Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks

Abstract

Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently pre/post differences for each individual outcome measure and task, either one or both of the active protocols appeared to modulate WM and EF. We critically discuss the value, potential explanations, and some plausible interpretations for this set of subtle impacts of left dlPFC TBS in humans.

Keywords: dorsolateral prefrontal cortex; executive functions; n-back; non-invasive brain stimulation; stroop test; tower of hanoi; transcranial magnetic stimulation; working memory.

Figure 1

Schematic drawing representing the details of the experimental procedure followed by participants. During session 1 active motor threshold was determined before performing the neuropsychological battery of tests used in the study. One week thereafter, during session 2, the neuropsychological battery was performed again following one of the three TBS stimulation conditions (iTBS, cTBS or sham). Behavioral tasks were always administered in the same order.

Figure 2

TMS target. Schematic figure showing on an MRI 3D reconstruction from a representative participant (with permission) the TMS targeted left dlPFC region identified according to standardized MNI coordinates (x = −40, y = 28, z = 31).

Figure 3

Representation of the different analyses performed on the current study to compare behavioral outcomes (pre, post stimulation, and delta post-pre stimulation change) across (Kruskal–Wallis H-test) and within (Wilcoxon signed rank test) stimulation conditions (i.e., sham, cTBS, and iTBS).

Figure 4

Representation of the standardized changes for each of the evaluated scores (mean/SD), across groups and tasks. The Kruskal–Wallis H-test revealed no statistically significant modulations of TBS patterns between conditions for any of the outcome measures. Acc., Accuracy; RT, reaction time; WR, Word Reading; CN, Color Naming; CW, Color-Word; IS, Interference Score; Mov., Number of movements.

Figure 5

Boxplots representing the pre (pale gray) and post (dark gray) distributions of each stimulation condition (i.e., sham, cTBS and iTBS) for (A) the number of strings completed in the Digits Backward test, (B) the number of correct responses in the 3-back task, (C) the interference score of the Stroop test, and (D) the time to complete the Tower of Hanoi. The asterisks (^*) represent statistically significant differences (p < 0.05) between pre- and post-TBS assessment in specific conditions and tests. Circles (°) represent outliers.