Advances in developmental amnesia

A team of researchers has embarked on a major programme to help children with memory impairment resulting from brain injuries. The five-year study will involve around 450 children who have experienced episodes of hypoxia - lack of oxygen - or ischaemia - inadequate flow of blood to the brain, leading to the syndrome of developmental amnesia (DA).

Led by Professor Faraneh Vargha-Khadem, one of the UK's leading cognitive neuroscientists, the Medical Research Council (MRC) funded study aims to understand the neurological causes of DA and develop rehabilitation methods for such children.

The study also involves UCL Professor of Cardiology John Deanfield's cohort of patients with congenital cardiac disease at Great Ormond Street Hospital, children who were born prematurely under the care of UCL's Professor John Wyatt at University College Hospital, and Professor Janet Stock's (UCL Institute of Child Health) cohort of patients with lung immaturity.

"All of the children involved in the study have suffered some event in infancy that has compromised the supply of oxygen to the brain. We have evidence to suggest that brain regions intimately involved with long term memory become damaged when there is lack of oxygen, and this can lead to severe problems with remembering everyday events and episodes," explained Professor Vargha-Khadem. "By employing neuropsychological, neurophysiological and magnetic resonance imaging (MRI) techniques, we can diagnose children with this type of memory disorder, relate their condition to the underlying brain abnormality, and hopefully develop approaches in due course to assist with the education and daily living difficulties of amnesic children."

"The injury may have occurred in infancy, but the memory disorder does not emerge until later in childhood, probably because the brain regions that serve long term recall of events and episodes mature only gradually. Parents of children with DA often report that the memory problems gradually appear from about age six or seven and seriously interfere with organization, learning, and independence by age nine or ten," said Professor Vargha-Khadem.

We all have two types of memory: semantic and episodic. Semantic memory refers to factual knowledge, for example, knowing that Paris is the capital of France, but not remembering where and when this knowledge was learned. Episodic memory relates to events in our lives, for example, what you had for breakfast this morning, or the route that you took to come to work this morning.

The hippocampus appears to be critical for episodic memory. Among the cohorts of children who have suffered hypoxia ischaemia, there are some with abnormality of the hippocampi and selective problems with memory for events and episodes of daily life. Although these children have pronounced problems with this aspect of memory, they have nevertheless been able to acquire an impressive amount of factual knowledge, and develop intelligence and literacy skills in the normal range. Therefore, they can remember that Paris is the capital of France, but they can't remember when they last visited this city, or where they stayed, etc. Professor Vargha-Khadem explained: "Typically, the neuropsychological profile of patients with DA shows a clear dissociation between episodic memory which is severely impaired, and semantic memory which is relatively spared.

This pattern of impaired and spared memory abilities in patients with DA is in contrast to the majority of adult cases with late onset of amnesia associated with hippocampal damage. Typically, such patients show deficits across both types of memory, episodic and semantic. Professor Vargha-Khadem said: "If you teach an amnesic adult something new, they will forget it, even if you were to repeat it many times. It is possible that some of the differences between adult-onset and child-onset memory disorders are related to the increased plasticity and compensation abilities of the immature brain. But increased plasticity alone cannot explain all the differences between the child and adult, and attention must be paid to the selectively of the hippocampal pathology, which in the case of the children with DA is very restricted.

Professor Vargha-Khadem added: "Experimental and clinical data suggest that children with early hippocampal damage grow into their episodic memory impairment - the memory problem becomes more noticeable and severe with increasing age - despite the general belief that early brain damage leads to less functional deficits than the same trauma acquired in adulthood. We believe that the gradual appearance of episodic memory problems in relation to increasing age indicates that the hippocampus gradually matures to subserve episodic memory functions. Information obtained from such studies can be used to identify as early in life as possible those infants at risk of developing serious memory problems, with a view to implementing remedial intervention programs to improve learning, and alleviate at least some of the profound socio-emotional and learning difficulties that often characterise the development of children with DA."

Another area of research in the unit relates to speech and language function and the ability of the immature brain to reorganize these functions when there is early damage to one cerebral hemisphere, often the so-called 'speech dominant' hemisphere. Young patients who sustain damage to the left hemisphere of the brain in infancy or early childhood do not develop chronic aphasia, in contrast to adults who do. The plasticity of the young brain allows speech and language functions to be transferred to the right hemisphere, resulting in clearly articulated and well structured language, even in cases where the left hemisphere has had to be removed completely to control severe convulsive fits.

These studies are among a number of events that contribute to making 2005 a key year for the unit. The team have already published two major reviews in their specialist fields in high profile publications. In February, a major review of research into FOXP2, the first gene associated with a profound speech and language disorder, was published in 'Nature Reviews Neuroscience.' In addition to covering the research on the behavioural and brain abnormalities associated with the mutation of FOXP2 in affected members of the KE family, the review also delved into research on the evolution of this gene in mammals, including our next of kin, the chimpanzee, and in song learning birds. "Speech and language disorders have long been known to run in families, and the mutation of one or more genes has been thought to be a likely cause," said Professor Vargha-Khadem. "The discovery of a mutation in the FOXP2 gene in a family with a speech and language disorder has enabled neuroscientists to trace the neural expression of this gene during embryological development, track the effects of this gene mutation on brain structure and function, and so begin to decipher that part of our neural inheritance that culminates in articulate speech."

In March, 'Current Opinions in Neurobiology' published a second review, this time comparing hippocampal-dependent functions in monkeys versus humans, and examining their maturational trajectories in each case.

Link: UCL's Developmental Cognitive Neuroscience Unit