Altered structural connectome of children with auditory processing disorder: a diffusion MRI study.

Auditory processing disorder (APD) is a listening impairment that some school-aged children may experience despite having normal peripheral hearing. Recent resting-state functional magnetic resonance imaging (MRI) has revealed an alteration in regional functional brain topology in children with APD. However, little is known about the structural organization in APD. We used diffusion MRI data to investigate the structural connectome of 58 children from 8 to 14 years old diagnosed with APD (n = 29) and children without hearing complaints (healthy controls, HC; n = 29). We investigated the rich-club organization and structural connection differences between groups. The APD group showed similar rich-club organization and edge-wise connection compared with the HC group. However, at the regional level, we observed increased average path length (APL) and betweenness centrality in the right inferior parietal lobule and inferior precentral gyrus, respectively, in the APD group. Only HCs demonstrated a positive association between APL and the listening-in-spatialized-noise-sentences task in the left orbital gyrus. In line with previous findings, the current results provide evidence for altered structural networks at the regional level in the APD group, suggesting the involvement of multimodal deficits and a role for structure-function alteration in the listening difficulties of children with APD.

Altered brain network topology in children with auditory processing disorder: A resting-state multi-echo fMRI study.

Children with auditory processing disorder (APD) experience hearing difficulties, particularly in the presence of competing sounds, despite having normal audiograms. There is considerable debate on whether APD symptoms originate from bottom-up (e.g., auditory sensory processing) and/or top-down processing (e.g., cognitive, language, memory). A related issue is that little is known about whether functional brain network topology is altered in APD. Therefore, we used resting-state functional magnetic resonance imaging data to investigate the functional brain network organization of 57 children from 8 to 14 years old, diagnosed with APD (n = 28) and without hearing difficulties (healthy control, HC; n = 29). We applied complex network analysis using graph theory to assess the whole-brain integration and segregation of functional networks and brain hub architecture. Our results showed children with APD and HC have similar global network properties -i.e., an average of all brain regions- and modular organization. Still, the APD group showed different hub architecture in default mode-ventral attention, somatomotor and frontoparietal-dorsal attention modules. At the nodal level -i.e., single-brain regions-, we observed decreased participation coefficient (PC - a measure quantifying the diversity of between-network connectivity) in auditory cortical regions in APD, including bilateral superior temporal gyrus and left middle temporal gyrus. Beyond auditory regions, PC was also decreased in APD in bilateral posterior temporo-occipital cortices, left intraparietal sulcus, and right posterior insular cortex. Correlation analysis suggested a positive association between PC in the left parahippocampal gyrus and the listening-in-spatialized-noise -sentences task where APD children were engaged in auditory perception. In conclusion, our findings provide evidence of altered brain network organization in children with APD, specific to auditory networks, and shed new light on the neural systems underlying children's listening difficulties.

Reproducibility and repeatability of magnetic resonance imaging in dementia.

PURPOSE: Individualised predictive models of cognitive decline require disease-monitoring markers that are repeatable. For wide-spread adoption, such markers also need to be reproducible at different locations. This study assessed the repeatability and reproducibility of MRI markers derived from a dementia protocol. METHODS: Six participants were scanned at three different sites with a 3T MRI scanner. The protocol employed: T1-weighted (T1w) imaging, resting state functional MRI (rsfMRI), arterial spin labelling (ASL), diffusion-weighted imaging (DWI), T2-weighted fluid attenuation inversion recovery (FLAIR), T2-weighted (T2w) imaging, and susceptibility weighted imaging (SWI). Participants were scanned repeatedly, up to six times over a maximum period of five years. One participant was also scanned a further three times on sequential days on one scanner. Fifteen derived metrics were computed from the seven different modalities. RESULTS: Reproducibility (coefficient of variation; CoV, across sites) was best for T1w derived grey matter, white matter and hippocampal volume (CoV < 1.5%), compared to rsfMRI and SWI derived metrics (CoV, 19% and 21%). For a given metric, long-term repeatability (CoV across time) was comparable to reproducibility, with short-term repeatability considerably better. CONCLUSIONS: Reproducibility and repeatability were assessed for a suite of markers calculated from a dementia MRI protocol. In general, structural markers were less variable than functional MRI markers. Variability over time on the same scanner was comparable to variability measured across different scanners. Overall, the results support the viability of multi-site longitudinal studies for monitoring cognitive decline.

Spatial variation of perfusion MRI reflects cognitive decline in mild cognitive impairment and early dementia.

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer's dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand. From CBF maps that included all grey matter, sCoV progressively increased across each group with increased cognitive deficit. A similar overall trend was found when examining sCoV solely in the temporal lobe. We conclude that sCoV, a simple to compute imaging metric derived from ASL MRI, is sensitive to varying degrees of cognitive changes and supports the view that vascular health contributes to cognitive decline associated with Alzheimer's disease.

