PY31002 Biopsych Lecture 4 full slides after lecture.pptx

Biological Psychology The Neurobiology of Memory & Classic Cases Dr Elaine H. Niven • Memory and its disorder • Be able to identify and explain what classic cases have contributed to our understanding of memory • What areas support memory? • Be able to discuss the involvement of a number of par...

Biological Psychology The Neurobiology of Memory & Classic Cases Dr Elaine H. Niven • Memory and its disorder • Be able to identify and explain what classic cases have contributed to our understanding of memory • What areas support memory? • Be able to discuss the involvement of a number of parts of the brain in supporting memory • Note developments to knowledge of that from classic cases • Synaptic change and memory • Be able to describe the mechanisms of learning and memory • Further study at home: where are memories stored in the brain Aims and learning outcomes • Early theorists: multi-store (‘modal’) model (e.g., Atkinson & Shiffrin, 1968) Sensory Stores Attention Decay Short-term Store Displacement Rehearsal Long-term Store Interference However: patient K.F Warrington & Shallice (1969) He had a Digit Span of 2 in comparison to normal span of 6-8 items Learning in other respects normal Memory ‘Architecture’: Early Model Classic case: H.M. H.M. was an epileptic who had his temporal lobes removed in 1953; bilateral medial temporal lobectomy His seizures were dramatically reduced—but so was his long-term memory H.M. experienced both mild retrograde amnesia and severe anterograde amnesia. - Retrograde (backward-acting): unable to remember the past - Anterograde (forward-acting): unable to form new memories • Retrograde (backward-acting) – unable to remember the past • Anterograde (forward-acting) – unable to form new memories Amnesia Classic case: H.M. H.M. was an epileptic who had his temporal lobes removed in 1953; bilateral medial temporal lobectomy His seizures were dramatically reduced—but so was his long-term memory H.M. experienced both mild retrograde amnesia and severe anterograde amnesia. - Retrograde (backward-acting): unable to remember the past - Anterograde (forward-acting): unable to form new memories While H.M. was unable to form most types of new long-term memories (LTM), his short-term memory (STM) was intact. Assessing H.M. - Short Term Memory • Digit span H.M. could repeat digits provided time between learning and recall is within the duration of STM i.e. immediate recall • Block-tapping memory-span test  this test demonstrated that H.M.s’ STM function was also good for spatial information - with immediate recall 4352718 19482756 Assessing H.M. – Long Term Memory • Digit span H.M. could repeat digits provided time between learning and recall is within the duration of STM i.e. immediate recall Does not benefit from repeated testing • Block-tapping memory-span test this test demonstrated that H.M.s’ STM function was also good for spatial information - with immediate recall 4 4 4 4 4 3 3 3 3 3 5 5 5 5 5 2 2 2 2 2 7 7 7 7 7 1 1 1 1 1 8 9 3 1 4 Mirror tracing Rotary pursuit Evidence of new learning Incomplete pictures Mirror tracing Rotary pursuit Evidence of new learning Incomplete pictures Scientific contributions of H.M.’s case • Medial temporal lobes are involved in memory • STM and LTM are distinctly separate – H.M. is unable to move memories from STM to LTM, a problem with memory consolidation • double dissociation with K.F. • Memory may exist but not be recalled – as when H.M. exhibits a skill he does not know he has learned (dissociation between explicit and implicit memory) • [Clive Wearing] • Musician and music scholar • Herpes simplex encephalitis; inflammation in left temporal lobe, with severe damage to hippocampus • “Clive knew that he was married, although he was unable to recall our wedding” • “Clive never knew we were divorced because he was incapable of knowing anything (new)” • “He knew facts about his childhood…after that his sense of his own autobiography got a bit hazy” • “If I said “St Marys,” Clive could say “Paddington,”, though he had no idea what it meant.” • “He could still read music” • “When I put my head round his door, his face registered a rush of delight and surprise as if he were about to dash to me as usual … but then he checked himself…he knew enough about himself to realise that although it might seem like months or years of absence to him, I might have been to the bathroom… He seemed to be learning” • “Clive says that he has never heard of John F. Kennedy or John Lennon” • “Clive could spell and speak back-to-front…some real intelligence alive in there” • “He is unable to provide definitions of a number of common words such as ‘tree’ and ‘eyelid’. He