Faster Stimulation Rates Research Articles

Auditory Neural Responses and Communicative Functioning in Children With Microcephaly Related to Congenital Zika Syndrome.

Children with microcephaly exhibit neurodevelopmental delays and compromised communicative functioning, yielding challenges for clinical assessment and informed intervention. This study characterized auditory neural function and communication abilities in children with microcephaly due to congenital Zika syndrome (CZS). Click-evoked auditory brainstem responses (ABR) at fast and slow stimulation rates and natural speech-evoked cortical auditory evoked potentials (CAEP) were recorded in 25 Brazilian children with microcephaly related to CZS ( M age: 5.93 ± 0.62 years) and a comparison group of 25 healthy children ( M age: 5.59 ± 0.80 years) matched on age, sex, ethnicity, and socioeconomic status. Communication abilities in daily life were evaluated using caregiver reports on Vineland Adaptive Behavior Scales-3. Caregivers of children with microcephaly reported significantly lower than typical adaptive functioning in the communication and socialization domains. ABR wave I latency did not differ significantly between the groups, suggesting comparable peripheral auditory function. ABR wave V absolute latency and waves I-V interwave latency were significantly shorter in the microcephaly group for both ears and rates. CAEP analyses identified reduced N2 amplitudes in children with microcephaly as well as limited evidence of speech sound differentiation, evidenced mainly by the N2 response latency. Conversely, in the comparison group, speech sound differences were observed for both the P1 and N2 latencies. Exploratory analyses in the microcephaly group indicated that more adaptive communication was associated with greater speech sound differences in the P1 and N2 amplitudes. The trimester of virus exposure did not have an effect on the ABRs or CAEPs. Microcephaly related to CZS is associated with alterations in subcortical and cortical auditory neural function. Reduced ABR latencies differ from previous reports, possibly due to the older age of this cohort and careful assessment of peripheral auditory function. Cortical speech sound detection and differentiation are present but reduced in children with microcephaly. Associations between communication performance in daily life and CAEPs highlight the value of auditory evoked potentials in assessing clinical populations with significant neurodevelopmental disabilities.

Vagus Nerve Stimulation Rate and Duration Determine whether Sensory Pairing Produces Neural Plasticity

Repeatedly pairing a brief train of vagus nerve stimulation (VNS) with an auditory stimulus drives reorganization of primary auditory cortex (A1), and the magnitude of this VNS-dependent plasticity is dependent on the stimulation parameters, including intensity and pulse rate. However, there is currently little data to guide the selection of VNS train durations, an easily adjusted parameter that could influence the effect of VNS-based therapies. Here, we tested the effect of varying the duration of the VNS train on the extent of VNS-dependent cortical plasticity. Rats were exposed to a 9 kHz tone 300 times per day for 20 days. Coincident with tone presentation, groups received trains of 4, 16, or 64 pulses of VNS delivered at 30 Hz, corresponding to train durations of 0.125 s, 0.5 s, and 2.0 s, respectively. High-density microelectrode mapping of A1 revealed that 0.5 s duration VNS trains significantly increased the number of neurons in A1 that responded to tones near the paired tone frequency. Trains lasting 0.125 or 2.0 s failed to alter A1 responses, indicating that both shorter and longer stimulation durations are less effective at enhancing plasticity. A second set of experiments evaluating the effect of delivering 4 or 64 pulses in a fixed 0.5 s VNS train duration paired with tone presentation reveal that both slower and faster stimulation rates are less effective at enhancing plasticity. We incorporated these results with previous findings describing the effect of stimulation parameters on VNS-dependent plasticity and activation of neuromodulatory networks to generate a model of synaptic activation by VNS.

