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It is shown on the examples of Moore and Gosper curves that two spatially shifted or twisted, preasymptotic space-filling curves can produce large-scale superstructures akin to moiré patterns. To study physical phenomena emerging from these patterns, a geometrical coupling coefficient based on the Neumann integral is introduced. It is found that moiré patterns appear most defined at the peaks of those coefficients. A physical interpretation of these coefficients as a measure for inductive coupling between radiofrequency resonators leads to a design principle for strongly overlapping resonators with vanishing mutual inductance, which might be interesting for applications in MRI. These findings are demonstrated in graphical, numerical, and physical experiments.

Magnetic resonance imaging (MRI) has emerged as a promising technique for non-invasive medical imaging. The primary challenge in MRI is the trade-off between image visual quality and acquisition time. Current MRI image denoising algorithms employ global thresholding to denoise the whole image, which leads to inadequate denoising or image distortion. This study introduces a novel pixel-wise (localized) thresholding approach of singular vectors, obtained from singular value decomposition, to denoise magnetic resonance (MR) images. The pixel-wise thresholding of singular vectors is performed using separate singular values as thresholds at each pixel, which is advantageous given the spatial noise variation throughout the image. The method presented is validated on MR images of a standard phantom approved by the magnetic resonance accreditation program (MRAP). The denoised images display superior visual quality and recover minute structural information otherwise suppressed in the noisy image. The increase in peak-signal-to-noise-ratio (PSNR) and contrast-to-noise-ratio (CNR) values of $\ge 18\%$ and $\ge 200\%$ of the denoised images, respectively, imply efficient noise removal and visual quality enhancement. The structural similarity index (SSIM) of $\ge 0.95$ for denoised images indicates that the crucial structural information is recovered through the presented method. A comparison with the standard filtering methods widely used for MRI denoising establishes the superior performance of the presented method. The presented pixel-wise denoising technique reduces the scan time by 2-3 times and has the potential to be integrated into any MRI system to obtain faster and better quality images.

Purpose: To evaluate the phenomenological significance of cerebral blood pulsatility imaging in aging research. Methods: N = 38 subjects from 20 to 72 years of age (24 females) were imaged with ultrafast MRI with a sampling rate of 100 ms and simultaneous acquisition of pulse oximetry data. Of these, 28 subjects had acceptable MRI and pulse data, with 16 subjects between 20 and 28 years of age, and 12 subjects between 61 and 72 years of age. Pulse amplitude in the circle of Willis was assessed with the recently developed method of analytic phase projection to extract blood volume waveforms. Results: Arteries in the circle of Willis showed pulsatility in the MRI for both the young and old age groups. Pulse amplitude in the circle of Willis significantly increased with age (p = 0.01) but was independent of gender, heart rate, and head motion during MRI. Discussion and conclusion: Increased pulse wave amplitude in the circle of Willis in the elderly suggests a phenomenological significance of cerebral blood pulsatility imaging in aging research. The physiologic origin of increased pulse amplitude (increased pulse pressure vs. change in arterial morphology vs. re-shaping of pulse waveforms caused by the heart, and possible interaction with cerebrospinal fluid pulsatility) requires further investigation.

Magnetic resonance guided focused ultrasound (MRgFUS) is a non-invasive therapeutic modality for neurodegenerative diseases that employs real-time imaging and thermometry monitoring of targeted regions. MRI is used in guidance of ultrasound treatment; however, the MR image quality in current clinical applications is poor when using the vendor built-in body coil. We present an 8-channel, ultra-thin, flexible, and acoustically transparent receive-only head coil design (FUS-Flex) to improve the signal-to-noise ratio (SNR) and thus the quality of MR images during MRgFUS procedures. Acoustic simulations/experiments exhibit transparency of the FUS-Flex coil as high as 97% at 650 kHz. Electromagnetic simulations show a SNR increase of $13\times $ over the body coil. In vivo results show an increase of the SNR over the body coil by a factor of 7.3 with $2\times $ acceleration (equivalent to $11\times $ without acceleration) in the brain of a healthy volunteer, which agrees well with simulation. These preliminary results show that the use of a FUS-Flex coil in MRgFUS surgery can increase MR image quality, which could yield improved focal precision, real-time intraprocedural anatomical imaging, and real-time 3D thermometry mapping.

