Granger causality analysis has been suggested as a method of estimating causal modulation without specifying the direction of information flow a priori. Using BOLD-contrast functional MRI (fMRI) ...data, such analysis has been typically implemented in the time domain. In this study, we used magnetic resonance inverse imaging, a method of fast fMRI enabled by massively parallel detection allowing up to 10 Hz sampling rate, to investigate the causal modulation at different frequencies up to 5 Hz. Using a visuomotor two-choice reaction-time task, both the spectral decomposition of Granger causality and isolated effective coherence revealed that the BOLD signal at frequency up to 3 Hz can still be used to estimate significant dominant directions of information flow consistent with results from the time-domain Granger causality analysis. We showed the specificity of estimated dominant directions of information flow at high frequencies by contrasting causality estimates using data collected during the visuomotor task and resting state. Our data suggest that hemodynamic responses carry physiological information related to inter-regional modulation at frequency higher than what has been commonly considered.
The blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal is a robust surrogate for local neuronal activity. However, it has been shown to vary substantially across subjects, brain ...regions, and repetitive measurements. This variability represents a limit to the precision of the BOLD response and the ability to reliably discriminate brain hemodynamic responses elicited by external stimuli or behavior that are nearby in time. While the temporal variability of the BOLD signal at human visual cortex has been found in the range of a few hundreds of milliseconds, the spatial distributions of the average and standard deviation of this temporal variability have not been quantitatively characterized. Here we use fMRI measurements with a high sampling rate (10Hz) to map the latency, intra- and inter-subject variability of the evoked BOLD signal in human primary (V1) visual cortices using an event-related fMRI paradigm. The latency relative to the average BOLD signal evoked by 30 stimuli was estimated to be 0.03±0.20s. Within V1, the absolute value of the relative BOLD latency was found correlated to intra- and inter-subject temporal variability. After comparing these measures to retinotopic maps, we found that locations with V1 areas sensitive to smaller eccentricity have later responses and smaller inter-subject variabilities. These correlations were found from data with either short inter-stimulus interval (ISI; average 4s) or long ISI (average 30s). Maps of the relative latency as well as inter-/intra-subject variability were found visually asymmetric between hemispheres. Our results suggest that the latency and variability of regional BOLD signal measured with high spatiotemporal resolution may be used to detect regional differences in hemodynamics to inform fMRI studies. However, the physiological origins of timing index distributions and their hemispheric asymmetry remain to be investigated.
•The BOLD latency and variability was measured with 0.1s precision.•The latency of the V1 BOLD signal evoked from 30 trials was 0.03±0.20s.•Smaller eccentricity locations have larger latency•Smaller eccentricity locations have smaller inter-subject variability.
Seeing the articulatory gestures of the speaker ("speech reading") enhances speech perception especially in noisy conditions. Recent neuroimaging studies tentatively suggest that speech reading ...activates speech motor system, which then influences superior-posterior temporal lobe auditory areas via an efference copy. Here, nineteen healthy volunteers were presented with silent videoclips of a person articulating Finnish vowels /a/, /i/ (non-targets), and /o/ (targets) during event-related functional magnetic resonance imaging (fMRI). Speech reading significantly activated visual cortex, posterior fusiform gyrus (pFG), posterior superior temporal gyrus and sulcus (pSTG/S), and the speech motor areas, including premotor cortex, parts of the inferior (IFG) and middle (MFG) frontal gyri extending into frontal polar (FP) structures, somatosensory areas, and supramarginal gyrus (SMG). Structural equation modelling (SEM) of these data suggested that information flows first from extrastriate visual cortex to pFS, and from there, in parallel, to pSTG/S and MFG/FP. From pSTG/S information flow continues to IFG or SMG and eventually somatosensory areas. Feedback connectivity was estimated to run from MFG/FP to IFG, and pSTG/S. The direct functional connection from pFG to MFG/FP and feedback connection from MFG/FP to pSTG/S and IFG support the hypothesis of prefrontal speech motor areas influencing auditory speech processing in pSTG/S via an efference copy.
Inverse imaging (InI) supercharges the sampling rate of traditional functional MRI 10–100 fold at a cost of a moderate reduction in spatial resolution. The technique is inspired by similarities ...between multi-sensor magnetoencephalography (MEG) and highly parallel radio-frequency (RF) MRI detector arrays. Using presently available 32-channel head coils at 3T, InI can be sampled at 10Hz and provides about 5-mm cortical spatial resolution with whole-brain coverage. Here we discuss the present applications of InI, as well as potential future challenges and opportunities in further improving its spatiotemporal resolution and sensitivity. InI may become a helpful tool for clinicians and neuroscientists for revealing the complex dynamics of brain functions during task-related and resting states.
