Understanding Human Anterograde Amnesia

1. Chapter 14 Relational Learning and Amnesia

2. Human Anterograde Amnesia • Anterograde amnesia - difficulty in learning new information, due to head injury or certain degenerative brain diseases; pure form is rare • Retrograde amnesia – inability to remember events that occurred prior to brain damage • Korsakoff’s syndrome – permanent anterograde amnesia caused by brain damage resulting from chronic alcoholism or malnutrition (due to thiamine deficiency); also have confabulations (reporting of memories that did not occur, without the intention to deceive) • Anterograde amnesia can be caused by damage to temporal lobes • e.g. patient H.M. – bilateral removal of medial temporal lobe to alleviate epilepsy; resulted in severe anterograde amnesia

3. Human Anterograde Amnesia • Basic description • Results from study with H.M. • The hippocampus is not the location of long-term memory (LTM); nor is it necessary for the retrieval of LTM • The hippocampus is not the location for short-term memory (STM) • The hippocampus is involved in converting STM into LTM • These results are too simple; anterograde amnesia is actually much more complex • Learning consists of at least 2 stages: • STM – immediate memory for events, which may or may not be consolidated into LTM; can only hold a limited amount of info • LTM – relatively stable memory of events that occurred in the more distant past, as opposed to STM; no limit on amount of info • Consolidation – the process by which STM are converted into LTM

4. Simple model of memory process • Sensory info enters STM • Rehearsal keeps that info in STM • Eventually, info will move into LTM via consolidation

5. Human Anterograde Amnesia • Spared learning abilities • Still capable of: • Perceptual learning • e.g. recognize broken drawings; also faces and melodies • Stimulus-response learning • Can acquire a classical conditioned eyeblink response • Motor learning • Mirror drawing task – subjects required to trace the outline of a figure while looking at the figure in a mirror

6. Human Anterograde Amnesia • Declarative and nondeclarative memories • Although patients can learn other tasks, they cannot recall ever learning them • Learning and memory involve different processes • 2 major categories of memories • Declarative memories – memory that can be verbally expressed, such as memory for events, facts, or specific stimuli; this is impaired with anterograde amnesia • Nondeclarative memories – memory whose formation does not depend on the hippocampal formation; a collective term for perceptual, stimulus-response, and motor memory; not affected by anterograde amnesia; these control behavior; cannot always be described in words

7. Human Anterograde Amnesia • Failure of relational learning • Verbal learning is disrupted in anterograde amnesia • e.g. H.M. did not learn any new words after his surgery (biodegradable = “two grades”) • Episodic memories – most complex form of declarative memory; memory of a collection of perceptions of events organized in time and identified by a particular context • e.g. explain what you did this morning after waking up • The hippocampal formation enables us to learn the relationship b/t the stimuli that were present at the time of an event (i.e. context) and then events themselves

8. Human Anterograde Amnesia • Anatomy of anterograde amnesia • Damage to the hippocampus or to regions that supply its inputs and receive its outputs causes anterograde amnesia • The most important input to the hippocampal formation is the entorhinal cortex, which receives inputs from the limbic cortex either directly or via the perirhinal cortex or the parahippocampal cortex • How does the hippocampus form new declarative memories? • Hippocampus receives info about what is going on from sensory and motor assc. cortex and from some subcortical regions • It processes this info and then modifies the memories being consolidated by efferent connections back to these regions • Experiences that lead to declarative memories activate the hippocampal formation • Patient R.B., suffered brain damage that lead to anterograde amnesia; after autopsy, found that field CA1 of the hippocampal formation was completely destroyed

9. Limbic cortex

10. Human Anterograde Amnesia • Anatomy of anterograde amnesia • Damage to other subcortical regions that connect with the hippocampus can cause memory impairments • Limbic cortex of the medial temporal lobe • Semantic memories – a memory of facts and general info; different from episodic memory • Destruction of hippocampus alone disrupts episodic memory only; must have damage to limbic cortex of medial temporal lobe to also impair semantic memory (and thus all declarative memory) • Fornix and mammillary bodies • Patients with Korsakoff’s syndrome suffer degeneration of the mammillary bodies • Most of the efferent axons of the fornix terminate in the mammillary bodies • Damage to any part of the neural circuit that includes the hippocampus, fornix, mammillary bodies and anterior thalamus cause memory impairments

11. Human Anterograde Amnesia • Role of the medial temporal lobe in spatial memory • Individuals with anterograde amnesia are unable to consolidate info about the location of rooms, corridors, buildings, roads, and other important items in their env’t • Bilateral medial temporal lobe lesions produce the most profound impairment on spatial memory, but enough damage to only the R hemisphere is sufficient • R hippocampal formation is activated when a person is remembering or performing a navigational task • Damage to this area also impairs ability to learn spatial arrangement of objects

