Unraveling the neural code of the anxious brain

Although our understanding of neuropsychiatric conditions, such as anxiety and depression, has advanced by leaps and bounds over the years, there are still vast gaps in our knowledge.

Trying to decipher the inner workings of the most complicated structure in the universe is bound to be fraught with difficulty.

In a process that still seems close to magic, our perceptions, our sense of self, and our emotions are weaved into one experience — consciousness. This is the result of trillions of connections between neurons.

Years of study have revealed the roles of various brain regions. For instance, we know that the hippocampus is important for memory and that the amygdala is involved in processing emotions.

However, merely identifying which regions relate to particular activities does not give us a deep understanding of how the brain produces such a vivid spectrum of experiences and emotions.

Delving into the complexity of mood

Everyone experiences emotional ups and downs. For some people, the fluctuations can be so severe that their lives are significantly disrupted. This makes mood an important topic of study.

Anxiety disorders affect an estimated 40 million adults in the United States, and in 2016, for example, more than 16 million U.S. adults experienced at least one major depressive episode.

The use of MRI scans and other imaging techniques has allowed scientists to observe the brain in new detail.

As a participant lies motionless in a device’s small tunnel, researchers can present them with emotionally charged stimuli, then observe how the brain responds, as emotions change from positive to negative.

Although these studies have unlocked information about the inner workings of our brains, lying inside an MRI scanner is about as far from real life as one can get.

Recently, and for the first time, researchers have designed an experiment that measures the neural correlates of mood in real-life situations.

Dr. Edward Chang, a neuroscientist, and Dr. Vikaas Sohal, Ph.D., a psychiatrist and neuroscientist, led the team. Both are members of the University of California, San Francisco Weill Institute for Neurosciences.

Measuring brain activity in real time

Observing the minute-by-minute workings of the human brain required a unique group of participants.

The researchers recruited 21 people with epilepsy who already had 40–70 electrodes implanted on the brain’s surface and within some deeper structures.

The participants had received the electrodes in preparation for surgery to remove sections of the brain responsible for seizures.

These implants allowed the scientists to chart brain activity for 7–10 days. Throughout this time, the participants recorded changes in mood using a tablet-based questionnaire.

In this way, the scientists could correlate changes in mood with brain activity using algorithms, which the study’s lead author, Lowry Kirkby, Ph.D., had designed. The group’s findings appeared today in the journal Cell.

Intrinsic coherence networks

Before studying the mood diaries, the scientists scoured the brain data, looking for intrinsic coherence networks.

These networks are groups of brain regions that tend to be active at the same times. Scientists take this coordinated activity to mean that the regions are working together and communicating.

When the scientists compared the data from all 21 participants, they found various “cliques” of brain regions that regularly fired together at the same frequency.

In 13 of the participants, one clique was particularly active. An earlier assessment of this group had indicated that they all experienced relatively high levels of anxiety.

The data showed that when this clique was active, it correlated with feelings of low mood.

Specifically, the researchers observed combined activity in the hippocampus and amygdala. The activity consisted of beta waves, which formed a rhythm that scientists had previously linked to anxious thinking.

Finding such a clear pattern in the groups’ brain activity took the researchers aback.

We were quite surprised to identify a single signal that almost completely accounted for bouts of depressed mood in such a large set of people.”

Dr. Vikaas Sohal, Ph.D.

Just the beginning

The study marked the start of this line of investigation, so encountering such an apparently clear-cut pattern early on was welcome. As Dr. Sohal says, “Finding such a powerfully informative biomarker was more than what we’d expected at this stage of the project.”

Discovering the characteristic brain activity in 13 participants was as surprising as noting its absence in the others, who did not have such pronounced anxiety.

These findings may provide clues about the different ways in which people prone to anxiety process emotional information.

“Based on what we know about these brain structures, this suggests that interactions between the amygdala and hippocampus might be linked to recalling emotional memories, and that this pathway is particularly strong in people with high levels of anxiety, whose mood might then be heavily influenced by recalling emotion-laden memories,” says Dr. Sohal.

Much more work will follow, but Dr. Sohal is already excited about the results. He explains, “As a psychiatrist, it’s deeply satisfying to begin to be able to provide a conceptual framework to patients to help them understand what they are going through when they feel down.”

This work may also contribute to advanced diagnostics. Dr. Chang explains, “The findings have scientific implications for our understanding of how specific brain regions contribute to mood disorders, but also practical implications for identifying biomarkers that could be used for new technology designed to treat these disorders.”

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