Edith V Sullivan

• Ph.D.
• Professor at Stanford Medicine

Grip strength is considered one of the simplest and reliable indices of general health. Although motor ability and strength are commonly affected in people with alcohol use disorder (AUD), factors predictive of grip strength decline in AUD have not been investigated. Here, we employed a data‐driven analysis predicting grip strength from measurement...

Objective Pharmacologically-treated people living with HIV infection have near-normal life spans with more than 50 % living into at-risk age for dementia and a disproportionate number relative to uninfected people engaging in unhealthy drinking. Accelerated aging in HIV occurs in some brain structures including the multinucleated thalamus. Unknown...

Neurodegenerative diseases manifest different motor and cognitive signs and symptoms that are highly heterogeneous. Parsing these heterogeneities may lead to an improved understanding of underlying disease mechanisms; however, current methods are dependent on clinical assessments and an arbitrary choice of behavioural tests. Here we present a data-...

Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drin...

Functional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral integrity. Whereas treatment is challenged by a multitude of substances that patients often use, no study has yet unraveled if inhibition and related cerebral integrity could prevent rel...

Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors typically focus on young adults who enrolled in 4-year residential college programs (4YCP) even though most high school graduates join the workforce, military, or community colleges....

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone‐based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict u...

Objective With aging, people living with HIV (PLWH) have diminishing postural stability that increases liability for falls. Factors and neuromechanisms contributing to instability are incompletely known. Brain white matter abnormalities seen as hyperintense (WMH) signals have been considered to underlie instability in normal aging and PLWH. We ques...

Background Childhood abuse is an underappreciated source of stress, associated with adverse mental and physical health consequences. Childhood abuse has been directly associated with risky behavior thereby increasing the likelihood of alcohol misuse and risk of HIV infection, conditions associated with brain structural and functional deficits. Here...

Importance Anomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD. Objective To test whether brain tissue declines...

Background Patients treated for Substance Use Disorders exhibit highly fluctuating patterns of craving that could reveal novel prognostic markers of use. Accordingly, we 1) measured fluctuations within intensively repeated measures of craving and 2) linked fluctuations of craving to connectivity indices within resting-state (rs) brain regions to as...

As direct evaluation of a mouse model of human neurodevelopment, adolescent and young adult mice and humans underwent MR diffusion tensor imaging to quantify age-related differences in microstructural integrity of brain white matter fibers. Fractional anisotropy (FA) was greater in older than younger mice and humans. Despite the cross-species commo...

Background: Antiretroviral treatment has enabled people living with HIV infection to have a near-normal lifespan. With longevity come opportunities for engaging in risky behavior, including initiation of excessive drinking. Given that both HIV infection and alcohol use disorder (AUD) can disrupt brain white matter integrity, we questioned whether...

Poor sleep can undermine health and may be especially disruptive to those with chronic conditions including HIV infection. Here, clinically well-described people living with HIV [PLWH] (74 men, 35 women) and healthy control (38 men, 35 women) participants were administered the Pittsburgh Sleep Quality Index (PSQI), a validated measure of subjective...

Experience of childhood trauma, especially physical, emotional, and sexual abuse, carries a risk for developing alcohol use disorder (AUD) and engaging in risky behaviors that can result in HIV infection. AUD and HIV are associated with compromised self-reported health-related quality of life (HRQoL) possibly intersecting with childhood trauma. To...

Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson’s disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning...

H-magnetic resonance spectroscopy (MRS) conducted in cirrhosis shows consistent CNS changes such as high levels of the combined resonances (Glx) of glutamate (Glu) + glutamine (Gln) and low levels of choline-containing compounds (Cho) and myo-Inositol (mI) relative to total creatine (tCr). Studies of hepatitis C virus (HCV) infection, however, note...

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS oppor...

Objectives: Determine the independent contributions of central nervous system (CNS) and peripheral nervous system (PNS) metrics to balance instability in people with HIV (PWH) compared with people without HIV (PWoH). Methods: Volumetric MRI (CNS) and two-point pedal discrimination (PNS) were tested as substrates of stance instability measured wi...

