Relationship between central autonomic effective connectivity and heart rate variability: A Resting-state fMRI dynamic causal modeling study.

The central autonomic network (CAN) serves as a regulatory hub with top-down regulatory control and integration of bottom-up physiological feedback via the autonomic nervous system. Heart rate variability (HRV)-the time variance of the heart's beat-to-beat intervals-is an index of the CAN's affective and behavioral regulatory capacity. Although neural functional connectivities that are associated with HRV and CAN have been well studied, no published report to date has studied effective (directional) connectivities (EC) that are associated with HRV and CAN. Better understanding of neural EC in the brain has the potential to improve our understanding of how the CAN sub-regions regulate HRV. To begin to address this knowledge gap, we employed resting-state functional magnetic resonance imaging and dynamic causal modeling (DCM) with parametric empirical Bayes analyses in 34 healthy adults (19 females; mean age= 32.68 years [SD= 14.09], age range 18-68 years) to examine the bottom-up and top-down neural circuits associated with HRV. Throughout the whole brain, we identified 12 regions associated with HRV. DCM analyses revealed that the ECs from the right amygdala to the anterior cingulate cortex and to the ventrolateral prefrontal cortex had a negative linear relationship with HRV and a positive linear relationship with heart rate. These findings suggest that ECs from the amygdala to the prefrontal cortex may represent a neural circuit associated with regulation of cardiodynamics.

Effect of scanning duration and sample size on reliability in resting state fMRI dynamic causal modeling analysis.

Despite its widespread use, resting-state functional magnetic resonance imaging (rsfMRI) has been criticized for low test-retest reliability. To improve reliability, researchers have recommended using extended scanning durations, increased sample size, and advanced brain connectivity techniques. However, longer scanning runs and larger sample sizes may come with practical challenges and burdens, especially in rare populations. Here we tested if an advanced brain connectivity technique, dynamic causal modeling (DCM), can improve reliability of fMRI effective connectivity (EC) metrics to acceptable levels without extremely long run durations or extremely large samples. Specifically, we employed DCM for EC analysis on rsfMRI data from the Human Connectome Project. To avoid bias, we assessed four distinct DCMs and gradually increased sample sizes in a randomized manner across ten permutations. We employed pseudo true positive and pseudo false positive rates to assess the efficacy of shorter run durations (3.6, 7.2, 10.8, 14.4 min) in replicating the outcomes of the longest scanning duration (28.8 min) when the sample size was fixed at the largest (n = 160 subjects). Similarly, we assessed the efficacy of smaller sample sizes (n = 10, 20, …, 150 subjects) in replicating the outcomes of the largest sample (n = 160 subjects) when the scanning duration was fixed at the longest (28.8 min). Our results revealed that the pseudo false positive rate was below 0.05 for all the analyses. After the scanning duration reached 10.8 min, which yielded a pseudo true positive rate of 92%, further extensions in run time showed no improvements in pseudo true positive rate. Expanding the sample size led to enhanced pseudo true positive rate outcomes, with a plateau at n = 70 subjects for the targeted top one-half of the largest ECs in the reference sample, regardless of whether the longest run duration (28.8 min) or the viable run duration (10.8 min) was employed. Encouragingly, smaller sample sizes exhibited pseudo true positive rates of approximately 80% for n = 20, and 90% for n = 40 subjects. These data suggest that advanced DCM analysis may be a viable option to attain reliable metrics of EC when larger sample sizes or run times are not feasible.

Geostatistical modeling of positive-definite matrices: An application to diffusion tensor imaging.

Geostatistical modeling for continuous point-referenced data has extensively been applied to neuroimaging because it produces efficient and valid statistical inference. However, diffusion tensor imaging (DTI), a neuroimaging technique characterizing the brain's anatomical structure, produces a positive-definite (p.d.) matrix for each voxel. Currently, only a few geostatistical models for p.d. matrices have been proposed because introducing spatial dependence among p.d. matrices properly is challenging. In this paper, we use the spatial Wishart process, a spatial stochastic process (random field), where each p.d. matrix-variate random variable marginally follows a Wishart distribution, and spatial dependence between random matrices is induced by latent Gaussian processes. This process is valid on an uncountable collection of spatial locations and is almost-surely continuous, leading to a reasonable way of modeling spatial dependence. Motivated by a DTI data set of cocaine users, we propose a spatial matrix-variate regression model based on the spatial Wishart process. A problematic issue is that the spatial Wishart process has no closed-form density function. Hence, we propose an approximation method to obtain a feasible Cholesky decomposition model, which we show to be asymptotically equivalent to the spatial Wishart process model. A local likelihood approximation method is also applied to achieve fast computation. The simulation studies and real data application demonstrate that the Cholesky decomposition process model produces reliable inference and improved performance, compared to other methods.