Characterization of optofluidic devices for the sorting of sub-micrometer particles.

In this work, we investigate methods of fabricating a device for the optical actuation of nanoparticles. To create the microfluidic channel, we pursued three fabrication methods: SU-8 to molded polydimethylsiloxane soft lithography, laser etching of glass, and deep reactive ion etching of fused silica. We measured the surface roughness of the etched sidewalls, and the laser power transmission through each device. We then measured the radiation pressure on 0.5-µm particles in the best-performing fabricated device (etched fused silica) and in a square glass capillary.

Relational processing demands and the role of spatial context in the construction of episodic simulations.

Reports on differences between remembering the past and imagining the future have led to the hypothesis that constructing future events is a more cognitively demanding process. However, factors that influence these increased demands, such as whether the event has been previously constructed and the types of details comprising the event, have remained relatively unexplored. Across two experiments, we examined how these factors influence the process of constructing event representations by having participants repeatedly construct events and measuring how construction times and a range of phenomenological ratings changed across time points. In Experiment 1, we contrasted the construction of past and future events and found that, relative to past events, the constructive demands associated with future events are particularly heightened when these events are imagined for the first time. Across repeated simulations, future events became increasingly similar to past events in terms of construction times and incorporated detail. In Experiment 2, participants imagined future events involving two memory details (person, location) and then reimagined the event either (a) exactly the same, (b) with a different person, or (c) in a different location. We predicted that if generating spatial information is particularly important for event construction, a change in location will have the greatest impact on constructive demands. Results showed that spatial context contributed to these heightened constructive demands more so than person details, consistent with theories highlighting the central role of spatial processing in episodic simulation. We discuss the findings from both studies in the light of relational processing demands and consider implications for current theoretical frameworks. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Creative, internally-directed cognition is associated with reduced BOLD variability.

In a range of externally-directed tasks, intra-individual variability of fMRI BOLD signal has been shown to be a stronger predictor of cognitive performance than mean BOLD signal. BOLD variability's strong association with cognitive performance is hypothesised to be due to it capturing the dynamic range of neural systems. Although increased BOLD variability is also speculated to play a role in internally-directed thought, particularly when creative and flexible cognition is required, there is a relative lack of research exploring whether BOLD variability is related to internally-directed cognition. Thus, we investigated the relationship between BOLD variability and a key component of creativity - divergent thinking - in various tasks that required participants to think flexibly. We also determined whether any associations between BOLD variability and creativity overlapped with, or differed, from associations between mean BOLD signal and creativity. First, we performed task Partial Least Squares (PLS) analyses that compared BOLD signal (either mean or variability) during two future imagination conditions that differed in the amount of cognitive flexibility required: a Congruent condition in which autobiographical details (people, places, objects) comprising an imagined event belonged to the same social sphere (e.g., university) and an Incongruent condition in which details belonged to different social spheres and required greater cognitive flexibility to integrate. Results indicated that the Incongruent condition was associated with a widespread reduction in both BOLD variability and mean signal (relative to the Congruent condition), but in largely non-overlapping regions. Next, we used behavioral PLS to determine whether individual differences in performance on future simulation tasks as well as the Alternate Uses Task relates to BOLD variability and mean BOLD signal. Better performance on these tasks was predominantly associated with increases in mean BOLD signal and decreases in BOLD variability, in a range of disparate brain regions. Together, the results suggest that, unlike tasks requiring externally-directed cognition, superior performance on tasks requiring creative internal mentation is associated with less (not more) variability.

Lens-axicon separation to tailor aberration free focused Bessel-Gaussian beams in the paraxial regime.

Lens-axicon doublets have been used to produce Bessel-Gaussian beams, a narrow non-diffracting beam of relatively constant width. One problem of using Bessel-Gaussian beams is that there is a compromise between achieving a long effective focal length with a small central core radius and distributing the beam intensity between the central core and the off-axis rings. Here, we explore the advantage of tuning the lens-axicon separation, which allows us to have an additional degree of freedom to tailor the beam profile. Moreover, the separation between the lens and the axicon reduces the spherical aberrations in the beam profile, which can then be modeled within the paraxial regime. We study the detrimental effects of the spherical aberrations and provide several options to minimize them. We examine both sharp and shallow axicons used in combination with different converging lenses. We perform a series of detailed experiments to image the structure of the beam through the Bessel region. The spatial light distribution of the lens-axicon system is analyzed by using high dynamic range imaging and complemented with consistent theoretical calculations within the paraxial regime.

Constructive episodic simulation, flexible recombination, and memory errors.