Background. Poor sleep can undermine the health of people in general and may be especially disruptive to those with chronic conditions including HIV infection. Methods. Here, clinically well-described people living with HIV infection [PLWH] (74 men, 35 women) and healthy control (38 men, 35 women) participants were administered the Pittsburgh Slee...

Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to qua...

Parkinson’s disease (PD) is a neurological disorder that has a variety of observable motor-related symptoms such as slow movement, tremor, muscular rigidity, and impaired posture. PD is typically diagnosed by evaluating the severity of motor impairments according to scoring systems such as the Movement Disorder Society Unified Parkinson’s Disease R...

Binge alcohol consumption is common among adolescents and may impair normal brain development. Emerging, longitudinal studies in adolescents suggest that the effects of binge alcohol exposure on brain structure differ between sexes. To test the hypothesis that the effects of binge alcohol exposure on developmental brain growth trajectories are infl...

To determine the persistent effects of the pandemic on mental health in young adults, we categorized depressive symptom trajectories and sought factors that promoted a reduction in depressive symptoms in high-risk individuals. Specifically, longitudinal analysis investigated changes in the risk for depression before and during the pandemic until De...

Expression of executive dysfunctions is marked by substantial heterogeneity in people living with HIV infection (PLWH) and attributed to neuropathological degradation of frontostriatal circuitry with age and disease. We compared the neurophysiology of executive function in older PLWH and Parkinson’s disease (PD), both affecting frontostriatal syste...

Excessive alcohol use curtails longevity by rendering intoxicated individuals vulnerable to heightened risk from accidents, violence, and alcohol poisoning and chronically heavy drinkers vulnerable to accelerating age-related medical and psychiatric conditions that can be life-threatening (Yoon et al., 2020). Thus, studies of factors influencing ag...

How disrupted sleep contributes to cognitive dysfunction over the dynamic course of Alcohol Use Disorder (AUD) is an emerging topic of investigation. Here, the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate subjective sleep in 90 individuals with AUD sober for an average of 3 months and in 50 healthy controls. Relative to controls, AUD...

Parkinson's disease (PD) is a neurological disorder that has a variety of observable motor-related symptoms such as slow movement, tremor, muscular rigidity, and impaired posture. PD is typically diagnosed by evaluating the severity of motor impairments according to scoring systems such as the Movement Disorder Society Unified Parkinson's Disease R...

Background Accurate measurement of trajectories in longitudinal studies, considered the gold standard method for tracking functional growth during adolescence, decline in aging, and change after head injury, is subject to confounding by testing experience. Methods We measured change in cognitive and motor abilities over four test sessions (baselin...

The COVID-19 pandemic led to unprecedented restrictions to mitigate disease spread, leading to consequences affecting mental health. Many studies examining COVID-19 pandemic effects on well-being and mental health initiated inquiry after the pandemic onset, whereas we used self-report questionnaires obtained before the pandemic to re-assess the sam...

BACKGROUND A neural substrate of alcohol-related instability of gait and balance is the cerebellum. Whether disruption of neural communication between cerebellar and cortical brain regions exerts an influence on ataxia in alcohol use disorder (AUD) was the focus of this study. METHODS Study groups comprised 32 abstinent AUD participants and 22 age...

People living with HIV infection (PWH) who are adequately treated pharmacologically are now likely to have a near normal life span. Along with this benefit of the aging HIV population are potential physical problems attendant to aging, including postural stability. Whether aging with HIV accelerates age-related liability for postural instability an...

Objective: Executive control continues to develop throughout adolescence and is vulnerable to alcohol use. Although longitudinal assessment is ideal for tracking executive function development and onset of alcohol use, prior testing experience must be distinguished from developmental trajectories. Method: We used the Stroop Match-to-Sample task...

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and Neuro...

Background The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could pr...

Alcohol use disorder (AUD) is recognized as harmful for the developing brain. Numerous studies have sought environmental and genetic risk factors that predict the development of AUD, but recently identified resilience factors have emerged as protective. This chapter reviews normal processes of brain development in adolescence and emerging adulthood...

