Memory, p.33
Memory, page 33
But that’s simply not so, according to some surprising new research. A memory is anything but static. Resurrecting a memory trace appears to render it completely fluid, as pliable and unstable as the moment it was first formed, and in need of fixing once again into the brain’s circuitry. Any meddling with this fixing process could alter the trace – or even erase it completely. Simply retelling a tale may be enough to change that memory for good. Long-term memory is effectively a myth.
What does it mean? Who are we if our personal memories are so volatile that the very act of remembering might allow past experiences to vanish into thin air? How can we trust our minds at all? Well, common sense tells us that our brains aren’t that bad at keeping a record of our lives. So maybe what needs changing here is how we think about memory. A memory trace that goes all floppy every time it gets used only seems a disaster if you believe the brain to be something like a computer where data needs to be preserved in fixed form. Fluidity, on the other hand, may be precisely what is required for memory to work as something much more organic – a living network of understanding rather than a dormant warehouse of facts.
The standard story on memory is that the brain first captures a snapshot of each moment. The firing of a particular arrangement of neurons leaves them electrochemically aroused and ready to fire again in the same pattern, primed to recreate the just-happened experience. But this short-term memory trace lasts barely a few seconds and needs to be turned into something more permanent by a complex cascade of brain events. One of the great goals of neuroscience is to unravel the fine detail of this process of memory consolidation.
In the past few years it has become clear that the transient sensitisation of nerve junctions – the synapses connecting neurons together – leads to an almost immediate swelling. The synapses bulk up with more receptors and more neurotransmitters, and become inflamed to make a stronger connection. Then after a few hours, the neurons begin to physically grow, sprouting new and thicker connections to wire in a permanent memory trace. A mass of protein, produced by a range of genes, will be employed to build a remodelled brain circuit.
What makes the process of consolidation so complex is that as well as the neural-level rewiring, the memory trace also migrates. When a memory pattern is fresh, it is stored in specialist memory organs such as the hippocampus, deep within the brain. But over a number of days, weeks or even years, it settles back across the brain and becomes lodged in more general areas. Rather like computer files being transferred from hard disc to back-up tape, old memories eventually get consigned to the vast, wrinkled vaults of the cortex.
Neuroscientists felt this hierarchical filing system was a little long-winded. But it sounded reliable. Once fossilised in some dusty forgotten corner of the brain, a memory trace might become a little harder to retrieve, yet it ought to remain absolutely stable. This was the accepted story until a very simple experiment blew it away.
To study memory consolidation, researchers interfere with steps in the fixing process in order to test their influence on long-term recall. While doing this kind of work, researchers including Karim Nader of McGill University, Montreal, and Joseph Ledoux of New York University noticed something odd. They trained rats to associate an electric shock to their paws with a darkened box. The rats learn that the box is ‘nasty’ and freeze the next time they are put back. If, a few days after training, the animals were given a drug to stop protein synthesis before being reminded of the conditioning stimulus – the sight of the training box – it made no difference to their ability to remember it. The memory seemed fixed and safely stored. But if the rats had a brief reminder of the stimulus just before the drug was given, then a memory that should have been fixed and stable seemed to be erased.
What did it mean? Nader and LeDoux coined the term reconsolidation, suggesting that the act of recalling something renders it flexible, giving the chance to expand or generalise the original memory trace – a form of reaffirmation. The drug given to the rats prevented this reconsolidation step, somehow leading to the decay of the original memory. The publication of their results in Nature caused quite a stir, and no small amount of scepticism.
But in a detailed follow-up published in the journal Neuron late last year, they made a more convincing case. Again the rats were put in a box and given an electric shock to their paws, and would freeze the next time they were put in the box. According to traditional consolidation theory, such memories are fixed locally by protein changes in a matter of hours and then safely filed to long-term storage in the cortex after about a month. The team waited a full 45 days to test the rats, by which time the memory trace should have been quite immune to interference.
As expected, the rats that were given no reminders of the original experience showed no memory loss when injected with the protein-blocking drugs – they froze when tested. Likewise the complete destruction of the hippocampus left the memory intact, as it was now resident in the vaults of the cortex.
But if the rats were reminded of the sight of the box just before the drug was injected, the result was precisely the opposite. Now the protein-blocking drug created amnesia. And destroying the hippocampus also erased the fear association. The rats nosed about the box quite unconcerned. At both the synaptic level and the anatomical level, it was as if the consolidated memory had been released and needed to undergo the whole fixing process again if it were to be remembered. Recall had made an established trace shaky.
‘The dogma was that once a memory trace has been consolidated, it is permanent,’ says Nader. ‘But here it was labile – subject to interference in exactly the same way as a brand-new experience.’ The old static picture of memory could not be right. ‘We were showing memory to be something incredibly dynamic.’
Some researchers, such as James McGaugh and Larry Cahill of the University of California at Irvine, were sceptical. They didn’t think this ‘reconsolidation’ effect would be replicated. Cahill describes the work as ‘iffy’ and feels a simpler interpretation of the results – such as some kind of suppression mechanism – might still be forthcoming.
