Semantic DementiaSemantic Dementia

• Temporal variant of Frontotemporal dementia

• Progressive atrophy of one or both temporal lobes

Regions of significant gray matter density reduction relative to age-matched controls, as measured by voxel-based morphometry (Mummery et al., 2000).

Cognitive ProfileCognitive Profile

Recent experiments suggest better retrieval of recent autobiographical memories compared to those from the distant past (e.g., Graham & Hodges, 1997).

• This implies that learning of new material may be relatively preserved in semantic dementia

Semantic Memory(all modalities of input

and output)

Phonology, syntaxProblem solvingVisuospatial Perception

ImpairedImpaired PreservedPreserved

StudyStudy

TestTest

Recognition MemoryRecognition Memory

We have investigated episodic learning in semantic dementia using objects, faces, and line drawings as stimuli (Graham et al., 2000; Simons et al., 2001).

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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.

Analysis of Individual PatientsAnalysis of Individual Patientswith Semantic Dementiawith Semantic Dementia

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• Most patients with semantic dementia have highly accurate recognition memory.

• But at advanced stages of the disease, evidence of emerging deficit?

What could be causing this recognition memory impairment at late stages of semantic dementia?

• Investigate relative contributions of recollection and familiarity (Mandler, 1980).

– Recollection: ‘Remembering’ item with associated context

– Familiarity: ‘Knowing’ that item has been experienced

Using:• Source monitoring task

• Associative memory test

• Relate memory performance to measures of atrophic disruption in associated neural regions (e.g., medial temporal lobe, prefrontal cortex)

The Present StudyThe Present StudyAims:Aims:

Source Monitoring TaskSource Monitoring Task

10 min delay

Study Phase 1Study Phase 1

30 line drawings

Study Phase 2Study Phase 2

30 different drawings

Test PhaseTest Phase

“Did you see the picture in Set 1, Set 2, or not at all?”

120 drawings: 30 from Set 1, 30 Set 2, 60 New

Associative Memory TestAssociative Memory Test

Study PhaseStudy Phase

32 door and sofa pairs

“Were these items paired together at study?”

Test PhaseTest Phase

48 door and sofa pairs: 16 old, paired together at study16 old, re-paired since study16 new, not seen at study

Recollection and the HippocampusRecollection and the Hippocampus

• ‘Recollection’ supported by hippocampal system• ‘Familiarity’ supported by perirhinal cortex system

Aggleton & Brown (1999):

Selective bilateral hippocampal damage impairs recall but spares recognition memory

Vargha-Khadem et al. (1997):

Much evidence links the hippocampus with recollection-based memory. For example:

Volumetric MRI AnalysisVolumetric MRI Analysis

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.

Areas totalled to produce a volume for each region, corrected for total brain volume by dividing by whole brain cross-sectional area.

Hippocampus and Source MemoryHippocampus and Source Memory

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r=-.4, n.s.r=-.4, n.s.

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n• No significant positive correlation between bilateral hippocampal volume and source memory.

• 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.

BackgroundBackground

Recollection and the Prefrontal CortexRecollection and the Prefrontal Cortex

Source memory correlates highly with scores on frontal lobe tests in healthy adults.• Schacter et al. (1984), Glisky et al. (1995):

Source memory impairment prominent feature of frontal lobe damage.• Schacter et al. (1984), Shimamura et al. (1990):

Currently no volumetric protocol for the prefrontal cortex, so two methods of testing this:

Compare recollection-based memory with performance on frontal lobe tests in patients with semantic dementia.

Examine source memory ability of patients with the frontal variant of frontotemporal dementia.

• Wisconsin Card Sorting Test• Tower of London• WMS-R Digit Span• WMS-R Spatial Span• Computerized Spatial Span• Computerized N-Back

Composite Composite Frontal Frontal ScoreScore

1) Battery of Frontal Lobe Tasks1) Battery of Frontal Lobe Tasks

• 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.

Frontal Battery and Recollective MemoryFrontal Battery and Recollective Memory

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• Composite frontal score correlates significantly with both source discrimination and associative memory.

2) Frontal Variant FTD2) Frontal Variant FTD

• Frontal variant of Frontotemporal dementia

• Progressive atrophy primarily affecting frontal lobes

• Earliest signs are changes in behavior and personality, followed by cognitive impairment (attention, executive function, etc.)

• Recognition memory deficit rarely observed, unless atrophy has spread to involve posterior cortical regions

Performance on the Source Monitoring TaskPerformance on the Source Monitoring Task

• Patients with frontal variant FTD had little difficulty with familiarity-based item memory.

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• But all patients tested were severely impaired at recollection-based source memory.

• 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

– 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.

ConclusionsConclusions

ReferencesReferencesAggleton, J.P. & Brown, M.W. (1999). Behavioral and Brain Sciences, 22, 425-489.

Glisky, E.L., Polster, M.R., & Routhieaux, B.C. (1995). Neuropsychology, 9, 229-235.

Graham, K.S. & Hodges, J.R. (1997). Neuropsychology, 11, 77-89.

Graham, K.S., Simons, J.S., et al. (2000). Neuropsychologia, 38, 313-324.

Mandler, G. (1980). Psychological Review, 87, 252-271.

Mummery, C.J., Patterson, K., et al. (2000). Annals of Neurology, 47, 36-45.

Schacter, D.L., Harbluk, J.L., & McLachlan, D.R. (1984). Journal of Verbal Learning and Verbal Behavior, 23, 593-611.

Shimamura, A.P., Janowsky, J.S., & Squire, L.R. (1990). Neuropsychologia, 28, 803-813.

Simons, J.S., Graham, K.S., et al. (2001). Neuropsychology, 15, 101-114.

Simons, J.S., Graham, K.S., & Hodges, J.R. (submitted). Journal of Memory and Language.

Vargha-Khadem, F., Gadian, D.G., et al. (1997). Science, 277, 376-380.

Familiarity-Based MemoryFamiliarity-Based Memory

• 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.

• Also similar to before, three patients at advanced stages of semantic dementia did show a significant deficit.

• Previous studies indicate that this pattern is not due to:

– Degraded semantic knowledge

– Disrupted perceptual processes

• But can be attributed to atrophy

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Patient confidence interval

(no overlap indicates impairment)

Key:

Patients (increasing severity )

affecting medial temporal lobe regions such as the perirhinal cortex (Simons et al., submitted).

Recollection-Based MemoryRecollection-Based Memory

• 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.

• Again, pattern not related to degraded semantic knowledge.

• Possible explanations? Atrophy progressing to affect the function of:

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****** Patients (increasing severity )

• Hippocampus? • Prefrontal Cortex?

Recollection-Based Memory in Frontotemporal DementiaRecollection-Based Memory in Frontotemporal DementiaJon S. Simons1*, Mieke Verfaellie2, Kim S. Graham1, Clare J. Galton3, Karalyn Patterson1,

and John R. Hodges1,3

Jon S. Simons1*, Mieke Verfaellie2, Kim S. Graham1, Clare J. Galton3, Karalyn Patterson1, and John R. Hodges1,3

1. MRC Cognition and Brain Sciences Unit, Cambridge, UK2. Memory Disorders Research Center, Boston University School of Medicine3. University Neurology Unit, Addenbrooke’s Hospital, Cambridge, UK

* Now at the Department of Psychology, Harvard University,Rm 860, William James Hall, 33 Kirkland St, Cambridge, MA 02138E-mail: jss@wjh.harvard.edu

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