The effects of stimulus rate on ABR morphology and its relationship to P1 CAEP responses and auditory speech perception outcomes in children with auditory neuropathy spectrum disorder: evidence from case reports

Objective: Auditory neuropathy spectrum disorder (ANSD) affects approximately 5–15% of children with sensorineural hearing loss (SNHL). ANSD is characterized by the presence of otoacoustic emissions (OAE) and an absent or abnormal auditory brainstem response (ABR). The purpose of this study was to investigate the prognostic value of slow-rate ABR in predicting the auditory cortical development and auditory speech perception outcomes in case studies of children with ANSD.Design: ABR waveform characteristics were collected at slow stimulation rates (5.1 clicks/second) and a fast stimulation rates (>11–31.1 clicks/second, rates typically used in a clinical setting) in three case reports of children with ANSD. P1 CAEP responses and measures of auditory speech perception using the Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS) were also collected in these children. Retrospective analysis was performed to evaluate the prognostic value of slow- versus fast-rate ABR in predicting P1 CAEP responses and auditory speech perception outcomes in these children.Study sample: Participants included case reports of three paediatric participants with a clinical diagnosis of ANSD.Results: Slow-rate ABR did not elicit significant improvements in waveform morphology compared to fast-rate ABR. P1 CAEP results were present in 2 out of 3 cases and were consistent with auditory speech perception outcomes.Conclusions: Even when ABR stimulation rates were slowed, ABR responses in these children with ANSD did not display any characteristic or replicable pattern, and ABR responses were not predictive of cortical auditory maturation or behavioural performance. In contrast, P1 CAEP responses provided valuable information regarding the maturational status of the auditory cortex and P1 CAEP responses were consistent with behavioural measures of auditory speech perception. Overall, results highlight the high prognostic value of P1 CAEP testing when used in conjunction with behavioural measures of auditory speech perception in children with ANSD.

The Orienting Response in Healthy Aging: Novelty P3 Indicates No General Decline but Reduced Efficacy for Fast Stimulation Rates.

Automatic orienting to unexpected changes in the environment is a pre-requisite for adaptive behavior. One prominent mechanism of automatic attentional control is the Orienting Response (OR). Despite the fundamental significance of the OR in everyday life, only little is known about how the OR is affected by healthy aging. We tested this question in two age groups (19–38 and 55–72 years) and measured skin-conductance responses (SCRs) and event-related brain potentials (ERPs) to novels (i.e., short environmental sounds presented only once in the experiment; 10% of the trials) compared to standard sounds (600 Hz sinusoidal tones with 200 ms duration; 90% of the trials). Novel and standard stimuli were presented in four conditions differing in the inter-stimulus interval (ISI) with a mean ISI of either 10, 3, 1, or 0.5 s (blocked presentation). In both age groups, pronounced SCRs were elicited by novels in the 10 s ISI condition, suggesting the elicitation of stable ORs. These effects were accompanied by pronounced N1 and frontal P3 amplitudes in the ERP, suggesting that automatic novelty processing and orientation of attention are effective in both age groups. Furthermore, the SCR and ERP effects declined with decreasing ISI length. In addition, differences between the two groups were observable with the fastest presentation rates (i.e., 1 and 0.5 s ISI length). The most prominent difference was a shift of the peak of the frontal positivity from around 300 to 200 ms in the 19–38 years group while in the 55–72 years group the amplitude of the frontal P3 decreased linearly with decreasing ISI length. Taken together, this pattern of results does not suggest a general decline in processing efficacy with healthy aging. At least with very rare changes (here, the novels in the 10 s ISI condition) the OR is as effective in healthy older adults as in younger adults. With faster presentation rates, however, the efficacy of the OR decreases. This seems to result in a switch from novelty to deviant processing in younger adults, but less so in the group of older adults.

Electrophysiological and psychophysical correlates of spatial summation to noxious heat: the possible role of A-delta fibers

