“For most of the time that I’ve been in this field, we’ve been limited in the tools we’ve been able to use, largely tools that give us gross measurements of structure and gross measurements of function,” said William Jagust, MD, Professor of Public Health and Neuroscience and Associate Dean of Academic Affairs at the University of California Berkeley School of Public Health. “But in the last five or 10 years, we’ve had an amazing ability to start looking at biochemistry and much more precise measures of brain function.” Dr. Jagust uses enhanced fMRI to examine aggregations of proteins such as amyloid-beta and tau, with the goal of understanding how the proteins grow and spread over decades in living brains.
“We have structural and functional measures that are showing changes [in the brain] before people have symptoms,” Dr. Jagust said. “Now there’s relatively good agreement that we can pick those kinds of things up with the current techniques.”
Scott A. Small, MD, has taken advantage of the increased resolution of fMRI to investigate separate sections within the hippocampus. For the first time, Dr. Small’s research is showing how one structure can hold the roots of schizophrenia in youth, memory loss in middle age, and Alzheimer’s disease in old age. “One can begin to dissect the hippocampus now and show that these disorders are different, based on patterns of regional vulnerability,” he said. Dr. Small is the Director of the Alzheimer’s Disease Research Center at Columbia University in New York City, where he is the Boris and Rose Katz Professor of Neurology.
Dr. Small and his colleagues can now identify “cell sickness” in the part of the hippocampus related to Alzheimer’s disease. This previously invisible stage—before brain cells die in the disease—may be “an easier place to intervene” when treating Alzheimer’s disease, Dr. Small said.
The goal of earlier intervention guides Catherine Limperopoulos, PhD, and her team as they combine ultrasound and fMRI to look for biochemical signs that a fetus is at risk for brain injury. In fetuses with congenital heart disease, for instance, the presence of lactate in the brain may be a sign that the fetus is low on oxygen.
Dr. Limperopoulos, Director of MRI Research of the Developing Brain and Director of Diagnostic Imaging and Radiology/Fetal and Transitional Medicine at Children’s Research Institute in Washington, DC, noted that physicians have few options for treating fetal brain injury in the third trimester, when many of these injuries occur. Her research may help to define where and when future therapies might be applied. “Our goal is to develop early and reliable biomarkers of injury before injury is consolidated, to see where this window is, and then work to develop ways to intervene.”
Brainstem Implants Bring Sound to Some Children
Cochlear implants have improved hearing for people born deaf or with severe hearing impairments, but they do not work for everyone. Researchers at the Keck School of Medicine of the University of Southern California and Children’s Hospital Los Angeles are testing a more invasive device called an auditory brainstem implant (ABI) in a small group of children for the first time.
The clinical trial began in March 2014 with the aim of testing the device’s safety and feasibility. The full trial eventually will include 10 children. So far, four children have had an ABI surgically implanted. Eric P. Wilkinson, MD, an otolaryngologist in private practice at the House Clinic in Los Angeles and an investigator on the trial, estimated that nearly 100 children in the US each year might benefit from an ABI.
Cochlear implants are electronic devices that are placed in the ear and mimic the auditory wiring there, a procedure that requires a functioning cochlear nerve. An ABI is placed deep within the brain itself, with a receiver fitted under the scalp and a millimeters-long electrode that lies on top of and directly stimulates the cochlear nucleus.
The FDA has approved the device for adults with tumors on the nerve that transmits information from the inner ear to the brain. The researchers conducting the current study hope to find out more about whether ABI surgery is safe and possible in children. The procedure is technically difficult, said Marc S. Schwartz, MD, a surgeon at House Clinic. “We have to provide parents with the information to determine whether it is worthwhile to go through an operation like this.”
When children first receive their ABIs, they hear things like a newborn baby might, said Laurie S. Eisenberg, PhD, a Professor of Research Otolaryngology at the Keck School of Medicine at the University of Southern California. The device produces a sort of “pixellated” signal from the brainstem that is not sorted into the normal acoustic patterns detected by hearing people. “The incoming stimulus for a child with an ABI is completely scrambled, and as a result, children with ABI require intensive long-term therapy and strong parental involvement,” Dr. Eisenberg said.