But confirmation has been pouring in. ‘Reconsolidation has now been demonstrated in all sorts of situations and all sorts of animals – crabs, slugs, chickens,’ says Nader. ‘This tells me it’s a basic feature of the memory system.’ He now believes that there’s no longer any question about whether the effect exists. Instead he’s keen to find out what it means.
For example, does it imply that our memory is always unreliable? Clearly not. But it isn’t completely stable either. But even if reconsolidation doesn’t yet convince all memory researchers of that fact, there’s another reason to suggest instability is inevitable – molecular turnover. The proteins, fats and other complex molecules making up a cell generally last an astonishingly short time, anything from a matter of days down to just a few minutes, and so need constant replacing. Cells are not static creations but fragile things that are continually renewing themselves.
For brain cells – where their shape and synaptic structures determine their function – the issue is all the more acute. The protein filaments that give the cells their internal shape have a half-life of just a few minutes. And the receptor proteins that stud the synapses need replacing every few days. As Joe Tsien, a neurobiologist at Princeton University in New Jersey, says, the brain you have this week is not the one you had last week. Even the DNA needs to be repaired. So if ‘you’ are essentially a pattern of synaptic connections, a tangled web of memories, then there is a big problem of how this pattern endures. ‘I don’t know how people ever got this static picture of the brain,’ says Tsien. ‘A memory trace would have to be a dynamic thing just because of molecular turnover.’
The idea that we enjoy a photographic record of the past is a myth that has also been exploded by experiments such as the eyewitness research of Elizabeth Loftus of the University of California at Irvine. Here, subjects incorporated overheard details about a staged bank robbery or car crash in their own memories of the event. Loftus’s work seems clear proof that our memories are fluid creations that can be edited or embroidered.
And the more you think about it, the more such dynamism makes sense. Susan Sara of the Pierre and Marie Curie University in Paris, who found indications of a reconsolidation effect in her own experiments in 1997, says the real problem for the brain is not how well it can preserve the past but how successful it is at integrating new learning with old learning. Memories exist to make sense of the present – to recognise and understand the world – and the brain needs to be able to optimise all its circuits, strengthening or generalising some connections while weakening or erasing others. Reconsolidation may seem a radical and unnecessary step for a brain that just wants to be a dormant warehouse. But, Sara says, if a memory becomes completely plastic every time it is roused, then it can be refiled in a carefully updated way. Active choices can be made about whether to merge the old and the new – or by contrast, to reinforce their separateness.
‘It’s just an accident that reconsolidation has been demonstrated by erasing memories,’ says Sara. This is what is creating the misconception of the shaky trace. It’s easier to interfere with the reconsolidation in this way than it is to show the opposite – a memory being strengthened. But Sara and her team hope to show that drugs which arouse the brain will reinforce an activated memory.
The bottom line is that there is no reason to believe that rousing your personal memories is a risky affair, she says. Thinking about the past probably does require a surprisingly drastic change in the state of a memory trace. They may not be simple snapshots of events that are passively read out but constructive and ever changing. However, there is no cause to think the brain does a poor job of reintegrating a memory that has been roused. Our memories may not be an infallible recording device, but frequently recalling a childhood memory seems more likely to reinforce it than erase it.
By the same token, the reconsolidation finding goes a long way to support the claims of psychologists like Loftus, who say that society needs to take better account of the essentially reconstructive nature of human memory. Loftus first demonstrated more than thirty years ago the ease with which the memories of eyewitnesses could be biased. But, she says, it is only recently that advances in DNA testing have brought a spate of wrongful convictions to light, forcing US legal authorities to take the issue more seriously. Loftus has also been at the centre of the false memory syndrome controversy, where the suggestive questioning style of psychotherapists has been blamed for creating imagined incidents of childhood abuse.
‘In most avenues of life, it doesn’t really matter if you make a few mistakes in your memory,’ says Loftus. ‘But if somebody’s liberty is at stake, or they are going to be involved in a horrible lawsuit of some sort, then very precise memory does matter.’ She has been calling for changes in legal and therapeutic interview practices so as to minimise the chances of contaminating the memory of witnesses.
Yet even Loftus confesses to be a little taken aback that neurology might prove the brain to be quite so labile. She often quotes the Uruguayan novelist, Eduardo Galeano, who said: ‘Memory is born every day, springing from the past, and set against it.’ Now, says Loftus, this may be even truer than anyone ever suspected.
New Scientist (3 May 2003)
From VILAYANUR RAMACHANDRAN, The Emerging Mind (2003)
Prosopognosia is very well known but there is another syndrome that is quite rare – the Capgras syndrome. A patient I saw not long ago had been in a car accident, sustaining a head injury, and was in a coma. He came out of the coma after a couple of weeks and was quite intact neurologically when I examined him. But he had one profound delusion – he would look at his mother and say, ‘Doctor, this woman looks exactly like my mother but she isn’t, she is an impostor.’ Why would this happen? Bear in mind that this patient, who I will call David, is completely intact in other respects. He is intelligent, alert, fluent in conversation (at least by American standards) and not emotionally disturbed in any other way.
