Biomedical subjects
Publications and source records attributed to R H Fitch.
The mechanisms by which human speech is processed in the brain are reviewed from both behavioral and neurobiological perspectives. Special consideration is given to the separation of speech processing as a complex acoustic-processing task versus a linguistic task. Relevant animal research is reviewed, insofar as these data provide insight into the neurobiological basis of complex acoustic processing in the brain.
The sex difference in the midsagittal area of the adult rat corpus callosum (CC) has been shown to be mediated, in part, by gonadal steroids in early development, with the sensitive period of hormone action in the female extending at least up to postnatal day 25. Given this prolonged sensitivity, the current study attempted to delineate organizational vs. activational influences of gonadal hormones on the female rat CC. In Experiment 1, callosal size was examined across the estrous cycle at 52 and 90 days of age. In Experiment 2, females were ovariectomized at 78 days and CC parameters assessed at 110 days. Last, in Experiment 3, females were ovariectomized at 78 days and sacrificed at 110 days; in addition, sham females were sacrificed during proestrus or estrus. Neither stage of estrous cycle nor adult ovariectomy affected midsagittal CC size. These results provide evidence for organizational effects of ovarian steroids on the female callosum, with the sensitive period of hormone action ending sometime between days 25 and 78.
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The rat corpus callosum (CC) is sexually dimorphic, with the male CC being larger. Ovariectomy (Ovx) on day 12 has been shown to eliminate this sex difference, with callosal values of Ovx females approaching those of male controls. This suggested that postnatal ovarian estrogen affects the size of the female CC. In the present experiment, one group of female rats received Ovx on day 12, and a second group received Ovx followed by chronic implantation of a silastic tube containing beta-estradiol on day 25. Unmanipulated males and sham females served as controls. Examination of the CC at 110 days confirmed our prior findings that males have larger callosa than females and that the Ovx group had increased CC's compared to sham controls. Our new finding was that estrogen treatment was capable of reversing the effects of Ovx. Ovx+estrogen-treated females had decreased CC size as compared to Ovx alone. Indeed, they also had smaller CC values than control females. These findings indicate that ovarian estrogen plays a role in determining CC morphology and that estrogen in the female acts to inhibit overall callosal growth as measured by changes in gross callosal size.
In 3 studies adult male rats showed significantly better discrimination of tone sequences with the right ear than with the left ear. This result parallels similar findings of left-hemisphere specialization for auditory temporal processing in humans and nonhuman primates. Furthermore, because clinical evidence supports a link between specialization of the left hemisphere for auditory temporal processing and for speech processing, these results may reflect evolutionary precursors to left-hemisphere language specialization. Because male rats showed a stronger ear advantage than female rats, the findings may relate to evidence of a stronger right ear advantage in men than in women. Finally, results suggest that neonatal handling enhances lateralization for auditory temporal processing in both sexes. Combined results implicate neuroendocrine mechanisms as important factors in the development of lateralization for auditory temporal processing.
Exposure of estrogen treated adult female guinea pigs to the alpha-1 antagonist prazosin has been shown to reduce levels of estrogen binding in the hypothalamus and preoptic area. To further investigate this interaction between the noradrenergic and neuroendocrine axes, newborn female rat pups received an s.c. implant of prazosin (0.0125 mg/day for 5 days) or placebo. In adulthood, subjects were sacrificed by perfusion with DMSO on the morning of proestrous. Tissue analysis of the medial preoptic area, corticomedial amygdala, and mediobassal hypothalamus revealed that cytosolic estrogen binding was significantly reduced in all three areas for the prazosin treated group as compared to controls. Ovarian weight was also significantly reduced in the prazosin treated group, although uterine weight was unaffected. Interestingly, prazosin treated females showed a post-pubertal increase in body weight characteristic of ovariectomized females, while controls showed no such increase. These results support the existence of a significant developmental interaction between the noradrenergic system and the neuroendocrine axis as measured by ovarian weight and estrogen binding in the brain.
