Dissociable Memory- and Response-Related Activity in Parietal Cortex During Auditory Spatial Working Memory

Attending and responding to sound location generates increased activity in parietal cortex which may index auditory spatial working memory and/or goal-directed action. Here, we used an n-back task (Experiment 1) and an adaptation paradigm (Experiment 2) to distinguish memory-related activity from that associated with goal-directed action. In Experiment 1, participants indicated, in separate blocks of trials, whether the incoming stimulus was presented at the same location as in the previous trial (1-back) or two trials ago (2-back). Prior to a block of trials, participants were told to use their left or right index finger. Accuracy and reaction times were worse for the 2-back than for the 1-back condition. The analysis of functional magnetic resonance imaging data revealed greater sustained task-related activity in the inferior parietal lobule (IPL) and superior frontal sulcus during 2-back than 1-back after accounting for response-related activity elicited by the targets. Target detection and response execution were also associated with enhanced activity in the IPL bilaterally, though the activation was anterior to that associated with sustained task-related activity. In Experiment 2, we used an event-related design in which participants listened (no response required) to trials that comprised four sounds presented either at the same location or at four different locations. We found larger IPL activation for changes in sound location than for sounds presented at the same location. The IPL activation overlapped with that observed during the auditory spatial working memory task. Together, these results provide converging evidence supporting the role of parietal cortex in auditory spatial working memory which can be dissociated from response selection and execution

Cognitive control for language switching in bilinguals: A quantitative meta-analysis of functional neuroimaging studies

In a quantitative meta-analysis, using the activation likelihood estimation method, we examined the neural regions involved in bilingual cognitive control, particularly when engaging in switching between languages. The purpose of this study was to evaluate the bilingual cognitive control model based on a qualitative analysis [Abutalebi, J., & Green, D. W. (2008). Control mechanisms in bilingual language production: Neural evidence from language switching studies. Language and Cognitive Processes, 23, 557-582.]. After reviewing 128 peer-reviewed articles, ten neuroimaging studies met our inclusion criteria and in each study, bilinguals switched between languages in response to cues. We isolated regions involved in voluntary language switching, by including reported contrasts between the switching conditions and high level baseline conditions involving similar tasks but requiring the use of only one language. Eight brain regions showed significant and reliable activation: left inferior frontal gyrus, left middle temporal gyrus, left middle frontal gyrus, right precentral gyrus, right superior temporal gyrus, midline pre-SMA and bilateral caudate nuclei. This quantitative result is consistent with bilingual aphasia studies that report switching deficits associated with lesions to the caudate nuclei or prefrontal cortex. It also extends the previously reported qualitative model. We discuss the implications of the findings for accounts of bilingual cognitive control

Lifelong Bilingualism Maintains White Matter Integrity in Older Adults

Previous research has shown that bilingual speakers have higher levels of cognitive control than comparable monolinguals, especially at older ages. The present study investigates a possible neural correlate of this behavioral effect. Given that white matter (WM) integrity decreases with age in adulthood, we tested the hypothesis that bilingualism is associated with maintenance of WM in older people. Using diffusion tensor imaging, we found higher WM integrity in older people who were lifelong bilinguals than in monolinguals. This maintained integrity was measured by fractional anisotropy (FA) and was found in the corpus callosum extending to the superior and inferior longitudinal fasciculi. We also hypothesized that stronger WM connections would be associated with more widely distributed patterns of functional connectivity in bilinguals. We tested this by assessing the resting-state functional connectivity of frontal lobe regions adjacent to WM areas with group differences in FA. Bilinguals showed stronger anterior to posterior functional connectivity compared to monolinguals. These results are the first evidence that maintained WM integrity is related to lifelong naturally occurring experience; the resulting enhanced structural and functional connectivity may provide a neural basis for “brain reserve.

Emotional evaluation and memory in behavioral variant frontotemporal dementia

Behavioral variant frontotemporal dementia (bvFTD) affects emotional evaluation, but less is known regarding the patients' ability to remember emotional stimuli. Here, bvFTD patients and age-matched controls studied positive, negative, and neutral pictures followed by a recognition memory test. Compared to controls, bvFTD patients showed a reduction in emotional evaluation of negative scenes, but not of positive or neutral scenes. Additionally, the patients showed an overall reduction in recognition memory accuracy, due to impaired recollection in the face of relatively preserved familiarity. These results show that bvFTD reduces the emotional evaluation of negative scenes and impairs overall recognition memory accuracy and recollection

Common and unique neural activations in autobiographical, episodic, and semantic retrieval

This study sought to explore the neural correlates that underlie autobiographical, episodic, and semantic memory. Autobiographical memory was defined as the conscious recollection of personally relevant events, episodic memory as the recall of stimuli presented in the laboratory, and semantic memory as the retrieval of factual information and general knowledge about the world. Our objective was to delineate common neural activations, reflecting a functional overlap, and unique neural activations, reflecting functional dissociation of these memory processes. We conducted an event-related functional magnetic resonance imaging study in which we utilized the same pictorial stimuli but manipulated retrieval demands to extract autobiographical, episodic, or semantic memories. The results show a functional overlap of the three types of memory retrieval in the inferior frontal gyrus, the middle frontal gyrus, the caudate nucleus, the thalamus, and the lingual gyrus. All memory conditions yielded activation of the left medial-temporal lobe; however, we found a functional dissociation within this region. The anterior and superior areas were active in episodic and semantic retrieval, whereas more posterior and inferior areas were active in autobiographical retrieval. Unique activations for each memory type were also delineated, including medial frontal increases for autobiographical, right middle frontal increases for episodic, and right inferior temporal increases for semantic retrieval. These findings suggest a common neural network underlying all declarative memory retrieval, as well as unique neural contributions reflecting the specific properties of retrieved memories

