Improvement of auditory discrimination learning by Ginkgo biloba extract EGb 761.

The effect of oral application of Ginkgo biloba extract EGb 761 on auditory discrimination learning in Mongolian gerbils was investigated using discrimination tasks with three different degrees of difficulty and two protocols for administration starting 2 weeks prior to or at the beginning of training. In comparison to placebo-treated controls we observed significant improvement of learning performance in EGb 761 treated gerbils in discrimination tasks of all degrees of difficulty, from the easiest to the most demanding. EGb 761 has been reported to increase the extracellular concentration of dopamine in prefrontal cortex of rats which plays a major role in the type of discrimination learning used in the present study. We, therefore, suppose that EGb 761 improves discrimination learning through its effect on the dopaminergic system.

Chronic ketamine impairs fear conditioning and produces long-lasting reductions in auditory evoked potentials.

Ketamine is an NMDA receptor antagonist with a variety of uses, ranging from recreational drug to pediatric anesthetic and chronic pain reliever. Despite its value in the clinical setting, little is known about the immediate and long-lasting effects of repeated ketamine treatment. We assessed the effects of chronic administration of a subanesthetic dose of ketamine on contextual fear conditioning, detection of pitch deviants and auditory gating. After four, but not two, weeks of daily ketamine injections, mice exhibited decreased freezing in the fear conditioning paradigm. Gating of the P80 component of auditory evoked potentials was also significantly altered by treatment condition, as ketamine caused a significant decrease in S1 amplitude. Additionally, P20 latency was significantly increased as a result of ketamine treatment. Though no interactions were found involving test week, stimulus and treatment condition, these results suggest that repeated ketamine administration impairs fear memory and has lasting effects on encoding of sensory stimuli.

The effect of methylphenidate on auditory information processing in healthy volunteers: a combined EEG/MEG study.

INTRODUCTION: The psychomotor stimulant methylphenidate (MPH) has been shown to improve attentional processes, reflected in behavioural measures such as vigilance, reaction time and visual attention tasks. The neural mechanisms of MPH action on sensory information processing, however, remain poorly understood. To the authors' knowledge, this present study is the first to investigate whether a single dose of MPH affects neural substrates of passive attention in healthy adults studied with simultaneous whole-head magnetoencephalography (MEG) and electroencephalography (EEG). METHODS: Monaural left-ear auditory stimuli were presented in an oddball paradigm with infrequent deviant tones differing in frequency and duration. Neuronal activity was recorded with simultaneous whole-head MEG and EEG in 13 healthy subjects (five females; aged 27 +/- 5 years) after oral administration of 40 mg MPH or placebo in a randomised, double-blind, cross-over design. We analysed both electric and magnetic N100, P200 and mismatch negativity (MMN) components. RESULTS: MPH increased arousal levels in visual analogue scales. MPH had no effect on the dipole strength of MMN or MMNm in either frequency or duration deviations. MPH did, however, reduce P200 amplitudes in EEG. CONCLUSIONS: The lack of effect of MPH on either MMN or MMNm suggests no association between catecholaminergic activities and MMN generation. However, our findings imply that MPH may change the neural bases of auditory information processing such as the early stimulus evaluation reflected in the P200 component. Dopamine and noradrenaline neurotransmitter systems could be responsible for the modulation of these processes. The exclusive effect of MPH on the P200 component could have a clinical application.

Tone-sequence analysis in the auditory cortex of awake macaque monkeys.

The present study analyzed neuronal responses to two-tone sequences in the auditory cortex of three awake macaque monkeys. The monkeys were passively exposed to 430 different two-tone sequences, in which the frequency of the first tone and the interval between the first and the second tone in the sequence were systematically varied. The frequency of the second tone remained constant and was matched to the single-tone frequency sensitivity of the neurons. Multiunit activity was recorded from 109 sites in the primary auditory cortex and posterior auditory belt. We found that the first tone in the sequence could inhibit or facilitate the response to the second tone. Type and magnitude of poststimulatory effects depended on the sequence parameters and were related to the single-tone frequency sensitivity of neurons, similar to previous observations in the auditory cortex of anesthetized animals. This suggests that some anesthetics produce, at the most, moderate changes of poststimulatory inhibition and facilitation in the auditory cortex. Hence many properties of the sequence-sensitivity of neurons in the auditory cortex measured in anesthetized preparations can be applied to neurons in the auditory cortex of awake subjects.

