PS3002: Brain & Cognition Cognitive neuroscience and memory John Beech School of Psychology

1. PS3002: Brain & Cognition Cognitive neuroscience and memory John Beech School of Psychology University of Leicester

2. Memory and the brain Introduction • Memory is extremely varied. What is the substrate of memory in the brain? • Is it different for different types of memory? how to ride a bike the relation between the sides of a triangle an episode in one’s life • Can use: animal models from simple invertebrates to mammals the study of what happens to memory in amnesia following brain damage brain imaging in volunteers to investigate normal encoding, storage, and retrieval – recall or recognition.

3. Structure of memory Learning vs memory • Squire (1987) distinguishes: Learning - process of acquiring new information Memory - persistence of learning in a state that can be revealed at a later time. • Learning has an outcome - memory - which itself has a further outcome - a change in future behaviour. • Learning need not imply any conscious attempt to learn. Simple repeated exposure can, and indeed usually does, lead to learning, and this is evinced by memory.

4. Structure of memory: encoding Encoding is divided into acquisition (registration) and consolidation Storage creates and maintains a permanent record Retrieval uses stored information to create a conscious representation, or to execute a learned behaviour. • If there is a deficit in memory, we don’t know at which stage this has occurred. • [flashbulb memories at times of traumatic or shocking events tend to be very vivid and detailed and readily recalled, but some studies have shown that it is not so much their accuracy which is improved, as the increase in subjective confidence].

5. Memory model of Atkinson & Shiffrin (1986) above. Sensory memory is sub-second to seconds, as when we can recover what was said when we weren’t paying attention. Short term is seconds to minutes, as with retaining a phone number. Long-term is longer—days, weeks, going up to years, or even a lifetime. Time base of memory

6. Peterson & Peterson(1959): Consonant trigrams (e.g.TDK) followed by a no. (e.g. 765). Counts back in 3s (765, 762, 759…) and recalled trigram on signal Rapid decline to <10% after 18s. Thus if rehearsal inhibited, decay is rapid. Is this decay over time or the processing of new information? Short-term memory

7. Glanzer & Cunitz (1966): Recalling list of words give U-shaped effect Expt 1: varied presentation rate. Improved recall on start and middle bits, but not on the last part. Slowness helps LTM but not STM. Expt 2: Immediate recall vs delayed interference (counting): affects only last part showing an effect on “recency”. STM v LTM

8. Sensory memory Neisser (1967): “iconic memory” (E.g. cigarette or sparkler in dark) and “echoic memory” (e.g. saying “what?” and then knowing what was said). Sensory memory

9. Sperling • Sperling (1963) - matrix shown 50ms, then tone signalled top, middle or bottom of array to recall. • If 67% of row recalled, he argued that 67% of whole array must therefore be available. • Varying probe length showed steep decline in memory to asymptote after only 250ms ( .25s). • Not stored by analysis of meaning.

10. Baddeley (1974) proposed that a central executive controls two storage areas. The phonological (articulatory) loop and the visuo-spatial scratchpad. The Central Executive coordinates these activities with LTM. Phonological (articulatory) loop is essentially acoustic, because errors in recalling letter strings presented visually are letters similar in sound rather than in form. Visuo-spatial scratch-pad is separate, and the introduction of a V-S task during retention does not interfere with recall of PA material. Working memory

11. Long term memory: different forms

12. LTM is regarded to be in 2 parts: Explicit and Implicit (Tulving and Schacter, 1990), OR Declarative and Non-declarative (Squire, 1987; Cohen 1993). Explicit or Declarative is conscious knowledge, to which we know we have access: facts, history Implicit or Non-declarative is unconscious knowledge, such as procedural, perceptual priming, conditioned habituation or sensitisation. Long term memory: different forms Analysis of nature of memory deficits will help to explore this distinction, as these 2 types are differentially affected by lesions. Explicit consists of episodic (stories about us, what happened in the past) and semantic (facts). Implicit memory (Schacter) - knowledge that can be revealed by behaviour in an appropriate test situation, and that can be observed in animals too. Humans do not retrieve it under conscious awareness, although they can do. Below Tulving & Schacter Implicit vs explicit memory

13. Implicit memory, on the other hand, is demonstrated by improved performance on a word completion task, even without conscious memory of the previous list. In contrast to explicit memory, the latter improvement is not time dependent, and performance is not further improved by encoding the original list more deeply. Hence explicit and implicit are truly separate memory processes, at a psychological level. Implicit memory in the perceptual representation system (PRS) If Ps are shown a list of words, their explicit memory can be assessed with a new list containing old and new words.