Development and Feasibility Study of an Addiction-Focused Phenotyping Assessment Battery.

BACKGROUND AND OBJECTIVES: Current methods of classifying individuals with substance use disorder (SUD) result in vast heterogeneity among persons within a given diagnosis. These approaches, while clinically allowing for distinctions between patient groups, are less than ideal when attempting to recruit a neurobehaviorally defined subset of subjects into clinical trials. To address this gap, alternative strategies have been proposed, including behavioral phenotyping. The NIDA Phenotyping Assessment Battery (PhAB) is a modular package of assessments and neurocognitive tasks that was developed for use in clinical trials. The goal of the present study is to assess the feasibility of the NIDA PhAB with regard to ease of administration and time burden. METHODS: Healthy controls, persons with cocaine use disorder (CocUD), opioid use disorder (OUD), cannabis use disorder (CanUD), and combined opioid and cocaine use disorder (OCUD) were recruited from various sources (N = 595). Participants completed screening and one to three assessment visits. Time to complete the measures was recorded and a satisfaction interview was administered. RESULTS: Of the participants enrolled, 381 were deemed eligible. The majority of eligible participants (83%) completed all assessments. The average completion time was 3 hours. High participant satisfaction ratings were noted, with over 90% of participants endorsing a willingness to participate in a similar study and recommend the study to others. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These findings corroborate the ease with which the PhAB may be easily incorporated into a study assessment visit without undue participant burden. The PhAB is an efficient method for behavioral phenotyping in addiction clinical trials. (Am J Addict 2021;00:00-00).

The 5-HT2A Receptor (5-HT2AR) Regulates Impulsive Action and Cocaine Cue Reactivity in Male Sprague-Dawley Rats.

Impulsivity and the attentional orienting response to cocaine-associated cues (cue reactivity) promote relapse in cocaine-use disorder (CUD). A time-dependent escalation of cue reactivity (incubation) occurs during extended, forced abstinence from cocaine self-administration in rats. The investigational serotonin (5-HT) 5-HT2A receptor (5-HT2AR) antagonist/inverse agonist M100907 suppresses impulsive action, or the inability to withhold premature responses, and cocaine-seeking behaviors. The present preclinical study was designed to establish the potential for repurposing the Food and Drug Administration-approved selective 5-HT2AR antagonist/inverse agonist pimavanserin as a therapeutic agent to forestall relapse vulnerability in CUD. In male Sprague-Dawley rats, pimavanserin suppressed impulsive action (premature responses) measured in the 1-choice serial reaction time (1-CSRT) task, similarly to M100907. We also used the 1-CSRT task to establish baseline levels of impulsive action before cocaine self-administration and evaluation of cue reactivity (lever presses reinforced by the discrete cue complex previously paired with cocaine delivery). We observed an incubation of cocaine cue reactivity between day 1 and day 30 of forced abstinence from cocaine self-administration. Baseline levels of impulsive action predicted incubated levels of cocaine cue reactivity in late abstinence. We also found that baseline impulsive action predicted the effectiveness of pimavanserin to suppress incubated cue reactivity in late abstinence from cocaine self-administration at doses that were ineffective in early abstinence. These data suggest that integration of clinical measures of impulsive action may inform refined, personalized pharmacotherapeutic intervention for the treatment of relapse vulnerability in CUD.

Cannabis Use as a Risk Factor for Takotsubo (Stress) Cardiomyopathy: Exploring the Evidence from Brain-Heart Link.

PURPOSE OF REVIEW: Recently, an association between cannabis use and Takotsubo (stress) cardiomyopathy (TTC) has been shown. With the current trend of legalization of cannabis, it is important to understand brain effects of cannabis use that could lead to cardiac disease, such as TTC. Here we review recent brain imaging studies in order to search for the evidence supporting the association between cannabis use, stress, and TTC. RECENT FINDINGS: There exist brain imaging studies showing similar findings across TTC, stress, and cannabis use. These similar findings are mainly centered on a key central autonomic network region amygdala, i.e., amygdala hyperactivity/hyperconnectivity when exposed to challenge, stress, or negative stimuli. This similarity supports a close association among cannabis use, stress, and TTC. Amygdala-centered neuronal circuits could underlie cannabis use as risk factor to TTC. Based on the findings, several directions for future studies are proposed.

