#10621 - The Neural Basis Of Amnesia Lec 3 - Neuropsychology of Memory

The Neural Basis of Amnesia

Problems with human data:

• Lesions are rarely localised to a single structure making it difficult to be precise about the exact pathology characteristic of amnesia (Aggleton & Pearce, 2001)

• Functional imaging can provide insight into which brain regions are active or inactive during healthy controls or amnesic patients during an episodic memory task BUT- cannot establish cause and effect from this further evidence from precise lesion studies is needed to substantiate the claims.

• The literature regarding amnesia, especially in rarer disorders, is based on evidence from single case studies due to a lack of sufficient cases available to researchers.

• Patients may have a mix of problems e.g. Clive Wearing – preserved semantic, intact STM but impaired LTM + confabulation unlikely to have damage limited to one area

Animal models of amnesia:

• Provides an opportunity to overcome some of these issues and has been necessary to further develop our understanding of the neural bases of amnesia

• Allows precise lesion, genetic and molecular techniques to be carried out that cannot be ethically applied to humans (Dere, 2006)

• Allows for the controlled conduction of experiments to assess the neurobiological basis of human memory dysfunction (Winters, 2010)

DMTS – Delayed Match to Sample Test

• One way of assessing episodic like memory (ELM) is the delayed non match (DMNS) and delayed match to sample (DMTS) task.

• An animal is first presented with a sample stimulus and after a retention delay, the sample object is presented alongside a novel stimulus.

• The subject is required to seek out the novel (DNMTS) or sample (DMS) stimulus in order to obtain a reward (Winters et al., 2010).

• Monkeys are typically good at this amnesia sensitive task however lesions to the hippocampal formation, parrahippocampal cortex and perirhinal cortex, crucial neural structures implicated in human amnesia, result in severe impairments (Zola-Morgan et al., 1993).

• Zola-Morgan et al (1993) lesioning several different combinations of areas in the monkey

• They demonstrated that their H++ lesion which includes the hippocampal formation, perirhinal cortex, - but sparing the amygdala produces the greatest memory deficit in the amnesia sensitive task of DMTS

• Hippocampus + surrounding cortex plays an important role in performing DMTS in monkeys

• Amygdala plays little or no role

• Hippocampus + surrounding cortex has become known as the medial temporal lobe memory system (MTLMS)

Support for the amygdala playing little or no role

Bechara et al (1995) Double dissociation of conditioning + declarative knowledge relative to the amygdala + the hippocampus

• Patient with selective bilateral damage to amygdala = impaired at conditioning autonomic (SCR’s) responses to visual/auditory stimuli – but did acquire the declarative facts about which visual/auditory stimuli were paired with the unconditioned stimulus

• Patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning

• Patient with bilateral damage to both amygdala + hippocampal formation acquired neither the facts nor the conditioning

• Demonstrates a double dissociation of conditioning + declarative knowledge relative to the human amygdala + hippocampus

Squire’s MTLMS (MEDIAL TEMPORAL LOBE MEMORY SYSTEM): (Squire, Stark & Clarke, 2004)

• MTLS includes system of anatomically related structures that are essential for declarative memory (conscious - facts + events) – makes a memory system

• Consists of the hippocampal region + the adjacent perirhinal + entorhinal + parahippocampal cortices

• Three pieces of evidence that the MTLMS contributes to declarative memory

1. Patients with damage limited to hippocampal region have a moderately severe memory impairment – less severe than those found in patients with larger lesions inc MT cortex (Corkin, 1997)

2. Systematic comparisons of monkeys with MTL lesions – monkeys with limited hippocampal lesions = moderately impaired but monkeys with lesions that inc hippo region + adjacent cortex = more severe memory impairment (Zola-Morgan et al, 1994)

3. Impairment is multimodal – memory affected regardless of sensory modality info is presented in consistent with the fact that structures of the MTL = convergent zones of cortical processing + receive input from all sensory modalities

