Excitation-modulation by anodal pulses in biphasic brain stimulation

Abstract

(Accepted February 1st, 1979) Intracranial electrical stimulation (ICS)is one of the most widely-used techni- ques for investigating brain function. Besides its extensive experimental use in laboratory animals, ICS is finding increasing clinical use in humans 3,1°. In light of the widespread use of ICS it is remarkable that so little information exists as to what are the most efficient and safe ways of stimulating nervous tissue. Since the relative merits of various electrode materials, configurations and stimulation waveforms have been discussed elsewhere a,4,6,s,9,11,1z, the present experiment is concerned solely with one important aspect of ICS that has received virtually no systematic attention. That is the excitation,modulating role of the anodal pulses in biphasic ICS. Although a case can be made for using monophasic cathodal pulses s, the inter- pulse intervals commonly used with monophasic ICS are too short to allow the elec- trode potential to completely decay between pulses t1,~2. The accumulated potential can disrupt neural functioning and may eventually cause lesions 6. Since most physiol- ogical and virtually all behavioral responses elicited by ICS require relatively long trains of rather high frequency stimulation, a biphasic wave-form should be used. Although it may be possible to prevent electrode polarization by other means 8, the use of a symmetrical biphasic waveform is by far the most common and best understood technique. The implicit assumption underlying the use of biphasic ICS is that the anodal component serves primarily or exclusively to prevent the occurrence of tissue damage and that it plays no role in modulating neuronal excitability. We now report that this fundamental assumption is incorrect. Anodal pulses exert a large influence on the responses elicited by cathodal pulses. The nature of these effects is critically dependent on the temporal relation between the anodal and cathodal pulses. Male Wistar rats were stereotaxically-implanted with stainless-steel monopolar electrodes aimed for the midbrain reticular formation or the posterior hypothalamus. The electrodes were 200 #m in diameter and were insulated except for the flat cross- section at their tips. After a one week recovery period the rats were given initial training in an 80 cm diameter, clear acrylic hemisphere wherein they received 15 sec trains of ICS separated by 30 sec intervals of no stimulation. The current-regulated ICS consisted of 50 Hz, 150 #A peak amplitude, 200 #sec cathodal pulses each followed 10 msec later (leading edge to leading edge) by a similar anodal pulse. Thus,