
Scott MackeyUniversity of Vermont | UVM · Department of Psychiatry
Scott Mackey
PhD
Exploring new opportunities in biotech. Glad to discuss if you have interesting ideas about this.
About
86
Publications
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Introduction
Working at the intersection of neuropsychopharmacology and imaging genetics my background is in cognitive neuroscience and classical neuroanatomy. I am passionate about the orbital and ventromedial frontal cortex and how this part of the brain contributes to decision-making. Recently, my research has focused on maladaptive value processes related to addiction and has leveraged large shared datasets to interrogate the neural and genetic bases of addiction.
Publications
Publications (86)
Background:
Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood.
Methods:
Impulsivity was estimated with a temporal discounting task. Voxel-base...
In the ventrolateral frontal lobe of the human brain there is a distinct entity, cytoarchitectonic area 44 (Broca's area), which is crucial in speech production. There has been controversy over whether monkeys possess an area comparable to human area 44. We have addressed this question in the macaque monkey by combining quantitative architectonic a...
Importance
A total of 25.7 million children in the United States are classified as overweight or obese. Obesity is associated with deficits in executive function, which may contribute to poor dietary decision-making. Less is known about the associations between being overweight or obese and brain development.
Objective
To examine whether body mass...
Objective::
Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of...
The orbital and ventromedial frontal cortical regions of the human and the macaque monkey brains include several spatially discrete areas which are defined histologically by their distinctive laminar architecture. Although considerable information has been collected on the function and anatomical connections of specific architectonic areas within t...
Background and Aim
Cannabis use disorder (CUD) is strongly influenced by genetic factors; however the mechanisms underpinning this association are not well understood. This study investigated whether a polygenic risk score (PRS) based on a genome‐wide association study for CUD in adults predicts cannabis use in adolescents and whether the associati...
Importance
The extent to which neuroanatomical variability associated with early substance involvement, which is associated with subsequent risk for substance use disorder development, reflects preexisting risk and/or consequences of substance exposure remains poorly understood.
Objective
To examine neuroanatomical features associated with early s...
Background and aims:
The brain age gap (BAG), calculated as the difference between a machine learning model-based predicted brain age and chronological age, has been increasingly investigated in psychiatric disorders. Tobacco and alcohol use are associated with increased BAG; however, no studies have compared global and regional BAG across substan...
Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demog...
Obesity is a highly prevalent metabolic risk factor that commonly coincides with additional metabolic, cardiovascular, and inflammatory abnormalities. Obesity has frequently been shown to affect brain physiology at multiple levels, and to increase the risk for the development of neuropsychiatric disorders such as major depression and dementia. Prev...
Correlating transcriptional profiles with imaging-derived phenotypes has the potential to reveal possible molecular architectures associated with cognitive functions, brain development and disorders. Competitive null models built by resampling genes and self-contained null models built by spinning brain regions, along with varying test statistics,...
Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of...
The extent to which neuroanatomical variability associated with substance involvement reflects pre-existing risk and/or consequences of substance exposure remains poorly understood. In the Adolescent Brain Cognitive Development SM (ABCD®) Study, we identify associations between global and regional differences in brain structure and early substance...
Importance
In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessmen...
Introduction
There are growing concerns about commonly inflated effect sizes in small neuroimaging studies, yet no study has addressed recalibrating effect size estimates for small samples. To tackle this issue, we propose a hierarchical Bayesian model to adjust the magnitude of single-study effect sizes while incorporating a tailored estimation of...
Background and Aims
Recently, we demonstrated that a distinct pattern of structural covariance networks (SCN) from magnetic resonance imaging (MRI)‐derived measurements of brain cortical thickness characterized young adults with alcohol use disorder (AUD) and predicted current and future problematic drinking in adolescents relative to controls. Her...
Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-a...
Leveraging ~10 years of prospective longitudinal data on 704 participants, we examined the effects of adolescent versus young adult cannabis initiation on MRI-assessed cortical thickness development and behavior. Data were obtained from the IMAGEN study conducted across eight European sites. We identified IMAGEN participants who reported being cann...
The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany a...
Importance:
Past studies have identified associations between brain macrostructure and alcohol use behaviors. However, identifying directional associations between these phenotypes is difficult due to the limitations of observational studies.
Objective:
To use mendelian randomization (MR) to identify directional associations between brain struct...
The parietal lobe is a region of especially pronounced change in human brain evolution. Based on comparative neuroanatomical studies, the inferior parietal lobe (IPL) has been shown to be disproportionately larger in humans relative to chimpanzees and macaques. However, it remains unclear whether the underlying histological architecture of IPL cort...
