Because calcium controls so much of the physiological behavior of cells, it is necessary to understand how its intracellular concentration is maintained in space and time. The research in our laboratory is directed toward understanding the processes that influence the movements of calcium within cells and the spatial and temporal gradients of intracellular free calcium that such movements generate.

Work in this laboratory is focused on the neural substrates of motor control in primates. Neurophysiological studies examine the response properties of individual neurons in various cortical and subcortical motor fields of awake, behaving monkeys. We also study the psychophysics of human motor control, both in normal subjects and in patients with various types of movement disorders associated with damage to cortical and subcortical motor fields. There is also an emphasis on developing neural network models of motor control circuitry. Connectionist models developed thus far include adaptive networks of artificial neurons that are capable of learning, without supervision, to control the three-dimensional reaching movements of a simulated robot arm.

My research focuses primarily on how volitional movement, motor learning, and organized motor behavior are represented in the human brain. We are interested in evaluating the effect of constraint-induced movement therapy on cortical motor reorganization following stroke using transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI). Future concerns address the use of complementary and alternative methods, such as mental imagery and virtual reality, as vehicles to expand rehabilitation interventional possibilities. We are interested in the relationship between molecular science and rehabilitation. Specifically, we seek to develop collaborations that permit ways to explore changes in the nervous system through blood samples or other biomarkers.

The focus of my research is to develop a new testing procedure to identify patients with mild cognitive impairment at the earliest stage possible. A subset of such patients go on to develop Alzheimer's disease. Early diagnosis would provide the opportunity to treat such patients at an earlier stage in order to reduce the rate of progression of the disease and improve their duration and quality of life.

Our research is directed at a better understanding of the functional organization of the basal ganglia and thalamus and the role of these structures in behavior and clinical disorders. We are particularly interested in the role of these structures in voluntary movement and in the pathophysiology of movement disorders. Our research employs the techniques of single cell recording from behaving animals, lesioning with neurotoxins, tract-tracing and combined anatomical/physiologic mapping.

The research projects in my laboratory investigate the molecular basis of the cell-to-cell communication which regulates the development, maintenance, regeneration, and plasticity of the vertebrate nervous system. In particular, we are focusing on understanding the biological activities of the neuregulin family of "growth and differentiation" (or "trophic") factors.

The theme of research in my laboratory is brain-body communication. Major questions include identifying the neurohumoral signals that inform the brain of the body's internal state, and identifying CNS pathways, neurotransmitters and synaptic receptors that participate in central autonomic, immune, cardiovascular, and endocrine regulation.

My research area is the decline in cognitive function with advancing age in the rhesus monkey, and the physiological and neural changes that accompany this decline.

Our laboratory focuses upon the organization and the role of the primate motor cortex in the control of learned, skilled movements. Two major areas of research are currently addressed. In the first, experiments are conducted with alert, behaving monkeys in which modern electrophysiological methods are used to examine the plasticity of motor cortical representations of the body. In the second series of experiments, we are examining the extent to which the discharge of motor cortical neurons can be brought under voluntary control by the alert animal.

The research in this laboratory uses neurochemical and behavioral techniques to study the mechanisms of drug action in the rat central nervous system (CNS). Comparing the effects of selective pharmacological probes and drug administration strategies we hope to better understand the neural basis of motor behaviors in animals.

My lab focuses on developing imaging methods to study networks of activity in the brain, primarily using magnetic resonance imaging (MRI) in rodent models. We have extended functional MRI studies to provide whole brain coverage in the rodent, allowing visualization of activated areas throughout the brain rather than solely somatosensory cortex (ref1, ref2). Current projects include using activation maps made with MRI as a basis for identifying genes that are differentially expressed during brain activity; using intrinsic signal fluctuations to map networks of synchronized activity in the rat brain; and investigating the effect of fear conditioning on olfactory activity using manganese-enhanced MRI.

Using a number of biochemical, physiological and molecular techniques, our lab is interested in the interactions between clinically useful psychotic drugs and neuropeptide transmitter systems in the brain. This includes investigation of 1) the role of neurotensin-containing neurons in the mechanism(s) of action of antipsychotic drugs, 2) the actions of antidepressant and anxiolytic drugs on the corticotropin-releasing factor (CRF) neurons in the CNS and 3) sex differences in the expression of peptide systems and the relevance of these differences to behavior. The overall goal of these studies is to investigate the therapeutic benefit of compounds targeting neuropeptide systems for the treatment of depression, anxiety and schizophrenia. An additional interest of the lab is the design and testing of short peptides which are synthesized based on nonlinear mathematical models of protein-protein interactions and may modulate membrane receptor function.

We study injury biomechanics and tissue engineering as they relate to traumatic brain and spinal cord injury. We use a multi-level approach to develop improved tolerance criteria and elucidate the acute cell and tissue response to traumatic loading. We have found that the neuronal plasma membrane is compromised following a traumatic insult and are investigating mechanisms of damage and repair, as well as possible therapeutic interventions. In addition, we have developed tissue engineering methods for the injured brain using bioactive scaffolds and neural stem cells as candidate donor cells. Scaffolds are designed to be injectable and to control cell behavior such as migration and differentiation.

My laboratory is engaged in research to understand the cellular and molecular mechanisms regulating the proliferation, migration and differentiation of neurons during the development of the mammalian forebrain. Our experiments will help elucidate the mechanisms underlying the directed migration of neurons in the developing CNS. We are also pursuing transplantation experiments to determine whether certain cells can substitute for the loss of neurons that occurs in Parkinson's disease or Huntington's disease.

My research interests are in the brain systems which control mood and motivation. Besides being of fundamental interest in the general problem of functional organization of the mammalian brain, these systems are also of interest for their possible roles in mood disorders and drug addiction. In my laboratory, we manipulate these systems and examine the resulting behavioral changes. In collaboration with the Justice laboratory in Chemistry, we manipulate these systems and examine the resulting neurochemical changes.

The Stress Neurobiology Laboratory is focused on the effects of stress hormones on the developing and adult brain, central nervous system regulation of the stress response, as well as the interaction between genes and early environment in programming the brain. A major focus of the lab is the study of the immediate and long-term consequences of early adverse experience (e.g., medical illness, abuse, neglect) on brain gene expression, behavioral, emotional, and neuroendocrine regulation as related to subsequent vulnerability to medical and psychiatric illnesses. The lab develops animal models in mice, rats and non-human primates as well as clinical studies.

My lab is interested in the brain systems and mechanisms that allow perceptual and cognitive abilities, such as object recognition, to emerge and reorganize during development and subsequent to brain injury. We perform neuroanatomical, electrophysiological and behavioral studies of the development, plasticity and comparative organization of the forebrain, with particular emphasis on extrastriate visual cortex in primates.

My research focuses on the interactions between central nervous system and muscle physiology to determine the fundamentals of motor control and its evolution in vertebrates. I believe that a comprehensive understanding of motor systems can best arise from comparative investigation of interactions between the multiple elements - cortex, brainstem, spinal cord, muscle - that control posture and movement. I am therefore pursuing this study through investigation of the basic neural principles that organize motor behavior and the phylogenetic constraints that limit and shape neuromuscular adaptation.