Local Variational Principle

A generalization of the Gibbs-Bogoliubov-Feynman inequality for spinless particles is proven and then illustrated for the simple model of a symmetric double-well quartic potential. The method gives a pointwise lower bound for the finite-temperature density matrix and it can be systematically improved by the Trotter composition rule. It is also shown to produce groundstate energies better than the ones given by the Rayleigh-Ritz principle as applied to the groundstate eigenfunctions of the reference potentials. Based on this observation, it is argued that the Local Variational Principle performs better than the equivalent methods based on the centroid path idea and on the Gibbs-Bogoliubov-Feynman variational principle, especially in the range of low temperatures.Comment: 15 pages, 5 figures, one more section adde

nnResting state fMRI scanner instabilities revealed by longitud inal phantom scans in a multi-center study

Quality assurance (QA) is crucial in longitudinal and/or multi-site studies, which involve the collection of data from a group of subjects over time and/or at different locations. It is important to regularly monitor the performance of the scanners over time and at different locations to detect and control for intrinsic differences (e.g., due to manufacturers) and changes in scanner performance (e.g., due to gradual component aging, software and/or hardware upgrades, etc.). As part of the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Canadian Biomarker Integration Network in Depression (CAN-BIND), QA phantom scans were conducted approximately monthly for three to four years at 13 sites across Canada with 3T research MRI scanners. QA parameters were calculated for each scan using the functional Biomarker Imaging Research Network\u27s (fBIRN) QA phantom and pipeline to capture between- and within-scanner variability. We also describe a QA protocol to measure the full-width-at-half-maximum (FWHM) of slice-wise point spread functions (PSF), used in conjunction with the fBIRN QA parameters. Variations in image resolution measured by the FWHM are a primary source of variance over time for many sites, as well as between sites and between manufacturers. We also identify an unexpected range of instabilities affecting individual slices in a number of scanners, which may amount to a substantial contribution of unexplained signal variance to their data. Finally, we identify a preliminary preprocessing approach to reduce this variance and/or alleviate the slice anomalies, and in a small human data set show that this change in preprocessing can have a significant impact on seed-based connectivity measurements for some individual subjects. We expect that other fMRI centres will find this approach to identifying and controlling scanner instabilities useful in similar studies

A Multi-Modal MRI Analysis of Cortical Structure in Relation to Gender Dysphoria, Sexual Orientation, and Age in Adolescents.

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Sex-differentiated brain regions are hypothesized to reflect the experienced gender in GD and may play a role in sexual orientation development. Magnetic resonance brain images were acquired from 16 GD adolescents assigned female at birth (AFAB) not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12-17 years) to examine three morphological and microstructural gray matter features in 76 brain regions: surface area (SA), cortical thickness (CT), and T1 relaxation time. Sexual orientation was represented by degree of androphilia-gynephilia and sexual attraction strength. Multivariate analyses found that cisgender boys had larger SA than cisgender girls and GD AFAB. Shorter T1, reflecting denser, macromolecule-rich tissue, correlated with older age and stronger gynephilia in cisgender boys and GD AFAB, and with stronger attractions in cisgender boys. Thus, cortical morphometry (mainly SA) was related to sex assigned at birth, but not experienced gender. Effects of experienced gender were found as similarities in correlation patterns in GD AFAB and cisgender boys in age and sexual orientation (mainly T1), indicating the need to consider developmental trajectories and sexual orientation in brain studies of GD

Quantitative examination of a novel clustering method using magnetic resonance diffusion tensor tractography

