Prediction of antidepressant response in both 2.25xthreshold RUL and fixed high dose RUL ECT

Some forms of electroconvulsive therapy (ECT) can result in generalized seizures that lack efficacy, therefore physiological markers of treatment adequacy would be helpful. EEG measures of seizure quality, such as EEG regularity and post-ictal suppression, have largely supplanted seizure duration as a marker for seizure adequacy, yet no predictive algorithm has gained wide clinical acceptance. Electrographic seizure durations of less than 25 s still prompt re-stimulation in many settings. We re-examined the utility of EEG seizure duration and other measures of EEG seizure as predictors of antidepressant response to right unilateral (RUL) ECT.MethodsSeventy-two adult patients with major depression were randomized to either titrated RUL ECT at 2.25 times initial seizure threshold or RUL ECT at a fixed dose of 403 mC. Intent-to-treat responder status (defined by 60% reduction in HRSD scores and final score of 12 or less after the last RUL ECT session) was identified as the dependent variable in a nominal logistic regression model including EEG seizure quality candidate variables, controlled for age and gender.ResultsA model including EEG seizure duration, EEG regularity, post-ictal suppression, age and gender and randomization status was significantly predictive of intent-to-treat responder status at treatment 2 (R2 = .21 p < .003; N = 66) and treatment 4 (R2 = .27 p < .0004; N = 67). The model remained significant at these time points even when randomization status (titrated moderately suprathreshold vs. high fixed dosage) was removed (Treatment 2: R2 = .18 p < .007; Treatment 4: R2 = .23 p < .0007).ConclusionEEG markers of seizure adequacy, including EEG seizure duration, are modestly predictive of antidepressant response for both titrated moderately suprathreshold and high fixed dosage RUL ECT.     

A report on mood and cognitive outcomes with right unilateral ultrabrief pulsewidth (0.3 ms) ECT and retrospective comparison with standard pulsewidth right unilateral ECT

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but its use is limited by the risk of cognitive side effects. This study explored the potential of a novel approach, ultrabrief pulsewidth (0.3 ms) right unilateral (RUL-UB) ECT, to minimise cognitive effects while preserving efficacy. METHODS: Mood and neuropsychological functioning were objectively rated in 30 patients over a course of RUL-UB ECT at 6 times seizure threshold. Results (mood outcomes, ECT treatment parameters) were compared with a retrospectively assessed group of 30 age and gender matched patients who received RUL ECT (1.0 ms pulsewidth, 3.5 times seizure threshold) at the same hospital. RESULTS: Six treatments of RUL-UB ECT resulted in relatively few cognitive side effects, compared to reports of previous studies. The number of responders did not differ between groups but significantly more treatments were required in the RUL-UB group, suggesting a slower speed of response. LIMITATIONS: Patients were not randomised to the two forms of ECT and data was obtained retrospectively in the RUL ECT comparison group. CONCLUSIONS: This study suggests that RUL-UB ECT can be effective in treating depression while incurring lesser cognitive side effects than a commonly used form of RUL ECT, but a greater number of treatments may be required for response.     

Do benzodiazepines moderate the effectiveness of bitemporal electroconvulsive therapy in major depression?

Background

Electroconvulsive therapy (ECT) is the most effective treatment for depression. However, the use of concomitant medications during ECT is controversial, especially benzodiazepines, as some past evidence suggests these may reduce the efficacy of ECT. This study analysed the effect of benzodiazepines on treatment outcomes in a group of depressed patients treated with bitemporal (BT) ECT.

Methods

90 patients with major depression who received BT ECT were analysed. Clinical, demographic and ECT data were extracted from clinical records. Mood improvement was rated by trained psychiatrists using the Hamilton Depression Rating Scale (HDRS-21) at baseline and after the final ECT treatment. The association between benzodiazepine dose and mood outcomes over the ECT course was examined with regression analyses, controlling for variables that may affect ECT efficacy.

