Within-subject reproducibility varies in multi-modal, longitudinal brain networks.

Network neuroscience provides important insights into brain function by analyzing complex networks constructed from diffusion Magnetic Resonance Imaging (dMRI), functional MRI (fMRI) and Electro/Magnetoencephalography (E/MEG) data. However, in order to ensure that results are reproducible, we need a better understanding of within- and between-subject variability over long periods of time. Here, we analyze a longitudinal, 8 session, multi-modal (dMRI, and simultaneous EEG-fMRI), and multiple task imaging data set. We first confirm that across all modalities, within-subject reproducibility is higher than between-subject reproducibility. We see high variability in the reproducibility of individual connections, but observe that in EEG-derived networks, during both rest and task, alpha-band connectivity is consistently more reproducible than connectivity in other frequency bands. Structural networks show a higher reliability than functional networks across network statistics, but synchronizability and eigenvector centrality are consistently less reliable than other network measures across all modalities. Finally, we find that structural dMRI networks outperform functional networks in their ability to identify individuals using a fingerprinting analysis. Our results highlight that functional networks likely reflect state-dependent variability not present in structural networks, and that the type of analysis should depend on whether or not one wants to take into account state-dependent fluctuations in connectivity.

Raman spectroscopy and neuroscience: from fundamental understanding to disease diagnostics and imaging.

Neuroscience would directly benefit from more effective detection techniques, leading to earlier diagnosis of disease. The specificity of Raman spectroscopy is unparalleled, given that a molecular fingerprint is attained for each species. It also allows for label-free detection with relatively inexpensive instrumentation, minimal sample preparation, and rapid sample analysis. This review summarizes Raman spectroscopy-based techniques that have been used to advance the field of neuroscience in recent years.

Individual differences in compliance and agreement for sleep logs and wrist actigraphy: A longitudinal study of naturalistic sleep in healthy adults.

There is extensive laboratory research studying the effects of acute sleep deprivation on biological and cognitive functions, yet much less is known about naturalistic patterns of sleep loss and the potential impact on daily or weekly functioning of an individual. Longitudinal studies are needed to advance our understanding of relationships between naturalistic sleep and fluctuations in human health and performance, but it is first necessary to understand the efficacy of current tools for long-term sleep monitoring. The present study used wrist actigraphy and sleep log diaries to obtain daily measurements of sleep from 30 healthy adults for up to 16 consecutive weeks. We used non-parametric Bland-Altman analysis and correlation coefficients to calculate agreement between subjectively and objectively measured variables including sleep onset time, sleep offset time, sleep onset latency, number of awakenings, the amount of wake time after sleep onset, and total sleep time. We also examined compliance data on the submission of daily sleep logs according to the experimental protocol. Overall, we found strong agreement for sleep onset and sleep offset times, but relatively poor agreement for variables related to wakefulness including sleep onset latency, awakenings, and wake after sleep onset. Compliance tended to decrease significantly over time according to a linear function, but there were substantial individual differences in overall compliance rates. There were also individual differences in agreement that could be explained, in part, by differences in compliance. Individuals who were consistently more compliant over time also tended to show the best agreement and lower scores on behavioral avoidance scale (BIS). Our results provide evidence for convergent validity in measuring sleep onset and sleep offset with wrist actigraphy and sleep logs, and we conclude by proposing an analysis method to mitigate the impact of non-compliance and measurement errors when the two methods provide discrepant estimates.

Acute Exercise Modulates Feature-selective Responses in Human Cortex.

