Emory neurosurgeon Robert Gross was recently quoted in a Tennessee newspaper article about a clinical trial of cell therapy for stroke. He used cautionary language to set expectations.
“We’re still in the very early exploratory phases of this type of work,” Gross told the Chattanooga Times Free Press. “In these cases, a significant area of the brain has been damaged, and simply putting a deposit of undifferentiated cells into the brain and magically thinking they will rewire the brain as good as new is naive. None of us think that.”
A more preliminary study (just 18 patients) using the same approach at Stanford and University of Pittsburgh was published this summer in Stroke, which says it was the “first reported intracerebral stem cell transplant study for stroke in North America.” The San Diego Union Tribune made an effort to be balanced in how the results were described:
Stroke patients who received genetically modified stem cells significantly recovered their mobility… Outcomes varied, but more than a third experienced significant benefit.
The newspaper articles made us curious about what these cells actually are. They’re mesenchymal stromal cells, engineered with an extra modified Notch gene. That extra gene drives them to make more supportive factors for neurons, but it doesn’t turn them into neurons. Read more
Optogenetics has taken neuroscience by storm in recent years because the technique allows scientists to study the brain conveniently in animals, activating or inhibiting selected groups of neurons at the flip of a switch.Â Most often, scientists use a fiber optic cable to deliver light into the brain.
Researchers at Emory and Georgia Tech have developed tools that could allow neuroscientists to put aside the fiber optic cable, and use a glowing protein from coral as the light source instead.
Biomedical engineering student Jack Tung and neurosurgeon/neuroscientist Robert Gross, MD, PhD have dubbed these tools â€œinhibitory luminopsinsâ€ because they inhibit neuronal activity both in response to light and to a chemical supplied from outside.
A demonstration of the luminopsinsâ€™ capabilities was published September 24 in the journal Scientific Reports.Â The authors show that these tools enabled them to modulate neuronal firing, both in culture and in vivo, and modify the behavior of live animals.
Tung and Gross are now using inhibitory luminopsins to study ways to halt or prevent seizure activity in animals.
â€œWe think that this approach may be particularly useful for modeling treatments for generalized seizures and seizures that involve multiple areas of the brain,â€ Tung says. â€œWeâ€™re also working on making luminopsins responsive to seizure activity: turning on the light only when it is needed, in a closed-loop feedback controlled fashion.â€ More here. Read more
These days, it sounds a bit old-fashioned to ask the question: â€œWhere is consciousness located in the brain?â€ The prevailing thinking is that consciousness lives in the network, rather than in one particular place. Still, neuroscientists sometimes get an intriguing glimpse of a critical link in the network.
A recent paper in the journal Epilepsy & Behavior describes an epilepsy patient who had electrodes implanted within her brain at Emory University Hospital, because neurologists wanted to understand where her seizures were coming from and plan possible surgery. Medication had not controlled her seizures and previous surgery elsewhere hadÂ not either.
MRI showing electrode placement. Yellow outline indicates the location of the caudate and thalamus. Image from Leeman-Markowsi et al, Epilepsy & Behavior (2015).
During intracranial EEG monitoring, implanted electrodes detected a pattern of signals coming from one part of the thalamus, a central region of the brain. The pattern was present when the patient was conscious, and then stopped as soon as seizure activity made her lose awareness.
The pattern of signals had a characteristic frequency â€“ around 35 times per second â€“ so it helps to think of the signal as an auditory tone. Lead author Beth Leeman-Markowski, director of EUHâ€™s Epilepsy Monitoring Unit at the time when the patient was evaluated, describes the signal as a â€œbuzz.â€
â€œThat buzz has something to do with maintenance of consciousness,â€ she says. Read more
As part of reporting on neurosurgeon Robert Grossâ€™s work with patients who have drug-resistant epilepsy, I interviewed a remarkable woman, Barbara Olds. She had laser ablation surgery for temporal lobe epilepsy in 2012, which drastically reduced her seizures and relieved her epilepsy-associated depression.
