Human amnesia Flashcards
Students should be able to:
- Describe the behavioural and cognitive profile in human amnesia, and various types of brain damage that can lead to this condition.
- Explain how animal models have helped us understand human amnesia, and in particular, deficits in object recognition memory.
- Discuss the evidence for a role for the hippocampus and related structures in certain types of spatial memory.
- Critically evaluate alternative, non-spatial accounts of hippocampal region function, in particular Configural Association Theory and Relational Memory Theory.
Human Amnesia
Memory has often been described by the use of metaphor, many early examples of which seem amusing to contemporary neurobiologists. Plato, for example, referred to memory as an aviary, the act of remembering corresponding to the capture of one of the resident birds (and the act of forgetting corresponding to the capture of the wrong bird). Both Plato and Aristotle likened memory to a cube of wax upon which various impressions could be made and stored for posterity. And both William James and Sigmund Freud conceived of memory as a house, with specific memories likened to objects in the house. But whatever the metaphor of choice, these early conceptions of memory envisaged an entity or process that is single, unitary, and indivisible. Arguably the most important single discovery in the modern era of memory research, therefore, was that memory cannot be regarded as a unitary entity or process; rather, there appear to be different kinds of memory, and these different kinds of memory are mediated by anatomically distinct regions of the brain.
Much research has been directed towards attempting to characterise these different divisions of memory, resulting in a variety of mnemonic taxonomies usually taking the form of a dichotomy, for example long versus short-term memory, or declarative versus procedural memory. In this series of lectures, we will explore the putative neurobiological underpinnings of these various types of memory. The experimental evidence has come from patients with disorders of memory, as well as animal models.
Short-term vs. long-term memory
Intuitively, we all know that there is a difference between short-term (or ‘working’) memory (STM) and long-term memory (LTM). We use short-term memory when we look up a phone number and remember it just long enough to dial it. Once the number is dialled, it is forgotten – it does not (necessarily) enter into LTM. LTM, in contrast, is memory that you have for, well, a long time: events in the past, facts about the world (e.g. the capital of Peru), and skills such as riding a bike are all examples of LTM.
You are likely already familiar with the idea of reverberating activity in a Hebbian cell assembly from the Synaptic Efficacy lectures (see Fig. 1). The idea is that information can be kept ‘on-line’ in short-term memory through the reverberation of neural loops in the CNS. With enough repetition, the synapses strengthen, perhaps via LTP-like mechanisms, and in this way the information is laid down – consolidated - in LTM. This neural model is compatible with psychological models that envisage information passing through STM in order to enter into LTM (see Fig. 2). Note - Because the information is consolidated in the same location in which it is encoded, this form of consolidation is sometimes referred to as ‘local’ or ‘cellular’ consolidation. Later we will discuss a different type of consolidation, ‘systems-level’ consolidation.
Multiple-storage model
This neural model is compatible with psychological models that envisage information passing through STM in order to enter into LTM (see Fig. 2). Note - Because the information is consolidated in the same location in which it is encoded, this form of consolidation is sometimes referred to as ‘local’ or ‘cellular’ consolidation. Later we will discuss a different type of consolidation, ‘systems-level’ consolidation.
Such a serial circuit is, however, incompatible with certain evidence from patients with brain damage. Patient KF, for example, had selective deficits in STM as indicated by digit span (the maximum number of random digits that a subject can successfully repeat 50% of the time; normally about 7 ± 2 digits). Despite his problem with STM, however, KF had quite normal LTM. This finding has cast doubt on the idea that information must pass through STM before becoming LTM.
Long-term memory
The remainder of these four lectures on memory will focus on LTM; you will return to working memory in Dr Clarke’s lectures. Just as memory is dissociable into STM and LTM, LTM can itself be dissociated into different types. Again, introspection indicates what some of these types might be. Remembering an event in your past – perhaps something interesting that happened to you during fresher’s week – is clearly different from remembering how to ride a bike. Similarly, both of these types of memory seem different from recalling a piece of factual information, like the capital of France. Currently the most influential framework for classifying the organisation of these various types of LTM is that advocated by Larry Squire and his colleagues (see Fig. 3).
Medial temporal lobe amnesia leads to which kind of memory loss
To illustrate this scheme, consider the famous amnesic patient HM. In 1953, at the age of 27, HM underwent bilateral removal of the medial temporal lobes to cure intractable epilepsy. His epileptic seizures were substantially reduced, but HM was left with severe amnesia in all modalities. Despite this severe deficit in LTM, however, HM had a digit span well within the normal range (about 6). Note that HM and KF together complete a double dissociation between LTM and STM.
HM’s pattern of memory deficits is illustrated perhaps most strikingly by anecdotal reports from his neuropsychologist Brenda Milner (see Bear p. 755). During short encounters HM would appear perfectly normal and intelligent (his IQ, too, is well within the normal range). But if Dr Milner left the room for a short while, when she came back HM had no recollection of ever meeting her. In short, HM appears to live his life within a single, brief moment. The tremendous impact of this kind of deficit is illustrated by Oliver Sack’s description of the patient he calls ‘The Lost Mariner’.
