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Reduced Neural Recruitment for Bayesian Adjustment of Inhibitory Control in Methamphetamine Dependence.

ABSTRACT: Delineating the processes that contribute to the progression and maintenance of substance dependence is critical to understanding and preventing addiction. Several previous studies have shown inhibitory control deficits in individuals with stimulant use disorder. We used a Bayesian computational approach to examine potential neural deficiencies in the dynamic predictive processing underlying inhibitory function among recently abstinent methamphetamine-dependent individuals (MDIs), a population at high risk of relapse. Sixty-two MDIs were recruited from a 28-day inpatient treatment program at the San Diego Veterans Affairs Medical Center and compared with 34 healthy control subjects. They completed a stop-signal task during functional magnetic resonance imaging. A Bayesian ideal observer model was used to predict individuals' trial-to-trial probabilistic expectations of inhibitory response, P(stop), to identify group differences specific to Bayesian expectation and prediction error computation. Relative to control subjects, MDIs were more likely to make stop errors on difficult trials and had attenuated slowing following stop errors. MDIs further exhibited reduced sensitivity as measured by the neural tracking of a Bayesian measure of surprise (unsigned prediction error), which was evident across all trials in the left posterior caudate and orbitofrontal cortex (Brodmann area 11), and selectively on stop error trials in the right thalamus and inferior parietal lobule. MDIs are less sensitive to surprising task events, both across trials and upon making commission errors, which may help explain why these individuals may not engage in switching strategy when the environment changes, leading to adverse consequences.

SUBMITTER: Harle KM

PROVIDER: S-EPMC5621759 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Reduced Neural Recruitment for Bayesian Adjustment of Inhibitory Control in Methamphetamine Dependence.

Harlé Katia M KM Zhang Shunan S Ma Ning N Yu Angela J AJ Paulus Martin P MP

Biological psychiatry. Cognitive neuroscience and neuroimaging 20160901 5

Delineating the processes that contribute to the progression and maintenance of substance dependence is critical to understanding and preventing addiction. Several previous studies have shown inhibitory control deficits in individuals with stimulant use disorder. We used a Bayesian computational approach to examine potential neural deficiencies in the dynamic predictive processing underlying inhibitory function among recently abstinent methamphetamine-dependent individuals (MDIs), a population a ...[more]

PMID: 28966988

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Project description:The Neural Systems, Inhibitory Control, and Methamphetamine Dependence study started in 2011 and is currently finishing data collection for its last participants. The study included methamphetamine abusing individuals and healthy control participants aged 18-55 years. Participants who qualified over the telephone were scheduled to visit the London Laboratory at the UCLA Semel Institute for Neuroscience and Human Behavior for the In-Person Screening Phase. The screening procedures, usually scheduled over two visits, determined if participants were eligible to complete the subsequent study visits. Both groups completed identical screening procedures, with the exception of more in-depth drug use questions for the methamphetamine users. After providing written consent, participants completed questionnaires about their mood, medical, psychiatric and drug use history, personality and life experiences. They also provided a urine sample to determine what drugs they recently used and a breath sample to determine the carbon monoxide levels in their system. The drug screen tested for recent methamphetamine, cocaine, opiates/opioids, benzodiazepines, THC and other amphetamines. Methamphetamine participants needed to test positive for methamphetamine at admission. If methamphetamine participants tested positive for any drugs other than methamphetamine or marijuana, and if healthy control participants tested positive for any drugs other than marijuana, they were excluded from the study. Additionally, the urine samples of female participants were tested for pregnancy; pregnant females were also excluded. If no exclusionary criteria were met during the first screening visit, participants completed a second screening visit to ensure they were mentally and physically healthy enough to participate. The second screening visit included a psychiatric diagnostic interview (DSM-IV (SCID-I) for first 500 participants and the MINI International Neuropsychiatric Interview M.I.N.I for the last 50 participants). Additionally, laboratory tests and procedures were completed by the UCLA General Clinical Research Center and interpreted by a study physician. Laboratory tests included vital signs (heart rate--BPM, blood pressure, and respirations), an electrocardiogram (ECG) to record the electrical activity of the heart, and an 18-cc blood sample to perform laboratory tests which included a complete chemistry and metabolic panel, hepatic panel, Hepatitis-C tests, and HIV test. The laboratory tests from this blood sample ensured that participants' liver and kidneys were functioning normally, and that their standard blood counts (red cell, white cell, and salts) were also normal. If a Hepatitis-C (HCV) or HIV test was positive, participants were not allowed to continue in the study and their results were reported to the California State Health Department. Participants deemed eligible to continue in the methamphetamine group participated on an outpatient basis or were admitted to the UCLA Medical Center to participate on an inpatient basis for up to 10 days. Typically, detectable levels of methamphetamine in urinalysis remain for 2-3 days, therefore inpatient days 0-3 served as a "washout period" and the methamphetamine abusing inpatient participants provided daily urine samples to test for recent drug use and pregnancy (female participants only). Outpatient participants were also required to remain abstinent from all drugs except nicotine and marijuana for at least 4 days prior to study sessions. Self-reported abstinence for outpatients was verified by urine toxicology and saliva screening at every visit to UCLA before completion of study procedures. Neurocognitive assessments, about three hours each, typically took place on two separate days. The purpose of the neurocognitive sessions were to assess participants' intellectual and neurocognitive functioning. On either the same day as the neurocognitive testing or on separate days, both methamphetamine abusers and healthy controls were administered a structural MRI to collect information on brain structure.

