The main task of this work is to design an algorithm for suppressing unwanted noise and artifacts in fMRI data using the analysis of independent components and multi-echo data. The theoretical part deals with the basic principles of magnetic resonance, including construction and image data processing. The practical part presents a pilot design of a method inspired by a professional publication in the Matlab software environment, where this design is subsequently tested on real fMRI data provided by the Laboratory of Multimodal and Functional Imaging, CEITEC MU.

Seeing is more than sight: it is the entire action-perception loop involved in taking in the world around us. Unlike a camera, our eyes can only resolve a small part of the environment sharply. Therefore, we must constantly move our eyes to scrutinise the parts of our environment that seem most worthy of our highest visual acuity. Eye movements are thus the observable consequences of a complex and crucial decision-making process that is fundamental to how we interact with the world. This thesis investigates properties and the neural basis of eye-movement behavior in humans and monkeys. In the interdisciplinary tradition of cognitive science, the thesis spans fields and utilizes computational models as explanatory vehicles. A central theme is the so-called saliency map model of attention, the de facto computational model of viewing behavior. The saliency map model assumes that attention is directed at the peaks of a map that encodes the saliency of locations in the visual field. Saliency can roughly be thought of as how worthy a location is of attention. It forms a common currency that allows different processes to influence the distribution of attention. The four different studies in this thesis provide four different perspectives on viewing behavior and the saliency map model. The first study establishes a methodology to evaluate the predictive power of models of viewing behavior, and determines which properties of viewing behavior are important for this evaluation. Applying this methodological foundation to the saliency map model reveals that state-of-the-art models do not provide satisfactory explanations of viewing behavior. The second study investigates spatio-temporal properties of eye-movements, finding that observers often re-fixate locations in pictures and that their eye movements possess a rich spatio-temporal structure. These results speak directly against a causal role of "inhibition of return", which is a popular component of many saliency map models. The third study shifts focus to the neural basis of the oculomotor behaviour. fMRI is used to probe the relationship between the computation of saliency and actual processing in the brain. Our results, in contrast to those of other studies, suggest that early visual areas do not compute saliency, but instead compute visual features upon which the saliency map operates. Much of what we know about the neural basis of oculomotor control comes from invasive studies in animals, but it is unclear to what extent saliency computations are comparable between species. Thus, the fourth study compares the viewing behavior of monkeys and humans, to look for evidence of the same underlying processes. We find a strong similarity between the species in saliency-driven viewing behavior. The many saliency-processing areas that have been identified in monkeys therefore likely have a role in saliency processing in the human brain as well. This thesis contributes to our understanding of oculomotor control on multiple levels. The results in this thesis suggest that models of viewing behavior should treat saccade-target selection as a dynamic process where past decisions influence future decisions and where saliency varies over time. This selection process likely takes place in a distributed network in the brain which receives bottom-up input from early visual areas. Encouraged by these results, we speculate that normative and embodied models of cognition offer an explanation of oculomotor control that takes these results into account. In turn, explaining oculomotor control is an important part of the much deeper question of how our mind interacts with the world.

Master's thesis focuses on processing fMRI data, which are mapping blood oxygenation level dependence in a state of brain activity. Usable and necessarily preprocessing tech- niques of the data, together with two main analysis approaches are introduced. The area of univariate methods, especially general linear model and multivariate principal or independent component analysis is explained. Practical application of the methods involved on the real fMRI data set is implemented. Relevant results as well as theirs mutual possible comparison is presented.

Research in olfaction is been quite diverse, for example with studies on semantics, brain activations, or distorted smells. Olfactory dysfunction can lead to reduced quality of life, poor dietary habits, sexual and/or mental dysfunctions. Especially in terms of the investigation of olfactory loss it is not only important to assess olfactory function with ratings subjectively assess but more objective measures should be considered. Use of EEG and fMRI has been quite well studied. I have focused my thesis on the use of newer or updated use of existing processing pipelines in order to understand olfaction in a better way.

