Date Published: June 3, 2019
Publisher: Public Library of Science
Author(s): Shuyan Han, Akitoshi Ogawa, Takahiro Osada, Akimitsu Suda, Masaki Tanaka, Hitoshi Nanjo, Yasushi Shimo, Nobutaka Hattori, Seiki Konishi, François Tremblay.
Transcranial magnetic stimulation (TMS) of the human lateral prefrontal cortex, particularly the ventral region, often causes considerable discomfort to subjects. To date, in contrast to abundant literature on stimulations to the dorsolateral prefrontal cortex, the ventrolateral prefrontal cortex has been less frequently stimulated, partly because some subjects are intolerable of stimulation to the ventrolateral prefrontal cortex. To predict the additional number of subjects required for the stimulation of the dorsolateral and ventrolateral prefrontal cortices, 20 young healthy subjects reported two evaluation scores: the discomfort caused by TMS and the resulting intolerability to complete the TMS experiments. Single-pulse stimulation (SPS) or theta-burst stimulation (TBS) was administered to the lateral prefrontal cortex. The high-resolution extended 10–20 system was used to provide accurate estimation of the voxelwise scores. The discomfort ratings with the SPS and TBS were relatively higher in the ventrolateral prefrontal cortex than those in the dorsolateral prefrontal cortex. Both the SPS and TBS elicited maximal discomfort at the stimulation position F8. The SPS and TBS to F8 under the standard TMS protocols were intolerable for approximately one half (11 and 10, respectively) of the subjects. The intolerability was further calculated for all voxels in the lateral prefrontal cortex, which enabled us to estimate the additional number of subjects required for specific target areas. These results suggest that prior knowledge of subjects’ discomfort during stimulation of the lateral prefrontal cortex can be of practical use in the experimental planning of the appropriate number of recruited subjects and provide the database for the probability of intolerability that can be used to predict the additional number of subjects.
Transcranial magnetic stimulation (TMS) of the lateral prefrontal cortex can be powerful in noninvasive studies of the causal relationship of brain regions with cognitive functions [1–8]. However, TMS research in the lateral prefrontal cortex is limited. Stimulation to the lateral prefrontal cortex often causes considerable discomfort to subjects [9–16] due to a greater density of muscles and nerves in the prefrontal regions [17–19]. Stimulation of the dorsal region of the lateral prefrontal cortex has frequently been reported [20–40], while fewer (approximately one-third, based on our PubMed search) studies have reported stimulation of the ventral region of the lateral prefrontal cortex [41–48]. Stimulation of brain regions that tend to elicit discomfort appears nonpreferred, partly because some subjects are intolerant of stimulation to the brain regions. The intolerability of unpreferred brain region stimulation results in data loss of some subjects and, therefore, the loss of study power. However, prior knowledge of intolerability caused by stimulation is helpful in the experimental planning of the appropriate sample size.
The present study investigated discomfort and intolerability for subjects during SPS and TBS administered to the lateral prefrontal stimulation positions of the high-resolution extended 10–20 system. The SPS and TBS of the ventrolateral prefrontal cortex elicited greater discomfort and intolerability than that of the dorsolateral prefrontal cortex. The magnitude of discomfort and intolerability was similar in the SPS and TBS, and the intolerability was maximal (~ 50%) at stimulation position F8, which indicates that the number of subjects to be recruited would have to be double the intended sample size. The image file of the voxelwise probability of intolerability in the lateral prefrontal cortex is provided as supplementary data (S1 File), which would be useful in estimating the additional number of subjects to be recruited.