MR diffusion tensor imaging (DTI) can measure and visualize organization of white matter fibre tracts in vivo. DTI is a relatively new imaging technique, and new tools developed for quantifying fibre tracts require evaluation. The purpose of this study was to compare the reliability of a novel clustering approach with a multiple region of interest (MROI) approach in both healthy and disease (schizophrenia) populations. DTI images were acquired in 20 participants (n=10 patients with schizophrenia: 56 ± 15 years; n=10 controls: 51 ± 20 years) (1.5 Tesla GE system) with diffusion gradients applied in 23 non-collinear directions, repeated three times. Whole brain seeding and creation of fibre tracts were then performed. Interrater reliability of the clustering approach, and the MROI approach, were each evaluated and the methods compared. There was high spatial (voxel-based) agreement within and between the clustering and MROI methods. Fractional anisotropy, trace, and radial and axial diffusivity values showed high intraclass correlation (p<0.001 for all tracts) for each approach. Differences in scalar indices of diffusion between the clustering and MROI approach were minimal. The excellent interrater reliability of the clustering method and high agreement with the MROI method, quantitatively and spatially, indicates that the clustering method can be used with confidence. The clustering method avoids biases of ROI drawing and placement, and, not limited by a priori predictions, may be a more robust and efficient way to identify and measure white matter tracts of interest

Predictors of variation in serum IGF1 and IGFBP3 levels in healthy African American and white men.

Background—Individual variation in circulating insulin-like growth factor-I (IGF1) and its major binding protein, insulin-like growth factor binding protein-3 (IGFBP3) have been etiologically linked to several chronic diseases, including some cancers. Factors associated with variation in circulating levels of these peptide hormones remain unclear. Methods—Multiple linear regression models were used to determine the extent to which sociodemographic characteristics, lifestyle factors, personal and family history of chronic disease, and common genetic variants, the (CA)n repeat polymorphism in the IGF1 promoter and the IGFBP3 -202 A/C polymorphism (rs2854744) predict variation in IGF1 or IGFBP3 serum levels in 33 otherwise healthy African American and 37 white males recruited from Durham Veterans Administration Medical Center. Results—Predictors of serum IGF1, IGFBP3 and the IGF1:IGFBP3 molar ratio varied by race. In African Americans, 17% and 28% of the variation in serum IGF1 and the IGF1:IGFBP3 molar ratio, respectively, was explained by cigarette smoking and carrying the IGF1 (CA)19 repeat allele, respectively. Not carrying at least one IGF1 (CA)19 repeat allele and a high BMI explained 8% and 14%, respectively, of the variation IGFBP3 levels. These factors did not predict variation of these peptides in whites. Conclusion—If successfully replicated in larger studies, these findings add to recent evidence suggesting known genetic and lifestyle chronic disease risk factors influence IGF1 and IGFBP3 circulating levels differently in African Americans and whites

Extracting Message Inter-Departure Time Distributions from the Human Electroencephalogram

The complex connectivity of the cerebral cortex is a topic of much study, yet the link between structure and function is still unclear. The processing capacity and throughput of information at individual brain regions remains an open question and one that could potentially bridge these two aspects of neural organization. The rate at which information is emitted from different nodes in the network and how this output process changes under different external conditions are general questions that are not unique to neuroscience, but are of interest in multiple classes of telecommunication networks. In the present study we show how some of these questions may be addressed using tools from telecommunications research. An important system statistic for modeling and performance evaluation of distributed communication systems is the time between successive departures of units of information at each node in the network. We describe a method to extract and fully characterize the distribution of such inter-departure times from the resting-state electroencephalogram (EEG). We show that inter-departure times are well fitted by the two-parameter Gamma distribution. Moreover, they are not spatially or neurophysiologically trivial and instead are regionally specific and sensitive to the presence of sensory input. In both the eyes-closed and eyes-open conditions, inter-departure time distributions were more dispersed over posterior parietal channels, close to regions which are known to have the most dense structural connectivity. The biggest differences between the two conditions were observed at occipital sites, where inter-departure times were significantly more variable in the eyes-open condition. Together, these results suggest that message departure times are indicative of network traffic and capture a novel facet of neural activity

Re-imagining the future:repetition decreases hippocampal involvement in future simulation

