Trains Of Biphasic Pulses Research Articles

The long lasting effects of electrical simulation of the medial preoptic area and medial amygdala on maternal behavior in female rats

A program of repeated electrical (kindling-like) stimulation of the medial preoptic area (MPOA) or the medial amygdala (MedAmyg) on maternal and other behaviors were investigated. Stimulation was applied daily for 14 days (or until a stage 3 motor seizure was observed) using 2 s trains of biphasic square wave pulses at 60 Hz, 1 ms duration and 300–500 μA. Confirmation of afterdischarge using these parametres was established. In the first experiment, maternally experienced (but not post-partum) MedAmyg stimulated animals became maternal more slowly than did MedAmyg not stimulated animals or than MPOA stimulated animals. In the second experiment, virgin animals were used. MPOA stimulation enhanced the female's preference for pup associated environments in the conditioned place preference (CPP) paradigm. MedAmyg stimulation had no effect on CPP performance, but produced a decreased preference for pup odors in a modified hole board test and increased `anxiety' in the open field. These results confirm that the MPOA and the MedAmyg are involved in facilitating and attenuating maternal responsiveness and related (precursor?) behaviors, respectively. It appears that chronic (kindling-like) stimulation of these neural substrates enhances their functions.

Loudness perception with pulsatile electrical stimulation: the effect of interpulse intervals.

The effect of interpulse intervals on the perception of loudness of biphasic current pulse trains was investigated in eight adult cochlear implantees at three different stimulus levels encompassing the psychophysical dynamic range. Equal-loudness contours and thresholds were obtained for stimuli in which two biphasic pulses were presented in a fixed repetition period (4 and 20 ms), and also for single-pulse/period stimuli with rates varying between 20 and 750 Hz. All stimuli were of 500-ms duration, and the phase durations of each pulse were 100 microseconds or less. The results of these experiments were consistent with predictions of a three-stage model of loudness perception, consisting of a peripheral refractory effect function, a sliding central integration time window, and a central equal-loudness decision device. Application of the model to the data allowed the estimation of neural refractory characteristics of the subjects' remaining peripheral neural population. The average neural spike probability for a 50-Hz stimulus was predicted to be about 0.77, with an associated neural refractory time of 7.3 ms. These predictions did not vary systematically with level, implying that the effect of increasing current level on loudness results more from recruitment of neurons than from any increase in average spike probability.

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates. II. Comparison of fixed amplitude with amplitude modulated stimuli

We have previously shown that acute electrical stimulation of the auditory nerve using charge-balanced biphasic current pulses presented continuously can lead to a prolonged decrement in auditory nerve excitability (Tykocinski et al., Hear. Res. 88 (1995), 124–142). This work also demonstrated a reduction in electrically evoked auditory brainstem response (EABR) amplitude decrement when using an otherwise equivalent pulse train with a 50% duty cycle. In the present study we have extended this work in order to compare the effects of electrical stimulation using both fixed amplitude electrical pulse trains and amplitude modulated (AM) pulse trains that more accurately model the dynamic stimulus paradigms used in cochlear implants. EABRs were recorded from guinea pigs following acute stimulation using AM trains of charge-balanced biphasic current pulses. The extent of stimulus-induced reductions in the EABR were compared with our previous results using either fixed amplitude continuous, or 50% duty cycle pulse trains operating at 0.34 μC/phase (2 mA, 170 μs/phase) at 400 or 1000 pulses/s (Tykocinski et al., Hear. Res. 88 (1995) 124–142). The AM pulse train, operating at the same rates, was based on a 1-s sequence of the most extensively activated electrode of a Nucleus Mini-22 cochlear implant using the SPEAK speech processing strategy exposed to 4-talker babble, and delivered the same total charge as the fixed amplitude 50% duty cycle pulse train. Two hours of continuous stimulation induced a significant, rate-dependent reduction in auditory nerve excitability, and showed only a slight post-stimulus recovery for monitoring periods of up to 6 hours. Following 2 or 4 h of stimulation using an otherwise equivalent pulse train with a 50% duty cycle or the AM pulse train, significantly less reduction in the EABR was observed, and recovery to pre-stimulus levels was generally rapid and complete. These differences in the extent of the recovery between the continuous waveform and both the 50% duty cycle and AM waveforms were statistically significant for both 400 and 1000 pulses/s stimuli. Consistent with our previous results, the stimulus changes observed using AM pulse trains were rate dependent, with higher rate stimuli evoking more extensive stimulus-induced changes. The present findings show that while stimulus-induced reductions in neural excitability are dependent on the extent of stimulus-induced neuronal activity, the use of an AM stimulus paradigm further reduces post-stimulus neural fatigue.

