Brain breakthrough: Hope for millions as area identified that triggers anxiety ‘freezing’

Sunday Brunch: Paddy McGuinness talks about his anxiety

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According to the World Health Organization, some 264-million people across the globe — around 3.6 percent of the world population — live with an anxiety disorder. Often found occurring in tandem with depression, mania and substance use disorders, these conditions induce irrational fear and worry in excess of what a normal person would feel as a result of everyday sources of stress. While drugs-based treatments for anxiety exist, they are not always effective for all patients and often come with unwanted side effects such as drowsiness, headaches and nausea — and so researchers are interested in finding alternative medications to provide more options.

In their study, a team of neuroscientists from the University of Bristol investigated a structure in the back of the brain called the cerebellum, which is known to be connected to many other regions of the brain that are associated with the survival networks that modulate fear.

In particular, the researchers wanted to investigate how the cerebellum influences activity in an area of the midbrain dubbed the periaqueductal grey.

This region is known to serve various critical roles, including in autonomic function, motivated behaviour, the suppression of pain, and behavioural responses to threats.

In fact, the periaqueductal grey lies at the heart of the brain networks that coordinate survival mechanisms and fear-triggered coping responses like “freezing”.

This “deer in headlights” reaction occurs when our bodies decide that neither of the classic “flight” or “fight” reactions to stress or danger are available — and so the brain opts to play dead instead, and is thought perhaps to even block memories of the upsetting threat.

The team’s experiments involved measuring brain activity within the periaqueductal grey of male rats — by means of implanted electrodes — during a so-called conditioning task.

This saw the researchers play the rodents a particular auditory tone while also giving them a small shock to their feet.

In response to these stimuli, the rats were seen to freeze — a visible behavioural sign of fear — and were expected to form a “fear memory” associating the tone with the shock.

Sure enough, the team found that a particular subset of brain cells in the periaqueductal grey increased their responsiveness to the tone, consistent with the encoding of a fear memory.

However, the researchers explained, when they interfered with cerebellar output during the conditioning task, the resulting activity in the periaqueductal grey changed.

Specifically, the timing of fear-related neuronal activity in the periaqueductal grey was found to become less precise, while the rats were seen to freeze in fear for longer periods.

This, the team said, confirms that interactions between the cerebellum and the periaqueductal grey play an important role in the fear condition process.

Furthermore, the neuroscientists found that when they manipulated the brain pathway that links the two regions, the rats were seen to freeze for longer and also engage in less fear-related ultrasonic vocalisations.

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The study was led by neurobiologists Dr Charlotte Lawrenson and Dr Elena Paci.

They said: “Until now, little was understood about how the cerebellum modulates neuronal activity in other brain regions, especially those related to fear and anxiety.

“Our results show that the cerebellum is part of the brain’s survival network that regulates fear memory processes at multiple timescales and in multiple ways.”

This finding, they explained, raises “the possibility that dysfunctional interactions in the brain’s cerebellar-survival network may underlie fear-related disorders and comorbidities.”

Given this, drugs that act on the cerebellum may have the potential to provide relief for individuals suffering from various anxiety disorders, including post-traumatic stress disorder.

The full findings of the study were published in the journal eLife.

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