Our long-term research goal is the development of new approaches to the treatment of epilepsy based on a clearer understanding of the necessary steps in seizure initiation and propagation.
The two major themes in the lab are neuronal ion transport and the spread of activity in neural networks. Neuronal ion transport underlies signaling at all fast synapses. The importance of neuronal ion transport was underscored by our recent discovery that reversed ion transport in the immature brain was blocking the effects of the anticonvulsants most commonly used to treat neonatal seizures, and that a safe and well-characterized diuretic could ameliorate this condition.
Our work on the spread of excitation in neural networks combines fluorescent imaging of network activity with computerized analysis and modeling to understand how normal and abnormal signaling progresses through neural networks. We have found evidence for reentrant or circular patterns of neural activity that resemble cardiac fibrillation and precede seizures. We are currently testing whether this reentrant activation of neural circuits is the earliest stage of a seizure, and the stage at which intervention is most effective. We are also testing whether long-term reductions in the strength of synaptic connections between neurons in epileptic networks can reduce the probability of seizures.
Kevin J. Staley, MD
Research Interests: Epilepsy, synaptic physiology, neuronal ion transport, neural network activity.
Research Techniques: Single cell electrophysiology, in vivo radiotelemetry, ion-sensitive fluorescent imaging of ion transport and neural network activity, computer modeling.
Diseases Studied: Epilepsy
Trevor Balena, PhD, Research Fellow
Volodymyr Dzhala, PhD, Instructor in Neurology
Kiyoshi Egawa, MD, PhD, Research Fellow
M. Zelime Elibol MD, R25 Research Fellow
Joseph Glykys, MD, PhD, R25 Research Fellow
Michael Gutnick DVM, PhD, Research Sabbatical
Kyle Lillis, PhD, Research Fellow
Albert Misko MD, Research Fellow
Waldemar Swiercz, PhD, Instructor in Neurology
Zemin Wang MD, PhD, Research Fellow
Michelle Mail, Technologist, Lab Manager
Yero Saponjian, Technician
Patti Staley, Staff Assistant
Larry Chen, University of Illinois at Urbana-Champaign
Hillary Mullan, Oberlin College, OH
William Neylon, Dublin Institute of Technology, Ireland
|Trevor Balena, PhD||Volodymyr Dzhala, PhD||Kiyoshi Egawa MD, PhD||Joseph Glykys, MD, PhD|
|Kyle Lillis, PhD||Michelle Mail||Albert Misko, MD||Yero Saponjian|
|Waldemar Swiercz, PhD||Zemin Wang, MD, PhD||M. Zelime Elibol, MD|
Kyung-IL Park, MD, PhD, Neurology Department, Seoul Paik Hospital, Inje University, South Korea
Ji Lee, MD, PhD, MGH Pediatric Neurology Resident
Kristopher Kahle MD, PhD, MGH Neurosurgery Resident
Yevgeny Berdichevsky, PhD, Assistant Professor, Department of Electrical and Computer Engineering, Lehigh University, PA
Sonya Jakawich, PhD, Project Manager, Salinergy
Helen Sabolek-Consiglio, PhD, Assistant Professor, Department of Psychology, Regis College, MA
Jonas Dyhrfjeld-Johnsen, PhD, Senior Scientist, Sensorion Company, France
Chris French, MD, PhD, Physiology Department, University of Melbourne, Australia
Jon Mousalliy, MD, Emergency Medicine, North Shore Medical Center, Salem, MA
Jennifer Hellier, PhD, Assistant Professor, Director of CREATE Health Scholars, University of Colorado
Camila Cabarello, MIT, Cambridge, MA
Yun Xiang Chu - Harvard medical student (HST program)
Elon Gaffin-Cahn, Union College, NY
This cover of the journal Neuron illustrates the study of Glykys et al. 2009.
Cortical Seizures in Newborn Infants
Seizure activity in the cerebral cortex of the brain (represented by the white electrographic discharges in the illustration) is transmitted through subcortical brain regions to the muscles of the body, causing convulsions. However, cortical seizures in newborns are frequently observed on electrographic recordings without accompanying convulsions, a dissociation that is exacerbated by anticonvulsant treatment. Most newborn convulsions are treated with anticonvulsant drugs that enhance the activity of GABA, a neurotransmitter that inhibits neuronal activity and seizures by increasing the flow of chloride ions into neurons.
DClamp - Free data acquisition and analysis software for epilepsy animal research.
The main goal of this project is to provide free, open-source data acquisition and analysis software to the epilepsy research community. Our goal is to establish a common platform to facilitate data exchange and cooperation between research centers. DClamp is designed for unsupervised detection of ictal-like and inter-ictal-like events in very large EEG datasets, for example from days to months of continuous recordings. It includes algorithms for automatic detection, quantification, and analysis of seizures (White et al. J Neurosci Methods, 15;152:255-66, 2006) and interictal spikes (Dyhrfjeld-Johnsen et al. J Clin Neurophysiol 27:418-24, 2010; White et al. Epilepsia 51:371-83, 2010).
Currently DClamp can also be used for acquisition of in-vivo and in-vitro signals from as many as 64 separate channels or animals. Examples include chronic EEG data, ECoG data, extracellular field potentials, intracellular potentials, intracellular currents (using low cost acquisition cards). We plan to expand compatible hardware. Future expansions will include synchronization of signal recordings with surveillance videos. Project will be distributed as open source allowing users to modify the code.
Chloride Concentrations and GABA Signaling in Nonconvulsive Seizures
Using a genetically expressed chloride sensor and multiphoton microscopy, we show in this paper that cortical neurons in the developing mammalian brain have much higher chloride concentrations than do subcortical neurons (in the illustration, hotter colors represent higher chloride concentrations). These differences in chloride concentration lead to oppositely directed chloride flow, GABA signaling, and anticonvulsant effects in these two regions. The response of cortical neurons to GABA could be made to match the subcortical response by blocking the transporter that accumulates chloride in cortical neurons. Under these conditions, cortical seizure activity could be controlled as readily as subcortical seizure activity.
These differences provide the first candidate explanation for the puzzling dissociation of convulsions and electrographic seizure activity in newborns, the exacerbation of the dissociation by anticonvulsants, and the potential utility of blocking chloride transporters to improve control of nonconvulsive seizures in newborns.
Read about and apply for residency, fellowship and observership programs at http://www.massgeneral.org/neurology/education/.
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Kevin J. Staley, MD
Kevin J. Staley, MD
Mailcode: CNY 114-2-2600
Massachusetts General Hospital, Neurology Research
114 16th Street, Room 2600
Charlestown, MA 02129
Patient Appointments & Clinical Office
General Child Neurology Clinic
Epilepsy Service at Mass General Hospital for Children
Clinical Mailing Address
Kevin J. Staley, MD
Mailcode: WACC 7-708D
Department of Neurology
Massachusetts General Hospital
55 Fruit Street
Boston, MA 02114