Interactions between pulse separation and pulse polarity order in cochlear implants

Interactions between pulse separation and pulse polarity order were examined using psychophysical studies of electrical detection thresholds in nonhuman primates. Subjects were trained using acoustic stimuli, then deafened in one ear and implanted with an electrode array for electrical stimulation of the cochlea. Threshold vs pulse separation functions for trains of biphasic electrical pulses were compared for constant and alternating leading phase polarity. When leading phase polarity was held constant, threshold vs pulse separation functions were nonmonotonic (U-shaped). Small polarity-dependent (cathodic vs anodic leading phase) differences in absolute thresholds were observed at long pulse separations, but function shape was independent of leading phase. When leading phase polarity alternated, there was a pronounced reduction in thresholds at short pulse separations (below about 1 ms), resulting in monotonically increasing threshold vs pulse separation functions. At long pulse separations, functions for alternating and constant polarity stimuli were similar. Polarity effects were most apparent for longer duration trains (20 pulses) at long pulse durations (1–2 ms/phase). For stimuli consisting of only two biphasic pulses, alternating polarity effects depended on whether cathodic or anodic phases were adjacent. The neural mechanisms underlying these effects probably include refractory properties and/or residual potentials.

Psychometric functions and temporal integration in electric hearing.

Temporal-integration functions and psychometric functions for detection were obtained in eight users of the Nucleus 22-electrode cochlear implant. Stimuli were 100-Hz, 200-microseconds/phase trains of biphasic pulses with durations ranging from 0.44 to 630.4 ms (1 to 64 pulses). Temporal-integration functions were measured for 21 electrodes. Slopes of these functions were considerably shallower than the 2.5 dB/doubling slopes typically observed in acoustic hearing. They varied widely across subjects and for different electrodes in a given subject, ranging from 0.06 to 1.94 dB/doubling of stimulus pulses, with a mean [standard deviation (s.d.)] value of 0.42 (0.38). Psychometric functions were measured for 11 of the same 21 electrodes. Slopes of psychometric functions also varied across subjects and electrodes, and were 2-20 times steeper than those reported by other investigators for normal-hearing and cochlear-impaired acoustic listeners. Slopes of individual psychometric functions for 1-, 2-, 4-, and 8-pulse stimuli ranged from 0.20 to 1.84 log d'/dB with a mean (s.d.) value of 0.77 (0.45). Psychometric-function slopes did not vary systematically with stimulus duration in most cases. A clear inverse relation between slopes of psychometric functions and slopes of temporal-integration functions was observed. This relation was reasonably well described by a hyperbolic function predicted by the multiple-looks model of temporal integration [Viemeister and Wakefield, J. Acoust. Soc. Am. 90, 858-865 (1991)]. Psychometric-function slopes tended to increase with absolute threshold and were inversely correlated with dynamic range, suggesting that observed differences in psychometric-function slopes across subjects and electrodes may reflect underlying differences in neural survival.

