Contact
Biomedical Research Center251 Bayview Boulevard
Baltimore, MD 21224
Email: BSalmeron@intra.nida.nih.gov
Education
B.A. - Mathematics and Economics, Rice University
M.D. - Baylor College of Medicine
M.A. - Bioethics, Medical College of Wisconsin
Research Interests
Dr. Salmeron received her B.A. in mathematics and economics in 1982 from Rice University. She received her M.D. from Baylor College of Medicine in 1989 and then completed a transitional internship at Baylor before completing a residency in general psychiatry at Massachusetts General Hospital (affiliated with Harvard Medical School) in 1994 where she served as Chief Resident of Inpatient Psychiatry. She then joined the Medical College of Wisconsin staff and later served as Director of Clinical Trials and Psychopharmacology Research at MCW. In 2002, she joined the Neuroimaging Research Branch as a staff clinician. In 2013, she completed an M.A. in Bioethics at the Medical College of Wisconsin. Her research interests include the nature of loss of control over drug use in addiction, predisposing factor versus consequences of addictive disease and ethical issues in clinical research.
Projects:
- The Effects of Expectation on Natural and Drug -Induced Rewards
- Characterization of Phenotypic and Genotypic Regressors for Imaging
- Prenatal Drug Exposure: Effects on the Adolescent Brain and Behavior Development (collaboration with Maureen Black, Ph.D., University of Maryland)
Publications
Selected Publications
2016
Fedota, John R; Matous, Allison L; Salmeron, Betty Jo; Gu, Hong; Ross, Thomas J; Stein, Elliot A
In: Neuropsychopharmacology, vol. 41, no. 10, pp. 2557–2565, 2016, ISSN: 1740-634X (Electronic); 0893-133X (Linking).
@article{Fedota2016,
title = {Insula Demonstrates a Non-Linear Response to Varying Demand for Cognitive Control and Weaker Resting Connectivity With the Executive Control Network in Smokers.},
author = {John R Fedota and Allison L Matous and Betty Jo Salmeron and Hong Gu and Thomas J Ross and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27112116},
doi = {10.1038/npp.2016.62},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2016},
date = {2016-04-26},
journal = {Neuropsychopharmacology},
volume = {41},
number = {10},
pages = {2557--2565},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.},
abstract = {Deficits in cognitive control processes are a primary characteristic of nicotine addiction. However, while network-based connectivity measures of dysfunction have frequently been observed, empirical evidence of task-based dysfunction in these processes has been inconsistent. Here, in a sample of smokers (n=35) and non-smokers (n=21), a previously validated parametric flanker task is employed to characterize addiction-related alterations in responses to varying (ie, high, intermediate, and low) demands for cognitive control. This approach yields a demand-response curve that aims to characterize potential non-linear responses to increased demand for control, including insensitivities or lags in fully activating the cognitive control network. We further used task-based differences in activation between groups as seeds for resting-state analysis of network dysfunction in an effort to more closely link prior inconsistencies in task-related activation with evidence of impaired network connectivity in smokers. For both smokers and non-smokers, neuroimaging results showed similar increases in activation in brain areas associated with cognitive control. However, reduced activation in right insula was seen only in smokers and only when processing intermediate demand for cognitive control. Further, in smokers, this task-modulated right insula showed weaker functional connectivity with the superior frontal gyrus, a component of the task-positive executive control network. These results demonstrate that the neural instantiation of salience attribution in smokers is both more effortful to fully activate and has more difficulty communicating with the exogenous, task-positive, executive control network. Together, these findings further articulate the cognitive control dysfunction associated with smoking and illustrate a specific brain circuit potentially responsible.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Deficits in cognitive control processes are a primary characteristic of nicotine addiction. However, while network-based connectivity measures of dysfunction have frequently been observed, empirical evidence of task-based dysfunction in these processes has been inconsistent. Here, in a sample of smokers (n=35) and non-smokers (n=21), a previously validated parametric flanker task is employed to characterize addiction-related alterations in responses to varying (ie, high, intermediate, and low) demands for cognitive control. This approach yields a demand-response curve that aims to characterize potential non-linear responses to increased demand for control, including insensitivities or lags in fully activating the cognitive control network. We further used task-based differences in activation between groups as seeds for resting-state analysis of network dysfunction in an effort to more closely link prior inconsistencies in task-related activation with evidence of impaired network connectivity in smokers. For both smokers and non-smokers, neuroimaging results showed similar increases in activation in brain areas associated with cognitive control. However, reduced activation in right insula was seen only in smokers and only when processing intermediate demand for cognitive control. Further, in smokers, this task-modulated right insula showed weaker functional connectivity with the superior frontal gyrus, a component of the task-positive executive control network. These results demonstrate that the neural instantiation of salience attribution in smokers is both more effortful to fully activate and has more difficulty communicating with the exogenous, task-positive, executive control network. Together, these findings further articulate the cognitive control dysfunction associated with smoking and illustrate a specific brain circuit potentially responsible.