Alcohol impairs the cognitive component of reaction time to an omitted stimulus: a replication and an extension.

OBJECTIVE: Research from a recent study indicates that cognitive performance is impaired by an acute dose of alcohol at blood alcohol concentrations (BACs) that do not affect motor performance. That study measured reaction time (RT) to the omission of a recurring stimulus and used behavioral criteria to fractionate premotor (cognitive) and motor components of RT when stimuli occurred at slow, 2-second intervals (0.5 Hz). The present experiment tested the generality of the evidence when stimuli occurred at slow or fast, 0.143-second intervals (7 Hz). Using muscle potential to fractionate RT, we tested the reproducibility of the findings obtained by a behavioral fractionation procedure. METHOD: Thirty male social drinkers were randomly assigned to two groups (n = 15 each) that received 0.8 g/kg alcohol or a placebo (0 g/kg). All participants performed a drug-free baseline test and a test during rising BACs. A test presented fast and slow frequency auditory stimuli in counterbalanced order within groups. RESULTS: Tests using both fast and slow frequency stimuli showed that alcohol slowed premotor RT and had no detectable effect on motor RT. CONCLUSIONS: Fractionated RT based on muscle potential reproduced the findings based on behavioral fractionation. The generality of the deleterious effects of alcohol on premotor RT was demonstrated by manipulating the frequency of the recurring stimuli. The consistent results obtained with the omitted stimulus paradigm provide a basis for new alcohol research that incorporates electrophysiological measures of the brain potential that are associated with the omission of a stimulus.

Duration selectivity organization in the inferior colliculus of the big brown bat, Eptesicus fuscus.

Duration selectivity of auditory neurons plays an important role in sound recognition. Previous studies show that GABA-mediated duration selectivity of neurons in the central nucleus of the inferior colliculus (IC) of many animal species behave as band-, short-, long- and all-pass filters to sound duration. The present study examines the organization of duration selectivity of IC neurons of the big brown bat, Eptesicus fuscus, in relation to graded spatial distribution of GABA(A) receptors, which are mostly distributed in the dorsomedial region of the IC but are sparsely distributed in the ventrolateral region. Duration selectivity of IC neuron is studied before and during iontophoretic application of GABA and its antagonist, bicuculline. Bicuculline application decreases and GABA application increases duration selectivity of IC neurons. Bicuculline application produces more pronounced broadening of the duration tuning curves of neurons at upper IC than at deeper IC but the opposite is observed during GABA application. The best duration of IC neurons progressively lengthens and duration selectivity decreases with recording depth both before and during drug application. As such, low best frequency neurons at upper IC have shorter best duration and sharper duration selectivity than high best frequency neurons in the deeper IC have. These data suggest that duration selectivity of IC neurons systematically varies with GABA(A) receptor distribution gradient within the IC.

Abnormal function of the brain system supporting motivated attention in medicated patients with schizophrenia: an fMRI study.

