AbstractAn important component of bioacoustical research is the description and quantification of the hearing capabilities of different animal species. This chapter reviews common behavioral and physiological methods used to examine the hearing of live animals and discusses some of their strengths and weaknesses. The focus is on audiometric studies that identify the frequency range and sensitivity of hearing, with examples provided from several different species. The methods discussed also are useful for quantifying other aspects of auditory perception such as sound frequency or intensity discrimination, sound localization, and the effects of noise on hearing.

Poorer-than-expected performance on cognitive-behavioral tasks may indicate malingering, or it could be an outcome of fatigue, resulting in false positives when suboptimal task performance is used to flag individuals feigning or exaggerating symptoms of traumatic brain injury (TBI). The primary goal of this study was to examine the P3 event-related potentials (ERP) and behavioral outcomes associated with TBI malingering and fatigue, in order to distinguish between them. A secondary goal was to determine if history of TBI (hTBI) is associated with differences in fatigue, ERPs, or performance on a short-term memory task. Participants completed the Mental Fatigue and Related Symptoms (SR-MF) questionnaire and were interviewed to assess TBI history, then they completed a computerized "old/new" (match-mismatch) task while ERPs were recorded, under three conditions: Normal, Malinger, and Fatigue. Participants reported mild fatigue at the end of study, with no difference between individuals reporting a history of TBI (n = 32) and healthy controls (n = 47). Fatigue was associated with prolonged P3 latency but was otherwise indistinguishable from Normal. In contrast, Malinger was clearly distinguished from Normal by significantly lower accuracy, longer reaction times, reduced P3 amplitude on Match trials, and a smaller old/new ERP effect. Individuals with a history of TBI reported clinical levels of fatigue at baseline but did not differ significantly from healthy controls on any behavioral or ERP measure. The results support the use of behavioral and ERP measures to identify malingering, without concern over confounding effects of mild subjective fatigue, including mild fatigue induced by testing.

Posttraumatic stress disorder (PTSD) is a serious mental health condition that affects some individuals who have witnessed or experienced a life-threatening or traumatic event. An enhanced or exaggerated acoustic startle response (ASR), reflecting heightened sensitivity to unexpected, loud sound, is a hallmark symptom of PTSD. Antidepressant medications, such as sertraline, are first-line pharmacotherapeutic agents in the treatment of PTSD, but concerns about potential side effects or taking synthetic drugs prompt discovery of naturalistic therapeutic agents. This study examined the relative effectiveness of a compound containing St. John's Wort (SJW), an herb widely prescribed for depression in Europe and sold as a dietary supplement in the United States, compared to sertraline (Zoloft) in a mouse model of PTSD. Thirty-six mice were tested for baseline ASR, then they were exposed to rats in a predator exposure paradigm known to induce PTSD-like symptoms. Mice were randomly divided into three groups for treatment (control, sertraline, SJW), and ASR was retested one week later. One-way ANOVAs found no significant group differences in ASR amplitude at baseline but a significant effect of Treatment Group after predator exposure, F(2, 33) = 5.645, p = .008, n(2) = .225, when SJW-treated mice had ASR amplitudes that were significantly lower than sertraline-treated mice (by 27%) and controls (by 26%). Fecal boli counts showed a similar pattern, with lowest counts in SJW-treated mice. These results suggest SJW could be considered for studies of PTSD treatment in humans as well.

Overt sexual prejudice is declining, but heterosexuals who report little to no prejudice may still harbor subtle biases against gay men and lesbians. We examined implicit prejudice in a sample of 37 heterosexual college students who reported little or no sexual prejudice, using the Affect Misattribution Procedure (AMP) and psychophysiological measures of affect. Skin conductance, heart rate, and facial electromyographic responses were recorded as participants viewed photos of mixed- and same-sex couples kissing and rated them on valence, arousal, and disgustingness. Sexual prejudice was evident in implicit (AMP) ratings and explicit ratings of valence and disgustingness, but not in psychophysiological responses. Results suggest that implicit prejudice harbored by young adults who endorse low levels of sexual prejudice is more cognitively than emotionally based, unlike the fear-based reactions commonly described for racism. Limitations and future directions for research are discussed.

