Parvalbumin interneurons (green) in the prefrontal cortex of a mouse with absence seizures. Image credit: Brielle Ferguson (CC BY 4.0)
People who experience absence seizures may go through brief lapses in consciousness hundreds of times a day. They also often have difficulties engaging and remaining focused on a task, which can severely limit their ability to study, work and go through their day-to-day life. These impairments in attention persist even when medication puts a stop to the seizures, suggesting that they are not directly linked to the epileptic episodes. In fact, recent work has indicated that these deficits may be caused instead by alterations in the activity of the prefrontal cortex, the brain area which helps to regulate attention and impulsivity. However, the exact nature of these changes remains unclear, making it difficult to design treatments that could improve patients’ quality of life.
To explore this question, Ferguson et al. developed a new behavioral test that allowed them to measure the attention levels of mice genetically engineered to have absence seizures. The experiments confirmed that these animals had impaired attention even when brain activity recordings showed that they were not experiencing seizures.
Further work revealed that poor performance on the behavioral test was linked to decreased activity in parvalbumin interneurons, a group of cells in the prefrontal cortex which can inhibit many other types of neurons. In mutant mice, this change was associated with alterations in network activity broadly in the cortex, including in electrical patterns which are linked to cognitive processes. Promisingly, increasing the activity of the interneurons during the attention task improved performance, suggesting that this type of cell could represent a therapeutic target for attention deficit in absence epilepsy.