Litters of female rat pups were handled daily from birth to weaning. When 12 days old the pups were ovariectomized or received sham surgery. At 70 days sham and ovariectomized animals were decapitated immediately or placed within a novel environment for 10, 20, or 40 min before decapitation. Basal plasma levels of androstenedione in ovariectomized animals were approximately half that of intact sham controls, and stress caused only a small rise in androstenedione in this group. Androstenedione levels in ovariectomized animals were consistently at or below the lower sensitivity of the radioimmunoassay, indicating that circulating levels of androstenedione in the female rat are primarily of ovarian origin. Basal ACTH and corticosterone levels did not differ significantly between the two groups. However, stress-induced levels of ACTH and corticosterone were significantly depressed in ovariectomized subjects compared to controls following exposure to the novel environment. Furthermore, while ACTH levels started to return to baseline by 40 min in controls, this effect was not observed in ovariectomized animals. These findings demonstrate that prepubertal removal of ovarian humoral factors can have a long-term impact on the responsiveness of the hypothalamic-pituitary-adrenal axis to stress.
The rat's corpus callosum is sexually dimorphic with the male's being larger. This difference appears to depend in part on the neonatal presence of testosterone in the male and ovarian hormones in the female. To further investigate the possibility that ovarian hormones participate in the differentiation of the rat's callosum, females received one of the following treatments on postnatal day 8, 12 or 16: (1) ovariectomy (Ovx); (2) 1 mg of testosterone propionate (TP); or (3) sham surgery. All animals were handled daily from birth until weaning. They were sacrificed at 110 days and a mid-sagittal section of the callosum was obtained. From this section measures of callosal area, perimeter, length, and 99 widths were derived. Widths were averaged into 7 factors as defined by prior factor analysis. Ovariectomy, whether on day 8, 12 or 16, enlarged callosal area and 3 of the callosal width factors. TP had no effect on any callosal variable when administered on day 8, 12 or 16. A comparison of control males and females replicated our prior findings of sexual dimorphism. We conclude that ovarian hormones act to feminize the female callosum, and that their removal results in defeminization. Furthermore, the fact that ovariectomy was effective as late as day 16, while TP treatment on day 8 or later had no effect, suggests that masculinization and feminization of this structure constitute separate processes with distinct sensitive periods.
A magnified drawing of a human or a rodent corpus callosum is traced on a digitizing tablet. From this tracing the computer calculates callosal area, perimeter, length, and 99 widths, one for each percentile location along the longitudinal axis of the callosum. In addition, the human program encloses the callosum within a rectangle to obtain several other measures. The use of percentile widths allows one to generate a callosum profile to compare different clinical groups or different species. The human callosum program is compared to one recently reported by another research group.
The male rat's corpus callosum is significantly larger than the female's. This dimorphism depends in part on the early presence of testosterone, since postnatal administration of testosterone to female pups enlarges their callosa in adulthood to the size of males. However, castrating males on day 1 is ineffective in reducing (demasculinizing) the size of their callosa as adults. We then addressed the question as to whether testosterone acts prior to day 1 to enlarge the callosa of males. To investigate this hypothesis pregnant rats were administered a non-steroidal androgen blocker, flutamide, during the last 5 days of pregnancy, while controls received vehicle only. Male pups from flutamide litters were castrated on day 3 to prevent postnatal recovery following clearance of flutamide, while others received sham surgery. Callosal sex differences were found between males and females of control litters, but not between males and females from flutamide litters. The absence of sex effects among flutamide litters was a consequence of small callosal size in flutamide-castrated males as compared to control males. We concluded that the prenatal production of testosterone in the male rat pup contributes to sexual dimorphism in the callosa of adult rats.
Previous research found that the corpus callosum of male rats is larger than that of females; handling rats in infancy enhances this sex difference; and female rat pups, when handled in infancy and given 1 injection of testosterone propionate (TP) on Day 4 of life, will have callosa as large as those of males. In 2 experiments, male pups were castrated on Day 1 or received sham surgery; female pups were injected with TP on Day 4 or received an oil injection. Litters were handled or nonhandled. The previous finding that females, when handled and given TP in infancy, have a larger callosum was confirmed; however, a TP effect when administered to nonhandled females was not found. Because handling is known to cause a corticosterone release, these findings were interpreted as evidence of a developmental interaction between adrenal and gonadal hormones at the cortical level.
