Discoveries

Error Neurons

The neurons that help us recognize our errors may hold the key to improving treatments for psychiatric and mental disorders.

Giulio Bonasera

When servers deliver our food with a hearty “Enjoy your dinner” and we absentmindedly reply, “You, too,” we tend to realize immediately that we misspoke. Now, thanks to a Cedars-Sinai study, we know which neurons in the brain enable us to catch such momentary glitches.

The identification of these brain policers—known as “error neurons”—could open the way to discovering treatments for schizophrenia, autism, memory disorders and other conditions that disrupt our brain’s ability to self-monitor.

“One of the brain areas known to be important for self-monitoring is the medial frontal cortex,” says principal investigator Ueli Rutishauser, PhD, Board of Governors Chair in Neurosciences. “But how exactly this process works—and why it fails—has been poorly understood.”

The study drew from patients undergoing surgical treatment for drug-resistant epilepsy. Using electrodes already placed in the subjects’ brains as part of their therapy, the investigators evaluated patients’ neuron responses to the Stroop test, which measures reaction time. Participants are asked to say the color of a word that doesn’t match its name. For example, the word “green” is printed in red ink. When subjects misidentify a color, they tend to notice their mistake right away.

“These electrodes allowed us to measure electrical activity of individual neurons and identify those that increase or decrease their activity when an error is detected,” says Adam Mamelak, MD, director of the Functional Neurosurgery Program.

The neurons’ activity generates an electrical signal well-known to neurologists as error-related negativity. “If you have someone perform a task where they knowingly make mistakes, you will detect that signal,” Mamelak explains. The team aimed to demonstrate how the error neurons may work in concert to generate it.

Pinpointing these neurons previously proved challenging because error-related negativity casts a broad signal, “as if you’re looking out at the ocean and just see a big wave of water,” Mamelak adds. “The new research allowed us to see the water molecules and the wind that generate the wave.”

Certain mental illnesses have long been associated with a modified error-related negativity response but the reason for this has remained unclear. People with obsessive-compulsive disorder have larger-than-normal responses, indicating that their brains are over-monitoring for errors, while patients with schizophrenia often exhibit a reduced response. “This new work pinpoints the exact neurons that likely are firing abnormally in people with these disorders,” Mamelak says.

The project was led by first author Zhongzheng Fu, a graduate student in the Rutishauser Laboratory. Rutishauser’s and Mamelak’s laboratories focus on understanding brain mechanisms that support cognitive functions such as error monitoring, which could one day lead to meaningful therapies for a variety of mental health conditions.