September 19, 2017 | Patti Wieser
Fiza Singh, MD. Photo by Kyle Dykes
There’s a saying: Neurons that fire together, wire together.
Wiring builds neural networks that enable critical cognitive functions such as memory. Fiza Singh, MD, is interested in improving memory in people with schizophrenia, who tend to exhibit abnormal neural coherence and synchrony.
In 2016, UC San Diego Altman Clinical and Translational Research Institute (ACTRI) awarded Dr. Singh a one-year pilot project grant to study how to enhance gamma band response in schizophrenia patients to improve working memory. Neuronal activity in the gamma frequency band, in frontal parts of the brain, controls memory. Dr. Singh’s project tested gamma-neurofeedback as a potential therapy for improving memory in people with schizophrenia.
Her study led to a prestigious five-year NIH R61 grant to build on this research. “The NIH grant is a direct result of the protected time that I received from the ACTRI pilot project funding, and I am really grateful to ACTRI,” said Dr. Singh, an assistant clinical professor in the Department of Psychiatry at UC San Diego. The R61 supports exploratory clinical trials of novel interventions for mental disorders.
Schizophrenia is a chronic debilitating mental disorder that affects 2.4 million Americans and leads to considerable individual and societal costs. “Patients with schizophrenia tend to have many positive symptoms, such as delusions and hearing voices. They also have cognitive problems with, for example, memory and attention. These problems can lead to many of the disabilities that stem from schizophrenia,” Dr. Singh said. “Schizophrenia patients may not, for example, be able to get a job, form relationships, or do well in school. We are looking for ways to improve quality of life.”
Dr. Singh said medications are helpful in treating the positive symptoms, but have not been very effective in treating cognitive deficits. “The main impetus for our study was to develop a therapy that could be useful in reducing cognitive deficits, mainly in working memory,” she said.
She collaborated with her mentor, Jaime Pineda, PhD, at the Cognitive Neuroscience Lab at UC San Diego. “We were interested in testing if this type of brain training – neurofeedback – could bring the gamma waves in coherence with each other and bring back that gamma synchronicity in the frontal part of the brain. If we could do that, it could lead to improvements in working memory,” Dr. Singh said.
The pilot study initially included 15 subjects, each of whom wore an EEG cap while seated in front of a computer screen. The cap recorded gamma waves in the frontal part of the brain in real time. “The information is digitized and presented on the computer in a visual metaphor,” Dr. Singh said. “For example, one of the visual metaphors is an airplane flying through the air. If a subject is having good coherence, the plane flies well. But if the coherence drops in the gamma waves, the plane doesn’t fly. That signals to the subject to try to get the plane to fly again.”
The pilot was a crossover study for eight weeks. During the first four weeks, half the subjects received neurofeedback training and the other half placebo training, and then switched training for the second four weeks. Twice weekly sessions lasted 45 minutes. The upcoming NIH study will include 30-minute sessions. “We learned through the pilot that the subjects want variety – different games and options – and shorter sessions,” Dr. Singh said. The research team is presently analyzing data and preparing for the $2.5 M NIH study, which is anticipated to begin this fall and include 100 subjects over five years.
Dr. Singh, a physician-researcher, was pleasantly surprised by the level of interest and amount of investment subjects had in these direct brain modulation studies. “Some of the subjects are patients I occasionally see in clinic, and they took the initiative to check in with me and say, ‘How’s the data, Dr. Singh? Will there be a treatment offered?’” she said. “There is a lot of enthusiasm and excitement for these non-medication treatments.”
In addition to her UC San Diego affiliation, Dr. Singh is a psychiatrist and the Medical Director of the CORE program, in the Division of Mental Health at the VA San Diego Healthcare System. She received a bachelor’s degree in chemistry from New York University and a medical degree from Mount Sinai School of Medicine. She was a resident physician in pathology at UC Davis and in psychiatry at UC San Francisco at Fresno and UC San Diego, where she was later a post-doctoral fellow in neurophysiology in schizophrenia. Dr. Singh is the author of numerous publications in professional journals and the recipient of several research grants.
“We are very pleased Dr. Singh has been awarded a five-year NIH grant to continue this important research to improve memory and attention in patients with schizophrenia,” said Murray B. Stein, MD, MPH, director of the ACTRI Pilot Project Program. “Her success story is a reflection of how ACTRI support can yield NIH funding for an early career investigator.”
About UC San Diego Altman Clinical and Translational Research Institute:
UC San Diego Altman Clinical and Translational Research Institute (ACTRI) is part of a national Clinical and Translational Science Award consortium, led by the National Institutes of Health National Center for Advancing Translational Science. Established in 2010, ACTRI provides infrastructure and support for basic, translational and clinical research throughout the San Diego region to bring discoveries from the laboratory to the bedside, and facilitates training and education of the next generation of researchers. ACTRI carries out its activities in collaboration with institutional and corporate partners and currently has more than 1,425 members.