Functional connectivity measured from fMRI data is widely used in neuroscience. Here the authors report an association between two types of breathing signature and obtained BOLD data, and associated sex differences.

ApoE4 is a risk factor for small vessel disease, which can lead to cognitive impairment. Here the authors assess the microvasculature of the corpus callosum using 3-photon microscopy and find that mice expressing the ApoE4 allele are more susceptible than wild-type to white matter injury and cognitive impairment in a model of hypoperfusion-induced hypoxia.

Tanja Veselinović,1,2 Ingo Vernaleken,1,2 Paul Cumming,3,4 Uwe Henning,5 Lina Winkler,1,2 Peter Kaleta,1,2 Michael Paulzen,1,2 Christian Luckhaus,6 Gerhard Gründer1,2,7 1Department of Psychiatry, Psychotherapy, and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, 2Translational Brain Medicine, Jülich Aachen Research Alliance (JARA), Jülich, Germany; 3IHBI, School of Psychology and Counselling, Queensland University of Technology, 4QIMR Berghofer Institute, Brisbane, Australia; 5Neurobiochemical Research Unit, Department of Psychiatry, Heinrich Heine University, Düsseldorf, 6LWL University Hospital Bochum, Department of Psychiatry, Division of Cognitive Neuropsychiatry and Psychiatric Preventive Medicine, Ruhr University Bochum, Bochum, 7Department of Molecular Neuroimaging, Central Institute of Mental Health, Mannheim, Germany Objectives: Off-label prescription of antipsychotics to patients without psychotic symptoms has become a routine matter for many psychiatrists and also some general practitioners. Nonetheless, little is known about the possibly detrimental effects of antidopaminergic medications on general psychopathology, subjective mental state, or a possible association with physiological parameters in nonpsychotic individuals.Methods: In this randomized, single-blinded study, groups of healthy volunteers (n=18) received low doses of reserpine, aripiprazole, haloperidol, or placebo on 7 successive days. Relevant physiological parameters (plasma prolactin, concentrations of catecholamine metabolites in plasma, and 24-hour urine) and each subject’s mental state (Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, visual analogue scale, Beck Depression Inventory II) were assessed at the start and end of the trial.Results: Of the three active treatments, only reserpine caused a significant increase in some plasma- and urine-catecholamine metabolites, but all three medications evoked objective and subjective changes in general psychopathology scores, which correlated with individual increases in plasma homovanillic acid concentrations. Both objective and subjective impairments were significantly more pronounced in the subgroup with greatest increase of plasma prolactin. Subjects experiencing the most pronounced side effects under haloperidol, which compelled them to drop out, showed significantly higher prolactin concentration increases than those who tolerated haloperidol well.Conclusion: We found consistent associations between altered markers of dopamine transmission and several objective and subjective mental impairments in healthy volunteers after 1 week’s treatment with antidopaminergic medications. These findings should draw attention to a more intensive risk–benefit evaluation in cases of off-label prescription of antipsychotic medications. Keywords: catecholamine metabolites, HVA, prolactin, dopamine, reserpine, aripiprazole, haloperidol, off-label prescription