While there is substantial evidence that cannabis use is associated with differences in human brain development, most of this evidence is correlational in nature. Bayesian causal network (BCN) modeling attempts to identify probable causal relationships in correlational data using conditional probabilities to estimate directional associations betwee...
Background and aims
Graph theoretic analysis of structural covariance networks (SCN) provides an assessment of brain organization that has not yet been applied to alcohol dependence (AD). We estimated whether SCN differences are present in adults with AD and heavy drinking adolescents at age 19 and age 14, prior to substantial exposure to alcohol....
Mixed findings exist in studies comparing brain responses to reward in adolescents and adults. Here we examined the trajectories of brain response, functional connectivity and task-modulated network properties during reward processing with a large-sample longitudinal design. Participants from the IMAGEN study performed a Monetary Incentive Delay ta...
Background
Nicotine and illicit stimulants are very addictive substances. Although associations between grey matter and dependence on stimulants have been frequently reported, white matter correlates have received less attention.
Methods
Eleven international sites ascribed to the ENIGMA-Addiction consortium contributed data from individuals with d...
A full list of affiliations appears at the end of the paper. T he ABCD Study ® aims to characterize adolescent development and evaluate many influences that might shape developmental trajectories. While numerous factors are plausibly associated with neurodevelopment (for example, nutrition, sleep, exercise, head injuries and substance use), we have...
Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume...
Objective
Start Treatment and Recover (STAR) is an emergency department (ED) program that expands access to medication for opioid use disorder by identifying patients with opioid use disorder and offering ED‐initiated buprenorphine/naloxone and rapid access to outpatient treatment. We sought to determine the impacts of the coronavirus disease 2019...
Males and females with alcohol dependence have distinct mental health and cognitive problems. Animal models of addiction postulate that the underlying neurobiological mechanisms are partially distinct, but there is little evidence of sex differences in humans with alcohol dependence as most neuroimaging studies have been conducted in males. We exam...
Gender-related differences in the susceptibility, progression and clinical outcomes of alcohol dependence are well-known. However, the neurobiological substrates underlying such differences remain unclear. Therefore, this study aimed to investigate gender differences in the neuroanatomy (i.e. regional brain volumes) of alcohol dependence. We examin...
Multimodal neuroimaging assessments were utilized to identify generalizable brain correlates of current body mass index (BMI) and predictors of pathological weight gain (i.e., beyond normative development) one year later. Multimodal data from children enrolled in the Adolescent Brain Cognitive Development Study® at 9-to-10-years-old, consisted of s...
Brain asymmetry reflects left‐right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are differ...
Abstract This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci as...
To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega‐analysis of previously published datasets from 2,034 AD and comparison participants spanni...
Objective:
It is unclear whether deviations in brain and behavioral development, that may underpin elevated substance use during adolescence, are predispositions for or are consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug naïve youth to identify possible predisposin...
Gray matter volume (GMV) in frontal cortical and limbic regions is susceptible to cocaine‐associated reductions in cocaine‐dependent individuals (CD) and is negatively associated with duration of cocaine use. Gender differences in CD individuals have been reported clinically and in the context of neural responses to cue‐induced craving and stress r...
Objective
Irritable mood, a common and impairing symptom in psychopathology, has been proposed to underlie the developmental link between oppositional problems in youth and depression in adulthood. Here, we examined the neural correlates of adolescent irritability in IMAGEN, a sample of 2024 14-year-adolescents from five European countries.
Method...
Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions , and until recently there has been few large-scale investigations to compare such fi...
In Reply In their letter, Goldstein et al bring attention to the interesting idea that the association between body mass index (BMI) and cortical thickness as reported in our study¹ may be complicated by an interaction with psychiatric status. Adolescents with significant psychiatric conditions are more likely to be receiving medications that may i...
Background
The search for neuroimaging biomarkers of alcohol use disorder (AUD) has primarily been restricted to significance testing in small datasets of low diversity. To identify neurobiological markers beyond individual differences, it may be useful to develop classification models for AUD. The ever-increasing quantity of neuroimaging data dema...
While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and subst...
Sometimes anticipation is more fun than the actual event, and sometimes, pleasantly, it's the reverse. The difference between the anticipated value of an action and its actual outcome provides important feedback, which shapes our behavior and future plans and is a central feature of all modern theories of incentivized learning.1 Contextually adapti...