Although spatial summation of pain (SSP) is central to the processing of pain intensity and quality, its mechanism is not fully understood. We previously found greater heat SSP in hairy than in glabrous skin, suggesting that perhaps A-mechano-heat II (AMH-II) nociceptors are the dominant subserving system. In order to further explore the role of A-delta fibers in heat-induced SSP, we analyzed the electrophysiological correlates of SSP under conditions that minimize the influence of skin thicknesses. Among 17 subjects, fast rate of rise (70°C/sec) heat stimuli that induced a pre-fixed, similar, SSP magnitude for hairy and glabrous skin were repeatedly administered using large and small probes, during which time the contact heat-evoked potentials (CHEPs) and pain ratings were recorded. Both N2 and P2 amplitudes were larger in hairy than in glabrous skin, but a differential effect of SSP was found on the CHEPs. Despite similar psychophysical SSP in hairy and glabrous skin, the electrophysiological SSP reflected in N2 but not P2 amplitude was larger in hairy skin. Nevertheless, regardless of skin type, SSP was manifested by an increase in P2 amplitudes. Considering the uniform psychophysical SSP for the two skin types, the fast stimulation rate and lower activity of AMH-II in glabrous skin, a greater electrophysiological SSP in hairy than in glabrous skin may suggest that SSP is mainly subserved by AMH nociceptors. The overall SSP effect, manifested in greater P2 amplitude, may reflect specific brain responses aimed to prepare the individual to an increased potential tissue damage.

Evoked Auditory Potentials Recorded at Fast Stimulation Rates

Evoked Auditory Potentials Recorded at Fast Stimulation Rates

Alterations of Nuclear Ca2+-Dependent Signalling in Heart Failure

A hallmark of heart failure is impaired Ca2+ handling of cardiomyocytes. We previously showed that specific alterations in nuclear Ca2+ handling precede changes in cytoplasmic Ca2+ handling as heart failure progresses. However, a direct link between changes of nucleoplasmic Ca2+ handling and altered excitation-transcription coupling during the heart failure progression was not previously established. We thus characterized changes of nuclear Ca2+ handling and the activation of nuclear Ca2+-dependent transcription factors under low and high pacing frequencies at the early and late stage of hypertrophy in mouse model of pressure overload.Ventricular cardiomyocytes were isolated 1 and 7 weeks after transverse aortic constriction (TAC) in adult wild-type mice. Subcellular [Ca2+] transients were recorded in electrically stimulated CMs loaded with Fluo-4/AM. Phosphorylation levels of CaMKII and nuclear accumulation of HDAC4 were quantified by immunocytostaining.During the early remodelling (i.e. 1 week after TAC intervention) - in contrast to diastolic [Ca2+] in the cytoplasm - diastolic [Ca2+] in the nucleus was already elevated at very low stimulation rate (0.5 Hz) as compared to the non-failing group, and than overproportionally increased with faster stimulation rates. In failing cardiomyocytes (7 weeks after TAC intervention), the changes in nucleoplasmic and cytoplasmic diastolic [Ca2+] were qualitatively comparable, though the increase was more pronounced in the nuclear compartment. High pacing frequency caused significantly higher phosphorylation of CaMKII and corresponding HDAC4 translocation in cardiomyocytes from hypertrophic hearts compared to healthy controls, with the significantly higher increase in CaMKII phosphorylation in the nucleoplasmic compartment as compared to cytoplasm.In conclusion, we found that the increased stimulation frequency led to a higher build-up of diastolic [Ca2+] in cardiomyocytes from hypertrophied hearts, especially in the nucleoplasmic compartment, which may be involved in the dysregulation of Ca2+-dependent gene transcription and progression of adverse cardiac remodeling.

Variations in Carrier Pulse Rate and the Perception of Amplitude Modulation in Cochlear Implant Users

