Functional neuroimaging of autobiographical memory.

Functional neuroimaging studies of autobiographical memory have grown dramatically in recent years. These studies are important because they can investigate the neural correlates of processes that are difficult to study using laboratory stimuli, including: (i) complex constructive processes, (ii) recollective qualities of emotion and vividness, and (iii) remote memory retrieval. Constructing autobiographical memories involves search, monitoring and self-referential processes that are associated with activity in separable prefrontal regions. The contributions of emotion and vividness have been linked to the amygdala and visual cortex respectively. Finally, there is evidence that recent and remote autobiographical memories might activate the hippocampus equally, which has implications for memory-consolidation theories. The rapid development of innovative methods for eliciting personal memories in the scanner provides the opportunity to delve into the functional neuroanatomy of our personal past.

Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.

Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.

Shifting Loyalties: World War I and the Conflicted Politics of Patriotism in the British Caribbean

This dissertation examines how the crisis of World War I impacted imperial policy and popular claims-making in the British Caribbean. Between 1915 and 1918, tens of thousands of men from the British Caribbean volunteered to fight in World War I and nearly 16,000 men, hailing from every British colony in the region, served in the newly formed British West Indies Regiment (BWIR). Rousing appeals to imperial patriotism and manly duty during the wartime recruitment campaigns and postwar commemoration movement linked the British Empire, civilization, and Christianity while simultaneously promoting new roles for women vis-à-vis the colonial state. In Jamaica and Trinidad and Tobago, the two colonies that contributed over seventy-five percent of the British Caribbean troops, discussions about the meaning of the war for black, coloured, white, East Indian, and Chinese residents sparked heated debates about the relationship among race, gender, and imperial loyalty.

To explore these debates, this dissertation foregrounds the social, cultural, and political practices of BWIR soldiers, tracing their engagements with colonial authorities, military officials, and West Indian civilians throughout the war years. It begins by reassessing the origins of the BWIR, and then analyzes the regional campaign to recruit West Indian men for military service. Travelling with newly enlisted volunteers across the Atlantic, this study then chronicles soldiers' multi-sited campaign for equal status, pay, and standing in the British imperial armed forces. It closes by offering new perspectives on the dramatic postwar protests by BWIR soldiers in Italy in 1918 and British Honduras and Trinidad in 1919, and reflects on the trajectory of veterans' activism in the postwar era.

This study argues that the racism and discrimination soldiers experienced overseas fueled heightened claims-making in the postwar era. In the aftermath of the war, veterans mobilized collectively to garner financial support and social recognition from colonial officials. Rather than withdrawing their allegiance from the empire, ex-servicemen and civilians invoked notions of mutual obligation to argue that British officials owed a debt to West Indians for their wartime sacrifices. This study reveals the continued salience of imperial patriotism, even as veterans and their civilian allies invoked nested local, regional, and diasporic loyalties as well. In doing so, it contributes to the literature on the origins of patriotism in the colonial Caribbean, while providing a historical case study for contemporary debates about "hegemonic dissolution" and popular mobilization in the region.

This dissertation draws upon a wide range of written and visual sources, including archival materials, war recruitment posters, newspapers, oral histories, photographs, and memoirs. In addition to Colonial Office records and military files, it incorporates previously untapped letters and petitions from the Jamaica Archives, National Archives of Trinidad and Tobago, Barbados Department of Archives, and US National Archives.

Chimpanzees and bonobos exhibit divergent spatial memory development.

Spatial cognition and memory are critical cognitive skills underlying foraging behaviors for all primates. While the emergence of these skills has been the focus of much research on human children, little is known about ontogenetic patterns shaping spatial cognition in other species. Comparative developmental studies of nonhuman apes can illuminate which aspects of human spatial development are shared with other primates, versus which aspects are unique to our lineage. Here we present three studies examining spatial memory development in our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (P. paniscus). We first compared memory in a naturalistic foraging task where apes had to recall the location of resources hidden in a large outdoor enclosure with a variety of landmarks (Studies 1 and 2). We then compared older apes using a matched memory choice paradigm (Study 3). We found that chimpanzees exhibited more accurate spatial memory than bonobos across contexts, supporting predictions from these species' different feeding ecologies. Furthermore, chimpanzees - but not bonobos - showed developmental improvements in spatial memory, indicating that bonobos exhibit cognitive paedomorphism (delays in developmental timing) in their spatial abilities relative to chimpanzees. Together, these results indicate that the development of spatial memory may differ even between closely related species. Moreover, changes in the spatial domain can emerge during nonhuman ape ontogeny, much like some changes seen in human children.

