Involvement of Medial Temporal Lobe Structures in Memory and Perception

1. Involvement of Medial Temporal Lobe Structures in Memory and Perception Review: Point/Counterpoint Mark G. Baxter Caitlin Mullin

2. Outline • Review Medial Temporal Lobe • MTLMS Hypothesis • Perceptual-Mnemonic Hypothesis • Evidence: • Monkey Lesion studies • Perceptual-Mnemonic Model • Human Lesion studies • Skip the criticisms – come back during discussion • Summary and Conclusion

3. Medial Temporal Lobe (MTL) • Hippocampus • Connected areas • Entorhinal cortex • Perirhinal cortex • Parahippocampal cortex Bird & Burgess, Nature Reviews Neuroscience 9, 182-194

4. Function of MTL • Principally concerned with memory • Operates with neocortex to establish and maintain long-term memory • Ultimately, through a process of consolidation, becomes independent of long-term memory MTL Simons & Spiers (2003) Nature Reviews Neuroscience4; 637-648

5. Landmark MTL Memory Study • Scoville & Milner, 1957 (J Neurol Neurosurg Psychiatry. 1957 Feb;20(1):11-21.) • Patient H.M • Large bilateral resection of the medial temporal lobe • Memory impairment • Severe, long-lasting • Limited to certain forms of memory • i.e. Declarative memory for facts and events • This became the standard view of the function of MTL Corkin (2002)Nature Reviews Neuroscience 3, 153-160

6. Medial Temporal Lobe Memory System Hypothesis (MTLMS) • The medial temporal lobe is specialized for declarative/relational memory function including both episodic and semantic memory with little or no substantial role in perception • This hypothesis is well accepted in the literature

7. MTL = Memory + Perception? • Approx. 15 years ago, investigations of MTL revealed a potential perceptual function: • Non-human primates • Humans • These discoveries opposed the MTLMS hypothesis

8. Perirhinal Cortex Contributes to Perception and Memory • Connections to perhirhinal cortex suggest involvement in object perception • According to MTLMS MTL plays no role in the perception of visual stimuli • Perirhinal cortex is definitively part of the MTL • The anatomical picture is misleading • The prevailing theory needs correction But... Murray et al (2007). Annu. Rev.Neurosci.30, 99-122

9. Perception/Mnemonic Hypothesis of MTL • MTL and in particular the perirhinal cortex play an essential role in visual perception as well as memory

10. Testing for Perception in Rhinal Cortex : Eacott et al. (1994) Sample • Macaque rhinal cortex lesioned • Delayed match-to sample (DMS) • Results of lesioned group • Good performance at short delays • Poor performance at long delays • Resembles pattern of human amnesic patients with MTL damage Delay Match

11. Testing for Perception in Rhinal Cortex : Eacott et al. (1994) Sample • Visual perceptual demands were increased • stimuli smaller and removing colour • “0-second” delay match-to-sample • choices appeared when the sample stimulus disappeared • Simultaneous match-to-sample • both the sample and the choices were visible at the same time Impaired performance in the absence of memory demands (simultaneous and 0 s matching conditions) suggested an impairment in some aspect of perceptual processing Delay ( 0’s or simultaneous) *Without long delays: Expect high performance Match

12. Testing for Perception in Rhinal Cortex : Buckley & Gaffan (1997,1998) • Monkeys with perirhinal cortex lesions impaired at: • Generalization of discrimination to new views of familiar objects • Discriminating large but not small stimulus set • Suggested that difficulty arose when required to visually discriminate a situation that would be perceptually demanding These findings support a role for perirhinal cortex in being able to perceptually identify objects, not just remember them.