A major focus of recent attempts to enhance cochlear implant (CI) systems has been to increase the rate at which pulses are delivered to the electrode array. One basis for these attempts has been the expectation that faster stimulation rates would lead to an enhanced representation of temporal modulation information. However, there is recent physiological and behavioral evidence to suggest that the reverse may be the case. Here, the effects of stimulation rate on the perception of amplitude modulation were assessed using both modulation detection and modulation frequency discrimination tasks for a range of pulse rates extending considerably higher than the highest rate tested in previous studies and for different speech-relevant modulation frequencies. Detection of sinusoidal amplitude modulation was assessed in five CI users using monopolar pulse trains presented to a single electrode at rates of 482, 723, 1447, 2894, and 5787 pulses per second (pps). Adaptive procedures were used to find the minimal detectable modulation depth at modulation frequencies of 10 and 100 Hz and at carrier levels of 25%, 50%, and 75% of the electrode's dynamic range. Discrimination of modulation frequency was examined for the same range of pulse rates for the highest carrier level. Similar adaptive procedures determined the minimum increase in modulation frequency that could be detected relative to reference modulation frequencies of 10, 100, and 200 Hz. In both tasks, level roving was implemented to minimize possible loudness cues. Consistent with previous evidence, modulation detection thresholds were better for higher carrier levels and lower modulation frequencies. When modulation depth at threshold was expressed in terms of the ratio of the depth of the modulation and the carrier level in dB (i.e., 20 log m), performance was significantly better at lower pulse rates. However, when modulation depth was expressed relative to dynamic range, the effect of pulse rate was no longer significant, reflecting the fact that dynamic range increases with pulse rate. Modulation frequency discrimination clearly worsened with increasing modulation frequency, but there was no significant effect of pulse rate. In contrast to some recent evidence, no clearly harmful effect of higher pulse rates on modulation perception was found. However, even with very fast stimulation rates, tested over a wide range of modulation frequencies and with two different tasks, there is no evidence of benefit from faster stimulation rates in the perception of amplitude modulation.

Late Sodium Current Contributes to the Reverse Rate-Dependent Effect of I Kr Inhibition on Ventricular Repolarization

The reverse rate dependence (RRD) of actions of I(Kr)-blocking drugs to increase the action potential duration (APD) and beat-to-beat variability of repolarization (BVR) of APD is proarrhythmic. We determined whether inhibition of endogenous, physiological late Na(+) current (late I(Na)) attenuates the RRD and proarrhythmic effect of I(Kr) inhibition. Duration of the monophasic APD (MAPD) was measured from female rabbit hearts paced at cycle lengths from 400 to 2000 milliseconds, and BVR was calculated. In the absence of a drug, duration of monophasic action potential at 90% completion of repolarization (MAPD(90)) and BVR increased as the cycle length was increased from 400 to 2000 milliseconds (n=36 and 26; P<0.01). Both E-4031 (20 nmol/L) and d-sotalol (10 μmol/L) increased MAPD(90) and BVR at all stimulation rates, and the increase was greater at slower than at faster pacing rates (n=19, 11, 12 and 7, respectively; P<0.01). Tetrodotoxin (1 μmol/L) and ranolazine significantly attenuated the RRD of MAPD(90,) reduced BVR (P<0.01), and abolished torsade de pointes in hearts treated with either 20 nmol/L E-4031 or 10 μmol/L d-sotalol. Endogenous late I(Na) in cardiomyocytes stimulated at cycle lengths from 500 to 4000 milliseconds was greater at slower than at faster stimulation rates, and rapidly decreased during the first several beats at faster but not at slower rates (n=8; P<0.01). In a computational model, simulated RRD of APD caused by E-4031 and d-sotalol was attenuated when late I(Na) was inhibited. Endogenous late I(Na) contributes to the RRD of I(Kr) inhibitor-induced increases in APD and BVR and to bradycardia-related ventricular arrhythmias.

The LQT1 Phenotype of the KCNQ1 H258R Mutant is Unmasked by Faster Stimulation Rates

The long QT syndrome is a cardiac disorder caused by a delayed ventricular repolarization. LQT1 is linked to mutations in the KCNQ1 gene that codes for the six transmembrane spanning α-subunit of the channel complex that underlies IKsin vivo. The LQT1 mutation H258R, located in the S4-S5 linker, resulted in subunits that failed to generate current in a homotetrameric condition. However, association with hKCNE1 ‘rescued’ the mutant subunit and generated IKs-like currents. Compared to WT hKCNQ1/hKCNE1, H258R/hKCNE1 displayed accelerated activation kinetics, slowed channel closure and a hyperpolarizing shift of the voltage-dependence of activation, thus predicting an increased K+ current. However, current density analysis combined with subcellular localization indicated that the H258R subunit exerted a dominant negative effect on channel trafficking. The co-expression hKCNQ1/H258R/hKCNE1, mimicking the heterozygous state of a patient, displayed similar properties. During repetitive stimulation the mutant yielded more current compared to WT at 1 Hz but this effect was counteracted by the trafficking defect at faster frequencies. Thus at faster stimulation rates there would be less repolarizing K+ current compared to WT, explaining the disease causing effect of the mutation. In terms of H258R being ‘rescued’ by hKCNE1, it seems less likely that this occurs through a pure chaperone-type mechanism and based on the altered gating kinetics we suggest that hKCNE1 rescues H258R by restoring the gating machinery. It has been proposed that hKCNE1 modulates hKCNQ1 kinetics by stabilizing the interaction between the S4-S5 linker and bottom part of S6. Therefore, we speculate that the H258R mutation disrupts the contact with S6 resulting in distorted subunit folding. The association with hKCNE1 then stabilizes the electromechanic coupling and in this way compensates for the destabilization caused by the H258R mutant.

