Dissecting the human medial temporal lobe memory system by functional MRI [Elektronische Ressource] / vorgelegt von Christine Susanne Weis

Dissecting the Human Medial Temporal Lobe Memory System by functional MRI


Von der Medizinischen Fakultät
der Rheinisch-Westfälischen Technischen Hochschule Aachen
zur Erlangung des akademischen Grades
einer Doktorin der Theoretischen Medizin
genehmigte Dissertation








vorgelegt von

Dipl.-Math. Christine Susanne Weis

aus

Kaiserslautern


Berichter: Herr Universitätsprofessor
Dr. rer. nat. Klaus Willmes-von Hinckeldey

Herr Privatdozent
Dr. med. Guillén Fernández




Tag der mündlichen Prüfung: 9. November 2004

Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfügbar. 21 SUMMARY ................................................................................................................................................5
2 INTRODUCTION .....................................................................................................................................7
WHAT IS EPISODIC MEMORY? ..................................................................................................................7
2.1 ANATOMY OF THE MEDIAL TEMPORAL LOBE ............................................................................9
2.2 EPISODIC MEMORY - EVIDENCE FROM FUNCTIONAL IMAGING ................................................13
2.2.1 Encoding.............................................................................................................................15
2.2.2 Retrieval .............................................................................................................................22
2.2.3 Event-related fMRI studies on Encoding and Retrieval of Source Memory .......................28
2.3 OVERVIEW OF THESIS...............................................................................................................33
2.4 LIST OF ABBREVIATIONS..........................................................................................................35
3 MATERIALS AND METHODS..37
3.1 FUNCTIONAL MAGNETIC RESONANCE IMAGING ......................................................................37
3.1.1 Non-invasive neuroimaging techniques..............................................................................37
3.1.2 The physics of NMR and MRI.............................................................................................38
3.1.3 Image formation: frequency and phase encoding...............................................................42
3.1.4 Ultra fast MRI sequences: Echo-Planar Imaging ..............................................................44
3.1.5 fMRI and the magnetic properties of blood ........................................................................44
3.1.6 Neurophysiology and BOLD...............................................................................................45
3.2 FMRI DATA ANALYSIS WITH SPM ..........................................................................................46
3.2.1 Spatial preprocessing .........................................................................................................48
3.2.2 Statistical parametric mapping...........................................................................................49
3.3 EVENT-RELATED FMRI............................................................................................................55
4 NEURAL CORRELATES OF SUCCESSFUL DECLARATIVE MEMORY FORMATION
AND RETRIEVAL: THE ANATOMICAL OVERLAP ...............................................................................57
4.1 INTRODUCTION ........................................................................................................................57
4.2 MATERIAL AND METHODS .......................................................................................................60
4.2.1 Subjects...............................................................................................................................60
4.2.2 Stimuli.........60
4.2.3 Task ....................................................................................................................................61
4.2.4 fMRI Data Acquisition........................................................................................................62
4.2.5 a Analysis63
4.3 RESULTS ..................................................................................................................................65
4.3.1 Behavioral Data .................................................................................................................65
4.3.2 Imaging Data......................................................................................................................66
4.4 DISCUSSION .............................................................................................................................79
5 NEURAL CORRELATES OF CONTEXTUAL RETRIEVAL AND ITEM RECOGNITION
ARE DISSOCIATED WITHIN THE HUMAN MEDIAL TEMPORAL LOBE ........................................85
5.1 INTRODUCTION ........................................................................................................................85
5.2 MATERIAL AND METHODS .......................................................................................................89
5.2.1 Subjects...............................................................................................................................89
5.2.2 Stimuli.........89
5.2.3 Task ....................................................................................................................................90
5.2.4 fMRI Data Acquisition........................................................................................................92
5.2.5 fMRI Data Analysis ............................................................................................................92
5.3 RESULTS ..................................................................................................................................94
5.3.1 Behavioral Results..............................................................................................................94
5.3.2 Imaging Data......................................................................................................................96
5.4 DISCUSSION108
6 GENERAL DISCUSSION.......114
7 REFERENCES.......................................................................................................................................118
8 ACKNOWLEDGEMENTS ..................................................................................................................131
9 CURRICULUM VITAE.........132
10 LIST OF PUBLICATIONS ..................................................................................................................134
4
1 Summary
The work presented in this thesis comprises two event-related functional magnetic
resonance imaging (fMRI) studies, which aim at dissociating the contributions of
different subregions of the human medial temporal lobe (MTL) to declarative memory
processes. The first study examines common neural correlates of memory encoding
and recognition. Healthy subjects were scanned both while they memorized complex
photographs of buildings and landscapes and while they tried to recognize these
pictures in a series of new photographs. Confirming earlier findings, declarative
memory formation correlated with an activity increase in the MTL and the inferior
prefrontal cortex. Further, during recognition, stronger brain responses to correctly
identified old items (hits) as compared to correctly identified new items were found in
the parietal lobe, the anterior prefrontal cortex, the anterior cingulate and the
cerebellum, replicating findings concerning the commonly used old/new effect. As an
innovation, a positive and a negative recognition effect were introduced, comparing
brain responses to hits and brain responses to misses (old items misclassified as new)
during test. This comparison gives a ‘purer’ measure of neural activity associated with
explicit recognition than the commonly used old/new effect. Thus, it can be used to
identify decreases and increases in brain activity associated with recognition success.
The positive recognition effect, stronger responses for hits than misses, identified
activations similar to the old/new effect in prefrontal, parietal, and cerebellar areas.
The negative recognition effect, weaker brain responses for hits than misses, which is
less contaminated by repetition priming than a reversed old/new effect, offers the
possibility to study whether recognition success can also be associated with regional
brain activity decreases. In line with electrophysiological findings, this effect identified
an activity decrease in the anterior MTL related to recognition success. The main
feature this study adds to the existing literature is the fact that memory encoding and
retrieval were examined in a single study-test experiment. Thus, it was possible to use
a conjunction analysis to directly compare encoding- and retrieval-related activations
within subjects. This analysis identified an integrated temporal-cerebellar network,
whose activity correlates with both memory formation and retr