BEhavioral nero: memory Flashcards

1
Q

Henry Molaison (patient HM)

A
  • HM is the most studied patient in history of neuroscience (see Corkin, 2002)
  • 1926 – 2008 (aged 82)
  • Severe temporal lobe epilepsy. Likely as a result of a bicycle accident as a child
  • Surgery to reduce the seizures. Did reduce seizures, BUT Profound and selective impact on HM’s memory function
  • catastrophic outcome ensured that the surgery was not repeated
  • HM is unique
  • And research on HM had a profound impact on models of memory function
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2
Q

Theories of memory prior to HM

A
  • In the mid 20th century, memory function was believed to be distributed throughout the cortex
  • memory thought to be well integrated with perceptual and intellectual functions
  • no region of the brain was believed to be disproportionately dedicated to memory
  • C.f. the known localization (at the time) of motor function and language (Broca’s area)
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3
Q

Models of memory after HM

A
  • studies of HM heralded the modern era of memory research. early descriptions of HM set the direction of subsequent work on memory
  • Basic findings
  • profound forgetfulness
  • absence of any general intellectual or perceptual deficit
  • impairment extended to both verbal and non-verbal material
  • affected information acquired through all sensory modalities
  • established the principle that memory is a distinct cerebral function
  • separable from perceptual and cognitive abilities
  • identified the medial aspect of the temporal lobe as important for memory
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4
Q

HM’s temporal lobe surgery

A
• Bilateral resection of extensive mesial temporal tissue 
• William Scoville 
• 1953 at age 27
Structures removed
• amygdala
• most of hippocampi
• part of parahippocampal gyrus
• Connections severed with the frontal cortex
• With unknown consequences
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5
Q

Anatomical views of HM’s brain

A

MRI BY Corkin et al. (1997)
• Scan made in 1998
• relatively low resolution (1mm)
• Post-mortem autopsy by Annese et al. (2014)
• orbitofrontal lesions likely during the surgery
• affecting working memory?
• cerebellar atrophy due to long term use of phenytoin

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6
Q

Medial Temporal Lobe and Hippocampal formation

A
Medial Temporal Lobe 
• Sagittal section
• Medial surface of right hemisphere
• Hippocampal formation 
• Bilateral view
• anterior(ish)
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7
Q

Impact of temporal lobe surgery on other fuction of HM

A
  • Tested in 1955, age 29 Scoville & Milner (1957)
  • Shown to have normal attention span, preserved intelligence
  • Retrograde memory recovered over time
  • Reported date as March 1953 (6 months before operation)
  • Believed he was 27 years old
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8
Q

Memory systems:

Retrograde vs. Anterograde amnesia

A
  • Retrograde amnesia
  • impairment for memories created prior to injury
  • Anterograde amnesia
  • impairment for memories created after injury
  • impairment in learning novel (new) information
  • HM had a severe anterograde amnesia
  • declarative vs. procedural
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9
Q

Memory systems:

Declarative vs. Procedural memory

A
  • Declarative memory
  • conscious access to information learned previously (fact and event)
  • Procedural memory
  • (nondeclarative) remembering ‘how to’
  • (e.g. playing piano)
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10
Q

HM’s Declarative memory

post-op

A
  • Declarative memory function severely impaired
  • Couldn’t navigate to find his new family home even after 10 months
  • Unable to recall names or faces of new people Despite frequent visits over the years
  • Remembered that his mother died But not that his uncle had, leading to perpetual grief everytime
  • Language largely frozen in 1950’s
  • Some exceptions (Ayatollah, Rock n Roll)
  • Could retain verbal information if rehearsed
  • Once distracted all information lost
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11
Q

HM’s Procedural memory(post-op)

A
  • Procedural memory function continued intact after surgery
  • Still able to learn new skills but has no recall of learning them (because of a declarative impairment)
  • Normal performance on procedural memory tasks
  • Spared ability to learn new perceptual-motor skills
  • mirror drawing
  • Corkin (2002)
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12
Q

What does HM tell us about function of mesial temporal lobe on memory?

A
  • Mesial temporal lobe structures essential for memory function
  • Mesial temporal lobe structures more essential for anterograde than retrograde memory
  • Distinction between Declarative and Procedural memory
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13
Q

The long term contribution of studies of HM (why is it important)

A
  • Non-human primate research in the 1980’s clarified which parts of HM’s lesion are important for memory Mishkin (1978)
  • The extent of HM’s surgery only fully understood post-mortem
  • Scoville failed to remove the caudal 2cm of HM’s hippocampus
  • The surgery likely damaged fibres linking the temporal pole with the frontal lobe
  • There was evidence of a lesion in the frontal lobe (from surgery)
  • Other patients with similar surgery were not systematically studied as neurological/psychiatric symptoms made them less desirable as a “pure” amnesic
  • Henry Molaison remains unique
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14
Q

What have we learned since HM?

