Download The Making, Keeping and Losing of Memory

The Royal Society of Edinburgh
The Making, Keeping and Losing of Memory
Professor Richard Morris CBE FRS FRSE FMedSci
Professor of Neuroscience and
Director, Centre for Cognitive and Neural Systems
University of Edinburgh
Thursday 16 April 2015, The Gailes Hotel, Irvine
Report by Kate Kennedy
Memory is fundamental to human life. 2014 has been a special year in which 'remembrance' has been
on people's minds as they reflect on the momentous events of 100 years ago. Our everyday use of
memory is, of course, very different; although it is also changing, with so many aspects of human
knowledge now available on the Internet. Using the themes of the 'making, keeping and losing' of
memory, this lecture offered examples of how the brain mediates memory. Professor Morris also
discussed some of the ongoing research aimed at better understanding how memory works and
considered the loss of personal memory, which remains greatly feared. The inability to recollect the
events of our life can develop from a minor irritation to a condition that undermines normal existence –
notably in Alzheimer's Disease.
In 2014, the 100-year anniversary of the start of World War One was marked with commemorations
throughout the United Kingdom; remembering how communities were ravaged by the War. Professor
Morris commented that “cultural memory is very important to our sense of identity; however,
remembrance is often, paradoxically, an act of new memory encoding”. Such memory is odd in being a
conscious act of remembering events or people we have never witnessed or seen, but which are
usually of great personal or public significance. Cultural memory is often a case of learning new things,
particularly by the next generation.
Much of memory is incidental and automatic; we do not have to make an effort to remember, for
example, what we had for breakfast or where a recent event happened. Some types of memory are
conscious and effortful; such as acquiring a skill such as riding a bicycle or learning a foreign language.
Other aspects of memory are not about past events; for example, the effort of remembering to do
something in the future. Furthermore, we do not retain every piece of information; we are selective.
Indeed, Professor Morris pointed out that “forgetting is also important to make memory work well”.
The human brain, although quite small, contains 1012 cells and carries out up to 104 synoptic
connections per cell. Therefore, the number of possible connections in the brain is vast. Through
cognitive experiments on humans, brain scanning and experiments with animals, progress has been
made in understanding the workings of the brain. One hundred years of formal research on memory
has revealed that there is more than one memory encoding system and, as such, there are differences
between the processes for making short-term and long-term memories. Short-term memory is an
active, conscious form of memory; for example, rehearsing a telephone number for short-term recall.
Breaking the stream of consciousness whilst rehearsing the information can cause a person to forget
the information. In contrast, long-term memory creates a representation in the brain that physically
changes the connections between cells. It is not necessary to actively hold the information in the brain
or rehearse it; the memory can come and go and be reactivated.
Initial research concluded that, in short-term memory, auditory and visual sensory registers hold
memory briefly, acting as a simple single store with limited capacity, and that the rehearsal of
information leads to remembering. Evidence for this came from experiments whereby subjects were
asked to remember digits and letters by continuously rehearsing these and then asked to recall the
details. Following this initial test, the subjects were then asked to repeat the task but also introduce an
additional element whereby they counted back from a given number in threes whilst attempting to
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remember the original information. In many cases, this caused a distraction from the initial task,
leading to less effective recollection. In the 1970s, however, Baddeley and Hitch disproved the idea of
short-term or working memory as a single simple system. Their experiments found that whilst people
got slower at remembering information when distracted, their accuracy remained good and the brain is
able to separate working memory and ‘holding onto’ memory. Baddeley and Hitch’s model of working
memory is now widely accepted as correct; the brain has a Central Executive System used for
reasoning and a separate short-term store for rehearsal and, as these are separate systems, there is
little interference between the two. On the basis of this type of experiment, researchers have been able
to devise and carry out human brain scanning to determine what happens in different areas of the
brain and specify the locations of the different components of the Baddeley and Hitch model. Most
memory encoding takes place in the frontal lobe and the Central Executive System is located in the left
hemisphere.
Experiments with human subjects have led to a better understanding of how short-term and long-term
memory work and interact. Long-term memory makes a distinction between learning skills and
declarative memory (knowledge, events and the meaning of things). Furthermore, different areas of the
brain mediate these differing aspects of long-term memory; the ventral striatum is important in learning
skills and the hippocampus is vital for encoding events which happen in life, known as episodic
memory. The learning of skills requires effort; they are slow to learn but, once achieved, are
remarkably immune to forgetting. Episodic memory, even for events that happen only once, requires
very little effort. The hippocampus can capture information immediately and combines events to the
places they happen in an act of automatic encoding. The case of patient HM illustrates how vital the
hippocampus is to long-term memory. In 1954, in an effort to relieve his epilepsy, HM underwent a
brain operation involving the bilateral removal of the medial temporal lobe that contains the
hippocampus. An unforeseen consequence was that he became very amnesic, despite his epilepsy
improving. HM’s perception remained excellent, he could copy drawings perfectly but was unable to
remember the activity or image only minutes later. Following the operation, he was also taught to do
mirror drawing and became very skilled at this. However, whilst he was able to show this skill when
asked to perform it, he had no knowledge of having learned the skill. Professor Morris states that this
shows an “amazing association between acquiring a complex skill but having no awareness in the
episodic sense of having done so. It shows that damage to the brain does not affect the ability to
acquire a skill governed by the ventral striatum, but does affect the memory of it because the
hippocampus is integral to making episodic memories”.