14. The PRS (Perceptual Representation System) • Priming studies have primarily been used to demonstrate the PRS (as in the previous experiment). In that experiment if the initial list of words is presented auditorily, the gain in implicit memory isn’t seen. Thus the effect is specifically on the visual word form, not on the auditory counterpart. • Priming can also be shown on nonverbal stimuli. Daniel Schacter et al. (1990) showed pictures of both possible and impossible forms (shown in the next figure) and on the initial viewing half the participants were instructed to look at each picture globally. Then the pictures were shown once more with the instruction to decide if each one was possible or impossible. Those instructed to look at the pictures globally were faster at doing this, but only for the possible objects, not for the impossible ones. Thus these showed priming for forms. • PRS develops early, and is preferentially maintained during ageing.

15. These figures to the right are examples of possible (top) and impossible (bottom) figures used by Schacter et al. Evidence from this and other studies suggests that implicit memory in priming involves a perceptual representation system (PRS) that subserves processing pictures and visual and auditory word forms. Schacter et al. (1990)

16. The neurobiology of different types of memory • Sources of information: human brain injury, animal lesions, imaging of brain during memory processes - the usual approaches (for us). • Deficits in memory as a result of damage, disease, or psychological trauma are called amnesias. • May be loss of ability to learn new things, and/or loss of previous knowledge. • The fact that different components can be lost, helps us to understand the organisation of memory.

17. The reality of amnesia • Suppose you meet someone who appears to have perfectly normal intelligence and behaves normally in terms of social conventions. • But you have to leave the room to meet someone briefly and then you return about 3 minutes later. • You find that when you return this person doesn’t have the slightest recollection that they’ve met you before and that they’ve been talking to you. • Suppose further that you’re a clinical psychologist and you can perform further tests and when you do you find that in practice this person cannot remember anything beyond 50 seconds. • When you probe for their memory of recent events (e.g. by news stories) you find that they have complete amnesia for many years of the past! • What must it be like to be deprived of your past like this? • How can such a person function and how do they relate to their family and friends? • Their memory for past events is “wiped clean” (although we will modify this later) back to the time when their brain was damaged AND memories some years before the damage took place. • Before we proceed we need to examine the structure of the temporal lobes which are strongly implicated in this condition…

18. In the MRI above TP is the “temporal pole” – the front of the temporal lobe. In the inner surface of the temporal lobe is the hippocampus outlined in white and marked HIP. AMG is the amygdala. The temporal lobes

19. The temporal lobe

21. Key to the anatomy The pictures are arranged A-D going left to right, top to bottom. A: Dorsallateral view, rear of head to the right. T Lobes in pink. B: Midsagittal – section down the middle with the rear of the head to the right. C. Basal – looking at the base – note how the lobes (in pink) wrap round but don’t meet. D. the coronal view – a section “ear to ear” cutting the brain into front and back halves. Click. Anatomy of the temporal lobes

22. 1940s and 50s: neurosurgical treatments for epilepsy. Removal of medial temporal lobe, including the hippocampal formation, resulted in dramatic memory impairments, only if bilateral. Patient HM. Worst case in a series of 10 patients reported by Brenda Milner. (Born in Manchester and moved to Canada after her degree at Cambridge.) Increasing frequency of his temporal lobe epilepsy led to bilateral surgery – 1953 when he was 27 years old. He remained of normal intelligence (IQ 112) and had no psychological illness. However, the surgery resulted in intense anterograde amnesia (Events taking place after surgery are never remembered for more than 60 sec). The temporal lobe and memory

23. The temporal lobe and memory • Two years later he reported the current date as being that of his surgery. • He failed to recognise doctors on their return, who had left the room only briefly. • Had clear recollections often only of distant events. Partial loss for 3 years preceding surgery (retrograde amnesia), and complete loss for events after (anterograde amnesia). • Short term memory was normal (sensory registers, immediate memory, digit span* – as is the case for other amnesics). Transfer to longer term memory was what was disrupted. (* note = digit span here is referring to starting with 4 numbers, and if correct adding a new number, to make 5 in a different sequence. This continues until errors are made in two trials for a given sequence.)