Previous studies have shown that social rejection leads to impaired performance on a variety of tasks that require self control, including the Stroop color-word interference task; however, mechanisms underlying the effect remain to be elucidated. We attempted to clarify the effects of social rejection on self control resources by measuring event-related potentials (ERPs) during a computerized Stroop test. Stroop performance and ERPs from 54 participants in rejected, control, and accepted groups were analyzed. A significant difference in the pattern of results for the N450 ERP was found, with rejected participants showing less negativity on incongruent trials and more on congruent trials compared to accepted participants and controls. The results suggest social rejection reduces the engagement of cognitive control mechanisms, and are more consistent with a limited strength resource model than with limited capacity resource models that focus on limitations in attention.

Auditory neuropathy is a hearing disorder characterized by normal function of outer hair cells, evidenced by intact cochlear microphonic (CM) potentials and otoacoustic emissions (OAEs), with absent or severely dys-synchronized auditory brainstem responses (ABRs). To determine if selective lesions of inner hair cells (IHCs) and auditory nerve fibers (ANFs) can account for these primary clinical features of auditory neuropathy, we measured physiological responses from chinchillas with large lesions of ANFs (about 85%) and IHCs (45% loss in the apical half of the cochlea; 73% in the basal half). Distortion product OAEs and CM potentials were significantly enhanced, whereas summating potentials and compound action potentials (CAPs) were significantly reduced. CAP threshold was elevated by 7.5 dB, but response synchrony was well preserved down to threshold levels of stimulation. Similarly, ABR threshold was elevated by 5.6 dB, but all waves were present and well synchronized down to threshold levels in all animals. Thus, large lesions of IHCs and ANFs reduced response amplitudes but did not abolish or severely dys-synchronize CAPs or ABRs. Pathologies other than or in addition to ANF and IHC loss are likely to account for the evoked potential dys-synchrony that is a clinical hallmark of auditory neuropathy in humans.

Modafinil is a psychostimulant approved for treating excessive sleepiness in adults; off-label uses (e.g., treatment of cognitive impairment in schizophrenia, ADHD and age-related dementias) are currently being explored. The effects and mechanisms of action of modafinil have not been fully established. In the present study, the effects of modafinil were examined in young adult (7-month-old) and middle-aged (21–22-month-old) rats, using the acoustic startle response (ASR) and prepulse inhibition (PPI). In the control condition, middle-aged rats showed lower activity levels, significantly lower ASR amplitudes and significantly longer ASR latencies compared to young adult rats. The effects of modafinil differed by age: activity levels and ASR amplitudes were significantly increased in middle-aged rats, whereas activity levels were lower and ASR amplitude was significantly decreased in young adult rats. Modafinil did not significantly alter PPI or startle latencies relative to the control condition. Amphetamine, used as a positive control, significantly decreased ASR amplitude in young adult rats and significantly impaired PPI for both age groups. Amphetamine-induced PPI impairment was greater for young adult rats (34% reduction in ASR amplitude) than for middle-aged rats (24% reduction). The results offer new insights into the effects of modafinil and its mechanism of action, and are consistent with the idea that modafinil enhances vigilance and cognitive functioning in individuals with deficits but not in normal, healthy individuals.

