Arnold B. Scheibel

The Hippocampal-Dentate Complex in Temporal Lobe Epilepsy.: A Golgi Study

The hippocampal‐dentate complex of 11 patients operated for temporal lobe epilepsy was studied by variations of the Golgi method. A spectrum of changes in hippocampal pyramids and dentate granular cells was found, ranging from minor pathology along single dendrites to massive degenerative changes involving many neurons, and culminating in cell death. Loss of dendritic spines and development of nodules along dendritic shafts were the mildest pathological changes. That pathology could be highly localized and could vary in degree in the same patient suggests an ongoing process rather than one due to discrete cortical insult in early life.

The postnatal development of the motor speech area: A preliminary study ☆

This preliminary study follows the maturation of motor speech areas and their adjacent orofacial motor zones in the right and left hemispheres of the human infant from 3 months to 72 months of age. Quantitative studies of basilar dendrite patterns of layer 5 cortical pyramids are reported in 17 age-graded subjects. The sequence of developmental changes is characterized by early (3 month) prominence of orofacial motor zones over motor speech areas and of the right hemisphere over the left as expressed in total basilar dendritic length and the length of proximal order dendritic segments. The complex series of changes which follow appear to involve increase in number and marked increase in length of the developing distal order segments and possible shortening of the proximal segments. During a variable sequence of apparent growth spurts and resorptions, dendrite arborizations of the motor speech areas overtake and exceed those of orofacial musculature and the total length of dendrite systems on the left finally exceeds those on the right, although even in the most mature group, (42-72 months), distal segment length in the right motor speech area still exceeds that of the left. The early structural primacy of right-sided dendrite systems and the progressive shift to left-sided primacy is considered in the light of the presence of a long phylogenetic and ontogenetic history of gross anatomical asymmetry favoring the left side. The possibility that developmental patterns of the cortical macroenvironment and microenvironment may be dissociated with the microenvironment depending heavily on epigenetic factors receives support from recent data suggesting the existence of a time window or critical period during which primary language proficiency must be attained if normal lateralization of language function is to occur.

Differential Changes with Aging in Old and New Cortices

Throughout recorded history, the tragedy of aging has been, not that it comes, but that so often, it brings with it a host of changes in the psychosocial patterns of the individual, changes that may degrade and enfeeble the most gallant and competent. We cannot fail to share, as psychiatrists and as human beings, the pain of subject, family, and friends walking this bitter path together. But we must not lose sight of the fact that where substrate mechanisms can be identified, there is hope, if not of a way back, then at least of a gentler path which may give to more of the aged, some measure of those much-celebrated compensations of age.

On the possible relationship of cortical microvascular pathology to blood brain barrier changes in Alzheimer's disease

A group of alterations in the structure of cortical microvessels is described in the brain tissue of neuropathologically confirmed patients with Alzheimers disease. These changes include irregular thickening of the vessel walls, infiltration with amyloid and the serum P component of amyloid, loss of the perivascular neural plexus and the frequent occurrence of pits and lacunae in vessel walls. The possibility that these alterations may be related to blood brain barrier defects is suggested.

The Rapid Golgi Method. Indian Summer or Renaissance

It is not unreasonably maintained that the golden days of Golgi morphology were already numbered by the turn of the century. The great flowering of descriptive histology in the hands of Golgi, Cajal, Van Gehuchten, Lenhossek, Held, Retzius, P. Ramon, and others was the kind of phenomenon which can only occur at one stage in the life of a powerful investigative technique. Once the maximal exploitation of its powers had occurred and “the cream was skimmed”, a more realistic assessment of its role in neurologic research was possible. It could then become part of the technological armamentarium available to all investigators and might expect the continued, if less heralded, utilization it had earned.

Dendritic Structure and Language Development

Quantitative studies of neuronal dendritic patterns in language-related cortical areas reveal progressive changes as language facility develops in the infant. Histological development of the right (non-language-dominant) hemisphere appears precocious at birth, but is gradually overtaken and surpassed by the left (language-dominant) hemisphere as language capability develops. It is suggested that a critical time window exists for such changes during the first 6–8 years of life. However, gross changes in the perisylvian language zone are found in the fetus, in early hominids and in apes and may represent a much more primitive stage of preparation for hand and language function.

The Development of Somatosensory Thalamus in Mammals

Consideration of the ontogenetic development of sensory thalamus and its interrelations with cerebral cortex is fraught with numerous problems, both technical and conceptual. The histological matrix is one of the most complex in the entire nervous system, comprising as it does a variety of highly specialized pre- and postsynaptic elements, linked together in part, by intricate synaptic ensembles or glomeruli (Famiglietti, 1970; Harding, 1971; Jones and Powell, 1969; Ralston, 1971; Ralston and Hermann, 1968; Scheibel et al., 1972; Spacer and Lieberman, 1974; Szentagothai, 1963; Szantagothai et al, 1966; Tombol, 1966). The physiological characteristics of this area are equally varied and have resulted in the development of a number of models, none of which is completely satisfying (Andersen and Andersson, 1968; Andersen et al, 1964; Purpura, 1969; Scheibel and Scheibel, 1966, 1967; Scheibel et al., 1973; Schlag and Waszak, 1971; Steriade and Wyzinski, 1972; Waszak, 1974). Knowledge of thalamic synaptic chemistry and pharmacology is still limited, although substantial advances have been made in the past decade (Andersen and Curtis, 1964; Gerebtzoff, 1970; Mc Cance et al., 1968; Mc Lennan et al., 1968). Finally, the functional role and clinical significance of thalamic activity remain enigmatic despite an abundant literature and the apparent success of a limited repertoire of surgical intervention (Cooper, 1969; Cooper et al., 1971; Hassler, 1959; Jasper and Bertand, 1966; Spiegel and Wycis, 1952; Van Buren and Bork, 1972).

