Losing the joy of eating, socialising, and general enthusiasm in life. These are a few clear signs of depression. Researchers across the globe are also investigating how brain waves influence the condition.
A joint team of researchers from Hungary and the USA is on the scent of a potential strategy to overcome depression — by manipulating waves produced in a brain region that processes the sense of smell.
Their new research published in Neuron (9 May) has found that the brain region that processes smell — called the olfactory bulb — contributes to gamma oscillations, which are brain waves that influence our mood and emotion.
Restoring the gamma oscillation levels in the olfactory bulb can reduce depression, says the research team from NYU Grossman School of Medicine, New York, USA, and the University of Szeged, Hungary, citing its experiments on mice.
Gamma waves
In the past decades, scientists have found that brain regions interact with each other through brain waves – which are a synchronous electrical activity of neurons. The neurons work in tandem and in a repetitive pattern — of activity and silence — generating oscillations. For example, gamma waves, which are one such rhythmic oscillation, repeat 30-80 times every second.
“Our experiments revealed a mechanistic link between deficient gamma activity and behavioural 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,” says Dr Antal Berényi in a statement. Dr Berényi is the corresponding author of the study and adjunct assistant professor at the Department of Neuroscience and Physiology, NYU Langone Health.
Connecting gamma with depression
Past studies have found that gamma oscillation is generated in the brain’s olfactory bulb, specifically a region called the piriform cortex. These studies also found that variations in these waves are tied to emotion and hence could be an electrophysiological marker of depression.
“[Gamma oscillations] affect the amygdala, hippocampus and cingulate cortex, collectively known as the ’emotional brain’. And indeed, when the activity in the bulb is reduced, the magnitude of gamma oscillations in these target structures is also reduced,” senior author of the study, Dr György Buzsáki, explains to Happiest Health.
Armed with this knowledge the team devised a method to reversibly shut off gamma oscillations from the piriform cortex in mice. They combined genetic engineering and cell signalling methods to block the function of the olfactory bulb neurons. The uniqueness of this strategy was that they could reverse the process.
They observed the rats for specific behaviours like anxiety, despair, consumption of sugar water as a pleasure activity, and how they avoided stressful situations in a maze activity.
When they suppressed the gamma oscillations, the rats showed continued depression-like behaviour, which persisted days after the suppression was removed.
To validate the link between the gamma waves and depression, they conducted another experiment. They fed the recorded gamma signals from the olfactory region in a feedback loop into the brain with the help of a custom device. This device could suppress or amplify the gamma oscillations as required.
How amplification worked
Interestingly, when gamma was amplified, it restored 40 per cent of normal gamma function in the olfactory bulb. In turn, it restored the function of the limbic system (the region that regulates emotions); This established that regulating the level of gamma waves in the smell processing centre could help with depression therapy.
“This work demonstrates the power of gamma enhancement as a potential approach for countering depression and anxiety in cases where available medications are not effective,” says Dr Berényi.
The next step
Dr Jamuna Rajeswaran, head of clinical psychology at the National Institute of Mental Health and Neurosciences, Bengaluru, says gamma oscillations are part of interactions across the brain. The study suggests there is a dynamic neural mechanism that links various areas of the brain. However, the transition from such a network is not yet fully understood, she adds.
Dr Buzsáki agrees that no one yet knows how the firing patterns of gamma waves are converted into emotions.  “We will be working to better understand this link in the bulb, and in the regions it connects to, as behaviour changes,” he adds.