Carboplatin produces progressive damage to auditory nerve fibers, spiral ganglion neurons (SGNs) and inner hair cells (IHC) in the chinchilla cochlea but leaves outer hair cells intact. Within 1 h after injection, many afferent terminals beneath IHCs and myelin lamellae surrounding SGN processes are vacuolated. One day after injection, approximately half of the nerve fibers are missing. IHCs are intact at 2 days, but 20-30% are missing at 3 days. We studied the electrophysiological correlates of this progressive morphological damage by recording cochlear microphonics (CM), distortion product otoacoustic emissions (DPOAE), summating potentials (SP), compound action potentials (CAP) and midbrain evoked potentials (IC-EVP) before and 1 h, 12 h, 1 days, 3 days, 5 days, 7 days and 14 days after carboplatin injection (75 mg/kg IP) in four chinchillas. CM and DPOAEs tended to be unchanged or enhanced. CAP and SP showed little change until Day 3, when amplitudes were reduced in all animals and CAP thresholds were elevated by 9 dB; amplitudes declined further between Days 3 and 5 but not thereafter. IC-EVP amplitudes decreased on Days 3 or 5 but thresholds were relatively unchanged. All animals showed some recovery of IC-EVP between Days 7 and 14, including one with 70% enhancement on Day 14. The results indicate that threshold and amplitude measures fail to detect peripheral pathology until some relatively high threshold level of damage has been exceeded. This has important implications for monitoring peripheral damage and interpreting electrophysiological test results in animals and humans.

The goals were to study the physiological effects of auditory nerve myelinopathy in chinchillas and to test the hypothesis that myelin abnormalities could account for auditory neuropathy, a hearing disorder characterized by absent auditory brainstem responses (ABRs) with preserved outer hair cell function. Doxorubicin, a cytotoxic drug used as an experimental demyelinating agent, was injected into the auditory nerve bundle of 18 chinchillas; six other chinchillas were injected with vehicle alone. Cochlear microphonics, compound action potentials (CAPs), inferior colliculus evoked potentials (IC-EVPs), cubic distortion product otoacoustic emissions and ABRs were recorded before and up to 2 months after injection. Cochleograms showed no hair cell loss in any of the animals and measures of outer hair cell function were normal (cubic distortion product otoacoustic emissions) or enhanced (cochlear microphonics) after injection. ABR was present in animals with mild myelin damage (n = 10) and absent in animals with severe myelin damage that included the myelin surrounding spiral ganglion cell bodies and fibers in Rosenthal's canal (n = 8). Animals with mild damage had reduced response amplitudes at 1 day, followed by recovery of CAP and enhancement of the IC-EVP. In animals with severe damage, CAP and IC-EVP thresholds were elevated, amplitudes were reduced, and latencies were prolonged at 1 day and thereafter. CAPs deteriorated over time, whereas IC-EVPs partially recovered; latencies remained consistently prolonged despite changes in amplitudes. The results support auditory nerve myelinopathy as a possible pathomechanism of auditory neuropathy but indicate that myelinopathy must be severe before physiological measures are affected.

PURPOSE:To determine whether children with a nonverbal learning disability (NVLD) have a higher incidence of auditory processing disorder (APD), especially in the tolerance-fading memory type of APD, and what associations could be found between performance on neuropsychological, intellectual, memory, and academic measures and APD.METHOD:Eighteen children with NVLD ranging in age from 6 to 18 years received a central auditory processing test battery to determine incidence and subtype of APD. Psychological measures for assessment of NVLD included the Wechsler Scales, Wide Range Assessment of Memory and Learning, and Wechsler Individual Achievement Test. Neuropsychological measures included the Category Test, Trails A and B, the Tactual Performance Test, Grooved Pegs, and the Speech Sounds Perception Test. Neuropsychological test scores of the NVLD+APD and NVLD groups were compared using analysis of covariance procedures, with Verbal IQ and Performance IQ as covariates.RESULTS:Sixty-one percent of the children were diagnosed with APD, primarily in the tolerance-fading memory subtype. The group of children with APD and NVLD had significantly lower scores on Verbal IQ, Digit Span, Sentence Memory, Block Design, and Speech Sounds Perception than children without APD. An ancillary finding was that the incidence of attention deficit/hyperactivity disorder was significantly higher in children with NVLD (with and without APD) than in the general population.CONCLUSION:The results indicate that children with NVLD are at risk for APD and that there are several indicators on neuropsychological assessment suggestive of APD. Collaborative, interdisciplinary evaluation of children with learning disorders is needed in order to provide effective therapeutic interventions.

