Sarah W. Feldstein Ewing

A Baseline for the Multivariate Comparison of Resting-State Networks

As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12–71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

Identifying Neurobiological Phenotypes Associated with Alcohol Use Disorder Severity

Although numerous studies provide general support for the importance of genetic factors in the risk for alcohol use disorders (AUDs), candidate gene and genome-wide studies have yet to identify a set of genetic variations that explain a significant portion of the variance in AUDs. One reason is that alcohol-related phenotypes used in genetic studies are typically based on highly heterogeneous diagnostic categories. Therefore, identifying neurobiological phenotypes related to neuroadaptations that drive the development of AUDs is critical for the future success of genetic and epigenetic studies. One such neurobiological phenotype is the degree to which exposure to alcohol taste cues recruits the basal ganglia, prefrontal cortex, and motor areas, all of which have been shown to have a critical role in addictive behaviors in animal studies. To that end, this study was designed to examine whether cue-elicited responses of these structures are associated with AUD severity in a large sample (n=326) using voxelwise and functional connectivity measures. Results suggested that alcohol cues significantly activated dorsal striatum, insula/orbitofrontal cortex, anterior cingulate cortex, and ventral tegmental area. AUD severity was moderately correlated with regions involved in incentive salience such as the nucleus accumbens and amygdala, and stronger relationships with precuneus, insula, and dorsal striatum. The findings indicate that AUDs are related to neuroadaptations in these regions and that these measures may represent important neurobiological phenotypes for subsequent genetic studies.

How Psychosocial Alcohol Interventions Work: A Preliminary Look at What fMRI Can Tell Us

BACKGROUND Current work in motivational interviewing (MI) has supported the role of in-session client and therapist language in predicting postintervention substance use outcomes. In particular, a relationship has been found between specific therapist language (e.g., MI-consistent behaviors), specific types of client speech (e.g., change talk; CT and counterchange talk; CCT), and subsequent drinking outcomes. One hypothesis to explain this phenomenon is that CT is an indication of a neurocognitive shift that happens during the course of a psychosocial intervention. And, it is possible that this shift is responsible for catalyzing and maintaining changes in drinking behaviors following MI interventions. To investigate this question, the effect of CT on blood oxygen level-dependent (BOLD) response during the presentation of alcohol cues was evaluated using functional magnetic resonance imaging. METHODS To examine changes in neural response to alcohol cues following client language, 10 adults with alcohol dependence (50% men; 40% Caucasian; 40% Hispanic; M age = 42.6; M years of education = 13.3) were presented with CT and CCT derived from their prescan MI session during the presentation of alcohol cues. RESULTS Following CCT, there was significant neural response to alcohol cues in several key reward areas (cluster-corrected p < 0.05, z > 2.3; orbitofrontal cortex, nucleus accumbens, anterior insula, posterior insula, caudate, and putamen). On the contrary, there were no areas of significant reward activation following CT. CONCLUSIONS These results indicate that CT may be effectively inhibiting activation in brain regions that respond to the salience of alcohol cues. These findings provide preliminary biological support of the psychosocial literature findings, highlighting the critical importance of change talk during psychosocial interventions.

The effect of alcohol consumption on the adolescent brain: A systematic review of MRI and fMRI studies of alcohol-using youth