A
  • Intact memory function relies on a neuroanatomical network, which involves many brain regions.
  • The Temporal Lobes (TL) are the ‘engine’ of memory.
  • Functional asymmetry of the brain
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15
Q

Schematic representation of Medial Temporal Lobe

A
  • Sensory information sent to hippocampal formation via association for long-term storage
  • Memories involve reciprocal connections between hippocampal formation and temporal neocortex
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16
Q

The Hippocampus and

Hippocampal Formation

A
  • Mesial temporal lobe bilaterally
  • CA1 to CA3 (CA4 is regarded as part of dentate gyrus)
  • Also known as Cornu ammonis (Ammon’s horn)
  • Hippocampal Formation
  • Dentate gyrus + Hippocampus (CA1 to CA3) +Subiculum
17
Q

Role of the Hippocampal Formation

A

• Hippocampal formation and surrounding structures are essential for learning and consolidating novel information
• Hippocampal formation necessary for relational memory
• Paired Associate Learning tasks
• Required to remember an association between arbitrary (unrelated) pieces of information
• e.g. word and object
The role of Hippocampal Formation in memory retrieval is not clear

18
Q

Principal extra-temporal connections to the medial temporal lobe
(talk about role and structure)

A
  • The role of the temporal lobes in memory function is well-known
  • Three regions beyond the temporal lobes also play an important role in memory:
  • Papez’s circuit
  • Frontal Lobes
  • Diencephalon
19
Q

Papez’s Circuit

A
  • 1937 – James Papez proposed that a specific brain circuit was devoted to emotional experience and expression
  • Papez’s circuit comprises:
  • Mammillary bodies
  • Fornix
  • anterior thalamic nuclei (ATN)
  • cingulate gyrus
  • hippocampus
  • The Limbic System = Papez’s circuit + Amygdala
20
Q

Papez’s Circuit lesions

A
  • The general view:
  • lesions to components of the Papez circuit result in declarative memory impairment (poor relational memory/encoding)
  • Lesions also affect function other than memory
  • A declarative memory impairment is most frequent when the hippocampus or anterior thalamic nuclei (ATN) are lesioned
21
Q

Role of the amygdala in memory

A
  • Key role in supporting memory for emotionally arousing experiences
  • Classical fear conditioning
  • Facilitates rich representations of emotional experiences
  • Lesions result in
  • loss of conditioned fear and impairment of new fear learning
  • Reduced memory for emotionally laden events
22
Q

The Frontal Lobes

A
Motor programming
• Planning and executing movement
• Physical action
• Eye movements
• Language
Cognitive control processes 
• Problem solving
• Planning
• Monitoring
• Self-correction
23
Q

The Frontal Lobes and Memory

A

Frontal lobes are involved in memory encoding and retrieval strategies
• Damage to the frontal lobes leads to impairments in remembering contextual details
• The source of information
• chronological order of memories
• Frontal lobes damage can result in confabulation: statements involving bizarre distortions of memory

24
Q

Diencephalon

A

-play a role in memory storage, make connection with other region of the lobe
• ‘interbrain’
• Thalamus
• Hypothalamus

25
Q

Thalamus and memory

A
  • No single area in the thalamus accounts for memory problems, but damage to;
  • The anterior and medial thalamus contributes to amnesia
  • The mammillo-thalamic tract (MMT) lead to deficit of episodic long-term memory. relative sparing of intellectual capacities and relative sparing of short-term memory
  • The dorsal medial nucleus :deficits in selecting the appropriate information to be retrieved
  • The Intralaminar/Midline nuclei results in deficits in memory retrieval and semantic memory(facts)
26
Q

Synaptic Plasticity & Hebb’s Rule

A
  • Learning involves changes in synaptic function
  • Synaptic plasticity
  • The biochemistry of synapses change
  • Alters the effect on the post-synaptic neuron
  • Hebb’s rule:
  • If neuron A repeatedly excites neuron B,
  • Changes take place in both neurons, so that
  • neuron B is more easily excited by neuron A
27
Q

LTP causes synaptic changes

A
  • Plasticity is usually associated with glutamatergic synapses
  • Glutamate is an excitatory neurotransmitter
  • LTP changes the efficacy of the synapse
  • increasing or decreasing the amount of neurotransmitter released
  • the number of receptors in the post-synaptic membrane
  • LTP also alters protein synthesis in post-synaptic dendrites
28
Q

Long-term Potentiation in Memory experiment

A
  • Schaffer collateral/CA1 synapses in the hippocampus of rat brain
  • Baseline EPSP for single electrical shock of .01 mA for 100 us duration
  • Tetanus of 100 electrical shocks in 1 sec
  • LTP seen as increased EPSP for subsequent single electrical stimulus
29
Q

Where does LTP occur in the brain

A
  • Structures associated with Temporal Lobe
  • Hippocampus
  • particularly CA1 and dentate gyrus
  • Entorhinal cortex
  • Amygdala
  • Structures beyond the Temporal Lobe
  • Prefrontal cortex
  • Motor cortex
  • Thalamus
  • Visual cortex
  • Reflects learning and memory across the brain
  • Both at the level of forming and retrieving memories
30
Q

Other mechanisms of synaptic plasticity

A

• Long-Term Depression
Low frequency stimulation at synapse can decrease synaptic strength
• Habituation
Repeated stimulation reduces strength of synaptic response (reduced neurotransmitter release)
• Sensitization
single noxious stimulus causes exaggerated synaptic response to repeat presentation of noxious stimulus