An organism's current behavioral state influences ongoing brain activity. Nonhuman mammalian and invertebrate brains exhibit large increases in the gain of feature-selective neural responses in sensory cortex during locomotion, suggesting that the visual system becomes more sensitive when actively exploring the environment. This raises the possibility that human vision is also more sensitive during active movement. To investigate this possibility, we used an inverted encoding model technique to estimate feature-selective neural response profiles from EEG data acquired from participants performing an orientation discrimination task. Participants (n = 18) fixated at the center of a flickering (15 Hz) circular grating presented at one of nine different orientations and monitored for a brief shift in orientation that occurred on every trial. Participants completed the task while seated on a stationary exercise bike at rest and during low- and high-intensity cycling. We found evidence for inverted-U effects; such that the peak of the reconstructed feature-selective tuning profiles was highest during low-intensity exercise compared with those estimated during rest and high-intensity exercise. When modeled, these effects were driven by changes in the gain of the tuning curve and in the profile bandwidth during low-intensity exercise relative to rest. Thus, despite profound differences in visual pathways across species, these data show that sensitivity in human visual cortex is also enhanced during locomotive behavior. Our results reveal the nature of exercise-induced gain on feature-selective coding in human sensory cortex and provide valuable evidence linking the neural mechanisms of behavior state across species.

Consciousness isn't all-or-none: Evidence for partial awareness during the attentional blink.

Alternative views of the nature of consciousness posit that awareness of an object is either an all-or-none phenomenon or that awareness can be partial, occurring independently for different levels of representation. The all-or-none hypothesis predicts that when one feature of an object is identified, all other features should be consciously accessible. The partial awareness hypothesis predicts that one feature may reach consciousness while others do not. These competing predictions were tested in two experiments that presented two targets within a central stream of letters. We used the attentional blink evoked by the first target to assess consciousness for two different features of the second target. The results provide evidence that there can be a severe impairment in conscious access to one feature even when another feature is accurately reported. This behavioral evidence supports the partial awareness hypothesis, showing that consciousness of different features of the same object can be dissociated.

Distractor suppression when attention fails: behavioral evidence for a flexible selective attention mechanism.

Despite consistent evidence showing that attention is a multifaceted mechanism that can operate at multiple levels of processing depending on the structure and demands of the task, investigations of the attentional blink phenomenon have consistently shown that the impairment in reporting the second of two targets typically occurs at a late, or post-perceptual, stage of processing. This suggests that the attentional blink phenomenon may represent the operation of a unique attentional mechanism that is not as flexible as other attentional mechanisms. To test whether the attentional blink is a fixed or flexible phenomenon, we manipulated first target task demands (i.e., difficulty) and measured the influence this had on processing a subsequently presented distractor and the second target. If the attentional blink represents a mechanism that is fixed and consistently fails at a single stage of processing, then manipulations of task difficulty should not affect distractor processing. However, if the attentional blink represents a more multifaceted and flexible mechanism, then task difficulty should modulate distractor processing. The results revealed that distractor processing during the AB was attenuated under high task difficulty. In addition, unlike previous studies, we failed to find a correlation between distractor processing and the severity of the attentional blink. Using a simulation, we demonstrate that the previously reported correlations may have been spurious and due to using variables that were not independent. Overall, the present results support the conclusion that the selectivity of attention during the AB is flexible and depends on the structure and demands of the task.

A week-long meditation retreat decouples behavioral measures of the alerting and executive attention networks.

PREVIOUS STUDIES HAVE EXAMINED THE INFLUENCE OF MEDITATION ON THREE FUNCTIONALLY DIFFERENT COMPONENTS OF ATTENTION: executive control, alerting, and orienting. These studies have consistently found that meditation training improves both executive attention and alerting, but there has not been a consistent and clear effect of meditation training on orienting. In addition, while previous studies have shown that the functional coupling of the alerting and executive networks increases the processing of task irrelevant stimuli, it is unknown if participating in a meditation retreat can decouple these components of attention and lead to improved performance. The current study investigated the influence of a week-long intensive meditation retreat on three components of attention by randomly assigning participants to either pre- or postretreat testing groups. A modified attention network test (ANT) was used. Executive attention was measured as the difference in response time (RT) between congruent and incongruent task irrelevant flankers (conflict effect). Reflexive and volitional orienting were measured by manipulating cue validity and stimulus onset asynchrony (SOA). The coupling of executive attention and alerting was measured by examining flanker interference as a function of the SOA of an alerting cue. The meditation retreat improved task based indices of executive attention, but not reflexive or volitional orienting. There was clear behavioral evidence of coupling between executive attention and alerting in the preretreat group, as the conflict effect peaked when an alerting cue was presented 300 ms before the target. Importantly, there was no increase in the conflict effect for the postretreat group. This is consistent with the notion that the retreat decoupled the executive and alerting networks. These results suggest that previously reported improvements in the executive and alerting networks after meditation training might be mediated by the same underlying mechanism.