This thesis describes the development, implementation and application of various quantitative functional magnetic resonance imaging (fMRI) approaches at ultra-high magnetic field including the assessment with regards to applicability and reproducibility. Functional MRI (fMRI) commonly uses the blood oxygenation level dependent (BOLD) contrast to detect functionally induced changes in the oxy-deoxyhaemoglobin composition of blood which reflect cerebral neural activity. As these blood oxygenation changes do not only occur at the activation site but also downstream in the draining veins, the spatial specificity of the BOLD signal is limited. Therefore, the focus has moved towards more quantitative fMRI approaches such as arterial spin labelling (ASL), vascular space occupancy (VASO) or calibrated fMRI which measure quantifiable physiologically and physically relevant parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV) or cerebral metabolic rate of oxygen (CMRO2), respectively. In this thesis a novel MRI technique was introduced which allowed the simultaneous acquisition of multiple physiological parameters in order to beneficially utilise their spatial and temporal characteristics. The advantages of ultra-high magnetic field were utilised to achieve higher signal-to-noise and contrast-to-noise ratios compared to lower field strengths. This technique was successfully used to study the spatial and temporal characteristics of CBV, CBF and BOLD in the visual cortex. This technique is the first one that allows simultaneous acquisition of CBV, CBF and BOLD weighted fMRI signals in the human brain at 7 Tesla. Additionally, this thesis presented a calibrated fMRI technique which allowed the quantitative estimation of changes in cerebral oxygen metabolism at ultra-high field. CMRO2 reflects the amount of thermodynamic work due to neural activity and is therefore a significant physical measure in neuroscience. The calibrated fMRI approach presented in this thesis was optimised for the use at ultra-high field by adjusting the MRI parameters as well as implementing a specifically designed radio-frequency (RF) pulse. A biophysical model was used to calibrate the fMRI data based on the simultaneous acquisition of BOLD and CBF weighted MRI signals during a gas-breathing challenge. The reproducibility was assessed across multiple brain regions and compared to that of various physiologically relevant parameters. The results indicate that the degree of intra-subject variation for calibrated fMRI is lower than for the classic BOLD contrast or ASL. Consequently, calibrated fMRI is a viable alternative to classic fMRI contrasts with regards to spatial specificity as well as functional reproducibility. This calibrated fMRI approach was also compared to a novel direct calibration technique which relies on complete venous oxygenation saturation during the calibration scan via a gas-breathing challenge. This thesis introduced several reliable quantitative fMRI approaches at 7 Tesla and the results presented are a step forward to the wider application of quantitative fMRI.:1 Introduction 3 2 Background to Functional Magnetic Resonance Imaging 7 2.1 Magnetic Resonance 7 2.1.1 Quantum Mechanics 7 2.1.2 The Classical Point of View 10 2.1.3 Radio Frequency Pulses 12 2.1.4 Relaxation Effects 13 2.1.5 The Bloch Equations 15 2.2 Magnetic Resonance Imaging 16 2.2.1 Data Acquisition 16 2.2.2 Image Formation 17 2.2.2.1 Slice Selection 17 2.2.2.2 Frequency Encoding 18 2.2.2.3 Phase Encoding 19 2.2.2.4 Mathematics of Image Formation 20 2.2.2.5 Signal Formation 22 2.3 Advanced Imaging Methods 24 2.3.1 Echo-Planar Imaging (EPI) 24 2.3.2 Partial Fourier Acquisition 25 2.3.3 Generalised Autocalibrating Partially Parallel Acquisition (GRAPPA) 25 2.3.4 Inversion Recovery (IR) 26 2.3.5 Adiabatic Inversion 26 2.3.5.1 Hyperbolic Secant (HS) RF pulses 28 2.3.5.2 Time Resampled Frequency Offset Corrected Inversion (tr-FOCI) RF Pulses 28 2.4 Physiological Background 29 2.4.1 Neuronal Activity 30 2.4.2 Energy Metabolism 31 2.4.3 Physiological Changes During Brain Activation 32 2.4.4 The BOLD Contrast 34 2.4.5 Disadvantages of the BOLD Contrast 35 2.5 Arterial Spin Labelling (ASL) 35 2.5.1 Pulsed Arterial Spin Labelling 37 2.5.2 Arterial Spin Labelling at Ultra-High Field 41 2.6 Vascular Space Occupancy (VASO) 42 2.6.1 VASO at Ultra-High Field 44 2.6.2 Slice-Saturation Slab-Inversion (SS-SI) VASO 45 2.7 Calibrated Functional Magnetic Resonance Imaging 47 2.7.1 The Davis Model 47 2.7.2 The Chiarelli Model 50 2.7.3 The Generalised Calibration Model (GCM) 52 3 Materials and Methods 53 3.1 Scanner Setup 53 3.2 Gas Delivery and Physiological Monitoring System 53 3.3 MRI