2015
Hu, Yuzheng; Salmeron, Betty Jo; Gu, Hong; Stein, Elliot A; Yang, Yihong
In: JAMA Psychiatry, vol. 72, no. 6, pp. 584–592, 2015, ISSN: 2168-6238 (Electronic); 2168-622X (Linking).
@article{Hu2015,
title = {Impaired functional connectivity within and between frontostriatal circuits and its association with compulsive drug use and trait impulsivity in cocaine addiction.},
author = {Yuzheng Hu and Betty Jo Salmeron and Hong Gu and Elliot A Stein and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25853901},
doi = {10.1001/jamapsychiatry.2015.1},
issn = {2168-6238 (Electronic); 2168-622X (Linking)},
year = {2015},
date = {2015-06-01},
journal = {JAMA Psychiatry},
volume = {72},
number = {6},
pages = {584--592},
address = {Neuroimaging Research Branch, Intramural Research Program National Institute on Drug Abuse, Baltimore, Maryland.},
abstract = {IMPORTANCE: Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood. OBJECTIVES: To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction. DESIGN, SETTING, AND PARTICIPANTS: A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status. MAIN OUTCOMES AND MEASURES: Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. RESULTS: Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012). CONCLUSIONS AND RELEVANCE: Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
IMPORTANCE: Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood. OBJECTIVES: To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction. DESIGN, SETTING, AND PARTICIPANTS: A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status. MAIN OUTCOMES AND MEASURES: Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. RESULTS: Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012). CONCLUSIONS AND RELEVANCE: Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.
Fedota, John R; Sutherland, Matthew T; Salmeron, Betty Jo; Ross, Thomas J; Hong, Elliot L; Stein, Elliot A
Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers. Journal Article
In: Neuropsychopharmacology, vol. 40, no. 8, pp. 2038–2046, 2015, ISSN: 1740-634X (Electronic); 0893-133X (Linking).
@article{Fedota2015b,
title = {Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers.},
author = {John R Fedota and Matthew T Sutherland and Betty Jo Salmeron and Thomas J Ross and Elliot L Hong and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25742873},
doi = {10.1038/npp.2015.54},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2015},
date = {2015-03-06},
urldate = {2015-03-06},
journal = {Neuropsychopharmacology},
volume = {40},
number = {8},
pages = {2038--2046},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.},
abstract = {Recidivism rates for cigarette smokers following treatment often exceed 80%. Varenicline is the most efficacious pharmacotherapy currently available with cessation rates of 25-35% following a year of treatment. Although the in vivo binding properties are well known, varenicline's neurobiological mechanisms of action are still poorly understood. Varenicline acts as a nicotinic receptor partial agonist or antagonist depending on the presence or absence of nicotine and has been implicated in the reduction of reward signaling more broadly. The current study probed anticipatory reward processing using a revised monetary incentive delay task during fMRI in cohorts of smokers and non-smokers who completed a two-drug, placebo-controlled, double-blind crossover study. All participants underwent ~17 days of order-balanced varenicline and placebo pill administration and were scanned under each condition wearing a transdermal nicotine or placebo patch. Consistent with nicotine's ability to enhance the rewarding properties of nondrug stimuli, acute nicotine administration enhanced activation in response to reward-predicting monetary cues in both smokers and non-smokers. In contrast, varenicline reduced gain magnitude processing, but did so only in smokers. These results suggest that varenicline's downregulation of anticipatory reward processing in smokers, in addition to its previously demonstrated reduction in the negative affect associated with withdrawal, independently and additively alter distinct brain circuits. These effects likely contribute to varenicline's efficacy as a pharmacotherapy for smoking cessation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Recidivism rates for cigarette smokers following treatment often exceed 80%. Varenicline is the most efficacious pharmacotherapy currently available with cessation rates of 25-35% following a year of treatment. Although the in vivo binding properties are well known, varenicline's neurobiological mechanisms of action are still poorly understood. Varenicline acts as a nicotinic receptor partial agonist or antagonist depending on the presence or absence of nicotine and has been implicated in the reduction of reward signaling more broadly. The current study probed anticipatory reward processing using a revised monetary incentive delay task during fMRI in cohorts of smokers and non-smokers who completed a two-drug, placebo-controlled, double-blind crossover study. All participants underwent ~17 days of order-balanced varenicline and placebo pill administration and were scanned under each condition wearing a transdermal nicotine or placebo patch. Consistent with nicotine's ability to enhance the rewarding properties of nondrug stimuli, acute nicotine administration enhanced activation in response to reward-predicting monetary cues in both smokers and non-smokers. In contrast, varenicline reduced gain magnitude processing, but did so only in smokers. These results suggest that varenicline's downregulation of anticipatory reward processing in smokers, in addition to its previously demonstrated reduction in the negative affect associated with withdrawal, independently and additively alter distinct brain circuits. These effects likely contribute to varenicline's efficacy as a pharmacotherapy for smoking cessation.