Post-perceptual processing during the attentional blink is modulated by inter-trial task expectancies.

The selective processing of goal-relevant information depends on an attention system that can flexibly adapt to changing task demands and expectations. Evidence from visual search tasks indicates that the perceptual selectivity of attention increases when the bottom-up demands of the task increase and when the expectations about task demands engendered by trial history are violated. Evidence from studies of the attentional blink (AB), which measures the temporal dynamics of attention, also indicates that perceptual selectivity during the AB is increased if the bottom-up task demands are increased. The present work tested whether expectations about task demands engendered by trial history also modulate perceptual selectivity during the AB. Two experiments tested the extent to which inter-trial switches in task demands reduced post-perceptual processing of targets presented during the AB. Experiment 1 indexed post-perceptual processing using the event-related potential (ERP) technique to isolate the context sensitive N400 ERP component evoked by words presented during the AB. Experiment 2 indexed post-perceptual processing using behavioral performance to determine the extent to which personal names survive the AB. The results of both experiments revealed that both electrophysiological (Exp. 1) and behavioral (Exp. 2) indices of post-perceptual processing were attenuated when consecutive trials differed in terms of their perceptual demands. The results are consistent with the notion that the selectivity of attention during the AB is modulated not only by within-trial task demands, but also can be flexibly determined by trial-by-trial expectations.

Multiple measures of visual attention predict novice motor skill performance when attention is focused externally.

Multiple lines of evidence indicate that the control of attention and motor skill performance are related. Athletes of various skill levels differ in terms of their control over the focus of attention and directing athletes to adopt an internal or external focus of attention modulates performance. However, it is unclear (a) whether the relationship between skill level and attentional control arises from preexisting individual differences in attention or from practice of the motor skill and (b) whether the effect of adopting an internal or external focus of attention on motor performance is influenced by individual differences in attention. To address these issues, individuals were measured on three distinct attention functions - orienting, alerting, and executive - prior to engaging in a novel golf-putting task performed with either external or internal focus instructions. The results indicated that, on average, attentional functioning and putting performance were related but that the strong relationships with orienting and executive attention were only present in the group given external focus instructions. These findings suggest that individual differences in attentional abilities are predictive of novel skill performance under an external focus of attention and they shed light on the mechanisms underlying the effects of focus instructions during motor performance.

Multimodal target detection using single trial evoked EEG responses in single and dual-tasks.

The detection of event-related potentials in the electroencephalogram signal is a common way for creating a brain-computer interface (BCI). Successful detection of evoked responses can be enhanced by the user selectively attending to specific stimuli presented in the BCI task. Because BCI users need a system that performs well in a variety of contexts, even ones that may impair selective attention, it is critical to understand how single trial detection is affected by attention. We tested 16 participants using a rapid serial visual/auditory presentation paradigm under three conditions, one in which they detected the presence of a visual target, one in which they detected the presence of an auditory target, and one in which they detected both visual and auditory targets. The behavioral performance indicates that the visual task was more difficult than the auditory task. Consistent with the higher behavioral difficulty of the visual task, single trial performance showed no difference between single and dual-task for the visual target detection (mean=0.76). However, the area under the curve for the auditory target detection was significantly lower than the dual-task (mean=0.81 for single task, 0.75 for dual-task). The results support the conclusion that single-trial target detection is impaired when attention is divided between multiple tasks.

Impact of target probability on single-trial EEG target detection in a difficult rapid serial visual presentation task.

