Israeli Scientist Leads the Way in Groundbreaking Tourette's Research
Haaretz
July 15, 2016

With his successful model, Prof. Izhar Bar-Gad is at the forefront of the shift in how the scientific community examines the oft-misunderstood syndrome.

The public is relatively familiar with Tourette syndrome. Though there’s a lot of ignorance on the subject, many have had the experience of noticing the tics and curses of those who suffer from it — at least the ones that conform to the image they have of the syndrome.

2528967433.jpg
Prof. Izhar Bar-Gad, a neurophysiologist at the Gonda Multidisciplinary Brain Research Center at Bar-Ilan University

Tourette’s is fairly common in childhood and in most cases disappears on its own. In fact, it’s not an illness and it is certainly not fatal. Nonetheless, of all the neurological disorders and behaviors, the syndrome has attained special status, not because of its severity but rather because of the way it sticks out in the human landscape. However, the interest society has shown in the syndrome over the years is in inverse proportion to its standing in scientific research.

“Even though the syndrome was discovered more than a hundred years ago, somehow research and science have not given it very much serious attention,” says Prof. Izhar Bar-Gad of the Gonda Multidisciplinary Brain Research Center at Bar-Ilan University in Ramat Gan. “Perhaps because of the cursing or its image it is perceived as a psychological-behavioral issue. Neurologists and brain researchers haven’t really dealt with Tourette’s. They have preferred to investigate motoric disorders like Parkinson’s, Huntington’s and other classical diseases.”

In recent years, though, this has begun to change. A shift has been occurring in the scientific community’s examination of the phenomenon, resulting in more and more research. In 2015, an Israeli study co-authored by Bar-Gad and published in The Journal of Neuroscience revealed the mechanism that determines the timing of the tics characteristic of Tourette syndrome.

Bar-Gad, a neurophysiologist originally from the worlds of mathematics and computers, has become a world-renowned expert in Tourette’s research. This fall, about 35,000 brain researchers from around the world will attend the Society for Neuroscience's annual conference in San Diego. Among the thousands of talks and posters on topics of Parkinson’s, Alzheimer’s, ALS and other brain disorders, the one and only talk on Tourette syndrome will be given by Bar-Gad.
Tourette syndrome is a common neurodevelopmental disorder characterized by the appearance of sudden and repeated utterances or movements due to muscle group activity. The tics are involuntary movements but they can sometimes be controlled for varying lengths of time.

The syndrome is more common among boys (girls make up only 20% of all cases) and it first appears at the age of 5 or 6, becoming exacerbated at the age of 10 to 12. “For most children the condition improves considerably by the end of their second decade, but there is a certain percentage for whom very serious tics remain,” explains Dr. Noa Ben Aroya-Milstein, director of the Neuropsychiatric Clinic for Tourette Syndrome and Tic Disorders at the Schneider Children’s Medical Center in Petah Tikva. The frequency of tics is influenced in part by exposure to stress or excitement and it often increases when these become more pronounced.

3482214244.jpg
Gal Levi-Hayoun, 29, was diagnosed with Tourette syndrome at the age of 7

Gal Levi-Hayoun, a 29-year-old woman, was diagnosed with Tourette syndrome at the age of 7. Ever since then, the tics have been with her: jerking her head back; raising her lips towards her nostrils; nostril flaring; uncontrolled blinking; lifting of her pupils; constant movements her fingers and toes. Frequent teeth-gnashing has forced her to use a special mouth guard, which couldn’t withstand the strain and broke. Half a year ago she made the decision to stop her attempts to conceal the tics that made her life difficult.

“When I worked at a call center, if you’re working under time quotas and under pressure, this stimulates the tics terribly. I was embarrassed to ‘bark,’” she relates, referring to making noises, “and the tics grew even stronger. The physical suffering also comes from the attempt to prevent the tics from appearing. I would fight with myself, but the more you hold it in, the more it bursts out afterwards.”

4231972879.jpg
Vered Avraham, 36, began having tics at age 8 but was diagnosed with Tourette syndrome only when she was 26

For Tourette Awareness Month, Levi-Hayoun wrote a touching post on the Esti Israeli Tourette Syndrome Association site, talking about how she had tried nearly every possible method to deal with the syndrome: acupuncture, shiatsu, homeopathy and more. “Psychiatric medications caused me side effects of depression and extreme mood swings, so I don’t have any real treatment,” she noted.

