Dr. Brenda Milner

Patient H.M.

Amnesia

• Retrograde Amnesia impairment of memory for events before the injury

• Anterograde Amnesia impairment of memory for events after injury; that is, an impairment in learning

Memory Systems in the Brain

Memory Systems in the Brain

Patient H.M.“Right now I'm wondering, Have I done or said anything amiss? You see, at this moment everything looks unclear to me, but what happened just before? That's what worries me. It's like waking from a dream; I just don't remember.”

“Every day is alone in itself, whatever enjoyment I've had, and whatever sorrow I've had.”

-- H.M.

Memory Systems in the Brain

Medial temporal lobe amnesia• Inability to form new explicit memories

(anterograde amnesia)

• Good IQ, good implicit learning

• Loss of memories from before injury

(retrograde amnesia)

Medial temporal (contains hippocampus) lesions and DNMS performance (working memory)

Medial Temporal Lobe Memory System

Visual Cortex

VentralStream

InferotemporalCortex

Perirhinalcortex

Parahippocampalcortex

Entorhinalcortex

hippocampus

Memory

Teng & Squire, 1999

Memory

Teng & Squire, 1999

Memory

Teng & Squire, 1999

MemoryModal view (eg. Alvarez & Squire, 1994; Eichenbaum & Cohen, 2001; McClelland et al., 1995): A representation of an event is stored very quickly as a readily induced pattern of LTP in limited-capacity hippocampal circuitryA very long-lasting representation is built up in slowly changing, very high-capacity neocortical circuitry as result of a lengthy process of repetitive patterned output from hippocampus.Hippocampal mnemonic specificity identical in retrograde and anterograde directions

MemoryOther view:

� There is a period of decreasing fragility of representations, but the process occurs within each network (not between)� Temporal gradients in retrograde amnesia arise because of a probabilistic degradation in a partially damaged network� If the hippocampus is intact, it is used (i.e. retrograde will have less specificity than anterograde)

Memory

Teng & Squire, 1999

Memory

Teng & Squire, 1999

Memory

Teng & Squire, 1999

Memory

Fanselow et al

Memory

Fanselow et al

Memory

Fanselow et al

Memory

1 4 12 3610

20

30

40

50

60

70

80

Control

HPC

First postsurgical no-platform probe

Training-surgery interval (wk)

Swim in correct quadrant (%)

Memory

1 4 12 362030405060708090100

ControlHPC

Postsurgery first dayVisual discrimination

Training-surgical interval (wk)

Percent correct

Memory

1 4 120

10

20

30

40

Control

HPC

Postsurgery responding to context

Training-surgery interval (wk)

Number of observations of freezing

Memory

1 4 12010203040

ControlHPC

Postsurgery responding to auditory stimulus

Training-surgery interval (wk)

Number of observations of freezing

SRT Results

before a f te r

Shi e t a l, Sc ie nc e 2 84 : 1 81 1 (11 J un 19 99 )

HippocampalDysfunction or lesion