Biomedical subjects

J A Kaltenbach

Publications and source records attributed to J A Kaltenbach.

At least 19 recordsLinked to original sources

PubMed2006

Origin of hyperactivity in the hamster dorsal cochlear nucleus following intense sound exposure.

This study sought to determine whether maintenance of noise-induced dorsal cochlear nucleus (DCN) hyperactivity depends on descending projections. Twenty-two hamsters were exposed under anesthesia to a 10-kHz tone at 125-130 dB SPL for 4 hr, and another 21 unexposed animals served as controls. After approximately 4-6 weeks of recovery, surgical transections were made to isolate the DCN from its adjacent brainstem structures. Spontaneous multiunit activity was recorded from the DCN surface 30-40 min after the surgical manipulations. Spontaneous rates were derived from the recording sites of the DCN along its mediolateral axis for each animal, yielding average spontaneous rates for both control and exposed groups. Histology was performed to assess the degree of sectioning of descending fiber tract connections to the cochlear nucleus, via the acoustic striae route, subpeduncular route, trapezoid body route, and ventral route of the olivocochlear bundle connection. The results showed that complete or nearly complete transections of descending inputs did not affect significantly the magnitude of DCN hyperactivity. However, this manipulation triggered a lateral shift of the peak mean rate, suggesting that descending inputs may play a modulatory role on the profile of DCN hyperactivity. Indeed, exposed animals with transection of only the strial route of entry manifested a level of hyperactivity much higher than that observed in exposed animals in which no sections were performed. This enhancement of DCN hyperactivity was weakened by damage to the subpeduncular or trapezoid routes of input, suggesting that the dorsally located inputs may have an inhibitory effect on DCN hyperactivity.

Acoustic Stimulation↗

PubMed2004

In vivo optical imaging of tone-evoked activity in the dorsal cochlear nucleus with a voltage sensitive dye.

We investigated the use of optical imaging for observing the spatial patterns of neural activation in the dorsal cochlear nucleus (DCN) of hamsters during tonal stimulation. The patterns of activation were studied in the DCN, in vivo, following application of a voltage sensitive dye, Di-2-ANEPEQ, to the DCN surface. Beginning 60-90 min following dye application, tones were presented to the ipsilateral ear. Electrophysiological recordings after dye application revealed no significant toxicity of Di-2-ANEPEQ that affected the frequency-tuning properties of DCN neurons. We examined areas of activation in response to each of a series of test stimuli consisting of pure tones ranging in frequency from 2 to 20 kHz. For each stimulus condition, images were collected over a stimulus interval of 400 msec and averaged over 32 stimulus repetitions. These images revealed areas of activation with definable epicenters. The epicenters shifted from lateral to more medial locations on the DCN surface with increases in stimulus frequency. Comparison with electrophysiological data indicated a close parallel between the tonotopic gradient defined by optical imaging and that defined by the distribution of characteristic frequencies. The principal temporal and spatial features of these optical responses are described.

Acoustic Stimulation↗

PubMed2003

Fos-like immunoreactivity in auditory and nonauditory brain structures of hamsters previously exposed to intense sound.

Fos-like immunoreactivity (FLI) was evaluated in auditory and nonauditory brain structures in hamsters that had been exposed previously to intense sound and tested behaviorally for tinnitus. The immunocytochemical results demonstrated a significant increase in exposed animals of FLI in auditory brain structures such as the lateral lemniscus, central nucleus of inferior colliculus, and auditory cortex, as well as in some nonauditory brain structures such as the locus coeruleus, lateral parabrachial nucleus, certain subregions of the hypothalamus, and amygdala. The behavioral scores suggest that animals that had been exposed to intense sound developed tinnitus. This is consistent with the hypothesis that FLI induced by intense sound exposure might represent a neural correlate of tinnitus or of plasticity associated with tinnitus. The possibility and the mechanisms underlying the increased FLI are discussed.

Acoustic Stimulation↗

PubMed2003

Changes in [14C]-2-deoxyglucose uptake in the auditory pathway of hamsters previously exposed to intense sound.