Electric Eigen-Portraits Face Shift

Electric Eigen-Portraits shows the human face in a state of externally triggered resonance. Eight facial muscles are subjected to a simple on/off stimulation pattern, with a repetition period that varies gradually between 2 seconds and 100 milliseconds. At fast stimulation rates, the external input loses its precise control of the muscle contractions: resonance patterns appear which are primarily determined by the intrinsic mechanical properties of the facial muscle system. The face thus displays its own mechanical properties on the face itself, a self-portrait of the face, maniarthur elsenaar Nottingham Trent University The Netherlands and United Kingdom arthur@artifacial.org

Spontaneous increases in impedance following cochlear implantation: Suspected causes and management

Modern cochlear implant systems deliver impulse transmission rates up to 50 000 pps. It emerged that the fast stimulation rates led to enhanced speech comprehension. Impedance measurement is an important aspect in cochlear implant testing procedures. Impedance values are a measure of the electrical resistance between the individual implant electrodes. Increased impedances were attributed frequently to inflammatory/tissue-related processes. In recent years, however, we have repeatedly found cases of impedance increase for which the inflammatory model did not provide a satisfactory explanation. The aim of this study is to evaluate increases in impedance in our cochlear implant population, to attempt to find their cause, and to formulate therapeutic hypotheses. In our cochlear implant programme (> 3000 recipients) we screened our database for impedance increases over time during device fitting. We found 16 patients with 18 affected ears in whom impedance increases were clearly demonstrated. We found that especially in cases without any sign of prior inflammation, increasing the pulse width of the stimulation strategy seems to be an effective tool to return increased impedances to normal levels.

Increased Ca 2+ Sensitivity of the Ryanodine Receptor Mutant RyR2 R4496C Underlies Catecholaminergic Polymorphic Ventricular Tachycardia

Cardiac ryanodine receptor (RyR2) mutations are associated with autosomal dominant catecholaminergic polymorphic ventricular tachycardia, suggesting that alterations in Ca(2+) handling underlie this disease. Here we analyze the underlying Ca(2+) release defect that leads to arrhythmia in cardiomyocytes isolated from heterozygous knock-in mice carrying the RyR2(R4496C) mutation. RyR2(R4496C-/-) littermates (wild type) were used as controls. [Ca(2+)](i) transients were obtained by field stimulation in fluo-3-loaded cardiomyocytes and viewed using confocal microscopy. In our basal recording conditions (2-Hz stimulation rate), [Ca(2+)](i) transients and sarcoplasmic reticulum Ca(2+) load were similar in wild-type and RyR2(R4496C) cells. However, paced RyR2(R4496C) ventricular myocytes presented abnormal Ca(2+) release during the diastolic period, viewed as Ca(2+) waves, consistent with the occurrence of delayed afterdepolarizations. The occurrence of this abnormal Ca(2+) release was enhanced at faster stimulation rates and by beta-adrenergic stimulation, which also induced triggered activity. Spontaneous Ca(2+) sparks were more frequent in RyR2(R4496C) myocytes, indicating increased RyR2(R4496C) activity. When permeabilized cells were exposed to different cytosolic [Ca(2+)](i), RyR2(R4496C) showed a dramatic increase in Ca(2+) sensitivity. Isoproterenol increased [Ca(2+)](i) transient amplitude and Ca(2+) spark frequency to the same extent in wild-type and RyR2(R4496C) cells, indicating that the beta-adrenergic sensitivity of RyR2(R4496C) cells remained unaltered. This effect was independent of protein expression variations because no difference was found in the total or phosphorylated RyR2 expression levels. In conclusion, the arrhythmogenic potential of the RyR2(R4496C) mutation is attributable to the increased Ca(2+) sensitivity of RyR2(R4496C), which induces diastolic Ca(2+) release and lowers the threshold for triggered activity.

