MEMORY

Tim Kimbrell, M.D.

OBJECTIVES

• overview of memory models

• differences between declarative (explicit) and procedural (implicit) memory

• kindling/sensitization and its relationship to memory

• neuropsychological basis of memory and common forms of amnesia

OVERVIEW

• Changes in neural networks must occur to encode and retrieve information

• A memory is access to previously learned information (experience)

• Bottom line: Brain function and ultimately Brain structure are changed with experience (learning)

MOTIVATION OR EMOTIONAL MEANING

• Classic example of inverted “U” curve applies to memory/learning, cerebral blood flow, performance, etc. (Gur and Gur)

• Mild to moderate attention/arousal are necessary

• Basic science courses re a marathon, not a sprint

• Fear of failure: desire to do your best

TYPES OF MEMORY

DECLARATIVE OR EXPLICIT MEMORY

• Conscious or cognitive memory

• Distinct facts and your awareness of knowing them (Arkansas won the Cotton Bowl)

• All important in Medical School

• Key: How long will you remember this stuff?

DECLARTAIVE/EXPLICIT MEMORY

• SHORT-TERM: SECONDS TO MINUTES

– Hear it/see it --think about it

• Association cortex -- Prefrontal cortex

– Working memory is an example

– Ask patient to remember 3 objects

DECLARATIVE/EXPLICIT MEMORY

• LONG-TERM: HOURS/DAYS TO A LIFETIME

Association Cortex

Medical temporal Prefrontal cortex

What did you have for breakfast on Tuesday?

What year were you married?

PROCEDURAL (IMPLICIT) MEMORY

• Knowing how to do things without “thinking” -- swing a golf club, play piano

• Storage mechanism: inherent to various sensory and motor areas

• Cerebellum/amygdala known to be important

MEMORIES AND CIRCUITS

• REVERBERATING MODEL: DYNAMIC IN NATURE

• Stimulus enters the pathway and continues to bounce back and forth

• Information “burned as a trace into the living” and thus localized

• Though discredited, probable role in autobiographical memory

CONVERGENCE MODEL

• Convergence of 2 excitatory signals giving change at a synaptic level (plastic)

• Similar to post tetanic potentiation

• Arousal is accounted for

• Localization is not required

• Experience changes the anatomy of the brain

APLYSIA STUDIES

• Kandel demonstrated plasticity and will win the Nobel Prize

• Studied a simple reflex in sea slug

• Photographed morphologic change with experience/learning

HABITUATION

• Repeated stimulation: attenuated/decreased response

• What causes the neuron to fire?

– Calcium influx decreases

• If not firing, less glutamate needed, decreased mobilization and receptor number

SENSITIZATION

• Restoration and potentiation of the response

• Apply a noxious stimuli to sensory system

• Increase neurotransmitter release

• Increase “active zones” at the synapse

• Inhibit protein synthesis-- block effect

PLASTICITY

Sensory and motor neurons “store” information in a distributed network that is modifiable by experience and results in a change in synaptic strength

LONG TERM POTENTIATION (LTP)

• Frequent stimulation/sensory input

• Glutamate release and binds to NMDA

receptors mediating increase in Calcium influx

• Activation of phosphoproteins and transcription pathways change post synaptic structure

LONG TERM DEPRESSION/HABITUATION

– Low frequency stimulation over time

– Inhibition of “Meaning/significance”

– Frequent half-ass attempts are not productive

ANATOMY

• All brain regions play a role

• Association cortex

– Visual/Verbal/olfactory = sensory long term storage

• Cerebellum: Procedural and declarative

• Frontal cortex: Awareness/Consciousness

LIMBIC SYSTEM

• Older, more primitive regions of brain

• Grande Lobule Limbique

• Emotional significance is contributed

• Arousal “system”

LIMBIC SYTEM (continued)

• Hippocampus/Amygdala; Cingulum septal region, anterior thalamus orbitofrontal cortex hypothalamus

• Emotional significance provides motivation median forebrain bundle/fornix

HIPPOCAMPUS/MEDIAL TEMPORAL

Most studied region related to memory

• Assimilates short term to long term memory distributes to cortical regions for storage

• perfused by end arteries: easily damaged

• concentrated Glucocorticoid receptors

KLUVER-BUCY SYNDROME

• Primates after undergoing bilateral temporal lobectomy

• Hyperorality, hypersexuality and placidity• Amygdala resection necessary for full

syndrome• Total amnesia: need bilateral injury to

Hippocampus and possibly other medial structures

PATIENT HM

• Most famous/studied patient in neurology

• Bilateral hippocampal resection

• Complete anterograde amnesia

• Dominant Hippocampus: Auditory deficits

• Non-dominant Hippocampus: Visual deficits

• Cueing: make use of what you have

PRIMING

• Interface between declarative and procedural

• Latency between presentation and identification

• HM insisted he hadn’t seen the picture

• Retention of procedural memory w/o declarative

PATIENT HM (continued)

• Mirror writing improved with practice

• Ribot’s Law: oldest memories are most resistant to damage or decay

• Natural decay: Review notes intermittently

PHARMACOLOGY

• Glutamate : excitatory; make $$$

• Glycine: spinal cord excitation

• GABA: inhibitory; benzodiazepine/ETOH

• Acetylcholine: Displace Mg ion at NMDA receptor

• Avoid anticholinergics in elderly

• nucleus basalis

AMNESIA

• Specific defect in declarative memory - other functions preserved

• Retrograde: Loss of stored memories

• Anterograde: Inability to form new memory

ALCOHOLIC BLACKOUTS

• ETOH mechanism of action

• Sensitization occurs

• Cross reactivity with Benzodiazepines

• Use long acting agents

WERNICKE-KORSAKOFF’S

• Occurs with alcohol dependence

• Destruction of mamillary bodies (loop of Papez)

• Can be arrested if caught early

SHORT DURATION AMNESIA

• Partial complex seizures: episodic

• Medial temporal lobe seizure focus

• Basilar artery migraines

• Origin of posterior cerebral arteries

LONG DURATION AMNESIA

• Herpes simplex encephalitis

• Attacks medial temporal lobe (anterograde amnesia)

• May resemble Kluver-Bucy

PSYCHOGENIC AMNESIA

• Fugues and dissociative disorders

• Stressor often involved

• Most often retrograde in nature

• Frequently clears with time

• Retains ability to form new memories

• “Knuckleheads” need best assessment

ASSESSMENT

• Complete history and physical

• Keep a wide differential diagnosis

• Examine sensory systems

• Make use of imaging/EEG