The current study evaluated changes in [14C]-2-deoxyglucose (2-DG) uptake along the auditory pathways of hamsters that were exposed unilaterally to intense sound. The measurement of the acoustically evoked auditory brainstem responses indicated that intense sound exposure caused asymmetrical hearing loss. The 2-DG results revealed some changes in metabolic activity in exposed animals, as compared to unexposed animals. Significant decreases in 2-DG uptake were found in the ipsilateral anteroventral and posteroventral cochlear nucleus, with respect to the exposed left ears. Exposed animals also showed significant increases in the ipsilateral nucleus of the lateral lemniscus, central nucleus of inferior colliculus and medial geniculate body. No significant changes in uptake were observed in the ipsilateral dorsal cochlear nucleus, superior olivary complex, auditory cortex and any contralateral structures. The mechanisms for the observed changes in 2-DG uptake are discussed.

Acoustic Stimulation↗

PubMed2000

Plasticity of spontaneous neural activity in the dorsal cochlear nucleus after intense sound exposure.

Increases in multiunit spontaneous activity (hyperactivity) can be induced in the dorsal cochlear nucleus (DCN) by intense sound exposure. This hyperactivity has been observed in the hamster and rat following exposure to a 10 kHz tone at a level of 125-130 dB SPL for a period of 4 h. The present study demonstrates that the onset of this hyperactivity is not immediate, but develops in the DCN between 2 and 5 days after exposure. Mean rates of multiunit spontaneous activity increased sharply from below normal levels at day 2 to higher than normal levels at day 5. The mean magnitude of activity continued to increase more gradually over the next 6 months. During this period, changes in the distribution of hyperactivity across the tonotopic array were also noted. The hyperactivity was more broadly distributed across the DCN at the early post-exposure times (5 and 14 days) than at later post-exposure recovery times (30 and 180 days), and peak activity was found at increasingly more medial positions over this time frame. These changes over time indicate that the mechanisms leading to hyperactivity following intense sound exposure are more complex than previously realized.

Animals↗

PubMed2000

Modulation of spontaneous activity by acetylcholine receptors in the rat dorsal cochlear nucleus in vivo.

In vitro studies have implicated muscarinic acetylcholine receptors (mAChRs) in the modulation of spontaneous activity (SA) of neurons in the rat dorsal cochlear nucleus (DCN) (Chen et al., 1994,1998). Early studies suggest that cholinergic pathways also modulate SA in vivo, but these effects have not been investigated pharmacologically. The purpose of the present study was to determine whether multiunit SA can be modulated in vivo by application of cholinergic agents to the surface of the DCN. Sprague Dawley rats were used in the current experiment. The influence of cholinergic activation on SA was tested by applying carbachol (5-500 microM) to the DCN surface while recording multiunit SA at a depth of 250 microm. Out of a total of 32 sites tested, all but 2 (94%) showed well-defined responses to carbachol, characterized by suppression, activation or a combination of both (two-component responses). The most common responses were pure suppression and suppression accompanied by transient activation. Both the proportion of sites showing suppressive responses and the magnitude of suppression averaged across sites increased with dose. Although the proportion of sites showing pure activation in response to carbachol decreased with dose, there was no clear trend in the magnitude of activation with dose. The suppressive responses to high doses of carbachol were blocked by pre-application of atropine. These results extend previous work by suggesting that muscarinic receptors play an important role in the modulation of SA in vivo.

Action Potentials↗

PubMed2000

Hyperactivity in the dorsal cochlear nucleus after intense sound exposure and its resemblance to tone-evoked activity: a physiological model for tinnitus.

Intense tone exposure induces increased spontaneous activity (hyperactivity) in the dorsal cochlear nucleus (DCN) of hamsters. This increase may represent an important neural correlate of noise-induced tinnitus, a condition in which sound, typically of very high pitch, is perceived in the absence of a corresponding acoustic stimulus. Since high pitch sounds are thought to be represented in central auditory structures by the place of activation across the tonotopic array; it is therefore possible that the high pitch of noise-induced tinnitus occurs because intense sound exposure induces a tonotopic distribution of chronic hyperactivity in the DCN similar to that normally evoked only under conditions of high frequency stimulation. To investigate this possibility we compared this tone-induced hyperactivity with the activity evoked in normal animals by presentation of a tone. This comparison revealed that the activity in the DCN of animals which had been exposed to an intense 10 kHz tone 1 month previously showed a striking similarity to the activity in the DCN of normal animals during presentation of low to moderate level tonal stimuli of the same frequency. In both test conditions similar patterns were seen in the topographic distribution of the increased activity along the tonotopic axis. The magnitude of hyperactivity in exposed animals was similar to the evoked activity in the normal DCN responding to a stimulus at a level of 20 dB SL. These results suggest that the altered DCN following intense tone exposure behaves physiologically as though it is responding to a tone in the absence of a corresponding acoustic stimulus. The relevance of these findings to noise-induced tinnitus and their implications for understanding its underlying mechanisms are discussed.

