Publications by authors named "Monica L Faulkner"

9 Publications

  • Page 1 of 1

Acute depletion of dopamine precursors in the human brain: effects on functional connectivity and alcohol attentional bias.

Neuropsychopharmacology 2021 Mar 16. Epub 2021 Mar 16.

Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.

Individuals who abuse alcohol often show exaggerated attentional bias (AB) towards alcohol-related cues, which is thought to reflect reward conditioning processes. Rodent studies indicate that dopaminergic pathways play a key role in conditioned responses to reward- and alcohol-associated cues. However, investigation of the dopaminergic circuitry mediating this process in humans remains limited. We hypothesized that depletion of central dopamine levels in adult alcohol drinkers would attenuate AB and that these effects would be mediated by altered function in frontolimbic circuitry. Thirty-four male participants (22-38 years, including both social and heavy drinkers) underwent a two-session, placebo-controlled, double-blind dopamine precursor depletion procedure. At each visit, participants consumed either a balanced amino acid (control) beverage or an amino acid beverage lacking dopamine precursors (order counterbalanced), underwent resting-state fMRI, and completed behavioral testing on three AB tasks: an alcohol dot-probe task, an alcohol attentional blink task, and a task measuring AB to a reward-conditioned cue. Dopamine depletion significantly diminished AB in each behavioral task, with larger effects among subjects reporting higher levels of binge drinking. The depletion procedure significantly decreased resting-state functional connectivity among ventral tegmental area, striatum, amygdala, and prefrontal regions. Beverage-related AB decreases were mediated by decreases in functional connectivity between the fronto-insular cortex and striatum and, for alcohol AB only, between anterior cingulate cortex and amygdala. The results support a substantial role for dopamine in AB, and suggest specific dopamine-modulated functional connections between frontal, limbic, striatal, and brainstem regions mediate general reward AB versus alcohol AB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-021-00993-9DOI Listing
March 2021

A neuroimaging investigation into the role of peripheral metabolic biomarkers in the anticipation of reward in alcohol use.

Drug Alcohol Depend 2021 Apr 16;221:108638. Epub 2021 Feb 16.

Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, MD 20814, USA; Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI 02903, USA; Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA; Department of Neuroscience, Georgetown University Medical Center, Washington DC 20057, USA. Electronic address:

Background: The relationship between alcohol use and metabolism has focused on the effects of alcohol use on metabolic factors. Metabolic factors, such as triglycerides, cholesterol, and glucose, have been shown to be associated with increased risk for heavy alcohol consumption and alcohol use disorder (AUD). It's been suggested that changes in metabolic factors may play a role in reward seeking behaviors and pathways. Studies on feeding behavior and obesity revealed the role of triglycerides in neural response to food cues in neurocircuitry regulating reward and feeding behaviors. This study aimed to explore the relationship of peripheral metabolism, alcohol use, and reward processing in individuals that use alcohol.

Methods: Ninety participants from a previously collected dataset were included in the analysis. Participants were treatment seeking, detoxified individuals with AUD and healthy individuals without AUD, with the following metabolic biomarkers: triglyceride, glucose, high- and low-density cholesterol, and HbA1c levels. Participants completed a neuroimaging version of the Monetary Incentive Delay task (MID).

Results: Correlations on peripheral metabolic biomarkers, alcohol use, and neural activity during reward anticipation and outcome during the MID task were not significant. Mediation models revealed triglycerides and high-density cholesterol had significant effects on left anterior insula during anticipation of potential monetary loss and this effect was not mediated by alcohol use.

Conclusion: Limbic recruitment by anticipation of monetary rewards revealed an independent relationship with peripheral metabolism and was not affected by individual differences in alcohol use, despite the effects of alcohol use on metabolic markers and reward processing neural circuitry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.drugalcdep.2021.108638DOI Listing
April 2021

Changes in Hemodynamic Response Function Resulting From Chronic Alcohol Consumption.

Alcohol Clin Exp Res 2020 05 27;44(5):1099-1111. Epub 2020 Apr 27.

Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: Functional MRI (fMRI) task-related analyses rely on an estimate of the brain's hemodynamic response function (HRF) to model the brain's response to events. Although changes in the HRF have been found after acute alcohol administration, the effects of heavy chronic alcohol consumption on the HRF have not been explored, and the potential benefits or pitfalls of estimating each individual's HRF on fMRI analyses of chronic alcohol use disorder (AUD) are not known.

Methods: Participants with AUD and controls (CTL) received structural, functional, and vascular scans. During fMRI, participants were cued to tap their fingers, and averaged responses were extracted from the motor cortex. Curve fitting on these HRFs modeled them as a difference between 2 gamma distributions, and the temporal occurrence of the main peak and undershoot of the HRF was computed from the mean of the first and second gamma distributions, respectively.