Effects of task instruction on autobiographical memory specificity in young and older adults

Older adults tend to retrieve autobiographical information that is overly general (i.e., not restricted to a single event, termed the overgenerality effect) relative to young adults' specific memories. A vast majority of studies that have reported overgenerality effects explicitly instruct participants to retrieve specific memories, thereby requiring participants to maintain task goals, inhibit inappropriate responses, and control their memory search. Since these processes are impaired in healthy ageing, it is important to determine whether such task instructions influence the magnitude of the overgenerality effect in older adults. In the current study participants retrieved autobiographical memories during presentation of musical clips. Task instructions were manipulated to separate age-related differences in the specificity of underlying memory representations from age-related differences in following task instructions. Whereas young adults modulated memory specificity based on task demands, older adults did not. These findings suggest that reported rates of overgenerality in older adults' memories might include age-related differences in memory representation, as well as differences in task compliance. Such findings provide a better understanding of the underlying cognitive mechanisms involved in age-related changes in autobiographical memory and may also be valuable for future research examining effects of overgeneral memory on general well-being. © 2013 Taylor & Francis.

Neural networks supporting autobiographical memory retrieval in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) affects the functional recruitment and connectivity between neural regions during autobiographical memory (AM) retrieval that overlap with default and control networks. Whether such univariate changes relate to potential differences in the contributions of the large-scale neural networks supporting cognition in PTSD is unknown. In the present functional MRI study, we employed independent-component analysis to examine the influence of the engagement of neural networks during the recall of personal memories in a PTSD group (15 participants) as compared to non-trauma-exposed healthy controls (14 participants). We found that the PTSD group recruited similar neural networks when compared to the controls during AM recall, including default-network subsystems and control networks, but group differences emerged in the spatial and temporal characteristics of these networks. First, we found spatial differences in the contributions of the anterior and posterior midline across the networks, and of the amygdala in particular, for the medial temporal subsystem of the default network. Second, we found temporal differences within the medial prefrontal subsystem of the default network, with less temporal coupling of this network during AM retrieval in PTSD relative to controls. These findings suggest that the spatial and temporal characteristics of the default and control networks potentially differ in a PTSD group versus healthy controls and contribute to altered recall of personal memory.

Effects of task instruction on autobiographical memory specificity in young and older adults.

Older adults tend to retrieve autobiographical information that is overly general (i.e., not restricted to a single event, termed the overgenerality effect) relative to young adults' specific memories. A vast majority of studies that have reported overgenerality effects explicitly instruct participants to retrieve specific memories, thereby requiring participants to maintain task goals, inhibit inappropriate responses, and control their memory search. Since these processes are impaired in healthy ageing, it is important to determine whether such task instructions influence the magnitude of the overgenerality effect in older adults. In the current study participants retrieved autobiographical memories during presentation of musical clips. Task instructions were manipulated to separate age-related differences in the specificity of underlying memory representations from age-related differences in following task instructions. Whereas young adults modulated memory specificity based on task demands, older adults did not. These findings suggest that reported rates of overgenerality in older adults' memories might include age-related differences in memory representation, as well as differences in task compliance. Such findings provide a better understanding of the underlying cognitive mechanisms involved in age-related changes in autobiographical memory and may also be valuable for future research examining effects of overgeneral memory on general well-being.

Age-related effects on the neural correlates of autobiographical memory retrieval.

Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and prefrontal cortex (PFC) underlie age-related reductions in episodic richness of the personal past.

Peace and war: trajectories of posttraumatic stress disorder symptoms before, during, and after military deployment in Afghanistan.

In the study reported here, we examined posttraumatic stress disorder (PTSD) symptoms in 746 Danish soldiers measured on five occasions before, during, and after deployment to Afghanistan. Using latent class growth analysis, we identified six trajectories of change in PTSD symptoms. Two resilient trajectories had low levels across all five times, and a new-onset trajectory started low and showed a marked increase of PTSD symptoms. Three temporary-benefit trajectories, not previously described in the literature, showed decreases in PTSD symptoms during (or immediately after) deployment, followed by increases after return from deployment. Predeployment emotional problems and predeployment traumas, especially childhood adversities, were predictors for inclusion in the nonresilient trajectories, whereas deployment-related stress was not. These findings challenge standard views of PTSD in two ways. First, they show that factors other than immediately preceding stressors are critical for PTSD development, with childhood adversities being central. Second, they demonstrate that the development of PTSD symptoms shows heterogeneity, which indicates the need for multiple measurements to understand PTSD and identify people in need of treatment.

