Doctoral Defense Pres SlideShare

Neural Networks Involved in

Spatial Pattern Separation and

Temporal Pattern SeparationMeera 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

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SPS TPS

Pro

po

rtio

n C

orr

ect

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

Reacti

on

Tim

e (

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

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


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 3






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

De

sign

Sco

res

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

Bra

in S

core

s

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

SIgn

al I

nte

nsi

ty C

han

ge (

%)

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

Sign

al I

nte

nsi

ty C

han

ge (

%)

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

Thank you!

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

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SPS TPS

Pro

po

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orr

ect

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

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2500

SPS TPS

Reacti

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Tim

e (

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

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sign

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Enc_Near

Enc_Far

Enc_Incorr

Letter

Ret_Near

Ret_Far

Ret_Incorr

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in S

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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

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-10

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in S

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Time-Lag

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sign

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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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