Project description:Methamphetamine abuse is associated with high rates of aggression but few studies have addressed the contributing neurobiological factors.To quantify aggression, investigate function in the amygdala and prefrontal cortex, and assess relationships between brain function and behavior in methamphetamine-dependent individuals.In a case-control study, aggression and brain activation were compared between methamphetamine-dependent and control participants.Participants were recruited from the general community to an academic research center.Thirty-nine methamphetamine-dependent volunteers (16 women) who were abstinent for 7 to 10 days and 37 drug-free control volunteers (18 women) participated in the study; subsets completed self-report and behavioral measures. Functional magnetic resonance imaging (fMRI) was performed on 25 methamphetamine-dependent and 23 control participants.We measured self-reported and perpetrated aggression and self-reported alexithymia. Brain activation was assessed using fMRI during visual processing of facial affect (affect matching) and symbolic processing (affect labeling), the latter representing an incidental form of emotion regulation.Methamphetamine-dependent participants self-reported more aggression and alexithymia than control participants and escalated perpetrated aggression more following provocation. Alexithymia scores correlated with measures of aggression. During affect matching, fMRI showed no differences between groups in amygdala activation but found lower activation in methamphetamine-dependent than control participants in the bilateral ventral inferior frontal gyrus. During affect labeling, participants recruited the dorsal inferior frontal gyrus and exhibited decreased amygdala activity, consistent with successful emotion regulation; there was no group difference in this effect. The magnitude of decrease in amygdala activity during affect labeling correlated inversely with self-reported aggression in control participants and perpetrated aggression in all participants. Ventral inferior frontal gyrus activation correlated inversely with alexithymia in control participants.Contrary to the hypotheses, methamphetamine-dependent individuals may successfully regulate emotions through incidental means (affect labeling). Instead, low ventral inferior frontal gyrus activity may contribute to heightened aggression by limiting emotional insight.

Project description:BackgroundIn epidemiological studies explanatory variables are frequently subject to measurement error. The aim of this paper is to develop a Bayesian method to correct for measurement error in multiple continuous exposures in individually matched case-control studies. This is a topic that has not been widely investigated. The new method is illustrated using data from an individually matched case-control study of the association between thyroid hormone levels during pregnancy and exposure to perfluorinated acids. The objective of the motivating study was to examine the risk of maternal hypothyroxinemia due to exposure to three perfluorinated acids measured on a continuous scale. Results from the proposed method are compared with those obtained from a naive analysis.MethodsUsing a Bayesian approach, the developed method considers a classical measurement error model for the exposures, as well as the conditional logistic regression likelihood as the disease model, together with a random-effect exposure model. Proper and diffuse prior distributions are assigned, and results from a quality control experiment are used to estimate the perfluorinated acids' measurement error variability. As a result, posterior distributions and 95% credible intervals of the odds ratios are computed. A sensitivity analysis of method's performance in this particular application with different measurement error variability was performed.ResultsThe proposed Bayesian method to correct for measurement error is feasible and can be implemented using statistical software. For the study on perfluorinated acids, a comparison of the inferences which are corrected for measurement error to those which ignore it indicates that little adjustment is manifested for the level of measurement error actually exhibited in the exposures. Nevertheless, a sensitivity analysis shows that more substantial adjustments arise if larger measurement errors are assumed.ConclusionsIn individually matched case-control studies, the use of conditional logistic regression likelihood as a disease model in the presence of measurement error in multiple continuous exposures can be justified by having a random-effect exposure model. The proposed method can be successfully implemented in WinBUGS to correct individually matched case-control studies for several mismeasured continuous exposures under a classical measurement error model.

Dataset Information

Reduced Neural Recruitment for Bayesian Adjustment of Inhibitory Control in Methamphetamine Dependence.

Publications

Reduced Neural Recruitment for Bayesian Adjustment of Inhibitory Control in Methamphetamine Dependence.

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