Estimating mechanical responses to pulsatile electrical stimulation of the cochlea

This study estimated the mechanical response of the cochlea to pulsatile electrical stimulation of the scala tympani of the cat. The auditory nerve compound action potential evoked by an acoustic probe was forward-masked by a train of charge-balanced biphasic current pulses. Masking as a function of probe frequency reflected the excitation pattern of the response to the masker and resembled the spectrum of the electrical stimulus. Both pulse rate and pulse width influenced the degree of masking. The vibration of a region of the basilar membrane was estimated by recording the local cochlear microphonic evoked by biphasic pulses. The amplitude of the cochlear microphonic was proportional to the amplitude of the spectral component of the electrical stimulus to which the local cochlear microphonic was tuned. These results are consistent with the generation of a mechanical response to the electrical stimulus.

Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex

The feasibility of producing a visual prosthesis for the blind using intracortical microstimulation (ICMS) of the visual cortex was studied in a 42-year-old woman who had been totally blind for 22 years secondary to glaucoma. Thirty-eight microelectrodes were implanted in the right visual cortex, near the occipital pole, for a period of 4 months. Percepts reported as small spots of light, called phosphenes, were produced with 34 of the 38 implanted microelectrodes. Threshold currents for phosphene generation with trains of biphasic pulses were as low as 1.9 microA, and most of the microelectrodes had thresholds below 25 microA. Phosphene brightness could be modified with stimulus amplitude, frequency and pulse duration. Repeated stimulation over a period of minutes produced a gradual decrease in phosphene brightness. Phosphenes did not flicker. The apparent size of phosphenes ranged from a pin-point' to a nickel' (20 mm diameter coin) held at arm's length. Phosphene size usually decreased as stimulation current was increased but increased slightly as the train length (TL) was increased. At levels of stimulation near threshold, the phosphenes were often reported to have colours. As the stimulation level was increased, the phosphenes generally became white, greyish or yellowish. Individual phosphenes appeared at different distances from the subject. When two phosphenes were simultaneously generated, the apparent distances of the individual phosphenes sometimes changed to make them appear to be at about the same distance. When three or more phosphenes were simultaneously generated, they became coplanar. Except for rare occasions, phosphenes extinguished rapidly at the termination of the stimulation train. When stimulation TLs were increased beyond 1 s, phosphenes usually disappeared before the end of the train. The duration of phosphene perception could be increased by interrupting a long stimulation train with brief pauses in stimulation. Intracortical microelectrodes spaced 500 microns apart generated separate phosphenes, but microelectrodes spaced 250 microns typically did not. This two-point resolution was about five times closer than has typically been achieved with surface stimulation. With some individual microelectrodes, a second closely spaced phosphene was sometimes produced by increasing the stimulation current. Phosphenes moved with eye movements. When up to six phosphenes were simultaneously elicited, they all moved with the same relative orientation during eye movements. All phosphenes were located in the left hemi-field with the majority above the horizontal meridian. There was a clustering of most of the phosphenes within a relatively small area of visual space. The potentially greater microelectrode density and lower power requirements of ICMS compared with surface stimulation appears encouraging for a visual prosthesis. However, further studies with blind subjects are required to optimize stimulation parameters and test complex image recognition before the feasibility of a visual prosthesis based on ICMS can be established.

Intensity discrimination as a function of stimulus level with electric stimulation