Results

Hierarchical multiple regression analysis found only current episode duration (t=−4.77, p<0.001) was a significant predictor of change in HDRS. Benzodiazepine dose was not associated with a change in HDRS (p>0.05, R²=0.39).

Limitations

This was a retrospective study. The use of the half-age dosing method for ECT did not permit examination of the effects of benzodiazepines on seizure threshold.

Conclusions

Benzodiazepines did not affect the efficacy of BT ECT with the dosing method used. However, these results may not generalise to other forms of ECT, ECT given with other methods of dose determination or to other populations less responsive to ECT.     

Does power matter with ECT?

BACKGROUND: To assess the incidence of depressed inpatients requiring high output ECT and the response of this group compared with a group requiring standard output ECT. METHODS: We reviewed the records of 59 consecutive inpatients that were treated with bilateral ECT between January 2001 and January 2004. Diagnosis of major depression was based on DSM IV criteria. Response and remission to ECT (respectively defined as a 50% reduction in score and a score of < or = 7 on the Hamilton Rating Scale for Depression; HRSD) of both groups were compared. RESULTS: Of the 59 patients, 13 (22%) required high output ECT. These patients needed significantly more ECT treatments than patients in the standard dose group (16.4+/-7.1 versus 10.4+/-4.5; p=0.01). In total, 31 of 46 patients (67%) requiring standard output ECT and 11 of the 13 patients (85%) requiring high output ECT responded to ECT. This difference is not significant. LIMITATIONS: This study has a retrospective nature and a rather homogenous sample. CONCLUSION: In this study 1 in 5 of the depressed inpatients needs a high dose energy of bilateral ECT to induce an adequate seizure. The efficacy of ECT in these patients is similar to that in the standard dose group. Considering these facts, high output ECT devices should be available for use in routine clinical practice.     

Theophylline reversal of electroconvulsive therapy (ECT) seizure inhibition

Oral sustained-release theophylline 200-400 mg, given 10 hours prior to electroconvulsive therapy (ECT) increased ECT seizure length in each of eight male patients who had shown unacceptably short seizures. The increase was on average 13.9 (+/- 6.0, SD) sec (p = .00016 by t test; p = .0000034 by exact probability). The absence of unduly prolonged seizures was attributed to previously demonstrated high seizure thresholds and to relatively low concentrations of theophylline. No adverse effects from theophylline were seen.     

Does higher cardiovascular response to ECT predict early antidepressant effect?

BACKGROUND: Effects of diencephalic seizure generalization during ECT, e.g., cardiovascular response, may be relevant in indexing its therapeutic potency. A trend for greater rate pressure product (RPP=heart rate x systolic blood pressure) response to modified ECT in responders than in nonresponders is reported. Atropine used in modified ECT is known to increase RPP. This study examined if cardiovascular response during ECT with or without atropine predicts antidepressant effect. METHODS: Twenty nine consenting, major depressive disorder patients received ECTs. Atropine premedication was randomly withheld in the second or third ECT session. RPP was recorded during ECT. Severity of depression was measured at twice weekly intervals. RESULTS: Fifteen patients remitted at the end of 2 weeks. These early remitters had significantly higher poststimulus RPP than the rest in the ECT session without atropine but not so in the session with atropine. Cumulative poststimulus RPP predicted the early antidepressant response. Corresponding motor or EEG seizure durations were not associated with antidepressant effect. LIMITATIONS: Most patients continued to receive antidepressants. ECT stimulus laterality was not controlled. The study focussed on only short term antidepressant effects. CONCLUSIONS: RPP response to ECT recorded under no-atropine condition may reflect its physiological effects relevant to therapeusis and may have the potential to index seizure adequacy.     