12. Human Anterograde Amnesia • Role of the medial temporal lobe in memory retrieval • The hippocampal formation and its related structures also play a role in memory retrieval • Anterograde amnesia is usually accompanied by retrograde amnesia; brain damage can either cause loss of memories or loss of access to memories • However, if damage is only limited to field CA1, patients do not show additional retrograde amnesia • Semantic dementia – loss of semantic memories caused by progressive degeneration of the neocortex of the lateral temporal lobes • Impairment for meaning of words, and functions of common objects

13. Human Anterograde Amnesia • Confabulation • May be a result of disruption of the normal functions of the prefrontal cortex • Frontal lobes may be involved in distinguishing b/t real and imaginary memories; may do this by helping us to distinguish items with general familiarity from specific items we have encountered before

14. Relational learning in lab animals • Lab animals with hippocampal formation lesions do not sow impairment in stimulus-response learning, but with relational learning tasks • Remembering places visited • Radial maze task – food placed at end of each arm, rats did not go down arm that they had already collected food from; lesions to hippocampus, fornix, or entorhinal cortex impaired this task; animals must remember which arm they have collected from that exact day (as opposed to another testing day)

15. Relational learning in lab animals • Spatial perception and learning • Lab animals with hippocampal lesions show problems with navigational tasks just as humans do • Morris water maze task – requires rat to find a particular location in the water drum, by means of visual cues external to the apparatus; if rats wit hippocampal lesions are released from same position every testing time, they perform fine (e.g. S-R learning), but if they are started from a different place, they cannot complete the task correctly (e.g. relational learning)

16. Relational learning in lab animals • Spatial perception and learning • Hippocampal lesions disrupt performance of homing pigeons • Hippocampal formation of animals that normally store seeds or food in hidden caches and later retrieve them is larger than that in animals without this ability • Role of hippocampal formation in memory consolidation • Brain activity in the hippocampus is increased in mice learning a spatial task; however, after 25 days of testing, the activity there decreases, suggesting that the hippocampus is involved in consolidating spatial memories for only a limited time

17. Relational learning in lab animals • Place cells in the hippocampal formation • When recording the activity of individual neurons in the hippocampus of an animals moving around its env’t, some neurons fired at a high rate only when the rat was in a particular location • The suggests evidence that different neurons have different spatial receptive fields (i.e. they responded when the animals were in different locations) – these neurons were named place cells • When placed on a circular platform that is rotated slowly within a larger chamber, rats will ignore local cues and orient themselves to face a cue card; the place cells however, oriented themselves to the local cues • When animals encounter new env’ts, they learn the layout and “maps” become established in their hippocampus; an animal’s location within each env’t is encoded by the pattern of firing of these neurons • Place cells are guided by both visual stimuli and internal stimuli (e.g. proprioceptive feedback) • Hippocampus receives spatial info via the entorhinal cortex

18. Relational learning in lab animals • Role of LTP in relational learning • When place cells become active when an animal is present in a particular location, this causes changes in the excitability of neurons in the hippocampal formation • Knockout mice for NMDA receptors specific for the field CA1: no establishment of LTP in field CA1, smaller and less focused spatial receptive fields, and learn Morris water maze task much slower • NMDA mediated LTP appears to be required for the consolidation of spatial receptive fields in field CA1 pyramidal cells but not their short-term establishment • Modulation of hippocampal functions • Hippocampal formation receives input from ACh, NE, DA, and 5-HT neurons • They appear to control the information-processing functions of the hippocampal formation • 5-HT has suppressive effect on establishment of LTP in hipp. form.

19. Relational learning in lab animals • Modulation of hippocampal functions (con’t) • NE has a facilitator effect, particularly on synapses of terminals of entorhinal neurons of the dentate gyrus • DA had excitatory effects on LTP and memory-related functions of the hippocampal formation • Synaptic plasticity is induced by simultaneous depolarization of hippocampal neurons and activation of DA receptors on these neurons • ACh neurons from medial septum project to hippocampus via fornix; activity of these neurons is responsible for hippocampal theta rhythms (medium amplitude, medium frequency waves) that influence the establishment of LTP in the hippocampus • If theta activity is disrupted, animals show deficits in learning tasks that are affected by hippocampal lesions • Theta behaviors – exploration or investigation • Nontheta behaviors – alert immobility, drinking, self-directed behaviors