Thyroid and embedded parathyroid glands were surgically removed (thyroparathyroidectomized) from adult chinchillas (Chinchilla laniger) to create an animal model of hypothyroidism. Thyroxine (T4) levels were measured at the time of surgery and one or two times after surgery from 10 thyroparathyroidectomized chinchillas and five sham controls to establish baseline serum T4 levels and to assess the degree and duration of hypothyroidism in this animal model. Baseline T4 levels ranged from 3.4 to 6.4 microg/dl (mean +/- 1 standard deviation, 5.25 +/- 0.84 microg/dl), with no differences between male and female chinchillas (5.4 +/- 0.6 microg/dl versus 5.2 +/- 1.0 microg/dl, respectively). T4 levels were significantly reduced in 80% of thyroparathyroidectomized chinchillas when measured 6 to 14 days after surgery, but reductions were variable, ranging from 9 to 89% in individual animals. There was rapid regrowth of thyroid tissue and a return of T4 levels to the baseline range in five of the seven animals followed for 1 to 2 months after surgery. T4 levels increased significantly in the sham-operated chinchillas, indicating a nonspecific effect of surgery. The results establish surgical procedures for creating a model of variable, transient hypothyroidism in the chinchilla. We also summarize published basal T4 values for various laboratory animals, to provide a convenient reference.

DBA/2J (D2) mice, which exhibit very early progressive sensorineural hearing loss, were treated nightly with an augmented acoustic environment (AAE) initiated before the onset of hearing, and consisting of repetitive bursts of a 70-dB sound pressure level (SPL), 4–25 kHz noise band. At 55 days of age, AAE-treated mice exhibited less elevation of auditory brainstem response thresholds, fewer missing hair cells, and greatly reduced loss of anteroventral cochlear nucleus (AVCN) volume and neuron number compared to untreated control mice. It was hypothesized that the central neuroprotective effect was associated with increased afferent input to AVCN neurons evoked by the AAE as well as a healthier cochlea.

Vitamin C (ascorbate) is a water-soluble, low molecular weight antioxidant that works in conjunction with glutathione and other cellular antioxidants, and is effective against a variety of reactive oxygen species, including superoxide and hydroxyl radicals that have been implicated in the etiology of noise-induced hearing loss (NIHL). Whereas most animals can manufacture their own vitamin C, humans and a few other mammals such as guinea pigs lack the terminal enzyme for vitamin C synthesis and must obtain it from dietary sources. To determine if susceptibility to NIHL could be influenced by manipulating dietary levels of vitamin C, albino guinea pigs were raised for 35 days on a diet with normal, supplemented or deficient levels of ascorbate, then exposed to 4 kHz octave band noise at 114 dB SPL for 6 h to induce permanent threshold shifts (PTS) of the scalp-recorded auditory brainstem response. Animals that received the highest levels of dietary ascorbate developed significantly less PTS for click stimuli and 4, 8, 12, and 16 kHz tones than animals on normal and deficient diets. Outer hair cell loss was minimal in all groups after noise exposure, but permanent damage to stereocilia were observed in noise-exposed ears. The results support the hypothesis that dietary factors influence individual susceptibility to hearing loss, and suggest that high levels of vitamin C may be beneficial in reducing susceptibility to NIHL.

derived neurotrophic factor 135 Brain plasticity 160

Some forms of ototoxicity appear to be mediated primarily by the superoxide radical; however, the exact role the superoxide radical plays in cochlear damage is not well understood because most ototoxic drugs produce multiple reactive oxygen species. To characterize the role of the superoxide radical in cochlear damage and the protective effect of compounds that inactivate superoxide, we treated mouse cochlear organotypic cultures for 24 h with paraquat, an herbicide that produces high levels of superoxide. M40403, a highly specific, nonpeptidyl mimetic of superoxide dismutase, was added to some cultures to inactivate the superoxide radical generated by paraquat. The number of outer hair cells (OHC) and inner hair cells (IHC) systematically decreased with increasing concentration of paraquat (0.01–10 mM). M40403 (10 µM) significantly increased OHC and IHC survival in cultures treated with 0.01–1.0 mM of paraquat. These results suggest that excess production of superoxide radical is a sufficient condition for hair cell loss.

