Gordon F. Sherman

Planum temporale asymmetry, reappraisal since Geschwind and Levitsky

Abstract This study utilizes the same brains reported by Geschwind and Levitsky [Science161, 186–187, 1968] and looks for indirect evidence for the Geschwind Hypothesis [Geschwind and Bahan, Proc. natn. Acad Sci., U.S.A.79, 5097–5100, 1982; Geschwind and Galaburda, Arch. Neurol.42, 428–459, 521–552, 634–654, 1985] that testosterone slows down the development of the left hemisphere and allows for compensatory growth of the right in order to produce a graded shift away from standard cerebral asymmetry. There are graded asymmetries of the planum temporal in the population, averaging on the side of leftward asymmetry. Changes away from asymmetry, however, involve increase in the size of the smaller side, rather than decrease in the size of the larger. Thus symmetrical brains differ from asymmetrical brains by having two large plana, each planum being equivalent in area to the larger planum of the asymmetrical cases. If testosterone has an effect in modifying brain asymmetry, it does not appear to do so by slowing one side and allowing the growth of the other, but rather through its promotion of the growth of the small side. We consider some likely developmental mechanisms for this action and offer some anatomical and functional comments.

INDIVIDUAL VARIABILITY IN CORTICAL ORGANIZATION: ITS RELATIONSHIP TO BRAIN LATERALITY AND IMPLICATIONS TO FUNCTION

The human brain and the brains of most mammals studied for this purpose demonstrate hemispheric asymmetry of gross anatomical landmarks and/or architectonic cortical subdivisions. The magnitude as well as the direction of these cortical asymmetries vary among individuals, and in some species there exist significant population directional biases. The magnitude, if not the direction, of cortical asymmetry is found to predict for relative numbers of neurons comprising a given pair of hemispheric architectonic homologues such that the more asymmetric the region is, the smaller the number of neurons. Similarly, the more asymmetric a region is, the smaller the density of interhemispheric connections and (probably) the greater the density of intrahemispheric connections. Developmentally, the decrease in the number of neurons characterizing the more asymmetrical regions appears to reflect mainly increased unilateral ontogenetic cell loss, and diminished callosal connectivity might signify increased developmental axonal pruning. These relationships between cell numbers, callosal connections, and presumed intrahemispheric relationships can be entertained to explain variability in anatomo-clinical correlations for language function and aphasia between left- and right-handers and men and women.

BRAIN AND BEHAVIORAL ASYMMETRIES FOR SPATIAL PREFERENCE IN RATS

Rats were handled daily for 3 min between birth and weaning, or were nonhandled controls. When adult, 4 males from each litter received a right neocortical ablation, a left ablation, a sham operation, or no surgery. A month later all animals were tested in the open field for 4 days, and their initial direction of movement from the starting square (whether right or left) was recorded. Non-handled rats with intact brains (sham-operated and no-surgery groups pooled) had a mean directionality score near zero, thus indicating no right-left spatial preference. However, non-handled animals without a left hemisphere were significantly more biased in going to the ipsilateral side than were their siblings with right-brain ablations. Thus, in non-handled animals behavioral symmetry in making spatial choices is due to balanced brain asymmetry, in which the right hemisphere biases the animal to move leftward while the left hemisphere acts to inhibit this response. In contrast, intact handled rats had a significant preference to go to the left, thus suggesting that in handled animals the right hemisphere controls spatial preference.

Dyslexia linked to talent: Global visual-spatial ability

Dyslexia has long been defined by deficit. Nevertheless, the view that visual-spatial talents accompany dyslexia has grown, due to reports of individuals with dyslexia who possess visual-spatial strengths, findings of elevated incidence of dyslexia in certain visual-spatial professions, and the hypothesis that left-hemisphere deficits accompany right-hemisphere strengths. Studies have reported superior, inferior, and average levels of visual-spatial abilities associated with dyslexia. In two investigations, we found an association between dyslexia and speed of recognition of impossible figures, a global visual-spatial task. This finding suggests that dyslexia is associated with a particular type of visual-spatial talent-enhanced ability to process visual-spatial information globally (holistically) rather than locally (part by part).

The Development of Induced Cerebrocortical Microgyria in the Rat

Placement of a freezing probe on the skull of neonatal rats produces four-layered microgyria, complete with a lamina dissecans and microsulcus. We studied the developmental course of this induced microgyria under light microscopy by examining changes in neurons, glia, and macrophages following a focal freezing insult on the day of birth (postnatal day [P]0). The destruction of neurons and glia induced by the freezing probe extends through the cortical plate and occasionally through the subplate, but the pial membrane appears undamaged and radial glial cells, while damaged, are not eliminated. Reactive astrocytes and macrophages arrive in the damaged area within 24 hours of the injury, and repair of the damaged tissue peaks within the first week. Damaged radial glial fibers regrow, and supragranular neurons migrate through this damaged area, also within the first week. The newly formed supragranular layer overlies the cell-free area. The damaged cortex begins to assume its adult-like microgyric appearance from P5 to P10. On PI 5 and P32, long glial fibers, resembling radial glia, are present and are immunoreactive for glial fibrillary acidic protein and radial glial fiber antibodies (vimentin and Rat-401). No such fibers appear at this age in the non-microgyric areas or in normal brains. We conclude that microgyria formation may be the consequence of brain repair mechanisms occurring during neuronal migration to the neocortex, and that it appears to preserve primitive features characteristic of the developing cortex.