To understand this disorder, you have to first realise that vision is not a simple process. When you open your eyes in the morning, it’s all out there in front of you and so it’s easy to assume that vision is effortless and instantaneous. But in fact within each eyeball, all you have is a tiny distorted upside-down image of the world. This excites the photoreceptors in the retina and the messages then go through the optic nerve to the back of your brain, where they are analysed in thirty different visual areas. Only after that do you begin to finally identify what you’re looking at. Is it your mother? Is it a snake? Is it a pig? And that process of indentification takes place partly in a small brain region called the fusiform gyrus – the region which is damaged in patients with face blindness or prosopognosia. Finally, once the image is recognised, the message is relayed to a structure called the amygdala, sometimes called the gateway to the limbic system, the emotional core of your brain, which allows you to gauge the emotional significance of what you are looking at. Is this a predator? Is it prey which I can chase? Is it a potential mate? Or is it my departmental chairman I have to worry about, a stranger who is not important to me, or something utterly trivial like a piece of driftwood? What is it?
In David’s case, perhaps the fusiform gyrus and all the visual areas are completely normal, so his brain tells him that the woman he sees looks like his mother. But, to put it crudely, the ‘wire’ that goes from the visual centres to the amygdala, to the emotional centres, is cut by the accident. So he looks at his mother and thinks, ‘She looks just like my mother, but if it’s my mother why don’t I feel anything towards her? No, this can’t possibly be my mother, it’s some stranger pretending to be my mother.’ This is the only interpretation that makes sense to David’s brain, given the peculiar disconnection.
How can an outlandish idea like this be tested? My student Bill Hirstein and I in La Jolla, and Haydn Ellis and Andrew Young in England, did some very simple experiments measuring galvanic skin response. We found – sure enough – that in David’s brain there was a disconnection between vision and emotion as predicted by our theory. Even more amazing is that when David’s mother phones him he instantly recognises her from her voice. There is no delusion. Yet if an hour later his mother were to walk into the room he would tell her that she looked just like his mother but was an impostor. The reason for this anomaly is that a separate pathway leads from the auditory cortex in the superior temporal gyrus to the amygdala, and that pathway perhaps was not cut by the accident. So auditory cognisance remains intact while visual cognisance has disappeared. This is a lovely example of the sort of thing we do: of cognitive neuroscience in action; of how you can take a bizarre, seemingly incomprehensible neurological syndrome – a patient claiming that his mother is an impostor – and then come up with a simple explanation in terms of the known neural pathways in the brain.
From WELLCOME TRUST, ‘Magic Memories’ (2004)
We seem to hold an internal map of the world in our heads. Understanding how the brain stores such maps could help people whose memory has been damaged by a stroke or other trauma.
In a study that generated considerable media interest (and won her an Ig Nobel Prize), in 2000 Dr Eleanor Maguire scanned the brains of 16 London black-cab drivers, who had spent an average of two years learning ‘the Knowledge’ – street names and routes in London. The taxi drivers had a larger right hippocampus than control subjects, and the longer they had been on the job the larger their hippocampus was. These findings seem to indicate that the right hippocampus plays an important role in storing spatial memories.
Dr Maguire, a Wellcome Trust Senior Research Fellow at the Wellcome Department of Imaging Neuroscience at University College London, is continuing her investigations into what happens in our brains when we navigate large-scale space. ‘When we travel down a route we are familiar with, we often can’t see our destination. Instead, we have an image of it in our mind, and a mental map of how to get there. But this mental map is very different from a street map. I’m trying to understand how we create internal three-dimensional representation of space and our position within it.’
She is also interested in another form of memory, linked to spatial memory, which appears to be mediated by the left, rather than the right hippocampus. ‘Having created an internal representation of large-scale space, how do we structure episodic memories – particular events and personal experiences that occurred at a specific time and place – within that environment?’
Dr Maguire will be using magnetic resonance imaging (MRI) techniquesfn2 to establish which neural elements, or brain circuits, are involved in storing and recollecting these two types of memory: spatial and episodic. Results from the MRI scans will be combined with findings from psychological tests to shed light on the cognitive processes that support neural activity in the formation of memory.
Together, she hopes these neural and cognitive findings will provide an integrated, holistic picture of how we understand who and where we are, by locating ourselves in the world and recalling the personal experiences that constitute our recent and distant past.
Measuring someone’s brain activity while they navigate large-scale space poses a challenge, since MRI techniques require the subject to lie in a brain scanner. Dr Maguire has therefore developed a series of virtual reality tasks that the subject can carry out, without physically moving, on a screen inside a scanner.fn3 The complex, naturalistic nature of these tasks closely mimics ‘real-life’ situations.
‘We ask subjects to find their way around a virtual city using a joystick or keypad, and scan their brains while they’re doing it, to find out which brain regions are activated,’ explains Dr Maguire. ‘We vary factors like familiarity by allowing some subjects to practise first; or we get people to take detours or short-cuts or we put a road block in their normal route.’ Developing these virtual-reality environments can be done by adapting commercially available video games. ‘A lot of video games have good editors and are therefore adaptable. We take out all the shooting and monsters so we’re left with the basic environment, which is ideal for our purposes.’