2014
Rose, Emma Jane; Salmeron, Betty Jo; Ross, Thomas J; Waltz, James; Schweitzer, Julie B; McClure, Samuel M; Stein, Elliot A
Temporal difference error prediction signal dysregulation in cocaine dependence. Journal Article
In: Neuropsychopharmacology, vol. 39, no. 7, pp. 1732–1742, 2014, ISSN: 1740-634X (Electronic); 0893-133X (Linking).
@article{Rose2014,
title = {Temporal difference error prediction signal dysregulation in cocaine dependence.},
author = {Emma Jane Rose and Betty Jo Salmeron and Thomas J Ross and James Waltz and Julie B Schweitzer and Samuel M McClure and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24569319},
doi = {10.1038/npp.2014.21},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2014},
date = {2014-01-29},
urldate = {2014-01-29},
journal = {Neuropsychopharmacology},
volume = {39},
number = {7},
pages = {1732--1742},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD, USA.},
abstract = {Cocaine dependence impacts drug-related, dopamine-dependent reward processing, yet its influence on non-drug reward processing is unclear. Here, we investigated cocaine-mediated effects on reward learning using a natural food reinforcer. Cocaine-dependent subjects (N = 14) and healthy controls (N = 14) learned to associate a visual cue with a juice reward. In subsequent functional imaging sessions they were exposed to trials where juice was received as learned, withheld (negative temporal difference error (NTDE)), or received unexpectedly (positive temporal difference error (PTDE)). Subjects were scanned twice in sessions that were identical, except that cocaine-dependent participants received cocaine or saline 10 min before task onset. In the insula, precentral and postcentral gyri NTDE signals were greater, and PTDE-related function was reduced in cocaine-dependent subjects. Compared with healthy controls, in the cocaine-dependent group PTDE signals were also reduced in medial frontal gyrus and reward-related function, irrespective of predictability, was reduced in the putamen. Group differences in error-related activity were predicted by the time as last self-administered cocaine use, but TDE function was not influenced by acute cocaine. Thus, cocaine dependence seems to engender increased responsiveness to unexpected negative outcomes and reduced sensitivity to positive events in dopaminergic reward regions. Although it remains to be established if these effects are a consequence of or antecedent to cocaine dependence, they likely have implications for the high-cocaine use recidivism rates by contributing to the drive to consume cocaine, perhaps via influence on dopamine-related reward computations. The fact that these effects do not acquiesce to acute cocaine administration might factor in binge-related escalated consumption.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cocaine dependence impacts drug-related, dopamine-dependent reward processing, yet its influence on non-drug reward processing is unclear. Here, we investigated cocaine-mediated effects on reward learning using a natural food reinforcer. Cocaine-dependent subjects (N = 14) and healthy controls (N = 14) learned to associate a visual cue with a juice reward. In subsequent functional imaging sessions they were exposed to trials where juice was received as learned, withheld (negative temporal difference error (NTDE)), or received unexpectedly (positive temporal difference error (PTDE)). Subjects were scanned twice in sessions that were identical, except that cocaine-dependent participants received cocaine or saline 10 min before task onset. In the insula, precentral and postcentral gyri NTDE signals were greater, and PTDE-related function was reduced in cocaine-dependent subjects. Compared with healthy controls, in the cocaine-dependent group PTDE signals were also reduced in medial frontal gyrus and reward-related function, irrespective of predictability, was reduced in the putamen. Group differences in error-related activity were predicted by the time as last self-administered cocaine use, but TDE function was not influenced by acute cocaine. Thus, cocaine dependence seems to engender increased responsiveness to unexpected negative outcomes and reduced sensitivity to positive events in dopaminergic reward regions. Although it remains to be established if these effects are a consequence of or antecedent to cocaine dependence, they likely have implications for the high-cocaine use recidivism rates by contributing to the drive to consume cocaine, perhaps via influence on dopamine-related reward computations. The fact that these effects do not acquiesce to acute cocaine administration might factor in binge-related escalated consumption.
2013
Carroll, Allison J; Sutherland, Matthew T; Salmeron, Betty Jo; Ross, Thomas J; Stein, Elliot A
In: Addict Biol, vol. 20, no. 2, pp. 377–389, 2013, ISSN: 1369-1600 (Electronic); 1355-6215 (Linking).
