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
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)
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
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
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
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)
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
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
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)
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
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)
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
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
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
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
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
Thalamus and memory
* 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
Synaptic Plasticity & Hebb’s Rule
* 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
LTP causes synaptic changes
* 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
Long-term Potentiation in Memory experiment
* 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
Where does LTP occur in the brain
* 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
Other mechanisms of synaptic plasticity
• 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
Bio Psy
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