Memory Processing Notes: Temporal Lobes and Beyond

Memory Processing: Temporal Lobes and Beyond

Introduction

• We're shifting from sensory processing and vision to memory as a distinct process.
• Today's focus: fundamental aspects of memory.
• Thursday: Jo Robson will discuss clinical work in dementia.
• We'll explore the temporal lobes' role in memory, building on our previous discussion of object recognition.

Clinical Case: Henry Molaison (H.M.)

• H.M. (Henry Molaison), the most studied patient in neuroscience, died in February 2008 at age 82.
• Crucial because we have pre-event functional data.
• Surgery aimed to reduce seizures from temporal lobe epilepsy due to limited treatment options at the time like surgical intervention.
• Seizure origin points in the temporal lobe were surgically removed, successfully reducing seizures but causing profound forgetfulness.
• This forgetfulness affected verbal and nonverbal material across all sensory modalities.
• H.M. had no intellectual or perceptual deficits; his ability to process information was intact.
• His case highlighted a specific memory deficit due to the surgery.
• H.M. was psychiatrically normal before the surgery, so changes were attributed to a specific memory deficit related to the specific lesion from the surgery.
• Prior to H.M., memory was thought to be distributed throughout the cortex.
• H.M.'s case led to the realization that memory is a distinct cerebral function.
• Multiple types of memory processes exist, separate from perception and cognition.
• The medial temporal lobe is particularly implicated in memory function.

Details of H.M.'s Surgery

• Bilateral resection of mesial temporal tissue.
• Areas targeted for surgical removal are dark areas.
• Structures removed: amygdala, most of the hippocampi, and part of the parahippocampal gyrus.
• Extensive tissue removal likely severed connections from neurons not directly removed, affecting connectivity.

Post-Mortem Analysis and Additional Findings

• MRI technology allowed structural analysis post-surgery.
• Postmortem autopsy in 2014 revealed additional signs of collateral damage: an orbitofrontal lesion potentially caused during surgery, possibly impacting working memory.
• Cerebellar atrophy was evident from long-term medication use.
• Functional changes in H.M. may not be solely due to the temporal lobe lesion.

Impact of Surgery on H.M.

• Two years post-surgery, no impact on personality, attention span, or verbal memory.
• Profound and selective impact on past memory; poor recollection of years prior to surgery.
• H.M. believed the date was March 1953 (six months before the operation).
• Past memory recovered over time, but the capacity to form new memories did not.
• H.M. couldn't remember events after the surgery, highlighting potential differences in brain regions for past vs. new memories.
• Retrograde amnesia: impairment for memories created prior to the injury.
• Anterograde amnesia: impairment for memories that you might want to create after an injury - impairment in learning novel information.
• Sensory information worked normally, but the ability to retain information was lost.

Types of Anterograde Amnesia

• Declarative memory (facts and events) vs. procedural memory (skills and tasks).
• Declarative memory: conscious access to learned information; abstract information.
• Procedural memory: remembering how to do things; skill-based learning.
• H.M.'s declarative memory was severely impaired post-op.
• He couldn't navigate to find his family home or recall names/faces of new acquaintances.
• Language was largely frozen in the 1950s.
• He could retain new information with active rehearsal but lost it upon distraction (working memory intact).
• Procedural memory was relatively unaffected; he could learn new skills with no memory of learning them. (like mirror drawing)

Mirror Drawing Task

• Task where person draws a star by looking in the mirror.
• Visual information says to move the pencil the right, but mirror reverses that.
• Requires learning a new mapping between visual input and motor sequencing.
• H.M. showed clear evidence of learning over days, despite lacking conscious memory of the task.

What H.M. Tells Us About Memory

• Temporal lobe (mesial temporal lobe) essential for memory function, more for anterograde than retrograde memory.
• Past memories rely on brain areas outside those removed during surgery.
• Difference between declarative and procedural memory, as H.M. could learn new tasks but not remember new information.
• Relationship between structure and memory function not completely clear.
• Extent of surgery only truly understood post-mortem.
• H.M. is one case study.
• Intact memory function relies on an extended network.
• Functional asymmetry in memory function (left and right sides play different roles).

Anatomy of the Temporal Lobes

• Lateral view of the right hemisphere shows superior, middle, and inferior temporal gyrus.
• Gyri: superior, middle, and inferior temporal gyrus.
• Sulci: superior temporal sulcus and the inferior temporal sulcus.
• Medial surface shows the hippocampus and parahippocampal gyrus.

