Bullet Notes: Biopsychology of Memory and Amnesia (Concise)

11.1 Amnesic Effects of Bilateral Medial Temporal Lobectomy

  • Case: H.M. underwent bilateral removal of medial temporal structures (hippocampus, amygdala, adjacent cortex).
  • Outcomes:
    • Generalized seizures largely eliminated; IQ increased from 104 to 118 post-surgery.
    • Severe anterograde amnesia: unable to form new long-term memories; short-term memory largely preserved.
    • Mild retrograde amnesia for events within about the 2 years before surgery; remote memory largely intact.
    • Short-term memory (e.g., digit span) preserved: typical span of 6 digits, but difficulty with longer sequences.
  • Memory dissociations observed:
    • Explicit (conscious) memory severely impaired for new information.
    • Implicit (unconscious) memory for new information preserved, demonstrated by learning in tasks without conscious awareness (mirror-drawing, incomplete-pictures, rotary-pursuit, etc.).
  • Key tests illustrating dissociations:
    • Digit Span Test: H.M. could repeat 5-6 digits but failed beyond that; shows preserved short-term memory but impaired explicit encoding.
    • Mirror-Drawing Test: improved with practice but could not recall having seen the task before.
    • Incomplete-Pictures Test: learned to recognize fragmented drawings without conscious recall of previous exposure.
    • Pavlovian conditioning (eye-blink): learned the conditioned response but had no conscious recollection after 2 years.
  • Three major contributions from H.M.’s case:
    1) Medial temporal lobes are critically involved in memory formation, not just diffuse brain regions.
    2) Distinction between short-term/long-term and explicit/implicit memory systems; consolidation disrupted for explicit long-term memories.
    3) Demonstrated explicit vs. implicit memory dissociation; amnesic patients can show preserved implicit memory.

11.2 Amnesia of Korsakoff's Syndrome

  • Korsakoff’s syndrome linked to thiamine deficiency (often from heavy alcohol use); diffuse brain damage.
  • Typical postmortem: lesions in the medial diencephalon (mediodorsal thalamic nuclei, mammillary bodies) with diffuse cortical and hippocampal involvement.
  • Memory profile:
    • Early prominent anterograde amnesia for explicit memories; progressive retrograde amnesia extending back into childhood.
    • Not attributable to a single structure; damage is diffuse but mediodorsal nuclei repeatedly implicated.
  • Notable case: N.A. – mediating damage to medial diencephalon (cribriform plate injury) with extensive retrograde and anterograde amnesia but preserved other cognitive functions.

11.3 Amnesia of Alzheimer's Disease

  • Alzheimer’s involves diffuse brain degeneration, including medial temporal lobe and basal forebrain.
  • Acetylcholine depletion (basal forebrain degeneration) is a key factor; strokes in basal forebrain can cause amnesia.
  • Memory profile:
    • Early deficits in explicit memory (both episodic and semantic) with variable explicit memory impairment.
    • Some implicit memory (sensorimotor) may be preserved; short-term memory and attentional deficits common.
  • Dysfunction across multiple regions contributes to amnesia, not a single locus.

11.4 Amnesia after Concussion: Evidence for Consolidation

  • Posttraumatic amnesia (PTA): retrograde amnesia for events before injury and anterograde amnesia for events after confusion period.
  • Consolidation theory: memory traces stabilize over time; disruption shortly after learning (e.g., ECS) impairs retention for events learned just before disruption.
  • Electroconvulsive shock (ECS) studies in animals show a gradient of retrograde amnesia with disruption strongest for memories learned within a short interval after learning (roughly between 10 ext{ min} and 1 ext{ hour}) – supports a consolidation window.
  • Standard consolidation theory vs. multiple-trace theory: long retrograde gradients suggest memory traces persist and are updated over time; reconsolidation suggests retrieved memories can re-enter a labile state.
  • Reconsolidation: when memories are retrieved, they become temporarily labile and may be disrupted unless reconsolidated.

11.5 Neuroanatomy of Object-Recognition Memory

  • Animal models (monkeys and rats) show that object-recognition memory depends on medial temporal structures.
  • Key findings:
    • Rhinal cortex lesions (especially perirhinal cortex) produce severe, lasting deficits in object recognition and delayed nonmatching-to-sample tasks.
    • Hippocampus lesions produce moderate or no deficits in object recognition, depending on species and task; amygdala lesions have little effect.
    • Ischemia-induced hippocampal damage can cause object-recognition deficits, but extrahippocampal damage also contributes; hemispheric differences and diffuse damage complicate attribution to the hippocampus alone.
  • Important concepts:
    • Perirhinal cortex supports object representations used in various processes (perception, memory).
    • Rhinal cortex (entorhinal + perirhinal) is critical for object recognition; entorhinal cortex involved in spatial processing with hippocampus.
    • Rat model (Mumby box) demonstrates delayed nonmatching-to-sample performance with hippocampal/rhinal lesions.

