Transcript Simons2001 CNS

Recollection-Based Memory in Frontotemporal Dementia
Clare J.
3
Galton ,
The Present Study
Semantic Dementia
Much evidence links the hippocampus with recollection-based memory.
For example:
Vargha-Khadem et al. (1997):
Selective bilateral hippocampal damage impairs recall but spares recognition memory
Aggleton & Brown (1999):
Using:
Progressive atrophy of one or both temporal lobes
• ‘Recollection’ supported by hippocampal system
• ‘Familiarity’ supported by perirhinal cortex system
• Source monitoring task
• Associative memory test
•
Test Phase
30 line drawings
Impaired
Preserved
Semantic Memory
(all modalities of input
and output)
Phonology, syntax
Problem solving
Visuospatial Perception
10 min delay
120 drawings: 30 from Set 1, 30 Set 2, 60 New
30 different drawings
•
Test Phase
32 door and sofa pairs
48 door and sofa pairs: 16 old, paired together at study
16 old, re-paired since study
16 new, not seen at study
“Were these items paired together at study?”
•
•
Recognition Memory
Study
•
•
(chance)
Controls
SD
•
AD
But at advanced
stages of the disease,
evidence of
emerging deficit?
Control
Mean
100
Percent Correct
•
90
80
70
60
•
50
40
30
0
-4
-3
-2
-1
0
r=.69, p=.056
-1
1
-5
-4
-3
-2
-1
0
1
Composite Frontal Score
Composite frontal score correlates significantly with both
source discrimination and associative memory.
•
Progressive atrophy primarily
affecting frontal lobes
GCB KH DM MB DC JH DE
Patients with Semantic Dementia
This is despite significant correlations
for other regions (e.g., between inferior
temporal lobe and semantic memory).
Suggests that, in semantic dementia at
least, hippocampal atrophy is not the
explanation for the pattern of
recollection-based memory
performance.
0.4
FM
What could be causing this recognition memory impairment at
late stages of semantic dementia?
•
0.3
0.2
•
Recognition memory deficit rarely observed, unless atrophy has spread to
involve posterior cortical regions
0.1
0
r=-.4, n.s.
-0.1
-3
1
1
-2.5
-2
-1.5
-1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
HC Volume Z-Score
Recollection and the Prefrontal Cortex
•
Currently no volumetric protocol for the prefrontal cortex, so two methods of testing this:
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.2
0.1
0.1
0
TA
WL
JGU
JWF
PL
Patients with frontal variant
FTD had little difficulty with
familiarity-based item memory.
•
TA
WL
JGU
PL
But all patients tested were
severely impaired at recollectionbased source memory.
0.7
• Schacter et al. (1984), Glisky et al. (1995):
Source memory correlates highly with scores on frontal lobe tests in healthy adults.
0.6
0.5
0.4
Control group confidence interval
Patient confidence interval
0.3
0.2
• Schacter et al. (1984), Shimamura et al. (1990):
Source memory impairment prominent feature of frontal lobe damage.
(no overlap indicates impairment)
0.1
0
WM
JP
SL
JC
DS
WJ
JH
Patients (increasing severity
VP
)
Conclusions
Compare recollection-based memory with performance on frontal lobe tests
in patients with semantic dementia.
Key:
JW
IF
Examine source memory ability of patients with the frontal variant of
frontotemporal dementia.
* * *
But can be attributed to atrophy
affecting medial temporal lobe regions such as the perirhinal cortex (Simons et al., submitted).
Again, pattern not related to
degraded semantic knowledge.
•
JWF
0.8
Degraded semantic knowledge
Disrupted perceptual processes
Recollection-based source
memory of seven patients not
significantly impaired relative to
controls (although two, WM and
IF, are borderline).
Three patients (JP, DS, and JW)
significantly impaired. No
obvious link between this deficit
and disease severity.
Earliest signs are changes in behavior and personality, followed by cognitive
impairment (attention, executive function, etc.)
Performance on the Source Monitoring Task
0.9
Previous studies indicate that this
pattern is not due to:
•
0
Recollection-Based Memory
•
Most patients with
semantic dementia
have highly accurate
recognition memory.
0.5
0.5
•
Item memory normal in most patients with semantic dementia; the most
severe patients may be impaired.
•
Source discrimination normal in some patients, impaired in others.
– Source memory not related to bilateral hippocampal volume
– Strong association with performance on frontal lobe tasks
1) Battery of Frontal Lobe Tasks
Analysis of Individual Patients
with Semantic Dementia
•
Also similar to before, three
patients at advanced stages of
semantic dementia did show a
significant deficit.
–
–
10
No significant positive correlation
between bilateral hippocampal
volume and source memory.
1
•
1
Source Discrimination
Mean No. Correct
20
•
Just like before, as a group, the
patients were not impaired relative
to controls at familiarity-based
item memory, F1,20 = 2.3, n.s.