Transcranial stimulation of the brain can be achieved by pulses of magnetic field delivered by a large electric coil. However, application of such pulses by rapidly moving small permanent magnets could offer several advantages in terms of ease of use, safety, multifocality, and portability. We have, therefore, developed a wearable brain stimulator consisting of small neodymium magnets that are spun at high speed by electric motors mounted on a cap. Here, we describe the operation of the stimulator and present initial evidence that its stimulation of the cerebral cortex produces physiological effects. We first physically tested the electromagnetic induction pattern produced by our stimulator compared with conventional transcranial magnetic stimulation. We then recorded the effects of stimulation of the primary motor cortical representation of the intrinsic muscles of the thumb including abductor pollicis brevis (APB). We studied these effects on spontaneously occurring electromyographic fasciculation potentials or spontaneous motor unit potentials (sMUPs) known to occur in healthy adult human subjects in resting APB, and compared them with the effects of sham stimulation. We found that while a single stimulus cannot elicit a motor-evoked potential, repetitive stimulation delivered by our stimulator modulates sMUP activity. This transcranial rotating permanent magnet stimulation could, therefore, produce neuromodulation at a single or multiple closely spaced cortical sites.

The eigenvector-eigenvalue identity relates the eigenvectors of a Hermitian matrix to its eigenvalues and the eigenvalues of its principal submatrices in which the jth row and column have been removed. We show that one-dimensional arrays of coupled resonators, described by square matrices with real eigenvalues, provide simple physical systems where this formula can be applied in practice. The subsystems consist of arrays with the jth resonator removed and, thus, can be realized physically. From their spectra alone, the oscillation modes of the full system can be obtained. This principle of successive single resonator deletions is demonstrated in two experiments of coupled radio-frequency resonator arrays with greater-than-nearest-neighbor couplings in which the spectra are measured with a network analyzer. Both the Hermitian as well as a non-Hermitian case are covered in the experiments. In both cases, the experimental eigenvector estimates agree well with numerical simulations if certain consistency conditions imposed by system symmetries are taken into account. In the Hermitian case, these estimates are obtained from resonance spectra alone without knowledge of the system parameters. It remains an interesting problem of physical relevance to find conditions under which the full non-Hermitian eigenvector set can be obtained from the spectra alone.

In many songbird species, males sing to attract females and repel rivals. How can gregarious, non-territorial songbirds such as zebra finches, where females have access to numerous males, sustain monogamy? We found that the dopaminergic reward circuitry of zebra finches can simultaneously promote social cohesion and breeding boundaries. Surprisingly, in unmated males but not in females, striatal dopamine neurotransmission was elevated after hearing songs. Behaviorally too, unmated males but not females persistently exchanged mild punishments in return for songs. Song reinforcement diminished when dopamine receptors were blocked. In females, we observed song reinforcement exclusively to the mate’s song, although their striatal dopamine neurotransmission was only slightly elevated. These findings suggest that song-triggered dopaminergic activation serves a dual function in social songbirds: as low-threshold social reinforcement in males and as ultra-selective sexual reinforcement in females. Co-evolution of sexually dimorphic reinforcement systems can explain the coexistence of gregariousness and monogamy.

Blood-oxygen-level-dependent (BOLD) imaging is the most important noninvasive tool to map human brain function. It relies on local blood-flow changes controlled by neurovascular coupling effects, usually in response to some cognitive or perceptual task. In this contribution we ask if the spatiotemporal dynamics of the BOLD signal can be modeled by a conservation law. In analogy to the description of physical laws, which often can be derived from some underlying conservation law, identification of conservation laws in the brain could lead to new models for the functional organization of the brain. Our model is independent of the nature of the conservation law, but we discuss possible hints and motivations for conservation laws. For example, globally limited blood supply and local competition between brain regions for blood might restrict the large scale BOLD signal in certain ways that could be observable. One proposed selective pressure for the evolution of such conservation laws is the closed volume of the skull limiting the expansion of brain tissue by increases in blood volume. These ideas are demonstrated on a mental motor imagery fMRI experiment, in which functional brain activation was mapped in a group of volunteers imagining themselves swimming. In order to search for local conservation laws during this complex cognitive process, we derived maps of quantities resulting from spatial interaction of the BOLD amplitudes. Specifically, we mapped fluxes and sources of the BOLD signal, terms that would appear in a description by a continuity equation. Whereas we cannot present final answers with the particular analysis of this particular experiment, some results seem to be non-trivial. For example, we found that during task the group BOLD flux covered more widespread regions than identified by conventional BOLD mapping and was always increasing during task. It is our hope that these results motivate more work towards the search for conservation laws in neuroimaging experiments or at least towards imaging procedures based on spatial interactions of signals. The payoff could be new models for the dynamics of the healthy brain or more sensitive clinical imaging approaches, respectively.