11.6 Hippocampus and Memory for Spatial Location

  • Hippocampus crucial for spatial memory; place cells in hippocampus fire in specific locations; grid cells in entorhinal cortex provide a metric for space.
  • Classic tasks:
    • Morris water maze: hippocampal lesions severely impair learning to find a hidden platform.
    • Radial arm maze: hippocampal lesions disrupt both reference memory (which arms are baited) and working memory (not revisiting arms within a day).
  • Cognitive map theory (O’Keefe & Nadel): hippocampus constructs allocentric maps of the external world; spatial context supports episodic memory.
  • Criticisms/alternative views emphasize that place-cell firing depends on more than pure space and that hippocampus may support broader, non-spatial memory processes as well.
  • Across species, hippocampus supports spatial memory; across primates, findings are more variable, possibly due to differences in how spatial memory is tested.

11.7 Where Are Memories Stored?

  • No single storage site identified; memories appear stored diffusely and are resistant to damage over time.
  • Storage occurs in distributed networks involving multiple brain regions; memories are re-encoded each time they are recalled, creating new engrams and increasing resistance to disruption.
  • Other brain areas implicated in memory storage and processing:
    • Inferotemporal cortex: supports memory for visual objects in concert with perirhinal cortex.
    • Amygdala: involved in emotional aspects of memory; strengthens emotionally significant memories.
    • Prefrontal cortex: supports working memory and temporal organization; different subregions contribute to different memory processes.
    • Cerebellum: stores sensorimotor memories (e.g., eyelid conditioning);
    • Striatum: stores stimulus-response/pattern learning (habits).
  • Notable points:
    • Case studies (e.g., Cook) illustrate sequence-proofing and planning deficits with prefrontal damage, highlighting functional specificity within large regions.

11.8 Synaptic Mechanisms of Learning and Memory

  • Core idea: enduring changes in synaptic efficacy (neuroplasticity) underlie learning and memory. Hebb proposed that enduring synaptic changes store memories.
  • Long-Term Potentiation (LTP): robust synaptic strengthening following high-frequency stimulation; first demonstrated in the hippocampus.
  • Induction of NMDA-receptor–mediated LTP:
    • Requires glutamate binding to NMDA receptors and partial depolarization of the postsynaptic neuron (co-incidence detection).
    • Calcium influx through NMDA receptors triggers intracellular cascades leading to potentiation.
  • Key properties of LTP:
    • Persistence: can last for months in brightened synapses.
    • Specificity: potentiation is input-specific due to dendritic-spine isolation of calcium signals.
  • Maintenance and expression involve both presynaptic and postsynaptic changes; retrograde signaling (e.g., nitric oxide) from postsynaptic to presynaptic terminals helps coordinate changes.
  • Structural changes and protein synthesis are critical for maintaining LTP; new synapses, spine growth, membrane changes, and dendritic remodeling contribute to long-term storage.
  • Additional players:
    • Astrocytes participate in synaptic transmission and modulate LTP.
    • LTD (long-term depression) complements LTP and collectively shapes memory by weakening synapses with low-frequency activity.
  • Overall view: LTP and its mechanisms provide a leading model for the neurobiological basis of learning and memory, though the full picture involves diverse mechanisms across brain regions.

11.9 Conclusion: Biopsychology of Memory and You

  • Infantile amnesia: adults remember little from infancy, but implicit memories can persist.
  • Nootropics (smart drugs) lack robust, generalizable evidence for memory enhancement in healthy individuals; reports are often inconclusive or not replicable.
  • Case of R.M. illustrates that posttraumatic amnesia can occurred with episodic memory loss, yet semantic memory may remain intact; theory and clinical implications emphasize memory systems rather than single sites.
  • Four themes recur:
    • Neuroplasticity as the basis for memory.
    • Clinical implications: memory disorders illuminate neural mechanisms but treatments remain limited.
    • Animal models: essential for causal tests beyond human case studies.
    • Evolutionary perspective and creative thinking prompts used to examine memory systems and their organization.
  • Think about it prompts (summary of key ideas):
    • Advances and future directions in memory research.
    • Difference between implicit and explicit memory.
    • Value and limitations of animal models.
    • Complexity and diversity of LTP/LTD mechanisms.
    • Role of case studies in advancing memory science.

Key Terms

  • Learning, Memory, Amnesia, Bilateral medial temporal lobectomy, Hippocampus, Amygdala, Lobotomy, Retrograde amnesia, Anterograde amnesia, Short-term memory, Long-term memory, Digit span, Global amnesia, Incomplete-pictures test, Remote memory, Memory consolidation, Explicit memories, Implicit memories, Medial temporal lobe amnesia, Repetition priming tests, Semantic memories, Episodic memories, Cerebral ischemia, Pyramidal cell layer, CA1 subfield, Korsakoff's syndrome, Mediodorsal nuclei, Medial diencephalic amnesia, Alzheimer's disease, Basal forebrain, Posttraumatic amnesia, Electroconvulsive shock, Standard consolidation theory, Multiple-trace theory, Engram, Delayed nonmatching-to-sample, Rhinal cortex, Entorhinal cortex, Perirhinal cortex, Mumby box, Morris water maze, Reference memory, Working memory, Place cells, Grid cells, Head-direction cells, Infotemporal cortex, Prefrontal cortex, Cerebellum, Striatum, Reconsolidation, Nootropics