Difference limens (DLs) for changes in electric current were measured from multiple electrodes in each of eight cochlear-implanted subjects. Stimuli were 200-microseconds/phase biphasic pulse trains delivered at 125 Hz in 300-ms bursts. DLs were measured with an adaptive three-alternative forced-choice procedure. Fixed-level psychometric functions were also obtained in four subjects to validate the adaptive DLs. Relative intensity DLs, specified as Weber fractions in decibels [10 log (delta I/I)] for standards above absolute threshold, decreased as a power function of stimulus intensity relative to absolute threshold [delta I/I = beta (I/I0) alpha] in the same manner as Weber fractions for normal acoustic stimulation reported in previous studies. Exponents (alpha) of the power function for electric stimulation ranged from -0.4 to -3.2, on average, an order of magnitude larger than exponents for acoustic stimulation, which range from -0.07 to -0.11. Normalization of stimulus intensity to the dynamic range of hearing resulted in Weber functions with similar negative slopes for electric and acoustic stimulation, corresponding to an 8-dB average improvement in Weber fractions across the dynamic range. Sensitivity to intensity change ¿10 log beta¿ varied from -0.42 to -13.5 dB compared to +0.60 to -3.34 dB for acoustic stimulation, but on average was better with electric stimulation than with acoustic stimulation. Psychometric functions for intensity discrimination yielded Weber fractions consistent with adaptive procedures and d' was a linear function of delta I. Variability among repeated Weber-fraction estimates was constant across dynamic range. Relatively constant Weber fractions across all or part of the dynamic range, observed in some subjects, were traced to the intensity resolution limits of individual implanted receiver/stimulators. DLs could not be accurately described by constant amplitude changes, expressed as a percentage of dynamic range ¿delta A(% DR)¿. Weber fractions from prelingually deafened subjects were no better or worse than those from postlingually deafened subjects. The cumulative number of discriminable intensity steps across the dynamic range of electric hearing ranged from as few as 6.6 to as many as 45.2. Physiologic factors that may determine important features of electric intensity discrimination are discussed in the context of a simple, qualitative, rate-based model. These factors include the lack of compressive cochlear preprocessing, the relative steepness of neural rate-intensity functions, and individual differences in patterns of neural survival.

The perceptual dimensions of single-electrode and nonsimultaneous dual-electrode stimuli in cochlear implantees.

The perceptual dimensions evoked by dual-electrode stimulation were investigated in four cochlear implantees. The dual-electrode stimulation consisted of biphasic current pulse trains, such that two intracochlear electrodes each received one pulse in a 250-Hz cycle. The experiments tested the hypothesis that perceptual qualities would be altered when there was an increased likelihood of interactions occurring between the two electrode places. The parameters of the stimulation which were manipulated to test this hypothesis were the time delay between the pulses on the two electrodes (2 ms and a value between 0.62 and 0.92 ms), the distance between the component electrode rings of each bipolar pair (3.75 mm and either 2.25 or 1.5 mm), and the distance between the two bipolar pairs in the dual-electrode stimuli (from 0.75 to 12.0 mm). Five set of 15 loudness balanced stimuli were created, each set having different stimulation parameters. These stimuli consisted of five single-electrode stimuli (a 250-Hz pulse train on each of five electrodes) and the ten dual-electrode stimuli formed by the combinations of those five electrodes. Two perceptual dissimilarity matrices were obtained for each subject and each set, and were analyzed using repeated nonmetric multidimensional scaling techniques. The resultant "stimulus spaces" were then examined to see how many perceptual dimensions the stimuli were best described by, and to what perceptual or stimulus qualities the dimensions might correspond. The results showed that the percept evoked by dual-electrode stimulation contained two main dimensions. Increasing the width of the current path to create substantially overlapping stimulation areas, or altering the temporal delay between the two electrodes, had very little effect on this percept. The position of the stimuli in the two-dimensional space was related to the distances of the two component electrodes along the electrode array. These results are relevant to speech processing strategies and electrode design for cochlear implants, as they imply that the creation of discrete, nonoverlapping areas of stimulation may not cause the percepts to be more distinct, and therefore may not necessarily lead to better speech perception.

Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex.

