Converging genetic and functional brain imaging evidence links neuronal excitability to working memory, psychiatric disease, and brain activity

Neuron. 2014 Mar 5;81(5):1203-1213. doi: 10.1016/j.neuron.2014.01.010. Epub 2014 Feb 13.


Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2,824) and in a large schizophrenia case-control sample (n = 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Brain / physiology
  • Calcium Channels / genetics*
  • Calcium Channels / physiology*
  • Case-Control Studies
  • Cerebellum / physiology
  • Cognition / physiology
  • Female
  • Genome-Wide Association Study / methods*
  • Healthy Volunteers
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Memory, Short-Term / physiology*
  • Parietal Lobe / physiology
  • Prefrontal Cortex / physiology
  • Schizophrenia / genetics
  • Schizophrenia / physiopathology*
  • Young Adult


  • Calcium Channels