Sequence Developments 55 3.3.1 Tr-FOCI Adiabatic Inversion 55 3.3.2 Optimisation of the PASL FAIR QUIPSSII Sequence Parameters 60 3.3.3 Multi-TE Multi-TI EPI 64 4 Experiment I: Comparison of Direct and Modelled fMRI Calibration 68 4.1 Background Information 68 4.2 Methods 69 4.2.1 Experimental Design 69 4.2.2 Visuo-Motor Task 70 4.2.3 Gas Manipulations 71 4.2.4 Scanning Parameters 71 4.2.5 Data Analysis 72 4.2.6 M-value Modelling 72 4.2.7 Direct M-Value Estimation 73 4.3 Results 74 4.4 Discussion 79 4.4.1 M-value Estimation 79 4.4.2 BOLD Time Courses 82 4.4.3 M-Maps and Single Subject Analysis 82 4.4.4 Effects on CMRO2 Estimation 83 4.4.5 Technical Limitations and Implications for Calibrated fMRI 84 4.5 Conclusion 89 5 Experiment II: Reproducibility of BOLD, ASL and Calibrated fMRI 90 5.1 Background Information 90 5.2 Methods 91 5.2.1 Experimental Design 91 5.2.2 Data Analysis 91 5.2.3 Reproducibility 93 5.2.4 Learning and Habituation Effects 95 5.3 Results 95 5.4 Discussion 101 5.4.1 Breathing Manipulations 102 5.4.2 Functional Reproducibility 107 5.4.3 Habituation Effects on Reproducibility 109 5.4.4 Technical Considerations for Calibrated fMRI 110 5.5 Conclusion 112 6 Experiment III: Simultaneous Acquisition of BOLD, ASL and VASO Signals 113 6.1 Background Information 113 6.2 Methods 114 6.2.1 SS-SI VASO Signal Acquisition 114 6.2.2 ASL and BOLD Signal Acquisition 114 6.2.3 Experimental Design 114 6.2.4 Data Analysis 115 6.3 Results 115 6.4 Discussion 116 6.5 Conclusion 120 7 Conclusion and Outlook 121

Muscle weakness is one of the major causes of post-stroke disability. Stroke rehabilitation programs now often incorporate the same type of resistance training that is used for healthy subjects; however, the training effects induced from these training strategies are often limited for stroke patients. An important resistance training principle is that an optimal level of stress is exerted on the neuromuscular system, both during concentric (shortening) and eccentric (lengthening) contractions. One potential problem for post-stroke patients might be difficulties achieving sufficient levels of stress on the neuromuscular system. This problem may be associated with altered muscular function after stroke. In healthy subjects, maximum strength during eccentric contractions is higher than during concentric contractions. In individuals with stroke, this difference in strength is often increased. Moreover, it has also been shown that individuals with stroke exhibit alteration with respect to how the strength varies throughout the range of motion. For example, healthy subjects exhibit a joint specific torque-angle relationship that normally is the same irrespective of contraction mode and contraction velocity. In contrast, individuals with stroke exhibit an overall change of the torque-angle relationship. This change, as described in the literature, consists of a more pronounced strength loss at short muscle length. In individuals with stroke, torque-angle relationships are only partially investigated and so far these relationships have not been analysed using testing protocols that include eccentric, isometric, and concentric modes of contraction.   This thesis investigates the torque-angle relationship of elbow flexors in subjects with stroke during all three modes of contractions – isometric, concentric, and eccentric ­– and the relative loading throughout the range of movement during a resistance exercise. In addition, this thesis studies possible central nervous system mechanisms involved in the control of muscle activation during eccentric and concentric contractions.   The torque-angle relationship during maximum voluntary elbow flexion was examined in stroke subjects (n=11), age-matched healthy subjects (n=11), and young subjects (n=11) during different contraction modes and velocities. In stroke subjects, maximum torque as well as the torque angle relationship was better preserved during eccentric contractions compared to concentric contractions. Furthermore, the relative loading during a resistance exercise at an intensity of 10RM (repetition maximum) was examined. Relative loading throughout the concentric phase of the resistance exercise, expressed as percentage of concentric torque, was found to be similar in all groups. However, relative loading during the eccentric contraction phase, expressed as the percentage of eccentric isokinetic torque, was significantly lower for the stroke group. In addition, when related to isometric maximum voluntary contraction, the loading for the stroke group was significantly lower than for the control groups during both the concentric and eccentric contraction phases. Functional