@article{Carroll2013,
title = {Greater externalizing personality traits predict less error-related insula and anterior cingulate cortex activity in acutely abstinent cigarette smokers.},
author = {Allison J Carroll and Matthew T Sutherland and Betty Jo Salmeron and Thomas J Ross and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24354662},
doi = {10.1111/adb.12118},
issn = {1369-1600 (Electronic); 1355-6215 (Linking)},
year = {2013},
date = {2013-12-13},
journal = {Addict Biol},
volume = {20},
number = {2},
pages = {377--389},
address = {Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD, USA.},
abstract = {Attenuated activity in performance-monitoring brain regions following erroneous actions may contribute to the repetition of maladaptive behaviors such as continued drug use. Externalizing is a broad personality construct characterized by deficient impulse control, vulnerability to addiction and reduced neurobiological indices of error processing. The insula and dorsal anterior cingulate cortex (dACC) are regions critically linked with error processing as well as the perpetuation of cigarette smoking. As such, we examined the interrelations between externalizing tendencies, erroneous task performance, and error-related insula and dACC activity in overnight-deprived smokers (n = 24) and non-smokers (n = 20). Participants completed a self-report measure assessing externalizing tendencies (Externalizing Spectrum Inventory) and a speeded Flanker task during functional magnetic resonance imaging scanning. We observed that higher externalizing tendencies correlated with the occurrence of more performance errors among smokers but not non-smokers. Suggesting a neurobiological contribution to such suboptimal performance among smokers, higher externalizing also predicted less recruitment of the right insula and dACC following error commission. Critically, this error-related activity fully mediated the relationship between externalizing traits and error rates. That is, higher externalizing scores predicted less error-related right insula and dACC activity and, in turn, less error-related activity predicted more errors. Relating such regional activity with a clinically relevant construct, less error-related right insula and dACC responses correlated with higher tobacco craving during abstinence. Given that inadequate error-related neuronal responses may contribute to continued drug use despite negative consequences, these results suggest that externalizing tendencies and/or compromised error processing among subsets of smokers may be relevant factors for smoking cessation success.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Attenuated activity in performance-monitoring brain regions following erroneous actions may contribute to the repetition of maladaptive behaviors such as continued drug use. Externalizing is a broad personality construct characterized by deficient impulse control, vulnerability to addiction and reduced neurobiological indices of error processing. The insula and dorsal anterior cingulate cortex (dACC) are regions critically linked with error processing as well as the perpetuation of cigarette smoking. As such, we examined the interrelations between externalizing tendencies, erroneous task performance, and error-related insula and dACC activity in overnight-deprived smokers (n = 24) and non-smokers (n = 20). Participants completed a self-report measure assessing externalizing tendencies (Externalizing Spectrum Inventory) and a speeded Flanker task during functional magnetic resonance imaging scanning. We observed that higher externalizing tendencies correlated with the occurrence of more performance errors among smokers but not non-smokers. Suggesting a neurobiological contribution to such suboptimal performance among smokers, higher externalizing also predicted less recruitment of the right insula and dACC following error commission. Critically, this error-related activity fully mediated the relationship between externalizing traits and error rates. That is, higher externalizing scores predicted less error-related right insula and dACC activity and, in turn, less error-related activity predicted more errors. Relating such regional activity with a clinically relevant construct, less error-related right insula and dACC responses correlated with higher tobacco craving during abstinence. Given that inadequate error-related neuronal responses may contribute to continued drug use despite negative consequences, these results suggest that externalizing tendencies and/or compromised error processing among subsets of smokers may be relevant factors for smoking cessation success.
2011
Zhang, Xiaochu; Salmeron, Betty Jo; Ross, Thomas J; Gu, Hong; Geng, Xiujuan; Yang, Yihong; Stein, Elliot A
Anatomical differences and network characteristics underlying smoking cue reactivity. Journal Article
In: Neuroimage, vol. 54, no. 1, pp. 131–141, 2011, ISSN: 1095-9572 (Electronic); 1053-8119 (Linking).