BACKGROUND: Patients with schizophrenia have an impaired ability to generate activity that is appropriate to current circumstances and goals. METHOD: We report a study using functional magnetic resonance imaging (fMRI) to examine cerebral activity during a three-tone auditory oddball target detection task in a sample of 28 patients with schizophrenia and 28 healthy controls. RESULTS: The patients exhibited significantly less activation in response to target stimuli relative to baseline in an extensive set of sites in association neocortex, paralimbic cortex, limbic structures and subcortical nuclei, yet demonstrated a normal level of activation in the sensorimotor cortex. Comparison of activity elicited by rare target stimuli with that elicited by equally rare novel stimuli makes it possible to distinguish cerebral activity associated with attention to behaviourally salient stimuli from activity associated with attending to other attention-capturing stimuli. This comparison revealed that the patients with schizophrenia also exhibited a deficit in activation of basal forebrain areas that mediate motivation during the processing of behaviourally salient stimuli, including the amygdala, ventral striatum, orbital frontal cortex and rostral anterior cingulate cortex. CONCLUSION: Patients with schizophrenia have a deficit in function of the brain system concerned with mediating motivation, in addition to a more general deficit in the cerebral response to attention-captivating stimuli.

Perception of complex sounds in budgerigars (Melopsittacus undulatus) with temporary hearing loss.

Songbirds and parrots deafened as nestlings fail to develop normal vocalizations, while birds deafened as adults show a gradual deterioration in the quality and precision of vocal production. Beyond this, little is known about the effect of hearing loss on the perception of vocalizations. Here, we induced temporary hearing loss in budgerigars with kanamycin and tested several aspects of the hearing, including the perception of complex, species-specific vocalizations. The ability of these birds to discriminate among acoustically distinct vocalizations was not impaired but the ability to make fine-grain discriminations among acoustically similar vocalizations was affected, even weeks after the basilar papilla had been repopulated with new hair cells. Interestingly, these birds were initially unable to recognize previously familiar contact calls in a classification task-suggesting that previously familiar vocalizations sounded unfamiliar with new hair cells. Eventually, in spite of slightly elevated absolute thresholds, the performance of birds on discrimination and perceptual recognition of vocalizations tasks returned to original levels. Thus, even though vocalizations may initially sound different with new hair cells, there are only minimal long-term effects of temporary hearing loss on auditory perception, recognition of species-specific vocalizations, or other aspects of acoustic communication in these birds.

Differential effects of indoleamines on auditory choice reaction, selective attention, and pitch discrimination.

The indoleamines serotonin and melatonin (MT) affected visual processing such as choice reaction. This study determined whether the indoleamines influence the processing of auditory stimuli. Serotonergic activity was increased using citalopram (CIT). We compared effects of single doses of 40 mg CIT, 1 mg MT, and placebo (randomized double-blind, cross-over design) in 18 healthy men. The applied tests assessed auditory choice reaction, selective attention, and serial discrimination using pitch variations as stimuli in each task. CIT reduced the performance in choice reaction and selective attention but not discrimination. MT tended to reduce selective attention and to improve discrimination. The findings suggest that indoleamines had different effects on distinct kinds of auditory processing. Serotonergic activation improved visual choice reaction, whereas the opposite effect was found in the auditory domain. We conclude that disorders and drugs affecting the indoleamines must be considered differentially in the auditory and the visual system.

Preliminary feasibility and efficacy of a brief motivational intervention with psychophysiological feedback for cocaine abuse.

Motivational interviewing (MI) with personalized feedback, particularly related to biological markers of risk or harm, has been found effective for alcohol use disorders, but has not been fully investigated in cocaine use disorders. A randomized, controlled pilot study evaluating the feasibility and preliminary efficacy of a brief MI intervention using EEG/ERP graphical feedback for cocaine abusers was conducted. Treatment-seeking cocaine abusers (N = 31) were randomly assigned to a two-session MI intervention or a minimal control condition. All participants received EEG assessments at intake and post-treatment. Results indicated that the MI intervention was feasible and the subjective impact of the EEG feedback was positive. Significant group differences in percentage of cocaine positive urine screens across the study were found, favoring the MI group; 84.9% for the control group and 62.6% in the MI group, p < .05. Further research must determine the specific conditions under which MI is most appropriate and efficacious.

Carbamazepine induced pitch shift and octave space representation.