magnetic resonance imaging was used to examine differences between recruited brain regions during the concentric and the eccentric phase of imagined maximum resistance exercise of the elbow flexors (motor imagery) in young healthy subjects (n=18) and in a selected sample of individuals with stroke (n=4). The motor and premotor cortex was less activated during imagined maximum eccentric contractions compared to imagined maximum concentric contraction of elbow flexors. Moreover, BA44 in the ventrolateral prefrontal cortex, a brain area that has been shown to be involved in inhibitory control of motor activity, was additionally recruited during eccentric compared to concentric conditions. This pattern was evident only on the contralesional (the intact hemisphere) in some of the stroke subjects. On the ipsilesional hemisphere, the recruitment in ventrolateral prefrontal cortex was similar for both modes of contractions.    Compared to healthy subjects, the stroke subjects exhibited altered muscular function comprising a specific reduction of torque producing capacity and deviant torque-angle relationship during concentric contractions. Therefore, the relative training load during the resistance exercise at a training intensity of 10RM was lower for subjects with stroke. Furthermore, neuroimaging data indicates that the ventrolateral prefrontal cortex may be involved in a mechanism that modulates cortical motor drive differently depending on mode of the contractions. This might partly be responsible for why it is impossible to fully activate a muscle during eccentric contractions. Moreover, among individuals with stroke, a disturbance of this system could also lie behind the lack of contraction mode-specific modulation of muscle activation that has been found in this population. The altered neuromuscular function evident after a stroke means that stroke victims may find it difficult to supply a sufficient level of stress during traditional resistance exercises to promote adaptation by the neuromuscular system. This insufficiency may partially explain why the increase in strength, in response to conventional resistance training, often has been found to be low among subjects with stroke. / Muskelsvaghet är en av orsakerna till funktionshinder efter stroke. I rehabiliteringsprogram för personer som drabbats av stroke förekommer det numera att styrketräning används i syfte att öka muskelstyrkan. Effekten av styrketräning har dock ofta visat sig vara begränsad. En viktig styrketräningsprincip är att muskulaturen belastas tillräckligt nära maximal styrka under både koncentriska kontraktioner (när man lyfter en vikt) och excentriska kontraktioner (när man kontrollerat sänker en vikt). Ett potentiellt problem skulle kunna vara att personer med stroke inte belastas optimalt under träning på grund av förändrad muskelfunktion. Efter stroke är muskelfunktionen ofta förändrad såtillvida att styrkenedsättningen är mer uttalad under koncentriska kontraktioner. Därutöver har man funnit att styrkenedsättningen är mest uttalad när muskeln är i sitt mest förkortade läge. Detta fenomen har dock inte studerats för alla tre kontraktionstyper, det vill säga excentriska, koncentriska och isometriska kontraktioner, hos personer med stroke.   Denna avhandling undersöker sambandet mellan styrka och ledvinkel över armbågsleden hos personer med stroke under alla tre kontraktionstyper – excentrisk, koncentrisk och isometrisk, samt relativ belastning genom rörelsebanan under en styrketräningsövning. Därutöver undersöker denna avhandling också hjärnans aktiveringsmönster under excentriska och koncentriska kontraktioner.   Sambandet mellan styrka och ledvinkel undersöktes hos personer med stroke (n = 11), åldersmatchade (n = 11) och unga försökspersoner (n = 11). Jämfört med kontrollgrupperna var maximal styrka för personer med stroke mest nedsatt, samt även den oproportionerligt stora styrkenedsättningen vid kort muskelängd som mest uttalad, under koncentriska kontraktioner. Denna avvikelse var minst uttalad vid excentriska kontraktioner. Vidare studerades hur hög belastningen på muskulaturen var i jämförelse med muskelns maximala styrka under en styrketräningsliknande övning för armbågsflexorer vid en träningsintensitet på 10RM. Den uppmätta belastningen under den koncentriska fasen av styrketräningsövningen, uttryckt som procent av den genomsnittliga koncentriska styrkan, var densamma för alla grupperna. Under den excentriska fasen av övningen var dock belastningen, uttryckt som procent av den maximala excentriska styrkan, signifikant lägre för personer med stroke. Träningsbelastningen utgjorde också en lägre andel av den maximala isometriska styrkan för personer med stroke, både under den koncentriska och under den excentriska fasen.   