Sergio L. Schmidt

The effects of hand preference and gender on finger tapping performance asymmetry by the use of an infra-red light measurement device.

We used an infra-red device to study the effects of gender and handwriting preference on manual asymmetry in tapping rate and intertap variability. Our sample (n=102) consisted of approximately equal number of subjects with respect to gender (52 women and 50 men) and handedness (52 right-handers and 50 left-handers). Data on overall performance indicated that men performed more quickly and regularly than women. The index used for measuring manual asymmetry was the difference between the hands as a proportion of the total. Therefore, the asymmetry index was adjusted to remove the influence of overall performance. The analyses based on asymmetry scores indicated a significant handedness effect: right-handers showed greater manual asymmetries than left-handers for both tapping rate and intertap variability. In addition, right handers exhibited a significant greater asymmetry for intertap variability than tapping rate. Taken together, these data may reflect greater hemispheric differences in right-handers, specially for intertap variability.

The effects of total and partial callosal agenesis on the development of morphological brain asymmetries in the BALB/cCF mouse

The corpus callosum fails to develop in some mice of the BALB/cCF strain. We report here a study on cerebral morphological asymmetry in males of this particular strain in order to test the hypothesis that the normal development of the corpus callosum is responsible for the establishment of brain asymmetries. In 46 animals the dorsal area and the weight of each hemisphere were measured. In order to identify the animals with callosal defects and check for size anomalies of the anterior commissure, the hemispheres were cut into sagittal sections and stained with cresyl violet. Measures of sagittal area of the anterior commissure did not support the hypothesis that this commissure is enlarged when the corpus callosum is reduced or absent. In normal animals, the mean difference between left and right dorsal cortical areas showed a significant directional asymmetry, the left being consistently greater than the right. A similar pattern was found for weight. In mice with callosal defects there were no significant differences, either between the dorsal areas or between the weights of the hemispheres. However, data on the absolute values of the hemispheric differences indicated the presence of a nondirectional asymmetry not only in normal animals, but also in mice with callosal defects. Therefore, our data suggest that the ontogenesis of the corpus callosum plays a role in directing the development of cerebral asymmetries.

Sex differences in sensitivity to seizures elicited by pentylenetetrazol in mice.

Sex differences in sensitivity to seizures elicited by intraperitoneally injected pentylenetetrazol (PTZ) were studied in 240 (120 males and 120 females) adult Swiss mice. Animals were separated into four groups according to the dose that was injected: 40, 50, 60 and 70 mg/kg. Seizure severity was expressed by the following scoring scale: (0) no abnormal behavior; (1) myoclonus; (2) running bouncing (RB) clonus; (3) tonic hind limb extension (THE). The analyses of the dose-response curves indicated that females were more susceptible than males when the 50- and 60-mg/kg doses were used. Specifically, females often displayed RB clonus, while males frequently displayed only myoclonus or no abnormal behavior. No significant sex differences were demonstrated when either the 40- or the 70-mg/kg doses were used. These data indicate that, for a specific range of doses, sex differences in seizure susceptibility can be clearly demonstrated with the use of intraperitoneally injected PTZ. In this sense, this method could be used as a tool to investigate the role played by sexual hormones in regulating the sensitivity of the gamma-aminobutiric acid (GABA(A)) receptor complex (GRC).

Dose-dependent occurrence of the aberrant longitudinal bundle in the brains of mice born acallosal after prenatal gamma irradiation.

Two groups of pregnant mice were gamma-irradiated at the 16th gestation day with doses of 2 or 3 Gy. All litters were born acallosal, but while the 3-Gy mice showed a severely hypotrophic neocortex without the aberrant longitudinal bundle typical of early disconnected rodents, in the 2-Gy group the cortex was less deranged and the aberrant bundle appeared consistently underneath the white matter.

Value of combining activated brain FDG-PET and cardiac MIBG for the differential diagnosis of dementia: differentiation of dementia with Lewy bodies and Alzheimer disease when the diagnoses based on clinical and neuroimaging criteria are difficult.

Dementia with Lewy bodies (DLB) is the second most common cause of dementia. The diagnosis of DLB is particularly important because these patients show good response to cholinesterase inhibitors. Clinical and neuroimaging criteria for DLB have not been acceptable for predictive accuracy. We report a case of progressive dementia in which the differentiation of DLB and Alzheimer disease (AD) on the basis of clinical criteria alone was not possible. The patient was admitted to the hospital because he became worse after he had started treatment for severe AD. Both MRI and brain magnetic resonance spectroscopy were normal. The patient underwent myocardial scintigraphy with I-123 MIBG showing marked reduction in cardiac MIBG accumulation. The heart to mediastinum ratio of MIBG uptake was impaired in both early and delayed images. FDG-PET scan before and after activation with a visual attention task showed occipital cortex hypometabolism as compared with AD and a normal control. This case illustrates the value of combining activated brain FDG PET and cardiac MIBG. The association of these 2 techniques could be used as a potential diagnostic tool in a patient with dementia misdiagnosed as AD.