Imagining or simulating future events has been shown to activate the anterior right hippocampus (RHC) more than remembering past events does. One fundamental difference between simulation and memory is that imagining future scenarios requires a more extensive constructive process than remembering past experiences does. Indeed, studies in which this constructive element is reduced or eliminated by “pre-imagining” events in a prior session do not report differential RHC activity during simulation. In this fMRI study, we examined the effects of repeatedly simulating an event on neural activity. During scanning, participants imagined 60 future events; each event was simulated three times. Activation in the RHC showed a significant linear decrease across repetitions, as did other neural regions typically associated with simulation. Importantly, such decreases in activation could not be explained by non-specific linear time-dependent effects, with no reductions in activity evident for the control task across similar time intervals. Moreover, the anterior RHC exhibited significant functional connectivity with the whole-brain network during the first, but not second and third simulations of future events. There was also evidence of a linear increase in activity across repetitions in right ventral precuneus, right posterior cingulate and left anterior prefrontal cortex, which may reflect source recognition and retrieval of internally generated contextual details. Overall, our findings demonstrate that repeatedly imagining future events has a decremental effect on activation of the hippocampus and many other regions engaged by the initial construction of the simulation, possibly reflecting the decreasing novelty of simulations across repetitions, and therefore is an important consideration in the design of future studies examining simulation

Impaired Structural Connectivity of Socio-Emotional Circuits in Autism Spectrum Disorders: A Diffusion Tensor Imaging Study

Abnormal white matter development may disrupt integration within neural circuits, causing particular impairments in higher-order behaviours. In autism spectrum disorders (ASDs), white matter alterations may contribute to characteristic deficits in complex socio-emotional and communication domains. Here, we used diffusion tensor imaging (DTI) and tract based spatial statistics (TBSS) to evaluate white matter microstructure in ASD.DTI scans were acquired for 19 children and adolescents with ASD (∼8-18 years; mean 12.4±3.1) and 16 age and IQ matched controls (∼8-18 years; mean 12.3±3.6) on a 3T MRI system. DTI values for fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity, were measured. Age by group interactions for global and voxel-wise white matter indices were examined. Voxel-wise analyses comparing ASD with controls in: (i) the full cohort (ii), children only (≤12 yrs.), and (iii) adolescents only (>12 yrs.) were performed, followed by tract-specific comparisons. Significant age-by-group interactions on global DTI indices were found for all three diffusivity measures, but not for fractional anisotropy. Voxel-wise analyses revealed prominent diffusion measure differences in ASD children but not adolescents, when compared to healthy controls. Widespread increases in mean and radial diffusivity in ASD children were prominent in frontal white matter voxels. Follow-up tract-specific analyses highlighted disruption to pathways integrating frontal, temporal, and occipital structures involved in socio-emotional processing.Our findings highlight disruption of neural circuitry in ASD, particularly in those white matter tracts that integrate the complex socio-emotional processing that is impaired in this disorder

Analysis of two methods of isometric muscle contractions during the anti-G straining maneuver

This study investigated the difference in Mean Arterial Pressure (MAP) and Cardiac Output (CO) between two methods of isometric muscle contractions during the Anti-G Straining Maneuver (AGSM). 12 subjects (ages 18 to 38 yrs, height 176.8 +/- 7.4 cm, body mass 78.8 +/- 15.6 kg, percent body fat 14.3 +/- 6.6%) participated in the study. The study was a one-way within-subject design with test conditions counterbalanced. Two methods of isometric muscle contractions lasting 30 seconds each were assessed; an isometric push contraction and an isometric muscle tensing contraction. The dependent parameters were MAP and CO. The average MAP during the push contraction was 123 mmHg, SD +/- 11 and for tense was 118 mmHg, SD +/- 8. CO was 7.6 L/min, SD +/- 1.6 for push and 7.9 L/min, SD +/- 2.0 for tense method. Dependent t-tests revealed t(11) = 1.517, p = 0.157 for MAP and t(11) = 0.875, p = 0.400 for CO. This study demonstrated that the two methods of isometric muscle contractions were not statistically different with regards to MAP and CO. Therefore, both forms of isometric contractions may be potentially useful when performing the muscle contraction portion of the AGSM