Doctoral Defense Pres SlideShare

Neural Networks Involved in
Spatial Pattern Separation and
Temporal Pattern Separation
Meera Paleja
Doctoral Defense
September 10, 2012

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

Episodic Memory and the
Hippocampus
 “Where” and “when”
 Spatial
 Temporal
 Encoding and retrieval
 Lepage et al.’s HIPER model
 Pattern separation and pattern completion

Encoding and Retrieval in the
MTL: the HIPER model
 Lepage et al. (1998)
 Anterior = Encoding
 Posterior = Retrieval

Encoding/Retrieval and
Information Type
 Spatial encoding:
 Hippocampus
 Parahippocampal gyrus
 Spatial retrieval:
 Hippocampus
 PFC

 Temporal encoding:
 Hippocampus
 PFC
 Temporal retrieval:
 Hippocampus
 PFC
Encoding/Retrieval and
Information Type

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

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

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).

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)

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

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

Methods
 Spatial Pattern Separation Task

Methods
 Temporal Pattern Separation Task

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
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
SPS TPS
ProportionCorrect
TASK
NEAR
FAR

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
ReactionTime(ms)
TASK
NEAR
FAR

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

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
DesignScores
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
BrainScores
Time-Lag

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

Lag 2

Lag 2 Lag 2

Non-Rotated Task PLS: TPS
LV (singular value = 195.13, p < .001):
-1.5
-1
-0.5
0
0.5
1
1.5
DesignScores
Enc_Near
Enc_Far
Enc_Incorr
Ret_Near
Ret_Far
Ret_Incorr
-10000
-8000
-6000
-4000
-2000
0
2000
4000
6000
8000
10000
1 2 3 4
BrainScores
Time-Lag

Network of regions includes R posterior HC (retrieval),
PFC, R parahippocampal gyrus, caudate.
Lag 1

Lag 3Lag 2

Lag 3

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

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

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

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
SIgnalIntensityChange(%)
Lag
Encoding
Retrieval
MNI: X = 30 Y = -24 Z = 10

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
SignalIntensityChange(%)
Lag
Encoding
Retrieval
MNI: X = 30 Y = -46 Z = 6

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

Discussion: Seed PLS
 Spatial pattern separation (MNI: X = 30 Y = -24 Z = 10)
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)
with clusters in bilateral medial frontal gyri, left inferior frontal gyri,
left parahippocampal gyrus

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

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

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

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

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

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

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
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
SPS TPS
ProportionCorrect
TASK
NEAR
FAR

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
1500
2000
2500
SPS TPS
ReactionTime(ms)
TASK
NEAR
FAR

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
0.1
0.2
0.3
0.4
0.5
DesignScores
Enc_Near
Enc_Far
Enc_Incorr
Letter
Ret_Near
Ret_Far
Ret_Incorr
-20
-15
-10
-5
0
5
10
15
1 2 3 4
BrainScores
Time-Lag

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
BrainScores
Time-Lag
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
DesignScores
Enc_Near
Enc_Far
Enc_Incorr
Letter
Ret_Near
Ret_Far
Ret_Incorr

GLM Analysis (SPM)
 SPS: R lingual gyrus, L
hippocampus, p<.001

GLM Analysis (SPM)
 TPS: prefrontal cortex
(BA 10), L superior
frontal gyrus,
cerebellum, p<.001

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Editor's Notes