Electroconvulsive therapy in Belgium: a nationwide survey on the practice of electroconvulsive therapy

OBJECTIVE: To review and describe the practice of electroconvulsive therapy (ECT) in Belgium. METHODS: A 30-item questionnaire on the practice of ECT was sent to all institutions providing ECT. RESULTS: In 2003 ECT was offered in 32 hospitals. Although ECT hospitals are equally spread over three regions, there is a significant difference in the ECT utilization rate. There are no major regional differences in the practice of ECT. Fifty-three percent of the hospitals reported less than 10 treatment sessions per month. The major indication for ECT was depression (89.7%). Propofol was the anesthetic most commonly used (75%). Eleven departments (34.3%) used a sine wave device. Bitemporal electrode placement was the preferred option in 65.6% of all departments, and 37% of these used the combination of bitemporal electrode placement and a fixed high stimulus dose. Continuation ECT and outpatient ECT were rarely used. LIMITATIONS: This questionnaire study relies upon answers given by psychiatrists, and did not audit actual practices. CONCLUSIONS: Although ECT is widely available in Belgium, it remains underused and the practice of ECT is amenable for improvement. Guidelines should be implemented and continuing education is needed.     

Post-seizure EEG fractal dimension of first ECT predicts antidepressant response at two weeks.

BACKGROUND: Duration of seizure by itself is an insufficient criterion for a therapeutically adequate seizure in ECT. Therefore, measures of seizure EEG other than its duration need to be explored as indices of seizure adequacy and predictors of treatment response. We measured the EEG seizure using a geometrical method-fractal dimension (FD) and examined if this measure predicted remission. METHODS: Data from an efficacy study on melancholic depressives (n = 40) is used for the present exploration. They received thrice or once weekly ECTs, each schedule at two energy levels - high or low energy level. FD was computed for early-, mid- and post-seizure phases of the ictal EEG. Average of the two channels was used for analysis. RESULTS: Two-thirds of the patients (n = 25) were remitted at the end of 2 weeks. As expected, a significantly higher proportion of patients receiving thrice weekly ECT remitted than in patients receiving once weekly ECT. Smaller post-seizure FD at first ECT is the only variable which predicted remission status after six ECTs. Within the once weekly ECT group too, smaller post-seizure FD was associated with remission status. CONCLUSIONS: Post-seizure FD is proposed as a novel measure of seizure adequacy and predictor of treatment response. CLINICAL IMPLICATIONS: Seizure measures at first ECT may guide selection of ECT schedule to optimize ECT. LIMITATIONS: The study examined short term antidepressant effects only. The results may not be generalized to medication-resistant depressives.     

Clinical thresholds to egg, hazelnut, milk and peanut: results from a single-center study using standardized challenges

BackgroundLarge studies of individual thresholds and risk profiles for foods are sparse. Previous reports indicate that thresholds adjusted for the protein content in foods would be comparable.ObjectiveTo establish and compare clinical threshold values for egg, hazelnut, milk and peanut, and correlating them to severity of symptoms.MethodsSeven hundred eighty-one challenges were performed in 487 patients (age range, 0.5–73.5 years). Using interval censoring survival analysis, the dose distribution of thresholds was fitted to a log-normal function. Symptom score was correlated to thresholds.ResultsBased on the 405 challenges resulting in objective signs, similar distribution of thresholds for hazelnut, milk, and peanut challenges were found, whereas individuals with egg allergy were bimodally distributed with a high or a low threshold. Eliciting dose in 10% (95% confidence interval) was 42.9 (24-76.8) mg whole eggs, 133.8 (95.9–186.6) mg whole hazelnut, 106.5 (59.7–190.6) mg roasted peanut, and 2.9 (1.5–5.4) mL milk. Adults showed more severe symptoms and signs than children, and peanut caused more severe reactions than the 3 other foods.ConclusionThresholds for the different foods were not comparable, and eliciting dose for the 4 foods differed, even if adjusted for protein content. Increasing age but not a low threshold dose is associated with severe symptoms on challenge. Peanuts elicit more severe reactions than the other foods.     