@article{Zhang2011,
title = {Anatomical differences and network characteristics underlying smoking cue reactivity.},
author = {Xiaochu Zhang and Betty Jo Salmeron and Thomas J Ross and Hong Gu and Xiujuan Geng and Yihong Yang and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20688176},
doi = {10.1016/j.neuroimage.2010.07.063},
issn = {1095-9572 (Electronic); 1053-8119 (Linking)},
year = {2011},
date = {2011-01-01},
journal = {Neuroimage},
volume = {54},
number = {1},
pages = {131--141},
address = {Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.},
abstract = {A distributed network of brain regions is linked to drug-related cue responding. However, the relationships between smoking cue-induced phasic activity and possible underlying differences in brain structure, tonic neuronal activity and connectivity between these brain areas are as yet unclear. Twenty-two smokers and 22 controls viewed smoking-related and neutral pictures during a functional arterial spin labeling scanning session. T1, resting functional, and diffusion tensor imaging data were also collected. Six brain areas, dorsal lateral prefrontal cortex (dlPFC), dorsal medial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex/cingulate cortex, rostral anterior cingulate cortex (rACC), occipital cortex, and insula/operculum, showed significant smoking cue-elicited activity in smokers when compared with controls and were subjected to secondary analysis for resting state functional connectivity (rsFC), structural, and tonic neuronal activity. rsFC strength between rACC and dlPFC was positively correlated with the cue-elicited activity in dlPFC. Similarly, rsFC strength between dlPFC and dmPFC was positively correlated with the cue-elicited activity in dmPFC while rsFC strength between dmPFC and insula/operculum was negatively correlated with the cue-elicited activity in both dmPFC and insula/operculum, suggesting these brain circuits may facilitate the response to the salient smoking cues. Further, the gray matter density in dlPFC was decreased in smokers and correlated with cue-elicited activity in the same brain area, suggesting a neurobiological mechanism for the impaired cognitive control associated with drug use. Taken together, these results begin to address the underlying neurobiology of smoking cue salience, and may speak to novel treatment strategies and targets for therapeutic interventions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A distributed network of brain regions is linked to drug-related cue responding. However, the relationships between smoking cue-induced phasic activity and possible underlying differences in brain structure, tonic neuronal activity and connectivity between these brain areas are as yet unclear. Twenty-two smokers and 22 controls viewed smoking-related and neutral pictures during a functional arterial spin labeling scanning session. T1, resting functional, and diffusion tensor imaging data were also collected. Six brain areas, dorsal lateral prefrontal cortex (dlPFC), dorsal medial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex/cingulate cortex, rostral anterior cingulate cortex (rACC), occipital cortex, and insula/operculum, showed significant smoking cue-elicited activity in smokers when compared with controls and were subjected to secondary analysis for resting state functional connectivity (rsFC), structural, and tonic neuronal activity. rsFC strength between rACC and dlPFC was positively correlated with the cue-elicited activity in dlPFC. Similarly, rsFC strength between dlPFC and dmPFC was positively correlated with the cue-elicited activity in dmPFC while rsFC strength between dmPFC and insula/operculum was negatively correlated with the cue-elicited activity in both dmPFC and insula/operculum, suggesting these brain circuits may facilitate the response to the salient smoking cues. Further, the gray matter density in dlPFC was decreased in smokers and correlated with cue-elicited activity in the same brain area, suggesting a neurobiological mechanism for the impaired cognitive control associated with drug use. Taken together, these results begin to address the underlying neurobiology of smoking cue salience, and may speak to novel treatment strategies and targets for therapeutic interventions.
2010
Gu, Hong; Salmeron, Betty Jo; Ross, Thomas J; Geng, Xiujuan; Zhan, Wang; Stein, Elliot A; Yang, Yihong
Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity. Journal Article
In: Neuroimage, vol. 53, no. 2, pp. 593–601, 2010, ISSN: 1095-9572 (Electronic); 1053-8119 (Linking).
@article{Gu2010,
title = {Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity.},
author = {Hong Gu and Betty Jo Salmeron and Thomas J Ross and Xiujuan Geng and Wang Zhan and Elliot A Stein and Yihong Yang},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20603217},
doi = {10.1016/j.neuroimage.2010.06.066},
issn = {1095-9572 (Electronic); 1053-8119 (Linking)},
year = {2010},
date = {2010-11-01},
journal = {Neuroimage},
volume = {53},
number = {2},
pages = {593--601},
address = {Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.},
abstract = {Preclinical models have consistently demonstrated the importance of the mesocorticolimbic (MCL) brain reward system in drug dependence, with critical molecular and cellular neuroadaptations identified within these structures following chronic cocaine administration. Cocaine dependent individuals manifest alterations in reward functioning that may relate to changes induced by cocaine or to pre-existing differences related to vulnerability to addiction. The circuit level manifestations of these drug-induced plastic changes and predispositions to drug dependence are poorly understood in preclinical models and virtually unknown in human drug dependence. Using whole-brain resting-state fMRI connectivity analysis with 'seed voxels' placed within individual nodes of the MCL system, we report network-specific functional connectivity strength decreases in cocaine users within distinct circuits of the system, including between ventral tegmental area (VTA) and a region encompassing thalamus/lentiform nucleus/nucleus accumbens, between amygdala and medial prefrontal cortex (mPFC), and between hippocampus and dorsal mPFC. Further, regression analysis on regions showing significant functional connectivity decrease in chronic cocaine users revealed that the circuit strength between VTA and thalamus/lentiform nucleus/nucleus accumbens was negatively correlated with years of cocaine use. This is the first evidence of circuit-related changes in human cocaine dependence and is consistent with the range of cognitive and behavioral disruptions seen in cocaine dependence. As potential circuit level biomarkers of cocaine dependence, these circuit alterations may be usefully applied in treatment development and monitoring treatment outcome.