Acoustic Stimulation↗

PubMed2000

Neurophysiologic mechanisms of tinnitus.

Research over the past decade has provided new insights into the neural mechanisms likely to produce the false percepts of sound associated with tinnitus. These insights have emerged mainly as a result of electrophysiologic studies, examining changes in brain activity, and behavioral studies, examining changes in perception, in animals that have been treated with well-known tinnitus inducers such as salicylates, quinine, and intense sound. The available evidence, based on electrophysiologic studies, suggests that tinnitus is associated with disturbances in spontaneous neural activity in the auditory system. These abnormalities include increases in spontaneous activity (hyperactivity), changes in the timing of neural discharges (i.e., the temporal firing properties of neurons), and an increase in bursting activity of neurons. Parallel studies using behavioral testing methods have demonstrated that agents, which produce these neural changes, also cause tinnitus in animals. This article reviews the literature concerned with both behavioral evidence for tinnitus in animal models and the associated changes that occur at peripheral and central levels of the auditory system.

Analgesics, Non-Narcotic↗

PubMed1998

Increases in spontaneous activity in the dorsal cochlear nucleus of the rat following exposure to high-intensity sound.

The effects of intense sound exposure on neural activity in the dorsal cochlear nucleus (DCN) were studied in the rat. Seventeen anesthetized adult rats were exposed to a 10-kHz tone at 125-130 dB SPL for 4 h. Fourteen unexposed rats served as controls. Spontaneous activity (SA) and neural thresholds at the characteristic frequency were measured in three rows of 8-12 sites along the mediolateral, tonotopic, axis of the DCN surface 27-61 days after exposure. The results showed that intense tone exposure induced chronic increases in SA. This hyperactivity was found to be distributed broadly across the DCN with an emphasis around the 10-kHz locus and was associated with shifted response thresholds. These findings demonstrate the usefulness of the rat for studies of physiological phenomena related to noise-induced tinnitus and hearing loss.

Animals↗

PubMed1998

Changes in spontaneous neural activity in the dorsal cochlear nucleus following exposure to intense sound: relation to threshold shift.

Previous studies have shown that the dorsal cochlear nucleus exhibits increased spontaneous activity after exposure to intense sound. Such increases were apparent 1-2 months after the exposure and were generally proportional to the shift in response thresholds induced by the same exposure. The purpose of the present study was to determine whether this sound-induced increase in spontaneous activity is an early event which can be observed shortly after exposure. As in previous studies, anesthetized hamsters ranging in postnatal age from 60-70 days were exposed to a 10-kHz tone at levels between 125 and 130 dB SPL for a period of 4 h. Control animals were similarly anesthetized but were not exposed to the intense tone. Exposed animals were examined in two groups, one at 30 days after exposure, the other at 2 days after exposure. Time of exposure was adjusted so that all animals were between 90 and 100 days of age when spontaneous activity was studied electrophysiologically. The results showed that the increases in spontaneous activity, which were evident at 30 days after exposure, were not observed in animals studied 2 days after exposure. This result contrasted with the effect of the intense tone exposure on neural response thresholds. That is, the shifts in response thresholds seen 2 days after exposure were similar to those observed in animals studied 30 days after exposure. These results indicate that changes in spontaneous activity reflect a more slowly developing phenomenon and occur secondarily after induction of threshold shift.

Animals↗

PubMed1997

Changes in the tonotopic map of the dorsal cochlear nucleus in hamsters with hair cell loss and radial nerve bundle degeneration.