The feasibility of producing a visual prosthesis for the blind using intracortical microstimulation (ICMS) of the visual cortex was studied in a 42-year-old woman who had been totally blind for 22 years secondary to glaucoma. Thirty-eight microelectrodes were implanted in the right visual cortex, near the occipital pole, for a period of 4 months. Percepts reported as small spots of light, called phosphenes, were produced with 34 of the 38 implanted microelectrodes. Threshold currents for phosphene generation with trains of biphasic pulses were as low as 1.9 microA, and most of the microelectrodes had thresholds below 25 microA. Phosphene brightness could be modified with stimulus amplitude, frequency and pulse duration. Repeated stimulation over a period of minutes produced a gradual decrease in phosphene brightness. Phosphenes did not flicker. The apparent size of phosphenes ranged from a "pin-point' to a "nickel' (20 mm diameter coin) held at arm's length. Phosphene size usually decreased as stimulation current was increased but increased slightly as the train length (TL) was increased. At levels of stimulation near threshold, the phosphenes were often reported to have colours. As the stimulation level was increased, the phosphenes generally became white, greyish or yellowish. Individual phosphenes appeared at different distances from the subject. When two phosphenes were simultaneously generated, the apparent distances of the individual phosphenes sometimes changed to make them appear to be at about the same distance. When three or more phosphenes were simultaneously generated, they became coplanar. Except for rare occasions, phosphenes extinguished rapidly at the termination of the stimulation train. When stimulation TLs were increased beyond 1 s, phosphenes usually disappeared before the end of the train. The duration of phosphene perception could be increased by interrupting a long stimulation train with brief pauses in stimulation. Intracortical microelectrodes spaced 500 microns apart generated separate phosphenes, but microelectrodes spaced 250 microns typically did not. This two-point resolution was about five times closer than has typically been achieved with surface stimulation. With some individual microelectrodes, a second closely spaced phosphene was sometimes produced by increasing the stimulation current. Phosphenes moved with eye movements. When up to six phosphenes were simultaneously elicited, they all moved with the same relative orientation during eye movements. All phosphenes were located in the left hemi-field with the majority above the horizontal meridian. There was a clustering of most of the phosphenes within a relatively small area of visual space. The potentially greater microelectrode density and lower power requirements of ICMS compared with surface stimulation appears encouraging for a visual prosthesis. However, further studies with blind subjects are required to optimize stimulation parameters and test complex image recognition before the feasibility of a visual prosthesis based on ICMS can be established.

Melody recognition and musical interval perception by deaf subjects stimulated with electrical pulse trains through single cochlear implant electrodes.

The perception of musical pitch was investigated in postlinguistically deaf subjects with cochlear implants. Stimuli consisted of sequences of biphasic electrical pulse trains at rates which represented the tones of the equal-tempered musical scale, delivered at equalized comfortable loudness levels to selected single bipolar electrodes along the array of the Nucleus cochlear implant. Seventeen subjects correctly identified a mean of 44% of rhythmically intact familiar tunes, presented in an open-set paradigm. Three subjects were tested with a closed set of melodies without rhythmic cues. The results showed relatively higher recognition scores at lower pulse rates, although melody recognition remained possible up to rates of approximately 600-800 pulses per second. Stimulation of apical electrodes yielded higher recognition scores than of basal electrodes. The perception of musical intervals, defined as frequency ratios between two trains of stimulus pulse rates, was investigated in an interval intonation labeling experiment, for intervals ranging from a minor 3rd to a major 6th. Within a range of low pulse rates, subjects defined the intervals mediated by electrical pulse rate by the same ratios which govern musical intervals of tonal frequencies in normal-hearing listeners. It may be concluded that temporal cues are sufficient for the mediation of musical pitch, at least for the lower half of the range of fundamental frequencies commonly used in music.

Electrical stimulation in forebrain nuclei elicits learned vocal patterns in songbirds

1. Microstimulation (trains of biphasic current pulses at 50-400 Hz lasting 2-4 s) was delivered unilaterally to known vocal control areas in the brains of zebra finches and canaries to elicit vocalizations. 2. Simple vocalizations were elicited from the midbrain, and the lowest thresholds were obtained from the dorsomedial nucleus of the intercollicular complex (DM). 3. Vocalizations elicited from forebrain vocal control nuclei higher vocal center (HVC) and robustus archistriatalis (RA) were complex, with features specific not only to the species, but to the individual bird's own learned song. 4. Complex acoustic features depended on innervation of the bird's vocal organ and were lost when the tracheosyringeal nerve was cut. 5. We suggest that stimulation of the forebrain vocal pathway activates a dedicated neural circuit that generates the temporal structure of song and whose specific pattern of activity is programmed during sensorimotor learning in each individual.