Medial Temporal Lobe Subregions

• Entorhinal cortex, perirhinal cortex, amygdala, hippocampus, and parahippocampal complex play distinct roles in memory function.
• Connectivity: Unimodal and polymodal association areas (frontal, temporal, and parietal areas) connect to the periorhinal cortex and the parahippocortex.
• Those make connections via the inter rhinal cortex to he hippocampal formation.
• Sensory information is sent to the hippocampal formation for long term storage; reciprocal connections between the hippocampal formation and temporal neocortex.

Hippocampal Formation

• Hippocampal formation essential for learning and consolidating novel information. The sub areas are CA1 to CA3.
• Necessary for relational memory, as demonstrated by paired associate learning tasks (arbitrary associations).
• Hippocampal formation is important for making those associations.
• Retrieving memories may involve processes outside the hippocampal formation.
• Direct connections exist between sensory areas and temporal areas.

Memory Structures Beyond the Temporal Lobes

• Papez circuit (amygdala, hippocampus, fornix, mammillary body, and cingulate gyrus) proposed by James Papez as a circuit for emotional experience and expression.
• The limbic system incorporates the amygdala.
• The anterior thalamic nuclei is involved in declarative memory.
• Alzheimer's disease associated with reduced neural activity in the Papez circuit.

Amygdala

• Key role in fear conditioning and emotional processing.
• Supports memory for emotionally arousing experiences.
• Lesions result in loss of conditioned fear, impaired fear learning, and reduced memory for emotionally charged events.

Frontal Lobes

• Important for memory encoding and retrieval strategies.
• Lesions cause impairments in contextual details (source, chronological order).
• Damage can result in confabulation (distortions of memories).
• Connections exist between frontal lobes and the hippocampus/parahippocampal areas.

Diencephalon (Thalamus and Hypothalamus)

• Thalamus plays a role in sensory information and has connectivity with memory-related areas.
• Anterior and medial thalamus contribute to amnesia.
• Damage to the mammalothalamic tract results in deficits of episodic long term memory, particularly, your ability to remember particular events.
• Dorsal medial nucleus damage: deficits in selecting appropriate information for retrieval.
• Intralaminal midline nuclei damage: deficits in memory retrieval and semantic memory.

Memory at the Level of the Individual Neuron

• Memory formation relies on changes at the level of individual neurons.
• A typical neuron has a cell body, dendrites (input), and axon (output).
• Neurons exist in a network with signals traveling to and from.

Synaptic Transmission

• At the synapse (between neurons), an electrical signal is converted into a chemical signal (neurotransmitter release).
• Neurotransmitters bind with receptors on the postsynaptic neuron, opening ion channels and causing electrical signal fluctuations.
• The amount of neurotransmitter released and the number of channels opened determine the response in the next neuron.
• One of the key things in memory formation is changing in the way that individual synapses work.

Synaptic Plasticity and Hebb's Rule

• All learning involves changes in synaptic function.
• Synaptic plasticity:Changes in the synapse, largely determined by the biochemistry of synaptic change.
• Hebbs Rule is an important principle in learning:
  $A$ and $B$, Heb's rule states that if neuron A repeatedly excites neuron B, there will be changes such that $B$ is more easily excited by $A$.
• Long-term potentiation (LTP): repeated excitation causes synaptic changes.
• Glutamine: the excitatory neurotransmitter in neurons.
• LTP changes the efficacy of the synapse but not by growing new connections.
• Repeated stimulation leads to changes in the synapse for that existing neural connection.

Long-Term Potentiation Details

• More vesicles = more neurotransmitter. Releasing more neurotransmitters and creating more open channels with stimulation leads and a bigger electrical change.
• The larger the electrical change in the postsynaptic neuron, the more inclined that electrical signal is to propagate on and be passed to the next neuron.
• This reflects fundamentally altered synapse electrical response between the neurons.

Locations of Synaptic Plasticity in the Brain

• Structures within the temporal lobe hippocampus (CA1, dentate gyrus), entorhinal cortex, and amygdala.
• Structures beyond the temporal lobe: prefrontal cortex, motor cortex, thalamus, and visual cortex.
• The key idea is: experience changes the way the network operates

Other Types of Synaptic Plasticity

• Long-term depression: decrease of synapse connectivity strength in synapse from low frequency stimulation.
• Habituation: repeated stimulation results in a weaker signal across time.
• Sensitization: a single stimulus causes an exaggerated synaptic response to subsequent repeated stimuli.

Conclusion

• H.M. provided considerable insights into memory function.