Nelly Alia-Klein

Icahn School of Medicine at Mount Sinai | MSSM · Department of Psychiatry

Drug addiction is accompanied by enhanced salience attributed to drug over nondrug cues. This objectively measured bias is reliable yet underutilized in informing clinical endpoints, as clinical trials largely employ subjective (i.e., self-report or interview-based drug use and craving) or simple categorical (e.g., drug in urine) measures, with lim...

Importance Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. White matter impairments in individuals with heroin use disorder (HUD) have been associated with drug craving, a reliable predictor of treatment outcomes; however, little is kn...

Objective: To study the sex and hormonal effects on cortico-striatal engagement during drug cue-reactivity and its regulation focusing on drug reappraisal. Methods: Forty-nine men (mean age=41.96; SD age=9.71) with heroin use disorder (HUD) and 32 age-matched women (mean age=38.85; SD age=9.84) with HUD (n=16) or cocaine use disorder (CUD; n=16) we...

Movies captivate groups of individuals (the audience), especially if they contain themes of common motivational interest to the group. In drug addiction, a key mechanism is maladaptive motivational salience attribution whereby drug cues outcompete other reinforcers within the same environment or context. We predicted that while watching a drug-them...

Background Heroin and other opioid use disorders (HUD and OUD) cause massive public health morbidity and mortality. Although standard-of-care medication assisted treatment (MAT) exists, little is known about potential predictors of change during recovery. Recovery can include normalization of the brain’s white matter (WM) microstructure, which is s...

Introduction: Abnormalities in goal-directed behavior, mediated by mesocorticolimbic reward function and structure, contribute to worse clinical outcomes including higher risk of treatment dropout and drug relapse in opioid users (OU). Material and Method: In a sham-controlled randomized study design, we measured whether robot-assisted 10Hz transcr...

Opioid use disorders cause major morbidity and mortality, and there is a pressing need for novel mechanistic targets and biomarkers for diagnosis and prognosis. Exposure to mu-opioid receptor (MOR) agonists causes changes in cytokine and inflammatory protein networks in peripheral blood, and also in brain glia and neurons. Individuals with heroin u...

Question The opioid epidemic causes massive morbidity, and males have substantially greater overdose mortality rates than females. It is unclear whether there are sex-related disparities at different stages in the trajectory of opioid use disorders, in “real world” settings. Goal To determine sex disparities in non-medical opioid use (NMOU) at the...

Background Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse, which poses challenges in treatment. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome in living individuals are limited. Therefore, we investigated the connection between drug use behaviors during abs...

Importance: Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment ou...

Opioid use disorders cause major morbidity and mortality, and there is a pressing need for novel mechanistic targets and biomarkers for diagnosis and prognosis. Exposure to mu-opioid receptor (MOR) agonists causes changes in cytokine and inflammatory protein networks in peripheral blood, and also in brain glia and neurons. Individuals with heroin u...

OBJECTIVES/GOALS: Using biomarkers to identify vulnerabilities from cocaine use disorder (CUD) is a focus of recent investigations. Current clinical efforts focus on psychiatric recovery in CUD, however other body systems are missed. Applying blood-based transcriptomics to investigate how clinical conditions relate to CUD can alter current treatmen...

Movies captivate groups of individuals (the audience), especially if they contain themes of common motivational interest to the group. In drug addiction, a key mechanism is maladaptive motivational salience attribution whereby drug cues outcompete other reinforcers within the same environment or context. We predicted that while watching a drug-them...

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective const...

Lapses in inhibitory control have been linked to relapse in human drug addiction. Evidence suggests differences in inhibitory control depending on abstinence duration, but the underlying neural mechanisms remain unknown. We hypothesized that early abstinence (2–5 days) would be characterized by the strongest impairments of inhibitory control and mo...

Opioid use disorder (OUD) is a major current cause of morbidity and mortality. Long-term exposure to short-acting opioids (MOP-r agonists such as heroin or fentanyl) results in complex pathophysiological changes to neuroimmune and neuroinflammatory functions, affected in part by peripheral mechanisms (e.g., cytokines in blood), and by neuroendocrin...