Corticotrophin-releasing factor-41, vasopressin and oxytocin release into hypophysial portal blood in the rat: effects of electrical stimulation of the hypothalamus, amygdala and hippocampus

The role of the paraventricular nuclei (PVN), amygdala and hippocampus in the control of the hypothalamic-pituitary-adrenal axis has been studied by determining the effect of electrical stimulation of the PVN, amygdala and hippocampus on the release of corticotrophin-releasing hormone (CRF-41) and arginine vasopressin (AVP) into hypophysial portal blood and ACTH and corticosterone into peripheral blood. Adult female Wistar rats were anaesthetized with sodium pentobarbitone and stimulation was carried out through previously implanted bipolar, glass-insulated platinum electrodes. Hypophysial portal blood was collected 30 min before and 30 min during the application of the stimulus which consisted of trains (30 s on and 30 s off) of biphasic rectangular pulses with a frequency of 50 Hz, pulse width 1 ms and amplitude 1 mA. Bilateral stimulation of the PVN increased while unilateral stimulation of the amygdala decreased the release of CRF-41 into hypophysial portal blood. The threefold increase in release of CRF-41 induced by PVN stimulation correlated with a marked increase in peripheral plasma concentrations of ACTH and corticosterone. Stimulation of the hippocampus had no significant effect on CRF-41 release, and stimulation of each of the three brain regions had no effect on AVP release into portal blood. These findings were extended in a second study to compare the effects of unilateral bipolar electrical stimulation of the PVN and of the supraoptic nucleus (SON) on the release of CRF-41, AVP and oxytocin. This study was carried out on adult male rats, anaesthetized with sodium pentobarbitone, in which the stimulus was applied through previously implanted concentric stainless-steel electrodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Perceptual responses to microstimulation of single afferents innervating joints, muscles and skin of the human hand.

1. Microneurographic techniques were used to isolate single afferent axons within cutaneous and motor fascicles of the median and ulnar nerves at the wrist in thirteen subjects. Of the sixty-five identified afferents, eleven innervated the interphalangeal and metacarpophalangeal joints, sixteen innervated muscle spindles, three innervated Golgi tendon organs and thirty-five supplied the glabrous skin of the hand. 2. Intrafascicular stimulation through the recording microelectrode, using trains of constant-voltage positive pulses (0.3-0.8 V, 0.1-0.2 ms, 1-100 Hz) or constant-current biphasic pulses (0.4-13.0 microA, 0.2 ms, 1-100 Hz), evoked specific sensations from sites associated with some afferent species but not others. 3. Microstimulation of eight of the eleven joint afferent sites (73%) evoked specific sensations. With four, subjects reported innocuous deep sensations referred to the relevant joint. With the other four, the subjects reported a sensation of joint displacement that partially reflected the responsiveness of the afferents to joint rotation. 4. Microstimulation of fourteen of the sixteen muscle spindle afferent sites (88%) generated no perceptions when the stimuli did not produce overt movement. However, subjects could correctly detect the slight movements generated when the stimuli excited the motor axons to the parent muscle. 5. With seven of the nine rapidly adapting (type RA or FAI) cutaneous afferents (88%) microstimulation evoked sensations of 'flutter-vibration', and with two of eight slowly adapting (type SAI) afferents (25%) it evoked sensations of 'sustained pressure'. Of the eighteen SAII afferents, which were classified as such by their responses to planar skin stretch, the majority (83%) generated no perceptions, confirming previous work, but three evoked sensations of movements or pressure. 6. The present results suggest a relatively secure transmission of joint afferent traffic to perceptual levels, and it is concluded that the human brain may be able to synthesize meaningful information on joint displacement on the basis of impulses in a single joint afferent. This could partly compensate for the low responsiveness of individual joint afferents within the physiological range of joint displacements. Although single muscle spindle afferents can adequately encode joint position and movement, the results suggest that the brain needs the information from more than one muscle spindle afferent to perceive changes in joint angle.