Older individuals infected by Human Immunodeficiency Virus (HIV) are at risk for developing HIV-Associated Neurocognitive Disorder (HAND), i.e., from reduced cognitive functioning similar to HIV-negative individuals with Mild Cognitive Impairment (MCI) or to Alzheimer’s Disease (AD) if more severely affected. Incompletely understood is how brain st...

Longitudinal MRIs are often used to capture the gradual deterioration of brain structure and function caused by aging or neurological diseases. Analyzing this data via machine learning generally requires a large number of ground-truth labels, which are often missing or expensive to obtain. Reducing the need for labels, we propose a self-supervised...

Background: Episodic memory deficits occur in alcohol use disorder (AUD), but their anatomical substrates remain in question. Although persistent memory impairment is classically associated with limbic circuitry disruption, learning and retrieval of new information also relies on frontal systems. Despite AUD vulnerability of frontal lobe integrity...

Parkinson’s disease (PD) is a brain disorder that primarily affects motor function, leading to slow movement, tremor, and stiffness, as well as postural instability and difficulty with walking/balance. The severity of PD motor impairments is clinically assessed by part III of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (M...

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory...

The age- and time-dependent effects of binge-drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume development was examined using longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Ad...

Longitudinal MRIs are often used to capture the gradual deterioration of brain structure and function caused by aging or neurological diseases. Analyzing this data via machine learning generally requires a large number of ground-truth labels, which are often missing or expensive to obtain. Reducing the need for labels, we propose a self-supervised...

Alcohol use disorder (AUD) is widely associated with cerebellar dysfunction and altered cerebro-cerebellar functional connectivity (FC) that lead to cognitive impairments. Evidence for this association comes from resting-state functional magnetic resonance imaging (rsfMRI) studies that assess time-averaged measures of FC across the duration of a ty...

Chronic, excessive alcohol consumption is associated with cerebrovascular hypoperfusion, which has the potential to interfere with cognitive processes. Magnetic resonance pulsed continuous arterial spin labeling (PCASL) provides a noninvasive approach for measuring regional cerebral blood flow (CBF) and was used to study 24 men and women with Alcoh...

Binge drinking is a widespread alcohol consumption pattern commonly engaged by youth. Here, we present the first systematic review focusing on emotional processes related to binge drinking. Capitalizing on a theoretical model describing three emotional processing steps (emotional appraisal/identification, emotional response, emotional regulation) a...

The extant literature supports the involvement of the thalamus in the cognitive and motor impairment associated with chronic alcohol consumption, but clear structure/function relationships remain elusive. Alcohol effects on specific nuclei rather than the entire thalamus may provide the basis for differential cognitive and motor decline in Alcohol...

Presence of bias (in datasets or tasks) is inarguably one of the most critical challenges in machine learning applications that has alluded to pivotal debates in recent years. Such challenges range from spurious associations between variables in medical studies to the bias of race in gender or face recognition systems. Controlling for all types of...

Importance Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alc...

Many neurological diseases are characterized by gradual deterioration of brain structure and function. Large longitudinal MRI datasets have revealed such deterioration, in part, by applying machine and deep learning to predict diagnosis. A popular approach is to apply Convolutional Neural Networks (CNN) to extract informative features from each vis...

Background In a previous study using Jacobian mapping to evaluate the morphological effects on the brain of binge (4‐day) intragastric ethanol (EtOH) on wild‐type Wistar rats, we reported reversible thalamic shrinkage and lateral ventricular enlargement, but persistent superior and inferior colliculi shrinkage in response to binge EtOH treatment....

Background Individuals with Alcohol Use Disorder (AUD) have a heightened risk of contracting HIV infection. The effects of these two diseases and their comorbidity on brain structure have been well described, but their effects on brain function have never been investigated at the scale of whole-brain connectomes. Methods In contrast with prior stu...

