Elisabeth de Castro Caparelli, Ph.D.

@article{Suchankova2015b,

title = {The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence.},

author = {P Suchankova and J Yan and M L Schwandt and B L Stangl and E C Caparelli and R Momenan and E Jerlhag and J A Engel and C A Hodgkinson and M Egli and M F Lopez and H C Becker and D Goldman and M Heilig and V A Ramchandani and L Leggio},

url = {https://www.ncbi.nlm.nih.gov/pubmed/26080318},

doi = {doi: 10.1038/tp.2015.68},

issn = {2158-3188 (Electronic); 2158-3188 (Linking)},

year  = {2015},

date = {2015-06-16},

journal = {Transl Psychiatry},

volume = {5},

pages = {e583},

abstract = {The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case-control analysis (N = 908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N = 3803) was used for confirmation purposes. Post hoc analyses were carried out on data from a human laboratory study of intravenous alcohol self-administration (IV-ASA; N = 81) in social drinkers and from a functional magnetic resonance imaging study in alcohol-dependent individuals (N = 22) subjected to a Monetary Incentive Delay task. In the preclinical study, a GLP-1R agonist was evaluated in a mouse model of alcohol dependence to demonstrate the role of GLP-1R for alcohol consumption. The previously reported functional allele 168Ser (rs6923761) was nominally associated with AUD (P = 0.004) in the NIAAA sample, which was partially replicated in males of the SAGE sample (P = 0.033). The 168 Ser/Ser genotype was further associated with increased alcohol administration and breath alcohol measures in the IV-ASA experiment and with higher BOLD response in the right globus pallidus when receiving notification of outcome for high monetary reward. Finally, GLP-1R agonism significantly reduced alcohol consumption in a mouse model of alcohol dependence. These convergent findings suggest that the GLP-1R may be an attractive target for personalized pharmacotherapy treatment of AUD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tomasi2014,

title = {Overlapping patterns of brain activation to food and cocaine cues in cocaine abusers: association to striatal D2/D3 receptors.},

author = {Dardo Tomasi and Gene-Jack Wang and Ruiliang Wang and Elisabeth C Caparelli and Jean Logan and Nora D Volkow},

url = {https://www.ncbi.nlm.nih.gov/pubmed/25142207},

doi = {10.1002/hbm.22617},

issn = {1097-0193 (Electronic); 1065-9471 (Linking)},

year  = {2014},

date = {2014-08-21},

journal = {Hum Brain Mapp},

volume = {36},

number = {1},

pages = {120--136},

address = {National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.},

abstract = {Cocaine, through its activation of dopamine (DA) signaling, usurps pathways that process natural rewards. However, the extent to which there is overlap between the networks that process natural and drug rewards and whether DA signaling associated with cocaine abuse influences these networks have not been investigated in humans. We measured brain activation responses to food and cocaine cues with fMRI, and D2/D3 receptors in the striatum with [11C]raclopride and Positron emission tomography in 20 active cocaine abusers. Compared to neutral cues, food and cocaine cues increasingly engaged cerebellum, orbitofrontal, inferior frontal, and premotor cortices and insula and disengaged cuneus and default mode network (DMN). These fMRI signals were proportional to striatal D2/D3 receptors. Surprisingly cocaine and food cues also deactivated ventral striatum and hypothalamus. Compared to food cues, cocaine cues produced lower activation in insula and postcentral gyrus, and less deactivation in hypothalamus and DMN regions. Activation in cortical regions and cerebellum increased in proportion to the valence of the cues, and activation to food cues in somatosensory and orbitofrontal cortices also increased in proportion to body mass. Longer exposure to cocaine was associated with lower activation to both cues in occipital cortex and cerebellum, which could reflect the decreases in D2/D3 receptors associated with chronicity. These findings show that cocaine cues activate similar, though not identical, pathways to those activated by food cues and that striatal D2/D3 receptors modulate these responses, suggesting that chronic cocaine exposure might influence brain sensitivity not just to drugs but also to food cues.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wang2013,

title = {Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues.},

author = {G-J Wang and D Tomasi and N D Volkow and R Wang and F Telang and E C Caparelli and E Dunayevich},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23924756},

doi = {10.1038/ijo.2013.145},

issn = {1476-5497 (Electronic); 0307-0565 (Linking)},

year  = {2013},

date = {2013-08-08},

journal = {Int J Obes (Lond)},

volume = {38},

number = {5},

pages = {682--688},

address = {1$]$ Department of Bioscience, Brookhaven National Laboratory, Upton, NY, USA $[$2$]$ Department of Radiology, Stony Brook University, Stony Brook, NY, USA.},

abstract = {OBJECTIVE: The significant weight loss observed with combination naltrexone-sustained release (SR) 32 mg and bupropion SR 360 mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment. METHODS: Forty women (31.1+/-8.1 years; body mass index: 32.5+/-3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (>100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation ( approximately 14 h) were assessed before and after treatment. RESULTS: The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues (P<0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P<0.05). CONCLUSIONS: Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Avti2013,