Results: ANOVA and regression analyses found that the timing of the HRF undershoot increased significantly as a function of total lifetime drinking. Although gray matter volume in the motor cortex decreased with lifetime drinking, this was not sufficient to explain undershoot timing shifts, and vascular factors measured in the motor cortex did not differ among groups. Comparison of random-effects analyses using custom-fitted and canonical HRFs for CTL and AUD groups showed better results throughout the brain for custom-fitted versus canonical HRFs for CTL subjects. For AUD subjects, the same was true except for the basal ganglia.

Conclusions: These findings suggest that excessive alcohol consumption is associated with changes in the HRF undershoot. HRF changes could provide a possible biomarker for the effects of lifetime drinking on brain function. Changes in HRF topography affect fMRI activation measures, and subject-specific HRFs generally improve fMRI activation results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acer.14327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233451PMC
May 2020

Contingency awareness, aging, and the parietal lobe.

Neurobiol Aging 2020 07 4;91:125-135. Epub 2020 Mar 4.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Contingency awareness is thought to rely on an intact medial temporal lobe and also appears to be a function of age, as older subjects tend to be less aware. The current investigation used functional magnetic resonance imaging, transcranial direct current stimulation, and eyeblink classical conditioning to study brain processes related to contingency awareness as a function of age. Older adults were significantly less aware of the relationship between the tone-airpuff pairings than younger adults. Greater right parietal functional magnetic resonance imaging activation was associated with higher levels of contingency awareness for younger and older subjects. Cathodal transcranial direct current stimulation over the right parietal lobe led to lower levels of awareness in younger subjects without disrupting conditioned responses. Older adults exhibited hyperactivations in the parietal and medial temporal lobes, despite showing no conditioning deficits. These findings strongly support the idea that the parietal cortex serves as a substrate for contingency awareness and that age-related disruption of this region is sufficient to impair awareness, which may be a manifestation of some form of naturally occurring age-related neglect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurobiolaging.2020.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953809PMC
July 2020

Neural Substrates Underlying Eyeblink Classical Conditioning in Adults With Alcohol Use Disorders.

Alcohol Clin Exp Res 2020 03 16;44(3):620-631. Epub 2020 Feb 16.

From the Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: Excessive alcohol consumption produces changes in the brain that often lead to cognitive impairments. One fundamental form of learning, eyeblink classical conditioning (EBC), has been widely used to study the neurobiology of learning and memory. Participants with alcohol use disorders (AUD) have consistently shown a behavioral deficit in EBC. The present functional magnetic resonance imaging (fMRI) study is the first to examine brain function during conditioning in abstinent AUD participants and healthy participants.

Methods: AUD participants met DSM-IV criteria for alcohol dependence, had at least a 10-year history of heavy drinking, and were abstinent from alcohol for at least 30 days. During fMRI, participants received auditory tones that predicted the occurrence of corneal airpuffs. Anticipatory eyeblink responses to these tones were monitored during the experiment to assess learning-related changes.

Results: Behavioral results indicate that AUD participants showed significant conditioning deficits and that their history of lifetime drinks corresponded to these deficits. Despite this learning impairment, AUD participants showed hyperactivation in several key cerebellar structures (including lobule VI) during conditioning. For all participants, history of lifetime drinks corresponded with their lobule VI activity.

Conclusions: These findings suggest that excessive alcohol consumption is associated with abnormal cerebellar hyperactivation and conditioning impairments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acer.14288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894057PMC
March 2020

Ghrelin: From a gut hormone to a potential therapeutic target for alcohol use disorder.

Physiol Behav 2019 05 7;204:49-57. Epub 2019 Feb 7.

Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research and National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Bethesda, MD, USA; Center on Compulsive Behaviors, National Institutes of Health, Bethesda, MD, USA; Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA. Electronic address:

Alcohol use disorder (AUD) is a leading cause of morbidity and mortality worldwide. However, treatment options, including pharmacotherapies, are limited in number and efficacy. Accumulating evidence suggests that elements of the gut-brain axis, such as neuroendocrine pathways and gut microbiome, are involved in the pathophysiology of AUD and, therefore, may be investigated as potential therapeutic targets. One pathway that has begun to be examined in this regard is the ghrelin system. Here, we review preclinical and clinical data on the relationship between ghrelin and alcohol-related outcomes, with a special focus on the role of the ghrelin system as a treatment target for AUD. Observational studies indicate that endogenous ghrelin levels are positively associated with craving for alcohol, subjective responses to alcohol, and brain activity in response to alcohol cues. Knockout rodent models suggest that deletion of the ghrelin peptide or receptor gene leads to reduction of alcohol intake and other alcohol-related outcomes. Different research groups have found that ghrelin administration increases, while ghrelin receptor (GHS-R1a) blockade reduces alcohol intake and other alcohol-related outcomes in rodents. Ghrelin administration in heavy-drinking individuals increases alcohol craving and self-administration and modulates brain activity in response to alcohol reward anticipation. PF-5190457, a GHS-R1a blocker, has been shown to be safe and tolerable when co-administered with alcohol. Furthermore, preliminary results suggest that this compound may reduce cue-elicited craving for alcohol in heavy-drinking individuals - a finding in need of replication. Collectively, the existing literature supports further examination of the ghrelin system as a therapeutic target for AUD. More research is also needed to understand the biobehavioral and molecular mechanisms underlying ghrelin's functions and to examine different interventional approaches to target the ghrelin system for AUD treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.physbeh.2019.02.008DOI Listing
May 2019

Attentional bias for nondrug reward is magnified in addiction.

Exp Clin Psychopharmacol 2013 Dec 14;21(6):499-506. Epub 2013 Oct 14.

Department of Neurology.

Attentional biases for drug-related stimuli play a prominent role in addiction, predicting treatment outcomes. Attentional biases also develop for stimuli that have been paired with nondrug rewards in adults without a history of addiction, the magnitude of which is predicted by visual working-memory capacity and impulsiveness. We tested the hypothesis that addiction is associated with an increased attentional bias for nondrug (monetary) reward relative to that of healthy controls, and that this bias is related to working-memory impairments and increased impulsiveness. Seventeen patients receiving methadone-maintenance treatment for opioid dependence and 17 healthy controls participated. Impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11; Patton, Stanford, & Barratt, 1995), visual working-memory capacity was measured as the ability to recognize briefly presented color stimuli, and attentional bias was measured as the magnitude of response time slowing caused by irrelevant but previously reward-associated distractors in a visual-search task. The results showed that attention was biased toward the distractors across all participants, replicating previous findings. It is important to note, this bias was significantly greater in the patients than in the controls and was negatively correlated with visual working-memory capacity. Patients were also significantly more impulsive than controls as a group. Our findings demonstrate that patients in treatment for addiction experience greater difficulty ignoring stimuli associated with nondrug reward. This nonspecific reward-related bias could mediate the distracting quality of drug-related stimuli previously observed in addiction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/a0034575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934504PMC
December 2013

An fMRI investigation of cerebellar function during verbal working memory in methadone maintenance patients.

Cerebellum 2012 Mar;11(1):300-10

Department of Neurology, Division of Cognitive Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Working memory is impaired in opioid-dependent individuals, yet the neural underpinnings of working memory in this population are largely unknown. Previous studies in healthy adults have demonstrated that working memory is supported by a network of brain regions that includes a cerebro-cerebellar circuit. The cerebellum, in particular, may be important for inner speech mechanisms that assist verbal working memory. This study used functional magnetic resonance imaging to examine brain activity associated with working memory in five opioid-dependent, methadone-maintained patients and five matched, healthy controls. An item recognition task was administered in two conditions: (1) a low working memory load "match" condition in which participants determined whether target letters presented at the beginning of the trial matched a probe item, and (2) a high working memory load "manipulation" condition in which participants counted two alphabetical letters forward of each of the targets and determined whether either of these new items matched a probe item. Response times and accuracy scores were not significantly different between the groups. FMRI analyses indicated that, in association with higher working memory load ("manipulation" condition), the patient group exhibited hyperactivity in the superior and inferior cerebellum and amygdala relative to that of controls. At a more liberal statistical threshold, patients exhibited hypoactivity in the left prefrontal and medial frontal/pre-SMA regions. These results indicate that verbal working memory in opioid-dependent individuals involves a disrupted cerebro-cerebellar circuit and shed light on the neuroanatomical basis of working memory impairments in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12311-011-0311-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248617PMC
March 2012

The effects of aging in delay and trace human eyeblink conditioning.

Psychol Aging 2010 Sep;25(3):684-90

Johns Hopkins University School of Medicine, Department of Neurology, Division of Cognitive Neuroscience, Baltimore, MD 21205, USA.

Normal aging has been shown to impact performance during human eyeblink classical conditioning, with older adults showing lower conditioning levels than younger adults. Previous findings showed younger adults can acquire both delay and trace conditioning concurrently, but it is not known whether older adults can learn under the same conditions. Present results indicated older adults did not produce a significantly greater number of conditioned responses during acquisition, but their ability to time eyeblink responses prior to the unconditioned stimulus was preserved. The decline in eyeblink conditioning that typically accompanies aging has been extended to concurrent presentations of delay and trace conditioning trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/a0017978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944000PMC
September 2010