13. Testing for Perception in Rhinal Cortex : Buckley et al., 2001 • Tested monkeys with perirhinal cortex lesions on oddity discriminations • Identify odd image for reward • No overt visual memory component • Results show impairment: • Different viewpoints of objects and faces • Degraded images of objects and scenes • No impairment on problems using: • Color, Shape or Size • Impairments were observed on discriminations taxing complex object discrimination This finding argues in favour of a perceptual deficit rather than a problem with memory

14. Formal Models of Perirhinal Cortex Involvement in Perceptual Function • Problem: • “the definition of what constitutes perception is nebulous” • Solution: • Bussey and Saksida (2002) developed a computational model to make explicit predictions of how damage to perirhinal cortex would affect performance in visual learning tasks • In this model, the perirhinal cortex is at the apex of a hierarchically organized system of visual cortical areas • The perirhinal cortex is required to resolve discriminations with a high degree of ‘‘feature ambiguity’’

15. What constitutes a feature? • Model suggests discrimination problems that can only be solved based on a combination of features requires the perirhinal cortex for their solution • Biconditional visual discrimination problem AB+, CD+, BC-, AD- • Each capital letter represents an individual feature • Each pair of letters represents an individual stimulus that is associated with reward (+) or nonreward (-) • Requires processing of feature conjunctions • Each individual feature is ambiguous—and should be impaired by perirhinal cortex damage These discrimination problems place equal demands on memory, because the number of stimuli to be associated with reward (or nonreward) is the same in each case

16. Testing the Model • Bussey et al., 2002 tested prediction in monkeys with perirhinal lesions • Training on visual discrimination problems in conditions of minimal intermediate, or maximal feature ambiguity • If PRC is only involved memory • Equivalent impairments in all three conditions • If PRC is involved in perception • Degree of impairment should interact with the perceptual demands of the visual discrimination

17. Results of Model • The greater the degree of feature ambiguity, the greater the magnitude of the impairment after perirhinal cortex lesions • According to the model the perirhinal cortex is most important for conjunctions of a relatively high level of complexity Bussey et al. (2002). Eur. J Neurosci. 17, 649

18. Human Lesion Studies: Barense et al., 2005 • Same pattern of impairment is seen in humans with temporal cortex lesions that include the perirhinal cortex Model accurately simulated the effects of lesions of perirhinal cortex in monkeys, as well as human Barense et al.,(2005) J Neurosci, 25

19. Human Lesion Studies: Morphed Images • Related experiments have used a ‘‘morphing’’ approach to create feature ambiguity between visual stimuli and have examined impairments in learning ‘‘morphed’’ discriminations Impairments emerge as the degree of feature ambiguity, created by ‘‘morphing,’’ increases Levy et al., 2005

20. Hippocampus and Perception • Humans with selective hippocampal lesions were impaired at oddity discriminations among virtual-reality ‘‘scenes’’ Oddity task stimuli Lee et al., 2005

21. Advancing the Understanding of the Organization of Brain Systems for Cognition Human Hippocampal Lesion Studies: • Graham et al., 2006 • Intact perceptual learning and categorization of faces, but not of virtual-reality scenes • Bird et al., 2008 • Recognition memory for scenes is impaired in patients with amnesia consequent to hippocampal damage, but recognition memory for faces is not • Bird & Burgess, 2008 • Impaired recognition memory for words, but intact recognition memory for faces in patients with hippocampal lesions • No reason to expect the hippocampus to be involved in memory for scenes but not faces if it has a general role in declarative memory A role for the hippocampus in representation of spatial or contextual information, used for both perception and memory, is able to account for all of these observations

22. Summary and Conclusions • MTLMS hypothesis is compelling • Most amnesic patients with MTL lesions present with amnesia rather than agnosia • However, we have seen impairments in performance when task become more perceptually demanding while attempting to keep memory stable • Delayed Match-to-Sample • Oddity Discrimination • Feature Conjunction task • Morphed Images task

23. Summary and Conclusions • Forces a reconsideration of the MTLMS view • Perceptual-mnemonic view of MTL • Many questions remain to be resolved… • Progress in this area depends on: • Acknowledging the possibility that the involvement of MTL structures in cognition extends beyond the domain of memory

24. Thank you