Dr. Vinogradov's research focuses on using cognitive training to target deficits of schizophrenia

Vinogradov Research Laboratory

Neuroscience-informed cognitive training for schizophrenia and other neuropsychiatric disorders

Sophia Vinogradov, M.D.
Professor and Vice-Chair, Department of Psychiatry, UCSF
Associate Chief of Staff, Mental Health Service, SFVAMC

 

Our Research Focus

For the past 10 years, our research has focused on the design, implementation, and evaluation of neuroscience-informed computerized cognitive training exercises that target cognitive deficits of schizophrenia.  For example, we have shown that 50 hours (10 weeks) of training of basic auditory processing and auditory/verbal working memory results in significant improvements in untrained measures of verbal learning and memory and general cognition in adults with schizophrenia.  We have also shown that this form of training is associated with quality of life improvements 6 months after training is completed; and that it “normalizes” brain activation patterns during basic auditory processing as well as higher-order complex cognitions.  We have investigated serum biomarkers associated with the intervention and have demonstrated that medication-induced anticholinergic burden adversely affects patients’ cognitive gains after training. Though in its early stages, this work is pointing the way for an entirely new treatment approach for schizophrenia and other neuropsychiatric illnesses.

The Neuroscience

This novel therapeutic approach for people with schizophrenia is grounded in two decades of advances in the systems neuroscience of learning-induced neuroplasticity, and has been carried out in collaboration with basic neuroscientist Michael Merzenich, PhD (Center for Integrative Neuroscience, UCSF and Brain Plasticity Institute, Inc.).  It is based on the premise that neuropsychiatric illnesses are due to dysfunction in distributed prefrontal neural systems that underlie perception, cognition, social interactions, emotion regulation, and motivation.  The high degree of learning-dependent plasticity in these networks—combined with the availability of advanced computerized technology – indicates that we can engineer very specific training programs that are designed to drive meaningful and enduring improvements in these impaired neural systems (8). Thus, in addition to longitudinal behavioral assessments, we probe brain activation changes via functional magnetic resonance imaging and magnetoencephalography in order to understand the underlying neural mechanisms that are associated with treatment response.  We also examine clinical factors, genetic polymorphisms, and serum biomarkers that are related to an individual’s response to cognitive training (6,7).  Finally, we have studies underway investigating how inherent factors related to motivation and reward-processing might play a key role in the response to this intervention (9,10).

What is the Goal of Cognitive Training?

The primary goal of this new treatment approach for schizophrenia is to develop “brain training” programs that drive enduring improvements in cognition and that translate into improved life functioning for people with the illness.  In order to accomplish this goal, we have recently moved our intervention out of the laboratory and into the community.  In collaboration with staff at San Francisco General Hospital Community Mental Health Services, we have begun a double-blind randomized controlled trial applying cognitive training in conjunction with supported employment services to participants with schizophrenia in an urban public mental health facility that treats seriously mentally ill clients.  We will test the hypothesis that individuals who receive supported employment plus cognitive training will show higher rates of employment and higher wages at 1 and 2 year follow-up compared to those who receive supported employment plus a computer games control condition.

 

Intervening Early in the Course of Illness

We have also been investigating neuroscience-informed cognitive training in young people who are “prodromal” for schizophrenia or who are in their first episode of the illness, with the ambitious goal of correcting some of the cognitive impairments that place the brain at risk for a debilitating downward trajectory into chronic mental illness.  These young participants—who are in their teens or early twenties-- are given laptops and do the cognitive training on their own schedule at home. We founded an early psychosis research program at UCSF in order to support these investigations, and with our program director, Rachel Loewy, PhD, and co-investigator Daniel Mathalon, MD, PhD, this research is now well underway and preliminary data are highly encouraging.  In addition to proximal behavioral and imaging measures, we are following these young people longitudinally to see whether our intervention improves community functioning and reduces the incidence of future psychotic episodes.

How this Research is Being Applied By Other Investigators

The methods we have developed and our promising data have led to an NIMH-funded multi-site feasibility study carried out by the Schizophrenia Trials Network (Scott Stroup, MD, and Richard Keefe, PhD, Duke University), an NIMH-funded trial in early-onset schizophrenia (Lin Sikich, MD, UNC), NIMH-funded trials with genetic high-risk adolescents (Christine Hooker, PhD and Larry Seidman, PhD, Harvard University) and with patients with bipolar illness (K.E. Lewandowski, PhD, Harvard University), and discussions for a VA Collaborative Study (Robert McCarley, MD, Harvard University and Erica Duncan, MD, Emory University).  Our work has also led to two NIMH SBIR grants to Brain Plasticity Institute (Henry Mahncke, PhD and Mor Nahum, PhD) for further development of the software and design of new exercises specifically for the needs of people with schizophrenia, as well as funding for the implementation of a multi-site efficacy trial that, if successful, will lead to an application for FDA approval as a medical device for the treatment of schizophrenia.

 

Collaborations with Developers in Entertainment Software

This research appears to be at the vanguard of an emerging new area of clinical neuroscience investigation.  Not surprisingly, the science behind our understanding of how to develop effective computerized training for the neural system dysfunction of psychiatric illness is occurring in parallel with the development of extremely sophisticated entertainment software that is already engaging millions of brains of all ages in learning experiences with cognitive and affective impact.  These advances in entertainment software indicate that cognitive training for schizophrenia can be developed that will generate the same interest, engagement, perceived value, and social acceptability as web-based games.  In order to foster a new area of collaboration between academia and industry, We have founded the “Entertainment Software and Cognitive Neurotherapeutics Society (ESCoNS)”, along with philanthropist George Rose (formerly of Activision), neurologist Adam Gazzaley, MD, PhD (UCSF), and neuroscientist Mor Nahum, PhD (Brain Plasticiy Institute).  The first ESCoNS meeting was held on September 19-20, 2011 in San Francisco and included a stellar line-up of scientists from around the world, as well as participants from NIH, DoD, industry, and science journalism.