Transcript Eldridge et al 2001, 2005

Fronto Limbic and Mem
Parallel Memory Systems
• Episodic Memory- Hippocampal based
• Procedural and “Habit” learning system:
Basal Ganglia
– Reward system effects on learning-ventral
striatum
• Frontal lobe contributions
– Retrieval systems
– Organization of input
• Priming
– Repetition priming/sensory based traces
– Frontal contributions to effortful learning/priming
Memory systems
• Hippocampal
– New associations
– Episodic - temporal signature
– Case examples
– Tests
– Paired associate learning
– Effect of retrieval cues
Hippocampal System
• H.M. first model of episodic memory
– Bilateral medial temporal lobectomy for epilepsy surgery
– Cured of epilepsy
– No new episodic encoding since surgery
• This memory deficit is the classic amnesia
syndrome
• Other good ways to get this deficit:
– Repeated temporal lobe seizures (mesial temporal
sclerosis
– Anoxia- at birth or acquired- HC especially sensitive to
anoxic damage
– Herpes encephalitis (limbic encephalitis). Herpes loves
the HC.
Neuropsych patterns in HCbased memory impairment
• Difficulty forming new associations
– E.g. Unrelated paired associate learning
– Face-name associations
• Steep forgetting curve
– Delayed recall specifically impaired
– Minimal to no benefit from retrieval cues
– Minimal to no benefit from recognition format
• Some evidence for content specificity
– left vs right, verbal vs spatial dissociation
Wada testing of HC function
• Anterior 2/3 HC fed by the anterior choroidal
artery which comes of the ICA
• During Wada testing, anesthetize 1 HC
• Present new information to learn (eg 6
objects)
• Wait 12 minutes (with distraction)
• Test for Memory for Episode (did we show
you anything?)
• Test for cued recall; finally, test recogntion
• ***Important assess for Episodic recall
Memory without episodic
recall: feeling of knowing
• HC memory is episodic: remember the
encoding episode (eg the objects I just
showed you 10 minutes ago)
• Distinguish from Explicit, but nonepisodic memory (eg, yes I have seen
this before, don’t remember the exact
episode: “feeling of knowing”
Recollection versus
Familiarity
• (R) Recollection - re-experiencing the
encoding event at the time of recall, true
episodic memory
• (K) - Know - the feeling of familiarity that
you’ve seen something before, but not
remembering the exact encoding event
– Not implicit because it is conscious
Eldridge et al 2001, 2005: Remember- Know Distinction in HC
R vs. K
• Eldridge et al have shown the HC is
selectively involved in R, not with K.
Novelty Encoding Paradigm
Alternating Blocks of Novel and Repeat Pictures
New
Rest
New
Repeat
Outdoor
New
Repeat
Indoor
Rest
Time Series for Subregions
Sustained
Parahippocampal
Fusiform
Late Activation
No Activation
CA 2, 3, DG
CA 1
Subiculum
Entorhinal
Non-episodic Memory:
Habit Learning System
Hippocampus
Striatum
Patient H.M. can learn…..
• Was able to navigate around his (new)
environment, eventually.
• Could learn new skills: initially, motor skills;
ultimately found to include cognitive skills
• Eg mirror reading (see next slide)
• Could perform the tower of Hanoi in the
optimal number of moves; but had to be
explained the directions repeatedly; no
memory of having seen it before
• Thus there was some unconscious, implicit
learning that was conceptual in nature
Imaging the striatal learning
system:Learning a new skill
• Mirror-reading: (Poldrack et al)
• College students were taught to read mirror-reversed
text for ~5 hours
• Scanned before and after learning using fMRI
• Activity in striatum during learning
• Normal in HC lesioned patients
Knowlton and Squire
• Performed a probabilistic learning task in
Parkinson’s patients and amnestic patients:
Weather Prediction Task
• In this task subjects learn an association between
a stimulus (a playing card) and an outcome (rain
or shine)
• Relationship was probabilistic, not deterministic;
66% probability of an outcome
• Subjects could not memorize the associations,
and ultimately guessed
• However their behavior showed a learning curve
despite no explicit knowledge of learning
Learning concepts without
consciousness
• Amnesic patients learned the associations
(without awareness)
• Parkinson’s patients did not
• Requires hundreds of trials
• Testing of explicit memory results in chance
• Behavior shows learning
• Considered an implicit, habit based learning
system
• What other skills do you learn this way?