According to Mahr & Csibra (M&C), the view that the constructive nature of episodic memory is related to its role in simulating future events has difficulty explaining why memory is often accurate. We hold this view, but disagree with their conclusion. Here we consider ideas and evidence regarding flexible recombination processes in episodic retrieval that accommodate both accuracy and distortion.

Scene Construction and Relational Processing: Separable Constructs?

Imagining hypothetical events often entails the construction of a detailed mental simulation. Despite recent advances, debate still surrounds the fundamental constructive process underpinning simulations supported by the hippocampus. Palombo et al. (2016) report findings that suggest that scene construction drives hippocampal engagement during imagination. However, they fail to consider the findings of a previous study using an extremely similar manipulation that generated similar hippocampal findings, but was interpreted in terms of event specificity and relational processing (Addis et al. 2011). While we applaud the general approach taken by Palombo et al. in attempting to distinguish components of mental simulation, a comparison of these 2 papers has brought into sharp relief how the lack of a common theoretical framework can result in significant interpretative ambiguities. In this commentary, we attempt to identify and clarify these as yet unresolved conceptual issues that will require empirical and theoretical attention in future research.

Reading network in dyslexia: Similar, yet different.

Dyslexia is a developmental disorder characterized by reading and phonological difficulties, yet important questions remain regarding its underlying neural correlates. In this study, we used partial least squares (PLS), a multivariate analytic technique, to investigate the neural networks used by dyslexics while performing a word-rhyming task. Although the overall reading network was largely similar in dyslexics and typical readers, it did not correlate with behavior in the same way in the two groups. In particular, there was a positive association between reading performance and both right superior temporal gyrus and bilateral insula activation in dyslexic readers but a negative correlation in typical readers. Together with differences in lateralization unique to dyslexics, this suggests that the combination of poor reading performance with high insula activity and atypical laterality is a consistent marker of dyslexia. These findings emphasize the importance of understanding right-hemisphere activation in dyslexia and provide promising directions for the remediation of reading disorders.

Identifying grey matter changes in schizotypy using partial least squares correlation.

Neuroimaging research into the brain structure of schizophrenia patients has shown consistent reductions in grey matter volume relative to healthy controls. Examining structural differences in individuals with high levels of schizotypy may help elucidate the course of disorder progression, and provide further support for the schizotypy-schizophrenia continuum. Thus far, the few studies investigating grey matter differences in schizotypy have produced inconsistent results. In the current study, we used a multivariate partial least squares (PLS) approach to clarify the relationship between psychometric schizotypy (measured by the Oxford-Liverpool Inventory of Feelings and Experiences) and grey matter volume in 49 healthy adults. We found a negative association between all schizotypy dimensions and grey matter volume in the frontal and temporal lobes, as well as the insula. We also found a positive association between all schizotypy dimensions and grey matter volume in the parietal and temporal lobes, and in subcortical regions. Further correlational analyses revealed that positive and disorganised schizotypy were strongly associated with key regions (left superior temporal gyrus and insula) most consistently reported to be affected in schizophrenia and schizotypy. We also compared PLS with the typically used General Linear Model (GLM) and demonstrate that PLS can be reliably used as an extension to voxel-based morphometry (VBM) data. This may be particularly valuable for schizotypy research due to PLS' ability to detect small, but reliable effects. Together, the findings indicate that healthy schizotypal individuals exhibit structural changes in regions associated with schizophrenia. This adds to the evidence of an overlap of phenotypic expression between schizotypy and schizophrenia, and may help establish biological endophenotypes for the disorder.

The Simpson's paradox and fMRI: Similarities and differences between functional connectivity measures derived from within-subject and across-subject correlations.

Task-related functional connectivity (fc-MRI) indexes the interaction of brain regions during cognitive tasks. Two general classes of methods exist to investigate fc-MRI: the most widely-used method calculates temporal correlations between voxels/regions within subjects, and then determines if within-subject correlations are reliable across subjects (ws-fcMRI); the other calculates the average (BOLD) signal within voxels/regions and then performs correlations across subjects (as-fcMRI). That is, while both methods rely on correlational techniques, the level at which correlations are calculated is fundamentally different. While conceptually distinct, it is not known how well these two methods of fc-MRI analyses converge on the same findings. The current study addresses this question across a number of analyses. First, using default-mode network regions as seeds, we show that as-fcMRI does not strongly predict ws-fcMRI during episodic simulation tasks. Next, we show that the relationship between as-fcMRI and ws-fcMRI is contingent on whether correlations are calculated between regions from the same functional network (default mode or dorsal attention networks) or between regions from different functional networks. Lastly, we compare seed partial least squares (PLS) - a well-established as-fcMRI method - with a novel version of seed PLS that combines the multivariate approach of PLS analyses and within-subject correlations. The results showed that while many regions exhibited congruent as-fcMRI and ws-fcMRI effects, in some regions the two analyses produced effects in opposite directions. Results are discussed in relation to the Simpson's Paradox, a phenomenon in which across-subject correlations are reversed within individuals present in a sample. Overall, our results suggest that the findings of as-fcMRI do not always map onto those from ws-fcMRI. We end by discussing the advantages associated with using ws-fcMRI to assess the task-related interactions between brain regions.