This condition was due to the destruction of the tissue of the medial temporal lobes (MTL), including the amygdala, the hippocampus, and the entorhinal and perirhinal cortices (see Fig. 4). Although in HM’s case the damage was a result of surgery, damage to the MTL can also be induced by stroke, infection, tumours, or closed head injury. In addition, the MTL is the first region to degenerate in Alzheimer’s disease.
HM patient with medial temproal lobe damage proved that MTL is related to
Formal testing of HM confirmed his severe impairment in LTM. Although HM had normal STM as demonstrated by his ability to retain strings of numbers in the digit span task, he performed poorly on digit span tasks that required the acquisition of new long-term memories. Unlike normal controls, his digit span did not improve with practice (see Fig. 5).
mirror tracing task illustrated what
Just as early researchers were becoming convinced that HM was completely unable to form any new memories, they got a bit of a shock. It was found that HM is perfectly able to acquire skills and habits, such as the mirror tracing task illustrated in Fig. 6. In the face of his devastating impairment in declarative memory, these aspects of his LTM appear to be intact.
What does it mean in HM patient with this result?
To return to Squire’s taxonomy of memory, we can now see how HM fits in. HM, according to Squire and colleagues, has deficits in declarative memory (memory for facts and events), while other types of memory – referred to simply as ‘nondeclarative’ – are unimpaired. We have already seen how HM performs well on the mirror-drawing task. Other examples of spared memory abilities in HM include classical conditioning and priming (see Fig. 7).
Episodic vs. semantic memory
It appears that declarative memory is also divisible into distinct processes. Episodic memory is the memory for events or personal experiences, whereas semantic memory is memory for facts. A double dissociation between episodic and semantic memory can be seen in two patient populations. Vargha-Khadem has studied a group of children who had severe hippocampal damage early in life. These children have essentially no episodic memory, yet they perform well on semantic memory tasks, and achieve average marks in school. Patients with semantic dementia, on the other hand, have intact episodic memory, yet they gradually lose factual information such as the names of objects or animals.
Anterograde vs. retrograde amnesia
HM’s deficit in LTM that we have been discussing so far is called anterograde (forward going) amnesia because he was unable to lay down new memories. This is in contrast to retrograde amnesia, in which memories already in LTM are abolished (Fig. 8). Thus, it seems that damage to the MTL affects the ability to acquire new long-term memories but does not affect most information that is in LTM at the time of the trauma.
Although the majority of HM’s LTM for events before his surgery was intact, he showed some retrograde amnesia extending backwards from his surgery for about 3 years (i.e. he couldn’t remember very well life events that occurred between the ages of 24-27 years). This has led to the suggestion that declarative information is first laid down in the MTL and then, through a gradual process of (‘systems-level’) consolidation, is transferred to LTM in the neocortex (see later). Thus, relatively recent memories that had not yet been transferred to LTM, and were therefore still resident in the MTL, were abolished due to HM’s surgery, leading to temporally graded retrograde amnesia.
However, William Scoville damaged a number of MTL structures when performing the surgery on HM, leaving an open question: which structure(s) in the MTL are necessary for episodic memory? This question has been addressed through the study of other human amnesic patients, and the use of animal models of memory. Let’s begin by considering patient evidence.
Ischaemic brain damage
RB
One case of MTL damage, that of RB, has had a major impact on theories of memory. At the age of 52, RB’s brain was damaged during cardiac bypass surgery. An equipment malfunction stopped the flow of blood to RB’s brain resulting in ischaemic brain damage that left RB amnesic. RB’s amnesia, though not as severe, was quite similar to that of H.M. However, post mortem analysis revealed that RB’s damage was restricted to the pyramidal cell layer of one part of the hippocampus, the CA1 subfield. This suggests that hippocampal damage by itself can produce amnesia. However, this conclusion has been seriously challenged, as you will see in the next lecture.
Diencephalic and Korsakoff’s amnesia
The MTL is not the only region of the brain which, when damaged, can lead to amnesia. Damage to structures within the diencephalon – the medial and anterior thalamic nuclei and the mammillary bodies – can also lead to amnesia. This damage can be caused by stroke, tumours or trauma. Medial diencephalic amnesia is exemplified in patient N.A., who was stabbed through the right nostril with a fencing foil. His damage is limited to the medial diencephalon. After his recovery, N.A.’s cognitive ability was normal, but he had retrograde amnesia of about two years and severe anterograde amnesia. Although his amnesia was less severe than H.M.’s, the quality of the deficit was very similar.
In addition, metabolic problems brought on by chronic alcoholism can lead to degeneration of the diencephalon, especially the dorsomedial nucleus of the thalamus and the mammillary bodies. This condition is referred to as Korsakoff’s syndrome. The amnesia of Korsakoff’s syndrome is similar to MTL amnesia in major respects: Korsakoff’s patients present with anterograde amnesia for explicit memories. However, in contrast to MTL amnesia and the amnesia demonstrated by N.A., Korsakoff’s amnesia is also associated with severe retrograde amnesia, often extending back to events experienced in childhood (Fig. 9).