Temporal and spatial frequencies interact in the contrast transfer function of the pattern electroretinogram

The contrast transfer function (CTF) of the pattern electroretinogram (PERG) depends on temporal frequency. For transient stimulation it is fully linear; at faster stimulation rates it becomes strongly non-linear with an accelerated shape. In this study we investigated a range of stimulus parameters with the aim of studying the influence of temporal and spatial frequencies, as well as contrast levels, on the CTF; effects were quantified via an “index of linearity” IL. Both reversal rate and check size influenced linearity ( p < .001), examples: At a constant check size of 0.8°, 7.7 rps: IL = 1.0; 0.8°/24 rps: IL = 0.5; at a constant reversal rate of 19 rps, IL was 0.5 for 0.8°, but rose to 0.8 both for 0.2° and 18°. The reason for this complex response surface remains a puzzle, it cannot be explained by varying parvo/magnocellular contributions, and its possible influences on recordings in patients merit further studies.

Objective measurements of auditory nerve recovery function in nucleus CI 24 implantees in relation to subjective preference of stimulation rate

ObjectiveSetting the optimal rate of stimulation for individual cochlear implant recipients is critical to the successful functional outcome of cochlear implantation. In the absence of an objective methodology, cochlear implants are currently fitted by means of a time-consuming (and therefore expensive) trial-and-error process of limited accuracy. The aim of this study was to evaluate a possible relationship between the patient's subjectively preferred stimulation rate and an objective measurement of auditory nerve recovery time.Material and MethodsEleven recipients of Nucleus CI 24 implants initially fitted with a speech processor using the ACE speech-coding strategy at a rate of 900 Hz were introduced to 2 other stimulation rate options, 1200 and 1800 Hz, at 2 different fitting sessions and asked to choose their preferred rate. Preferences were compared with objective measurements of auditory nerve recovery time obtained using the refractory recovery function of neural response telemetry.ResultsThe auditory nerve recovery time for individuals with a subjective preference for a slow stimulation rate was longer than that for individuals who preferred a fast stimulation rate, with significant differences between the 2 groups for 3 tested electrodes (7, 11 and 15): p=0.024, 0.009 and 0.03, respectively (Mann–Whitney test).ConclusionThe association observed between the subjective stimulation rate preference and measurements of auditory nerve recovery time indicates that the measured auditory nerve recovery time can be used as a reliable predictor for setting up a basic stimulation rate of a particular individual's map, thus reducing the cost of the technology and significantly increasing its effectiveness.

Objective measurements of auditory nerve recovery function in nucleus CI 24 implantees in relation to subjective preference of stimulation rate

ObjectiveSetting the optimal rate of stimulation for individual cochlear implant recipients is critical to the successful functional outcome of cochlear implantation. In the absence of an objective methodology, cochlear implants are currently fitted by means of a time-consuming (and therefore expensive) trial-and-error process of limited accuracy. The aim of this study was to evaluate a possible relationship between the patient's subjectively preferred stimulation rate and an objective measurement of auditory nerve recovery time.Material and MethodsEleven recipients of Nucleus CI 24 implants initially fitted with a speech processor using the advanced combination encoders speech-coding strategy at a rate of 900 Hz were introduced to 2 other stimulation rate options, 1200 and 1800 Hz, at 2 different fitting sessions and were asked to choose their preferred rate. Preferences were compared with objective measurements of auditory nerve recovery time obtained with the refractory recovery function of neural response telemetry.ResultsThe auditory nerve recovery time for individuals with a subjective preference for a slow stimulation rate was longer than that for individuals who preferred a fast stimulation rate, with significant differences between the 2 groups for 3 of the tested electrodes (Nos. 7, 11 and 15): p=0.024, 0.009 and 0.03, respectively (Mann–Whitney test).ConclusionsThe association observed between subjective stimulation rate preference and measurements of auditory nerve recovery time indicates that the measured auditory nerve recovery time can be used as a reliable predictor for setting up a basic stimulation rate of a particular individual's map, thus reducing the cost of the technology and significantly increasing its effectiveness.