Can model all types of amnesia through the use of animals:

• DMTS = AA memory

• Spared abilities (motor + cognitive skills) Zola-Morgan & Squire (1984)

• Monkeys with conjoint lesions to the hippocampus + amygdala (modelling HM)

• Exhibited normal acquisition of two motor skills tasks – manoeuvring a bread stick – keep intact

• Procedural learning spared in amnesia

Zola-Morgan & Squire (1990) – RA with temporal gradient

• RA studied prospectively in monkeys to understand the contribution of the hippocampal formation to memory function

• Monkeys learned to discriminate 100 pairs of objects beginning 16, 12, 8, 4 + 2 weeks before surgery to remove the hippocampal formation

• Two weeks after surgery memory was assessed by presenting each of the 100 objects pairs for a single-choice trial

• Normal monkeys exhibited forgetting - remembered recently presented objects better

• Monkeys with hippocampal damage were severely impaired at remembering recently presented objects – but they remembered objects learnt long ago as well as normal monkeys – remembered these sig better than objects presented recently TEMPORAL GRADIENT (but in humans usually yrs not wks)

• Show that hippocampal formation is required for memory storage for only a limited period of time after learning

• As time passes its role diminishes + a more permanent memory gradually develops independently of the hippocampal formation - probably in neocortex

SQUIRES VIEWS:

• MTLMS is the neural substrate of declarative memory - damage to this system results in amnesia

• The greater the amount of damage to the MTLMS then the greater memory of the impairments

• The hippocampus is needed to temporarily bind together distributed sites in neocortex that together represent the whole memory (Squire, 1992)

• There is a gradual process of reorganisation or consolidation within declarative memory because the contribution of the hippocampus + related structures gradually diminishes + the neocortex alone gradually becomes capable of supporting usable permanent memories (Squire, 1992)

• Memories are stored in the neocortex

• Hippocampus works with the neocortex to allow memories to be encoded + accessible consolidation

• When fully established (consolidated) memories can be accessed without the hippocampus

• This theory explains spared abilities AA, RA + temporal gradient of AA – what about time scale problem?

PROBLEMS WITH SQUIRES VIEW

• How long does this consolidation take?

• Doesn’t address the issue of why just declarative (episodic) memory is impaired why don’t other memories need consolidation?

ALTERANTIVE VIEWPOINT – THE SPATIAL HYPOTHESIS

• The hippocampus as a cognitive map (O’Keefe & Nadel, 1978)

• Argued that a cognitive map is formed + used by the hippocampus

• Suggested that the processing, storage + retrieval of spatial information is the primary + pehaps exclusive role of this area (O’Keefe, 1999)

• Evidence

• Cells within the hippocampus of rats + monkeys are sensitive to the spatial location they are in (O’Keefe & Dostrovsky, 1971)

• Hippocampal damage has consistently been shown to disrupt animals performance on spatial navigation task of the Morris water maze (Morris et al, 1992)

• Maguire et al (1997) route recall in London taxi drivers produced greater right hippocampal FRMI activation than recall of non-spatial info

• Maguire et al (2000) – London taxi drivers had larger posterior hippocampal + smaller anterior hippocampal relative to controls

• Maguire et al (2000) right hippocampal size difference correlated with the length of time spent working as a taxi driver - indicating this is a consequence of experience

• Problems with the cognitive mapping idea

• Animals with hippocampal lesions can learn some spatial tasks to the same level as controls – albeit more slowly

• Animals with hippo lesions are impaired on some non-spatial problems

• Neurons in hippo reflect more info than just space – visual cues, context, task – so the maps not a very good (Smith & Mizumori, 2008)

GAFFAN (1994) – SCENE MEMORY (variant on the spatial hypothesis)

• Scene construction = process of mentally generating and maintaining a complex + coherent scene or event - achieved by the retrieval + integration of relevant info...