The coevolutionary relationships between brood parasites and their hosts are often studied by examining the egg rejection behaviour of host species using artificial eggs. However, the traditional methods for producing artificial eggs out of plasticine, plastic, wood, or plaster-of-Paris are laborious, imprecise, and prone to human error. As an alternative, 3D printing may reduce human error, enable more precise manipulation of egg size and shape, and provide a more accurate and replicable protocol for generating artificial stimuli than traditional methods. However, the usefulness of 3D printing technology for egg rejection research remains to be tested. Here, we applied 3D printing technology to the extensively studied egg rejection behaviour of American robins, Turdus migratorius. Eggs of the robin’s brood parasites, brown-headed cowbirds, Molothrus ater, vary greatly in size and shape, but it is unknown whether host egg rejection decisions differ across this gradient of natural variation. We printed artificial eggs that encompass the natural range of shapes and sizes of cowbird eggs, painted them to resemble either robin or cowbird egg colour, and used them to artificially parasitize nests of breeding wild robins. In line with previous studies, we show that robins accept mimetically coloured and reject non-mimetically coloured artificial eggs. Although we found no evidence that subtle differences in parasitic egg size or shape affect robins’ rejection decisions, 3D printing will provide an opportunity for more extensive experimentation on the potential biological or evolutionary significance of size and shape variation of foreign eggs in rejection decisions. We provide a detailed protocol for generating 3D printed eggs using either personal 3D printers or commercial printing services, and highlight additional potential future applications for this technology in the study of egg rejection.

How well a songbird learns a song appears to depend on the formation of a robust auditory template of its tutor's song. Using functional magnetic resonance neuroimaging we examine auditory responses in two groups of zebra finches that differ in the type of song they sing after being tutored by birds producing stuttering-like syllable repetitions in their songs. We find that birds that learn to produce the stuttered syntax show attenuated blood oxygenation level-dependent (BOLD) responses to tutor's song, and more pronounced responses to conspecific song primarily in the auditory area field L of the avian forebrain, when compared to birds that produce normal song. These findings are consistent with the presence of a sensory song template critical for song learning in auditory areas of the zebra finch forebrain. In addition, they suggest a relationship between an altered response related to familiarity and/or saliency of song stimuli and the production of variant songs with stuttered syllables.

The relationship between anatomic connectivity of large-scale brain networks and their functional connectivity is of immense importance and an area of active research. Previous attempts have required complex simulations which model the dynamics of each cortical region, and explore the coupling between regions as derived by anatomic connections. While much insight is gained from these non-linear simulations, they can be computationally taxing tools for predicting functional from anatomic connectivities. Little attention has been paid to linear models. Here we show that a properly designed linear model appears to be superior to previous non-linear approaches in capturing the brain's long-range second order correlation structure that governs the relationship between anatomic and functional connectivities. We derive a linear network of brain dynamics based on graph diffusion, whereby the diffusing quantity undergoes a random walk on a graph. We test our model using subjects who underwent diffusion MRI and resting state fMRI. The network diffusion model applied to the structural networks largely predicts the correlation structures derived from their fMRI data, to a greater extent than other approaches. The utility of the proposed approach is that it can routinely be used to infer functional correlation from anatomic connectivity. And since it is linear, anatomic connectivity can also be inferred from functional data. The success of our model confirms the linearity of ensemble average signals in the brain, and implies that their long-range correlation structure may percolate within the brain via purely mechanistic processes enacted on its structural connectivity pathways.