Inhibition and rTMS

Imagine your phone is ringing and just as you reach for it, it stops ringing - the caller hung up. Chances are, you were able to inhibit your movement and didn't pick up the phone. What brain regions implement this kind of "stop signal"?

Neuroimaging and neuropsychological investigations have revealed that the right inferior frontal gyrus (IFG), the middle frontal gyrus, and the right inferior parietal cortex appear to be important for such inhibition. However, as Chambers et al point out in a recent issue of the Journal of Cognitive Neuroscience, each of these techniques has its drawbacks. Imaging can only tell you which regions are associated with a given function, not which are causally responsible. And while neuropsychological investigations of brain damaged patients does provide information about causality, the power of these studies may be limited due to the tendency of brain-damaged patients to show some functional reorganization as a response to brain injury.

Enter repetitive transcranial magnetic stimulation (rTMS). rTMS involves directing strong magnetic fields towards a specific area of the brain. This has the effect of temporarily disrupting normal activity in that region. Using this technology, we should be able to identify which of these regions is causally responsible for inhibition, and which are merely associates.

This is exactly what Chambers et al did in two sets of experiments. First, they calibrated the stop signal reaction time (SSRT) for each of 16 subjects - SSRT is the amount of time it takes you to cancel an intended motor action. This is calculated by telling subjects to press a button every time an "X" or an "O" appears, and then telling them to "stop" on 25% of trials. Critically, the amount of delay between presentation of the stimulus and the signal to "stop" is varied. The amount of time required for subjects to successfully inhibit their response 50% of the time is called the SSRT.

Next, they put each of these subjects into an MRI scanner to identify the location of the inferior frontal, middle frontal, and angular gyri in each subject's brain. They then performed rTMS on each of these regions, accompanied by "sham TMS" conditions in which the magnet was on but directed away from their heads, in order to identify which would most significantly increase the required stop signal reaction time in each participant.

The results were striking. Disruption of activity within the right IFG, but not in either of the other regions, led to a selective increase in the SSRT relative to the sham condition - an increase of almost 30 miliseconds.

What if rTMS of the IFG results merely in suppression of arousal? In other words, wouldn't we expect a similar pattern if the right IFG was responsible for keeping subjects awake? The authors considered this possibility, but show that neither pupil diameter change (a putative measure of arousal) nor changes in reaction time or accuracy on "go" trials (trials in which the stop signal was not provided).

Interestingly, rTMS of the right IFG had no effect after about 30 minutes, suggesting that this regions is capable of extremely rapid functional reorganization.