Asymmetrical charge-balanced biphasic stimuli, consisting of a long-duration low-amplitude cathodic prepulse phase followed by a short-duration high-amplitude anodic stimulus phase, enabled selective activation of local cells.

. Extracellular stimulation of the CNS with symmetrical charge balanced biphasic stimuli resulted in activation of fibers of passage, axon terminals, and local cells around the electrode at similar thresholds. While high stimulus frequencies enhanced activation of fibers of passage, a much more robust technique to achieve selective activation of targeted neuronal populations was via alterations in the stimulus waveform. Asymmetrical charge-balanced biphasic stimuli, consisting of a long-duration low-amplitude cathodic prepulse phase followed by a short-duration high-amplitude anodic stimulus phase, enabled selective activation of local cells.

Conversely, an anodic prepulse phase followed by a cathodic stimulus phase enabled selective activation of fibers of passage

Conversely, an anodic prepulse phase followed by a cathodic stimulus phase enabled selective activation of fibers of passage. The threshold for activation of axon terminals in the vicinity of the electrode was lower than the threshold for direct activation of local cells, independent of the stimulus waveform.

As a result, stimulation induced trans-synaptic influences (indirect depolarization/hyperpolarization) on local cells altered their neural output, and this indirect effect was dependent on stimulus frequency

As a result, stimulation induced trans-synaptic influences (indirect depolarization/hyperpolarization) on local cells altered their neural output, and this indirect effect was dependent on stimulus frequency. If the indirect activation of local cells was inhibitory, there was little effect on the stimulation induced neural output of the local cells. However, if the indirect activation of the local cells was excitatory, attempts to activate selectively fibers of passage over local cells was limited. These outcomes provide a biophysical basis for understanding frequency-dependent outputs during CNS stimulation and provide useful tools for selective stimulation of the CNS.

Knowing what neural elements are activated by the stimulus is of fundamental importance in understanding the behavioral response

Knowing what neural elements are activated by the stimulus is of fundamental importance in understanding the behavioral response, and in the case of neural prostheses, selective activation of targeted populations is required for device efficacy.

We have previously developed asymmetric biphasic charge-balanced stimuli that increased the threshold difference between neurons with their cell bodies near the electrode (local cells) and fibers of passage (McIntyre and Grill 2000). However, this analysis was limited to idealized neural orientations and single stimuli.

The first goal of the present study was to determine if asymmetric biphasic charge-balanced stimulus waveforms are effective in increasing the selectivity between cells and fibers in a specific instance of intraspinal microstimulation. The second goal was to determine if the waveforms are effective under repetitive activation with trains of stimuli. Our hypothesis was that stimulus trains would provide enhanced selectivity because of differences in the post-action potential excitability of cells and fibers of passage.

The influence of extracellular electric fields on neurons is related to the second difference of the extracellular potential along the extent of the individual neurons and will cause both regions of depolarization and regions of hyperpolarization in the same neuron

Cathodic or anodic stimuli result in different sites of action potential initiation (API) in local cells and fibers of passage