2013

Dr. Pfaff’s research has focused on the effects of steroid hormones on nerve cells as they direct instinctive behaviors, as well as the influences of hormones and genes on generalized brain arousal.

Episodic memories can be thought of as a complex web of associations resulting from the co-occurrence of representations in experience. However, there are many stages of transformation, from the initial encoding of the experience to multiple reactivations of the memory. We know that, at each of these stages in the life of memory, there are critical processes that determine its ultimate fate. I will present our most recent work addressing the factors that determine the long-term fate of encoded associative memories. How do these memories stabilize over time? Evidence suggests that these initial memory traces subsequently become integrated into a distributed cortical system both during offline rest and online task performance. Further, hippocampal-cortical interactions during post- encoding awake rest and during conscious reactivation predict later associative memory performance, suggesting not only that memories become distributed over time but that this transformation is beneficial to memory stability.

Dr. Sullivan's research interests include understanding the neurobiology of infant attachment to the caregiver and the impact of attachment quality on cognitive and emotional development.

Parkinson’s disease (PD) is a chronic, progressive neurologic disorder that causes impairment of movement. Available treatments for PD offer relief of symptoms, but none are able to restore the neural structures that have degenerated. Neuroscientists have long believed that surviving mature neurons in the brain are incapable of new axon growth. However, there is emerging evidence that this belief is not true, that surviving neurons may be induced to re-grow axons by re-activation of molecular processes that are active during normal brain development. Our research explores gene therapy approaches to re-activation of these axon growth processes. The motor impairments in PD are due to the degeneration of dopaminergic neurons and their axons. We have investigated the ability of two genes that are active in axon growth during development: a kinase Akt and one of its downstream targets, the GTPase hRheb. We have found that both Akt and hRheb, when expressed in dopamine neurons by use of a viral vector, induce robust new axon growth and achieve partial restoration of function. At the time of first diagnosis of PD, 70% of the neurons of the substantia nigra still survive. If they can be induced to re-grow their axons, and re-establish their ability to release dopamine, it may be possible to offer substantial neurorestoration with clinical benefit. The promise of this approach is that this benefit will be achieved by endogenous dopamine neurons, in their normal locations, with intact connections and with normal regulatory mechanisms in place.

Dr. Sparrow’s research interest in automatic processes has guided her research in social cognition in two directions (a) the impact of others on feelings of authorship for our actions, and (b) the impact of priming on behavior as well as strategies for overcoming that impact. She also looks at how having constant access to information online, through search engines like Google, may be impacting our memory and cognitive processing.

The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult, as well as developing brain, possess a remarkable ability to show structural and functional plasticity in response to stressful and other experiences, including neuronal replacement, dendritic remodeling, and synapse turnover. This is particularly evident in the hippocampus, where all three types of structural plasticity have been recognized and investigated, using a combination of morphological, molecular, pharmacological, electrophysiological and behavioral approaches. The amygdala and the prefrontal cortex, brain regions involved in anxiety and fear, mood, cognitive function and behavioral control, also show structural plasticity. Acute and chronic stress cause an imbalance of neural circuitry subserving cognition, decision making, anxiety and mood that can increase or decrease expression of those behaviors and behavioral states. In the short term, such as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive; but, if the danger passes and the behavioral state persists along with the changes in neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies, as is the case for chronic or mood anxiety disorders. There are important sex differences in how the brain responds to stressors that are in urgent need of further exploration. Moreover, adverse early life experience, interacting with alleles of certain genes, produce lasting effects on brain and body via epigenetic mechanisms. While prevention is most important, the plasticity of the brain gives hope for therapies that take into consideration brain-body interactions.

Dr. Schiller's line of research focuses on the neural mechanisms underlying emotional control. Because the environment we live in is constantly changing, our learned emotional responses need to be continuously updated to appropriately reflect current circumstances. Understanding the neural mechanisms that make such emotional flexibility may shed light on the impairments leading to anxiety disorders and may also promote new forms of treatment.

The Silver Neurobiology Laboratory is examining how, at a molecular and cellular level, Circadian rhythms regulate our day-to-day life physiology and behaviors. A second line of research in her laboratory explores the functional role of immune system-mast cells in the neurobiology of behaviors including arousal, fear, and anxiety.

Dr. Gerber's research expertise lies in studying developmental psychopathology, attachment, as well as designing and performing trials of psychothotherapeutic process and efficacy. Dr. Gerber is leading the development of a novel paradigm for social cognition in the fMRI environment. He is interested in the association between surface morphology of the amygdala, hippocampus, and frontal cortex and measures of social adaptation.

Dr. Kennedy is part of the Nestler laboratory. The Nestler lab works to better understand the molecular mechanisms of addiction and depression. They use animal models of these disorders to identify the ways in which long-term exposure to drugs of abuse or stress changes the brain to lead to addiction- or depression-like syndromes. A major focus of this work is on drug- and stress-induced changes in gene expression and chromatin structure within the brain's reward circuitry.

Dr. LeDoux's work has focused on the study of the neural basis of emotions, especially fear and anxiety. His work has elaborated in detail how the brain detects and responds to danger, and learns and forms memories about threats.

Brain imaging is simply a tool, a technique. It does not provide scientifically privileged data, it alone cannot generate valid findings, and it cannot substitute for good study design. In most studies designs, imaging provides only correlational data and cannot inform us about the mechanisms of pathogenesis or treatment response. The next generation of imaging studies will increasingly yoke brain imaging to studies with designs that can provide greater causal inference for brain-based disease mechanisms and treatment responses, such as epidemiologicalstudies, longitudinal studies, high risk samples, and randomized clinical trials. Examples of each and their relevance to understanding disease mechanisms and informing real-world clinical care will be provided.

Dr. Neria’s research has been focused on the mental health consequences of exposure to extreme traumatic events among high-risk populations including war veterans, disaster survivors, and patients with severe mental illness (e.g., bipolar illness; depression; schizophrenia). He is also involved in developing and testing novel, neuroscience informed treatments for PTSD.

Dr. Appelbaum's research interests include informed consent, decisional competence, research ethics, prediction and management of violence by persons with mental illnesses, coercion in medical treatment and research, and other aspects of law and ethics in medicine. Among the issues he has been looking at are the use of behavioral genetic, neuroimaging, and electrophysiological data in the courts, and the return of genomic research results to research subjects