Specific Postnatal Threats to Brain Development: Dendritic Changes

Our approach to the problem of brain damage in infancy and childhood is a bit different from that of some of the other contributors to this book. For we have had the opportunity to see what are presumed to be remote consequences, structural and behavioral, in a series of patients who have come to surgery in middle life with various patterns of intractable partial epilepsy. (8. 12) The seizure equivalent states and the electrical storms which have been shown to accompany them have been found characteristically associated with the temporal lobes of these patients (17) slightly more than half of whom have histories of difficult and prolonged deliveries or infantile febrile convulsions.

Valiant neurons and inexorable aging

Despite an enormous number of variables, both genetic and epigenetic, most neuronal systems eventually show age-related changes. Although no simple description is possible because of the age, species, locus and state specificities of these alterations, the robust metabolic-synthetic load carried by most neurons is eventually reflected in the regressive changes shown by increasing numbers of them. Nonetheless, their remarkable capacity for selective dendritic and spine growth into the period of advanced old age underlines the biological resiliency built into these post-mitotic elements.

The right way, the wrong way, and the army way: A dendritic parable

We suggest that neither selectionism nor constructivism alone are responsible for learning-based changes in the brain. On the basis of quantitative structural studies of human brain tissue it has been possible to find evidence of both increase and decrease in tissue mass at synaptic and dendritic levels. It would appear that both processes are involved in the course of learning-dependent changes. The neurosciences have seen more than their share of impassioned conceptual dualities. Reticularism versus neuronism and “soup versus spark” synaptic transmission dynamics are two among many that come to mind. It is interesting to recall that neural reality was finally determined to encompass both poles of each duality. Neurons were indubitably separate entities but in the case of gap junctions, virtually continuous through the agency of connexions establishing structural continuity for ion flow. Neurons clearly communicate through the agency of neurotransmitter release but “electrical” transmission remains a reality at gap junctions. I would suggest that we may be dealing with another impassioned duality in the matter of “selectionism versus constructivism.” Quartz & Sejnowski (QS 1975; 1988) and in a number of other findings. Our own quantitative histological studies of human cerebral cortex argued strongly for causal links between computational complexity and structural complexity (Scheibel et al. 1990). Thus dendritic elaboration in the primary sensory cortical representational area for hand and fingers was significantly greater than that in the adjacent area for trunk representation. Furthermore, there were “suggestive associations between the complexity of dendrite systems of the handfinger zone of the primary receptive area and the nature of the work with which the individual had been associated during his/her working life” (Scheibel et al. 1990, p. 85). Furthermore the conjoint development of language facility and waxing dendrite elaboration in Broca’s area of the language-dominant hemisphere (Simmonds & Scheibel 1989) provided correlative if not causal relations between escalating cognitive demands and expanding neuropil. Arguments can also be advanced for selectionism, however. In several series of electron microscope studies performed on rodents, measurable and significant decreases in the number of synaptic terminals in cortical axo-spino-dendritic synapses accompanied exposure to enriched environments (e.g., Mollgard et al. 1971). Individual synaptic terminals showed significant increase in the length of the postsynaptic thickening, thereby suggesting the presence of fewer, but larger and more effective synapses in environmentally enriched animals. Further analysis of these changes indicated that the effects of enriched environmental input as expressed in loss of synaptic terminals and enlargement of the remainder actually increased with age (Diamond et al. 1975). And the enriched rats were quicker maze-learners than their nonenriched mates (Diamond 1988)! Assuming that a complex interweaving of dendritic/synaptic gain and loss are involved in the maturation-learning process, a third mechanism seems intertwined with these two, adding to the richness and subtlety of the process. Quantitative comparisons of dendritic tissue in Broca’s area of left and right hemispheres revealed an unexpected result (Scheibel et al. 1985). There was no significant difference between the total dendritic length of neurons on either side. What did differ was the amount of dendritic length ‘invested’ in various portions of each dendritic tree. On the right, the non-language-dominant side, most of the dendrite length was involved in the first three orders of dendrite branching. On the language-dominant side, a much greater proportion of dendrite length was devoted to the outer branches (fourth, fifth, sixth order dendrite branches, etc.). Note that the inner, lower order branches developed earlier in the developmental history of the individual, while the outer branching segments developed later. Thus both temporal patterns of development and position on the dendrite tree were significant parameters in CNS growth and maturation. Note also, that successive additions to the periphery of the dendrite ensemble should (at least theoretically) not affect the more central parts of the dendrite system where synaptic patterns had presumably already been established. However, more than a tidy “add-on” effect was noted here. Our data (Simmonds & Scheibel 1989) strongly suggested that along with the pattern of use-dependent centrifugal growth there was also a related (and presumably use-dependent) partial resorption of lower order branches more centrally located within the dendrite ensemble. Simultaneous involvement of cortical dendritic tissue gain and loss during the maturation-learning process argues for the inextricable combination of constructivist and selectionist processes. Neural constraints on cognitive modularity?