Vered Avraham, 36, began having tics at age 8 but was diagnosed with Tourette syndrome only when she was 26. “When I was a child there wasn’t any awareness of the issue,” she says. “I never heard the word ‘tics.’ When I got older, I discovered what it is and I started reading and learning what it’s about. It’s not something you ‘suffer from’ – it’s something you live with and there are periods when there’s more and there are periods when there is less. Socially, it hasn’t hurt me. Everyone understands and accepts me with open arms and we, my friends with Tourette, have our own humor. I think I wouldn’t be who I am without it.”

A short circuit in the brain
The lack of scientific interest in researching Tourette, which has lasted for many years, does not stem only from the syndrome’s vague standing among brain researchers relative to classical brain disorders. There are also more objective reasons which have kept the study of the syndrome on the margins of brain research: Scientists find it difficult to create sufficiently good models of the syndrome in lab animals – “unlike Parkinson’s, for which models had already been created in animals decades ago that enabled the research to progress,” explains Bar-Gad.

“When we talk about Tourette, there are two questions at the base of our research: where and when. The ‘where’ relates to which organ in the body will activate the syndrome and the ‘when’ relates to the timing mechanisms and what affects them.”

Seven years ago, Bar-Gad succeeded in developing a model of Tourette syndrome as part of a study funded by the Tourette Association of America. Three years ago, he and his team succeeded in modeling the syndrome in rats. In parallel, in the course of another study he conducted, he found an answer to the first basic question he aimed to study: the “where” – the process in the brain that determines in which organ the tic will occur.

A few months ago, Bar-Gad published his new study in which he succeeds in answering the question of “when.” Various studies indicate a failure in the process of communication between two areas of the brain, focusing on the striatum, which is located deep inside the brain and is part of the basal ganglia. Scientific literature recognizes it as involved in planning and controlling motor activity as well as other cognitive and emotional processes.

“One of the striatum’s important roles is preventing involuntary movements,” says Bar-Gad. “It’s an area that ordinarily is flooded with signals by means of nerve cells that come from the area of the cortex, which intend to carry out many and varied simultaneous motoric actions. In contrast to other mechanisms that are involved in carrying out motoric actions, the striatum’s role is reversed – it helps the mechanism of choosing movements by suppressing most of the signals coming into the cortex and enables the correct selection of the desired movement. Without a mechanism like this, the body would lose its motor control.”

According to Bar-Gad’s research, what is behind the tics is a disturbance – with varying degrees of severity – of the striatum’s activity. In their most recent study, Bar-Gad and his team conducted a precise analysis of neuron activity in the brains of rats with involuntary movements. In their study, they also present the mechanism that determines the timing and frequency of tics.

“Basically, there is a mechanism of flooding and release,” explains Bar-Gad. “You can compare this to a cup leaning on its side that empties out every time it fills up completely. What happens in the production of a tic is that the striatum takes in more and more messages by means of nerve cells until it reaches a certain threshold, at which it dumps the overload by means of carrying an involuntary movement – a tic. The moment the tic happens there is a recalibration and the dynamic begins again, and so on. In our study we clearly show the processes of accumulation and release.”

The process Bar-Gad describes does not remain in the depths of the brain. It is closely connected to the individual’s psychological and environmental situation. In stressful situations, for example, the striatum is bombarded by a great deal of neuron activity and the flooding and release mechanism operates at a faster pace.

A disturbance in the activity of the striatum causes a tic to occur. But what determines whether the tic will be manifested in rapid blinking, a jerk of the hand or a head movement? Here, too, the answer lies in the striatum. In an earlier study, the researchers in Bar-Gad’s lab succeeded in mapping the striatum according to its influence on the motor activity of various body parts. “In effect, the body part or parts in which tics will appear are an outcome of the areas of the striatum that are affected,” says Bar-Gad. “For example, if the part is connected to the activity of the eye, flooding it with signals from the cortex will cause blinking, and the same holds for other body parts, and sometimes several of them at once.”

Figuring out the brain mechanisms behind tics and the symptoms of Tourette syndrome is more than scientific curiosity. Most of the people who grapple with the syndrome will feel considerable improvement when the symptoms disappear in their adulthood, but about 20% of those diagnosed will continue to live with it. Among them is a small group with a particularly severe form of the syndrome.

“Severe cases of Tourette’s seriously affect the quality of the patients’ lives,” says Bar-Gad. “We aren’t talking about cases of blinking but rather about phenomena like patients whose tic is punching themselves with their fist in the chest or in the ribs, who have to go around in special protective garments after having broken their own ribs, or a tic of sharply jerking the head backwards that damages the spine. There are also serious social repercussions at an early age.”

According to Bar-Gad, in recent years there has been a tendency towards understanding the need to research the phenomenon in the context of the reality that people with Tourette’s face.