Importance: Valid biomarkers that can predict longitudinal clinical outcomes at low cost are a holy grail in psychiatric research, promising to ultimately be used to optimize and tailor intervention and prevention efforts. Objective: To determine if baseline linguistic markers in natural speech, as compared to non-speech clinical and demographic me...

Objective: The authors investigated cortico-striatal reactivity to drug cues (as compared with neutral and food cues), drug cue reappraisal, food cue savoring, and their correlations with heroin craving in individuals with heroin use disorder compared with healthy control subjects. Methods: Cross-sectional changes in functional MRI blood-oxygen-...

Drug overdoses from opioids and stimulants are a major cause of mortality in the United States. It is unclear if there are stable sex differences in overdose mortality for these drugs across states, whether these differ across the lifespan, and if so, whether they can be accounted for by different levels of drug misuse. This was a state-level analy...

Importance: Heroin addiction and related mortality impose a devastating toll on society, with little known about the neurobiology of this disease or its treatment. Poor inhibitory control is a common manifestation of prefrontal cortex (PFC) impairments in addiction, and its potential recovery following treatment is largely unknown in heroin (or any...

Importance Drug overdoses from opioids like fentanyl and heroin and stimulant drugs such as methamphetamine and cocaine are a major cause of mortality in the United States, with potential sex differences across the lifespan. Objective To determine overdose mortality for specific drug categories across the lifespan of males and females, using a nat...

Heroin addiction imposes a devastating toll on society, with little known about its neurobiology. Excessive salience attribution to drug over non-drug cues/reinforcers, with concomitant inhibitory control decreases, are common mechanisms underlying drug addiction. While inhibitory control alterations generally culminate in prefrontal cortex (PFC) h...

Neuroimaging studies in substance use disorder have shown widespread impairments in white matter (WM) microstructure suggesting demyelination and axonal damage. However, substantially fewer studies explored the generalized vs. the acute and/or specific drug effects on WM. Our study assessed whole-brain WM integrity in three subgroups of individuals...

Different drugs of abuse impact the morphology of fronto-striatal dopaminergic targets in both common and unique ways. While dorsal striatal volume tracks with addiction severity across drug classes, opiates impact ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAcc) neuroplasticity in preclinical models, and psychostimulants alter i...

The habenula (Hb) is central to adaptive reward- and aversion-driven behaviors, comprising a hub for higher-order processing networks involving the prefrontal cortex (PFC). Despite an established role in preclinical models of cocaine addiction, the translational significance of the Hb and its connectivity with the PFC in humans is unclear. Using di...

Heroin addiction imposes a devastating toll on society, with little known about its neurobiology. Excessive salience attribution to drug over non-drug cues/reinforcers, with concomitant inhibitory control decreases, are common mechanisms underlying drug addiction. While inhibitory control alterations generally culminate in prefrontal cortex (PFC) h...

We present here a unifying framework for affective phenomena: the Human Affectome. By synthesizing a large body of literature, we have converged on definitions that disambiguate the commonly used terms—affect, feeling, emotion, and mood. Based on this definitional foundation, and under the premise that affective states reflect allostatic concerns,...

Importance Heroin addiction is rampant and persistent, with devastating consequences to the public health, necessitating further study into the neurobiological mechanisms of drug cue-reactivity and craving-reducing interventions (e.g., reappraisal and savoring). Objective To document cortico-striatal reactivity during passive viewing, reappraisal,...

Objective Individuals with an evening chronotype prefer to sleep later at night, wake up later in the day and perform best later in the day as compared to individuals with morning chronotype. Thus, college students without ADHD symptoms with evening chronotypes show reduced cognitive performance in the morning relative to nighttime (i.e., desynchro...