Following these revelations, the next step involved research into understanding how the hippocampus
actually makes memories. It is, however, very difficult to do studies on the human brain; no one allows
intervention in the brain in healthy people. Whilst there are ethical issues associated with using animals
for such experiments, these are often the only option available to researchers. In one such experiment,
Professor John O’Keefe discovered place cells in the hippocampus. These are brain cells that ‘fire’ and
become active when an animal enters a particular place in the environment. His discoveries led to the
development of the idea that the hippocampus functions as a cognitive map of where things are
located and links events to places. O’Keefe also collaborated with other scientists in performing
imaging experiments on London taxi drivers to test their spatial memory. They discovered that, in
addition to place cells being activated in the hippocampus when drivers were following different routes,
the size of the posterior hippocampus gradually increased in line with the number of years employed
as a taxi driver and, thus, experience led to structural changes in the brain.
Professor Morris, inspired by O’Keefe’s work, developed in St Andrews a novel behavioural procedure
for studying spatial learning and memory called the ‘water maze’. The procedure involves placing a rat
in a pool of water containing a hidden platform that allows it to escape from the pool. The task shows
that the rat relies on spatial memory to remember the location of this platform within a pool of water,
even looking for it in the same place when it is removed. However, if the rat’s hippocampus is
damaged, it is unable to locate the platform. The water maze experiment can assist in the
understanding of the anatomy of the hippocampus, which contains an elaborate network of neurons.
Understanding this, with additional knowledge from neurologists and pharmacologists, can lead to the
development of medical cognitive enhancing drugs by pharmaceutical companies, highlighting the
practical and beneficial purpose of such experiments.
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Professor Morris went on to comment that a “curious paradox exists in memory. Whilst novelty aids
memory, the similarity of new information to existing knowledge also makes new things easier to
remember”. For novel events and information, modulatory pathways in the brain are activated, exciting
the hippocampus and making it remember better. However, in terms of similarity, it is thought that new
information is easier to remember because the hippocampus transfers information to the cortex, the
final repository of long-term memory, and there it is assimilated into existing networks of knowledge. It
is easier to do this if what is being assimilated is similar to things in which a person has an interest or
of which they have previous knowledge. Professor Morris also mentioned ‘flashbulb’ memories,
whereby people remember trivial details of important days. It is suggested that a particular memory
circuit exists that activates the hippocampus in situations of novelty, such that other trivial details are
also remembered. Professor Morris commented that current research is attempting to further
understand this and, in doing so, aspects of optogenetics are being applied to studies. Within the
human retina, Rhodopsin converts light energy into electrical energy, enabling sight. It is thought that
other ‘opsins’ could be genetically engineered into brain cells and placed anywhere in the brain. By
using viral vectors and molecular ‘tricks’, it is possible to make some neurons in the brain sensitive to
light. Light guides, as fine as the human hair, could then be placed in the brain and, using blue light,
could be used to make these engineered cells fire. It may then be possible to work out the causal
mechanism that might be responsible for the novelty-induced enhancement of memory.
Many people, in older age, complain about their loss of or ‘bad’ memory. Professor Morris commented
that it is “reassuring that memory failure in older age is very normal and nothing to worry about”. In his
book Seven Sins of Memory, Professor Dan Schacter of Harvard University identifies the ‘sins’ of
transience, absent-mindedness, blocking, misattribution, suggestibility, bias and persistence. He
suggests that all of these are exacerbated by age, but are not failures at all, as they may reflect the
proper operation of a very finely tuned system. They are the price we pay for the processes and
functions that serve us well in many respects. Professor Morris stated, “as one gets older, there is
certainly more forgetfulness, but most of this is fairly benign and reflects slight changes in the balance
of a fine-tuned system.
However, degenerative neurological diseases do happen, such as Alzheimer’s Disease. Around 45
million people worldwide suffer from dementia, affecting all races and ethnic groups. There is currently
no cure or effective treatment. A lot of neuro-genetic research has been carried out on familial
Alzheimer’s Disease. Whilst this only accounts for up to 4% of sufferers, it is thought that studying this
group might provide insight into the particular genes that are involved in the development of the
disease. The hippocampus is affected relatively early in Alzheimer’s and it is hoped that early
diagnostic tests and tools may be developed. With early detection, researchers stand more chance of
developing treatments. Professor Morris commented, “the terrible truth is that, currently, by the time
someone is fully confirmed as having Alzheimer’s Disease, it is almost too late to do anything which
has an effect”.
Professor Morris briefly discussed whether it is possible that the Internet and new technologies are
changing the way we use memory. Today, we are far less likely to make the effort of remembering
something such as a telephone number, as we have devices capable of doing this for us. However,
information overload, multi-tasking, more distraction, stress and less sleep, all of which are associated
with technology, have implications for memory. Additionally, if we make less effort to remember things
ourselves, we may be less inclined to share information and experiences socially, to the detriment of
everyone, particularly in terms of family and community. These are hidden costs that we need to reflect
upon.
Professor Morris concluded by stating “memory is very important, it enables us to transcend the
immediate moment, it is central to family life and vital to science, literature, music and the visual arts.
Indeed, memory and remembrance is a foundation of human culture”.
The Vote of Thanks was given by Mr Patrick Wiggins, Irvine Bay Regeneration Company.
Opinions expressed here do not necessarily represent the views of the RSE, nor of its Fellows
The Royal Society of Edinburgh, Scotland’s National Academy, is Scottish Charity No. SC000470
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