The Comparison of Early Hemodynamic Response to Single-Pulse Transcranial Magnetic Stimulation following Inhibitory or Excitatory Theta Burst Stimulation on Motor Cortex

Abstract

We present a new study design aiming to enhance the understanding of the mechanism by which continuous theta burst stimulation (cTBS) or intermittent theta burst stimulation (iTBS) paradigms elicit cortical modulation. Using near-infrared spectroscopy (NIRS), we compared the cortical hemodynamics of the previously inhibited (after cTBS) or excited (after iTBS) left primary motor cortex (M1) as elicited by single-pulse TMS (spTMS) in a cross-over design. Mean relative changes in hemodynamics within 6 s of the stimulus were compared using a two-sample t-test (p < 0.05) and linear mixed model between real and sham stimuli and between stimuli after cTBS and iTBS. Only spTMS after cTBS resulted in a significant increase (p = 0.04) in blood volume (BV) compared to baseline. There were no significant changes in other hemodynamic parameters (oxygenated/deoxygenated hemoglobin). spTMS after cTBS induced a larger increase in BV than spTMS after iTBS (p = 0.021) and sham stimulus after cTBS (p = 0.009). BV showed no significant difference between real and sham stimuli after iTBS (p = 0.37). The greater hemodynamic changes suggest increased vasomotor reactivity after cTBS compared to iTBS. In addition, cTBS could decrease lateral inhibition, allowing activation of surrounding areas after cTBS.

Keywords: cerebral blood volume; hemodynamics; motor cortex; near-infrared; neuroimaging; spectroscopy; transcranial magnetic stimulation.

Figure 1

Illustration of the stimulation paradigms used. Using near-infrared spectroscopy (NIRS), the hemodynamic changes were measured when TMS blocks of single pulses, both real (25 pulses at 100% of resting motor threshold, marked as solid red lines) and sham (25 pulses that produce a clicking sound that was the same as an active TMS pulse but without actual stimulation of the brain, which were marked in blue dash lines), were applied across M1 before (3 blocks of real and 3 blocks of sham stimulus, which were randomized) and after (5 blocks of real and 5 blocks of sham stimulus, which were randomized) transcranial magnetic theta burst stimulation at 80% of active motor threshold. The theta burst stimulation pattern (TBS), in which 3 pulses of stimulation were given at 50 Hz, repeated every 200 ms (5Hz). In the continuous theta burst stimulation paradigm (cTBS), a 40 s train of uninterrupted TBS was given (600 pulses). In the intermittent theta burst stimulation pattern (iTBS), a 2 s train of TBS was repeated every 10 s for a total of 190 s (600 pulses). Randomly determined inter-block interval (IBI) was 4–10 s. The randomized inter-stimulus interval (IBI) was 6–10 s. Therefore, one session lasted about 40 to 58 min, depending on the randomized ISI, IBI, and the TBS paradigm (i.e., cTBS or iTBS).

Figure 2

Summary of the evoked changes in NIRS measurements. Mean normalized relative changes in cerebral blood volume (BV) (a), oxygenated hemoglobin (HbO₂) (b), and deoxygenated hemoglobin (HHb) (c) elicited by real and sham single-pulse TMS stimulation before theta burst stimulation (preTBS), after continuous theta burst stimulation (cTBS), and after intermittent theta burst stimulation (iTBS). The error bar represents standard error. The p-values above the horizontal lines indicate that the values at the two ends of the lines are significantly different (p < 0.05) or tend to be significantly different (p < 0.1).