Neuroimaging studies in substance use disorder have shown widespread impairments in white matter (WM) microstructure suggesting demyelination and axonal damage. However, substantially fewer studies explored generalized vs. acute/specific drug effects on WM. Our study assessed whole-brain WM integrity in three subgroups of addicted individuals, enco...

Introduction: Drug addiction is characterized by impaired response inhibition and salience attribution (iRISA), where the salience of drug cues is postulated to overpower that of other reinforcers with a concomitant decrease in self-control. However, the neural underpinnings of the interaction between the salience of drug cues and inhibitory contr...

Drugs of abuse impact cortico-striatal dopaminergic targets and their morphology across substance types in common and unique ways. While the dorsal striatum drives addiction severity across drug classes, opiates impact ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAcc) neuroplasticity in preclinical models, and psychostimulants alt...

Drug addiction is characterized by neuroadaptations in mesocorticolimbic networks regulating reward and inhibitory control. The habenula (Hb) is central to adaptive reward and aversion-driven behaviors, serving as a hub connecting emotion/cognitive processing regions including the prefrontal cortex (PFC). However, its role in human drug addiction h...

Drug-related cues hijack attention away from alternative reinforcers in drug addiction, inducing craving and motivating drug-seeking. However, the neural correlates underlying this biased processing, its expression in the real-world, and its relationship to cue-induced craving are not fully established, especially in opioid addiction. Here we track...

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...

Drug addiction is characterized by impaired Response Inhibition and Salience Attribution (iRISA), where the salience of drug cues is postulated to overpower that of other reinforcers with a concomitant decrease in self-control. However, the neural underpinnings of the interaction between the salience of drug cues and inhibitory control in drug addi...

Significance This study assessed whether habitual (drug-related) attentional processes can be disrupted by cognitive reappraisal, an adaptive emotion regulation strategy that is presumed to deploy prefrontal cortex–mediated cognitive control, in cocaine-addicted individuals. The novelty of the current study is in the multimethod integration of outc...

RationaleEmotion recognition is impaired in drug addiction. However, research examining the effects of cocaine use on emotion recognition yield mixed evidence with contradictory results potentially reflecting varying abstinence durations.Objectives Therefore, we investigated emotion recognition and its neural correlates in individuals with cocaine...

Impaired inhibitory control accompanied by enhanced salience attributed to drug‐related cues, both associated with function of the dorsolateral prefrontal cortex (dlPFC), are hallmarks of drug addiction, contributing to worse symptomatology including craving. dlPFC modulation with transcranial direct current stimulation (tDCS) previously showed cra...

The enzyme aromatase catalyzes the final step in estrogen biosynthesis, converting testosterone to estradiol, and is expressed in the brain of all mammals. Estrogens are thought to be important for maintenance of cognitive function in women, whereas testosterone is thought to modulate cognitive abilities in men. Here, we compare differences in cogn...

Impaired inhibitory control accompanied by enhanced salience attributed to drug-related cues, both dorsolateral prefrontal cortex (dlPFC) functions, are hallmarks of drug addiction, contributing to worse symptomatology including craving. dlPFC modulation with transcranial direct current stimulation (tDCS) showed craving reduction in inpatients with...

Significance Obesity is a major public health problem in a growing proportion of children and adults in the developed world. Estrogen influences body weight and behavioral responses to appetitive stimuli. Estrogen biosynthesis is catalyzed by the enzyme aromatase in all organs measured, including the brain. Using the aromatase radiotracer [ ¹¹ C]vo...

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...

Background Multiple psychopathologies feature impaired clinical insight. Emerging evidence suggests that insight problems may similarly characterize addiction, perhaps due to aberrant functioning of self-referential brain circuitry, including the rostral anterior cingulate and ventromedial prefrontal cortices (rACC/vmPFC). We developed a new fMRI t...

Background: High blood pressure (BP) is associated independently with cocaine use and lead exposure. It is not known whether cocaine use and lead exposure act jointly to disrupt cardiovascular health. Objective: To determine whether cocaine use modifies the association between cumulative lead levels and elevated BP. Materials and Methods: We measur...