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Preclinical models have consistently demonstrated the importance of the mesocorticolimbic (MCL) brain reward system in drug dependence, with critical molecular and cellular neuroadaptations identified within these structures following chronic cocaine administration. Cocaine dependent individuals manifest alterations in reward functioning that may relate to changes induced by cocaine or to pre-existing differences related to vulnerability to addiction. The circuit level manifestations of these drug-induced plastic changes and predispositions to drug dependence are poorly understood in preclinical models and virtually unknown in human drug dependence. Using whole-brain resting-state fMRI connectivity analysis with 'seed voxels' placed within individual nodes of the MCL system, we report network-specific functional connectivity strength decreases in cocaine users within distinct circuits of the system, including between ventral tegmental area (VTA) and a region encompassing thalamus/lentiform nucleus/nucleus accumbens, between amygdala and medial prefrontal cortex (mPFC), and between hippocampus and dorsal mPFC. Further, regression analysis on regions showing significant functional connectivity decrease in chronic cocaine users revealed that the circuit strength between VTA and thalamus/lentiform nucleus/nucleus accumbens was negatively correlated with years of cocaine use. This is the first evidence of circuit-related changes in human cocaine dependence and is consistent with the range of cognitive and behavioral disruptions seen in cocaine dependence. As potential circuit level biomarkers of cocaine dependence, these circuit alterations may be usefully applied in treatment development and monitoring treatment outcome.
Waltz, James A; Schweitzer, Julie B; Ross, Thomas J; Kurup, Pradeep K; Salmeron, Betty J; Rose, Emma J; Gold, James M; Stein, Elliot A
Abnormal responses to monetary outcomes in cortex, but not in the basal ganglia, in schizophrenia. Journal Article
In: Neuropsychopharmacology, vol. 35, no. 12, pp. 2427–2439, 2010, ISSN: 1740-634X (Electronic); 0893-133X (Linking).
@article{Waltz2010,
title = {Abnormal responses to monetary outcomes in cortex, but not in the basal ganglia, in schizophrenia.},
author = {James A Waltz and Julie B Schweitzer and Thomas J Ross and Pradeep K Kurup and Betty J Salmeron and Emma J Rose and James M Gold and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20720534},
doi = {10.1038/npp.2010.126},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2010},
date = {2010-08-18},
journal = {Neuropsychopharmacology},
volume = {35},
number = {12},
pages = {2427--2439},
address = {Department of Psychiatry, University of Maryland School of Medicine, Maryland Psychiatric Research Center, Baltimore, MD 21228, USA. jwaltz@mprc.umaryland.edu},
abstract = {Psychosis has been associated with aberrant brain activity concurrent with both the anticipation and integration of monetary outcomes. The extent to which abnormal reward-related neural signals can be observed in chronic, medicated patients with schizophrenia (SZ), however, is not clear. In an fMRI study involving 17 chronic outpatients with SZ and 17 matched controls, we used a monetary incentive delay (MID) task, in which different-colored shapes predicted gains, losses, or neutral outcomes. Subjects needed to respond to a target within a time window in order to receive the indicated gain or avoid the indicated loss. Group differences in blood-oxygen-level-dependent responses to cues and outcomes were assessed through voxel-wise whole-brain analyses and regions-of-interest analyses in the neostriatum and prefrontal cortex (PFC). Significant group by outcome valence interactions were observed in the medial and lateral PFC, lateral temporal cortex, and amygdalae, such that controls, but not patients, showed greater activation for gains, relative to losses. In the striatum, neural activity was modulated by outcome magnitude in both groups. Additionally, we found that ratings of negative symptoms in patients correlated with sensitivity to obtained losses in medial PFC, obtained gains in lateral PFC, and anticipated gains in left ventral striatum. Sensitivity to obtained gains in lateral PFC also correlated with positive symptom scores in patients. Our findings of systematic relationships between clinical symptoms and neural responses to stimuli associated with rewards and punishments offer promise that reward-related neural responses may provide sensitive probes of the effectiveness of treatments for negative symptoms.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Psychosis has been associated with aberrant brain activity concurrent with both the anticipation and integration of monetary outcomes. The extent to which abnormal reward-related neural signals can be observed in chronic, medicated patients with schizophrenia (SZ), however, is not clear. In an fMRI study involving 17 chronic outpatients with SZ and 17 matched controls, we used a monetary incentive delay (MID) task, in which different-colored shapes predicted gains, losses, or neutral outcomes. Subjects needed to respond to a target within a time window in order to receive the indicated gain or avoid the indicated loss. Group differences in blood-oxygen-level-dependent responses to cues and outcomes were assessed through voxel-wise whole-brain analyses and regions-of-interest analyses in the neostriatum and prefrontal cortex (PFC). Significant group by outcome valence interactions were observed in the medial and lateral PFC, lateral temporal cortex, and amygdalae, such that controls, but not patients, showed greater activation for gains, relative to losses. In the striatum, neural activity was modulated by outcome magnitude in both groups. Additionally, we found that ratings of negative symptoms in patients correlated with sensitivity to obtained losses in medial PFC, obtained gains in lateral PFC, and anticipated gains in left ventral striatum. Sensitivity to obtained gains in lateral PFC also correlated with positive symptom scores in patients. Our findings of systematic relationships between clinical symptoms and neural responses to stimuli associated with rewards and punishments offer promise that reward-related neural responses may provide sensitive probes of the effectiveness of treatments for negative symptoms.