Automatic estimation of detector radial position for contoured SPECT acquisition using CT images on a SPECT/CT system

An algorithm was developed to estimate noncircular orbit (NCO) single-photon emission computed tomography (SPECT) detector radius on a SPECT/CT imaging system using the CT images, for incorporation into collimator resolution modeling for iterative SPECT reconstruction. Simulated male abdominal (arms up), male head and neck (arms down) and female chest (arms down) anthropomorphic phantom, and ten patient, medium-energy SPECT/CT scans were acquired on a hybrid imaging system. The algorithm simulated inward SPECT detector radial motion and object contour detection at each projection angle, employing the calculated average CT image and a fixed Hounsfield unit (HU) threshold. Calculated radii were compared to the observed true radii, and optimal CT threshold values, corresponding to patient bed and clothing surfaces, were found to be between -970 and -950 HU. The algorithm was constrained by the 45 cm CT field-of-view (FOV), which limited the detected radii to < or = 22.5 cm and led to occasional radius underestimation in the case of object truncation by CT. Two methods incorporating the algorithm were implemented: physical model (PM) and best fit (BF). The PM method computed an offset that produced maximum overlap of calculated and true radii for the phantom scans, and applied that offset as a calculated-to-true radius transformation. For the BF method, the calculated-to-true radius transformation was based upon a linear regression between calculated and true radii. For the PM method, a fixed offset of +2.75 cm provided maximum calculated-to-true radius overlap for the phantom study, which accounted for the camera system's object contour detect sensor surface-to-detector face distance. For the BF method, a linear regression of true versus calculated radius from a reference patient scan was used as a calculated-to-true radius transform. Both methods were applied to ten patient scans. For -970 and -950 HU thresholds, the combined overall average root-mean-square (rms) error in radial position for eight patient scans without truncation were 3.37 cm (12.9%) for PM and 1.99 cm (8.6%) for BF, indicating BF is superior to PM in the absence of truncation. For two patient scans with truncation, the rms error was 3.24 cm (12.2%) for PM and 4.10 cm (18.2%) for BF. The slightly better performance of PM in the case of truncation is anomalous, due to FOV edge truncation artifacts in the CT reconstruction, and thus is suspect. The calculated NCO contour for a patient SPECT/CT scan was used with an iterative reconstruction algorithm that incorporated compensation for system resolution. The resulting image was qualitatively superior to the image obtained by reconstructing the data using the fixed radius stored by the scanner. The result was also superior to the image reconstructed using the iterative algorithm provided with the system, which does not incorporate resolution modeling. These results suggest that, under conditions of no or only mild lateral truncation of the CT scan, the algorithm is capable of providing radius estimates suitable for iterative SPECT reconstruction collimator geometric resolution modeling.     

Single-unit responses in the inferior colliculus: different consequences of contralateral and ipsilateral auditory stimulation

Monaural excitatory responses of 181 single units in the central nucleus of the inferior colliculus of 15 anesthetized gerbils (Meriones unguiculatus) were examined quantitatively. Pure-tone stimuli were presented monaurally through sealed, calibrated sound-delivery systems. Most units were excited only by contralateral stimulation (EO); 23% were bilaterally excitable (EE). The threshold frequency tuning curves for contralateral stimulation of EE units were significantly broader than those produced by ipsilateral stimulation of EE units and those produced by contralateral stimulation of EO units. The frequency at which threshold was lowest (best frequency), or BF) was very similar for ipsilateral and contralateral stimulation of individual EE units; however, ipsilateral BFs were slightly but significantly lower than contralateral BFs. For EE units, ipsilateral BF thresholds (mean: 29.2 dB SPL) were significantly higher than contralateral BF thresholds (mean: 14.9 dB SPL). Monotonic and nonmonotonic relationships between discharge rate and stimulus intensity at BF were observed in responses evoked both by contralateral and ipsilateral stimulation. Interestingly, for individual EE units it was not uncommon for the rate/intensity function for one monaural condition to be monotonic although the relationship for stimulation of the other ear was markedly nonmonotonic. There was no qualitative difference between rate/intensity functions evoked by contralateral stimulation in EO and EE units. Ipsilateral discharge rates were characteristically much lower than contralateral rates for a given stimulus intensity. For 50 BF tones of 100 ms duration, the median peak numbers of discharges for contralateral stimulation of EO and EE units were 361 and 339, respectively; the median for ipsilateral stimulation of EE units was 102. The dynamic range of each rate/intensity function was calculated by measuring the intensity range associated with an increase in spike count from 10 to 90% of the peak rate. No differences were detected between the distributions of dynamic range for contralateral stimulation in EO or EE units, or between contralateral and ipsilateral dynamic ranges within individual EE units. For all response types the distributions of dynamic range were approximately normal, with means near 20 dB. The minimum mean latency to the first spike at BF was generally longer for ipsilateral than for contralateral responses.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of testing age and fostering experience on seizure susceptibility of rats treated prenatally with chlorpromazine.

