Scientific Career and Research Findings:

My first series of studies examined the development of lateralization of function in two special populations - infants between two and four months of age and congenitally deaf children. Contrary to earlier claims, the infants showed no evidence of a right-ear (i.e. left-hemisphere) advantage for dichotically presented syllables.  The deaf children showed abnormal lateralization of function, in that, unlike hearing children, they processed faces better in the right rather than in the left visual field (indicating a left- rather than the normal right-hemisphere superiority for this ability), and failed to show many of the other visual asymmetries shown by the normally hearing.  The results thus demonstrated an unexpectedly strong influence of speech and aural language acquisition on the hemispheric lateralization of other functions.

Although the ontogenetic development of functional lateralization has continued as a theme throughout my research career, I soon moved into the study of the effects of early brain injuries on the maturation of this and other aspects of cerebral organization.  Some of the major findings, often derived from collaborative studies with magnetic resonance (MR) scientists at the Institute of Child Health, are summarized below for each of the principal domains of function I have investigated.

Speech and language.  Large, unilateral, hemiplegia-causing lesions of either hemisphere nevertheless spare speech and language, provided the injuries occur before the age of about five and are unaccompanied by seizures.  The same is true even for complete hemispherectomy on either side, provided the initial insult is congenital.  However, if unilateral congenital lesions are associated with a history of seizures beginning at some point during the first five years of life, then speech and language impairments do occur.  A striking example of this was found in a boy with unilateral Sturge-Weber disease accompanied by seizures, who remained mute until the age of nine, when he suddenly began to develop speech several months after his seizures were abolished by a left hemispherectomy.  The likely explanation of these seizure effects is that the electrographic abnormalities (or their pharmacological treatment) cause bilateral interference or even bilateral pathology.  This possibility is supported by evidence from another child, who, in the absence of seizures, has suffered from severe and permanent dysphasia and dyspraxia as a result of congenital bilateral lesions limited to Broca's area on the left and a closely corresponding area on the right.  On the basis of the above results, we also suspected the presence of bilateral pathology in the perisylvian or other oromotor areas in the affected members of a large family I have been studying who have an inherited speech and language disorder associated with severe orofacial dyspraxia.  Recent MR studies have now confirmed that, indeed, the caudate nucleus of the affected family members is abnormally small bilaterally.  On the basis of the behavioural phenotype identified through our detailed neuropsychological evaluations of the family, linkage studies have now identified the mutated gene FOXP2, the first gene to be linked to speech and language functions.

Perception.  There is a cost to the brain reorganization that underlies the remarkable preservation of speech and language in cases of early and extensive left hemisphere damage: the visuospatial functions normally mediated by the right hemisphere are "crowded out" by the higher priority speech and language functions that have been taken over by this hemisphere.  This is reflected as a significant impairment in visuospatial ability, though the impairment is not as great as that produced by early and extensive damage to the right hemisphere.  However, just as other  functions show full to partial escape after early damage, so do perceptual abilities. Examples we have uncovered include detection of targets in the visual field opposite a hemispherectomy in each of two infants, preserved tactile perception in the hand contralateral to a hemispherectomy in a 10-year-old whose initial insult occurred prenatally, and largely spared auditory verbal processing after congenital unilateral lesions of the perisylvian areas in hemiplegic children.  These numerous instances of preservation of  perceptual as well as language functions after early injury attest to the remarkable neural plasticity of the immature brain.

Memory.  Just as language functions are seriously impaired by early lesions to the perisylvian and oromotor areas only if they are bilateral, cognitive memory suffers severely only after bilateral damage to the medial temporal lobe and associated areas.  A case in point is our recent discovery of an unusual form of amnesia in patients who had suffered hypoxic-ischaemic episodes at some time during childhood.  All 15 such patients studied so far show severely impaired episodic memory (i.e. memory for everyday events), and yet their semantic memory (i.e. factual knowledge, general intelligence, language and literacy, social skills, etc.)  is  essentially normal, even when the amnesia-inducing episode occurred at birth.  Quantitative MR studies suggest that the responsible pathology is bilateral damage to the hippocampus, which was found to be reduced in volume bilaterally by 25-50% in each case.  It now appears from another investigation motivated by the above study that some pre-term infants requiring ventilation may also sustain bilateral hippocampal damage, although the volume reduction is much less marked (~15%) than it is after frank hypoxic-ischaemic episodes.  The associated memory disorder is also less marked, in that although such cases are significantly more forgetful than normal for everyday events, they cannot be classified as amnesic.  Together, the recent findings have led to a new proposal regarding the functional organization of the medial temporal lobe, namely, that context-free semantic memory depends mainly on the subhippocampal cortices, which link the sensory association areas to the hippocampus, whereas the hippocampus itself, located at the top of the hierarchy, is essential only for the most complex form of memory, namely, for context-rich episodes.