Alcohol use disorder is common, and treatments are currently inadequate. Some of the acute effects of alcohol on the brain, such as altering the decision-making and future thinking capacities, mirror the effects of chronic alcohol use. Therefore, interventions that can address these shortcomings may be useful for reducing the negative effects of alcohol use disorder in combination with other therapies. The signature of those interventions may also be evident in the signature of large-scale, dynamic brain networks, which can show whether an intervention is effective. One such intervention is episodic future thinking, which has been shown to reduce delay discounting and orient people toward pro-social, long-term outcomes. To better understand decision making in high-risk individuals, we examined delay discounting in an adolescent population. When the decision-making faculties were challenged with difficult choices, adolescents made decisions inconsistent with their predicted preference, complemented by increased brain activity in the central executive network and salience network. Using these results and the hypothesis that the default mode network would be implicated in future thinking and intertemporal choice, we examined the neural effects of a brief behavioral intervention, episodic future thinking, that seeks to address these impairments. We showed that episodic future thinking has both acute and longer-lasting effects on consequential brain networks at rest and during delay discounting compared to a control episodic thinking condition in alcohol use disorder. Our failure to show group differences in default mode network prompted us to scrutinize it more carefully, from a position where we could measure the ability to self-regulate the network rather than its resting-state tendency. We implemented a real-time fMRI experiment to test the degree to which people along the alcohol use severity spectrum can self-regulate this network. Our results showed that default mode network suppression is impaired as alcohol use disorder severity increases. In the process, we showed that direct examination of resting-state networks with these methods will provide more information than measuring them at rest alone. We also characterized the default mode network along the real-time fMRI pipeline to show the whole-brain spatial pattern of regions associated and unassociated with the network. Our results indicate that resting-state brain networks are important markers for outcomes in alcohol use disorder and that they can be manipulated under experimental conditions, potentially to the benefit of the afflicted individual. / Doctor of Philosophy / Alcohol is the most widely-used mind-altering substance in the United States. Even though most people do not develop a problem with alcohol use, many people will at some point develop drinking patterns that classify as an alcohol use disorder. Brain damage from drinking can come from the toxicity of alcohol, but also as a result of behaviors associated with drinking too much, including injury, violence, accidents, and other health-related issues. Interventions at the behavioral level can be effective at curbing drinking patterns before damage accrues, and a better understanding of those interventions at the level of the brain may make them more effective. This work investigated the decision-making processes and the ability to think clearly about the future, two faculties that begin to become diminished in alcohol use disorder. In our first set of studies, we tested a brief behavioral intervention called episodic future thinking, which helps people orient themselves away from short-term rewards like alcohol and toward long-term goals that could happen if they stopped drinking as much. We showed that one hour-long, intensive session produced changes in the connectivity between the prefrontal cortex and the lower brain. We also generated data in a long-term experiment suggesting repeated reminders of the episodic future thinking intervention produce changes in large-scale brain networks that are disrupted in substance use disorders. In a separate set of experiments, we showed that people can gain control over one of these networks, called the default mode network, to the point of being able to control a brain-machine interface just by following simple instructions. However, we demonstrated that the degree to which someone can control this brain activity was associated with their drinking severity. In other words, the more people drank, in terms of volume and frequency, the less control they had over their own brain activity. This finding is important because many researchers have shown that activity in this brain region is related to many psychopathologies, including substance use disorders. Other researchers have been developing ways in which the ability to control this brain activity can be trained. While we did not find evidence of a training effect in a small group of healthy people (5), it may be the case that people impaired by alcohol use disorder can improve through practice or through cutting back on drinking. Ultimately, we hope that the research presented here will help to guide the development of treatments for alcohol use disorder to be more effective.

Yes / It has been suggested that the isolation rearing paradigm models certain aspects of schizophrenia symptomatology. This study aimed to investigate whether isolation rearing impairs rats’ performance in two models of cognition: the novel object recognition (NOR) and attentional set-shifting tasks, tests of episodic memory and executive function, respectively. Two cohorts of female Hooded-Lister rats were used in these experiments. Animals were housed in social isolation or in groups of five from weaning, post-natal day 28. The first cohort was tested in the NOR test with inter-trial intervals (ITIs) of 1 min up to 6 h. The second cohort was trained and tested in the attentional set-shifting task. In the NOR test, isolates were only able to discriminate between the novel and familiar objects up to 1-h ITI, whereas socially reared animals remembered the familiar object up to a 4-h ITI. In the attentional set-shifting task, isolates were significantly and selectively impaired in the extra-dimensional shift phase of the task (P < 0.01). Rats reared in isolation show impaired episodic memory in the NOR task and reduced ability to shift attention between stimulus dimensions in the attentional set-shifting task. Because schizophrenic patients show similar deficits in performance in these cognitive domains, these data further support isolation rearing as a putative preclinical model of the cognitive deficits associated with schizophrenia.