Implicit learning
Basal Ganglia and learning
• What else is learned implicitly?
– Language learning and grammar: based on
probabilistic word boundaries and
repetition to learn syntactic structures
– Social skills: how close to stand to people,
how loud to talk, where to stand in an
elevator, how much eye contact, etc
Striatum is Involved in Language &
Communication
Grammatical > Non-Grammatical
(14,6,0)
Lieberman et al., 2004 J Cog Neuro
• Artificial grammar learning
(Lieberman et al., 2004)
• Subjects given sequences of
letters with probabilistic
sequences
• Presented novel sequences
that follow the same rules
• Subjects can correctly classify
them as right or wrong without
knowing the rules or having
learned the specific examples!
Implicit learning and dorsal
striatum
• Dorsal striatum (Ca/Pu) is implicated in
implicit or “habit” learning (Knowlton and
Squire)
• Language acquisition and social
learning are thought to rely on implicit
learning mechanisms
– Probabilistic learning tasks (vs. deterministic) are
implicit, subconscious, and rely on dorsal striatum
Implicit Learning and Reward
• Probabilistic Classification Task
• Reported by Knowlton and Squires- impaired in PD,
intact in amnesia
• Inversely related to hippocampal activity
• Reward variant- social vs. monetary
– Stimuli predict a given outcome (1 or 2); 50% deterministic,
50% random
– Reward and Cognitive (Correct / Incorrect) feedback
Adults: BG
activity during
probabilistic
learning
Source: D. Ghahremani
Response to Rewards
Every occurrence of a reward (any type) vs. no-reward
Reward response in VS
0.25
TD
ASD
Magnitude (mean %)
0.2
0.15
0.1
0.05
0
Social
Monetary
Effect of rewards on implicit
learning
Total Performance
100.00
90.00
80.00
Percent Correct
70.00
60.00
ASD Money Total
TD Money Total
50.00
ASD Social Total
TD Social Total
40.00
30.00
20.00
10.00
0.00
1
2
Time
3
Dorsal Striatum deficits in
ASD during implicit learning
R
L
Typical children > ASD children
Variation in VS activity in typical
children predicts social reciprocity
R
Word Segmentation & Language
Learning
• Identifying word boundaries is one of the earliest
steps in language learning (Kuhl 2002)
• Infant studies suggest heavy reliance on statistical
learning for word segmentation (Saffran et al., 1996;
Aslin et al., 1998)
• Prosodic cues (e.g., stress) aid speech parsing
(Johnson & Juscyzk, 2001; Thiessen & Saffran,
2003)
• Adapt well-established paradigm from infant literature
Implicit Language Learning Study
Unstressed
Language
Stressed
Language
Random
Syllables
Transitional
Probabilities
Only
Transitional
Probabilities
+ Prosodic Cues
No Transitional
Probabilities
No Prosodic Cues
nimoluvorifaliduramanuto…
do la go ro
bi ku da
bu
pa tu ti pi
pabikugolatudaropitibudo…
pabiku
daropi
golatu
tibudo
po ba
vu
gi
no
fu ko
ga
fi
mu ka
vi
kagipovuganomubakafufibako…
li
lu to
fa
du ma
ri
ra mo nu
vo
ni
novuka
pofimu
vikoga
bafugi
lidura
vorifa
manuto
nimolu
Implicit Language Learning
Paradigm
Unstressed
Language
Stressed
Language
144s
30s
144s
Random
Syllables
30s
TIME (seconds)
144s
Comparisons with Baseline (Rest)
in typical adults
Random
Syllables
RH
LH
RH
LH
RH
LH
Unstressed
Language
Stressed
Language
McNealy et al., 2006
Language learning compared to Rest:
indexed by signal increases over exposure
U
S
R
TD > ASD Children
Stressed
TD kids show
significantly
greater signal
increases in
striatum than
ASD
Unstressed
Random
RH
LH
Implicit Learning and Reward
• Rewards augment implicit learning
• Probabilistic Classification Task
• Reward variant– Stimuli predict a given outcome (1 or 2) either 17% 50% or 83%
– Reward and Cognitive (Correct / Incorrect) feedback
• Reward type varied: Monetary Rewards or Social Rewards
– Equal number of reward and cognitive feedback trials
Source: D. Ghahremani
Frontal contributions to
memory
• Attention to incoming information
• Organization of incoming information
– Pre-organized
– Semantic categorization
• Working memory capacity
• Organized memory retrieval
(Brodmanns area 10 found to be
involved in controlled retrieval)
Frontal lobe memory deficits
• Information size effects (supraspan)
– LM story 2 second rep;
• Interference (proactive)
– Eg: CVLT 5,7,10,9,8
•
•
•
•
Benefit from cues
Reduced spontaneous categorization
Confabulation
Prospective memory impairment
Some examples to discuss
• Patient 1:
– CVLT: 4,7,12,15,9 2 I, 4 P
– List B: 4
– SF: 7 cued 9
– LF: 9 cued 12
– Recognition 15/16 3 FP
• What does this pattern suggest?