Zhang, Xiaochu; Salmeron, Betty Jo; Ross, Thomas J; Geng, Xiujuan; Yang, Yihong; Stein, Elliot A
Factors underlying prefrontal and insula structural alterations in smokers. Journal Article
In: Neuroimage, vol. 54, no. 1, pp. 42–48, 2010, ISSN: 1095-9572 (Electronic); 1053-8119 (Linking).
@article{Zhang2010b,
title = {Factors underlying prefrontal and insula structural alterations in smokers.},
author = {Xiaochu Zhang and Betty Jo Salmeron and Thomas J Ross and Xiujuan Geng and Yihong Yang and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20699124},
doi = {10.1016/j.neuroimage.2010.08.008},
issn = {1095-9572 (Electronic); 1053-8119 (Linking)},
year = {2010},
date = {2010-08-10},
journal = {Neuroimage},
volume = {54},
number = {1},
pages = {42--48},
address = {Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.},
abstract = {Based upon previous reports of alterations in white matter integrity and gray matter density in smokers, we examined these markers in a large, well-matched sample of smokers and non-smokers. We further investigated the effect of heavy cigarette exposure by using pack-years and the effects of two relatively stable, highly heritable traits in smokers (Fagerstrom Test of Nicotine Dependence (FTND), a measure of severity of nicotine dependence and Toronto Alexithymia Scale (TAS-20), a stable personality trait related to smoking). Forty-eight nicotine-dependent subjects and 48 matched controls were included in the analyses, with smokers also subdivided into high/low dependence and high/low pack-years smokers. White matter integrity (fractional anisotropy (FA)) and gray matter density (voxel-based morphometry (VBM)) were measured and compared across groups. Gray matter density was lower in left prefrontal cortex (PFC) in high pack-years smokers and was inversely related to pack-years. In contrast, left insular cortex gray matter density was higher in smokers and associated with TAS-20 total score and with difficulty-identifying-feelings factor. Further, the most highly dependent smokers showed lower prefrontal FA, which was negatively correlated with FTND. There was no correlation between pack-years and FTND in our smoker population. These data suggest chronic tobacco use is correlated with prefrontal gray matter damage , while differences in insula gray matter and PFC white matter appear to reflect stable and heritable differences between smokers and non-smokers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Based upon previous reports of alterations in white matter integrity and gray matter density in smokers, we examined these markers in a large, well-matched sample of smokers and non-smokers. We further investigated the effect of heavy cigarette exposure by using pack-years and the effects of two relatively stable, highly heritable traits in smokers (Fagerstrom Test of Nicotine Dependence (FTND), a measure of severity of nicotine dependence and Toronto Alexithymia Scale (TAS-20), a stable personality trait related to smoking). Forty-eight nicotine-dependent subjects and 48 matched controls were included in the analyses, with smokers also subdivided into high/low dependence and high/low pack-years smokers. White matter integrity (fractional anisotropy (FA)) and gray matter density (voxel-based morphometry (VBM)) were measured and compared across groups. Gray matter density was lower in left prefrontal cortex (PFC) in high pack-years smokers and was inversely related to pack-years. In contrast, left insular cortex gray matter density was higher in smokers and associated with TAS-20 total score and with difficulty-identifying-feelings factor. Further, the most highly dependent smokers showed lower prefrontal FA, which was negatively correlated with FTND. There was no correlation between pack-years and FTND in our smoker population. These data suggest chronic tobacco use is correlated with prefrontal gray matter damage , while differences in insula gray matter and PFC white matter appear to reflect stable and heritable differences between smokers and non-smokers.