Funktionell magnetresonanstomografi (fMRI) användes för att undersöka hjärnans aktiveringsmönster hos unga försökspersoner (n = 18) och hos individer med stroke (n = 4) när de föreställde sig att de utförde maximal styrketräning för armbågsflexorer (motor imagery). Resultatet visade att primära motorbarken och premotoriska barken var mindre aktiverade när unga friska försökspersonerna föreställde sig utföra maximala excentriska, jämfört med maximala koncentriska kontraktioner. Dessutom var en region i ventrolaterala prefrontala barken, som i tidigare studier visat sig vara inblandat i reglering och hämning av muskelaktivering, mer aktiverade under föreställda excentriska kontraktioner. Detta aktiveringsmönster i den prefrontala barken återfanns dock endast i den icke skadade hjärnhalvan hos personer med stroke.   Jämfört med kontrollgrupperna uppvisade försökspersonerna med stroke en förändrad muskelfunktion som bestod av en specifik nedsättning av styrkan under koncentriska kontraktioner samt också ett mer avvikande samband mellan styrka och ledvinkel under koncentriska kontraktioner. Den relativa belastningen under utförandet av en styrketräningsövning med en intensitet på 10RM var på grund av dessa avvikelser lägre för försökspersoner med stroke. Hjärnavbildnings-studierna indikerade att ventrolaterala prefrontala barken verkar vara involverat i ett kortikalt moduleringssystem som reglerar muskel-aktivering olika beroende på kontraktionstyp under maximala kontraktioner. Detta skulle kunna vara en underliggande mekanism bakom den hittills obesvarade frågan varför det är omöjligt att aktivera muskulaturen maximalt under excentriska kontraktioner. En störning av detta moduleringssystem hos personer med stroke verkar också kunna ligga bakom den förändrade regleringen av muskelaktivering som visat sig förekomma hos personer med stroke. Neuromuskulär funktion efter stroke är förändrad i flera avseenden vilket verkar medföra att muskulaturen inte belastas optimalt under konventionell styrketräning. Detta kan vara en delförklaring till varför styrkeökningen som svar på träning ofta är liten hos personer med stroke.

Empirical evidence suggests that complex cognitive processes such as decision-making can be influenced by incidental affect (i.e. emotional states unrelated to the decision), which may have importance implications for furthering our understanding and treatment of mood disorders. Following up on previous behavioral findings suggesting that sad mood leads to biases in social decision-making, the present research first investigated how such biases are implemented in the brain. Nineteen adult participants made decisions that involved accepting or rejecting monetary offers from others in an Ultimatum Game (a well known economic task), while undergoing functional magnetic resonance imaging (fMRI). Prior to each set of decisions, participants watched a short video clip aimed at inducing either sadness or a neutral emotional state. Results indicated that sad participants rejected more "unfair" offers than those in the neutral condition, thereby replicating our previous findings. Neuroimaging analyses revealed that receiving unfair offers while in a sad mood elicited activity in brain areas related to aversive emotional states and somatosensory integration (anterior insula) and to cognitive conflict (anterior cingulate cortex). Sad participants also showed a diminished sensitivity in neural regions associated with reward processing (ventral striatum). Importantly, insular activation uniquely mediated the relationship between sadness and decision bias, demonstrating how subtle mood states can be integrated at the neural level to bias decision-making.In a second study, we assessed to what extent such affect infusion in decision-making may translate to clinical depression, a mood disorder involving chronic sad affect. Fifteen depressed and twenty-three nondepressed individuals made decisions to accept or reject monetary offers from other players in the Ultimatum Game. Like transiently sad, but healthy, individuals, depressed participants reported a more negative emotional reaction to unfair offers. However, unlike sad healthy individuals, they accepted significantly more of these offers than did controls. A positive relationship was observed in the depressed group, but not in controls, between acceptance rates of unfair offers and resting cardiac vagal tone, a physiological index of emotion regulation capacity. These findings suggest distinct biasing processes in depression, which may be related to higher reliance on regulating negative emotion.