Brain network activity in monolingual and bilingual older adults

Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life

A Novel TLR4-Mediated Signaling Pathway Leading to IL-6 Responses in Human Bladder Epithelial Cells

The vigorous cytokine response of immune cells to Gram-negative bacteria is primarily mediated by a recognition molecule, Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide (LPS) and initiates a series of intracellular NF-κB–associated signaling events. Recently, bladder epithelial cells (BECs) were reported to express TLR4 and to evoke a vigorous cytokine response upon exposure to LPS. We examined intracellular signaling events in human BECs leading to the production of IL-6, a major urinary cytokine, following activation by Escherichia coli and isolated LPS. We observed that in addition to the classical NF-κB–associated pathway, TLR4 triggers a distinct and more rapid signaling response involving, sequentially, Ca(2+), adenylyl cyclase 3–generated cAMP, and a transcriptional factor, cAMP response element–binding protein. This capacity of BECs to mobilize secondary messengers and evoke a more rapid IL-6 response might be critical in their role as first responders to microbial challenge in the urinary tract

Brain reserve, cognitive reserve, compensation, and maintenance: operationalization, validity, and mechanisms of cognitive resilience

Significant individual differences in the trajectories of cognitive aging and in age-related changes of brain structure and function have been reported in the past half-century. In some individuals, significant pathological changes in the brain are observed in conjunction with relatively well-preserved cognitive performance. Multiple constructs have been invoked to explain this paradox of resilience, including brain reserve, cognitive reserve, brain maintenance, and compensation. The aim of this session of the Cognitive Aging Summit III was to examine the overlap and distinctions in definitions and measurement of these constructs, to discuss their neural and behavioral correlates and to propose plausible mechanisms of individual cognitive resilience in the face of typical age-related neural declines

Influence of aging on the neural correlates of autobiographical, episodic, and semantic memory retrieval

We used fMRI to assess the neural correlates of autobiographical, semantic, and episodic memory retrieval in healthy young and older adults. Participants were tested with an eventrelated paradigm in which retrieval demand was the only factor varying between trials. A spatio-temporal partial least square analysis was conducted to identify the main patterns of activity characterizing the groups across conditions. We identified brain regions activated by all three memory conditions relative to a control condition. This pattern was expressed equally in both age groups and replicated previous findings obtained in a separate group of younger adults. We also identified regions whose activity differentiated among the different memory conditions. These patterns of differentiation were expressed less strongly in the older adults than in the young adults, a finding that was further confirmed by a barycentric discriminant analysis. This analysis showed an age-related dedifferentiation in autobiographical and episodic memory tasks but not in the semantic memory task or the control condition. These findings suggest that the activation of a common memory retrieval network is maintained with age, whereas the specific aspects of brain activity that differ with memory content are more vulnerable and less selectively engaged in older adults. Our results provide a potential neural mechanism for the well-known age differences in episodic/autobiographical memory, and preserved semantic memory, observed when older adults are compared with younger adults

Disturbed sleep is associated with reduced verbal episodic memory and entorhinal cortex volume in younger middle-aged women with risk-reducing early ovarian removal

INTRODUCTION: Women with early ovarian removal (&lt;48 years) have an elevated risk for both late-life Alzheimer's disease (AD) and insomnia, a modifiable risk factor. In early midlife, they also show reduced verbal episodic memory and hippocampal volume. Whether these reductions correlate with a sleep phenotype consistent with insomnia risk remains unexplored.METHODS: We recruited thirty-one younger middleaged women with risk-reducing early bilateral salpingo-oophorectomy (BSO), fifteen of whom were taking estradiol-based hormone replacement therapy (BSO+ERT) and sixteen who were not (BSO). Fourteen age-matched premenopausal (AMC) and seventeen spontaneously peri-postmenopausal (SM) women who were ~10y older and not taking ERT were also enrolled. Overnight polysomnography recordings were collected at participants' home across multiple nights (M=2.38 SEM=0.19), along with subjective sleep quality and hot flash ratings. In addition to group comparisons on sleep measures, associations with verbal episodic memory and medial temporal lobe volume were assessed.RESULTS: Increased sleep latency and decreased sleep efficiency were observed on polysomnography recordings of those not taking ERT, consistent with insomnia symptoms. This phenotype was also observed in the older women in SM, implicating ovarian hormone loss. Further, sleep latency was associated with more forgetting on the paragraph recall task, previously shown to be altered in women with early BSO. Both increased sleep latency and reduced sleep efficiency were associated with smaller anterolateral entorhinal cortex volume.DISCUSSION: Together, these findings confirm an association between ovarian hormone loss and insomnia symptoms, and importantly, identify an younger onset age in women with early ovarian removal, which may contribute to poorer cognitive and brain outcomes in these women.</p