Activation of the auditory pre-attentive change detection system by tone repetitions with fast stimulation rate

The human automatic pre-attentive change detection system indexed by the mismatch negativity (MMN) component of the auditory event-related brain potential is known to be highly adaptive. The present study showed that even infrequent repetitions of tones can elicit MMN, independently of attention, when tones of varying frequency are rapidly presented in an isochronous rhythm. This demonstrates that frequency variation can be extracted as an invariant feature of the acoustic environment revealing the capacity for adaptation of the auditory pre-attentive change detection system. It is argued that this capacity is related to the temporal-window of integration.

Isoproterenol specifically modulates reverse rate-dependent effects of d,l-sotalol, d-sotalol, and dofetilide.

The modulation of antiarrhythmic and proarrhythmic properties of antiarrhythmic compounds by increased sympathetic activity is of experimental and clinical interest. However, the interaction of adrenergic stimulation with the rate-response pattern of class III antiarrhythmic agents is not well established. Using standard microelectrode techniques, we evaluated the effects of isoproterenol (iso) on the action of d,l-sotalol (d,l-sot), d-sotalol (d-sot), and dofetilide (dof) on action-potential parameters recorded from isolated canine cardiomyocytes. The cell-isolation procedure was performed from the endocardial layers of left ventricular myocardium from healthy beagle dogs. The following electrophysiologic parameters were recorded: resting membrane potential (RMP), action-potential amplitude (APA), action-potential duration at 90% repolarization (APD 90), and effective refractory period (ERP). After exposure to iso, the class III activity of d,l-sot was well maintained over the entire range of frequencies studied. In contrast, iso differentially antagonized the action of d-sot and dof. In comparison to dof, the class III action of d-sot was particularly sensitive to iso, predominantly at faster stimulation rates. Our observations demonstrate specific rate regulation of the class III action of d,l-sot, d-sot, and dof in response to adrenergic stimulation. The unfavorable rate-response pattern of d-sot compared with d,l-sot and dof might prove disadvantageous in high-catecholamine states.

Auditory-evoked brainstem responses in the torpid deermouse

This study examined auditory-evoked brainstem responses (ABR) in the deermouse (Peromyscus maniculatus) during torpor and arousal. The ABR of the euthermic deermouse consisted of five waves occurring in a time frame of 10 ms. During torpor, ABR wave I could be elicited at slow, but not fast stimulation rates indicating variability in neural activity along the auditory pathway. Arousal was heralded by the appearance of all the components of the ABR evoked in response to both slow and fast click rates signaling functional restoration of auditory neural activity during this phase.

Elektrophysiologische Korrelate der selektiven Aufmerksamkeit bei Schizophrenen

Attentional dysfunctions are considered to be core schizophrenic symptoms. Selective attention to specific attributes of auditory stimuli results in characteristic changes of event-related brain potentials. Depending on stimulation rate, either an Nl enlargement or a more enduring „processing negativity” (19) is found. Twelve schizophrenics, diagnosed according to DSM III-R, 12 patients with alcohol dependency, and 12 matched normal controls took part in an auditory selective attention task with fast (2 Hz) or slow (1 Hz) stimulation rate. Schizophrenics made more errors and had slower reaction times, as compared with both other groups. This behavioral impairment was paralleled by a significantly smaller early phase (200-400 ms) of the processing negativity (Nd, fig. 2). Groups did not differ for a later phase of Nd. The smaller N1 amplitude of schizophrenics was probably a concomitant of neuroleptic medication, because group differences for N1-amplitude disappeared when neuroleptic dosage was statistically controlled for. Alcoholics, but not schizophrenics did have a smaller P300 amplitude than normals (fig. 3). The results are consistent with the assumption that an impaired matching process between stored and momentary information underlies some of the attentional difficulties in schizophrenia.