also has difficulty in recognising some common objects, for example jam and honey which he cannot distinguish from one another” Episodic and semantic Memory O Unlike episodic memory, semantic memory does not involve conscious recollection of the past O Extent of amnesia effects on each is different - episodic memory generally suffers more greatly (e.g., Spiers et al., 2001; Tulving, 2002; Vargha-Khadem et al., 1997) -but some patients show more specifically semantic memory deficits (e.g., Yasuda et al., 1997) O Different involvement of brain areas during encoding and retrieval (Wheeler et al., 1997) Autobiographical Memory • Patient K.C. • A double dissociation between impairments of personal and semantic memory has been observed (Dalla Barba et al., 1990; De Renzi et al., 1987; Hodges & McCarthy, 1993) • Neuroimaging data suggest that: visual imagery and emotion centres in the brain, as well as frontal areas involved in self-referential processing, are important for autobiographical memories (Cabeza et al., 2004; Conway et al., 2003; Greenberg et al., 2005) Amnesia: A Modal Model • Baddeley (see 2001) summarised a ‘modal model’ that accounted for most of the findings: Episodic memory learning involves associating items with their context using ‘mnemonic glue’ to tie episodes to context Recall and recognition involve the same underlying storage processes Semantic memory built from episodic memory A Problem for the Modal Model of Amnesia? O The case of Jon - developmental amnesia due to premature birth and anoxia, which resulted in specific, severe hippocampal damage - memory problems appeared obvious from age 5 - however, above average intelligence, good semantic memory - interestingly, impaired recall, but largely intact recognition (e.g., Baddeley, Vargha-Khadem, & Mishkin, 2001) Remember/know distinction Effects of Cerebral Ischemia on the Hippocampus and Memory • R.B. suffered damage to just one part of the hippocampus (CA1 pyramidal cell layer) and developed amnesia • R.B.’s case suggests that hippocampal damage alone can produce amnesia • H.M.’s damage – and amnesia – was more severe than R.B.’s Posttraumatic amnesia • Concussions may cause retrograde amnesia for the period before the blow and some anterograde amnesia after • The same is seen with comas, with the severity of the amnesia correlated with the duration of the coma • Period of anterograde amnesia suggests a temporary failure of memory consolidation Amnesia after Concussion: Evidence for Consolidation Gradients of Retrograde Amnesia and Memory Consolidation • Concussions disrupt consolidation (storage) of recent memories • Hebb’s theory – memories are stored in the short term by neural activity • Interference with this activity prevents memory consolidation. Examples: • Blows to the head (i.e., concussion) • ECS (electronconvulsive shock) Retrograde Amnesia • Often anterograde amnesia presents with retrograde amnesia also, but not always the case - have been shown to be independent (e.g., Baddeley & Wilson, 1986) • Unlike anterograde amnesia, there are assessment issues - one attempt used famous faces, and demonstrated Ribot’s law (Ribot, 1882), that older memories are more durable - other assessment scales involve news, sport, and entertainment - can also probe patients’ autobiographical memories - Autobiographical Memory Interview (Kopelman, Wilson, & Baddeley, 1990) assesses personal semantic memories and episodic memory The Hippocampus and Consolidation • Proposal that the hippocampus stores memories temporarily (standard consolidation theory) • Consistent with the temporally graded retrograde amnesia seen in experimental animals with temporal lobe lesions • Or, perhaps the hippocampus is involved in establishing memories, but they become “stronger” and less dependent on hippocampus over time Neuroanatomy of Object-Recognition Memory • Early animal models of amnesia involved implicit memory i.e recognition memory and assumed the hippocampus was key • 1970s – monkeys with bilateral medial temporal lobectomies show LTM deficits in explicit memory, the delayed nonmatching-to-sample test • Like H.M., performance was normal when memory needed to be held for only a few seconds (within the duration of STM) Delayed non-matching-to-sample test for monkeys • Aspiration used to lesion the hippocampus in monkeys – resulting in additional cortical damage • Extraneous damage is limited in rats due to lesion methods used • Bilateral damage to rat hippocampus, amygdala, and rhinal cortex produces the same deficits seen in monkeys with hippocampal lesions Delayed Nonmatching-to-Sample Test for Rats Object-Recognition Deficits and Medial Temporal Lobectomy Neuroanatomical basis of resulting deficits: