Psychiatrists Receive Neuroimaging Research Grants

Research Grants: The Iris & Junming Le Foundation Supports Four Neuroimaging Pilot Projects

The Iris & Junming Le Foundation Awards Committee at Mount Sinai Medical Center has selected four neuroimaging pilot projects to receive research grants for 2012-2013. The funding for these studies is made possible by a $250,000 gift from the Le Foundation to advance neuroimaging research conducted by young scientists in the early stages of their careers.

“The proposals we selected have the potential to make an enormous scientific and clinical impact in four key areas of psychiatry: autism spectrum disorders, major depression, obsessive-compulsive disorder (OCD) and post-traumatic stress disorders,” says Wayne K. Goodman, MD, Chairman and the Esther and Joseph Klingenstein Professor in the Department of Psychiatry at Mount Sinai. “These projects will help advance our understanding of the neurocircuitry of these disorders using state-of-the-art brain imaging.”

The award recipients are:

A. Ting Wang, PhD
Assistant Professor of Psychiatry and Neuroscience
Proposal: A Pilot Neuroimaging Study of 22q13 Deletion Syndrome

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by difficulties with social interaction, communication, and repetitive behaviors. Mutations and deletions of the SHANK3 gene, which results in 22q13 deletion syndrome, are a known cause of ASD. However, little is known about the brain systems underlying this syndrome.

Dr. Wang’s research will investigate the effects of SHANK3 deletions and mutations on brain function by comparing the neural circuitry of developmentally delayed individuals to those that have 22q13 deletion syndrome. Participants will undergo structural MRI to examine brain structure and volume, diffusion tensor imaging to examine white matter integrity, resting state fMRI to measure intrinsic brain activity, and fMRI to assess speech perception.

She hypothesizes that patients with 22q13 deletion syndrome will exhibit specific and unique differences in the regions of the brain associated with motor function, language skills, and social-emotional processing; decreased coherence in motor, language, and default mode networks; and reduced activation of the language regions.

“Characterizing the neural phenotype of this syndrome will help bridge the gap between SHANK3 mutations and the resulting behavioral features, and may be important in guiding the design of targeted treatments,” says Dr. Wang.

James W. Murrough, MD
Assistant Professor of Psychiatry and Neuroscience
Proposal: Functional Connectivity Biomarkers of Antidepressant Response to Ketamine

Approximately one in every three patients who are properly treated for major depression continue to suffer from significant depressive symptoms. Recently, the drug, ketamine, has been identified as an effective therapy for treatment-resistant depression (TRD). However, the mechanisms that cause ketamine to achieve an antidepressant response in the brain are still unknown.

“Currently, there is no reliable biological marker of the antidepressant response in patients,” says Dr. Murrough. “It is like trying to treat diabetes without a blood glucose test.”

Using functional neuroimaging techniques, Dr. Murrough will study the antidepressant response to ketamine that occurs in the brains of patients with TRD before and after they are treated with ketamine. In particular, he will investigate the impact of ketamine on the interaction between brain networks governing emotion generation and cognitive emotion regulation.

“The goal of this research program is to identify a valid and reliable biomarker that characterizes antidepressant response,” explains Dr. Murrough. “This will allow the field to move forward in developing more effective, urgently needed treatments.”

Heather Berlin, PhD, MPH, Assistant Professor of Psychiatry
Emily Stern, PhD, Assistant Professor of Psychiatry and Neuroscience
Proposal: Modulation of the Insula During Emotion Regulation Using Real-time Functional MRI

Monitoring and regulating emotional reactions are important for treating mood and anxiety disorders, including depression and obsessive-compulsive disorder. In Drs. Stern and Berlin’s study, healthy participants will learn to regulate negative emotional reactions to disgusting images by using real-time monitoring of their brain activity.

Previous studies have found that using cognitive strategies—such as distancing oneself emotionally from a stimulus—to reduce emotional reactions is associated with decreased activity in the regions of the brain that process negative emotion, such as the insula. However, Drs. Stern and Berlin suspect that individual differences in strategy have a large impact on the success of emotion regulation, particularly in patients with psychiatric disorders.

“Individual variability is not well addressed in most approaches to emotion regulation,” explains Dr. Stern. “Often, it is seen as a hindrance to scientific inquiry, rather than an aid.”

The study will compare how different regions of the insula (posterior vs. anterior) help the participants to reduce feelings of disgust. They will also try to determine whether certain neurofeedback signals are more effective for reducing disgust than others.

“A number of patient populations could benefit from learning to modulate their reaction to aversive, disorder-specific stimuli, including patients with obsessive-compulsive disorder, post-traumatic stress disorder, phobias, addiction, and anorexia nervosa,” says Dr. Berlin. “The ultimate goal is for patients to employ their own personalized strategy developed in the lab as an everyday coping mechanism.”

Daniela Schiller, PhD
Assistant Professor of Psychiatry and Neuroscience
Proposal: Neuroimaging of Personal Olfactory Memories

The olfactory system, which is responsible for the sensation of smell, is unique among the senses because it has the ability to form powerful and emotional memory associations. Previous research has shown that olfactory memories are more powerful and last longer than those elicited by other sensory modalities.

Dr. Schiller’s research seeks to understand the neural underpinnings of olfaction and memory, along with their relationship. Her study will examine brain activity during the perception of personally relevant odors, non-relevant odors, and subsequent memory recall. Participants will identify odors that they associate with autobiographical memories and be examined using fMRI scans. By targeting olfactory memory, Dr. Schiller expects to see robust, consistent activation in brain regions that serve the olfactory system as well as memory and emotional function.

The goal of the study is to identify a novel method for observing autobiographical memories as dynamic neural events unfold over many seconds. Dr. Schiller also hopes it will help gain insight into the cortical network that underlies memory recall as it relates to olfaction.

“Greater knowledge of olfactory memories may be valuable to the treatment and research of fear-related psychiatric disorders such as Post-traumatic Stress Disorder, which involves vivid memory episodes that are sometimes recalled through olfaction,” says Dr. Schiller.