In a new study published in the journal Biological Psychiatry, researchers discover that cognitive problems that often plague people with schizophrenia may be due to disruptions in the brain’s visuospatial working memory network.
Researchers at the University of Pittsburgh studied the patterns of the neurotransmitters glutamate and GABA in a network of brain regions that temporarily maintain and process visual information about the location of objects in space. This cognitive ability is known as visuospatial working memory.
Their findings suggest that the exact balance between glutamate (the excitatory or “accelerator” neurotransmitter) and GABA (the inhibitory or “brake” neurotransmitter) might be shifted in certain brain regions in schizophrenia patients.
Optimal function of visuospatial working memory requires a precise balance of the activity between glutamate and GABA, so these alterations may be what’s causing the disrupted visuospatial working memory in the disorder.
In the study, first author Gil Hoftman, M.D., Ph. D., and colleagues mapped the normal levels of gene products involved in the production and use of glutamate and GABA in brain tissue from deceased subjects with and without schizophrenia.
They looked at four regions of the cortex, the outermost layers of the brain where high level thinking takes place, that form the network responsible for visuospatial working memory.
Levels of the gene products existed in distinct patterns across the regions. Compared to the healthy brains, the levels of the gene products were altered in the cortical regions in postmortem individuals with schizophrenia — increased or decreased in some regions, and unchanged in others.
The findings shed new light into the brain mechanics of working memory and how it goes wrong in schizophrenia.
“First, in the normal human brain, the relative weighting of markers of excitatory and inhibitory neurotransmission differ markedly across the distributed cortical network that mediates working memory,” said David Lewis, M.D., who led the study.
“Second, in schizophrenia this weighting is disrupted by region-specific alterations in markers of both excitatory and inhibitory neurotransmission,” he added.
The findings suggest that multiple disruptions may occur as information passes through the different regions in the network.
“This paper highlights that differences in the cortical abnormalities across brain regions may give rise to the profile of symptoms associated with schizophrenia,” said Dr. John Krystal, editor of Biological Psychiatry.
Schizophrenia is a chronic debilitating mental disorder characterized by psychotic “positive” symptoms, such as delusions, hallucinations, paranoia, and disordered thinking, as well as “negative” symptoms. The latter include loss of motivation or judgment, memory problems, slowed movement, lost interest in hygiene, and social withdrawal.