More than 100 genes important for memory have been identified in humans by a new study. The research is thought to be among the first to clearly identify correlations between gene expression data and brain activity during memory processing. The work was presented yesterday at the Cognitive Neuroscience Society’s annual conference in San Francisco by Genevieve Konopka, Ph.D..
“This is very exciting because the identification of these gene-to-behaviour relationships opens up new research avenues for testing the role of these genes in specific aspects of memory function and dysfunction,” said Dr. Konopka. “It means we are closer to understanding the molecular mechanisms supporting human memory and thus will be able to use this information someday to assist with all kinds of memory issues.”
This study is one of several new advancements in the field of ‘imagining genetics’, which works to relate changes in a person’s genome with variations in their brain function and anatomy. Previous work has attempted to connect genes with human behaviours, but this was largely unsuccessful as the researchers lacked knowledge the neural markers which bridge the two. Improvements in the easy and affordability of genotyping and increased access to brain imaging and electrophysiology datasets have made this kind of research more accessible and as a result, our understanding of the underlying biology has been growing.
“Probing the genes-brain relationship is likely to yield a rich understanding of the human cognitive and neural architecture, including insights into human uniqueness in the animal kingdom,” said Evalina Fedorenko, Ph.D., Chair of the symposium on imaging genetics at the CNS conference.
One of the main advantages of combining cognitive neuroscience with genomics is that there is a range of different approaches possible. This study involved examining the pattern of gene expression across the cortex and correlating it to the observed patterns in brain architecture from previous data. The goal was to identify the genes that were most important for ‘normal cognitive activities’, such as memory and learning.
Previous neurological studies had displayed that altered gene expression at select loci of the genome was linked to cognitive deficiencies, which the team could focus on. The study also involved using prior analysis of fMRI data created by the same team in charge of this work. They used RNA data from post-mortem brain tissue and intracranial EEG (iEEG) data from epileptic patients collected during episodic memory tasks with electrode monitoring. The collective dataset was the largest of its kind currently available.
“We measure RNA as a proxy for gene expression in the brain,” said Konopka. “Quantitating RNA in the brain requires extracting RNA from the brain tissue itself. Thus, we are limited to accessing brain tissue post-mortem, or, in rare occasions, can obtain tissue from surgical resections of the brain.”
The identified genes were shown to be distinct from genes previously linked to cognitive processing and the results were confirmed to be unrelated to the epilepsy of the participants. The team did find that many of the genes they identified overlapped with genomic loci linked to autism development, which might help to influence future studies in the area.
While these results are promising, the researchers acknowledge that it is still in the very early stages, and that the robustness and reproducibility have yet to be seen. With more work, they hope that their work will be able to expand and improve the standards of future studies within the field.
“We, as a field, need to increase our standards of rigor and require results to be replicated at least across two datasets before they are published, so as not to flood the literature with false positives,” Fedorenko said.