Hamsters were exposed to an intense tone (10 kHz) at levels and durations sufficient to cause hair cell loss and radial nerve bundle degeneration. A previous study reported changes in the tonotopic map of the dorsal cochlear nucleus (DCN) in hamsters with tone-induced stereocilia loss. Such changes appear similar to those observed by others in the auditory nerve following acoustic trauma, and suggest that the map alterations have a peripheral origin. However, the potential for tonotopic map reorganization after more severe lesions involving cellular degeneration in the cochlea has not yet been determined. The purpose of the present study was to determine how the tonotopic map of the DCN appears in animals with severe cochlear injury involving hair cell loss and radial nerve bundle degeneration. Neural population thresholds and tonotopic organization were mapped over the surface of the DCN in normal unexposed animals and those showing tone-induced lesions. The results indicate that cochlear lesions characterized mainly by radial bundle degeneration in a restricted portion of the organ of Corti cause changes in a corresponding region of the tonotopic map which reflect primarily changes in the shape and thresholds of neural tuning curves. In many cases the center of the lesion was represented in the DCN as a distinct characteristic frequency (CF) gap in the tonotopic map in which responses were either extremely weak or absent. In almost all cases the map area representing the center of the lesion was bordered by an expanded region of near-constant CF, a feature superficially suggestive of map reorganization (i.e., plasticity). However, these expanded map areas had abnormal tip thresholds and showed other features suggesting that their CFs had been shifted downward by distortion and deterioration of their original tips. Such changes in neural tuning following tone-induced loss of anatomical input to the central auditory pathway are similar to those observed in our previous study and by others in the auditory nerve following less severe acoustic trauma, and thus would seem to have a peripheral origin. Thus, changes in the DCN tonotopic map can be explained by peripheral modifications and do not seem to involve plastic changes (i.e., reorganization).

Acoustic Stimulation↗

PubMed1997

Comparison of five agents in protecting the cochlea against the ototoxic effects of cisplatin in the hamster.

The purpose of this investigation was to study the ameliorating effects of four agents on cisplatin-induced ototoxicity. Hamsters were given a series of five cisplatin injections either alone or in combination with sodium thiosulfate (STS), diethyldihydrothiocarbamate (DDTC), and S-2(3-aminopropylamino) ethylphosphorothioic acid (WR-2721), or fosfomycin. Ototoxicity was assessed anatomically by quantifying the extent of cochlear damage with the scanning electron microscope and physiologically with measures of the auditory brain stem response. When administered alone, cisplatin induced widespread loss of outer hair cells (OHCs) along much of the cochlea in the hamster, especially in the basal and middle turns, with an average survival of only 56% of the OHC population. In contrast, inner hair cells resisted cisplatin ototoxicity in the hamster. Thus the ameliorative effects of the different test agents were assessed by counting the number of surviving OHCs in each treatment group and comparing with cisplatin-treated controls. STS provided the most effective protection against the ototoxic effects of cisplatin, yielding 91% survival of OHCs. DDTC also reduced the ototoxic effects of cisplatin, yielding 68% survival of OHCs. Cotreatment with WR-2721 and fosfomycin yielded 45% and 52% OHC survival, respectively, and thus did not provide any chemoprotection. The results closely paralleled those based on auditory brain stem response recordings in that the magnitude of threshold shift was proportional to the amount of OHC loss; also, the amount of threshold shift at each frequency was in good agreement with the pattern of hair cell loss along the cochlear spiral. Thus both histologic and physiologic results suggest that STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin chemotherapy.

Amifostine↗

PubMed1997

Changes in dorsal cochlear nucleus blood flow during noise exposure.

Changes in dorsal cochlear nucleus (DCN) blood flow during noise exposure were assessed using both intravital microscopy (IVM) and laser Doppler flowmetry (LDF). Mature Syrian golden hamsters were anesthetized, tracheotomized and implanted with a carotid artery catheter for monitoring blood pressure and infusion of fluorescent dye. An occipital craniectomy was performed and the cerebellum partly aspirated for access to the DCN. Fluorescent dye was infused to enhance observations of the DCN surface using a customized IVM. Red blood cell velocity, vessel diameter and blood pressure were continuously monitored. Subjects were presented with 110 dB SPL broad-band noise for 15 min. A second group was presented with the same protocol for laser Doppler assessment of blood-flow changes. Control groups included animals not exposed to noise using both IVM and laser Doppler measures. Additional control measurements were obtained for noise-exposed and control groups with laser Doppler measures obtained from the obex, a brainstem structure with no known auditory function. Arterioles of the DCN showed a low-frequency oscillatory pattern of red blood cell velocity in control animals and in baseline conditions of the noise-exposure group. Presentation of noise abolished these velocity oscillations. Additionally, significant decreases in both red blood cell velocity and vessel diameter were measured during stimulation. These microvascular measures recovered slightly during the post-stimulus period. Laser Doppler measures of the overall blood flow in the nucleus were consistent with IVM findings. Measurements from DCN and obex in groups not exposed to noise, and animals exposed to noise and measured from the obex, showed stable oscillatory flow. These data show exposure to noise eliminates oscillatory patterns of blood flow and induces decreases in vascular perfusion. Furthermore, these changes appear specific to the auditory structure studied.

