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Brain chemical potential new hope in controlling Tourette Syndrome tics

Posted on 2 October 2014 by Seonaid Anderson

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A chemical in the brain plays a vital role in controlling the involuntary movements and vocal tics associated with Tourette Syndrome (TS), a new study has shown.

Although the exact cause of TS is unknown, research has shown that people with TS have alterations in brain circuits that are involved in producing and controlling movements.  Put simply, people with TS receive too many signals to areas in the cortex that are involved in planning and executing movements, which results in unwanted or inappropriate movements. Two such cortical areas, the primary motor cortex (M1) and the supplementary motor area (SMA), are thought to be “hyper-excitable” in TS, which mean they have too much activity.

We used a technique called magnetic resonance spectroscopy (MRS) in a 7T MRI brain scanner to measure the concentration of certain chemicals in the brain, known as neurotransmitters, which reflect brain activity.  The chemicals were measured from 3 regions: M1, the SMA, and an area that is involved in visual processing (V1) which was a control site.  We tested a group of young people with TS and an age and gender-matched group of typical young people who had know known disorders. Our most interesting result was that the people with TS had elevated concentrations of a neurotransmitter called GABA in the SMA only.

The role of GABA in the brain is to inhibit neuronal activity by reducing the probability that a cell will fire. The brain is very noisy, with lots of signals being sent every second, and that noise is higher than average in people with TS. You can think of increased GABA as a way of “turning down the volume” on the all that noise, so that only the strongest signals get through and produce a movement.

We then used different neuroscience techniques to explore this result in more detail. What we found was having more GABA in the SMA meant the TS group had less activity (measured this time by fMRI) in the SMA when we asked them to tap their fingers. Using another technique called transcranial magnetic stimulation (TMS), we found that those with the most GABA dampen down their brain activity in M1 when they are preparing to make a voluntary movement.  In contrast, the typically developing group increased their activity during movement preparation.

Finally, we considered how GABA was related to brain structure; specifically the white matter fibre bundles that connect the 2 hemispheres of the brain together; a structure called the corpus callosum. We were only interested in the section of the corpus callosum that joins together the SMA across hemispheres. We found that the people with the highest levels of GABA also had the most connecting fibres. We believe that this is because the more connecting fibres there are, the more excitatory signals there are, which means you would need even more GABA to reduce the excess activity. 
 Taken together, these results suggest that higher levels of inhibitory neurotransmitter GABA in the SMA helps to dampen down the excess noise in the brains of people with TS. This is likely to be an adaptation the brain has made to help people with TS produce a voluntary movement without interference from tics. Reducing this excess excitatory activity could also be a long term contributing factor to the remission of tics.

This result is important because new brain stimulation techniques, such as tdcs, can be used to increase or decrease GABA in targeted areas of the cortex. Perhaps using such techniques to increase the levels of GABA in the SMA could help young people with TS gain control over their tics.

Professor Stephen Jackson added: “This finding is paradoxical because prior to our finding, most scientists working on this topic would have thought that GABA levels in TS would be reduced and not increased as we show. This is because 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.”

What does this mean for people with TS?
Perhaps using such techniques to increase the levels of GABA in the SMA could help young people with TS gain control over their tics.
New tdcs devices, similar to commercially-available TENS machines, could potentially be produced to be used by young people with TS to ‘train’ their brains to help them gain control over their tics, offering the benefit that they could be relatively cheap and could be used in the home while performing other tasks such as watching television.

We are very grateful to all the young people and their families who took part in these studies.

The full paper can be accessed here.

 Draper, A., Stephenson, M.C., Jackson, G.M, Pepes, S., Morgan, P.S., Morris. P.G. & Jackson, S.R.  Increased GABA contributes to enhanced control over motor excitability in Tourette syndrome. Current Biology 2014 Oct 6; 24(19): 2343–2347.

The University of Nottingham press release can be read here.

 

 For more details on Tourettes Action research projects, please contact TA Research Manager, Seonaid Anderson.


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