Neurology of Learning Disabilities: What Will the Future Bring? The Answer Comes from the Successes of the Recent Past

Abstract

My involvement with learning disabilities (LD) began approximately 25 years ago, at a time when formal research training was uncommon for medical doctors, and the apprenticeship model was the way most of us began our research careers. Of all the topics I had heard Norman Geschwind--at that time my neurology chairman and mentor--speak about, language held particular fascination for me, perhaps because of my own experience with having to learn and become competitive in a new language at age 15. After completing my residency, I began to work on anatomic brain asymmetries in an attempt to further understand the biological specialization of the left hemisphere for many aspects of language function. Then, Geschwind invited Friedrich Sanides, a late student of Oskar and Cecile Vogt (Brodmann was an earlier student), to travel to Boston from West Germany and spend a year here teaching me about cytoarchitectonics as a neuroanatomical tool to deepen the study of brain asymmetries. This took place in 1977. In 1978, Geschwind suggested that I take over a project begun by Dr. Brooke Seckel, a resident two years my senior, who had decided to change careers (I often wondered whether it was the project that did it). It concerned the study of a brain from an individual with developmental dyslexia who had died as a result of a fall down an elevator shaft. His brain had become part of the Yakovlev Collection at the Boston City Hospital, where all of this took place. Brooke had been testing the hypothesis, advanced by Geschwind, that the brain of a dyslexic would show two small plana temporale. In 1968 Geschwind and his then student Walter Levitsky had shown in the general population that the planum temporale, comprising part of the auditory association cortex involved in linguistic functions, was large on the left and small on the right, perhaps explaining language lateralization to the left hemisphere. Some normal brains showed the reverse asymmetry, and still others showed lack of asymmetry, with a large planum on both sides. It made sense to Geschwind, a believer in the phrenological principles that had been launched at the start of the nineteenth century, that in a condition with poor language function, the plana would be bilaterally small (in one interpretation of phrenology, more brain tissue means more function). Here is where I became involved. As it turned out, the plana temporale were not small in the dyslexic brain, but were shown to be large in several specimens of dyslexic brains; later, additional alterations in planum asymmetry were reported. Animal experiments showed that under some conditions symmetry in a cortical area could be a response to a disorder of neuronal migration. In fact, the first dyslexic brain and many other brains showed cortical dysplasias and ectopias resulting from abnormal neuronal migration to the cerebral cortex during mid-gestation. This finding began a productive area of research that lasted the better part of two decades. Initially, it was important to establish that these focal cortical malformations significantly disrupted cortico-cortical organization and cortico-thalamic interactions, to explain linguistic deficits, which was done after it was possible to model the anomalies in experimental rodent models. Second, it was necessary to show that the cortical malformations and the cortico-thalamic anomalies produced (and were not simply correlated with) functional deficits. Thus, it was shown that induction of cortical malformations in the rat, similar to those found in the dyslexic brain, produced a variety of cognitive deficits, and that disturbances in cortico-thalamic networks were associated with perceptual deficits involving processing of rapidly changing sound stimuli. Thus, a causal interaction was established between focal disorders of neuronal migration and some behaviors that mimicked deficits found in populations of dyslexic individuals. A second focus of research concerned the origin of the cortical and thalamic malformations in the dyslexic brain. …