24. Areas removed from HM shown in red. Note that the resection is only illustrated here on one side, but HM’s lesions were bilateral. The very top diagram is an underside view of both hemispheres. A-D are the 4 sections at the bottom of the figure. (Sections A and B, where the areas were removed, are nearer the front of the head and C and D, where there is probably atrophy, are situated at the back.) The temporal lobe & memory

25. The figure on the right shows digit span for amnesic patients (blue) and controls (red). They were given 5 numbers and had to repeat these back. If correct another number was added to the next sequence. When they were incorrect the same sequence of numbers was repeated until they could report it correctly. It can be seen that, e.g. for 8 numbers it only takes about 3 trials on average to learn this sequence for controls but about 12 trials for amnesic patients. Conclusion: they find learning (transferring into LTM) very difficult. Learning digit sequences

26. The temporal lobe and memory • Returning to HM, on the other hand, implicit memory was normal, and skills improved normally – e.g. drawing a star seen in a mirror. • The area of hippocampus removed in HM turned out to be smaller (and more anterior i.e. nearer the front) than at first reported. However posterior hippocampus may have been partly atrophied. • Another case, RB had similar pattern of amnesia after an ischaemic episode (i.e. reduction of blood to the brain) during by-pass surgery. Had specific lesion restricted to the “CA-1” cellular subfield of each hippocampus (which is particularly vulnerable to ischaemia). This case was important because it showed that hippocampus damage was sufficient and that the amygdala didn’t need to be damaged as well. • In summary, the hippocampus appears to be particularly crucial in the laying down of new explicit memories.

27. The temporal lobes and memory • Much earlier memories are not impaired, thus hippocampus is not a permanent storage area for explicit knowledge. • hippocampus is involved [with other cortical areas] in consolidation, a longer term process taking months to years (note retrograde amnesia in hippocampus lesion patients for up to 3 yrs). • Consolidation is understood to involve biological changes taking place in those other areas of cortex, and involving strengthening of the associations between multiple stimulus inputs and previously stored information. • Once this has fully taken place, the hippocampus is not required for retrieval.

28. This is also illustrated by the amnesic effects of electroconvulsive therapy, which typically extend for 6 months before treatment and 2 months after (i.e. Memories are in labile [easily altered] form in this amnesic period). Memory impairment from physical trauma (e.g. a car crash) is similar. Damage to cortex, especially areas in front of the hippocampus, such as the front part or anterior temporal cortex, results in a dense retrograde amnesia going back several decades, but with preservation of the ability to form new memories. Hence the anterior temporal lobe is a major repository for LTM. BUT it is not the only possible one, since new long-term memories forwards in time from the lesion can be formed. The temporal lobe and memory

29. Features of amnesia What are the features of the amnesic syndrome? • Can learn some new information with difficulty, e.g. semantic knowledge, new vocabulary, details related to people. Typically, patients are then unsure of the source of this information. • There or no great intellectual impairments, nor any problems in language (i.e. aphasia). • Retrograde amnesia – there are partial losses of information that has been acquired before injury. For example, HM lost some knowledge in the period 3 years leading up to his operation. But he can recall older memories very well.

30. Features of amnesia What are the features of the amnesic syndrome? (continued) • Dense anterograde amnesia – a permanent problem with acquiring new information. For instance, can’t remember names of new people, nor his way back home – HM’s family moved house after the operation. • Normal STM – HM has normal digit span (7 forward, 5 backwards). Can carry on conversations including rephrasing sentences, do mental arithmetic.

31. Features of amnesia What are the features of the amnesic syndrome? (continued) • Rehearsal – if HM is distracted just for a moment from what he’s rehearsing he’ll completely forget it – thus rehearsal does not serve to transfer to LTM. • Learning is not completely absent – he shows unimpaired implicit memory on procedural tasks by showing priming effects equivalent to controls and he acquired the classically conditioned eye-blink reflex. He also learned mirror drawing. Skills such as riding a bike – procedurally based skills – are preserved and amnesics can acquire new skills after injury without any problems.

32. Sergei Korsakoff at the end of the 19th century reported anterograde and retrograde amnesia associated with alcoholism. Imbibing a lot of alcohol in the long term produces vitamin deficiencies leading to brain damage (thiamine deficiency (vitamin B1) => periventricular damage). This is more specifically in the diencephalon* (thalamus and mammilliary bodies). The same kind of damage can be produced by strokes or tumours. Recent work by Sullivan & Marsh (2003) has also found deficits in the hippocampus and not just the diencephalon. (*Note that the diencephalon is a subcortical [portion of the brain just below the cerebral cortex] structure made up of the thalamus and the hypothalamus.) Alcoholic Korsakoff’s Syndrome

33. The similarities in Korsakoff’s (implicit memory OK but lose explicit memories) has led people to suggest that the medial temporal lobe is not the only part of the brain for forming explicit memories of facts and events. However, the recent work of Sullivan and Marsh casts some doubt. Korsakoffs patients also confabulate caused by frontal lobe damage. This is not deliberate deception as they appear to believe themselves. This could be due to damage to frontal lobes which have a control function in memory retrieval. Alcoholic Korsakoff’s Syndrome

34. Korsakoff’s syndrome Cermak, Naus & Reale (1976) demonstrated the memory impairment (in LTM) in this condition. Note the strong recency effect showing an intact STM.