• What would WMS LM look like?
Example 2
•
•
•
•
•
•
CVLT 8,10,12,13,14
B8
Sdfree 8 cued 8
Ldfree 4 cued 5
Recognition 10/16 0 FP
What else would you be likely to see?
What would WMS LM look like?
Emotion effects on memory
• Flashbulb memory: where were you on 9/11?
• Most can remember exquisite details of highly
emotionally charged events
• Close contact between amygdala and HC facilitate
strong emotional memories
• Interestingly, these memories are modifiable- details
are altered with retelling, easily tampered with
• People retain their emotional traces, which includes a
strong conviction of the accuracy of their memory for
emotional events
• This is exactly why eyewitness testimony is so poor.
Neuroanatomy of psychiatric
conditions
• Eg schizophrenic auditory
hallucinations: strong activity in TTG
and A2 during hallucinations
• Many studies of psychiatric disorders
have used emotional faces as stimuli
Facial Emotions: Experimental
Paradigm
“Match”
“Label”
Match Expressions: Perception only;
implicit emotional processing
Label Expressions: Explicit cognitive
analysis
Control
Match Affect- normal adults
-seeing negative face expressions activates Face and Fear brain c
amygdala
face area
Hariri et al., 1999
Label Affect
-interpreting negative face expressions activates Face
center … down regulates the amygdala
amygdala
Hariri et al., 1999
Cortical Influence During “Label”
-this frontal lobe region regulates and controls Fear brain center
Hariri et al., 1999
FFA Response
2.5
% signal change
2
1.5
1
0.5
0
-0.5
-1
3
28
53
78
103
128
153
178
Time (sec)
203
228
253
278
Bipolar Disorder- Manic State: Altshuler et al 2005
fMRI in Mania
(Altshuler et al 2005)
fMRI of Panic Imagery
(Bystritsky et al 2001)
Emotional Face Processing in
OCD (S. Rausch)
Disgust and Threat
Responses in OCD (Shapiro
2002)
Disgust
Threat
Control
OCD
Mirror Neurons and Autism
• A dysfunctional mirror neuron
system (MNS) in autism?
(Williams et al 2001)
• Mirror neurons: class of neurons first discovered in ventral
premotor cortex (area F5) of the macaque (Gallese et al
1996; Rizzolatti et al 1996); Pars opercularis (BA 44), inferior
frontal gyrus, is human homologue.
• Neurons fire during both the performance and observation of
motor behavior; respond to intention: only fire for meaningful
actions
Mirror Neuron function in autism:
Imitating and Observing
emotions
Angry
Fearful
Happy
Sad
Neutral
I.
II.
faces
Watch faces
Imitate expressions
+
2s
+
2 Separate Functional Runs
“Just look at the expression on each face”
“Imitate the expression you see on each face ”
2s
+
2s
Activity During Imitation
Motor areas
TD Imitate
Mirror
neuron
area
Visual areas
R
L
6
5
4
t
ASD Imitate
3
2
1
R
L
0
Imitate:
TD > ASD
p<.05,
corrected at
cluster level
R
L
Imitation: TD > Autism
Anterior Insula
z: -12
z: 8
Connection
from mirror
centers to
emotion
centers
L
R
Amygdala: fear centers
Negative faces
L
R
Ventral
striatum:
Reward
Centers
(happy faces)