Detection of gaps in sinusoids and pulse trains by patients with cochlear implants.

Gap detection thresholds were measured in patients with the Nucleus and Symbion cochlear implants as a function of several current waveform parameters. Detection of gaps in an electrical sinusoidal stimulus or in a train of biphasic pulses by implanted patients was similar to detection of gaps in comparable acoustic stimuli by normal listeners. Threshold gaps were 20-50 ms for low-level stimuli and improved with stimulus level to 2-5 ms for high-level stimuli. Gap detection performance was not affected by the electrode position in the cochlea or by the distance between stimulating electrodes. The data from most patients were well fitted by a trading relation between the duration of the gap and the square of stimulus intensity, indicating energy detection. The similarity of gap thresholds for normal subjects and implant patients suggests that many details of the peripheral neural activity are probably not important for this task, and that there is no retrocochlear loss of auditory temporal resolution with sensorineural hearing loss.

Detection of modulation in pulse trains by patients and cochlear implants

Detection of amplitude and pulse‐width modulation was measured in patients with the Symbion and Nucleus cochlear implants as a function of modulation frequency. The resulting temporal modulation transfer functions (TMTFs) are similar to those of normally hearing listeners [N. F. Viemeister, J. Acoust. Soc. Am. 66, 1364–1380 (1979)]. Modulation detection functions are basically low pass, with best sensitivity to modulation frequencies of 20–100 Hz and decreasing sensitivity for modulation frequencies above 100 Hz. Modulation detection performance is similar whether the carrier is an analog sinusoidal stimulus or a biphasic pulse train. These results suggest that envelope detection mechanisms are intact in these implanted patients, even though their cochleae are not functioning and the pattern of activation in their auditory nerves are quite different from any normal acoustic pattern of activity. [Work supported by NIH NS24754.]

Real-time characterization of dopamine overflow and uptake in the rat striatum

The rate of overflow and disappearance of dopamine from the extracellular fluid of the rat striatum has been measured during neuronal stimulation. Overflow of dopamine was induced by electrical stimulation of the medial forebrain bundle with biphasic pulse trains. The instantaneous concentration of dopamine was measured with a Nafion-coated, carbon fiber microelectrode implanted in the brain. The measurement technique, fast-scan cyclic voltammetry, samples the concentration of dopamine in < 10 ms at 100 ms intervals. Identification of dopamine is made with cyclic voltammetry. Stimulated overflow was measured as a function of electrode position, stimulation duration, stimulation frequency, and after administration of l-DOPA and nomifensine. The observed concentration during a 2-s, 60-Hz stimulation was found to alter with position of the carbon fiber electrode. For stimuli of 3 s or less the amount of overflow was found to be a linear function of stimulus duration at a fixed electrode position. The observed overflow was found to be steady-state at a frequency of 30 Hz. suggesting a balance between uptake and synaptic overflow under these conditions. The experimental data was found to be successfully modelled when the balance of uptake and stimulated overflow was considered. It was assumed that each stimulus pulse releases a constant amount of dopamine (125 nM), and that uptake follows a Michaelis Menten model for a single uptake site with K m = 200nM and V max= 5μM/s. The increase in stimulated overflow observed after l-DOPA (250 mg/kg) could be modelled by a 1.6-fold increase in the amount of dopamine release with no alteration of the uptake parameters. The increase in stimulated overflow after nomifensine (2 or 20 mg/kg), a competititve inhibitor of uptake, could be modelled by an increase in K m In addition, the fit of the modelled data to the experimental data was improved when diffusion from the release and uptake sites was considered.