35. As previously mentioned, damage to the front part (anterior) of the temporal lobe produces dense retrograde amnesia (forgetting of events before the brain damage). In the case of Alzheimer’s disease or herpes simplex encephalitis this can go back for decades before the amnesia. Temporal gradient (Ribot’s Law, 1882) autobiographical memories that are more recent are much more easily damaged compared to early memories. It was first noted in Korsakoff’s syndrome patients. But WHY does it occur? Korsakoff’s patients were in a more drunken state when learning! But temporal gradients occur in amnesics who do not abuse alcohol. Parts of the diencephalon, the thalamus (blue) and the hypothalamus (red). Retrograde Amnesia – temporal gradients

36. Retrograde Amnesia – temporal gradients Temporal gradient (Ribot’s Law, 1882) • Korsakoff’s patients were in a more drunken state when learning! But temporal gradients occur in amnesics who do not abuse alcohol. • Squire (1992): 2 major areas involved in initial and long term storage in memory: (1) The hippocampal formation is responsible for initial processing and then after rehearsal (2) the medial temporal lobes consolidate these memories. This predicts that those with lesions to the hippocampus (e.g. HM), but who have intact anterior temporal lobe structures (as in early onset Alzheimer’s disease) will have severe anterograde amnesia (no new memories).

37. Retrograde Amnesia – temporal gradients Temporal gradient (Ribot’s Law, 1882) Squire (continued): But those with semantic dementia (e.g. Snowden et al. 1989) have the reverse damage – no anterograde amnesia, but severe retrograde amnesia (able to have new memories, but recent autobiographical memory impaired). To digress about semantic dementia – this is also called “fluent progressive aphasia” meaning that their actual speech is fluent; however their understanding and recognising of words and putting names to faces and familiar objects gradually worsens (i.e. semantic knowledge deteriorates). There is evidence that the temporal lobes are mainly implicated with memory for words in the left temporal lobe and for faces in the right (Snowden et al. 2004).

38. Retrograde Amnesia – temporal gradients Temporal gradient (Ribot’s Law, 1882) Patients with damage to the anterior temporal lobes have resulting dense retrograde amnesia (forgetting lots of events/autobiography before damage) but some patients may still form new long term memories. So the anterior temporal lobes are useful for information storage, but other areas also seem to be capable of acquiring new information. As mentioned before such patients have poorer recall of episodes close to the beginning of the disease (or onset of injury) with gradually better recall further back (i.e. temporal gradient).

39. Dissociation of episodic memory within explicit memory • Tulving et al. (1991) studied a patient KC who had had subdural hematoma (pool of blood under the sheath covering the brain). He’d had a motorcycle crash at 30 yrs of age. • Damage included bilateral damage to the medial temporal lobe especially on left, but also other cortices – frontal, parietal and occipital. More damage to left hem. (See next figure). IQ of 94. • Could not remember any events from his life, although he knew things that pertained to his life. Thus severe retrograde amnesia - he could recall very few autobiographical episodes from his life before the injury. (This is as if his episodic memory had been wiped clean.) ALSO severe anterograde amnesia. But intact semantic memory, and procedural memory. • Thus this patient had a specific loss of episodic memory.

40. Tulving et al. 1991 • KC’s lesions are shown on outline drawings of horizontal sections of his brain, starting from the top moving down going from left to right in the drawings, using computed tomography (CT). The red parts are the lesions due to trauma.

41. Tulving et al. (1991) Implicit memory tested by giving three-word sentences together with a related picture. In each the final word critical. Later KC presented with a fragment or conceptual cue consisting of the other two words. KC showed priming effect with the word fragments and they lasted 12 months. Priming in this context means that he was better at generating words from the fragments compared to words previously unseen. Surprisingly he could learn new semantic information – it took him longer to learn information than controls, but he forgot it at the same rate. Results like these suggest a separation of the underlying structures subserving semantic and episodic memories.