title = {Cytotoxicity, cytocompatibility, cell-labeling efficiency, and in vitro cellular magnetic resonance imaging of gadolinium-catalyzed single-walled carbon nanotubes.},

author = {Pramod K Avti and Elisabeth D Caparelli and Balaji Sitharaman},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23686792},

doi = {10.1002/jbm.a.34643},

issn = {1552-4965 (Electronic); 1549-3296 (Linking)},

year  = {2013},

date = {2013-05-18},

journal = {J Biomed Mater Res A},

volume = {101},

number = {12},

pages = {3580--3591},

address = {Department of Biomedical Engineering, Rm #115, Bioengineering Building, Stony Brook University, Stony Brook, New York 11794-5281.},

abstract = {Cell tracking by magnetic resonance imaging (MRI) is an emerging technique that typically requires the use of MRI contrast agents (CAs). A MRI CA for cellular imaging should label cells efficiently at potentially safe concentrations, have high relaxivity, and not affect the cellular machinery. In this article, we report the cytotoxicity, cytocompatibility, and cell labeling efficiency in NIH/3T3 fibroblasts of novel, single-walled carbon nanotubes synthesized using gadolinium nanoparticles as catalysts (Gd-SWCNTs). Cells incubated with the Gd-SWCNT showed a dose- (50-100 microg/mL nanotube concentration) and time- (12-48 h) dependent decrease in viability. 30% cell death was observed for cells incubated with Gd-SWCNTs at the maximum dose of 100 microg/mL for 48 h. Cells incubated with the Gd-SWCNTs at concentrations between 1-10 mug/mL for 48 h showed no change in viability or proliferation compared to untreated controls. Additionally, at these potentially safe concentrations, up to 48 h, the cells showed no phosphatidyl serine externalization (pre-apoptotic condition), caspase-3 activity (point of no return for apoptosis), genetic damage, or changes in their division cycle. Localization of Gd-SWCNTs within the cells was confirmed by transmission electron microscopy (TEM) and Raman microscopy, and these results show 100% cell labeling efficiency. Elemental analysis also indicates significant uptake of Gd-SWCNTs by the cells (10(8) -10(9) Gd(3+) ions per cell). Finally, T1 -weighted MRI at 3 T of Gd-SWCNT-labelled cells show up to a four-fold increase in MR signal intensities as compared to untreated cells. These results indicate that Gd-SWCNTs label cells efficiently at potentially safe concentrations, and enhance MRI contrast without any structural damage to the cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2013,

title = {Computerized MRS voxel registration and partial volume effects in single voxel 1H-MRS.},

author = {Hedok Lee and Elisabeth Caparelli and Haifang Li and Amit Mandal and David S Smith and Shaonan Zhang and Thomas V Bilfinger and Helene Benveniste},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23659770},

doi = {10.1016/j.mri.2013.04.001},

issn = {1873-5894 (Electronic); 0730-725X (Linking)},

year  = {2013},

date = {2013-05-06},

journal = {Magn Reson Imaging},

volume = {31},

number = {7},

pages = {1197--1205},

address = {Department of Anesthesiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA. hedoklee@gmail.com},

abstract = {Partial volume effects in proton magnetic resonance spectroscopy in the brain have been studied previously in terms of proper water concentration calculations, but there is a lack of disclosure in terms of voxel placement techniques that would affect the calculations. The purpose of this study is to facilitate a fully automated MRS voxel registration method which is time efficient, accurate, and can be extended to all imaging modalities. A total of thirteen healthy adults underwent single voxel 1H-MRS scans in 3.0T MRI scanners. Transposition of a MRS voxel onto an anatomical scan is derived along with a full calculation of water concentration with a correction term to account for the partial volume effects. Five metabolites (tNAA, Glx, tCr, mI, and tCho) known to yield high reliability are studied. Pearson's correlation analyses between tissue volume fractions and metabolite concentrations were statistically significant in parietal (tCr, Glx, and tNAA) lobe and occipital lobe (tNAA). MRS voxel overlaps quantified by dice metric over repeated visits yielded 60%~70% and coefficients of variance in metabolites concentration were 4%~10%. These findings reiterate an importance of considering the partial volume effects when tissue water is used as an internal concentration reference so as to avoid misinterpreting a morphometric difference as a metabolic difference.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tomasi2010,

title = {Methylphenidate enhances brain activation and deactivation responses to visual attention and working memory tasks in healthy controls.},

author = {D Tomasi and N D Volkow and G J Wang and R Wang and F Telang and E C Caparelli and C Wong and M Jayne and J S Fowler},

url = {https://www.ncbi.nlm.nih.gov/pubmed/21029780},

doi = {10.1016/j.neuroimage.2010.10.060},

issn = {1095-9572 (Electronic); 1053-8119 (Linking)},

year  = {2010},

date = {2010-10-26},

journal = {Neuroimage},

volume = {54},

number = {4},

pages = {3101--3110},

address = {National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. tomasi@bnl.gov},

