Researchers have used functional magnetic resonance imaging (fMRI) to gain new insights into the changes in memory and brain function associated with schizophrenia. The results point to deficiencies in so-called “relational” memory, which is accompanied by deficits in activity in specific regions of the brain.

In a study published online July 22 in JAMA Psychiatry, the researchers combined previously established tests for cognitive function with fMRI to pinpoint how memory and brain function change in patients with schizophrenia. The research team was led by John Daniel Ragland, Ph.D., a 2004 NARSAD Independent Investigator, and Cameron Carter, M.D., a 1994 and 1997 NARSAD Young Investigator grantee, a 2007 NARSAD Distinguished Investigator, and a member of the Foundation’s Scientific Council.

Patients with schizophrenia often have difficulty with long-term memory, but the defects underlying these symptoms are poorly understood. Long-term memories can be formed in two different ways: so-called “item-specific” memories are based on recalling aspects of a single object, like the redness of an apple. In contrast, memories can be formed based on classes of associated things, a type of memory known as “relational,” for instance the smell of bread and your mother who bakes bread.

This research team had previously devised a cognitive test (called the Relational and Item-Specific Encoding paradigm, or RiSE) to measure and define defects in long-term memory for patients with schizophrenia. Their initial studies found that patients were able to use item-specific memory but had significant problems when trying to recall information they had learned using relational memory.  

Now, the team led by Ragland and Carter have used RiSE along with fMRI to identify brain regions associated with these defects in relational memory. They found that people with schizophrenia have reduced activity in the prefrontal cortex and hippocampus, two subregions of the brain commonly associated with memory and thought. These effects were both regionally specific (involving the dorsolateral but not ventrolateral prefrontal cortex) and functionally specific (involving relational memory but not item-specific memory).

More broadly, the work suggests that RiSE can be used to detect both functional and neuroanatomical strengths and weaknesses. Ultimately, it’s hoped the results will help inform the development of compensatory strategies and targeted treatments to improve memory and functioning in patients.

In addition to Ragland and Carter, the research team also included Deanna M. Barch, Ph.D., a 1995 and 2000 NARSAD Young Investigator, a 2006 NARSAD Independent Investigator, and a 2013 Distinguished Investigator; James Gold, Ph.D., a 1989 and 1997 NARSAD Young Investigator; Angus MacDonald, III, Ph.D., a 2005 and 2008 NARSAD Young Investigator; Tara Niendam, Ph.D., a 2012 NARSAD Young Investigator; and Steven Silverstein, Ph.D., a 2004 NARSAD Independent Investigator.

Read the paper.