42. Dissociation of episodic memory within explicit memory It might be noted that there is currently a controversy and Bayley and Squire (2002) have suggested that KC’s problems in retrieval of autobiographical information may be unrelated to his medial temporal lobe damage because of a more recent report of a patient (EP) who has more extensive medial temporal lobe damage, but who has better recall of autobiographical episodes. So we may still be a little way away from distinguishing the functions of the hippocampus and other medial temporal lobe structures.

43. Procedural learning in amnesia • The test above examines serial reaction time: Ss have to push buttons according to flashes of lights in a complex sequence. Their index finger corresponds to the first light, the second finger to the second light and so on. The sequence can be random or else they can appear to be random, but in practice there is a complex repetitive sequence. In the repeated sequence situation RT reduces over time as shown on the right hand side. Afterwards it is clear that Ss are unaware when there are these complex repetitions. This is a good paradigm to test procedural learning (or implicit memory) • Amnesics (and Korsakoff’s patients) also improve their performance. Thus they have reasonable implicit memory, while great difficulties with episodic memory.

44. We need to look for a double dissociation; a loss of implicit memory, without loss of explicit memory (having shown a loss of explicit memory and no loss in implicit memory in amnesics.) Gabrielli et al. 1995 tested a patient MS who had a right occipital lobe lesion. Areas 18,19, leaving a LVF hemianopia… When shown words for later recall, he had explicit memory for them, but failed to show implicit perceptual priming (decreased exposure time needed to identify a familiar word compared to time for an unfamiliar one). In detail: before both tasks a list of words were presented briefly and then read aloud. (Note that this meant they saw them perceptually, but briefly and also then heard the words). In the implicit memory task the words were presented visually and then masked (XXXX). Durations of presentation increased from 16ms until the word could be read. If they had implicit memory, they should be faster with the words they had previously seen, compared with new words. Double dissociation

45. In search of double dissociation between implicit and explicit memory • In the explicit memory task again a list of words was shown and then in the recognition task old and new words were presented and they had to identify the old words. The patient was good at this task, but failed to show implicit perceptual priming. • Hence this lesion impaired implicit but not explicit memory.

46. Gabrielli et al. 1995 Summary: Occipital lobe lesion patient List of words briefly shown List of words only heard Implicit memory Word XXXX old + new RT task Results – patient good at recognition task, but poor at implicit memory – in other words, has a poor implicit memory Explicit memory old + new Recognition task

47. Atkinson & Shiffrin proposed in their model above attended items go from sensory memory into STM and if rehearsed move into LTM. Along the way processes of decay and interference (either or both) results in information loss. An important aspect was its serial nature – information moves from one stage to the next. But the evidence doesn’t support this. Shallice and Warrington (1969), patient with left perisylvian* damage who had reduced digit span (2 instead of the normal 5-9 items), but amazingly he had an intact ability to form long-term memories (e.g. could talk about the latest news). Hence it cannot be the case that information going into short term memory is a necessary precursor to it going into long term memory. It means that information can go straight from sensory memory into LTM. (*the perisylvian area is in the upper part of the temporal lobes in both hemispheres, and is implicated in language functioning in the left hemisphere. It is typically larger in the left hemisphere than in the right.) Evidence against the Atkinson & Shiffrin model

48. This points to a double dissociation between STM and LTM: The Shallice & Warrington patient shows a patient with a very impaired STM, but with an intact LTM. We have also seen how it is possible for LTM structures to be destroyed in the anterior medial temporal lobes but the STM left intact in semantic dementia. The patient HM is an illustration that the hippocampus structures are important for the transfer/consolidation of episodic information into LTM, even though HM’s STM was intact and a proportion of the structures in LTM were intact. Given the shortcomings of the serial model of memory, there was a need for a different perspective, which was the motivation for the working memory model developed by Alan Baddeley. Below in order: Tim Shallice, Elizabeth Warrington and Alan Baddeley Another double dissociation: this time between STM and LTM

49. Brain structures & STM • Going back to the Baddeley model, there is some neurological evidence for the brain structures involved in this, in that function of the phonological loop is impaired by lesions of the supra-marginal gyrus (Brodmann area 40) and/or left pre-motor region (area 44). [In the absence of deficits in speech comprehension and production]. • Baddeley’s visuo-spatial scratchpad is impaired by lesions in parieto-occipital regions. • Right sided lesions have more effect. Difficulty with spatial tasks such as repeating a sequence of objects touched. • Left sided lesions => problems with STM of visually presented material.