Emory Medicineâ€™s editor decided to focus on deep brain stimulation, rather than ablative surgery, so Ms. Oldsâ€™ experiences were not part of the magazine feature. Still, talking with her highlighted some interesting questions for me.
Emory neuropsychologist Dan Drane, who probes the effects of epilepsy surgery on memory and languageÂ abilities, had identified Olds as a good example of how the more precise stereotactic laser ablation procedure pioneered by Gross can preserve those cognitive functions, in contrast to an open resection. Read more
Space considerations in printÂ forced usÂ to slim down the feature on deep brain stimulation for drug resistant epilepsy, which appears in the Spring 2015 issue of Emory Medicine.Â While I encourage you to please read ourÂ story profilingÂ playwright Paula Moreland, here are some take-away points:
*Surgery is a viable option for many patients with drug-resistant epilepsy, but not all of them, because the regions of the brain where the seizures start canÂ have important functions. (Look for an upcoming post describing a patient I met for whom theÂ surgical option was helpful.)
*Deep brain stimulation can reduce seizure frequency and improve quality of life for patients with drug-resistant epilepsy.
*In the large clinical trials on deep brain stimulation for epilepsy that have been run so far (SANTE and RNS), most participants do not see their seizures eliminated. Ms. Moreland is an exception.Â Read more
To go along with the (new) Spring 2015Â Emory Medicine magazine set of features on deep brain stimulation for depression, movement disordersÂ and epilepsy, here is a fascinating 2013 case report from Emory neurosurgeon Robert Gross and colleagues. The first author is electrical engineer Otis Smart.
Itâ€™s an example of the kinds of insights that can be obtained from implantable electrical stimulation devices, which can record signals from seizures inside the brain over long periods of time (more than a year).
As the authors write, â€œthe technology can record brain activity while the patient is in a more naturalistic environment than a hospital, becoming an invasive ambulatory EEG.â€ Read more
It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After divertingÂ some of these topics into the 2015 crystal ball
,Â I corralledÂ them into themes.
1. Cardiac cell therapy
2. Mobilizing the body’s own regenerative potential
4. Parkinson’s disease therapeutic strategies
(Gary Miller, better packaging for dopamine could avoidÂ stress to neurons).
5. Personal genomics/exome sequencing
, likeÂ Emory’s Robert Gross
and Costas Hadjpanayis, do amazing things
7. Fun vsÂ no fun
Our Web expert
tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
It’s been a little while since we had an Intriguing Image. This video illustrates a surgical technique for the treatment of medication-resistant temporal lobe epilepsy.
In this procedure, which is designed to minimize cognitive side effects, the surgeon carefully uses a laser probe to heat and ablate the regions of the brain doctors think are important for seizures. Magnetic resonance imaging allows the temperature in the brain to be precisely monitored. The video was provided by Robert Gross, MD, PhD, and accompanies an upcoming paper in the journal Neurosurgery. More discussion of this procedureÂ here and here.
The epilepsy patient Henry Molaison, known for most of the 20th century as H.M., is one of the most famous in neuroscience. His case played an important role in telling scientists about structures of the brain that are important for forming short-term and long-term memories.
To control H.M.â€™s epilepsy, neurosurgeon William Scoville http://www.raybandasoleit.com/ removed much of the hippocampi, amygdalae and nearby regions on both sides of his brain. After the surgery, H.M. suffered from severe anterograde amnesia, meaning that he could not commit new events to explicit memory. However, other forms of his memory were intact, such as short-term working memory and motor skills.
This classic case helps us understand the advances that neurosurgeons at Emory are achieving today. The surgeries now used to treat some medication-resistant forms of epilepsy are similar to what was performed on H.M., although they are considerably less drastic. Usually tissue on only one side of the brain is removed. Still, there can be cognitive side effects: loss of visual or verbal memory abilities, and deficiencies in the ability to name or recognize objects, places or people.
Neurosurgeon Robert Gross has been a pioneer in testing a more precise procedure, selective laser amygdalohippocampotomy (SLAH), which appears to control seizures while having less severe side effects. Neuropsychologist Daniel Drane reported at the recent American Epilepsy Society meeting on outcomes from a series of SLAH surgeries performed at Emory.