Neural mechanisms of tDCS: Insights from an in-vivo rodent model across a range of electric field strengths.

BACKGROUND

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that uses low-amplitude currents to generate low electric fields in the brain, influencing cognition, motor skills, and behavior. Despite its potential, the neural mechanisms underlying tDCS remain unclear, in part because many prior studies have used electric field strengths (10-40 V/m) in animal models that exceed those typically achieved in humans.

OBJECTIVE

To better characterize how cortical neurons respond across a range of electric field strengths, we developed an in-vivo rat model to examine the effects of both low and high electric fields.

METHODS

Currents of 0.005-0.3 mA were applied in 9 rats, generating electric fields of 0.5-35 V/m in the somatosensory cortex. In an anesthetized rat model, we recorded neural activity across cortical layers with a multichannel silicone probe. Somatosensory evoked potentials (SSEP) elicited by foot shocks were recorded, and spike waveforms were used to distinguish regular spiking (RS) and fast-spiking (FS) neurons.

RESULTS

Anodal tDCS was associated with SSEP hyperpolarization in superficial cortical regions and depolarization in deeper regions, with cathodal stimulation producing an asymmetric reversal of this pattern. Changes in spiking activity were observed in RS neurons at lower electric fields, whereas higher field strengths were required to influence spiking activity in FS neurons. Across measures, effect magnitudes scaled with electric field strength and were well described by linear mixed-effects models. Changes in spiking activity were correlated with changes in SSEP polarity.

CONCLUSION

These findings demonstrate that electric field-dependent modulation of cortical activity can be detected in vivo across a wide range of stimulation intensities, including weak fields comparable to those induced by human tDCS, although effects are substantially larger at higher field strengths. This work provides direct in-vivo evidence linking cortical polarization to changes in neuronal spiking and helps constrain mechanistic interpretations of tDCS effects observed in humans.