In non-invasive brain-computer interface (BCI), the analysis of event-related potentials (ERP) has typically focused on averaged trials, a current trend is to analyze single-trial evoked response individually with new approaches in pattern recognition and signal processing. Such single trial detection requires a robust response that can be detected in a variety task conditions. Here, we investigated the influence of target probability, a key factor known to influence the amplitude of the evoked response, on single trial target classification in a difficult rapid serial visual presentation (RSVP) task. Our classification approach for detecting target vs. non target responses, considers spatial filters obtained through the maximization of the signal to signal-plus-noise ratio, and then uses the resulting information as inputs to a Bayesian discriminant analysis. The method is evaluated across eight healthy subjects, on four probability conditions (P=0.05, 0.10, 0.25, 0.50). We show that the target probability has a statistically significant effect on both the behavioral performance and the target detection. The best mean area under the ROC curve is achieved with P=0.10, AUC=0.82. These results suggest that optimal performance of ERP detection in RSVP tasks is critically dependent on target probability.

Perceptual load modulates the processing of distractors presented at task-irrelevant locations during the attentional blink.

The distribution of attention in both space and time is critical for processing our dynamic environment. Studies of spatial attention suggest that the distribution of attention is decreased when the perceptual load of a task increases, resulting in decreased processing of task-irrelevant distractors. Studies of the attentional blink (AB) suggest that the temporal distribution of attention also influences distractor processing, such that distractor processing increases during the AB relative to outside the AB (Jiang & Chun, 2001). Two experiments are reported in which the extent to which the difficulty of the first target task (T1) modulates the processing of task-irrelevant distractors during the AB was tested. To investigate this issue, both the first and second target tasks (T1 and T2) required identifying a central stimulus that was flanked by low-load or high-load distractors. Consistent with previous studies of the AB, there was evidence of more distractor processing during the AB than outside the AB. Critically, however, the interference caused by distractors presented simultaneously with T2 during the AB was reduced when T1 perceptual load was high relative to when it was low. These results suggest that increasing T1 perceptual load decreases distractor processing during the AB and that perceptual processes influence both the temporal and spatial distribution of attention.

Electrophysiological evidence for both perceptual and postperceptual selection during the attentional blink.

When two masked targets are presented in rapid succession, correct identification of the first target (T1) leads to a dramatic impairment in identification of the second target (T2). Several studies of this so-called attentional blink (AB) phenomenon have provided behavioral and physiological evidence that T2 is processed to the semantic level, despite the profound impairment in T2 report. These findings have been interpreted as an example of perception without awareness and have been explained by models that assume that T2 is processed extensively even though it does not gain access into consciousness. The present study reports two experiments that test this assumption. In Experiment 1, the perceptual load of the T1 task was manipulated and T2 was a word that was either related or unrelated to a context word presented at the beginning of each trial. The event-related potential (ERP) technique was used to isolate the context-sensitive N400 component evoked by the T2 word. The ERP data revealed that there was a complete suppression of the N400 during the AB when the perceptual load was high, but not when perceptual load was low. Experiment 2 replicated the high-load condition of Experiment 1 while ruling out two alternative explanations for the reduction of the N400 during the AB. The results of both experiments demonstrate that word meanings are not always accessed during the AB and are consistent with studies that suggest that attention can act to select information at multiple stages of processing depending on concurrent task demands.

Rietveld refinements and spectroscopic structural studies of a Na-free carbonate apatite made by hydrolysis of monetite.