Bilateral removal of the rhinal cortex consistently results in objectrecognition deficits Bilateral removal of the hippocampus produces no or moderate effects on object recognition Bilateral removal of the amygdala has no effect on object recognition To support materials in the book and activities above: Hippocampus and Memory for Spatial Location • The rhinal cortex plays an important role in object recognition. • The hippocampus plays a key role in memory for spatial location. • Hippocampectomy produces deficits in Morris maze and radial arm maze performance. • Many hippocampal cells are place cells, responding when a subject is in a particular place (and to other cues). • Grid cells are also found in the entorhinal cortex. Hippocampus and Memory for Spatial Location What areas support learning? Classical conditioning Investigate at home: Prefrontal Cortex -Prospective Cerebellum -Skills Striatum -Perception/Action • Hebb (1949) proposed that changes in synaptic efficiency are the basis of LTM • long-term learning comes about from cell assemblies • Simultaneous excitation of two or more cells • “neurons that fire together wire together”! How are memories made at the cellular level? Long-term potentiation (LTP) is consistent with the synaptic changes hypothesized by Hebb. • Synapses are effectively made stronger by repeated stimulation. • LTP can last for many weeks. • LTP only occurs if presynaptic firing is followed by postsynaptic firing. Synaptic Mechanisms of Learning and Memory • Elicited by HighFrequency Electrical Stimulation of Presynaptic Neuron; Mimics Normal Neural Activity • LTP effects are greatest in brain areas involved in learning and memory. • Learning can produce LTP-like changes. LTP as a Neural Mechanism of Learning and Memory LTP as a Neural Mechanism of Learning and Memory (Con’t) • Much indirect evidence supports a role for LTP in learning and memory. • Observation of Associative LTP • LTP can be viewed as a three-part process. • Induction (learning) • Maintenance (memory) • Expression (recall) Associated video for LTP to support following slides: https://www.youtube.com/watch?v=vso9jgfpI_c • Most Commonly Studied Where NMDA Glutamate Receptors Are Prominent • NMDA receptors do not respond maximally unless glutamate binds and the neuron is already partially depolarized. • Ca2+ channels do not open fully unless both conditions are met. Induction of LTP: Learning • Ca2+ influx only occurs if there is the co-occurrence that is needed for LTP, leading to the binding of glutamate at an NMDA receptor that is already depolarized. • Ca2+ influx may activate protein kinases • Protein kinase C • And CaM-KII • that induce changes, causing LTP. Induction of LTP: Learning (Con’t) • Pre- and Postsynaptic Changes • LTP is only seen in synapses where it was induced. • Protein synthesis (structural changes) underlies long-term changes. • LTP begins in the postsynaptic neuron, which signals the presynaptic neuron. Maintenance and Expression of LTP: Storage and Recall • How are presynaptic and postsynaptic changes coordinated? • Nitric oxide synthesized in postsynaptic neurons in response to Ca2+ influx may diffuse back to presynaptic neurons. • Structural changes are now a well-established consequence of LTP. Maintenance and Expression of LTP: Storage and Recall (Con’t) • Most LTP research has focused on NMDA-receptor– mediated LTP in the hippocampus, but LTP is mediated by different mechanisms elsewhere. • LTD (long-term depression) also exists. • Much of LTP and the neural basis of memory is still a mystery, despite many research discoveries. Variability of LTP • Memory and its disorder • Be able to identify and explain what classic cases have contributed to our understanding of memory • What areas support memory? • Be able to discuss the involvement of a number of parts of the brain in supporting memory • Note developments to knowledge of that from classic cases • Synaptic change and memory • Be able to describe the mechanisms of learning and memory • Further study at home: where are memories stored in the brain Aims and learning outcomes Investigate at home: Activity: Where Are Memories Stored? • Each memory is stored diffusely throughout the brain structures that were involved in its formation. • Some structures have particular roles in storage of memories: find the evidence in your texts, and past and future lectures • Hippocampus: spatial location • Perirhinal cortex: object recognition • Mediodorsal nucleus: roles evident through Korsakoff’s symptoms • Basal forebrain: roles evident through Alzheimer’s symptoms Investigate at home: Activity: Where Are Memories Stored? • Damage to a variety of structures results in memory deficits. • Inferotemporal