Despite the life-extending success of antiretroviral pharmacotherapy in HIV infection (HIV), the prevalence of mild cognitive impairment in HIV remains high. Near-normal life expectancy invokes an emerging role for age-infection interaction and a potential synergy between immunosenescence and HIV-related health factors, increasing risk of cognitive...

Postural stability is a multi‐factorial skill maintained implicitly. Components of quiet standing can decline with Alcohol Use Disorder (AUD), cause instability, and disrupt activities of daily living (ADL). To examine how stability factors contribute to ADL and balance, 638 force platform testing sessions measured sway paths acquired during quiet...

Functional connectivity between brain regions is often estimated by correlating brain activity measured by resting-state fMRI in those regions. The impact of factors (e.g., disorder or substance use) are then modeled by their effects on these correlation matrices in individuals. A crucial step in better understanding their effects on brain function...

Minor artifacts introduced during image acquisition are often negligible to the human eye, such as a confined field of view resulting in MRI missing the top of the head. This cropping artifact, however, can cause suboptimal processing of the MRI resulting in data omission or decreasing the power of subsequent analyses. We propose to avoid data or q...

The Blood-Oxygen-Level-Dependent (BOLD) signal of resting-state fMRI (rs-fMRI) records the temporal dynamics of intrinsic functional networks in the brain. However, existing deep learning methods applied to rs-fMRI either neglect the functional dependency between different brain regions in a network or discard the information in the temporal dynami...

Parkinson’s disease (PD) is a progressive neurological disorder primarily affecting motor function resulting in tremor at rest, rigidity, bradykinesia, and postural instability. The physical severity of PD impairments can be quantified through the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a widely used clinical...

Critical changes in adolescence involve brain cognitive maturation of inhibitory control processes that are essential for a myriad of adult functions. Cognitive control advances into adulthood as there is more flexible integration of component processes, including inhibitory control of conflicting information, overwriting inappropriate response ten...

The application of data-driven deep learning to identify sex differences in developing brain structures of pre-adolescents has heretofore not been accomplished. Here, the approach identifies sex differences by analyzing the minimally processed MRIs of the first 8,144 participants (age 9 and 10 years) recruited by the Adolescent Brain Cognitive Deve...

Despite mounting evidence for the role of inflammation in Major Depressive Disorder (MDD), in vivo preclinical investigations of inflammation-induced negative affect using whole brain imaging modalities are scarce, precluding a valid model within which to evaluate pharmacological interventions. Here we used an E. coli lipopolysaccharide (LPS)-based...

Traditionally, the desired successful recovery from alcohol dependence has required complete abstinence, without transgression, for a sustained period, ideally the rest of one’s life. This stringent definition marks a goal that is unachievable by a majority of men and women with Alcohol Use Disorder (AUD) despite sincere efforts to stop drinking. W...

Parkinson's disease (PD) is a progressive neurological disorder primarily affecting motor function resulting in tremor at rest, rigidity, bradykinesia, and postural instability. The physical severity of PD impairments can be quantified through the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), a widely used clinical...

An overarching goal of our research has been to develop a valid animal model of alcoholism with similar imaging phenotypes as those observed in humans with the ultimate objective of assessing the effectiveness of pharmacological agents. In contrast to our findings in humans with alcohol use disorders (AUD), our animal models have not demonstrated e...

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3‐...

Most neurological diseases are characterized by gradual deterioration of brain structure and function. To identify the impact of such diseases, studies have been acquiring large longitudinal MRI datasets and applied deep-learning to predict diagnosis label(s). These learning models apply Convolutional Neural Networks (CNN) to extract informative fe...

The BOLD signal of resting-state fMRI (rs-fMRI) records the functional brain connectivity in a rich dynamic spatio-temporal setting. However, existing methods applied to rs-fMRI often fail to consider both spatial and temporal characteristics of the data. They either neglect the functional dependency between different brain regions in a network or...

Objectives: The comorbidity of Human Immunodeficiency Virus (HIV) infection and alcoholism (ALC) is prevalent. Wernicke’s encephalopathy (WE), a neurological disorder resulting from thiamine depletion, has been generally associated with alcoholism but has also been reported in HIV infection. This study examined whether subclinical WE signs could co...