Routes to the past: neural substrates of direct and generative autobiographical memory retrieval.

Models of autobiographical memory propose two routes to retrieval depending on cue specificity. When available cues are specific and personally-relevant, a memory can be directly accessed. However, when available cues are generic, one must engage a generative retrieval process to produce more specific cues to successfully access a relevant memory. The current study sought to characterize the neural bases of these retrieval processes. During functional magnetic resonance imaging (fMRI), participants were shown personally-relevant cues to elicit direct retrieval, or generic cues (nouns) to elicit generative retrieval. We used spatiotemporal partial least squares to characterize the spatial and temporal characteristics of the networks associated with direct and generative retrieval. Both retrieval tasks engaged regions comprising the autobiographical retrieval network, including hippocampus, and medial prefrontal and parietal cortices. However, some key neural differences emerged. Generative retrieval differentially recruited lateral prefrontal and temporal regions early on during the retrieval process, likely supporting the strategic search operations and initial recovery of generic autobiographical information. However, many regions were activated more strongly during direct versus generative retrieval, even when we time-locked the analysis to the successful recovery of events in both conditions. This result suggests that there may be fundamental differences between memories that are accessed directly and those that are recovered via the iterative search and retrieval process that characterizes generative retrieval.

Age-related neural changes in autobiographical remembering and imagining.

Numerous neuroimaging studies have revealed that in young adults, remembering the past and imagining the future engage a common core network. Although it has been observed that older adults engage a similar network during these tasks, it is unclear whether or not they activate this network in a similar manner to young adults. Young and older participants completed two autobiographical tasks (imagining future events and recalling past events) in addition to a semantic-visuospatial control task. Spatiotemporal Partial Least Squares analyses examined whole brain patterns of activity across both the construction and elaboration of autobiographical events. These analyses revealed that that both age groups activated a similar network during the autobiographical tasks. However, some key age-related differences in the activation of this network emerged. During the construction of autobiographical events, older adults showed less activation relative to younger adults, in regions supporting episodic detail such as the medial temporal lobes and the precuneus. Later in the trial, older adults showed differential recruitment of medial and lateral temporal regions supporting the elaboration of autobiographical events, and possibly reflecting an increased role of conceptual information when older adults describe their pasts and their futures.

Hippocampal contributions to the episodic simulation of specific and general future events.

Recent studies have demonstrated that remembering past experiences and imagining future scenarios recruits a core network including the hippocampus. Even so, constructing future events engages the hippocampus more than remembering past events. This fMRI study examined whether increased hippocampal activity for future events includes both specific and general events. Participants constructed specific and general past and future events during fMRI scanning. We replicated previous findings of increased activity in the right anterior hippocampus when constructing future relative to past events, and when constructing specific relative to general events. Importantly, both effects were driven by a significant interaction between temporal direction and specificity, with specific future events resulting in more activity than other conditions, including general future events. No regions exhibited greater activity during the construction of past relative to future events, or general relative to specific events. These results suggest that the process of constructing a detailed representation of a novel and specific future event differentially engages the right anterior hippocampus compared with other forms of event simulation and recall. Future work is needed to disambiguate the role of encoding, novelty and detail recombination in engaging the right anterior hippocampus during simulation.

Cerebral asymmetries: complementary and independent processes.

Most people are right-handed and left-cerebrally dominant for speech, leading historically to the general notion of left-hemispheric dominance, and more recently to genetic models proposing a single lateralizing gene. This hypothetical gene can account for higher incidence of right-handers in those with left cerebral dominance for speech. It remains unclear how this dominance relates to the right-cerebral dominance for some nonverbal functions such as spatial or emotional processing. Here we use functional magnetic resonance imaging with a sample of 155 subjects to measure asymmetrical activation induced by speech production in the frontal lobes, by face processing in the temporal lobes, and by spatial processing in the parietal lobes. Left-frontal, right-temporal, and right-parietal dominance were all intercorrelated, suggesting that right-cerebral biases may be at least in part complementary to the left-hemispheric dominance for language. However, handedness and parietal asymmetry for spatial processing were uncorrelated, implying independent lateralizing processes, one producing a leftward bias most closely associated with handedness, and the other a rightward bias most closely associated with spatial attention.