Autobiographical memory for stressful events: the role of autobiographical memory in posttraumatic stress disorder.

To provide the three-way comparisons needed to test existing theories, we compared (1) most-stressful memories to other memories and (2) involuntary to voluntary memories (3) in 75 community dwelling adults with and 42 without a current diagnosis of posttraumatic stress disorder (PTSD). Each rated their three most-stressful, three most-positive, seven most-important and 15 word-cued autobiographical memories, and completed tests of personality and mood. Involuntary memories were then recorded and rated as they occurred for 2 weeks. Standard mechanisms of cognition and affect applied to extreme events accounted for the properties of stressful memories. Involuntary memories had greater emotional intensity than voluntary memories, but were not more frequently related to traumatic events. The emotional intensity, rehearsal, and centrality to the life story of both voluntary and involuntary memories, rather than incoherence of voluntary traumatic memories and enhanced availability of involuntary traumatic memories, were the properties of autobiographical memories associated with PTSD.

Dynamic neural networks supporting memory retrieval.

How do separate neural networks interact to support complex cognitive processes such as remembrance of the personal past? Autobiographical memory (AM) retrieval recruits a consistent pattern of activation that potentially comprises multiple neural networks. However, it is unclear how such large-scale neural networks interact and are modulated by properties of the memory retrieval process. In the present functional MRI (fMRI) study, we combined independent component analysis (ICA) and dynamic causal modeling (DCM) to understand the neural networks supporting AM retrieval. ICA revealed four task-related components consistent with the previous literature: 1) medial prefrontal cortex (PFC) network, associated with self-referential processes, 2) medial temporal lobe (MTL) network, associated with memory, 3) frontoparietal network, associated with strategic search, and 4) cingulooperculum network, associated with goal maintenance. DCM analysis revealed that the medial PFC network drove activation within the system, consistent with the importance of this network to AM retrieval. Additionally, memory accessibility and recollection uniquely altered connectivity between these neural networks. Recollection modulated the influence of the medial PFC on the MTL network during elaboration, suggesting that greater connectivity among subsystems of the default network supports greater re-experience. In contrast, memory accessibility modulated the influence of frontoparietal and MTL networks on the medial PFC network, suggesting that ease of retrieval involves greater fluency among the multiple networks contributing to AM. These results show the integration between neural networks supporting AM retrieval and the modulation of network connectivity by behavior.

The temporal distribution of autobiographical memory: changes in reliving and vividness over the life span do not explain the reminiscence bump.

When autobiographical memories are elicited with word cues, personal events from middle childhood to early adulthood are overrepresented compared to events from other periods. It is, however, unclear whether these memories are also associated with greater recollection. In this online study, we examined whether autobiographical memories from adolescence and early adulthood are recollected more than memories from other lifetime periods. Participants rated personal events that were elicited with cue words on reliving or vividness. Consistent with previous studies, most memories came from the period in which the participants were between 6 and 20 years old. The memories from this period were not relived more or recalled more vividly than memories from other lifetime periods, suggesting that they do not involve more recollection. Recent events had higher levels of reliving and vividness than remote events, and older adults reported a stronger recollective experience than younger adults.

Event memory: A theory of memory for laboratory, autobiographical, and fictional events.

An event memory is a mental construction of a scene recalled as a single occurrence. It therefore requires the hippocampus and ventral visual stream needed for all scene construction. The construction need not come with a sense of reliving or be made by a participant in the event, and it can be a summary of occurrences from more than one encoding. The mental construction, or physical rendering, of any scene must be done from a specific location and time; this introduces a "self" located in space and time, which is a necessary, but need not be a sufficient, condition for a sense of reliving. We base our theory on scene construction rather than reliving because this allows the integration of many literatures and because there is more accumulated knowledge about scene construction's phenomenology, behavior, and neural basis. Event memory differs from episodic memory in that it does not conflate the independent dimensions of whether or not a memory is relived, is about the self, is recalled voluntarily, or is based on a single encoding with whether it is recalled as a single occurrence of a scene. Thus, we argue that event memory provides a clearer contrast to semantic memory, which also can be about the self, be recalled voluntarily, and be from a unique encoding; allows for a more comprehensive dimensional account of the structure of explicit memory; and better accounts for laboratory and real-world behavioral and neural results, including those from neuropsychology and neuroimaging, than does episodic memory.