Octave-circular pitch perception, the repetition of pitch scale qualities when surpassing the octave interval, has been observed in behavioral data from humans and monkeys, but the underlying anatomy and physiology is still unknown. Here we analyze octave circularity in a concert pianist with absolute pitch, both under medication with the neurotropic drug carbamazepine (CBZ) and without medication. Analysis of 4619 responses in a pitch identification task revealed an internal tone-scale representation, based on the norm-tone scale re A4=440 Hz, with an octave-circular pattern of strongly and weakly represented tones. CBZ caused a global down-shift of pitch (ca. 1 semitone at 500 Hz), but no down-shift of the octave-circular pattern of tone characteristics. This pattern was similar in the six tested octave ranges (32.7-2093 Hz), both under the control and the CBZ condition. Pattern repetition always occurred at octave intervals and did not reflect the stretched octaves of piano tuning. The results indicate that CBZ influences pitch detection peripheral of an octave-circular pitch representation. Thus they support previous evidence for pitch detection in the auditory midbrain and for octave-circular pitch mapping in the auditory thalamus.

Sources of auditory selective attention and the effects of methylphenidate in children with attention-deficit/hyperactivity disorder.

BACKGROUND: The aim of this study was to determine 1) whether abnormal auditory selective attention in children with attention-deficit/hyperactivity disorder (ADHD), as reflected in the processing negativity (PN) of the event-related potential, is related to impaired frontal functioning; and 2) how methylphenidate (MPh) affects attentional functioning in ADHD. METHODS: Sources of electrical brain activity were estimated in healthy control children, in ADHD children without medication, and in children with ADHD during a placebo-controlled medication trial involving MPh. RESULTS: The source models showed that the PN is generated in the auditory cortex. Children with ADHD showed less activity related to selective attention in this brain region. Administration of MPh resulted in more frontally located sources. CONCLUSIONS: The results showed no evidence for an important role of the frontal cortex in abnormalities in selective attention in children with ADHD. Also, the data did not indicate that MPh normalizes brain activity in these children.

Half pitch lower sound perception caused by carbamazepine.

We report a 16-year-old woman with secondary generalization of partial seizure, who complained of an auditory disturbance after carbamazepine (CBZ) administration. She had been taking sodium valproate (VPA) from the age of 15. However, her seizures remained poorly controlled. We changed her antiepileptic drug from VPA to CBZ. At 1 week after CBZ administration, she noticed that electone musical performances were heard as a semitone lower. When oral administration of CBZ was stopped, her pitch perception returned to normal. If she had not been able to discern absolute pitch, she might have been unable to recognize her lowered pitch perception. Auditory disturbance caused by CBZ is reversible and very rare.

Changes in CAP adaptation in experimentally induced endolymphatic hydrops.

OBJECTIVE: To determine the effect of experimentally induced endolymphatic hydrops (ELHs) on compound action potential (CAP) adaptation. METHODS: The CAP was recorded 1 month after surgical treatment to produce ELH. The CAP threshold in response to click stimuli showed no significant differences between the hydropic and control groups. The CAP was elicited from the retroauricular-exposed round window using a silver ball electrode. Click trains consisting of 10 clicks with an interclick interval (Deltat) of either 4 or 8 ms were delivered through a loudspeaker placed in front of the animals' ears. The patterns of adaptation to these click trains were evaluated as functions of Deltat and intensity level. RESULTS: An abnormal pattern of CAP adaptation was observed in hydropic ears. CONCLUSIONS: These findings suggest that early ELH influences CAP adaptation.

The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attention-deficit hyperactivity disorder.