Background A large proportion of adolescents drink alcohol, with many engaging in high-risk patterns of consumption, including binge drinking. Here, we systematically review and synthesize the existing empirical literature on how consuming alcohol affects the developing human brain in alcohol-using (AU) youth. Methods For this systematic review, we began by conducting a literature search using the PubMED database to identify all available peer-reviewed magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) studies of AU adolescents (aged 19 and under). All studies were screened against a strict set of criteria designed to constrain the impact of confounding factors, such as co-occurring psychiatric conditions. Results Twenty-one studies (10 MRI and 11 fMRI) met the criteria for inclusion. A synthesis of the MRI studies suggested that overall, AU youth showed regional differences in brain structure as compared with non-AU youth, with smaller grey matter volumes and lower white matter integrity in relevant brain areas. In terms of fMRI outcomes, despite equivalent task performance between AU and non-AU youth, AU youth showed a broad pattern of lower task-relevant activation, and greater task-irrelevant activation. In addition, a pattern of gender differences was observed for brain structure and function, with particularly striking effects among AU females. Conclusions Alcohol consumption during adolescence was associated with significant differences in structure and function in the developing human brain. However, this is a nascent field, with several limiting factors (including small sample sizes, cross-sectional designs, presence of confounding factors) within many of the reviewed studies, meaning that results should be interpreted in light of the preliminary state of the field. Future longitudinal and large-scale studies are critical to replicate the existing findings, and to provide a more comprehensive and conclusive picture of the effect of alcohol consumption on the developing brain.

Do genetic and individual risk factors moderate the efficacy of motivational enhancement therapy? Drinking outcomes with an emerging adult sample.

Research indicates that motivational enhancement therapy (MET) helps catalyze reductions in problem drinking among emerging adults. However, moderators of this intervention remain relatively unknown. Therefore, the objectives of this study were: (1) to test whether a single session of MET increased motivation to reduce drinking and drinking outcomes; and (2) to examine whether genetic dopamine D4 receptor L (DRD4 L) and individual personality risk factors (impulsivity and novelty seeking) moderated the effects of the MET. These hypotheses were evaluated by randomly assigning a sample of emerging adult problem drinkers (n = 67) to receive a single session of MET or alcohol education. Follow‐up data indicated that only individuals who were low in impulsivity, novelty seeking and/or who had the short DRD4 variable number of tandem repeats genotype evidenced differentially increased behavior change (taking steps toward reducing drinking) following the MET.

Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: emerging translational approaches that bridge biology and behavior.

Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real-time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examine brain-based mechanisms of change, whereas others examine brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors.

Exploring the relationship between depressive and anxiety symptoms and neuronal response to alcohol cues.

BACKGROUND Depressive and anxiety symptoms tend to co-occur with heavy drinking. Specifically, their presence may exacerbate the severity and intractability of heavy drinking. Similarly, heavy drinking may increase the risk for and experience of depressive and anxiety symptoms. Although depressive and anxiety symptoms have been significantly correlated with alcohol craving in cue-exposure paradigms, physiological responses have not always mapped onto emotional responses. Therefore, this study sought to examine the role of depressive and anxiety symptoms using a more basic science approach, through examining functional brain changes. METHODS Seventy nontreatment seeking, heavy drinking adults were recruited through a college campus (n = 45 men; mean age = 22.8). They completed measures of drinking, smoking, depressive symptoms, anxiety symptoms, and a functional magnetic resonance imaging (fMRI) cue-exposure paradigm. RESULTS As hypothesized, depressive symptoms were positively correlated with activation during the alcohol (vs. appetitive control) cue in the insula, cingulate, ventral tegmentum, striatum, and thalamus (cluster-corrected p < 0.05, z = 2.3). Similarly, anxiety symptoms were positively correlated with activation during the alcohol (vs. appetitive control) cue in the striatum, thalamus, insula, and inferior frontal, mid-frontal, and cingulate gyri (cluster-corrected p < 0.05, z = 2.3). CONCLUSIONS Significant correlations were found between depressive symptoms, anxiety symptoms, and differential brain activation in response to an alcohol versus an appetitive control cue in an fMRI paradigm. Moreover, the pattern of activation mapped onto expected regions. This study strongly supports the posited relationships between depressive symptoms, anxiety symptoms, and differential brain activation in an alcohol cue-exposure paradigm with a sample of heavy drinking adults.

