Research Briefing: Targeting "silent" brain areas with TMS

A major challenge in neuroscience is how to study brain processes that are securely encased within the skull. Over the last twenty years, there has been enormous progress in non-invasive brain imaging methods. In particular, functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) allow researchers to measure brain activity from outside the head.

Although brain imaging methods allow us to peer inside the head and watch the brain in action, we also need to be able to perturb brain function to understand more fully what observed brain activity is actually doing. We will never understand the brain by just watching it - we also need to be able to poke around to see what happens when certain processes are disrupted. In formal terms, we can only verify causality by disrupting brain activity and observing the consequences.

The most effective method for non-invasive brain disruption is transcranial magnetic stimulation (TMS). TMS is able to disrupt brain activity by delivering a focal magnetic pulse to the overlying scalp surface. The magnetic field passes through the scalp and skull, stimulating brain cells, thereby disrupting brain function.

TMS is the only method currently available in human neuroscience to disrupt specific brain areas and measure the consequence on brain function. TMS has been in use in labs across the world for more than 25 years, and sophisticated methods have been developed for targeting specific brain areas (see neuronavigation, pictured right). Nevertheless, it remain relatively unclear exactly how best to set stimulate intensity.

Setting the right stimulation level is essential for safe and effective use of TMS. Over-stimulation can cause adverse effects, such as seizure. From an experimental point of view, over-stimulation also reduces the focality of disruption, therefore complicating the interpretation of any effects. On the other hand, under-stimulation could compromise treatment in clinical settings, and lead to false negative results in research. Poor control over the stimulation intensity also compromises experimental comparisons between treatment conditions.

In a series of methodological studies performed with Chris Chambers and others, we previously explored the effect of skull thickness on brain stimulation. It is well known that the flux density of a magnetic field declines as a function of distance. As a direct consequence, if people have thicker skulls, they will require a higher intensity field at the scalp surface to activate underlying brain areas. To quantify this dependency, we varied TMS distance over motor cortex.


When TMS is applied to primary motor cortex, stimulation triggers a twitch in the muscle associated with the stimulated portion of the motor map (pictured left). This an extremely reliable and repeatable effect, and therefore provides a very useful tool for assessing the effect of TMS. We simply varied distance between the stimulation coil and the target brain region to characterise the relationship between distance and TMS effect (pictured right). From these initial studies, we suggested that TMS protocols could be usefully calibrated at motor cortex, and corrected for distance to derive a distance-independent estimate of cortical excitability. Distance-corrected levels could then be used to determine the appropriate stimulation intensity for 'silent' brain areas, such as non-motor brain areas for which there is no simple index of effective stimulation.

However, distance adjusted TMS still relies on the assumption that individual differences in response to TMS are due to variations in a general factor of cortical excitability. In this new study we tested this key assumption. We compared peoples' sensitivity to stimulation of motor cortex with stimulation of their visual cortex (indexed by a visual percept known as a phosphene). We found a systematic relationship between individual differences in sensitivity across stimulation sites, consistent with the idea that a common factor of cortical excitability might account for individual differences in the response to TMS.

In conclusion, this research suggests that TMS intensity can be calibrated to distance adjusted motor threshold, and applied to other brain areas. For further information, please see our paper here, or contact me directly.


References

Stokes, Barker, Dervinis, Verbruggen, Maizey, Adams & Chambers (2013) Biophysical Determinants of Transcranial Magnetic Stimulation: Effects of Excitability and Depth of Targeted Area. Journal of Neurophysiology, 109: 437– 444 [pdf]

Stokes, Chambers, Gould, English, McNaught, McDonald & Mattingley (2007) Distance-adjusted motor threshold for transcranial magnetic stimulation. Clinical Neurophysiology, 118(7): 1617-1625 [pdf]

Stokes, Chambers, Gould, Henderson, Janko, Allen & Mattingley (2005) A simple metric for scaling motor threshold based on scalp-cortex distance: application to studies using transcranial magnetic stimulation. Journal of Neurophysiology, 94(6): 4520-4527 [pdf]

Helium and Neuroscience

Modern cognitive neuroscience critically depends on helium. The most advanced methods for non-invasive brain imaging, function magnetic resonance imaging (fMRI) and magnetoencephalography (MEG), operate at near absolute zero (~4° Kelvin). This operating temperature can only be maintained with liquid helium. Although helium is the second most abundant element in the universe, helium supplies are strictly limited on Earth.

Recently, global helium shortages have forced many MEG centres into temporary shut down. MRI facilities have so far been less affected, because they require less frequent helium re-fills. But if the situation was to get much worse, then even MRI centres will be forced to shut down. Cooling down the magnet at the heart of MRI can cause major structural damage, potentially requiring a complete refit.

Writing for the The Independent, science editor Steven Conner explains some of the key factors at play [here]. In an accompanying piece, I  provide some more specific details of how recent shortages have affected our research at the Oxford Centre for Human Brain Activity [here]. It is impossible to predict how neuroscience methods will have advanced by the time the world's supply has been depleted in the next 30 years or so, but let's hope we have found new methods for non-invasive brain imaging that don't depend on an unavailable element.

References:
The Independent: A ballooning problem: the great helium shortage
The Independent: Our research is on ice due to shortage of helium