epilepsy

Because the severe autism-like condition Christianson syndrome was first reported only in 1999 and some symptoms take more than a decade to appear, families and doctors urgently need fundamental information about it. A new study that doubles the number of cases now documented in the scientific literature provides the most definitive characterization of CS to date. The authors of the study propose the first diagnostic criteria for the condition. “We’re hoping that clinicians will use these criteria and that there will be more awareness among clinicians and the community about Christianson syndrome,” said Dr. Eric Morrow, assistant professor of biology and psychiatry and human behavior at Brown University and senior author of the study in press in Annals of Neurology. “We’re also hoping this study will impart an opportunity for families to predict what to expect for their child and what’s a part of the syndrome.”

The Department of Defense on Tuesday announced a $40 million investment in what has become the fastest-moving branch of neuroscience: direct brain recording. Two centers, one at the University of Pennsylvania and the other at the University of California, Los Angeles, won contracts to develop brain implants for memory deficits. Their aim is to develop new treatments for traumatic brain injury, the signature wound of the wars in Iraq and in Afghanistan. Its most devastating symptom is the blunting of memory and reasoning. Scientists have found in preliminary studies that they can sharpen some kinds of memory by directly recording, and stimulating, circuits deep in the brain. Unlike brain imaging, direct brain recording allows scientists to conduct experiments while listening to the brain’s internal dialogue in real time, using epilepsy patients like Ralph or people with Parkinson’s disease as active collaborators.

Optogenetics, a technology that allows scientists to control brain activity by shining light on neurons, relies on light-sensitive proteins that can suppress or stimulate electrical signals within cells. This technique requires a light source to be implanted in the brain, where it can reach the cells to be controlled. MIT engineers have now developed the first light-sensitive molecule that enables neurons to be silenced noninvasively, using a light source outside the skull. This makes it possible to do long-term studies without an implanted light source. The protein, known as Jaws, also allows a larger volume of tissue to be influenced at once. This noninvasive approach could pave the way to using optogenetics in human patients to treat epilepsy and other neurological disorders, the researchers say, although much more testing and development is needed.

A newly discovered biomarker – visible in brain scans for hours after febrile seizures – predicts which individuals will subsequently develop epilepsy, according to UC Irvine researchers. This diagnostic ability could lead to improved use of preventive therapies for the disorder. “This promising study raises the possibility of identifying children who might be at the highest risk of long-term injury,” said Brandy Fureman, program director at National Institute of Neurological Disorders and Stroke. “It also may help scientists develop effective ways to prevent brain injury after febrile status epilepticus.”

A new research protocol developed at Stanford University in California improves on their previous technological breakthrough and lets neuroscientists visualize a brain across multiple scales, says program manager Dr. Justin Sanchez. Stanford scientists earlier developed a method called Clear, Lipid-exchanged, Acrylamide-hybridized Rigid, Imaging/immunostaining compatible, Tissue hydrogel (CLARITY) to study brain tissue. The method uses a chemical to transform intact biological tissues into a hydrogel hybrid, which makes the brain tissues transparent. “Brains are not clear to begin with, therefore if you’re trying to use, let’s say, a microscope to study the volume of tissue of the brain, the light can’t transverse through all of the structure,” Sanchez explains. “However, if you do ‘clarify’ it using this very novel technique, then you are able to get through a volume of tissue and study all of the circuitry.” Under the CLARITY protocol, Sanchez says, it could take upwards of 80 years to conduct the imaging process for a complete human brain. But the new protocol accelerates the process so that the same technique now takes 220 days.

“Our study shows that the inhibitory neurons are the master regulators that contact hundreds or thousands of cells and make sure that the inhibitory synapses at each of these contacts is matched to the different amounts of excitation that these cells are receiving,” Scanziani explained. If, for example, the level of excitatory stimulation that a nerve cell is receiving is doubled, the inhibitory synapses over a period of a few days will also double their strength. In terms of clinical applications, the scientists said that neurological diseases such as autism, epilepsy and schizophrenia are believed to be a problem, at least in part, of the brain’s ability to maintain an optimal E/I ratio.

When you look at the brain, what you see is the fatty outer covering of the nerve cells within, which blocks microscopes from taking images of the intricate connections between deep brain cells. The idea behind CLARITY was to eliminate that fatty covering while keeping the brain intact, complete with all its intricate inner wiring. To help expand the use of CLARITY, the team devised an alternate way of pulling out the fat from the hydrogel-embedded brain – a technique they call passive CLARITY. It takes a little longer, but still removes all the fat, is much easier and does not pose a risk to the tissue. “Electrophoretic CLARITY is important for cases where speed is critical, and for some tissues,” said Deisseroth, who is also the D.H. Chen Professor. “But passive CLARITY is a crucial advance for the community, especially for neuroscience.” Passive CLARITY requires nothing more than some chemicals, a warm bath and time. Many groups have begun to apply CLARITY to probe brains donated from people who had diseases like epilepsy or autism, which might have left clues in the brain to help scientists understand and eventually treat the disease. But scientists, including Deisseroth, had been wary of trying electrophoretic CLARTY on these valuable clinical samples with even a very low risk of damage. “It’s a rare and precious donated sample, you don’t want to have a chance of damage or error,” Deisseroth said. “Now the risk issue is addressed, and on top of that you can get the data very rapidly.”