Impulsivity and decision making in older and younger cocaine-dependent participants: A preliminary study.

BACKGROUND AND OBJECTIVES: Substance misuse is increasing in the older population, which may have differing effects on behavior compared to younger substance participants. Differences in trait and state impulsivity were assessed in younger and older cocaine-dependent participants. METHODS: Thirty-one younger cocaine-dependent participants (n = 31) and 21 older cocaine-dependent participants (n = 21) were assessed using the Barrett Impulsiveness Scale-11 and the Immediate Memory Task. RESULTS: Younger participants showed higher trait impulsivity than older participants (p =.027). However, older participants demonstrated higher state impulsivity than younger participants (p =.018). CONCLUSION: Higher state impulsivity in older cocaine participants suggests that cocaine use may have accelerating effects on the aging brain. SCIENTIFIC SIGNIFICANCE: This preliminary study adds the limited research on how cocaine use affects normal aging. Current treatments are based on younger adults, therefore the needs of older adults should be taken into consideration and studied more. (Am J Addict 2018;27:557-559).

Rapid-Response Impulsivity Predicts Depression and Posttraumatic Stress Disorder Symptomatology at 1-Year Follow-Up in Blast-Exposed Service Members.

OBJECTIVE: To determine if elevated rapid-response impulsivity after blast exposure (as a putative marker of ventral prefrontal cortex [vPFC] damage) is predictive of future elevated affective symptomatology in blast-exposed service members. DESIGN: Longitudinal design with neurocognitive testing at initial assessment and 1-year follow-up assessment of psychiatric symptomatology by telephone interview. SETTING: Veterans Administration medical centers and postdeployment assessment centers at military bases. PARTICIPANTS: Blast-exposed U.S. military personnel (N=84) ages 19 to 39 years old. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Center for Epidemiological Studies-Depression Scale (CES-D) scores, Posttraumatic Stress Disorder Checklist Version 5 (PCL-5) scores, and Alcohol Use Disorders Identification Test-C (AUDIT-C) scores at the 12-month follow-up telephone interview. RESULTS: After controlling for age and affective symptom scores reported at the initial assessment, commission errors on the Continuous Performance Test-II of the initial assessment were predictive of higher symptom scores on the CES-D and PCL-5 at follow-up, but were not predictive of AUDIT-C scores. CONCLUSIONS: Elevated rapid-response impulsivity, as a behavioral marker of reduced top-down frontocortical control, is a risk factor for elevated mood and posttraumatic stress disorder symptoms over time in blast-exposed individuals. Future longitudinal studies with predeployment neurobehavioral testing could enable attribution of this relation to blast-related vPFC damage.

Liver transplantation significantly improves global functioning and cerebral processing.

The functional basis of cognitive and quality of life changes after liver transplant is unclear. We aimed to evaluate the neurometabolic and functional brain changes as modulators of cognition and quality of life after transplant in patients with cirrhosis who were with/without pretransplant cognitive impairment and hepatic encephalopathy (HE). Patients with cirrhosis underwent detailed cognitive and quality of life assessment at enrollment and 6 months after transplant. A subset underwent brain magnetic resonance imaging (functional magnetic resonance imaging [fMRI], diffusion tensor imaging [DTI], and magnetic resonance spectroscopy [MRS]) before and after transplant. Changes before and after transplant were analyzed in all patients and by dividing groups in those with/without pretransplant cognitive impairment or with/without pretransplant HE. MRS evaluated ammonia-related metabolites; fMRI studied brain activation for correct lure inhibition on the inhibitory control test; and DTI studied white matter integrity. Sixty-six patients (mean Model for End-Stage Liver Disease score, 21.8; 38 HE patients and 24 cognitively impaired [CI] patients) were enrolled. Quality of life was significantly worse in CI and HE groups before transplant, which improved to a lesser extent in those with prior cognitive impairment. In the entire group after transplant, there was (1) significantly lower brain activation needed for lure inhibition (shown on fMRI); (2) reversal of pretransplant ammonia-associated changes (shown on MRS); and (3) improved white matter integrity (shown on DTI). Importantly, study findings suggest that pretransplant cognitive impairment serves as a marker for clinical outcomes. Regardless of pretransplant history of HE, it was the pretransplant cognitive impairment that was predictive of both posttransplant cognitive and psychosocial outcomes. Therefore, when working with patients and their families, a clinician may rely on the pretransplant cognitive profile to develop expectations regarding posttransplant neurobehavioral recovery. We conclude that functional brain changes after liver transplant depend on pretransplant cognitive impairment and are ultimately linked with posttransplant cognition and quality of life in cirrhosis. Liver Transplantation 22 1379-1390 2016 AASLD.