Comparative research on event memory has typically focused on the binding of spatial and temporal information in memory, but much less is known about how animals remember information about the source of their memories (i.e., whether the event is something they performed themselves or whether they observed it). The purpose of the present study was to examine how rhesus monkeys (n = 8) and 3- to 4- year-old children (n = 20) remember this information along with other relevant event features (object identity, spatial location, temporal properties and contextual features) in working memory. In Experiment 1, rhesus monkeys completed five different delayed matching-to-sample tasks to assess independent encoding of these five event components. In Experiment 2, the monkeys either performed or observed an event and then had to respond to a randomly selected pair of memory tests used in the previous experiment. In Experiment 3, children were presented with the same memory task, but were given a brief demonstration to learn how to perform the task. Both children and monkeys responded to these tests using photos and shapes (for the identity and spatial tests) and icons (for the temporal, agency and context tests). The monkeys demonstrated significantly above-chance performance on the identity, spatial, temporal and agency tasks. The children were above chance on the one component the monkeys had difficulty with (context), but conversely demonstrated difficulty on the temporal memory test. There was evidence of feature integration in both monkeys and children. Specifically, the children were significantly more likely to respond correctly to the second memory test if they had also been correct on the first memory test. Two of five rhesus monkeys also showed this effect, indicating that for these individuals, the features were integrated in working memory. Implications of this research are discussed in relation to self-awareness and episodic memory research in children and nonhuman species.

Comparative research on event memory has typically focused on the binding of spatial and temporal information in memory, but much less is known about how animals remember information about the source of their memories (i.e., whether the event is something they performed themselves or whether they observed it). The purpose of the present study was to examine how rhesus monkeys (n = 8) and 3- to 4- year-old children (n = 20) remember this information along with other relevant event features (object identity, spatial location, temporal properties and contextual features) in working memory. In Experiment 1, rhesus monkeys completed five different delayed matching-to-sample tasks to assess independent encoding of these five event components. In Experiment 2, the monkeys either performed or observed an event and then had to respond to a randomly selected pair of memory tests used in the previous experiment. In Experiment 3, children were presented with the same memory task, but were given a brief demonstration to learn how to perform the task. Both children and monkeys responded to these tests using photos and shapes (for the identity and spatial tests) and icons (for the temporal, agency and context tests). The monkeys demonstrated significantly above-chance performance on the identity, spatial, temporal and agency tasks. The children were above chance on the one component the monkeys had difficulty with (context), but conversely demonstrated difficulty on the temporal memory test. There was evidence of feature integration in both monkeys and children. Specifically, the children were significantly more likely to respond correctly to the second memory test if they had also been correct on the first memory test. Two of five rhesus monkeys also showed this effect, indicating that for these individuals, the features were integrated in working memory. Implications of this research are discussed in relation to self-awareness and episodic memory research in children and nonhuman species.

The Diploma thesis is concerned with the human episodic-like memory and its changes during the course of healthy ageing. Episodic memory represents a memory of specific events and their spatiotemporal relations, involving conscious retrieval and mental time travel. As a testable analogy in animals, a concept of episodic-like memory has been suggested and defined as a memory of spatiotemporal location of a certain event in the past ("what-where-when"). Firstly, we focused on a methodological comparison of standard psychological tests of episodic memory and a novel non-verbal computer-based Episodic-Like Memory Test (EMT) with several variants of varying difficulty, capable of discerning the memory for pictures, their sequence and position (Vlček et al., 2009). The second goal of our study was to demonstrate the applicability of the concept of episodic-like memory ("what- where-when") as a model in the testing of human episodic memory. Compared with other tests of episodic memory, EMT test does not depend on the verbalization of content. Contrasting the results obtained from EMT and other standard tests was, therefore, of interest. The results from the EMT test were compared across three age cohorts (N = 58; young, middle-aged, aged) of healthy volunteers. In the spatial domain of episodic-like...

Episodic memory enables us to remember and recall life events from the past. Episodic memory is a specific type of long-term declarative memory, which undergoes changes in ontogeny. To examinate of episodic memory, "episodic-like memory model", was developed. This model focuses on three basic components of episodic memory: "What happened", "Where did it happen" and "When did it happen". The aim of this diploma thesis is to develop and to validate of particular tests of episodic memory with consideration for their feasibility for preschool children. In order to study episodic memory we used an "episodic-like memory model" and experiments which focused on: children's verbal ability, differentiation of two perspectives during remembering of events and timing memories on an autobiographical axis. We aimed to inspect the effect of age on performance in these tests, possible links between performance in these experiments and the effect of level and the three components of episodic memory on number of errors made. In our dataset we found a significant effect of the age of children in Sentence repetition test and in test of Object collection in the virtual house, in the same test we found a effect of the level on number of errors. We also found a significant correlation between correct responses in verbal...

