BACKGROUND: Methylation of serotonin-related genes has been proposed as a plausible gene-by-environment link which may mediate environmental stress, depressive and anxiety symptoms. DNA methylation is often measured in blood cells, but little is known about the association between this peripheral epigenetic modification and brain serotonergic architecture. Here, we evaluated the association between whole-blood-derived methylation of four CpG sites in the serotonin transporter (SLC6A4) and six CpG sites of the tryptophan hydroxylase 2 (TPH2) gene and in-vivo brain levels of serotonin transporter (5-HTT) and serotonin 4 receptor (5-HT4) in a cohort of healthy individuals (N = 254) and, for 5-HT4, in a cohort of unmedicated patients with depression (N = 90). To do so, we quantified SLC6A4/TPH2 methylation using bisulfite pyrosequencing and estimated brain 5-HT4 and 5-HTT levels using positron emission tomography. In addition, we explored the association between SLC6A4 and TPH2 methylation and measures of early life and recent stress, depressive and anxiety symptoms on 297 healthy individuals.
RESULTS: We found no statistically significant association between peripheral DNA methylation and brain markers of serotonergic neurotransmission in patients with depression or in healthy individuals. In addition, although SLC6A4 CpG2 (chr17:30,236,083) methylation was marginally associated with the parental bonding inventory overprotection score in the healthy cohort, statistical significance did not remain after accounting for blood cell heterogeneity.
CONCLUSIONS: We suggest that findings on peripheral DNA methylation in the context of brain serotonin-related features should be interpreted with caution. More studies are needed to rule out a role of SLC6A4 and TPH2 methylation as biomarkers for environmental stress, depressive or anxiety symptoms.

Photoacoustic tomography (PAT) is a newly developed medical imaging modality, which combines the advantages of pure optical imaging and ultrasound imaging, owning both high optical contrast and deep penetration depth. Very recently, PAT is studied in human brain imaging. Nevertheless, while ultrasound waves are passing through the human skull tissues, the strong acoustic attenuation and aberration will happen, which causes photoacoustic signals\' distortion. In this work, we use 180 T1 weighted magnetic resonance imaging (MRI) human brain volumes along with the corresponding magnetic resonance angiography (MRA) brain volumes, and segment them to generate the 2D human brain numerical phantoms for PAT. The numerical phantoms contain six kinds of tissues, which are scalp, skull, white matter, gray matter, blood vessel and cerebrospinal fluid. For every numerical phantom, Monte-Carlo based optical simulation is deployed to obtain the photoacoustic initial pressure based on optical properties of human brain. Then, two different k-wave models are used for the skull-involved acoustic simulation, which are fluid media model and viscoelastic media model. The former one only considers longitudinal wave propagation, and the latter model takes shear wave into consideration. Then, the PA sinograms with skull-induced aberration is taken as the input of U-net, and the skull-stripped ones are regarded as the supervision of U-net to train the network. Experimental result shows that the skull\'s acoustic aberration can be effectively alleviated after U-net correction, achieving conspicuous improvement in quality of PAT human brain images reconstructed from the corrected PA signals, which can clearly show the cerebral artery distribution inside the human skull.

In this letter, we evaluate antenna designs for ultra-high frequency and field (UHF) human brain magnetic resonance imaging (MRI) at 10.5 tesla (T). Although MRI at such UHF is expected to provide major signal-to-noise gains, the frequency of interest, 447 MHz, presents us with challenges regarding improved B1 + efficiency, image homogeneity, specific absorption rate (SAR), and antenna element decoupling for array configurations. To address these challenges, we propose the use of both monopole and dipole antennas in a novel hybrid configuration, which we refer to as a mono-dipole hybrid antenna (MDH) array. Compared to an 8-channel dipole antenna array of the same dimensions, the 8-channel MDH array showed an improvement in decoupling between adjacent array channels, as well as ~18% higher B1 + and SAR efficiency near the central region of the phantom based on simulation and experiment. However, the performances of the MDH and dipole antenna arrays were overall similar when evaluating a human model in terms of peak B1 + efficiency, 10 g SAR, and SAR efficiency. Finally, the concept of an MDH array showed an advantage in improved decoupling, SAR, and B1 + near the superior region of the brain for human brain imaging.