The rat's corpus callosum is sexually dimorphic, with the male's being larger. In addition, giving rats extra stimulation in infancy via handling increases callosal area in males, but not in females. To determine if this dimorphism is testosterone-dependent, male pups were castrated on Day 1 of life while females received an injection of testosterone propionate (TP) on Day 4. Control males had sham surgery and control females received an injection of sesame oil. All animals were handled daily from birth until weaning. Animals were sacrificed at 110 days and a mid-sagittal section of the callosum was obtained. From this section measures of callosal area, perimeter, length, and 99 widths were derived. We verified our previous finding that the male callosum is larger than that of the female. Neonatal TP treatment masculinized the callosa of the females, but castration did not affect the males. TP treatment affected the width dimension of the callosum but not callosal length or brain weight. In a related study the synthetic estrogen DES did not increase callosal size for castrated males or for intact females, while the estrogen blocker, tamoxifen, had a defeminizing effect on females' callosa. These findings suggest that there is an estrogen-dependent active process of feminization of cortical tissue in the female brain.
Previous work from our laboratory (Berrebi et al., Brain Research, 438 (1988) 216-224) demonstrated region-specific sexual dimorphisms in the size of the rat's corpus callosum, which are modifiable by extra stimulation in early life. These differences are assumed to reflect regional corticocortical fibers of passage which are altered differentially by gender and our experimental manipulations. In this paper, we report our findings when the original data are reanalyzed using a newly developed computer program. This program not only reproduced, with very high accuracy, the original means, but also permitted us to examine computer generated callosal width scores via a factor analysis procedure. Such a procedure yields useful information concerning the clustering of callosal fibers and thus contributes significantly to our hypothesis that discrete cortical regions are selectively sensitive to experimental variables. Factor analyses of the callosal variables and brain weight of 155 rats found 7 width factors, and an eighth factor which contained the variables of brain weight, callosal length, and callosal perimeter. Callosal area did not load significantly on any of these factors. The percentile locations of the width factors, starting at the anterior (genu) end were: widths 1-5, 6-17, 24-38, 46-57, 62-72, 79-95 and 96-99. Use of these factor scores in analyses of variance revealed that the male callosum is wider than the female's, with the differences most pronounced in the genu and the most posterior portion of the splenium. Both age and early handling experience influenced the callosal width factors.(ABSTRACT TRUNCATED AT 250 WORDS)
In infancy, rats were provided handling stimulation and compared at 110 and 215 days of age with non-handled controls. Measurements were made of corpus callosum area, perimeter and length; and width measures were taken at 7 points along the longitudinal axis of the callosum. Callosal size was larger in males than in females, even when adjusted for the larger brain weight of the male. At 110 days handling stimulation increased callosal parameters and resulted in a more regular callosum in males, but this effect was no longer apparent by 215 days. Within the callosum, region-specific effects were found, suggesting that certain callosal fiber populations were involved. Handled males have previously been shown to be more lateralized than non-handled males; thus at least in this experimental system, increased callosal size and regularity is associated with greater hemispheric specialization.
Studies have shown the existence of minor developmental cortical malformations, including microgyria, in the brains of dyslexics. Concomitant studies have shown that language-impaired individuals exhibit severe deficits in the discrimination of rapidly presented auditory stimuli, including phonological and nonverbal stimuli (i.e., sequential tones). In an effort to relate these results, male rats with neonatally induced microgyria were tested in an operant paradigm for auditory discrimination of stimuli consisting of two sequential tones. Subjects were shaped to perform a go/no-go target identification, using water reinforcement. Stimuli were reduced in duration from 540 to 249 msec across 24 d of testing. Results showed that all subjects were able to discriminate at longer stimulus durations. However, bilaterally lesioned subjects showed specific impairment at stimulus durations of 332 msec or less, and were significantly depressed in comparison to shams. Right- and left-lesioned subjects were significantly depressed in comparison to shams at the shortest duration (249 msec). These results suggest a possible link between the neuropathologic anomalies and the auditory temporal processing deficits reported for language-impaired individuals.