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 (10-40V/m) in animal models that exceed those typically achieved in humans. 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. Currents of 0.005-0.3mA were applied in 9 rats, generating electric fields of 0.5-35V/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. 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. 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.

High-channel-count neuroprostheses could one day restore functional vision in blind individuals by delivering electrical pulses to electrodes in the visual cortex that elicit perceptions known as 'phosphenes'. However, if a high number of electrodes are used, it becomes challenging and time-consuming to map the visual field locations of all phosphenes. Furthermore, many blind users are not able to maintain stable fixation, impeding the localization of phosphenes, or may perceive spontaneous visual phenomena that interfere with detection of electrically induced phosphenes. To introduce and evaluate NEural Unsupervised electrode mapping (NEUmap), a rapid, largely automated method for phosphene mapping that extracts spatial patterns from spontaneous activity across the visual cortex. As correlations between neuronal activity on nearby electrodes are stronger than those between distant electrodes, we first use dimensionality-reduction algorithms to generate maps of relative positions of electrodes. We then determine visual field coordinates of phosphenes. To this aim, the subject manually reports phosphene locations for a small subset of electrodes, which we call 'anchor points', e.g. by pointing or drawing phosphene locations on a tablet. NEUmap then aligns the anchor points to the map of relative distances to obtain an estimate of the visual field coordinates of all phosphenes. NEUmap was applied to data recorded from 896 V1 electrodes in each of two sighted monkeys, and 96 V1/V2 electrodes in each of 3 blind human volunteers. NEUmap generated high quality maps across ∼300-700 electrodes in each of the monkeys and across 73-91 electrodes in each of the human volunteers. Existing clinical methods of phosphene mapping on many electrodes are tedious. NEUmap can alleviate some of this burden for future prosthesis users by permitting the mapping of hundreds of electrodes using less than a second of resting-state data.