Our Research

At the Neuropsychoimaging of Addiction and Related Conditions (NARC) Research Program at Mount Sinai, our research team explores the human brain functions as they relate to drug addiction. Our research helps us learn how to improve the lives of people with addictions.  

Our current studies include:

Mindfulness-Oriented Recovery Enhancement for Treatment of Heroin Use Disorder

Overdose deaths related to opioid use (including heroin) continue to soar in the United States, with very little known about the neurobiology of heroin addiction or its treatment. According to seminal research in our lab, drug-biased salience attribution, accompanied by impairments in inhibitory control, characterizes the core symptomology of drug addiction. A promising addiction intervention that targets these deficits is the Mindfulness-Oriented Recovery Enhancement (MORE) program, an eight-week behavioral therapy that aims to reduce the excessive salience ascribed to drug cues, while enhancing natural reward responsiveness. In this randomized clinical trial, we assess neural function (e.g., reactivity to drug cues, inhibitory control) and structure in inpatient, medication-assisted individuals with heroin use disorder, before and after randomization into MORE or standard group therapy. We also focus on fluctuations in important clinical endpoints via naturalistic and longitudinal examinations of motivation, craving, and drug-use behaviors. The results from these investigations will contribute to our understanding of the brain bases of heroin addiction recovery and offer translational insights for effective therapeutic interventions.

This work is funded by NCCIH R01 AT010627. Clinical trial ID: NCT04112186.

Relevant Publications:

Sex Differences in the Neural Correlates Underlying Cocaine and Heroin Addiction

The Sex Differences project seeks to investigate the neurobiological underpinnings of sex differences in substance use disorder (SUD), with a specific focus on cocaine addiction in women. Despite evidence demonstrating that women are at a greater risk of experiencing more severe addiction-related symptoms and drug-use patterns, as well as relapse, neuroimaging studies have largely overlooked women participants. The project aims to address this research gap and examine the effect of the menstrual cycle (i.e., follicular versus luteal phase) on the functions of reward/salience attribution and inhibitory control under the impaired response inhibition and salience attribution (iRISA) model. By recruiting equal numbers of women and men, including individuals with SUD and healthy controls, the project aims to elucidate the mechanisms underlying SUD in women and develop gender-tailored interventions to reduce craving and improve treatment outcomes. Through this research, the project hopes to make a significant contribution to addressing the unique public health concern of the rapid increase in drug use among women in the United States.

This work is funded by NIDA R01 DA048301-01A1.

Relevant Publications:

Transcranial Direct Current Stimulation (tDCS) for Treatment of Cocaine Use Disorder

Transcranial direct current stimulation (tDCS) is a brain stimulation technique that uses weak constant currents and produces lasting functional changes in the central nervous system. It is a noninvasive, low-cost, well tolerated, and importantly in the current context, portable device that can be used outside of clinical settings. The goal of this clinical trial is to establish the efficacy of repeated tDCS over the dorsolateral prefrontal cortex in reducing cravings in individuals with cocaine use disorder living in inpatient drug-rehabilitation facilities, where self-administration using home-tDCS devices could improve treatment reach and compliance. Individuals with cocaine use disorder receive 15 sessions of tDCS over five weeks and multiple EEG recordings and behavioral assessments to measure changes in objective and subjective drug cravings as well as general drug-related clinical variables, cognitive functioning, and sleep/wake cycle variability.

This work is funded by NIDA 271201800035C-0-0-1.
Clinical trial IDs: NCT03833583 (phase I) and NCT04994821 (phase II)

Relevant Publications:

Imaging Atherosclerosis in Drug Addiction

This multidisciplinary project is led by Principal Investigator Nelly Alia-Klein, PhD. People with cocaine use disorders (CUD) often have years of exposure to the drug, reaching into middle adulthood and later. It is known that people with SUD are at increased risk of strokes, often triggered by buildup of atherosclerotic plaque in coronary arteries. The neurovascular effects of chronic cocaine can also result in cognitive dysfunction. The goal of this study is to determine if coronary artery disease, as examined by ultrasound and clinical methods, will correlate with cognitive processing and brain function as examined with functional MRI. Results from this multidisciplinary study could identify major risk factors for the decline in quality of life and cognitive function that could be observed in people with chronic cocaine exposure.

This work is funded by NIDA R01 DA049547-01.