RATIONALE AND OBJECTIVES: The present study investigated attentional modification of prepulse inhibition of startle among boys with and without attention-deficit hyperactivity disorder (ADHD). Two hypotheses were tested: (1) whether ADHD is associated with diminished prepulse inhibition during attended prestimuli, but not ignored prestimuli, and (2) whether methylphenidate selectively increases prepulse inhibition to attended prestimuli among boys with ADHD. METHODS: Participants were 17 boys with ADHD and 14 controls. Participants completed a tone discrimination task in each of two sessions separated by 1 week. ADHD boys were administered methylphenidate (0.3 mg/kg) in one session and placebo in the other session in a randomized, double-blind fashion. During each series of 72 tones (75 dB; half 1200-Hz, half 400-Hz), participants were paid to attend to one pitch and ignore the other. Bilateral eyeblink electromyogram startle responses were recorded in response to acoustic probes (50-ms, 102-dB white noise) presented following the onset of two-thirds of tones, and during one-third of intertrial intervals. RESULTS: Relative to controls, boys with ADHD exhibited diminished prepulse inhibition 120 ms after onset of attended but not ignored prestimuli following placebo administration. Methylphenidate selectively increased prepulse inhibition to attended prestimuli at 120 ms among boys with ADHD to a level comparable to that of controls, who did not receive methylphenidate. CONCLUSIONS: These data are consistent with the hypothesis that ADHD involves diminished selective attention and suggest that methylphenidate ameliorates the symptoms of ADHD, at least in part, by altering an early attentional mechanism.

Inner hair cell loss and steady-state potentials from the inferior colliculus and auditory cortex of the chinchilla.

Steady-state evoked potentials were measured from unanesthetized chinchillas both before and after carboplatin-induced selective inner hair cell loss. Recordings were made from both the inferior colliculus (IC) and the auditory cortex (AC). The steady-state potential was measured in the form of the envelope following response (EFR), obtained by presenting a two-tone stimulus (f1 = 2000 Hz; f2 = 2020, 2040, 2080, 2160, or 2320 Hz), and measuring the magnitude of the Fourier coefficient at the f2-f1 difference frequency. From the IC, precarboplatin, EFR amplitude vs difference tone frequency showed a bandpass pattern, with maximum amplitude at either 160 or 80 Hz, depending upon stimulus level. Postcarboplatin, the preferred difference frequency was 80 Hz for all stimulus levels. From the AC, EFR amplitude versus difference tone frequency also showed a bandpass pattern, with the maximum amplitude at 80 Hz both pre- and postcarboplatin. EFR amplitude from the IC was decreased for some conditions postcarboplatin, while the amplitude from the AC showed no significant change.

One source for distortion product otoacoustic emissions generated by low- and high-level primaries.

Distortion product otoacoustic emissions (DPOAE) elicited by tones below 60-70 dB sound pressure level (SPL) are significantly more sensitive to cochlear insults. The vulnerable, low-level DPOAE have been associated with the postulated active cochlear process, whereas the relatively robust high-level DPOAE component has been attributed to the passive, nonlinear macromechanical properties of the cochlea. However, it is proposed that the differences in the vulnerability of DPOAEs to high and low SPLs is a natural consequence of the way the cochlea responds to high and low SPLs. An active process boosts the basilar membrane (BM) vibrations, which are attenuated when the active process is impaired. However, at high SPLs the contribution of the active process to BM vibration is small compared with the dominating passive mechanical properties of the BM. Consequently, reduction of active cochlear amplification will have greatest effect on BM vibrations and DPOAEs at low SPLs. To distinguish between the "two sources" and the "single source" hypotheses we analyzed the level dependence of the notch and corresponding phase discontinuity in plots of DPOAE magnitude and phase as functions of the level of the primaries. In experiments where furosemide was used to reduce cochlear amplification, an upward shift of the notch supports the conclusion that both the low- and high-level DPOAEs are generated by a single source, namely a nonlinear amplifier with saturating I/O characteristic.

Interaction between adenosine triphosphate and mechanically induced modulation of electrically evoked otoacoustic emissions.

