Tackling Tourette syndrome: Therapeutic clues from MRI
SpectrospcopyNow.com
October 1, 2014

GABA and TS
Tackling Tourette's: Therapeutic clues from MRI Credit: Jackson et al/Curr Biol
Magnetic resonance imaging scans can show the patterns of neurotransmitters in people with Tourette syndrome that are associated with particular brain activity. The details could lead to new therapeutic targets for disorder.

The neurotransmitter GABA (gamma-aminobutyric acid) plays an important role in controlling the involuntary movements and vocal tics associated with Tourette Syndrome (TS), new research shows. The work carried out by psychologists at The University of Nottingham, UK, and detailed in the latest edition of the journal Current Biology, might eventually lead to a new way to treat the inherited disorder.

TS has a genetic basis and onset of symptoms is usually seen in childhood, characterized by various "motor" tics and by definition at least one vocal, or phonic, tic. Symptoms come and go but are often preceded by awareness of their imminence in the sufferer. The condition is not quite as rare as it was once considered to be. Moreover, the tabloid description of it as being associated with socially inappropriate outbursts and expletives is rarely a symptom manifest in the majority of people with TS.

Signals
Both the primary motor cortex (M1) and the supplementary motor area (SMA) are thought to be hyperactive in the brains of those with TS, causing the tics which can be both embarrassing and disruptive, especially for children who often find it difficult to concentrate at school.

Now, Amelia Draper working under the supervision of Stephen Jackson, has used MRI to investigate the brain chemistry and activity in patients. The team found that higher levels of GABA in a part of the brain known as the supplementary motor area (SMA) help to dampen hyperactivity in the cortical areas that produce movement. As such, only the strongest signals lead to movement. The team measured in the M1, the SMA and an area involved in visual processing (V1) which was used as a control (comparison) site, testing group of young people with TS and a matched group of young people with no known disorders. They demonstrated that those with TS had higher concentrations of GABA, which inhibits neuronal activity, in the SMA.

Draper suggests that the finding points to a way to control the tics of TS wherein new brain stimulation techniques might be used to increase or decrease GABA in targeted areas of the cortex. Modulating GABA in this way could be used to help young people with TS gain greater control over their tics. Draper says.

Brain training
Commonly, TS sufferers must use great concentration if they are to control their tics, but the mental effort required can leave them feeling exhausted. Moreover, such attempts to control their tics can lead to a bounce back when they relax in which suppressed symptoms emerge stronger than they otherwise might. Nevertheless, the majority of people diagnosed with TS in childhood do gain control of their tics as they get older until only mild symptoms by early adulthood, but this can be too late in terms of their social and educational development where relationships and the person's learning may have been significantly disrupted by their symptoms throughout their formative years.

The researchers have also used other neuroscience techniques to explore the relationship between GABA and activity in the SMA. They found that people with TS had less activity in the SMA when asked to perform a simple motor task, in this case tapping their finger, which the team was able to measure using functional MRI. They then used transcranial magnetic stimulation (TMS) in which a magnetic field is passed over the brain to stimulate neuronal activity, to determine whether those with the most GABA would experience a dampening down of the brain activity in the M1 when readying themselves to make a movement, which was indeed the case. By contrast, the non-TS group displayed increased activity as they prepared to make a movement.

Jackson explains that the finding is paradoxical because previous understanding suggested that GABA levels in TS would be reduced and not increased as the team demonstrated. He adds that, "A distinction should be made between brain changes that are causes of the disorder (e.g. reduced GABA cells in some key brain areas) and secondary consequences of the disorder (e.g. increased release of GABA in key brain areas) that act to reduce the effects of the disorder."

The work suggests that new transcranial direct-current stimulation (TDCS) devices, similar to commercially available TENS machines used for pain relief, might be devised to benefit young people with TS and to help them "train" themselves to gain control over their tics.
"Our next step is to examine if other brain areas, particularly the frontal and insular cortices also show increases in GABA in TS that are associated with tic severity," Jackson told SpectroscopyNow. "We also plan to investigate this issue in other, related, neurodevelopmental disorders such as obsessive compulsive disorder (OCD) and autism. Long term we want to develop safe and effective non-drug treatments for altering localised cortical excitability."

Related Links
Curr Biol, 2014, 24, online: "Increased GABA Contributes to Enhanced Control over Motor Excitability in Tourette Syndrome"

Related reporting (Forum Post)