Freezing Lesions of the Developing Rat Brain: A Model for Cerebrocortical Microgyria

Cerebrocortical microgyri were induced by placing a freezing probe on the skull of P0 and PI rat pups. Freezing lesions resulted in laminar necrosis of the infragranular layers and the subsequent migration of supragranular neurons through the region of damage. The result was most often a region of four-layered microgyric cortex consisting of a molecular layer, a thickened layer ii, a lamina dissecans (corresponding to the necrotized layers IV, V, and VIa), and a neuronal layer iv which corresponded to layer VIb of the intact cortex. Immunocytochemical investigation of the microgyric cortex with antibodies to neurofilament, glial fibrillary acidic protein and glutamate showed more widespread disruption of neocortical architecture than could be seen from Nissl preparations. In contrast, vasoactive intestinal peptidecontaining neuronal bodies appeared to be distributed normally in the microgyric region although their processes were sometimes distorted. These results are considered in the light of previous research on induced microgyria, and possible implications for the behavioral consequences of focal, developmental neuropathologic lesions are discussed.

Neuroanatomical anomalies in autoimmune mice

SummaryThe cerebral cortex was examined for sings of pathology in the NZB, BXSB, and MRL autoimmune strains of mice, crosses among these strains, and control mice. Previously, we reported that 20% of NZB mice had ectopic collections of neurons in layer I of the cortex. In this study we replicated this finding in the NZB, and extended it to the BXSB strain, and BXSB/NZB and MRL/NZB hybrids. The MRL strain, however, did not have a large number of individuals with brain anomalies. Thus, a number of autoimmune mice strains and hybrids develop brain anomalies, although at least one autoimmune strain does not. We suggest that in certain autoimmune strains maternal autoantibodies cross the placenta and damage the developing fetal brain, and that these strains may be useful experimental models for studying the development of brain anomalies seen in the dyslexic human.

Spatial learning, discrimination learning, paw preference and neocortical ectopias in two autoimmune strains of mice

NZB and BXSB mice were given a battery of behavioral tests including paw preference, water escape, Lashley III maze, and discrimination learning. Their brains were then evaluated for cortical ectopias. The incidence of ectopias was 40.5% in NZBs and 48.5% in BXSBs. In the NZB strain left-pawed ectopic mice (both male and female) had the fastest swimming time in the water escape test, while right-pawed ectopics were the slowest. The same findings were obtained for left- and right-pawed ectopic BXSB males, but not for the females. However, on discrimination learning the BXSB males had the exact opposite pattern: right-pawed ectopics were the best learners while left-pawed ectopics were the worst. Male BXSBs and both male and female NZBs were manifesting autoimmune disease at the time of testing, while female BXSBs were not, suggesting that autoimmunity is a necessary background condition for the differential expression of ectopias and paw preference upon learning processes. The finding that the left-pawed ectopic BXSB mice, who were the poorest learners in the non-spatial discrimination learning test, learned best in the spatial water escape test is in agreement with the Geschwind hypothesis that pathological events during brain development may, in some instances, produce superiority of function.

Brain abnormalities in immune defective mice

Mouse strains with or without immune disorders were examined in order to further assess the incidence of brain anomalies in immune-disordered strains. The brain was examined in Nissl-stained serial sections under a light microscope for the presence of abnormalities, with specific attention to ectopic collections of neurons in layer I of the neocortex, as reported in the autoimmune New Zealand Black (NZB) and BXSB strains. The present study was designed to survey additional strains with immune disorders (Snell dwarf, C57BL/6J-nu/nu, BALB/cByJ-nu/nu, and SJL) and 7 control strains without immune disorders. In addition, we attempted to replicate past findings in the highly affected BXSB strain and the MRL/1 strain, which develops autoimmune disease, but has a low incidence of brain abnormalities. The largest number of brain abnormalities (20-40%) were seen in the C57BL/6J-nu/nu, Snell dwarf and BXSB strains. The anomalies in the C57BL/6J-nu/nu and BXSB mice consisted of ectopic neurons in layer I of the neocortex, whereas the Snell dwarf mice had either neuron-free areas in the cortex, or rippling of cortical layers II-IV, and one case had agenesis of the corpus callosum. Between 4% and 8% of the mice from the SJL, MRL/1, and MRL +/+ strains had either neuron-free areas in the cortex or ectopic neurons in layer I. The BALB/cByJ-nu/nu and control strains did not have any cortical abnormalities. Future studies will be designed to determine whether immune-based alterations to the developing brain are responsible for the brain anomalies present in immune-disordered strains.

Interhemispheric connections differ between symmetrical and asymmetrical brain regions

Coronal sections from the brains of male Wistar rats that underwent corpus-callosectomy in adulthood were stained with Cresyl Violet for Nissl substance or by the Fink-Heimer method for terminal axonal degeneration. Measurements of volumetric asymmetry of neocortical region SM-I were made, and the per cent of terminal degeneration computed. As in previous studies, there was a negative correlation between asymmetry coefficient and total (right plus left) architectonic volume, indicating that symmetrical brain regions are larger than the average of the corresponding regions in asymmetrical brains. It was also found that as volumetric asymmetry increased, the per cent of axonal termination decreased, partly as a result of a decrease in the number of patches of callosal axonal termination. These results are interpreted in the light of what is known about the ontogenesis of callosal connectivity, and mechanisms for the development of architectonic asymmetry in the cerebral cortex are postulated.