Three-dimensional (3-D) super-resolution microwave imaging of human brain is a typical electromagnetic (EM) inverse scattering problem with high contrast. It is a challenge for the traditional schemes based on deterministic or stochastic inversion methods to obtain high contrast and high resolution, and they require huge computational time. In this work, a dual-module 3-D EM inversion scheme based on deep neural network is proposed. The proposed scheme can solve the inverse scattering problems with high contrast and super-resolution in real time and reduce a huge computational cost. In the EM inversion module, a 3-D full convolution EM reconstruction neural network (3-D FCERNN) is proposed to nonlinearly map the measured scattered field to a preliminary image of 3-D electrical parameter distribution of the human brain. The proposed 3-D FCERNN is completely composed of convolution layers, which can greatly save training cost and improve model generalization compared with fully connected networks. Then, the image enhancement module employs a U-Net to further improve the imaging quality from the results of 3-D FCERNN. In addition, a dataset generation strategy based on the human brain features is proposed, which can solve the difficulty of human brain dataset collection and high training cost. The proposed scheme has been confirmed to be effective and accurate in reconstructing the distribution of 3-D super-resolution electrical parameters distribution of human brain through noise-free and noisy examples, while the traditional EM inversion method is difficult to converge in the case of high contrast and strong scatterers. Compared with our previous work, the training of FCERNN is faster and can significantly decrease computational resources.

Magnetoencephalography (MEG) measures the small magnetic fields generated by current flow in neural networks, providing a noninvasive metric of brain function. MEG is well established as a powerful neuroscientific and clinical tool. However, current instrumentation is hampered by cumbersome cryogenic field-sensing technologies. In contrast, MEG using optically pumped magnetometers (OPM-MEG) employs small, lightweight, noncryogenic sensors that provide data with higher sensitivity and spatial resolution, a natural scanning environment (including participant movement), and adaptability to any age. However, OPM-MEG is new and the optimum way to design a system is unknown. Here, we construct a novel, 90-channel triaxial OPM-MEG system and use it to map motor function during a naturalistic handwriting task. Results show that high-precision magnetic field control reduced background fields to ∼200 pT, enabling free participant movement. Our triaxial array offered twice the total measured signal and better interference rejection compared to a conventional (single-axis) design. We mapped neural oscillatory activity to the sensorimotor network, demonstrating significant differences in motor network activity and connectivity for left-handed versus right-handed handwriting. Repeatability across scans showed that we can map electrophysiological activity with an accuracy ∼4 mm. Overall, our study introduces a novel triaxial OPM-MEG design and confirms its potential for high-performance functional neuroimaging.

Significance: By incorporating multiple overlapping functional near-infrared spectroscopy (fNIRS) measurements, high-density diffuse optical tomography (HD-DOT) images human brain function with fidelity comparable to functional magnetic resonance imaging (fMRI). Previous work has shown that frequency domain high-density diffuse optical tomography (FD-HD-DOT) may further improve image quality over more traditional continuous wave (CW) HD-DOT. Aim: The effects of modulation frequency on image quality as obtainable with FD-HD-DOT is investigated through simulations with a realistic noise model of functional activations in human head models, arising from 11 source modulation frequencies between CW and 1000 MHz. Approach: Simulations were performed using five representative head models with an HD regular grid of 158 light sources and 166 detectors and an empirically derived noise model. Functional reconstructions were quantitatively assessed with multiple image quality metrics including the localization error (LE), success rate, full width at half maximum, and full volume at half maximum (FVHM). All metrics were evaluated against CW-based models. Results: Compared to CW, localization accuracy is improved by >40% throughout brain depths of 13 to 25 mm below the surface with 300 to 500 MHz modulation frequencies. Additionally, the reliable field of view in brain tissue is enlarged by 35% to 48% within an optimal frequency of 300 MHz after considering realistic noise, depending on the dynamic range of the system. Conclusions: These results point to the tremendous opportunities in further development of high bandwidth FD-HD-DOT system hardware for applications in human brain mapping.

