Neural summation in human motor cortex by subthreshold transcranial magnetic stimulations

Abstract

Integration of diverse synaptic inputs is a basic neuronal operation that relies on many neurocomputational principles, one of which is neural summation. However, we lack empirical understanding of neuronal summation in the human brains in vivo. Here, we explored the effect of neural summation on the motor cortex using two subthreshold pulses of transcranial magnetic stimulation (TMS), each with intensities ranging from 60 to 95% of the resting motor threshold (RMT) and interstimulus interval (ISI) varying from 1 to 25 ms. We found that two subthreshold TMS pulses can produce suprathreshold motor response when ISIs were less than 10 ms, most prominent at 1, 1.5 and 3 ms. This facilitatory, above-threshold response was evident when the intensity of the subthreshold pulses was above 80% of RMT but was absent as the intensity was 70% or below. Modeling of the summation data across intensity suggested that they followed an exponential function with excellent model fitting. Understanding the constraints for inducing summation of subthreshold stimulations to generate above-threshold response may have implications in modeling neural operations and potential clinical applications.

Fig. 1

Effect of interstimulus interval (ISI) and intensity of subthreshold stimulus on motor evoked potential (MEP). The peak-to-peak amplitudes of MEP were shown. Dotted horizontal line marks the amplitude of MEP with at-threshold single pulse stimulation. The facilitation occurred as a function of ISI and intensity of the subthreshold stimuli. Compared with non-response at 70% resting motor threshold (RMT), some summation effects can been seen at ISI as far apart as 15 ms. However, compared with at-threshold single pulse stimulaiton, summation occured mainly at 1, 1.5 and 3 ms ISIs with the higher subthreshold stimulation, marked with ‘*’ (p<.05). Error bar indicates SE

Fig. 2

Effect of interstimulus interval (ISI) from 1.0 to 2.2 ms at 95% of resting motor threshold (RMT) on motor evoked potential (MEP). Dotted line indicates amplitude of MEP with at-threshold single stimulation. ‘*’ indicates p<.05. Error bar indicates SE

Fig. 3

Subthreshold summation effects followed a similar exponential function across different ISI. The exponential equation and curve-fit were shown for each ISI that exhibited summation effect (a, b and c). Although the amplitudes were quite different in different ISIs, the fits were excellent and the parameters of the exponential functions were similar