Expertise:
Brain
electrophysiology; voltage clamping; dissociated neurons;
brain slice; whole animal brain recording; computer modeling;
physiological control; epilepsy; electromagnetics; hippocampus
Using feedback stimulation to control
epileptic seizures:
Epileptic seizures are a common disease that afflicts over
2.5 million Americans. These seizures can sometimes be prevented
with pharmaceutical treatment; however, over 25% of epilepsy
patients cannot be helped by antiepileptic drugs. For these
patients in whom seizures are sufficiently severe, the only
remaining option is surgical removal of brain tissue which
can sometimes result in severe neurological deficits. The
ultimate goal of this research is to engineer a less invasive
and potentially far less damaging alternative to surgery
for drug-refractory epilepsy patients. The overall goal is
to engineer a device similar in concept to an implantable
cardiac defribrillator in that it would detect the earliest
stages of a seizure and prevent or revert it using electrical
stimulation. This research requires exploration in diverse
but related fields such as nonlinear chaos theory and computer
programming as well as expertise in experimental biology.
Experiments are currently being focused on the hippocampus
and motor cortex, two regions of the brain that are frequent
foci for generation of epileptiform electrical activity.
Initial experiments have been performed using nonlinear mathematical
analysis and testing of control algorithms on rat hippocampal
slices which can be induced to produce spontaneous discharges
analogous to epileptic behavior seen in whole animals. Current
experiments being conducted in my laboratory are now trying
to apply these findings in in vivo studies in rats
to see whether the same dynamics and control principles apply
in the intact brain as in the brain slice and, if not, how
these control algorithms could be modified appropriately.
Recent advances in understanding and controlling chaotic
systems have provided an invaluable opportunity to apply
these principles toward manipulation of pathological electrical
activity in the brain. It would ultimately permit the ability
to prevent or revert seizures in the brain which would have
enormous benefits to public health as well as overall cost
savings to society.
Transcranial magnetic stimulation
for modulating brain activity:
Several modalities currently exist for the non-invasive
imaging of brain structures and functions with fairly high
spatial resolution. However, the equivalent ability to innervate
and excite brain structures non-invasively with high spatial
resolution is currently not available. Such capabilities
would have multiple uses in both medical and basic research
applications. For instance, the ability to precisely activate
specific brain structures that are pre-disposed to generating
epileptiform electrical activity (e.g., a seizure focus)
may help in both the diagnosis of the specific pathology
underlying the seizures as well as a possible means of disrupting
and reverting the aberrant electrical state of the tissue.
Alternatively, the capacity to activate specific neuronal
circuitry in the brain would be a powerful tool for deciphering
complex neuronal structure-function relationships and would
complement conventional neuroimaging. Currently, there does
exist a tool for non-invasively activating brain structures
known as transcranial magnetic stimulation (TMS). Use of
TMS in a clinical setting has already been reported for a
number of applications including the treatment of depression,
assessment of motor cortical function, and used with other
diagnostic modalities to investigate connectivity between
brain regions. However, many disadvantages exist with TMS
in its current state. These disadvantages include: (1) a
lack of firm understanding of the relationship between magnetic
fields and induced electrical states in the brain; (2) an
inability to excite deep brain structures without strongly
activating more superficial brain regions; (3) a lack of
coil designs explicitly tailored to different excitation
protocols; and (4) poor spatial specificity. There have been
some prior studies analyzing the effects of electromagnetic
fields on the brain relevant to TMS, however many of these
have made significant mathematical compromises which have
diminished their relevance. Therefore, the overall goal of
this research is to apply computational electromagnetics
and electrical design principles in order to improve and
further refine the technique of transcranial magnetic stimulation.
Specific research projects:
--EPILEPSY: My laboratory is studying the use of linear
and nonlinear control feedback techniques to suppress, revert,
or prevent epileptic seizures by application of electrical
stimulation to a seizure focus. We are also examining mechanisms
by which neural network organization in the brain can result
in seizure generation.
--TMS: We are employing computational
analysis (using finite element modeling, Maxwell’s
equations, and data from non-invasive imaging techniques)
of transcranial magnetic stimulation (TMS) for the purpose
of refining and improving this technique of noninvasive
stimulation of brain tissue via the use of dynamic magnetic
fields.
--NEURAL STEM CELLS: NewNeural, LLC has developed a patented
technique to convert bone-marrow derived stem cells into
functional neurons and then transplanting them into the brains
of experimental animals. Working with NewNeural, my laboratory
is studying how these new autologous implanted neurons compare
with native brain neurons in experimental animals with respect
to their electrophysiological characteristics.
-- NEAR IR IMAGING: We are developing the technology in
our lab to non-invasively record oxygenation and blood flow
levels in the brain using near infrared imaging. Such techniques
can be used to look at changes to blood flow and neural activity
prior or during seizures as well as to investigate alterations
in cerebral blood flow in response to diabetes.
Laboratory personnel:
M. Efkan Colpan, MD, Research Fellow
colpan@iit.edu
Yue (Colin) Li , Graduate Student
colinliyue@hotmail.com
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