memory tim kimbrell, m.d.. objectives overview of memory models differences between declarative...
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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
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