Freestanding graphene-edge probes for scanning tunneling microscopy were demonstrated. Graphene was prepared on a Cu wire by thermal chemical vapor deposition (CVD) from solid carbon sources. Follow ...by a mechanical cutting process which was controlled by a micromanipulator and an optical microscope. The freestanding graphene probes were then fabricated. Our previous study of electron emission patterns from a field emission microscope demonstrated the layered structure of the graphene edge. We found that a single-layer of graphene emitted electrons comes from a limited number of atoms only when the graphene probe was conditioning carefully to achieve a stable emission current. In this research, we applied such activated graphene probes for use in scanning tunneling microscopes for surface morphology detection. The preconditioned, multi-layer graphene probe presented well resolution that was comparable to conventional Pt-Ir probes. Our study generated a practical method for applying individual freestanding graphene for surface probe microscopy with a cost effective process.
In this paper, a theory of lexicographic optimization for convex and compact feasible sets is presented. Existence, globality, unimodality, and uniqueness of the solution to the problem are proved. ...Also, necessary and sufficient conditions are derived that establish the relationship between the lexicographic problem and the maxmin problem. This framework is shown to be useful in the problem of designing flow control protocols. Towards this objective, a theory of bottleneck ordering is introduced, which unveils the convergence properties of the flow control problem.
Entry into tertiary education is a critical juncture where adolescents proceed to adulthood. This study aimed to determine the prevalence of depression and anxiety, and factors associated with such ...symptoms, among university undergraduate students in Hong Kong.
A cross-sectional questionnaire study was employed. A total of 1200 undergraduate students from eight University Grants Committee-funded universities were invited to complete three sets of questionnaires, including the 9-item patient health questionnaire for screening of depressive symptoms, the 7-item generalised anxiety disorder scale for screening of anxiety symptoms, and a socio-demographic questionnaire.
Among the valid responses (n=1119) analysed, 767 (68.5%) respondents indicated mild to severe depressive symptoms, which were associated with mild to severe anxiety symptoms. Several lifestyle and psychosocial variables, including regular exercise, self-confidence, satisfaction with academic performance, and optimism towards the future were inversely related with mild to severe depressive symptoms. A total of 599 (54.4%) respondents indicated mild to severe anxiety symptoms, which were associated with level of academic difficulty. Satisfaction with friendship, sleep quality, and self-confidence were inversely associated with mild to severe anxiety symptoms.
More than 50% of respondents expressed some degree of depressive and anxiety symptoms (68.5% and 54.4%, respectively). Approximately 9% of respondents exhibited moderately severe to severe depressive symptoms; 5.8% exhibited severe anxiety symptoms. Respondents reporting regular exercise, higher self-confidence, and better satisfaction with both friendship and academic performance had fewer depressive and anxiety symptoms.
To evaluate the contribution of germline genetics to regulating the briskness and diversity of T cell responses in CRC, we conducted a genome-wide association study to examine the associations ...between germline genetic variation and quantitative measures of T cell landscapes in 2,876 colorectal tumors from participants in the Molecular Epidemiology of Colorectal Cancer Study (MECC).
Germline DNA samples were genotyped and imputed using genome-wide arrays. Tumor DNA samples were extracted from paraffin blocks, and T cell receptor clonality and abundance were quantified by immunoSEQ (Adaptive Biotechnologies, Seattle, WA). Tumor infiltrating lymphocytes per high powered field (TILs/hpf) were scored by a gastrointestinal pathologist. Regression models were used to evaluate the associations between each variant and the three T-cell features, adjusting for sex, age, genotyping platform, and global ancestry. Three independent datasets were used for replication.
We identified a SNP (rs4918567) near RBM20 associated with clonality at a genome-wide significant threshold of 5 × 10
, with a consistent direction of association in both discovery and replication datasets. Expression quantitative trait (eQTL) analyses and in silico functional annotation for these loci provided insights into potential functional roles, including a statistically significant eQTL between the T allele at rs4918567 and higher expression of ADRA2A (P = 0.012) in healthy colon mucosa.
Our study suggests that germline genetic variation is associated with the quantity and diversity of adaptive immune responses in CRC. Further studies are warranted to replicate these findings in additional samples and to investigate functional genomic mechanisms.
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