2009
Waltz, James A; Schweitzer, Julie B; Gold, James M; Kurup, Pradeep K; Ross, Thomas J; Salmeron, Betty Jo; Rose, Emma Jane; McClure, Samuel M; Stein, Elliot A
Patients with schizophrenia have a reduced neural response to both unpredictable and predictable primary reinforcers. Journal Article
In: Neuropsychopharmacology, vol. 34, no. 6, pp. 1567–1577, 2009, ISSN: 1740-634X (Electronic); 0893-133X (Linking).
@article{Waltz2009,
title = {Patients with schizophrenia have a reduced neural response to both unpredictable and predictable primary reinforcers.},
author = {James A Waltz and Julie B Schweitzer and James M Gold and Pradeep K Kurup and Thomas J Ross and Betty Jo Salmeron and Emma Jane Rose and Samuel M McClure and Elliot A Stein},
url = {https://www.ncbi.nlm.nih.gov/pubmed/19052540},
doi = {10.1038/npp.2008.214},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2009},
date = {2009-05-01},
urldate = {2009-05-01},
journal = {Neuropsychopharmacology},
volume = {34},
number = {6},
pages = {1567--1577},
address = {Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228, USA. jwaltz@mprc.umaryland.edu},
abstract = {One prevalent theory of learning states that dopamine neurons signal mismatches between expected and actual outcomes, called temporal difference errors (TDEs). Evidence indicates that dopamine system dysfunction is involved in negative symptoms of schizophrenia (SZ), including avolition and anhedonia. As such, we predicted that brain responses to TDEs in dopamine midbrain nuclei and target areas would be abnormal in SZ. A total of 18 clinically stable patients with chronic SZ and 18 controls participated in an fMRI study, which used a passive conditioning task. In the task, the delivery of a small amount of juice followed a light stimulus by exactly 6 s on approximately 75% of 78 total trials, and was further delayed by 4-7 s on the remaining trials. The delayed juice delivery was designed to elicit the two types of TDE signals, associated with the recognition that a reward was omitted at the expected time, and delivered at an unexpected time. Main effects of TDE valence and group differences in the positive-negative TDE contrast (unexpected juice deliveries-juice omissions) were assessed through whole-brain and regions of interest (ROI) analyses. Main effects of TDE valence were observed for the entire sample in the midbrain, left putamen, left cerebellum, and primary gustatory cortex, bilaterally. Whole-brain analyses revealed group differences in the positive-negative TDE contrast in the right putamen and left precentral gyrus, whereas ROI analyses revealed additional group differences in the midbrain, insula, and parietal operculum, on the right, the putamen and cerebellum, on the left, and the frontal operculum, bilaterally. Further, these group differences were generally driven by attenuated responses in patients to positive TDEs (unexpected juice deliveries), whereas responses to negative TDEs (unexpected juice omissions) were largely intact. Patients also showed reductions in responses to juice deliveries on standard trials, and more blunted reinforcer responses in the left putamen corresponded to higher ratings of avolition. These results provide evidence that SZ patients show abnormal brain responses associated with the processing of a primary reinforcer, which may be a source of motivational deficits.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
One prevalent theory of learning states that dopamine neurons signal mismatches between expected and actual outcomes, called temporal difference errors (TDEs). Evidence indicates that dopamine system dysfunction is involved in negative symptoms of schizophrenia (SZ), including avolition and anhedonia. As such, we predicted that brain responses to TDEs in dopamine midbrain nuclei and target areas would be abnormal in SZ. A total of 18 clinically stable patients with chronic SZ and 18 controls participated in an fMRI study, which used a passive conditioning task. In the task, the delivery of a small amount of juice followed a light stimulus by exactly 6 s on approximately 75% of 78 total trials, and was further delayed by 4-7 s on the remaining trials. The delayed juice delivery was designed to elicit the two types of TDE signals, associated with the recognition that a reward was omitted at the expected time, and delivered at an unexpected time. Main effects of TDE valence and group differences in the positive-negative TDE contrast (unexpected juice deliveries-juice omissions) were assessed through whole-brain and regions of interest (ROI) analyses. Main effects of TDE valence were observed for the entire sample in the midbrain, left putamen, left cerebellum, and primary gustatory cortex, bilaterally. Whole-brain analyses revealed group differences in the positive-negative TDE contrast in the right putamen and left precentral gyrus, whereas ROI analyses revealed additional group differences in the midbrain, insula, and parietal operculum, on the right, the putamen and cerebellum, on the left, and the frontal operculum, bilaterally. Further, these group differences were generally driven by attenuated responses in patients to positive TDEs (unexpected juice deliveries), whereas responses to negative TDEs (unexpected juice omissions) were largely intact. Patients also showed reductions in responses to juice deliveries on standard trials, and more blunted reinforcer responses in the left putamen corresponded to higher ratings of avolition. These results provide evidence that SZ patients show abnormal brain responses associated with the processing of a primary reinforcer, which may be a source of motivational deficits.