abstract = {Methylphenidate (MPH) is a stimulant drug that amplifies dopamineric and noradrenergic signaling in the brain, which is believed to underlie its cognition enhancing effects. However, the neurobiological effects by which MPH improves cognition are still poorly understood. Here, functional magnetic resonance imaging (fMRI) was used together with working memory (WM) and visual attention (VA) tasks to test the hypothesis that 20mg oral MPH would increase activation in the dorsal attention network (DAN) and deactivation in the default mode network (DMN) as well as improve performance during cognitive tasks in healthy men. The group of subjects that received MPH (MPH group; N=16) had higher activation than the group of subjects who received no medication (control group: N=16) in DAN regions (parietal and prefrontal cortex, regions increasingly activated with increased cognitive load) and had increased deactivation in the insula and posterior cingulate cortex (regions increasingly deactivated with increased cognitive load) and these effects did not differ for the VA and the WM tasks. These findings provide the first evidence that MPH enhances activation of the DAN whereas it alters DMN deactivation. This suggests that MPH (presumably by amplifying dopamine and noradrenergic signaling) modulates cognition in part through its effects on DAN and DMN.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Caparelli2010,

title = {Simultaneous TMS-fMRI of the Visual Cortex Reveals Functional Network, Even in Absence of Phosphene Sensation.},

author = {E C Caparelli and W Backus and F Telang and G-J Wang and T Maloney and R Z Goldstein and D Anschel and F Henn},

url = {https://www.ncbi.nlm.nih.gov/pubmed/21686319},

doi = {10.2174/1874440001004010100},

issn = {1874-4400 (Electronic); 1874-4400 (Linking)},

year  = {2010},

date = {2010-08-12},

journal = {Open Neuroimag J},

volume = {4},

pages = {100--110},

address = {Medical Department, Brookhaven National Laboratory, Upton, NY, USA.},

abstract = {Phosphene sensation is commonly used to measure cortical excitability during transcranial magnetic stimulation (TMS) of the occipital cortex. However, some individuals lack this perception, and the reason for it is still unknown. In this work, we used functional magnetic resonance imaging (fMRI) to detect brain activation during local TMS of the occipital cortex in twelve healthy subjects. We found that TMS modulated brain activity in areas connected to the stimulation site, even in people unable to see phosphene. However, we observed a trend for a lower blood-oxygenation-level dependent (BOLD) signal, and smaller brain-activation clusters near the stimulated site than in the interconnected brain areas, suggesting that TMS pulse is more effective downstream than at its application site. Furthermore, we noted prominent differences in brain activation/deactivation patterns between subjects who perceived phosphene and those who did not, implying a functional distinction in their neuronal networks that might explain the origin of differences in phosphene generation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Volkow2010,

title = {Effects of low-field magnetic stimulation on brain glucose metabolism.},

author = {Nora D Volkow and Dardo Tomasi and Gene-Jack Wang and Joanna S Fowler and Frank Telang and Ruiliang Wang and Dave Alexoff and Jean Logan and Christopher Wong and Kith Pradhan and Elisabeth C Caparelli and Yeming Ma and Millard Jayne},

url = {https://www.ncbi.nlm.nih.gov/pubmed/20156571},

doi = {10.1016/j.neuroimage.2010.02.015},

issn = {1095-9572 (Electronic); 1053-8119 (Linking)},

year  = {2010},

date = {2010-02-13},

journal = {Neuroimage},

volume = {51},

number = {2},

pages = {623--628},

address = {National Institute on Drug Abuse, Bethesda, MD 20892, USA. nvolkowchar64nida.nih.gov},

abstract = {Echo planar imaging (EPI), the gold standard technique for functional MRI (fMRI), is based on fast magnetic field gradient switching. These time-varying magnetic fields induce electric (E) fields in the brain that could influence neuronal activity; but this has not been tested. Here we assessed the effects of EPI on brain glucose metabolism (marker of brain function) using PET and 18F 2-fluoro-2-deoxy-D-glucose ((18)FDG). Fifteen healthy subjects were in a 4 T magnet during the (18)FDG uptake period twice: with (ON) and without (OFF) EPI gradients pulses along the z-axis (G(z): 23 mT/m; 250 mus rise-time; 920 Hz). The E-field from these EPI pulses is non-homogeneous, increasing linearly from the gradient's isocenter (radial and z directions), which allowed us to assess the correlation between local strength of the E-field and the regional metabolic differences between ON and OFF sessions. Metabolic images were normalized to metabolic activity in the plane positioned at the gradient's isocenter where E=0 for both ON and OFF conditions. Statistical parametric analyses used to identify regions that differed between ON versus OFF (p<0.05, corrected) showed that the relative metabolism was lower in areas at the poles of the brain (inferior occipital and frontal and superior parietal cortices) for ON than for OFF, which was also documented with individual region of interest analysis. Moreover the magnitude of the metabolic decrements was significantly correlated with the estimated strength of E (r=0.68, p<0.0001); the stronger the E-field the larger the decreases. However, we did not detect differences between ON versus OFF conditions on mood ratings nor on absolute whole brain metabolism. This data provides preliminary evidence that EPI sequences may affect neuronal activity and merits further investigation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}