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Neural Networks Involved in
Spatial Pattern Separation and
Temporal Pattern SeparationMeera Paleja
Doctoral Defense
September 10, 2012
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Overview Episodic memory
Spatial and temporal
Encoding and retrieval
Pattern separation and pattern completion
Highlights from present work
Pattern separation and stage of processing
Pattern separation and information type
Discussion and future directions
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Episodic Memory and the
Hippocampus “Where” and “when”
Spatial
Temporal
Encoding and retrieval
Lepage et al.’s HIPER model
Pattern separation and pattern completion
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Encoding and Retrieval in the
MTL: the HIPER model Lepage et al. (1998)
Anterior = Encoding
Posterior = Retrieval
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Encoding/Retrieval and
Information Type Spatial encoding:
Hippocampus
Parahippocampal gyrus
Spatial retrieval:
Hippocampus
Parahippocampal gyrus
PFC
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Temporal encoding:
Hippocampus
Parahippocampal gyrus
PFC
Temporal retrieval:
Hippocampus
PFC
Encoding/Retrieval and Information Type
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Pattern Separation and
Completion Pattern separation: process of forming or transforming similar
memories into different non-overlapping representations
Pattern completion: process of completing well-established
representations from partial/incomplete spatial information
Trade-off between separation and completion
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Pattern Separation and Information
Type Pattern separation: process of forming or transforming similar
memories into different non-overlapping representations
Spatial pattern separation: separating objects and/or events
in space
Temporal pattern separation: separating objects and/or
events in time
Gilbert, Kesner, & Lee (2001)
Spatial pattern separation: DG
Temporal pattern separation: CA1
No study has systematically examined spatial and temporal
pattern separation in humans
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Pattern Separation: Encoding or
Retrieval? PS often conceptualized as encoding-based process, and PC
as retrieval-based
Kesner & Hopkins (2006): Pattern separation involved at
encoding and retrieval to reduce interference.
Hippocampally lesioned rats impaired at locating previously
presented spatial location when presented with four possible
options, compared to rodents without hippocampal lesions
(KiMattia & Kesner, 1988).
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Pattern Separation: Unexamined
Areas Whole-brain patterns of activity and neural networks
Neural correlates based on information type (i.e., spatial
versus temporal pattern separation)
Pattern separation and stage of processing (i.e., encoding
versus retrieval)
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Hypotheses Experiment 1 (behavioural)
Accuracy should increase and reaction time decrease as separation distances increase
between targets and foils
Experiment 2 (fMRI)
More hippocampal involvement when more pattern separation required at encoding for
subsequent successful retrieval
Areas involved in spatial versus temporal pattern separation encoding should map onto
general spatial (HC, PHG) and temporal memory (HC, PHG, PFC) encoding tasks
Qualitatively distinct neural networks when pattern separation more heavily engaged
(more MTL and additional recruitment from other regions) compared to when it is less
engaged
Neural networks should differ by information type (spatial versus temporal) consistent
with general spatial (HC, PHG) and temporal memory (HC, PHG, PFC) context literature
Pattern separation at encoding versus retrieval should show anterior HC at encoding,
posterior HC at retrieval
Functional connectivity of hippocampus during spatial versus temporal pattern
separation should reveal greater connectivity of temporal PS HC seed with frontal
regions
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Methods Participants
Experiment 1: 19 healthy adults (ages 20-59, Mage=31.9, SD=13.96;
12 female)
Experiment 2: 14 healthy young adults (ages 18-55, Mage=27.4,
SD=9.22; 9 female, FSIQe=118)
Fluent in English
Normal or corrected-to-normal vision
Exclusionary criteria: neurological impairment, Axis I disorder, history
of or current drug/alcohol dependence, first degree relatives with
psychotic illness
Meet MRI scanning requirements (Experiment 2)
Tested at BIM lab at Ryerson and St. Joseph’s Hospital in Hamilton
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Methods Spatial Pattern Separation Task
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Methods Temporal Pattern Separation Task
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Results: Experiment 1 Significant accuracy differences between separation
conditions for both SPS, t(18)= -9.895, p<.001, d=2.27, and
TPS, t(18)= -4.938, p<.001, d=1.13.
0
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0.5
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SPS TPS
Pro
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TASK
NEAR
FAR
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Results: Experiment 1 Significant RT differences between separation conditions in
both SPS, t(18)= 3.737, p=.002, d=0.857, and TPS, t(18)=
5.538, p<.001, d=1.27.