The effect of corpus callosum agenesis on neocortical thickness and neuronal density of BALB/cCF mice

We used acallosal and normal adult BALB/cCF mice to test the hypothesis that the development of the corpus callosum is relevant for the establishment of a normal structure of the neocortex. Neuronal density and thickness of individual layers were analyzed in neocortical regions with abundant callosal connections (area 6 and the 17/18a border) and in the relatively acallosal area 17. In area 6, acallosal mice exhibited a total neocortical thickness smaller than that of normal mice, as well as thinner layers II+III and IV. Similar data were obtained at the 17/18a border, where the total thickness of the cortex and of layers II+III was smaller in the acallosal mice than in normal ones. In contrast, no significant thickness differences were documented in area 17 of acallosal versus normal mice. The quantitative data obtained in the analyzed neocortical regions did not show differences in neuronal density between acallosal and normal mice. The reduced cortical thickness, associated with the comparatively normal neuronal density in neocortical regions which normally have abundant callosal connections, provides indirect indication of a reduction in the number of cortical neurons in acallosal mice. This assumption was also supported by the lack of evidence of neocortical alterations in the acallosal area 17. The present findings suggest that during development neocortical neurons destined to receive a massive callosal input may die as a result of lack of afferents. Altogether the present data indicate that the input provided by callosal axons is necessary for a normal development of the neocortex.

Effects of sex and laterality on the rotatory swimming behavior of normal mice.

Clockwise and counterclockwise full turns are commonly used to assess lateralization in circling behavior. Although previous studies have reported that the rotatory swimming (ROSW) test is simple and reliable, little is known about lateralization of turns lower than 360 degrees and the amount of turning close to the wall, and even less is known about alternation of direction during a session. Here we investigated the effects of consistency of laterality and sex on 30 degree turns in center and in periphery of the swimming apparatus, and on alternation of direction upon three sessions. Approximately 80% of the turns occurred when mice swam along the wall. In side-consistent turners, this suggests the existence of an intrinsic sensorimotor asymmetry that determines the adhesion to the preferred side. Regarding categorization of side preferences, there was a high percentage of agreement between center and periphery, as well as between full turns and extra 30 degree turns (30 degree turns that do not contribute to full turns). Therefore, behavioral asymmetry in the ROSW can be assessed using 30 degree turns. There was no significant directional bias in the population, and side preference was found to be independent of sex. By contrast, after the second minute of each session, males exhibited a significantly higher number of reversal of direction (RD) as well as a higher number of RD per turn than females. The amount of RD presented by each animal is not predicted by the animals side preference. Thus, RD is independent of preferred side of turning and depends on sex.

Neonatal transection of the corpus callosum affects paw preference lateralization of adult Swiss mice

In the present work, the hypothesis that the ontogenetic development of the corpus callosum (CC) affects the establishment of behavioral lateralization was tested by studying paw preference performance in adult Swiss mice that were subjected to mid-sagittal transection of the CC on the first postnatal day. Magnitude and direction of laterality were evaluated independently. No significant differences between groups were found for the magnitude of paw preference. On the other hand, the transected group presented a significant populational bias favoring the left paw that was not present in the control groups. These results lend support to the hypothesis that the development of the CC plays a role in the establishment of the normal pattern of behavioral lateralization.

Morphological brain asymmetries in male mice withcallosal defects due to prenatal gamma irradiation

We have previously suggested a relationship between the development of the corpuscallosum and the direction of cerebral asymmetries (Schmidt and Caparelli‐Dáquer, 1989 ; Schmidt et al., 1991). Here we report a study on morphological brainasymmetries using a distinct experimental approach. At embryonic day 16, mice were exposed toa gamma source, receiving a total dose of 2 Gy. At adulthood 32 irradiated and 28 normal maleSwiss mice were evaluated for individual and populational interhemispheric asymmetries ofweight, dorsal area, and neocortical volume. All irradiated mice showed callosal defects rangingfrom total absence to a partial reduction of the midsagittal callosal area. The normal and irradiatedgroups displayed a pronounced individual asymmetry in all measurements. In contrast,populational asymmetry could be identified only in the normal group. These results are consistentwith our previous data in acallosal mutant mice and support the hypothesis that the corpuscallosum may play a role in directing interhemispheric morphological brain asymmetries.

Effects of rotational side preferences on immobile behavior of normal mice in the forced swimming test

It has been suggested that side preferences in spontaneous rotational behavior are determinant of differences in vulnerability to the effects of the learned helplessness paradigm. The purpose of the present study was to investigate the effects of side preferences of rotational behavior in another animal model of depression, the forced swimming test. Immobility was also investigated upon repeated testing sessions and in interaction with sex. Swiss mice (69 males and 73 females) were submitted to three sessions (test time = 5 min) of forced swimming. Immobile and turning behaviors were measured for each session and within each testing session. Consistency of laterality was defined considering the persistence of the same side turning preference in the three sessions. In general, there was an increase in immobility as test progressed and upon repeated testing sessions. Marked interindividual differences in mice immobile behavior were observed when consistency of laterality was considered. Consistent-right-turners presented greater immobility in the first session and better test-retest reliability, indicating that for this group, the adoption of immobile behavior was faster and more reliable over time. Immobility was higher for side-consistent males than for side-consistent females in the first session. This difference became even greater when consistent-right-turner males were compared to consistent-left-turner females. These results reinforce the idea that side preferences of spontaneous rotational behavior may account for interindividual differences in animal models of depression.