Item Detection
Test
Typically, patients with semantic
dementia (SD) show intact
recognition memory for these kinds
of pictures. Patients with early
Alzheimer’s disease (AD), however,
exhibit marked impairment.
*
r=.72, p<.05
Frontal variant of Frontotemporal
dementia
0.6
Familiarity-Based Memory
40
30
1
-0.5
•
Hippocampus and Source Memory
Study Phase
This implies that learning of new material may be relatively
preserved in semantic dementia
(Graham et al., 2000; Simons et al., 2001).
1.5
“Did you see the picture in Set 1, Set 2,
or not at all?”
Recent experiments suggest better retrieval of recent autobiographical
memories compared to those from the distant past (e.g., Graham & Hodges, 1997).
We have investigated episodic learning
in semantic dementia using objects,
faces, and line drawings as stimuli
2
2) Frontal Variant FTD
Areas totalled to produce a volume
for each region, corrected for total
brain volume by dividing by whole
brain cross-sectional area.
Associative Memory Test
•
0.4
•
Volumetric analysis of the
hippocampus (and other temporal
lobe regions) conducted by manually
tracing on 1.5mm contiguous coronal
MRI slices using Analyze software
on a Sun Sparcstation 20.
Study Phase 1
Study Phase 2
0.5
0.3
-5
Volumetric MRI Analysis
Source Monitoring Task
Cognitive Profile
2.5
Composite Frontal Score
Relate memory performance to measures of atrophic disruption in associated neural
regions (e.g., medial temporal lobe, prefrontal cortex)
Regions of significant gray matter density reduction relative to age-matched
controls, as measured by voxel-based morphometry (Mummery et al., 2000).
0.6
Source Discrimination
•
Investigate relative contributions of recollection and familiarity (Mandler, 1980).
– Recollection: ‘Remembering’ item with associated context
– Familiarity: ‘Knowing’ that item has been experienced
Temporal variant of Frontotemporal dementia
Frontal Battery and Recollective Memory
Item Detection
•
and John R.
Recollection and the Hippocampus
Aims:
•
1,3
Hodges
* Now at the Department of Psychology, Harvard University,
Rm 860, William James Hall, 33 Kirkland St, Cambridge, MA 02138
E-mail: [email protected]
1. MRC Cognition and Brain Sciences Unit, Cambridge, UK
2. Memory Disorders Research Center, Boston University School of Medicine
3. University Neurology Unit, Addenbrooke’s Hospital, Cambridge, UK
Background
Karalyn
1
Patterson ,
Associative Memory
Kim S.
1
Graham ,
Source Discrimination
Mieke
2
Verfaellie ,
Source Discrimination
Jon S.
1
Simons *,
•
0.9
0.8
•
0.7
Tests chosen to reflect different aspects of frontal lobe function, such as temporal
sequencing, planning, holding and manipulating within working memory.
Z-scores for each individual patient calculated for each frontal test, relative to mean
performance of healthy controls.
Composite frontal score then computed for each patient by taking the average of the
frontal test z-scores.
– Patients with frontal variant FTD very impaired on source
•
In seeking to understand the neural substrates of long-term memory, we
should not forget the important role played by the prefrontal cortex.
References
0.6
0.5
0.4
0.3
0.2
0.1
Possible explanations? Atrophy
progressing to affect the function
of: • Hippocampus? • Prefrontal Cortex?
0
WM
JP
*
SL
JC
DS
*
WJ
JH
VP
Patients (increasing severity
JW
)
*
IF
•
•
•
•
•
•
Wisconsin Card Sorting Test
Tower of London
WMS-R Digit Span
WMS-R Spatial Span
Computerized Spatial Span
Computerized N-Back
Composite
Frontal
Score
Aggleton, J.P. & Brown, M.W. (1999). Behavioral and Brain
Sciences, 22, 425-489.
Schacter, D.L., Harbluk, J.L., & McLachlan, D.R. (1984).
Journal of Verbal Learning and Verbal Behavior, 23, 593-611.
Glisky, E.L., Polster, M.R., & Routhieaux, B.C. (1995).
Neuropsychology, 9, 229-235.
Shimamura, A.P., Janowsky, J.S., & Squire, L.R. (1990).
Neuropsychologia, 28, 803-813.
Graham, K.S. & Hodges, J.R. (1997). Neuropsychology, 11, 7789.
Simons, J.S., Graham, K.S., et al. (2001). Neuropsychology, 15,
101-114.
Graham, K.S., Simons, J.S., et al. (2000). Neuropsychologia, 38,
313-324.
Simons, J.S., Graham, K.S., & Hodges, J.R. (submitted).
Journal of Memory and Language.
Mandler, G. (1980). Psychological Review, 87, 252-271.
Vargha-Khadem, F., Gadian, D.G., et al. (1997). Science, 277,
376-380.
Mummery, C.J., Patterson, K., et al. (2000). Annals of
Neurology, 47, 36-45.