Background: Chronic cocaine use is associated with stroke, coronary artery disease and myocardial infarction, resulting in severe impairments or sudden mortality. In the absence of clear cardiovascular symptoms, individuals with cocaine use disorder (iCUD) seeking addiction treatment receive mostly psychotherapy and psychiatric pharmacotherapy, wi...

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 impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six...

Anger is considered a unique high-arousal and approach-related negative emotion. The influence of individual differences in trait anger on the processing of visual stimuli is relevant to questions about emotional processing and remains to be explored. Using functional magnetic resonance imaging (fMRI), we explored the neural responses to standardiz...

Results and discussion. Functional MRI activations to pleasant IAPS conditions of high and low arousal, inclusive of results and discussion on response to pleasant images. (DOCX)

Background: Childhood trauma affects neurodevelopment and promotes vulnerability to impaired constraint, depression, and addiction. Reduced gray matter concentration (GMC) in the mesocorticolimbic regions implicated in reward processing and cognitive control may be an underlying substrate, as documented separately in addiction and for childhood tra...

Impairments in response inhibition and salience attribution (iRISA) have been proposed to underlie the clinical symptoms of drug addiction as mediated by cortico-striatal-thalamo-cortical networks. The bulk of evidence supporting the iRISA model comes from neuroimaging research that has focused on cortical and striatal influences with less emphasis...

Background The choice for drugs over alternative reinforcers is a translational hallmark feature of drug addiction. The neural basis of such drug-biased choice is not well-understood, particularly in individuals with protracted drug abstinence who cannot ethically participate in studies that offer drug-using opportunities. Methods We developed an...

The neurobiological mechanisms that underlie the resistance of drug cue associations to extinction in addiction remain unknown. Fear extinction critically depends on the ventromedial prefrontal cortex (VMPFC). Here, we tested if this same region plays a role in extinction of non-fear, drug and pleasant cue associations. Eighteen chronic cocaine use...

Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use...

Background: Increased attention bias toward drug-related cues over non-drug-related intrinsically pleasant reinforcers is a hallmark of drug addiction. In this study we used the late positive potential (LPP) to investigate whether such increased attention bias toward drug-related relative to non-drug-related cues changes over a protracted period o...

Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation i...

A core deficit in drug addiction is the inability to inhibit maladaptive drug-seeking behavior. Consistent with this deficit, drug-addicted individuals show reliable cross-sectional differences from healthy nonaddicted controls during tasks of response inhibition accompanied by brain activation abnormalities as revealed by functional neuroimaging....

In some psychiatric patients, negative emotions are expressed as agitation and anger, which could lead to aggressive and violent behaviors, endangering the patient and others. This chapter describes diagnosis and management of patients who exhibit agitation and aggression. Psychiatric disorders in the DSM-5 such as antisocial and borderline persona...

The propensity for reactive aggression (RA) which occurs in response to provocation has been linked to hyperresponsivity of the mesocorticolimbic reward network in healthy adults. Here, we aim to elucidate the role of the mesocorticolimbic network in clinically significant RA for two competing motivated behaviors, reward-seeking vs. retaliation. 18...

Background: Increased attention bias toward drug-related cues over non-drug-related intrinsically pleasant reinforcers is a hallmark of drug addiction. In this study we used the late positive potential (LPP) to investigate whether such increased attention bias toward drug-related relative to non-drug-related cues changes over a protracted period o...

Deficits in prefrontal cortical (PFC) function have been consistently reported in individuals with cocaine use disorders (iCUD), and have separately been shown to improve with longer-term abstinence. However, it is less clear whether the PFC structural integrity possibly underlying these deficits is also modulated by sustained reduction in drug use...

Dysfunctional self-awareness has been posited as a key feature of drug addiction, contributing to compromised control over addictive behaviors. In the present investigation, we showed that, compared with healthy controls (n=13) and even individuals with remitted cocaine use disorder (n=14), individuals with active cocaine use disorder (n=8) exhibit...