Differential effects of caffeine, picrotoxin, and pentylenetetrazol on hippocampal afterdischarge activity and wet dog shakes

We identified changes in hippocampal afterdischarge activity that follow administration of subconvulsant doses (one-half the convulsant dose) of analeptic agents with known pharmacological action. Long-Evans rats ( N = 104) with chronic bipolar electrodes implanted in the dorsal hippocampus, were injected i.p. with saline, caffeine (75 mg/kg), picrotoxin (2 mg/kg), or pentylenetetrazol (20 mg/kg) in 1 ml/kg volume 15 min before testing. Body temperature was measured at the beginning of the session to determine if significant change was associated with any of the treatments. Beginning at 10 μA, current (2-s train of 50-Hz biphasic pulses) was applied to hippocampal electrodes and intensity was increased in 10-μA steps until the afterdischarge sequence was elicited. Afterdischarge threshold, wet dog shake frequency, and the duration of the primary afterdischarge, the postprimary depression, and the rebound afterdischarge were measured. Caffeine administration produced a dramatic prolongation of the rebound afterdischarge, without affecting the duration of the primary afterdischarge. All other afterdischarge variables were unchanged by the caffeine treatment. Because caffeine blocks adenosine receptors at physiologic concentrations, adenosine action is implicated in the termination of the second, but not the first, spike train. Picrotoxin and pentylenetetrazol had no influence on the EEG, despite evidence of slight (1°C) hypothermia. A decrease in wet dog shake frequency, however, was associated with picrotoxin administration. As picrotoxin and pentylenetetrazol are known γ-aminobutyric acid (GABA) antagonists, the results suggest that GABA is involved minimally, if at all, in the hippocampal afterdischarge sequence.

Influence of a 14-day regimen of electrical stimulation involving large portions of the cerebral mass on later habit acquisition in the rat.

Four groups of rats, one of which served as a normal, nonoperated group, were used. The other three groups were operated and fitted with an electrode carrier of eight electrodes of varying lengths arranged in a 7.5 mm X 5 mm rectangle. About 10 or 12 days after surgery, the following groups of animals underwent a 14-day regimen wherein each animal spent 15 min in a deep, metal, electrically insulated cylinder: Group A, normal, nonoperated group, with no intervention; Group B, stimulated each day with 45 trains of rectangular biphasic pulses (3 trains per min) at the rate of 20 pulses per second (pps); Group C, the same but at the rate of 100 pps; Group D, the same but 180 pps. After a 48-hr fast and without benefit of shaping, each animal was placed for 60 min in a lever-pressing device and was rewarded with a pellet after each three to four presses. The resulting performance curves showed no improvement in pressing rate for Group A; marginal improvement for Group B; definite improvement for Group C; and the greatest improvement for Group D, the terminal rate being almost twice that of Group C.

Perceptual dissimilarity and discrimination studies using two-electrode stimulation with a multiple-channel cochlear implant patient

The stimuli used in the two studies were trains of biphasic current pulses delivered to pairs of the ten electrodes implanted in the patient's scala tympani. The first study investigated the perceptual dissimilarities of ten two-electrode stimuli by the method of triadic comparisons. Electrode separations from 1.5–10.5 mm were used. A nonmetric multi-dimensional scaling analysis of the data obtained showed a two-dimensional solution to be appropriate with dimensions corresponding to the position of: (i) the more basal electrode, and (ii) the more apical electrode of the combinations. In the second study, pulse period discrimination was assessed for a set of two-electrode combinations in a same-different task. Electrode separations from 3–9 mm were used. Analysis using nonparametric indices of discriminability and response bias showed that the discrimination improved with increasing electrode separation, and for constant separation discrimination was better for more apical combinations.