Study reveals hyperactive brain wave activity as an underlying cause of essential tremor

Researchers at the Irving Medical Center at Columbia University say that hyperactive brain wave activity is the underlying cause of essential tremor, a common movement disorder that causes involuntary rhythmic tremors in about 4% of people over 40.

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His study, recently published in the journal. Medicine Translational MedicineThey found that people with this movement disorder generate hyperactive brain waves in the cerebellum, a region of the brain involved in the coordination of voluntary movement.

The cause of the essential tremor has been difficult to identify, which has posed challenges in the development of possible treatments. Although researchers have already identified structural changes in the brains of affected people, it remains a mystery exactly how those changes cause tremor.

“Previous studies have identified changes in brain structure in people with essential tremor, but we didn’t know how those changes caused tremors,” said Sheng-Han Kuo, an assistant professor of neurology at the University of Vagelos College of Physicians and Surgeons.

“This study determines how those structural changes affect brain activity to boost tremor.”

Now, the discovery that it is the hyperactive brain waves that feed the tremors increases the possibility that new approaches can be used to diagnose and treat the condition more effectively.

“Understanding the pathophysiology of tremor could help develop effective therapeutic approaches to treat ET,” the team writes.

More about essential tremor

Essential tremor is the most frequent movement disorder in the United States, which affects approximately 10 million Americans. Involuntary tremor affects the hands and is aggravated by activities such as tying shoelaces, closing the zipper of a coat or handling utensils, which can have a significant impact on the quality of daily life.

The condition tends to be more common in people over 40, and the symptoms become more severe as a person ages.

Currently, beta blockers (blood pressure medications) and antiepileptics are used to help reduce symptoms, but these are not always effective and cause adverse side effects, such as difficulty breathing and fatigue. Kuo says that this is not surprising, since scientists have not yet fully understood the cause of the condition.

Identify hyperactive brain waves in the cerebellum

Kuo and the team had already identified structural changes in the cerebellum of patients with essential tremor. For the current study, the researchers used a new cerebellar encephalogram (EEG) technique that they had developed to examine the patterns of brain wave activity in this brain region. The recording of electrical signals in the cerebellum is not possible with standard EEG machines.

The team observed some brain wave activity that only occurred in people with essential tremor. Strong oscillations between 4 and 12 Hz were detected among patients with the condition that was not detected in healthy control subjects. In addition, patients who experienced more severe tremors had stronger oscillations.

The oscillations were originally identified in mice.

Initially, Kuo and his colleagues had detected abnormal cerebellar brain wave activity in mice that had tremors such as those observed in patients with essential tremor. They discovered that they could stop or start tremors in animals by stimulating certain neurons in their brains that triggered or suppressed oscillations.

“These results established a causal relationship between brain oscillations and tremor, which cannot be evaluated directly in patients,” says Kuo.

What causes abnormal oscillations?

By studying the postmortem brain tissue of patients with essential tremor, the team had also previously established that these patients had an abnormally high number of synapses that connected nerve cells in the cerebellum called climbing fibers and Purkinje cells (PC and FC).

In the current study, the team used postmortem brain tissue again to study the formation of these synapses, which they said appeared to be influenced by a protein called glutamate delta 2 receptor (GluRδ2).

When GluRδ2 is underexpressed, excess synapse formed between the climbing fibers and Purkinje cells is not eliminated, resulting in too many neuronal connections, Kuo explains.

The case of GluRδ2 insufficiency as a contributor to essential tremor became even stronger when the team studied mice designed to reduce receptor expression. The animals developed tremors similar to those observed in humans with the condition. The tremors also became more severe as the animals grew older.

In addition, when the team corrected GluRδ2 deficiency by restoring protein function, tremor symptoms improved, indicating that GluRδ2 plays a key role in essential tremor.

Possible new treatments

The researchers say the findings could pave the way for possible new treatments:

“Our findings identify a pathophysiological contribution to tremor at the molecular level (GluRd2), structural (synapse of CF to PC), physiological (cerebellar oscillations) and behavioral levels (kinetic tremor) that could have clinical applications for the treatment of ET [essential tremor]”, Writes the team.

“Using cerebellar EEG as a guide, we can use neuromodulation techniques such as tDCS or TMS (transcranial direct current stimulation or transcranial magnetic stimulation) to reduce tremor or even medications to reduce transmission between climbing fibers and Purkinje cells.” says Kuo

The team also plans to apply its results to future studies that prove the effectiveness of medications to reduce tremor and Kuo is already trying to develop agents that increase the expression of GluRδ2 in the brain.

Sources:

Hyperactive brain waves cause an essential tremor. Medical Express 2020. Available at: https://medicalxpress.com/news/2020-01-overactive-brain-trigger-essential-tremor.html

A new study finds that hyperactive brain waves cause a common movement disorder called essential tremor. Discover 2020. Megan Schmidt. Available at: https://www.discovermagazine.com/mind/new-study-says-essential-tremor-is-caused-by-overactive-brain-waves

Journal reference:

Pan M, et al. Cerebellar oscillations are driven by synaptic pruning deficits of cerebellar climbing fibers that contribute to the pathophysiology of tremor. Sci. Transl. Medicine. 12, every 1769 (2020).

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