Gentamicin, an aminoglycoside antibiotic, and cisplatin, a platinum-based anticancer drug, are two commonly used clinical drugs with ototoxic side effects. The ototoxicity of gentamicin and cisplatin has been linked to the production of reactive oxygen species (ROS), although the specific ROS pathways have not been identified. One ROS that might play a role in ototoxicity is the superoxide radical, which is enzymatically dismutated to molecular oxygen and hydrogen peroxide by endogenous superoxide dismutase (SOD) enzymes. M40403, a manganese-based nonpeptidyl molecule that mimics the activity of SOD, was tested for its ability to protect against gentamicin and cisplatin toxicity in cochlear organotypic cultures from neonatal C57BL/10J mice. Cultures were treated with gentamicin or cisplatin alone or in combination with M40403. M40403 alone had no effect on outer hair cell (OHC) or inner hair cell (IHC) survival at doses of 1, 5, and 10 μM, but a high dose of 30 μM reduced hair cell numbers by approximately 30%. Gentamicin alone and cisplatin alone killed OHCs and IHCs in a dose-dependent manner. The addition of M40403 to gentamicin-treated cultures significantly increased OHC and IHC survival in a dose-dependent manner, whereas M40403 failed to protect hair cells in cisplatin-treated cultures at any dose. The results suggest that the toxicity of gentamicin and cisplatin to cochlear hair cells are mediated by different pathways. Clinically, increased levels of SOD or SOD mimetics might provide significant protection against aminoglycoside ototoxicity.

Objective Carboplatin selectively destroys inner hair cells (IHC)and typeⅠspiral ganglion neurons in the chinchilla cochlea;however,its effects on the central auditory system are largely unknown.The aim of this study was to determine if carboplatin treatment affects neuron survival in the cochlear nucleus (CN),inferior colliculus(IC)or auditory cortex(AC)of the chinchilla.Methods Chinchillas were treated with carboplatin(100mg/kg IP).Three weeks later,they were sacrificed and perfused intracardially with fixative.Surface preparations of Corti's organ were analyzed for hair cell loss.Serial frozen sections taken from the CN, IC and AC were stained with toluidine blue,and neurons were counted in representative sections from two normal(control)and four carboplatin-treated chinchillas. Results The results showed that carboplatin destroyed approximately 80% of the IHC,but almost none of the outer hair cells (OHC). In the central auditory system, carboplatin resulted in a significant loss of neurons in the anteroventral, posteroventral and dorsal divisions of the CN, but not in the IC or AC. Conclusionon Future studies will determine if the loss of neurons in the CN is a direct result of carboplatin neurotoxicity or a secondary effect of inner hair cell and spiral ganglion neuron loss in the auditory periphery.

Ethacrynic acid (EA) is known to interact with aminoglycoside antibiotics such as gentamicin (GM). In the chinchilla, co-administration of GM and EA can produce hair cell lesions ranging from a small loss of outer hair cells (OHCs) in the base of the cochlea to complete destruction of all hair cells, depending on dosing parameters. Although hair cell loss has been characterized, little is known about the fate of efferent fibers or spiral ganglion neurons (SGNs) in this model. To study the time course of efferent fiber and SGN loss, chinchillas were injected with GM (125 mg/kg IM) followed immediately by EA (40 mg/kg IV). Estimates of efferent fiber loss and density changes were made after 3 days or 1, 2, 3, or 4 weeks of survival. Estimates of SGN loss and density changes were made after 15 days or 1, 2, 4, or 6 months of survival. Cochlear function was rapidly abolished and all cochlear hair cells were missing within 24 h after treatment. Inner hair cells (IHCs) in the middle turn of the cochlea died earlier than cells in the apex or base, and OHCs in Rows 1 and 2 died earlier than OHCs in Row 3. Degeneration of efferent nerve fibers began 3–7 days post-injection, versus 15–30 days for SGNs, and the loss of efferent fibers was essentially complete within 1 month, versus 2–4 months for SGNs. The rapid time course of efferent fiber and SGN loss in the chinchilla may make it a practical model for studying mechanisms of neural loss and survival in the mammalian inner ear.