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding.

Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Researchers compared 12-lead ECGs from 97 treatment-seeking cocaine-dependent patients, with ECG parameters from 8,513 non-cocaine-using control patients from the Atherosclerosis Risk in Communities study. After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use.

The etiology of cirrhosis is a strong determinant of brain reserve: A multimodal magnetic resonance imaging study.

Poor brain reserve in alcoholic cirrhosis could worsen insight regarding disease severity and increase the patients' vulnerability toward further deterioration. The aim of this study was to analyze brain reserve in abstinent alcoholic cirrhotic (Alc) patients compared to nonalcoholic cirrhotic (Nalc) patients in the context of hepatic encephalopathy (HE) and to evaluate relative change in brain reserve between groups over time and before and after elective transjugular intrahepatic portosystemic shunt (TIPS) placement. The cross-sectional study included 46 Alc and 102 Nalc outpatients with or without HE. Cognitive tests were followed by magnetic resonance imaging (MRI), including proton magnetic resonance spectroscopy (1 H-MRS), diffusion tensor imaging, and T1-weighted imaging. The prospective study included 1H-MRS on a subset of 10 patients before and after TIPS placement. Another subset of 26 patients underwent (1) H-MRS at least 1 year apart. For the cross-sectional study, Alc patients were worse on cognitive tests than Nalc patients. MRI results suggest a greater effect of hyperammonemia, brain edema, and significantly higher cortical damage in Alc as compared to Nalc patients. The effect of HE status on cognitive tests and brain reserve was more marked in the Nalc than in the Alc group. For the TIPS study, Nalc patients showed a greater adverse relative change after TIPS compared to the Alc group. At 1-year follow-up, both groups remained stable between the 2 visits. However, Alc patients continued to show poor brain reserve compared to Nalc patients over time. In conclusion, Alc patients, despite abstinence, have a poor brain reserve, whereas Nalc patients have a greater potential for brain reserve deterioration after HE and TIPS. Information regarding the brain reserve in cirrhosis could assist medical teams to refine their communication and monitoring strategies for different etiologies.

Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder.

The oxytocin receptor is important in several domains of social behavior, and administration of oxytocin modulates social responding in several mammalian species, including humans. Oxytocin has both therapeutic and scientific potential for elucidating the neural and behavioral mechanisms governing social behavior. In the present study, operationally-defined aggressive behavior of six males with Antisocial Personality Disorder (ASPD) was measured following acute intranasal oxytocin dosing (12, 24, and 48 international units) and placebo, using a well-validated laboratory task of human aggression (Point-Subtraction Aggression Paradigm, or PSAP). The PSAP provides participants with concurrently available monetary-earning and operationally-defined aggressive response options, maintained by fixed ratio schedules of consequences. Shifts in response rates and inter-response time (IRT) distributions were observed on the aggressive response option following oxytocin doses, relative to placebo. Few changes were observed in monetary-reinforced responding. However, across participants the direction and magnitude of changes in aggressive responding were not systematically related to dose. No trends were observed between psychometric or physiological data and oxytocin dosing or aggressive behavior. While this report is to our knowledge the first to examine the acute effects of oxytocin in this population at high risk for violence and other forms of antisocial behavior, several limitations in the experimental design and the results cast the study as a preliminary report. Strategies for more extensive future projects are discussed.

Stochastic dynamic causal modeling of working memory connections in cocaine dependence.