Adults can mentally relive experiences from their past and anticipate possible future events, a process called mental time travel (MTT). Recently, several theorists have argued that the ability to mentally travel through time may not emerge until 3- to 5-years of age. This proposal is based on evidence from a wide range of research, including investigations into children’s recall, planning and differentiation of the times of events in the past and the future. However, as yet there has been no dedicated effort to find out how and when MTT develops. The current series of studies brought together a wide range of resources with the aim of designing a series of novel paradigms to measure aspects of MTT development between 3- and 5-years of age. The first of these novel approaches asked children to report events that occurred to them “yesterday” and would occur to them “tomorrow”, revealing that by 4- to 5-years of age most children could accurately do so. Another series of studies examined children’s ability to anticipate a different, future situation, finding that only by 4- to 5-years did children’s behaviour reflect differences in an anticipated future environment. Subsequent studies focusing on children’s discrimination of past and future also suggested that by 4- to 5-years children could distinguish the different causal impact of past and future events on the present. Another task revealed that during the preschool years children become better at differentiating the times of events from throughout their own lifespan. These new data provide support for the claim that the ability to mentally travel into one’s own past and future emerges during the preschool years. This thesis describes the first directed investigation into the development of MTT as a whole, bringing together much of the empirical and theoretical literature for the first time. The tasks designed are new approaches to investigating MTT and represent a starting point for future research. This thesis also introduces and discusses theories for the development of MTT, aiming to stimulate discussion not just of when it emerges, but how, and what processes may underlie the transition.

Adults can mentally relive experiences from their past and anticipate possible future events, a process called mental time travel (MTT). Recently, several theorists have argued that the ability to mentally travel through time may not emerge until 3- to 5-years of age. This proposal is based on evidence from a wide range of research, including investigations into children’s recall, planning and differentiation of the times of events in the past and the future. However, as yet there has been no dedicated effort to find out how and when MTT develops. The current series of studies brought together a wide range of resources with the aim of designing a series of novel paradigms to measure aspects of MTT development between 3- and 5-years of age. The first of these novel approaches asked children to report events that occurred to them “yesterday” and would occur to them “tomorrow”, revealing that by 4- to 5-years of age most children could accurately do so. Another series of studies examined children’s ability to anticipate a different, future situation, finding that only by 4- to 5-years did children’s behaviour reflect differences in an anticipated future environment. Subsequent studies focusing on children’s discrimination of past and future also suggested that by 4- to 5-years children could distinguish the different causal impact of past and future events on the present. Another task revealed that during the preschool years children become better at differentiating the times of events from throughout their own lifespan. These new data provide support for the claim that the ability to mentally travel into one’s own past and future emerges during the preschool years. This thesis describes the first directed investigation into the development of MTT as a whole, bringing together much of the empirical and theoretical literature for the first time. The tasks designed are new approaches to investigating MTT and represent a starting point for future research. This thesis also introduces and discusses theories for the development of MTT, aiming to stimulate discussion not just of when it emerges, but how, and what processes may underlie the transition.

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Doctor of Philosophy / Department of Psychological Sciences / Richard Jackson Harris / In recent years, Baddeley (2010) has added a new component, the episodic buffer, to his Working Memory (WM) model. The episodic buffer binds information from long-term memory (LTM) to the central executive but has been researched very little, especially with respect to its use with a second language. In fact, Juffs and Harrington (2011) stated, “To date there has been no research on the possible role of the episodic buffer in L2 learning and use” (p. 140). One goal of this study was to do just that. Domain knowledge (DK) in baseball (Experiment 1) and English proficiency levels (Experiment 2) were used as proxies for difficulty level to study how inference processing under different conditions of domain knowledge and cognitive load in native (L1) and non-native (L2) English readers contribute to understanding the episodic buffer. In Experiment 1, 67 participants varying in domain knowledge about baseball read stories related to baseball with or without a concurrent cognitive load task of responding to tones while reading; they then answered comprehension questions of varying degrees of inferential difficulty. In Experiment 2, three groups varying in English reading proficiency, split into groups based on their lexical decision task scores (72 native, 40 intermediate, 40 beginner readers) read general stories with or without cognitive load and answered comprehension questions requiring varying degrees of inferential difficulty. Accuracy and Reaction Time (RT) were differentially affected by working memory (OSpan), cognitive load, and inferential complexity. In Experiment 1, greater DK explained variance in effectiveness (accuracy) and efficiency (RT) as inferential complexity increased. In Experiment 2 OSpan was needed even at lower levels of inferential complexity for beginning readers. Surprisingly, for both experiments, participants responded faster under cognitive load conditions, although not at the expense of accuracy. This suggests that the episodic buffer is important for different levels of DK and proficiency, especially as the task becomes more difficult. Theoretical and practical implications of these findings are discussed.