Seven nominally identical samples of Na-free carbonate apatite (CO(3)Ap) were prepared by reaction of CaHPO(4) with ammonium carbonate solution at 70 degrees C over 3 days. They were studied by chemical analysis, Rietveld analysis of powder X-ray diffraction (XRD) data, Ca/P ratio determinations (quantitative phase analysis of CaO, Ca(OH)(2) and hydroxyapatite formed after heating to 900 degrees C from Rietveld analysis of XRD data), He pycknometry, (1)H, (13)C and (31)P MAS NMR spectrometry and Fourier transform infrared and Raman spectroscopy. Spectroscopy showed the apatite products were B-type CO(3)Aps (CO(3)(2-) replacing PO(4)(3-)) and XRD that one sample contained 1.6 wt% calcite with a trace in another. Mean results of the six essentially calcite-free samples were: a=9.405(5)A, c=6.896(2)A; 11.2 wt% CO(3); unit cell contents, Ca(8.241)(PO(4))(4.344)(CO(3))(1.656)(OH)(0.139) x 2.29H(2)O; mole Ca/P ratio from chemical analyses, 1.897(22) and from powder XRD phase analysis of samples decarbonated at 900 degrees C, 1.892(25). Density determinations indicated that the 2.29mol of H(2)O were in the unit cell. Rietveld refinements were undertaken without and with explicit modelling of the CO(3)(2-) ion. The latter used constraints to maintain the CO(3)(2-) ion in its known geometry and the total of PO(4)(3-) and CO(3)(2-) ions per unit cell at six. Without the CO(3)(2-) ion in the model, PO(4) volume, P-O bond lengths and P occupancy were apparently reduced, consistent with CO(3)(2-) replacing PO(4)(3-) ions. With the CO(3)(2-) ion modelled, the reductions were less and the CO(3)(2-) ion occupied the "sloping" face of the replaced PO(4)(3-) ion in two-fold disorder about the mirror plane. The angle between the normal to the plane of the ion and the c-axis was 34 degrees , close to 35.3 degrees , the equivalent angle for the PO(4)(3-) ion. When modelled, the CO(3)(2-) ion occupancy was 1.81 ions per unit cell, in reasonable agreement with unit cell contents determined chemically (1.66). The OH(-) ion occupancy was elevated (2.33 ions per unit cell versus 0.14 inferred from the charge balance), which we ascribe to H(2)O molecules occupying sites in c-axis channels. The Ca/P ratio from occupancies (2.31) was also elevated over that determined chemically (1.90). We attribute this to loss of Ca from Ca sites increasing the apparent anisotropic displacement parameters of remaining Ca atoms, leading to an apparently increased occupancy.

Three-dimensional study of human dental fissure enamel by synchrotron X-ray microtomography.

The three-dimensional morphology of human tooth fissures and the quantification of mineral distribution in fissure enamel are pertinent to the development and diagnosis of caries. Synchrotron X-ray microtomography was used to measure linear attenuation coefficients (at 25 keV) at high spatial resolution with a volume-imaging element (cubic voxel) of 4.9x4.9x4.9 microm3 in a block from a human premolar that included part of a stained fissure. From the linear attenuation coefficient, the mineral concentration, expressed as gHAp cm-3 (where HAp is stoichiometric hydroxyapatite), was calculated. The mean mineral concentration in bulk enamel was 2.84 gHAp cm-3. Well-defined regions (1.5-2.6 gHAp cm-3), extending up to approximately 130 microm from the base of some narrower lengths of the fissure and up to approximately 50 microm deep from the fissure surface, were attributed to hypomineralization. Other regions of low mineral concentration, some (1.4-2.3 gHAp cm-3) lying within the expected course of the fissure base and some (2.2-2.7 gHAp cm-3) deep to the pit, were also considered to be of developmental origin. However, a diffuse distribution of low mineral concentrations (2.2-2.7 gHAp cm-3) in the pit walls was attributed primarily to demineralization from caries. The fissure contained heterogeneous material (

Scanning microradiographic study on the influence of diffusion in the external liquid on the rate of demineralization in hydroxyapatite aggregates.

Subsurface demineralization in enamel caries is known to entail diffusion of reagents and products both within the lesion and within the plaque biofilm external to the lesion. However, development of a predictive mathematical model for subsurface demineralization is hindered by limited quantitative understanding of the effects of these diffusion processes. The purpose of this quantitative study was to investigate and understand the effect of external diffusion length on the rate of demineralization in a simple model system. Ten, 500-microm thick sections cut from a porous hydroxyapatite (HAP) pellet were inserted in scanning microradiography (SMR) cells. The exposed thin edges of the sections were initially separated by columns of water (diffusion lengths) of 0-0.9 cm from a 1-l reservoir of demineralizing buffer (pH 4). Buffer was found to diffuse from the reservoir through the increasing diffusion lengths to the exposed HAP surface, whilst dissolved product diffused along the reverse path. Rates of HAP loss (from SMR measurements) decreased as the diffusion length increased. Experimental data were fitted to a general diffusion-reaction model. This showed that the solution near the HAP surface was almost completely saturated with HAP, and that the diffusion of dissolution products, rather than of buffer species, was rate limiting.