0
500
1000
1500
2000
2500
SPS TPS
Reacti
on
Tim
e (
ms)
TASK
NEAR
FAR
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Methods: Experiment 2 Scanning
4 runs of functional imaging (2 SPS, 2 TPS)
3T MRI scanner
Anatomical Data: MP-RAGE sequence
Functional images: T2*-weighted EPI (voxel size: 3x3x4 mm3, TR
= 3000ms, TE = 30ms, FOV = 196mm, flip angle = 90 degrees)
Axial slices to minimize overheating and signal loss in inferior
frontal lobe
B0 maps to correct for magnetic field inhomogeneities
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Non-Rotated Task PLS: SPS
LV (singular value = 57.09, p < .001):
Encoding (near/far/incorrect) vs.
Retrieval (recognition)
-1.5
-1
-0.5
0
0.5
1
1.5
De
sign
Sco
res
Enc_Near
Enc_Far
Enc_Incorr
Ret_Near
Ret_Far
Ret_Incorr
-800
-600
-400
-200
0
200
400
600
800
1000
1 2 3 4
Bra
in S
core
s
Time-Lag
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Non-Rotated Task PLS: SPS
Network of regions includes bilateral anterior HC (encoding) and
R posterior HC (retrieval), L and R parahippocampal gyrus,
bilateral PFC, R superior temporal gyrus, L superior frontal gyrus
Encoding vs. Retrieval
Lag 2 Lag 3
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Non-Rotated Task PLS: SPS
Network of regions includes bilateral anterior HC (encoding) and
R posterior HC (retrieval), L and R parahippocampal gyrus,
bilateral PFC, R superior temporal gyrus, L superior frontal gyrus
Encoding vs. Retrieval
Lag 2
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Non-Rotated Task PLS: SPS
Network of regions includes bilateral anterior HC (encoding) and
R posterior HC (retrieval), L and R parahippocampal gyrus,
bilateral PFC, R superior temporal gyrus, L superior frontal gyrus
Encoding vs. Retrieval
Lag 2 Lag 3
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Non-Rotated Task PLS: SPS
Network of regions includes bilateral anterior HC (encoding) and
R posterior HC (retrieval), L and R parahippocampal gyrus,
bilateral PFC, R superior temporal gyrus, L superior frontal gyrus
Encoding vs. Retrieval
Lag 2 Lag 2
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Non-Rotated Task PLS: TPS
LV (singular value = 195.13, p < .001):
Encoding vs. Retrieval
-1.5
-1
-0.5
0
0.5
1
1.5
De
sign
Sco
res
Enc_Near
Enc_Far
Enc_Incorr
Ret_Near
Ret_Far
Ret_Incorr
-10000
-8000
-6000
-4000
-2000
0
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6000
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10000
1 2 3 4
Bra
in S
core
s
Time-Lag
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Non-Rotated Task PLS: TPS
Network of regions includes R posterior HC (retrieval),
PFC, R parahippocampal gyrus, caudate.
Encoding vs. Retrieval
Lag 1
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Non-Rotated Task PLS: TPS
Network of regions includes R posterior HC (retrieval),
PFC, R parahippocampal gyrus, caudate.
Encoding vs. Retrieval
Lag 3Lag 2
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Non-Rotated Task PLS: TPS
Network of regions includes R posterior HC (retrieval),
PFC, R parahippocampal gyrus, caudate.
Encoding vs. Retrieval
Lag 3
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Discussion: Nonrotated Task
Analysis Unique networks identified for encoding and retrieval for both
spatial and temporal PS
Spatial encoding:
Bilateral anterior hippocampus, bilateral PHG, bilateral PFC, R
superior temporal gyrus, L superior frontal gyrus
Spatial retrieval
R posterior hippocampus, bilateral PHG, bilateral PFC
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Discussion: Nonrotated Task
Analysis Unique networks identified for encoding and retrieval for both
spatial and temporal PS
Temporal encoding:
Bilateral PFC (including orbitofrontal), caudate
Temporal retrieval
R posterior hippocampus, R PHG, bilateral PFC
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Discussion: Nonrotated Task
Analysis
Data consistent with HIPER model discussed previously
Bilateral anterior hippocampal activation in Spatial PS
encoding
Right posterior hippocampal activation in Spatial and
Temporal PS retrieval
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Seed Analysis: SPS
Clusters functionally connected to
HC seed: L inferior and middle
temporal gyri, L anterior lobe, L
superior parietal lobule, R middle
temporal gyrus
-0.05
-0.04
-0.03
-0.02
-0.01
0
0.01
0.02
0.03
1 2 3 4
SIgn
al I
nte
nsi
ty C
han
ge (
%)
Lag
Encoding
Retrieval
MNI: X = 30 Y = -24 Z = 10
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Seed Analysis: TPS
Clusters functionally connected to
HC seed: L parahippocampal
gyrus, L and R medial frontal
gyrus, L inferior gyrus, postcentral
gyrus, L superior temporal gyrus
-0.08
-0.06
-0.04
-0.02
0
0.02
0.04
0.06
0.08
1 2 3 4
Sign
al I
nte
nsi
ty C
han
ge (
%)
Lag
Encoding
Retrieval
MNI: X = 30 Y = -46 Z = 6
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Discussion: Seed PLS Spatial pattern separation (MNI: X = 30 Y = -24 Z = 10)