It was shown previously that electrically evoked otoacoustic emissions (EEOAEs) can be amplitude modulated by low-frequency bias tones and enhanced by application of adenosine triphosphate (ATP) to scala media. These effects were attributed, respectively, to the mechano-electrical transduction (MET) channels and ATP-gated ion channels on outer hair cell (OHC) stereocilia, two conductance pathways that appear to be functionally independent and additive in their effects on ionic current through the OHC. In the experiments described here, the separate influences of ATP and MET channel bias on EEOAEs did not combine linearly. Modulated EEOAEs increased in amplitude, but lost modulation at the phase and frequency of the bias tone (except at very high sound levels) after application of ATP to scala media, even though spectral components at the modulation sideband frequencies were still present. Some sidebands underwent phase shifts after ATP. In EEOAEs modulated by tones at lower sound levels, substitution of the original phase values restored modulation to the waveform, which then resembled a linear summation of the separate effects of ATP and low-frequency bias. While the physiological meaning of this procedure is not clear, the result raises the possibility that a secondary effect of ATP on one or more nonlinear stages in the transduction process, which may have caused the phase shifts, obscured linear summation at lower sound levels. In addition, "acoustic enhancement" of the EEOAE may have introduced nonlinear interaction at higher levels of the bias tones.

Cocaine's effects on the discrimination of simple and complex auditory stimuli by baboons.

The effects of cocaine on tone frequency discriminations by baboons were examined and compared with previous data for more complex acoustic stimuli (speech sounds) to see if cocaine's perceptual effects on these discriminations depends upon the type of stimulus employed (i.e., tones vs. speech sounds). Baboons pressed a lever to produce one repeating "standard" tone and released the lever only when one of four other "comparison" tones occasionally occurred in place of the standard tone. Cocaine's effects were assessed once or twice weekly by giving an intramuscular injection of cocaine hydrochloride (0.01-0.56 mg/kg) immediately prior to performing the task and by examining correct detections and reaction times for each tone following drug administration. Cocaine impaired tone discriminability, with greater impairments occurring for those tones that were more similar in frequency to the standard tone. Cocaine's perceptual effects occurred within 20-70 min following drug administration. Cocaine also impaired or facilitated the speed of responding to auditory stimuli, depending upon the drug dose and subject. The results demonstrate that cocaine can impair auditory discriminations involving simple tones, as well as speech sounds, and further supports the suggestion that cocaine's effects are focused on CNS mechanisms related to the use of pitch cues.

Role of mammalian auditory cortex in the perception of elementary sound properties.

Studies in several mammalian species have demonstrated that bilateral ablations of the auditory cortex have little effect on simple sound intensity and frequency-based behaviors. In the rat, for example, early experiments have shown that auditory ablations result in virtually no effect on the rat's ability to either detect tones or discriminate frequencies. Such lesion experiments, however, typically examine an animal's performance some time after recovery from ablation surgery. As such, they demonstrate that the cortex is not essential for simple auditory behaviors in the long run. Our study further explores the role of cortex in basic auditory perception by examining whether the cortex is normally involved in these behaviors. In these experiments we reversibly inactivated the rat primary auditory cortex (AI) using the GABA agonist muscimol, while the animals performed a simple auditory task. At the same time we monitored the rat's auditory activity by recording auditory evoked potentials (AEP) from the cortical surface. In contrast to lesion studies, the rapid time course of these experimental conditions preclude reorganization of the auditory system that might otherwise compensate for the loss of cortical processing. Soon after bilateral muscimol application to their AI region, our rats exhibited an acute and profound inability to detect tones. After a few hours this state was followed by a gradual recovery of normal hearing, first of tone detection and, much later, of the ability to discriminate frequencies. Surface muscimol application, at the same time, drastically altered the normal rat AEP. Some of the normal AEP components vanished nearly instantaneously to unveil an underlying waveform, whose size was related to the severity of accompanying behavioral deficits. These results strongly suggest that the cortex is directly involved in basic acoustic processing. Along with observations from accompanying multiunit experiments that related the AEP to AI neuronal activity, our results suggest that a critical amount of activity in the auditory cortex is necessary for normal hearing. It is likely that the involvement of the cortex in simple auditory perceptions has hitherto not been clearly understood because of underlying recovery processes that, in the long-term, safeguard fundamental auditory abilities after cortical injury.