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Fear, your brain’s pathways and mental health

March 14, 2017 | John Murray
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You may not know it, but that sense of fear you feel while watching a scary movie, when the killer appears on screen for the first time or the heroine finally recognizes what trouble she’s in — that’s your amygdala talking to your hippocampus.

Your what?

The amygdala and hippocampus are regions deep in the brain known to have some relationship to the way your mind processes emotions like fear.

Now, for the first time, UCI Health researchers have identified a key neural pathway between the two that explains how the human brain processes feelings of fear and anxiety.

The finding could help scientists unlock new ways to treat mental health disorders.

Why we remember what scares us

“People are motivated to remember fearful events, because this information is useful for daily survival,” says Dr. Jack Lin, a UCI Health professor of neurology and senior author of the neural pathway study recently published in the journal Nature Communications. “Yet over-interpretation of fear may lead to anxiety and other mental disorders.”

“Understanding how the human brain processes fearful information has been a topic of intense scientific research,” he says. “Until now, the brain circuit underlying fear has only been mapped in rodents. “

Researchers recorded neuronal activity of nine people as they watched scenes from horror movies to stimulate the recognition of fear. Electrodes had been inserted into their amygdala and hippocampus, providing the information.

“Deep brain electrodes capture neurons firing millisecond by millisecond, revealing in real time how the brain attends to fearful stimuli,” says Jie Zheng, a UC Irvine graduate student and the study’s first author.

An exchange of signals

Researchers demonstrated that these two regions, which play a key role in recognizing emotional stimuli and encoding them in memories, are directly exchanging signals.

“In fact, neurons in the amygdala fired 120 milliseconds earlier than the hippocampus. It is truly remarkable that we can measure the brain dynamics with such precision,” says Zheng.

“Further, the traffic patterns between the two brain regions are controlled by the emotion of the movie; a unidirectional flow of information from the amygdala to the hippocampus only occurred when people were watching fearful movie clips but not while watching peaceful scenes.”

Human and animal studies have established the amygdala’s role in fear processing and a parallel role the hippocampus plays in enhanced memory processing of emotional events. Despite the breadth of this research, Lin says it was not previously known how these two nearby brain regions interact during the recognition of fearful stimulus.

“Most studies focus on each brain region in isolation,” says Lin. “Our study unifies the varied literature on the roles of the amygdala and hippocampus in emotional processing, with direct evidence that the amygdala first extracts emotional relevance and then sends this information to the hippocampus to be processed as a memory.”

Developing treatments for mental disorders

Understanding the activation of the exact brain network in processing fearful stimuli is critical to develop new treatment for psychiatric disorders in the era of personalized medicine.

“This is the first study in humans to delineate the mechanism by which our brain processes fear at the circuitry level,” Lin says. “This has huge implications for treating neuropsychiatric disorders. For example, current drugs available to treat anxiety disorder bind to large areas of the brain, leading to unwanted side effects.

“Our hope is that we will one day be able to target and manipulate the precise amygdala-hippocampal circuit involved in processing negative emotions while preserving positive ones,” he says. “This study brings the promise of targeted therapy a step closer.”

Measurements were collected from electrodes implanted by UCI Health neurosurgeons in nine patients with medication-resistant epilepsy as part of an assessment of their seizure activity. Electrode placement was guided exclusively by these patients’ clinical needs, says Lin, medical director of the UCI Health Comprehensive Epilepsy Program.

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