Although reduced working memory brain activation has been reported in several brain regions of cocaine-dependent subjects compared with controls, very little is known about whether there is altered connectivity of working memory pathways in cocaine dependence. This study addresses this issue by using functional magnetic resonance imaging-based stochastic dynamic causal modeling (DCM) analysis to study the effective connectivity of 19 cocaine-dependent subjects and 14 healthy controls while performing a working memory task. Stochastic DCM is an advanced method that has recently been implemented in SPM8 that can obtain improved estimates, relative to deterministic DCM, of hidden neuronal causes before convolution with the hemodynamic response. Thus, stochastic DCM may be less influenced by the confounding effects of variations in blood oxygen level-dependent response caused by disease or drugs. Based on the significant regional activation common to both groups and consistent with previous working memory activation studies, seven regions of interest were chosen as nodes for DCM analyses. Bayesian family level inference, Bayesian model selection analyses, and Bayesian model averaging (BMA) were conducted. BMA showed that the cocaine-dependent subjects had large differences compared with the control subjects in the strengths of prefrontal-striatal modulatory (B matrix) DCM parameters. These findings are consistent with altered cortical-striatal networks that may be related to reduced dopamine function in cocaine dependence. As far as we are aware, this is the first between-group DCM study using stochastic methodology.

New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity.

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.

Using a single screening question for depressive symptoms in patients with acute coronary syndrome.

BACKGROUND: Despite the prevalence of depressive symptoms and increased risk for future cardiovascular events, depressive symptoms frequently go underrecognized in patients hospitalized for acute coronary syndrome (ACS). Identifying an effective approach to depressive symptom screening is imperative in this population. OBJECTIVE: The purpose of this cross-sectional study was to explore the agreement between Beck Depression Inventory-II (BDI-II) scores and a single screening question for depressive symptoms in 1122 patients hospitalized for ACS. METHODS: Independent-samples t tests and χ tests were used to compare the groups with BDI-II scores of 14 or higher and lower than 14. Three separate agreement analyses were conducted using categorized BDI-II scores (≥14, ≥20, and ≥29). Agreement of the BDI-II categories with the responses to the single screening question was assessed with the simple κ statistic. Sensitivity and specificity were calculated using the BDI-II categories as the criterion standards for depressive symptom screening. RESULTS: The agreement analysis revealed a moderate level of agreement (κ coefficient = 0.42) between the BDI-II scores of 14 or higher and the single screening question. Of the participants who reported a BDI-II score of 14 or higher, 61.65% answered yes to the single screening question (sensitivity, 0.62). For those who had BDI-II scores of lower than 14, a total of 82% responded no to the single screening question (specificity, 0.82). When using higher BDI-II scores to define depressive symptoms (≥20 and ≥29), the level of agreement decreased, whereas sensitivity increased to 0.76 and 0.90, with a trade-off in specificity (0.79 and 0.74, respectively). CONCLUSIONS: These results suggest that the single screening question for depressive symptoms correctly identifies depressive symptoms 62% of the time but inappropriately identifies depressive symptoms 18% of the time in patients hospitalized for ACS. This suggests that the single screening question for depressive symptoms may be used with caution to initially screen patients with ACS, who can then undergo a more thorough assessment for clinical depression.

Insomnia symptoms and neurofunctional correlates among adults receiving buprenorphine for opioid use disorder.

OBJECTIVES: Insomnia symptoms are negatively related to opioid use disorder (OUD) treatment outcomes, possibly reflecting the influence of sleep on neurofunctional domains implicated in addiction. Moreover, the intersection between OUD recovery and sleep represents an area well-suited for the development of novel, personalized treatment strategies. This study assessed the prevalence of clinically significant insomnia symptoms and characterized its neurofunctional correlates among a clinical sample of adults with OUD receiving buprenorphine. METHODS: Adults (N = 129) receiving buprenorphine for OUD from an outpatient clinic participated in a cross-sectional survey. Participants completed an abbreviated version of NIDA's Phenotyping Assessment Battery, which assessed 6 neurofunctional domains: sleep, negative emotionality, metacognition, interoception, cognition, and reward. Bivariate descriptive statistics compared those with evidence of clinically significant insomnia symptoms (Insomnia Severity Index [ISI] score of ≥11) to those with minimal evidence of clinically significant insomnia symptoms (ISI score of ≤10) across each of the neurofunctional domains. RESULTS: Roughly 60% of participants reported clinically significant insomnia symptoms (ISI score of ≥11). Experiencing clinically significant insomnia symptoms was associated with reporting greater levels of depression, anxiety, post-traumatic stress, stress intolerance, unhelpful metacognition, and interoceptive awareness (ps<0.05). Participants with evidence of clinically significant insomnia were more likely to report that poor sleep was interfering with their OUD treatment and that improved sleep would assist with their treatment (ps<0.05). CONCLUSIONS: Insomnia was prevalent among adults receiving buprenorphine for OUD. Insomnia was associated with neurofunctional performance, which may impact OUD treatment trajectories. Our findings indicate potential targets in the development of personalized treatment plans for patients with co-morbid insomnia and OUD. To inform the development of novel treatment strategies, more research is needed to understand the potential mechanistic links between sleep disturbances and substance use.