Offspring of rats treated with 2 mg/kg body weight chlorpromazine (CPZ) on Days 5-8 of gestation had lower seizure thresholds than offspring of saline-treated controls at 30, 60, 90, and 120 days of age. The CPZ-treated offspring were also heavier than controls prior to weaning. Further analysis using cross-fostered litters indicated that at least part of the drug effect on seizure thresholds took place before birth, although a postnatal component was also demonstrated. A striking effect of the fostering experience itself on the seizure threshold prevented conclusions about the relative importance of prenatal and postnatal influences.     

Electrode placement in ECT: cognitive effects

Forty patients suffering from a major depressive disorder, for whom electroconvulsive therapy (ECT) was clinically indicated, were assigned to one of three electrode placement groups: bitemporal (BT), right unilateral (RU) or bifrontal (BF). Comparisons of these groups in terms of cognitive status showed that the BF placement, which avoided both temporal regions, spared both verbal and nonverbal functions. These differential effects, which were independent of the degree of clinical depression, were not, however, evident three months after the last ECT.     

Spontaneous deletion of epilepsy gene orthologs in a mutant mouse with a low electroconvulsive threshold

The electroconvulsive threshold (ECT) test has been used extensively to determine the protection conferred by antiepileptic drug candidates against induced seizures in rodents. Despite its clinical relevance, the potential of ECT to identify mouse epilepsy models in genetic studies has not been thoroughly assessed. We adopted the ECT test to screen the progeny of ethylnitrosourea treated male C57BL/6J mice. In a small-scale screen, several mutant lines conferring a low threshold to ECT minimal clonic seizures were mapped to the telomeric region of mouse chromosome 2 in independent founder families. This high incidence was suggestive of a single spontaneous event that pre-existed in the founders of mutagenized stock. Genetic and physical mapping led to the discovery that several lines shared a single mutation, Szt1 (seizure threshold-1), consisting of a 300 kb deletion of genomic DNA involving three known genes. Two of these genes, Kcnq2 and Chrna4, are known to be mutated in human epilepsy families. Szt1 homozygotes and heterozygotes display similar phenotypes to those found in the respective Kcnq2 knockout mutant mice, suggesting that Kcnq2 haploinsufficiency is at the root of the Szt1 seizure sensitivity. Our results provide a novel genetic model for epilepsy research and demonstrate that the approach of using ECT to study seizures in mice has the potential to lead to the identification of human epilepsy susceptibility genes.     