Acoustic Stimulation↗

PubMed1997

The development of the reticular lamina in the hamster: an examination of transitory features and their functional roles.

This study examines the development of the reticular lamina in the Syrian golden hamster postriatally from birth to adulthood at 2 day intervals using the scanning electron microscope. During this period, numerous transitory features emerged whose roles were concerned primarily with the development of the tectorial membrane (TM). The principal findings were as follows. (1) The surface of the developing organ of Corti produced all the fibrous material composing the minor tectorial membrane (mTM) including radial and longitudinal fiber bundles which formed the skeleton of the TM, and spongy, amorphous material which formed its intervening ground substance. (2) Throughout most of the cochlear spiral, radial fiber bundles were seen extending from the microvilli of supporting cells and projecting toward the major tectorial membrane (MTM). In most of the basal turn, but not in the apical turn, these radial bundles were interwoven with longitudinal fiber bundles which emerged from the surface of Hensen's cells. These findings indicate that the architecture of the TM is more complex in the basal turn than in the apex. (3) Increases in the dimensions of the reticular lamina resulted from the emergence of pillar cell headplates and growth in the diameter of hair cells and supporting cells. The emergence of pillar cell headplates was the principal factor contributing to increases in the radial dimension of the reticular lamina. This emergence was most dramatic between 10 and 12 days after birth (DAB) after the mTM completed its growth. Since the mTM appears to be bound medially to the MTM and laterally to the marginal pillars by 10 DAB, it seems likely that the growth of the reticular lamina after 10 DAB causes some stretching of the mTM both radially and longitudinally. (4) Completion of outer hair cell stereocilia growth at 8 DAB was followed by loss of supporting cell attachments of the TM (trabeculae) by 10 DAB, and coincided with the formation of marginal pillars from the third row of supporting cells. It is suggested that the formation of marginal pillars may be required for coupling of the TM to the tips of outer hair cell stereocilia and for induction of radial tension of the mTM. (5) Removal of the marginal pillar attachments occurred following completion of hair cell growth. (6) All structures on the reticular lamina appeared to have adult-like characteristics by 20 DAB.

Animals↗

PubMed1997

Hearing, speech, language, and vestibular disorders in the fetal alcohol syndrome: a literature review.

Fetal alcohol syndrome (FAS) is characterized in part by mental impairment, as well as craniofacial and ocular anomalies. These conditions are traditionally associated with childhood hearing disorders, because they all have a common embryonic origin in malformations of the first and second branchial arches, and have similar critical periods of vulnerability to toxic insult. A review of human and animal research indicates that there are four types of hearing disorders associated with FAS. These are: (1) a developmental delay in auditory maturation, (2) sensorineural hearing loss, (3) intermittent conductive hearing loss due to recurrent serous otitis media, and (4) central hearing loss. The auditory and vestibular systems share the same peripheral apparatuses (the inner ear and eighth cranial nerve) and are embryologically and structurally similar. Consequently, vestibular disorders in FAS children might be expected. The evidence for vestibular dysfunction in FAS is ambiguous, however. Like other syndromes associated with craniofacial anomalies, hearing disorders, and mental impairment, FAS is also characterized by a high prevalence of speech and language pathology. Hearing disorders are a form of sensory deprivation. If present during early childhood, they can result in permanent hearing, language, and mental impairment. Early identification and intervention to treat hearing, language, and speech disorders could therefore result in improved outcome for the FAS child. Specific recommendations are made for intervention and future research.

Animals↗

PubMed1997

Efferent neurons and vestibular cross talk in the frog.

