Neuropsychoimaging Research Program Explores Addiction and Related Conditions

Dr. Goldstein studies disorders that affect decision-making and self-control such as drug addiction and intermittent explosive disorder

Each of our brains has regions that fuel what we feel and what is salient, or important to us. Our brains also have a control tower—a vast expanse of interconnected regions that participate in the choices we make based on the outcomes we may achieve. Scientists have long hypothesized that the key to uncovering what goes astray in individuals with addiction and other disorders that affect decision-making and self-control, lies in understanding how emotional signals are relayed to and from this area of our brain, known as the prefrontal cortex.

Rita Z. Goldstein, PhD, Professor of Psychiatry and Chief of the Neuropsychoimaging of Addiction and Related Conditions (NARC) Research Program at Icahn School of Medicine at Mount Sinai, has spent her entire career trying to understand the circuitry, pathways, and chemicals that affect this area of the brain. Under the direction of Dr. Goldstein and Nelly Alia-Klein, PhD, Associate Professor of Psychiatry and co-Chief of NARC, the research group conducts neuroimaging studies centering on individuals with self-control disorders. In particular, the NARC group explores how disturbances in self-control and intense emotional states contribute to craving and relapse in drug addiction or intense anger as in intermittent explosive disorder.

“Our laboratory focuses on understanding self-regulatory processes dependent on the prefrontal cortex—for example, one’s ability to evaluate and change one’s actions—and how they differ between healthy individuals and individuals suffering from substance use disorders or intermittent explosive disorder,” says Dr. Goldstein. “With a better understanding of this process, we may be able to develop and tailor therapies that could help individuals control disadvantageous impulses, and minimize or even prevent their risk of relapse.”

Dr. Goldstein was among the first scientists to report that individuals with drug addiction have deficits in higher-level cognitive functions such as self-control and salience attribution that are associated with activity in the prefrontal cortex. She is also one of the few scientists in the field who conducts neuroimaging in people with drug addiction as part of a model known as Impairments in Response Inhibition and Salience Attribution (iRISA). Dr. Alia-Klein applies this model and neuroimaging techniques to people with intermittent explosive disorder.

“Our multi-modality program of research is guided by the underlying working hypothesis that drug addicted individuals disproportionately attribute reward value to their drug of choice at the expense of other potentially but no-longer-rewarding stimuli, with an associated decrease in the ability to inhibit maladaptive drug use,” explained Dr. Goldstein in a press release in 2011.

Specifically, to better understand why some individuals have an impaired ability to control their behavior, the NARC lab utilizes a range of neuroimaging tools including functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and electroencephalography (EEG). These imaging tools are used in conjunction with neuropsychological tools, which are tests of cognition, emotion, and personality. Results on these tests help ground the imaging results in a comprehensive and in-depth study of human behavior.

Recently, the NARC lab has produced several highly cited studies. Using fMRI, one area of research shows that particular areas of the brain—that automatically tag stimuli as salient—respond strongly when cocaine addicted individuals are presented with drug-related words. This response may contribute to more drug use in susceptible individuals. Other studies have found impairments in sensitivity to reward and in sustained motivation in cocaine addiction. A PET study, which measured the activity of the enzyme monoamine oxidase A (MAO-A) in the brain of adults, found that individuals who have less activity of this enzyme also have high scores on personality measures of aggression.

The study of these individual differences has been a major focus of the NARC lab. The lab is also known for its pursuit of uncovering the effects of withdrawal and abstinence in addicted individuals. Results show that short-term withdrawal may be associated with worse emotional processing while longer-term withdrawal may be associated with worse cognitive function and information processing.

The NARC lab is also exploring how genetics may play a role in iRISA. For example, genetic contributions to drug cue reactivity as modulated by withdrawal are being explored. These more recent studies that target dopaminergic genes complement the lab’s previous focus on the monoamine oxidase gene, which has been associated with a detrimental effect on the morphological integrity of the prefrontal cortex in cocaine addicted individuals.

Specifically, individuals with cocaine addiction who have one variant of the monoamine oxidase gene, which is associated with impulsivity and aggression and is known as the “warrior” gene, had less grey matter in the prefrontal cortex than those with a different variant of this gene. It remains to be studied whether this research could help explain why some individuals with cocaine addiction have more severe outcomes than others. The NARC lab further plans to expand these efforts to include other genes and gene networks that are thought to be implicated in addiction and self-regulation.

Another important focus of the NARC lab is to develop interventions to decrease relapse and improve outcomes in individuals with drug addiction or intermittent explosive disorder. Previously, using pharmacological fMRI, Dr. Goldstein has discovered that oral methylphenidate, a mild stimulant commonly used in patients with ADHD, can improve self-control and normalize function in the prefrontal cortex of individuals addicted to cocaine. Methylphenidate has a similar action to cocaine in that it blocks the dopamine transporter but, administered orally, it does not increase craving.

The NARC lab plans to expand on these initial promising neuroimaging findings by testing the clinical efficacy of methylphenidate in combination with cognitive behavioral training. Scientists will explore if this stimulant, in combination with cognitive exercises, helps reduce drug use in addicted individuals and anger outbursts in individuals with intermittent explosive disorder. The lab is also testing the efficacy of neurofeedback in reducing disadvantageous behaviors and strong negative emotions.

Individuals with self-control impairments often show compromises in awareness of their own choices and severity of their disorder. Understanding the neurobiological underpinnings of these self-awareness deficits could help reduce disadvantageous choices and improve long-term outcome in these disorders. As a result, such imaging studies in humans have the potential to reduce harm from drug addiction and other disorders of self-control.