Alterations to cerebral white matter tracts have been associated with cognitive decline in aging and Alzheimer\'s disease (AD). In particular, the fornix has been implicated as especially vulnerable given that it represents the primary outflow tract of the hippocampus. Despite this, little work has focused on the fornix using a potential early marker of white matter degeneration-myelin water fraction (MWF; an in vivo marker of myelin content). Therefore, we sought to (1) clarify associations between MWF in the fornix and memory functioning, and (2) examine whether fornix MWF relates to memory performance above and beyond hippocampal volume and conventional imaging measures of white matter that may not be as specific to alterations in myelin content. Forty nondemented older adults (mean age = 72.9 years) underwent an MRI exam and neuropsychological assessment. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) was used to quantify fornix MWF and diffusion tensor imaging (DTI) was used to measure fornix fractional anisotropy (FA). Adjusting for age, sex, education, and vascular risk factors, linear regression models revealed that, lower fornix MWF was significantly associated with poorer memory functioning (β = 0.405, p = .007) across our sample of older adults. Notably, fornix MWF remained a significant predictor of memory functioning (β = 0.380, p = .015) even after adjusting for fornix DTI FA and hippocampal volume (in addition to the above covariates). Given the observed associations between myelin and memory in older adults without dementia, MWF may be a useful early marker of dementia risk.

Three-dimensional (3D) Magnetic resonance fingerprinting (MRF) permits whole-brain volumetric quantification of T1 and T2 relaxation values, potentially replacing conventional T1-weighted structural imaging for common brain imaging analysis. The aim of this study was to evaluate the repeatability and reproducibility of 3D MRF in evaluating brain cortical thickness and subcortical volumetric analysis in healthy volunteers using conventional 3D T1-weighted images as a reference standard. Scan-rescan tests of both 3D MRF and conventional 3D fast spoiled gradient recalled echo (FSPGR) were performed. For each sequence, the regional cortical thickness and volume of the subcortical structures were measured using standard automatic brain segmentation software. Repeatability and reproducibility were assessed using the within-subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), and mean percent difference and ICC, respectively. The wCV and ICC of cortical thickness were similar across all regions with both 3D MRF and FSPGR. The percent relative difference in cortical thickness between 3D MRF and FSPGR across all regions was 8.0 ± 3.2%. The wCV and ICC of the volume of subcortical structures across all structures were similar between 3D MRF and FSPGR. The percent relative difference in the volume of subcortical structures between 3D MRF and FSPGR across all structures was 7.1 ± 3.6%. 3D MRF measurements of human brain cortical thickness and subcortical volumes are highly repeatable, and consistent with measurements taken on conventional 3D T1-weighted images. A slight, consistent bias was evident between the two, and thus careful attention is required when combining data from MRF and conventional acquisitions.

Metadata are what makes databases searchable. Without them, researchers would have difficulty finding data with features they are interested in. Brain imaging genetics is at the intersection of two disciplines, each with dedicated dictionaries and ontologies facilitating data search and analysis. Here, we present the genetics Brain Imaging Data Structure extension, consisting of metadata files for human brain imaging data to which they are linked, and describe succinctly the genomic and transcriptomic data associated with them, which may be in different databases. This extension will facilitate identifying micro-scale molecular features that are linked to macro-scale imaging repositories, facilitating data aggregation across studies.

Imagine you were asked to investigate the workings of an engine, but to do so without ever opening the hood. Now imagine the engine fueled the human mind. This is the challenge faced by cognitive neuroscientists worldwide aiming to understand the neural bases of our psychological functions. Luckily, human ingenuity comes to the rescue. Around the same time as the Society for Neuroscience was being established in the 1960s, the first tools for measuring the human brain at work were becoming available. Noninvasive human brain imaging and neurophysiology have continued developing at a relentless pace ever since. In this 50 year anniversary, we reflect on how these methods have been changing our understanding of how brain supports mind.