Depression Countered by Restoring Key Brain Rhythm

Brain regions including the olfactory bulb adjacent to the nasal cavity, which is thought to be a source of brain-wide gamma oscillations could be a controller of depressive symptoms. This is according to a study published in the journal Neuron. Major depressive disorder is a common, severe psychiatric illness often resistant to drug therapy, the researchers say. The prevalence of the condition has dramatically increased since the start of the pandemic, with more than 53 million new cases estimated.

Role of Hampered Gamma Oscillations in Major Depressive Disorder

Disease-causing changes in the timing and strength of gamma signals, potentially caused by infections, trauma, or drugs, from the olfactory bulb to other brain regions of the limbic system, such as the piriform cortex and hippocampus, may alter emotions.

However, the research team is not sure why. In one theory, depression arises, not within the olfactory bulb, but in changes to its outgoing gamma patterns to other brain targets.

The new study results revolve around nerve cells (neurons), which “fire” – or emit electrical signals – to transmit information. Researchers in recent years discovered that effective communication between brain regions requires groups of neurons to synchronize their activity patterns in repetitive periods.

One such rhythm, called “gamma,” repeats about 30 times or more in a second, and is an important timing pattern for the encoding of complex information, potentially including emotions (1^✔ ✔Trusted Source
Gamma oscillations as a biomarker for major depression: an emerging topic.

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Although its causes remain poorly understood, depression is reflected in gamma oscillation changes, according to past studies, as an electrophysiological marker of the disease in brain regions that manage the sense of smell, which have also been tied to emotions.

To test this theory, researchers shut down the function of the bulb using genetic and cell signaling techniques, observed a related increase of depression-like behaviors in study rodents, and then reversed these behaviors using a device that boosted gamma signals of the brain at their natural pace.

Gamma Enhancement Could be a Potential Approach for Countering Depression

These experiments revealed a mechanistic link between deficient gamma activity and behavioral decline in mice and rat models of depression, with the signal changes in the olfactory and connected limbic systems similar to those seen in depressed patients.

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This work also demonstrates the power of gamma-enhancement as a potential approach for countering depression and anxiety in cases where available medications are not effective.

To show the effect of the loss of gamma oscillation in the olfactory bulb, the team used several standard rodent tests of depression, including measures of anxiety which is one of its main symptoms.

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Specifically, the tests looked at how long animals would spend in an open space (a measure of anxiety), whether they stopped swimming earlier when submerged (measures of despair), whether they stopped drinking sugar water (took less pleasure in things), and whether they refused to enter a maze (avoided stressful situations) (2^✔ ✔Trusted Source
Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents.

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The researchers next used a custom-made device that recorded the natural gamma oscillations from the olfactory bulb and sent those paced signals back into the rodents’ brains as closed-loop electrical stimulation.

The device was able to suppress gamma in healthy animals or amplify it. Suppression of gamma oscillations in the olfactory lobe induced behaviors resembling depression in humans.

In addition, feeding an amplified olfactory bulb signal back into the brains of depressed rats restored normal gamma function in the limbic system, and reduced the depressive behaviors by 40 percent (almost to normal). Moving forward, researchers will be working to better understand this link in the bulb, and in the regions it connects to, as behavior changes.

References:

1. Gamma oscillations as a biomarker for major depression: an emerging topic - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123432/)
2. Reinstating olfactory bulb-derived limbic gamma oscillations alleviates depression-like behavioral deficits in rodents - (https://doi.org/10.1016/j.neuron.2023.04.013)

Source-Eurekalert