MIT neuroscientists have managed to block compulsive behavior in mice by activating a brain circuit that controls compulsive behavior.

The finding could help drive the development of better treatment for obsessive-compulsive disorder (OCD) and Tourette's syndrome.

Close to 1 percent of American adults have OCD and treatment usually involves a combination of therapy and medication (involving antianxiety drugs or antidepressants).

Some people who don't respond to those treatment options undergo brain stimulation, which delivers electrical impulses in the brain. According to research conducted at Brown University, electrical stimulation of a brain network can rebalance the emotional state of patients most severely afflicted with OCD, helping them respond to conventional therapy that had not been effective.

Step towards perfecting brain stimulation treatment

A new technique employed in neuroscience, called optogenetics, allowed the researchers to configure neuronal activity - this technique isn't ready to be used in humans yet.

What is optogenetics?



However, this study could help experts identify brain activity patterns by indicating when the most effective time is to deliver treatment.

Senior study author, Ann Graybiel, an Institute Professor at MIT, and member of MIT's McGovern Institute for Brain Research, said: "You don't have to stimulate all the time. You can do it in a very nuanced way."

Graybiel used a mouse model developed by Feng to try and prevent compulsive behaviors.

Some of the mice in the study lacked a gene called Sapap3, which codes proteins in the synapses of neurons, located in the striatum. This part of the brain is responsible for addiction, repetitive behavioral problems, and decision-making.

Through Pavlovian conditioning a group of mice (both normal and without the gene) were trained to compulsively groom after the sound of a tone which occurred seconds before the researchers dropped water on their nose. This allowed the scientists to try and interrupt the compulsion (grooming) at a specific time.

The normal mice and the mice without the Sapap3 gene were eventually fully conditioned to groom upon hearing the tone.

However, after several hundred trials the behavior of the two groups began to change. The normal mice waited until just before the water reached them to begin grooming - this type of behavior is called optimization.

While mice without the gene never picked up this behavior optimization. They continued to groom as soon as they heard the tone.

This clearly suggests that their ability to stop compulsive behavior was impaired. The investigators believed that it could be due to failed communication between the striatum and neocortex.

Using light the researchers controlled cell activity of the mice by engineering the cells to express light-sensitive proteins.

The mice completely stopped their compulsive behavior as soon as the researchers stimulated their light-sensitive cortical cells - which sent signals to the striatum when the tone stopped. The mice without the gene were no longer compulsive and only groomed when the water was dropped on them.

The cure is thought to be a result of signals sent from cortical neurons to a group of inhibitory neurons in the striatum, which controls the activity of striatal cells.

The paper's lead author, Eric Burguière, said: "Through the activation of this pathway, we could elicit behavior inhibition, which appears to be dysfunctional in our animals."

In addition, the researchers conducted the same optogenetic intervention when the mice groomed normally in their cages. After three minutes of light stimulation the mice lacking Sapap3 groomed less than they did before.

The next step for Graybiel and Burguière is to identify markers of brain activity that indicate when people are about to engage in compulsive behavior. This could significantly help improve deep brain stimulation treatment.

Neuron imaging at MIT could provide insight into the origin of OCD

MIT neuroscientists have also developed a way to monitor how brain cells coordinate with each other to control specific behaviors. Their new imaging technique is based on the detection of calcium ions in neurons. This could help map brain circuits which will offer insight into the causes of OCD.



Written by Joseph Nordqvist