Abstract
Electrical microstimulation has been widely used to artificially activate neural circuits on fast time scales. Despite the ubiquity of its use, little is known about precisely how it activates neural pathways. Current is typically delivered to neural tissue in a manner that provides a locally balanced injection of positive and negative charge, resulting in negligible net charge delivery to avoid the neurotoxic effects of charge accumulation. Modeling studies have suggested that the most common approach, using a temporally symmetric current pulse waveform as the base unit of stimulation, results in preferential activation of axons, causing diffuse activation of neurons relative to the stimulation site. Altering waveform shape and using an asymmetric current pulse waveform theoretically reverses this bias and preferentially activates cell bodies, providing increased specificity. In separate studies, measurements of downstream cortical activation from sub-cortical microstimulation are consistent with this hypothesis, as are recent measurements of behavioral detection threshold currents from cortical microstimulation. Here, we compared the behavioral and electrophysiological effects of symmetric vs. asymmetric current waveform shape in cortical microstimulation. Using a go/no-go behavioral task, we found that microstimulation waveform shape significantly shifts psychometric performance, where a larger current pulse was necessary when applying an asymmetric waveform to elicit the same behavioral response, across a large range of behaviorally relevant current amplitudes. Using voltage-sensitive dye imaging of cortex in anesthetized animals with simultaneous cortical microstimulation, we found that altering microstimulation waveform shape shifted the cortical activation in a manner that mirrored the behavioral results. Taken together, these results are consistent with the hypothesis that asymmetric stimulation preferentially activates cell bodies, albeit at a higher threshold, as compared to symmetric stimulation. These findings demonstrate the sensitivity of the pathway to varying electrical stimulation parameters and underscore the importance of designing electrical stimuli for optimal activation of neural circuits.
Highlights
Electrical microstimulation has been used for over a century to better understand the brain’s natural circuitry and to perturb that circuitry to generate percepts [1]
The majority of electrical microstimulation studies have used as the base unit of stimulation a symmetric current pulse waveform, in which the shape of the cathode phase is the same as the shape of the anode phase
Recent in vivo work has shown that electrical stimulation does not activate cells around the stimulation site as was originally proposed [25] but rather activates axons passing near the electrode tip, resulting in sparse activation of neurons [26,27]
Summary
Electrical microstimulation has been used for over a century to better understand the brain’s natural circuitry and to perturb that circuitry to generate percepts [1]. Electrical stimulation has been used to generate percepts in the somatosensory system [14,15] and extensively in the visual system at the level of the visual cortex [16,17,18], thalamus [19,20], and more recently in the retina [21,22]. Despite its long and varied use, precisely how electrical microstimulation activates neural circuits is not well understood. Recent in vivo work has shown that electrical stimulation does not activate cells around the stimulation site as was originally proposed [25] but rather activates axons passing near the electrode tip, resulting in sparse activation of neurons [26,27]. In order to activate neural tissue and generate more reliable and robust percepts, it is important to develop methodologies to preferentially activate cell bodies over axons
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