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics throughMeta Analysis) Consortium, a global alliance of over 1,400 scientists across 43 countries, studying the humanbrain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicatedgenetic loci associated wi...
In structural neuroimaging studies, reduced cerebral cortical thickness in orbital and ventromedial prefrontal regions is frequently interpreted as reflecting an impaired ability to downregulate neuronal activity in the amygdalae. Unfortunately, little research has been conducted in order to test this conjecture. We examine the extent to which amyg...
Scatter plot of quadratic association.
Scatter plot depicting quadratic association between residualized average thickness of right vmPFC cluster (adjusted for age, total brain volume, sex, site, handedness, Performance IQ, Verbal IQ, SES and pubertal development) and angry minus neutral face contrast value (mean value for left and right amygdalae)...
Objective:
To characterize the structural and functional neurobiology of a large group of adolescents exhibiting a behaviorally and emotionally dysregulated phenotype.
Method:
Adolescents aged 14 years from the IMAGEN study were investigated. Latent class analysis (LCA) on the Strengths and Difficulties Questionnaire (SDQ) was used to identify a...
Background: Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may inform the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents have appeared and those available include small samples. In addit...
Rates of cannabis use among adolescents are high, and are increasing concurrent with changes in the legal status of marijuana and societal attitudes regarding its use. Recreational cannabis use is understudied, especially in the adolescent period when neural maturation may make users particularly vulnerable to the effects of Δ-9-tetrahydrocannabino...
Background
Research suggests that substance use disorders and disordered eating are often comorbid. In light of the ongoing opioid epidemic, the purpose of the current study was to understand the prevalence and health-related correlates of loss of control (LOC) eating in adults seeking methadone maintenance treatment primarily for addiction to hero...
Cannabis use initiated during adolescence might precipitate negative consequences in adulthood. Thus, predicting adolescent cannabis use prior to any exposure will inform the etiology of substance abuse by disentangling predictors from consequences of use. In this prediction study, data were drawn from the IMAGEN sample, a longitudinal study of ado...
Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structu...
BACKGROUND: Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. Herein, we investigate the relatio...
[11C]-dihydrotetrabenazine (DTBZ) Positron Emission Tomography (PET) was used to evaluate the vesicular monoamine transporter type 2 as an index of dopaminergic function in the striatum of adult Sprague-Dawley rats obtained from two different animal sources (Charles River Laboratories [CR] or UBC's Animal Care Centre [ACC]) and later submitted to t...
Understanding how humans weigh long-term and short-term goals is important for both basic cognitive science and clinical neuroscience, as substance users need to balance the appeal of an immediate high vs. the long-term goal of sobriety. We use a computational model to identify learning and decision-making abnormalities in methamphetamine-dependent...
In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working g...
Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n = 70) of 14-year olds with a history of cannabis use to a group (n = 70) of never-using controls matched on numerous characteristics including IQ, SES,...
The field of neuroimaging has truly become data rich, and novel analytical
methods capable of gleaning meaningful information from large stores of imaging
data are in high demand. Those methods that might also be applicable on the
level of individual subjects, and thus potentially useful clinically, are of
special interest. In the present study, we...
Since the sample size of a typical neuroimaging study lacks sufficient statistical power to explore unknown genomic associations with brain phenotypes, several international genetic imaging consortia have been organized in recent years to pool data across sites. The challenges and achievements of these consortia are considered here with the goal of...
The significance of why a similar set of brain regions are associated with the default mode network and value-related neural processes remains to be clarified. Here, we examined i) whether brain regions exhibiting willingness-to-pay (WTP) task-related activity are intrinsically connected when the brain is at rest, ii) whether these regions overlap...
According to embodied cognition theories, concepts are contextually situated and grounded in neural systems that produce experiential states. This view predicts that processing mental state concepts recruits neural regions associated with different aspects of experience depending on the context in which people understand a concept. This neuroimagin...
A previous report identified the location of comparable architectonic areas in the ventral frontal cortex of the human and macaque brains [S. Mackey & M. Petrides (2010) Eur. J. Neurosci., 32, 1940-1950]. The present article provides greater detail with regard to the definition of architectonic areas within the ventromedial part of the human ventra...
In the human brain, areas 44 and 45 constitute Broca's region, the ventrolateral frontal region critical for language production. The homologues of these areas in the macaque monkey brain have been established by direct cytoarchitectonic comparison with the human brain. The cortical areas that project monosynaptically to areas 44 and 45B in the mac...