A method for recording resistance changes non-invasively during neuronal depolarization with a view to imaging brain activity with electrical impedance tomography

Abstract

Electrical impedance tomography (EIT) is a recently developed medical imaging method which has the potential to produce images of fast neuronal depolarization in the brain. The principle is that current remains in the extracellular space at rest but passes into the intracellular space during depolarization through open ion channels. As current passes into the intracellular space across the capacitance of cell membranes at higher frequencies, applied current needs to be below 100 Hz. A method is presented for its measurement with subtraction of the contemporaneous evoked potentials which occur in the same frequency band. Neuronal activity is evoked by stimulation and resistance is recorded from the potentials resulting from injection of a constant current square wave at 1 Hz with amplitude less than 25% of the threshold for stimulating neuronal activity. Potentials due to the evoked activity and the injected square wave are removed by subtraction. The method was validated with compound action potentials in crab walking leg nerve. Resistance changes of -0.85+/-0.4% (mean+/-SD) occurred which decreased from -0.97+/-0.43% to -0.46+/-0.16% with spacing of impedance current application electrodes from 2 to 8 mm but did not vary significantly with applied currents of 1-10 microA. These tallied with biophysical modelling, and so were consistent with a genuine physiological origin. This method appears to provide a reproducible and artefact free means for recording resistance changes during neuronal activity which could lead to the long-term goal of imaging of fast neural activity in the brain.

Fig. 1

The recorded signal V from the crab nerve or the scalp was a composite signal which comprised three components: 1) A bi-polar square wave baseline b, 2) Neuronal activity v triggered by visual stimuli (black arrows) or stimulating pulses to the crab nerve and 3) a deflection δ in the baseline due to the resistance decrease. The dotted line in the recorded signal (4) is the VEP as in (2) that would appear in the recorded signal (solid) if the resistance decrease δ was not present. The stimuli were delayed by 150 ms from the beginning of each of the square wave polarities and for the human case were expected to produce the main component of the VEP, the P100, about half way into the 500 ms half square wave cycle.

Fig. 2

Derivation of the final v and δ waveforms (bottom, red) from the average of the control and active recordings (left) using summation and subtraction of the two polarities (right) followed by a second subtraction between the control and active recordings. For the purpose of explanation, the square wave is shown as square; in practice it was a falling exponential of variable shape. Sum_c, Diff_c and Sum_a, Diff_a are the summation and subtraction of the two polarities of the square wave for the control and active recordings respectively.

Fig. 3

Electrode array and experimental setup for crab nerve.

Fig. 4

Instrumentation setup.

Fig. 5

Group display of all recordings with different current and drive electrode spacing. In each box, the CAP is in black (positive waveforms, mV units on the leftmost axes) and the resistance changes δ are in black or in red for the significant regions (negative waveforms, percentage units on the rightmost axes). Individual waveforms are the estimation after averaging over the 1 minute recording. The stimulus was applied at 0 ms. a-d: different current levels for a fixed current drive spacing of 2 mm. e-g: different current drive spacing for a fixed current of 2 μA (b and e are identical).

Fig. 6

Peak changes in δ (±1 SE) for (a) the different current levels with n = 7, 12, 4 and 6 recordings and (b) the different current drive spacing with n = 12, 6 and 8 recordings.

Fig. 7

Delay from stimulus of peak CAP (black, bottom line) or changes in δ (red, top line) (±1 SE) for (a) the different current levels and (b) the different current drive spacing.