Functional connectivity and cannabis use in high-risk adolescents

Abstract Background: Adolescence is a unique neurodevelopmental period when regions of the brain most able to assess risk and reward are still in development. Cannabis use during adolescence has been associated with persistent negative outcomes. Although measures of resting brain activity are useful in assessing functional connectivity, such measures have not been broadly applied in adolescent cannabis-users. Objectives: The goal of the present study was to analyze the associations between cannabis use and resting brain activity in a sample of high-risk adolescents. Methods: Eighty-two high-risk youth between 14–18 years old were recruited from a juvenile justice day program. Youth completed a brief neurocognitive battery including assessments of cannabis use and a 5-minute resting functional magnetic resonance imaging (fMRI) scan. Intrinsic connectivity networks were extracted using the GIFT toolbox. Brain activity in a fronto-temporal network was compared in youth with high cannabis use vs. low cannabis use using an independent-samples t-test with alcohol use entered as a covariate. Results: Analysis revealed two elements within the fronto-temporal network related to cannabis use: one in middle frontal gyrus related to high cannabis use, and one in middle temporal gyrus related to low cannabis use. Only the frontal source survived application of a cluster size threshold and was significant at p < 0.005. Conclusions: These results are consistent with patterns of activity in adult cannabis-users. The observed effect may reflect either pre-existing risk factors or near-term consequences of cannabis use. Prevention and intervention strategies that address fronto-temporal functioning may be particularly helpful in this population.

Exploring racial/ethnic differences in substance use: a preliminary theory-based investigation with juvenile justice-involved youth.

BackgroundRacial/ethnic differences in representation, substance use, and its correlates may be linked to differential long-term health outcomes for justice-involved youth. Determining the nature of these differences is critical to informing more efficacious health prevention and intervention efforts. In this study, we employed a theory-based approach to evaluate the nature of these potential differences. Specifically, we hypothesized that (1) racial/ethnic minority youth would be comparatively overrepresented in the juvenile justice system, (2) the rates of substance use would be different across racial/ethnic groups, and (3) individual-level risk factors would be better predictors of substance use for Caucasian youth than for youth of other racial/ethnic groups.MethodsTo evaluate these hypotheses, we recruited a large, diverse sample of justice-involved youth in the southwest (N = 651; M age = 15.7, SD = 1.05, range = 14-18 years); 66% male; 41% Hispanic, 24% African American, 15% Caucasian, 11% American Indian/Alaska Native). All youth were queried about their substance use behavior (alcohol, marijuana, tobacco, illicit hard drug use) and individual-level risk factors (school involvement, employment, self-esteem, level of externalizing behaviors).ResultsAs predicted, racial/ethnic minority youth were significantly overrepresented in the juvenile justice system. Additionally, Caucasian youth reported the greatest rates of substance use and substance-related individual-level risk factors. In contrast, African American youth showed the lowest rates for substance use and individual risk factors. Contrary to predictions, a racial/ethnic group by risk factor finding emerged for only one risk factor and one substance use category.ConclusionsThis research highlights the importance of more closely examining racial/ethnic differences in justice populations, as there are likely to be differing health needs, and subsequent treatment approaches, by racial/ethnic group for justice-involved youth. Additionally, this study highlights the need for timely, empirically supported (developmentally and cross-culturally) substance abuse interventions for all justice-involved youth.

Two approaches to tailoring treatment for cultural minority adolescents

At this time, compared with mainstream (Caucasian) youth, cultural minority adolescents experience more severe substance-related consequences and are less likely to receive treatment. Although several empirically supported interventions (ESIs), such as motivational interviewing (MI), have been evaluated with mainstream adolescents, fewer published studies have investigated the fit and efficacy of these interventions with cultural minority adolescents. In addition, many empirical evaluations of ESIs have not explicitly attended to issues of culture, race, and socioeconomic background in their analyses. As a result, there is some question about the external validity of ESIs, particularly in disadvantaged cultural minority populations. This review seeks to take a step toward filling this gap, by addressing how to improve the fit and efficacy of ESIs like MI with cultural minority youth. Specifically, this review presents the existing literature on MI with cultural minority groups (adult and adolescent), proposes two approaches for evaluating and adapting this (or other) behavioral interventions, and elucidates the rationale, strengths, and potential liabilities of each tailoring approach.