Electroconvulsive therapy in depressive illness that has not responded to drug treatment

BACKGROUND: Antidepressant medication resistance is the commonest indication for electroconvulsive therapy (ECT) in Scotland. Evidence from the USA suggests that clinical response is reduced for medication resistant patients. The aim of the present study was to establish if the American results were generalisable to routine clinical practice in Edinburgh. METHOD: Fifty eligible depressed patients consecutively referred for a new course of bilateral ECT at the Royal Edinburgh Hospital were prospectively assessed as part of the National Audit of ECT in Scotland. The patients were categorised into those who had received adequate drug treatment pre-ECT (and could therefore be classed as medication resistant) and those who had not, using five operational definitions. The clinical response of the ECT was then compared between groups, using the Montgomery-Asberg Rating Scale for Depression (MADRS) and Clinical Global Impression Scale (CGI). RESULTS: Patients defined as medication resistant had an identical response to patients who were not defined as medication resistant (in both groups 60% met the predetermined criterion for clinical response), and this was consistent across the five operational definitions. CONCLUSIONS: The hypothesis that medication resistance is associated with a reduced probability of clinical response to ECT was not supported. LIMITATIONS: Some patients who were inadequately drug treated might have proven eventually to be medication resistant, which would have obscured a potential difference in clinical response. It is not known how generalisable the results are to clinical practice in the rest of the UK.     

Facilitatory and inhibitory frequency tuning of combination-sensitive neurons in the primary auditory cortex of mustached bats

Mustached bats, Pteronotus parnellii parnellii, emit echolocation pulses that consist of four harmonics with a fundamental consisting of a constant frequency (CF(1-4)) component followed by a short, frequency-modulated (FM(1-4)) component. During flight, the pulse fundamental frequency is systematically lowered by an amount proportional to the velocity of the bat relative to the background so that the Doppler-shifted echo CF(2) is maintained within a narrowband centered at approximately 61 kHz. In the primary auditory cortex, there is an expanded representation of 60.6- to 63. 0-kHz frequencies in the "Doppler-shifted CF processing" (DSCF) area where neurons show sharp, level-tolerant frequency tuning. More than 80% of DSCF neurons are facilitated by specific frequency combinations of approximately 25 kHz (BF(low)) and approximately 61 kHz (BF(high)). To examine the role of these neurons for fine frequency discrimination during echolocation, we measured the basic response parameters for facilitation to synthesized echolocation signals varied in frequency, intensity, and in their temporal structure. Excitatory response areas were determined by presenting single CF tones, facilitative curves were obtained by presenting paired CF tones. All neurons showing facilitation exhibit at least two facilitative response areas, one of broad spectral tuning to frequencies centered at BF(low) corresponding to a frequency in the lower half of the echolocation pulse FM(1) sweep and another of sharp tuning to frequencies centered at BF(high) corresponding to the CF(2) in the echo. Facilitative response areas for BF(high) are broadened by approximately 0.38 kHz at both the best amplitude and 50 dB above threshold response and show lower thresholds compared with the single-tone excitatory BF(high) response areas. An increase in the sensitivity of DSCF neurons would lead to target detection from farther away and/or for smaller targets than previously estimated on the basis of single-tone responses to BF(high). About 15% of DSCF neurons show oblique excitatory and facilitatory response areas at BF(high) so that the center frequency of the frequency-response function at any amplitude decreases with increasing stimulus amplitudes. DSCF neurons also have inhibitory response areas that either skirt or overlap both the excitatory and facilitatory response areas for BF(high) and sometimes for BF(low). Inhibition by a broad range of frequencies contributes to the observed sharpness of frequency tuning in these neurons. Recordings from orthogonal penetrations show that the best frequencies for facilitation as well as excitation do not change within a cortical column. There does not appear to be any systematic representation of facilitation ratios across the cortical surface of the DSCF area.     

Methodologic factors which contribute to variations in experimental pain threshold reported for older people

Using the same study groups and psychophysical methods, we have tested the hypothesis that variations in pain threshold with advancing age are best explained by variations in stimulus duration. Fifteen young adults and 15 older people without clinical evidence of neurologic disease or psychologic dysfunction had pain thresholds determined with heat and electrical stimuli using the method of limits; for electrical stimulation a double random staircase design was used. The stimulus duration was 1-100 s for heat and 50-5000 ms for electrical stimulation. It was found that older people have an increased threshold for thermal and electrically induced pain if the stimulus duration is kept short. This result explains much of the variability in age associated pain threshold in the literature.     

