We’ve all had that annoying feeling when we fail to find a word that’s just at the tip of our tongues. Usually, these moments are passing nuisances, but they are a more severe impediment for a British family known as JR. Eight of them suffer from an unusual problem with “semantic cognition” – the ability to bind words to their meanings during thought or communication.
They can’t remember words, names, or topics of conversation – all of us get this, but the JR family experiences a more extreme version. They make errors in everyday conversations when they use words with related meanings in the wrong places. Their comprehension falters to the extent that reading books or following films is hard work.
These difficulties have caused them much social anxiety, and hampered their ability to cope with school and work. But for scientists, they are undeniably exciting because they seem to stem from a single errant gene. If that’s the case, the gene apparently affects the intertwining of concepts and language, but not any other mental abilities – the affected family members are otherwise intelligent and articulate. The JR family could lead us to new insights about language, thought and memory, just as similar families have done in the past.
David Skuse from University College London first met the JR clan when one of their members– a six-year-old boy – was referred to his clinic at Great Ormond Street Hospital because of problems with remembering words. Skuse realised that the boy’s mother shared the same problem, and both she and her son used stock answers to divert attention from their difficulty. She, for example, would say that she couldn’t remember the English version of a word, even though she was a native English speaker.
Skuse probed further, and found that many members of the extended family, across four generations, have the same problem. “This illustrates how interesting new findings sometimes crop up unexpectedly,” says Dorothy Bishop, who studies language impairments at the University of Oxford and has worked with Skuse before. “The intriguing pattern of deficits in this family could easily have been missed, because the problems are rather subtle and don’t fall into any pre-existing category of developmental learning difficulty.”
Bishop adds, “I suspect that many clinicians seeing such a child would end up diagnosing autism spectrum disorder and would not pick up on the memory difficulties. Several affected family members were described as shy, withdrawn, or poor at socialising, yet these problems appear to be secondary to the verbal memory problem, rather than evidence of a core autistic deficit.”
Skuse’s team, including Josie Briscoe and Rebecca Chilvers, have been working with the JR family ever since to understand the nature of their difficulty. They interviewed and tested all the affected family members. About half of them share the same problems, which develop from an early age and don’t get progressively worse. This suggests that a dominant gene is involved – a single copy can cause the full suite of problems.
Their difficulties became apparent whenever they had to remember words, or extract meanings from them. Compared to other people of the same age, they weren’t as good at: remembering story details; identifying related words; recalling the names of unfamiliar things; extracting information from passages they had heard; or recalling word lists even if they were tested immediately.
These difficulties are unusual in how specific they are – they all involve matching words to ideas. The family didn’t have any such difficulties if they were asked to remember nonsense words, or numbers. They understood grammar and they could extract meaning from pictures. They were otherwise highly intelligent, and many scored score above the board on several non-verbal tests.
“We believe the core deficit is in the binding of concepts, meaning and words,” says Skuse. “That ‘binding’ is much weaker than would normally be the case, so the cues we use to remind us about that word we are searching for aren’t as accessible to them as they are to most people.” Something in their brains, at the crossroads of memory and language, doesn’t quite work properly.
Briscoe and Chilvers also scanned the family’s brains using magnetic resonance imaging (MRI). They found that affected members had less grey matter – the stuff that includes the bodies of neurons – in several regions in the inferior temporal cortex – an area at the bottom of the brain, thought to be involved in semantic cognition.
Many JR members have used their smarts to disguise their problems with elaborate techniques, often involving complex visualisation and mnemonic strategies. “You wouldn’t notice anything unusual about them in casual conversation,” says Skuse. “They are sociable and empathic, and they can hold interesting conversations about a wide range of topics.”
Still, the family find it hard to cope with their condition. “They are always aware that they may make socially inappropriate comments or responses,” says Skuse. “This does feed their anxiety about social situations, particularly their difficulty following group conversations, as at a party.”
The task ahead is clear: find the gene responsible for the JR family’s challenges. There are few people better suited to the task than Simon Fisher from the Max Planck Institute for Psycholinguistics. In 2001, his team studied another British family known as KE, which suffered from language problems far more severe than those of JR. They have trouble with grammar, writing and comprehension, and they can’t coordinate their mouths and faces well enough to speak fluidly.
Fisher identified FOXP2 as the gene behind their problems. It was the first time that a gene had been implicated in a speech and language disorder and FOXP2 was quickly dubbed as “the language gene”. (It’s actually much more complicated than that – full story here) Now, Fisher is working together with Skuse’s team to analyse the JR family’s genes. “Tracking down the gene will be a challenge but the rapid advances in DNA sequencing technologies can only help,” he says. “If a responsible gene can be identified then it could open up a new molecular window into human cognition, which would be rather exciting.”
Reference: Briscoe, Chilvers, Baldeweg & Skuse. 2012. A specific cognitive deficit within semantic cognition across a multi-generational family. Proc Roy Soc B. http://dx.doi.org/10.1098/rspb.2012.0894
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