A galvanic stimulus (30- to 120-s, 0.3-mA constant current pulse) was used to depolarize the spike-generating region of horizontal and anterior canal afferent neurons. The galvanically induced spike activity from these neurons served as a driving input to the efferent vestibular system in the bullfrog. Efferent-mediated effects were assessed by intracellular recordings of posterior canal afferent spike activity, either ipsilateral or contralateral to the driving stimulus. Ipsilateral to the driving stimulus, efferent-mediated spike rate changes occurred in 62 (39%) of 158 posterior canal afferent neurons. Ipsilateral efferent-mediated effects were overwhelmingly excitatory (92%). Of responding units, 3% were inhibited during stimulus application and 5% showed mixed responses involving 3-20 s of inhibition followed by facilitation. Contralateral to the driving stimulus, efferent-mediated spike rate changes occurred in 18 (23%) of 77 posterior canal afferent neurons. Contralateral efferent-mediated effects were overwhelmingly inhibitory (95%). Only one unit was facilitated during stimulation and no mixed responses to contralateral stimulation were observed. Analysis of the coefficient of variation in interspike intervals (CV) before and during stimulation showed no significant efferent-mediated effects on spike train noise. Comparisons of resting spike rates between units showing efferent-mediated effects and those that did not were in general agreement with previous studies. Responding units had a lower mean spike rate (6.8 +/- 0.70 spikes/s, mean +/- SE) than did nonresponding units (10.7 +/- 0.42 spikes/s, mean +/- SE; P < 0.001; 2-tailed t-test of log-normalized data). Comparison between groups in the regularity of their resting spike rates, as quantified by CV, showed considerable overlap. When responding and nonresponding units with similar resting spike rates were compared, responding units had more irregular resting spike rates than did nonresponding units (P < 0.004; 2-tailed, paired t-test). In most cases (77%) the temporal pattern and general shapes of efferent-mediated responses mirrored the driving input of the galvanically activated afferent neurons. The other 23% of efferent-mediated responses exhibited a marked adaptation of the response. Adapting and nonadapting units were not significantly different in their mean resting spike rates or in the regularity of their resting spike rates.

Animals↗

PubMed1996

Dorsal cochlear nucleus blood flow during acoustic stimulation.

Dynamic in vivo changes in dorsal cochlear nucleus blood flow during pure-tone stimulation were assessed with intravital microscopy. Subjects were stimulated with 5-, 10-, or 15-kHz pure tones at 70, 80, and 90 dB sound pressure level. Measurements in red blood cell velocity and vessel diameter were made in capillaries overlying the 10-kHz isofrequency band of the dorsal cochlear nucleus. Stimulation with 10 kHz induced intensity-dependent increases in local blood flow in the 10-kHz isofrequency band of the dorsal cochlear nucleus. Stimulation with 5 kHz and 15 kHz, frequencies represented in remote locations on the dorsal cochlear nucleus surface, did not significantly alter blood flow in the defined 10-kHz isofrequency band. These data demonstrate a direct relationship between spectral and intensity-dependent pure-tone stimulation of the dorsal cochlear nucleus and increases in local blood flow. These findings suggest that tonal stimulation of the dorsal cochlear nucleus induces an increase in local metabolic demands with resultant rapid blood flow increases.

Acoustic Stimulation↗

PubMed1996

Effects of prenatal alcohol exposure and aging on auditory function in the rat: preliminary results.

This study investigated select aspects of peripheral and central auditory dysfunction, as well as the pathological effects of aging, In an animal model of fetal alcohol syndrome (FAS). Pregnant rats consumed liquid alcohol diets containing 0, 17.5, or 35% ethanol-derived calories, from gestation day 7 to parturition. A fourth group was untreated. Offspring of these mothers were tested for auditory and neurological function, using the auditory brainstem response at 6, 12, and 18 months of age. Some animals in the alcohol-exposed groups showed a peripheral auditory disorder in the form of congenital sensorineural hearing loss. This was correlated with punctate lesions and malformed stereocilia on the auditory sensory receptor cells of the inner ear. Alcohol-exposed animals also showed a central auditory processing disorder characterized by prolonged transmission of neural potentials along the brainstem portion of the auditory pathway. Animals in the highest dose group also showed an augmentation in the age-related deterioration of auditory acuity. Thus, increased peripheral and central auditory dysfunctions and pathological deterioration of auditory function in old age may be sequelae of FAS. Such morbidities have important implications for the long-term clinical assessment and management of FAS patients.

Age Factors↗