced craving. We used blood oxygen level dependent (BOLD) functional MRI (fMRI) to characterize brain responses to smoking-related cues prior to and during NRT-maintained abstinence. BOLD response patterns were comparable to previously reported findings in smoking-cue fMRI studies but anatomical distributions differed based on smoking status. Nigrostriatal activation was greater in smokers in the abstinent versus pre-abstinent state. Since in abstinence, this circuit participates in drug seeking reinstatement, our findings suggest that treatments that modulate nigrostriatal activity may reduce cue-induced brain activations and craving, and may improve smoking cessation outcomes.
12:18 438. Live Brain MRI Detection of Glia Activation by Psychostimulant Exposure
    Christina H. Liu1, Jia Q. Ren, Pradeep G. Bhide2, Philip K. Liu3
Radiology, Massachusetts General Hospital, Charlestown, MA, USA; 2Neurology, Massachusetts General Hospital, USA; 3Radiology, Massachusetts General Hospital, USA
    Electrophysiological data from cell cultures or brain slice preparations show that an important component of drug abuse is the interaction that occurs between glia and neurons. While most addiction research has focused on the molecular adaptation of neurons, our understanding in glial response to psychostimulants at the transcriptional level is very limited. Here we report an MR imaging technique that allows us to identify vulnerable brain regions to glia activation after acute or chronic exposure to amphetamine in live animals. This technique will facilitate and broaden our understanding on molecular processes at transcription level that attribute to drug addiction.