Cortex • Visual perception of objects • Changes in activity seen with visual recall • Amygdala • Emotional learning • Lesions of the amygdalae disrupt fear learning. Investigate at home: Activity: Where Are Memories Stored? • Prefrontal Cortex • Temporal order of events and working memory • Tasks involving a series of responses • Different parts of the prefrontal cortex may mediate different types of working memory. • Some evidence from functional brain imaging studies Investigate at home: Activity: Where Are Memories Stored? • Cerebellum and Striatum • Cerebellum • Stores memories of sensorimotor skills • Striatum • Habit formation To support materials in the book and activities above: • The most common type of dementia (over 50% of cases) • Characterised by an increasingly severe deficit in episodic memory • Difficult to diagnose at the early stage due to the range of symptoms - diagnosis requires memory impairment along with at least two other cognitive deficits, such as executive function, language • Two signs of AD at the level of the brain are: 1) Amyloid plaques, and 2) neurofibrillary tangles Alzheimer’s Disease To support materials in the book and activities above: O Initial stages of disease involve medial temporal lobes and hippocampus, hence the memory problems - other cortical areas are affected with disease progression (prefrontal cortex) - progression is varied (Becker, 1988; Baddeley et al., 1991) - but, episodic memory impairment is the defining feature (Salthouse & Becker, 1998) O In fact, deterioration in social ability and personality can be most concerning for relatives Alzheimer’s Disease To support materials in the book and activities above: Alzheimer’s Disease To support materials in the book and activities above: • Patients show episodic memory deficits for verbal and visual material, with recall and recognition (Greene et al., 1996) - tend to exhibit the recency effect until more advanced stages - as disease progresses, semantic memory also deteriorates, which is associated with temporal lobe damage (e.g., Hodges et al., 1994) • Implicit learning has been observed for rather automatic tasks (Beauregard et al., 2001; Heindel et al., 1989; Moscovitch, 1982) • WM moderately affected, but dual-tasking ability specifically impaired (e.g., Baddeley et al., 2001) – help earlier diagnosis? Alzheimer’s Disease To support materials in the book and activities above: • Most commonly seen in individuals with alcohol addiction (or others with a thiamine deficiency) • Amnesia, confusion, personality changes, and physical problems • Typically damage in the medial diencephalon – medial thalamus + medial hypothalamus • Amnesia comparable to medial temporal lobe amnesia in the early stages • Anterograde amnesia for episodic memories • Differs in later stages • Severe retrograde amnesia develops • Differs in that it is progressive, complicating its study Amnesia of Korsakoff’s Syndrome To support materials in the book and activities above: • Hypothalamic mammillary bodies? • No – Korsakoff’s amnesia is seen in cases without such damage • Thalamic mediodorsal nuclei? • Possibly – damage is seen here when there is no mammillary damage • Cause is not likely to be damage to a single diencephalic structure What Damage Causes the Amnesia Seen in Korsakoff’s? To support materials in the book and activities above: • Progressive loss of conceptual knowledge • Impairment associated with progressive loss of neurons in left temporal lobe • Semantic knowledge is associated with anterior temporal lobes Semantic dementia • Pinel (whatever edition) “Biopsychology” chapter on ‘Learning, Memory and Amnesia’ (chapter 11 in 11th, 10th and 9th Editions) • You may wish to revisit synaptic transmission more generally: ‘Neural Conduction and Synaptic Transmission’ is chapter 4 in 11th, 10th and 9th Editions And again: • Genes to Cognition online: http://www.g2conline.org (for use of 3D brain tool) Required Reading • http://www.youtube.com/watch?v=Lu9UY8Zqg-Q • http://www.youtube.com/watch?v=xCyvzI2aVUo • http://www.youtube.com/watch?v=9BrCBq2FY_U • http://www.youtube.com/watch?v=UKxr08GEE54&featu re=related A more extended version of Clive Wearing Documentary (4 parts) Additional (strongly!) suggested readings • Article by Deborah Wearing: • https://www.telegraph.co.uk/news/health/3313452/The-m an-who-keeps-falling-in-love-with-his-wife.html • Article by Oliver Sacks; https://www.newyorker.com/mag azine/2007/09/24/the-abyss • Recent paper by Alan Baddeley on reconsidering the modal model: https://doi.org/10.1016/j.neuropsychologia.2020.107590 • Recent paper showing single cell recording as part of wider investigation: https://doi.org/10.1016/j.tics.2019.03.006