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Improving Quality Of Life In Epilepsy By Predicting Seizures

The first study to examine the activity of hundreds of individual human brain
cells during seizures has found that seizures begin with extremely diverse
neuronal activity, contrary to the classic view that they are characterized by
massively synchronized activity. The investigation by Massachusetts General
Hospital (MGH) and Brown University researchers also observed pre-seizure
changes in neuronal activity both in the cells where seizures originate and in
nearby cells. The report will appear in Nature Neuroscience and is
receiving advance online publication.

“Our findings suggest that
different groups of neurons play distinct roles at different stages of
seizures,” says Sydney Cash, MD, PhD, of the MGH Department of Neurology, the
paper’s senior author. “They also indicate that it may be possible to predict
impending seizures, and that clinical interventions to prevent or stop them
probably should target those specific groups of neurons.”

Epileptic
seizures have been reported since ancient times, and today 50 million
individuals worldwide are affected; but much remains unknown about how seizures
begin, spread and end. Current knowledge about what happens in the brain during
seizures largely comes from EEG readings, which reflect the average activity of
millions of neurons at a time. This study used a neurotechnology that records
the activity of individual brain cells via an implanted sensor the size of a
baby aspirin.

The researchers analyzed data gathered from four patients
with focal epilepsy – seizures that originate in abnormal
brain tissues – that could not be controlled by medication. The participants had
the sensors implanted in the outer layer of brain tissue to localize the
abnormal areas prior to surgical removal. The sensors recorded the activity of
from dozens to more than a hundred individual neurons over periods of from five
to ten days, during which each patient experienced multiple seizures. In some
participants, the recordings detected changes in neuronal activity as much as
three minutes before a seizure begins and revealed highly diverse neuronal
activity as a seizure starts and spreads. The activity becomes more synchronized
toward the end of the seizure and almost completely stops when a seizure ends.

“Even though individual patients had different patterns of neural
activity leading up to a seizure, in most of them it was possible to detect
changes in that activity before the upcoming seizure,” says co-lead and
corresponding author Wilson Truccolo, PhD, Brown University Department of
Neuroscience and an MGH research fellow. “We’re still a long way from being able
to predict a seizure – which could be a crucial advance in treating epilepsy –
but this paper points a direction forward. For most patients, it is the
unpredictable nature of epilepsy that is so debilitating, so just knowing when a
seizure is going to happen would improve their quality of life and could someday
allow clinicians to stop it before it starts.”

Cash adds, “We are using
ever more sophisticated methods to handle the large amounts of data we are
collecting from patients. Now we are assessing how well we actually can predict
seizures using ensembles of single neurons and are continuing to use these
advanced recording techniques to unravel the mechanisms that cause human
seizures and leveraging this knowledge to make the most of animal models.” Cash
is an assistant professor of Neurology at Harvard Medical School, and Truccolo
an assistant professor of Neuroscience (Research) at Brown.

Notes:

This study is an outgrowth of a continuing collaboration between
researchers at MGH, Brigham and Women’s Hospital (BWH), Brown and the Providence
VA Medical Center to develop and test technologies that record and monitor
neural activity both to assist with the diagnosis and treatment of neurological
disorders and also to restore communication, mobility and independence to
individuals with neurologic disease, injury or limb loss. The experimental
recording technology used in this study, the NeuroPort array, is closely related
to the BrainGate array that has enabled individuals with spinal cord injuries
and other neurological disorders to control a computer cursor with their
thoughts alone.

Jacob Donoghue of MGH Neurology is the co-lead author of
the Nature Neuroscience paper. Additional co-authors are Leigh Hochberg,
MD, PhD, MGH/BWH Neurology and Brown University; Emad Eskandar, MD, MGH
Neurology; Emery Brown, MD, PhD, MGH Anesthesia; Joseph Madsen, MD, and William
Anderson, MD, PhD, BWH Neurosurgery; and Eric Halgren, PhD, University of
California, San Diego. Truccolo and Hochberg are also affiliated with the
Providence VA Medical Center. The study was supported by grants from the Center
for Integration of Medicine and Innovative Technology, the National Institutes
of Health, Howard Hughes Medical Institute, the Klingenstein Foundation, the
Department of Veterans Affairs and the Doris Duke Charitable Foundation.

Source: Massachusetts General Hospital &Medical News Today

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