The extensive prenatal developmental growth period of the cerebellum renders it vulnerable to unhealthy environmental agents, especially alcohol. Fetal alcohol spectrum disorders (FASD) is marked by neurodysmorphology including cerebral and cerebellar volume deficits, but the cerebellar lobular deficit profile has not been delineated. Legacy MRI da...

A generally accepted framework derived predominately from animal models asserts that repeated cycles of chronic intermittent ethanol (EtOH; CIE) exposure cause progressive brain adaptations associated with anxiety and stress that promote voluntary drinking, alcohol dependence, and further brain changes that contribute to the pathogenesis of alcohol...

Adolescence is a time of continued cognitive and emotional evolution occurring with continuing brain development involving synaptic pruning and cortical myelination. The hypothesis of this study is that heavy myelination occurs in cortical regions with relatively direct, predetermined circuitry supporting unimodal sensory or motor functions and sho...

Volumes of thalamic nuclei are differentially affected by disease-related processes including alcoholism and human immunodeficiency virus (HIV) infection. This MRI study included 41 individuals diagnosed with alcohol use disorders (AUD, 12 women), 17 individuals infected with HIV (eight women), and 49 healthy controls (24 women) aged 39 to 75 years...

The tracking of dynamic functional connectivity (dFC) states in resting-state fMRI scans aims to reveal how the brain sequentially processes stimuli and thoughts. Despite the recent advances in statistical methods, estimating the high dimensional dFC states from a small number of available time points remains a challenge. This paper shows that the...

Presence of bias and confounding effects is inarguably one of the most critical challenges in machine learning applications that has alluded to pivotal debates in the recent years. Such challenges range from spurious associations of confounding variables in medical studies to the bias of race in gender or face recognition systems. One solution is t...

With recent advances in deep learning, neuroimaging studies increasingly rely on convolutional networks (ConvNets) to predict diagnosis based on MR images. To gain a better understanding of how a disease impacts the brain, the studies visualize the salience maps of the ConvNet highlighting voxels within the brain majorly contributing to the predict...

Neuropathy, typically diagnosed by the presence of either symptoms or signs of peripheral nerve dysfunction, remains a frequently reported complication in the antiretroviral (ART)-treated HIV population. This study was conducted in 109 healthy controls and 57 HIV-infected individuals to investigate CNS regions associated with neuropathy. An index o...

Objective: Alcohol use disorder (AUD) is a complex, dynamic condition that waxes and wanes with unhealthy drinking episodes and varies in drinking patterns and effects on brain structure and function with age. Its excessive use renders chronically heavy drinkers vulnerable to direct alcohol toxicity and a variety of comorbidities attributable to n...

Background: The cerebellum is a target of alcoholism-related brain damage in adults, yet no study has prospectively tracked deviations from normal cerebellar growth trajectories in adolescents before and after initiating drinking. Methods: Magnetic resonance imaging tracked developmental volume trajectories of 10 cerebellar lobule and vermis tis...

Background Among the neurological consequences of alcoholism is peripheral neuropathy. Relative to human immunodeficiency virus (HIV) or diabetes‐related neuropathies, neuropathy associated with alcohol use disorders (AUD) is understudied. In both the diabetes and HIV literature, emerging evidence supports a central nervous system (CNS) component t...

Recent advances in robust and reliable methods of MRI-derived cerebellar lobule parcellation volumetry present the opportunity to assess effects of Alcohol Use Disorder (AUD) on selective cerebellar lobules and relations with indices of nutrition and motor functions. In pursuit of this opportunity, we analyzed high-resolution MRI data acquired in 2...

With recent advances in deep learning, neuroimaging studies increasingly rely on convolutional networks (ConvNets) to predict diagnosis based on MR images. To gain a better understanding of how a disease impacts the brain, the studies visualize the salience maps of the ConvNet highlighting voxels within the brain majorly contributing to the predict...