Neuroimaging Biomarkers in Addiction.

As a neurobiological process, addiction involves pathological patterns of engagement with substances and a range of behaviors with a chronic and relapsing course. Neuroimaging technologies assess brain activity, structure, physiology, and metabolism at scales ranging from neurotransmitter receptors to large-scale brain networks, providing unique windows into the core neural processes implicated in substance use disorders. Identified aberrations in the neural substrates of reward and salience processing, response inhibition, interoception, and executive functions with neuroimaging can inform the development of pharmacological, neuromodulatory, and psychotherapeutic interventions to modulate the disordered neurobiology. Based on our systematic search, 409 protocols registered on ClinicalTrials.gov include the use of one or more neuroimaging paradigms as an outcome measure in addiction, with the majority (N=268) employing functional magnetic resonance imaging (fMRI), followed by positron emission tomography (PET) (N=71), electroencephalography (EEG) (N=50), structural magnetic resonance imaging (MRI) (N=35) and magnetic resonance spectroscopy (MRS) (N=35). Furthermore, in a PubMed systematic review, we identified 61 meta-analyses including 30 fMRI, 22 structural MRI, 8 EEG, 7 PET, and 3 MRS meta-analyses suggesting potential biomarkers in addictions. These studies can facilitate the development of a range of biomarkers that may prove useful in the arsenal of addiction treatments in the coming years. There is evidence that these markers of large-scale brain structure and activity may indicate vulnerability or separate disease subtypes, predict response to treatment, or provide objective measures of treatment response or recovery. Neuroimaging biomarkers can also suggest novel targets for interventions. Closed or open loop interventions can integrate these biomarkers with neuromodulation in real-time or offline to personalize stimulation parameters and deliver the precise intervention. This review provides an overview of neuroimaging modalities in addiction, potential neuroimaging biomarkers, and their physiologic and clinical relevance. Future directions and challenges in bringing these putative biomarkers from the bench to the bedside are also discussed.

Aggression, impulsivity, and psychopathic traits in combined antisocial personality disorder and substance use disorder.

Aggression, impulsivity, and psychopathic traits are prominent in both antisocial personality disorder (ASPD) and substance use disorders (SUD), but have rarely been examined collectively. The authors' results show that all three variables were elevated in adults with comorbid ASPD/SUD, relative to SUD-only and control subjects.

Executive control network resting state fMRI functional and effective connectivity and delay discounting in cocaine dependent subjects compared to healthy controls.

Resting state functional magnetic resonance imaging (fMRI) has been used to study functional connectivity of brain networks in addictions. However, most studies to-date have focused on the default mode network (DMN) with fewer studies assessing the executive control network (ECN) and salience network (SN), despite well-documented cognitive executive behavioral deficits in addictions. The present study assessed the functional and effective connectivity of the ECN, DMN, and SN in cocaine dependent subjects (CD) (n = 22) compared to healthy control subjects (HC) (n = 22) matched on age and education. This study also investigated the relationship between impulsivity measured by delay discounting and functional and effective connectivity of the ECN, DMN, and SN. The Left ECN (LECN), Right ECN (RECN), DMN, and SN functional networks were identified using FSL MELODIC independent component analysis. Functional connectivity differences between CD and HC were assessed using FSL Dual Regression analysis and FSLNets. Effective connectivity differences between CD and HC were measured using the Parametric Empirical Bayes module of Dynamic Causal Modeling. The relationship between delay discounting and functional and effective connectivity were examined using regression analyses. Dynamic causal modeling (DCM) analysis showed strong evidence (posterior probability > 0.95) for CD to have greater effective connectivity than HC in the RECN to LECN pathway when tobacco use was included as a factor in the model. DCM analysis showed strong evidence for a positive association between delay discounting and effective connectivity for the RECN to LECN pathway and for the DMN to DMN self-connection. There was strong evidence for a negative association between delay discounting and effective connectivity for the DMN to RECN pathway and for the SN to DMN pathway. Results also showed strong evidence for a negative association between delay discounting and effective connectivity for the RECN to SN pathway in CD but a positive association in HC. These novel findings provide preliminary support that RECN effective connectivity may differ between CD and HC after controlling for tobacco use. RECN effective connectivity may also relate to tobacco use and impulsivity as measured by delay discounting.