Hippocampal seed (CA field) displayed functional connectivity
with clusters in left inferior temporal gyrus, bilateral middle
temporal gyrus, superior parietal lobule, cerebellum
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Discussion: Seed PLS Spatial pattern separation (MNI: X = 30 Y = -24 Z = 10)
Hippocampal seed (CA field) displayed functional connectivity
with clusters in left inferior temporal gyrus, bilateral middle
temporal gyrus, superior parietal lobule, cerebellum
Temporal pattern separation (MNI: X = 30 Y = -46 Z = 6)
Hippocampal seed (CA field) displayed functional connectivity
with clusters in bilateral medial frontal gyri, left inferior frontal gyri,
left parahippocampal gyrus
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General Discussion Findings in line with Lepage’s HIPER model
Spatial Pattern Separation
Bilateral anterior HC involved at encoding
Right posterior HC involved at retrieval
Temporal Pattern Separation
Right posterior HC involved at retrieval
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General Discussion R posterior HC seed in spatial PS functionally connected to
independent clusters primarily in temporal and superior
parietal area
R posterior HC seed in temporal PS functionally connected to
independent clusters primarily in frontal regions
Differences in functional connectivity of HC during pattern
separation retrieval based on information type
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Future Directions Pattern separation in older adults, Mild Cognitive Impairment,
Alzheimer’s Disease
Spatial and temporal pattern separation and pattern
completion in Schizophrenia
Pattern separation and sensory modality
Pattern separation and aerobic exercise
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Thank you!
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Hippocampal Anatomy Medial temporal lobe: hippocampus, amygdala,
parahippocampal gyrus
Hippocampal subregions DG, CA1, CA2, CA3, CA4
Two projection pathways
Entorhinal DG CA3 CA1 fornix
Entorhinal CA1 fornix
Washington University School
of Medicine
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Bakker et al. (2008):
Presented object might be new, a repetition, or a lure
If lure treated like new stimulus in a region, should show activation
similar to that of new stimulus: PS
If lure treated like old stimulus by a region, activation decreased
compared to that of new stimulus: PC
PS: DG/CA3
PC: CA1
Pattern Separation and the
Hippocampus
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Processes Animal Human Computational
Pattern Separation DG vs. CA1 DG/CA3 vs. CA1 DG, CA3
Pattern Completion CA3 vs. CA1 CA1 vs. CA3 CA3
Hippocampal Subregional Involvement in Pattern Separation and Completion
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Results: Experiment 2 Behavioural
Data Significant accuracy differences between separation
conditions in SPS, t(13)= -5.845, p<.001, d= 1.56, but not
TPS, t(13)= -2.68, p=.312, d= .28.
0
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SPS TPS
Pro
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TASK
NEAR
FAR
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Results: Experiment 2 Behavioural
Data Significant reaction time differences between separation
conditions in both SPS, t(13)= 2.621, p=.021, d= .70, and
TPS t(13)= 3.858, p=.002, d=.1.02.
0
500
1000
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2000
2500
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Reacti
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Tim
e (
ms)
TASK
NEAR
FAR
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Mean-Centered PLS: TPS
LV1 (singular value= 203.81, p<.001): Differentiates
between letter/retrieval and encoding
LV2 (not shown): Differentiates between letter and
recognition
Network of regions includes
frontal pole (BA 10), bilateral
medial frontal gyri (BA 6), R
HC, and caudate.-0.5
-0.4
-0.3
-0.2
-0.1
0
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De
sign
Sco
res
Enc_Near
Enc_Far
Enc_Incorr
Letter
Ret_Near
Ret_Far
Ret_Incorr
-20
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1 2 3 4
Bra
in S
core
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Time-Lag
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Mean-Centered PLS: SPS LV
LV (singular value= 61.82,
p<.001): Differentiates
between letter/retrieval and
encoding
Network of regions includes
frontal pole (BA 10),
parahippocampal gyrus (BA
36), hippocampus, and
caudate nucleus.
-20
-15
-10
-5
0
5
10
15
1 2 3 4
Bra
in S
core
s
Time-Lag
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
De
sign
Sco
res
Enc_Near
Enc_Far
Enc_Incorr
Letter
Ret_Near
Ret_Far
Ret_Incorr
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GLM Analysis (SPM) SPS: R lingual gyrus, L
hippocampus, p<.001
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GLM Analysis (SPM) TPS: prefrontal cortex
(BA 10), L superior
frontal gyrus,
cerebellum, p<.001