Rapid‐onset clinical and mechanistic effects of anti‐C5aR treatment in the mouse collagen‐induced arthritis model

Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid arthritis (RA). To support ongoing clinical development of an anti‐C5aR monoclonal antibody, we have investigated for the first time the mechanism of action and the pharmacodynamics of a blocking anti‐murine C5aR (anti‐mC5aR) surrogate antibody in mouse collagen‐induced arthritis (CIA). First, efficacy was demonstrated in a multiple‐dose treatment study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti‐mC5aR‐treated mice. Then, the mechanism of action was examined by looking for early effects of anti‐mC5aR treatment in single‐dose treatment studies. We found that 48 h after single‐dose treatment with anti‐mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)‐α, interleukin (IL)‐6 and IL‐17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore, dose‐setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti‐C5aR antibody in rheumatoid arthritis patients, by identifying potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR.     

Role of cutaneous feedback in ventral rubbing in the male Mongolian gerbil

Increased arousal levels in pregnant rats were produced via electrical stimulation of the reticular formation (RF) on Days 6–16 of gestation. Current levels between 0.02 and 0.06 mA were selected depending on the threshold for overt motor response to stimulation in the individual animal. Offspring were tested at 30 days of age for threshold of flurothyl-induced convulsion, and at 90 days of age for percent avoidance in a shock avoidance task. In comparison to offspring of implanted controls, RF-stimulated offspring had elevated seizure thresholds (males and females) and enhanced avoidance performance (females only). Further studies using fostering showed that the effect on avoidance performance was mediated both prenatally and postnatally. The relative importance of prenatal and postnatal influences on seizure threshold could not be determined. These results are compared to previous studies of the behavioral effects of prenatal chlorpromazine threatment.     

Effect of electrical stimulation of the crossed olivocochlear bundle on auditory nerve response to tones in noise

The discharge rates of single auditory-nerve fibers responding to best-frequency (BF) tones of varying level presented simultaneously with fixed level broadband noise were recorded with and without electrical stimulation of the crossed olivocochlear bundle (COCB). In the absence of COCB stimulation, monotonic increases in noise level produce monotonic increases in the low-level noise-driven response rate of auditory nerve fibers. As a result of adaptation, these increases in noise-driven response rate produce monotonic decreases in saturation discharge rate. At high noise levels, these compressive effects may eliminate the differential rate response of auditory nerve fibers to BF tones. COCB stimulation can restore this differential rate response by producing large decreases in noise-driven response rate and large increases in saturation discharge rate. In backgrounds of quiet, COCB stimulation is known to shift the dynamic range of single auditory nerve fiber BF tone responses to higher stimulus levels. In the presence of background noise, COCB stimulation produces upward shift of dynamic range, which decreases with increasing noise level. At high noise levels, COCB-induced decompression of rate-level functions may occur with little or no dynamic range shift. This enables auditory nerve fibers to signal changes in tone level with changes in discharge rate at lower signal-to-noise ratios than would be possible otherwise. Broadband noise also produces upward shift of the dynamic range of single auditory nerve fiber BF tone response. Noise-induced dynamic range shift of BF tone response was measured as a function of noise level with and without COCB stimulation. COCB stimulation elevates the threshold of noise-induced dynamic range shift. This shift is thought to result from two-tone rate suppression. Increases in the threshold of noise-induced shift due to COCB stimulation therefore suggests an interaction between the mechanism of two-tone rate suppression and the mechanism by which COCB stimulation produces dynamic range shift. These interactions were further investigated by recording auditory nerve fiber rate responses to fixed-level BF excitor tones presented simultaneously with fixed-frequency variable level suppressor tones. Rate responses were recorded with and without COCB stimulation. Experimental results were quantified using a phenomenological model of two-tone rate suppression presented by Sachs and Abbas.