Recent functional neuroimaging evidence suggests that recalling autobiographical memories, imagining fictitious autobiographical episodes, and taking the perspective of another person activate a similar network of brain regions. Results from the two studies presented here provide further evidence of this common neural network. Previous evidence also suggests that recalling autobiographical memories from a first person or from a third person perspective can influence the way in which those memories are experienced as well as the brain regions that are engaged; however, the effect of perspective on imagining autobiographical events remains unclear. Results from Study 1 indicated that brain regions implicated in both remembering and imagining were differentially engaged during these tasks depending on whether a first person or a third person perspective was taken. In addition, while recalling autobiographical memories from a third person perspective can result in the feeling that a past self is more like another person, imagining oneself in the position of another person can result in the feeling that that person is more similar to oneself; this suggests a possible link between perspective in memory and social perspective taking. In Study 2, we identified several brain regions exhibiting a pattern of increasing or decreasing activation as a function of whether socially interactive events were recalled from a first person perspective, by imagining oneself as one's partner, or from a third person perspective (i.e., as a function of distance from one's own perspective). Together, our findings suggest that perspective plays an important role in the way in which brain regions that are part of this common neural network are engaged during memory, imagination, and socially interactive tasks.

Pain is a remarkably complex and a multifaceted process, involving the interaction between physiological and psychological factors in unique ways. Among many other factors, the size of the affected surface area contributes to the pain experience, altering one’s pain perception. Spatial summation is the term used to describe this phenomenon, and is characterized by an increase in pain perception, or a decrease in pain threshold, when the affected surface area is increased. This project investigated the neuronal processes underlying spatial summation of heat sensations in healthy female volunteers, by means of functional magnetic resonance imaging (fMRI) of the central nervous system. The first study of this project involved increasing the surface area of skin stimulated by manipulating the number of thermal probes delivering thermal stimulation, which was delivered just below participants’ measured pain threshold. Surface area was increased on one hand and across two hands to determine the extent of spatial summation, and furthermore, to determine the effect on neural activity in the spinal cord and brainstem. The second study of this project involved increasing the surface area of skin stimulated by a noxious heat stimulus and its effect on pain perception and corresponding neural activity in the spinal cord, brainstem, and brain. Results from this project suggest that the central mechanisms contributing to the spatial summation of heat sensations involve many of many of the brainstem and brain regions involved in processing the emotional, motivational, and cognitive aspects of pain. Therefore, increasing the surface area of stimulation may alter pain perception by influencing the affective dimension of the sensation, rather than the sensory/discriminatory component. The combination of such structures may interact in a unique way to protect the body from potential, or further damage, by increasing the perception of pain through emotional, motivational and cognitive mechanisms. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2013-07-15 19:01:37.694

We examined the neural and cognitive processes engaged during auditory verbal recognition performance under full attention (FA) and divided attention (DA) conditions in younger and older adults. Recognition was disrupted by a word (DA-word), but not digit-based (DA-digit) distracting task, performed concurrently with retrieval. In Study 1, a multivariate functional magnetic resonance imaging analysis technique, Partial Least Squares (PLS) was used to identify distributed patterns of brain activity most related to the different conditions and behaviours. We found that similar retrieval networks were recruited during the FA and DA-digit, but not DA-word, condition in both age groups, mirroring behavioural performance. There was, however, an age-related change in the brain regions that predicted successful memory performance. In addition, we found that a neural network relating to hippocampal activity predicted memory success during the FA and DA-digit, but not DA-word, condition in younger, but not older, adults. In study 2, we used a Remember-Know paradigm to examine how manipulations of DA affect recollective and familiarity-based retrieval processes. Younger and older adults showed an increase in false Remember responses during both DA conditions and decreased accuracy in Know responses only during the word-based DA condition. In addition, aging was associated with decreased accuracy in Remember, but not Know, responses, in both DA conditions. In a follow-up experiment, we showed that these results cannot be accounted for by differences in difficulty level of the chosen distracting tasks. Results suggest that recollective processes rely on attentional resources during retrieval. Together these studies show that declines in available attentional resources, common with advancing age, affect both the neural networks used during retrieval, and the qualitative nature of the memories that are retrieved. Results also suggest that familiarity processes rely on the reactivation of content-specific representations, mediated by a neural network relating to hippocampal activity in younger, but not older, adults.