Relevant Publications

Targeting Neural, Behavioral, and Pharmacological Mechanisms of Drug Memories with Methylphenidate

Salient memories of the drug use contribute to craving and relapse even after long periods of abstinence. Traditional cue-exposure therapies aimed at extinguishing these memories have not been effective at preventing relapse, warranting the development of alternative strategies. The goal of this project is to identify a pharmacologically enhanced learning and memory approach that aims to decrease craving and relapse in drug addiction. Here, we target the mechanisms underlying memory reconsolidation, a time-dependent process in which specific consolidated memories may become amenable to change (e.g., memory disruption). We will enhance this behavioral approach pharmacologically in individuals with cocaine use disorder (iCUD), using methylphenidate (MPH, a dopamine agonist) as a cognitive enhancer to promote learning-induced neural plasticity in iCUD. In a placebo-controlled design, we will psychophysiologically measure memory modification via functional magnetic resonance imaging and skin conductance responses following MPH, with a follow-up the following day, permitting the assessment of drug-cue memory disruption and effects on craving. Results from this project could ultimately be used to develop effective cue-exposure therapies to reduce cue-induced craving and relapse.

This work is funded by NIDA 1R21DA054281-01.
Clinical trial ID: NCT05978167

Relevant publications:

Neurofeedback During Naturalistic Stimuli to Reduce Craving in Heroin Addiction

Support groups are an important component of addiction treatment, where individuals at more stable stages of their recovery help others by sharing personal experiences. This phenomenon suggests that the brain states of individuals further along in their recovery process may be useful in guiding those who are at an earlier stage. In this project, we will test this idea and develop a personalized therapeutic tool based on real-time fMRI neurofeedback, whereby individuals with heroin use disorder (iHUD) early in treatment will learn to modulate their own brain state to more closely align with iHUD who are at later stages of treatment.  Specifically, iHUD exhibit heightened reactivity to naturalistic drug cues in brain networks underlying salience attribution, reward processing, executive function and others.  This fMRI brain hyperactivity pattern is reduced, concomitant with craving reductions, with about 3 months of inpatient treatment. In this neurofeedback project, iHUD who are beginning treatment will view naturalistic drug cues and receive feedback about how similar their brain activity is to the target recovery pattern, learning to modulate their own brain activity to reduce drug cue reactivity and craving.  This study will offer insights into the mechanisms of recovery in addiction, particularly as coordinated across individuals with shared experience and goals.  If successful, the neurofeedback-based training may lead to new brain-based and personalized tools for recovery in this devastating disorder.

This work is funded by NIDA R21DA058801-01.

Craving Incubation and Cognitive Reappraisal in Cocaine Addiction

Among the many addictions, cocaine addiction is particularly treatment-resistant, with estimated relapse rates greater than 45%. While most abstaining individuals with cocaine use disorders (iCUD) relapse within the first few weeks and months of abstinence, relapse continues to occur long after acute withdrawal has abated. Re-exposure to cues previously associated with drug use that evoke intense craving and associated brain reactivity that can be psychophysiologically measured (i.e., cue-induced craving) is a major contributing factor in relapse to drug use. Studies show cue-induced craving to increase with time into abstinence before decreasing, an incubation of craving that renders abstaining iCUD vulnerable to relapse. Using electroencephalography, we tracked attention to salient stimuli including drug-cues in initially abstaining iCUD, with longitudinal results replicating cross-sectional ones in demonstrating this dynamic vulnerability factor. In the current longitudinal project, performed at carefully selected abstinence durations, we will test whether this drug cue reactivity, and incubation of craving itself, can be suppressed with cognitive reappraisal of salient drug cues, a prefrontal cortex-mediated emotion regulation strategy. We will also explore whether the expected reductions in incubation of cue-reactivity track treatment response and predict clinical outcomes at 6 months follow-up. The ultimate goal is to improve clinical outcomes (e.g., reduce craving and prolong cocaine abstinence duration during the first 6 months of abstinence in iCUD).

This work is funded by NIDA R01DA041528-02 and R01DA058039-01A1.  

Relevant publication:

Diagnostic and prognostic biomarkers for subtypes of addictions-related circuit dysfunction

In collaboration with Conor Liston, MD, PhD, of Weil Cornell, we are using a recently developed and validated approach to discovering and diagnosing subtypes of SUD using functional magnetic resonance imaging (fMRI) measures of functional connectivity. In a secondary data analysis, we are leveraging multiple deeply characterized and large-scale neuroimaging datasets. Our central hypothesis is that individual differences in mechanisms underlying iRISA are mediated by distinct forms of dysfunctional connectivity in addiction-related circuits, which in turn interact and give rise to distinct neurophysiological addiction subtypes. Here we are using statistical clustering and machine-learning methods to delineate these subtypes and optimize classifiers (fMRI biomarkers) for diagnosing them in individual patients, focusing initially on cocaine addiction. Then, we validate these subtype-specific biomarkers by first replicating them in a new dataset and then evaluating their longitudinal stability and predictive utility. Finally, we will test whether subtype-specific circuit mechanisms generalize to mediate iRISA functions in other forms of addiction, and define their interactions with distinct mechanisms mediating anhedonia and anxious arousal in patients with comorbid depression and anxiety.

This work is funded by NIDA R01 DA047851-01A1.