Rietveld refinements and spectroscopic studies of the structure of Ca-deficient apatite.

Nine samples of Ca-deficient apatite (Ca-def Ap) were prepared from suspensions of CaHPO4 (monetite) at 90 degrees C by raising the pH from approximately 4 through release of NH3 produced by the hydrolysis of urea. Products were dried at 100 degrees C for 24h and studied by chemical analyses, X-ray powder diffraction (XRPD) (and Rietveld analysis of this data), Ca/P ratio determination (quantitative phase analysis of samples after heating to 900 degrees C from Rietveld analysis of XRPD data), scanning electron microscopy, He pycknometry, 1H and 31P MAS NMR spectrometry and Fourier transform infrared and Raman spectroscopy. All samples contained apatite, but three also contained monetite. Infrared and Raman spectroscopy confirmed the presence of HPO4(2-) and absence of carbonate ions in the six monetite-free samples. Mean results for the six samples were: a = 9.4320(40), c = 6.8751(31) A; unit cell formula from chemical analysis neglecting protonation of phosphate ion, Ca(9.303(50))(PO4)6(OH)(0.606(99)).1.97(12)H2O; theoretical density 3.10 g cm(-3); experimental density (mean for three samples) 3.15 g cm(-3); and Ca/P mole ratio from chemical analysis and phase analysis after heating to 900 degrees C, 1.550(8) and 1.550(2), respectively. An earlier assignment of a line at 6 ppm in the 1H NMR spectrum of similar samples to HPO4(2-) ions could not be confirmed; hence no information about the HPO4(2-) ion content could be derived, in disagreement with the previous NMR study. A shoulder at approximately 0.9 ppm relative to 85 wt% H3PO4 in the 31P NMR spectrum was assigned to HPO4(2-) ions. Occupancies from the Rietveld structure refinements indicated preferential loss of Ca from Ca2 sites compared with Ca1, but the loss was substantially smaller than expected from chemical analyses. It is suggested that imperfect modelling of the structure in the refinement, particularly disorder associated with the Ca2 site, resulted in errors in Ca2 occupancies. The P-O bonds were slightly shorter than those in stoichiometric hydroxyapatite, rather than longer as might be expected from protonation of phosphate tetrahedra. However, consideration of known acid phosphate structures indicated that it was unlikely that the increase in P-O lengths would be sufficient to be detected. The observed decrease was tentatively assigned to the presence of Ca2+ ion vacancies.

Rietveld structure refinement of precipitated carbonate apatite using neutron diffraction data.

X-ray and time of flight neutron diffraction data, FTIR and MAS-NMR spectra, and ICP-AES and carbonate analyses have been collected from a sodium-containing carbonate apatite (CO(3) content 12.5(7)wt%). A structural model based on Holly Springs hydroxyapatite without CO(3)(2-) ions showed an apparent reduction in the PO(4) tetrahedral volume which is ascribed to CO(3)(2-) replacing PO(4)(3-) ions in the lattice. Four structural models from the literature with the CO(3)(2-) ion explicitly modelled were fitted to the neutron diffraction data by the Rietveld method. The best fit was obtained with the CO(3)(2-) ion in disorder between the mirror symmetry related faces of a vacant PO(4)(3-) site and with the normal to the plane of the CO(3)(2-) ion at approximately 30 degrees to the c-axis. This angle is consistent with results from previous polarised IR measurements on single crystals of francolite (a fluorocarbonate apatite) and human dental enamel. Further refinement of the model revealed a hitherto unknown atom site close to the unit cell origin, (possibly a water molecule). The refined hexagonal unit cell parameters from the neutron diffraction data were a=9.3446(3)A and c=6.9199(4)A.