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Introduction The mildly invasive 18F-fluorodeoxyglucose positron emission tomography ( FDG- PET) is a well-established imaging technique to measure 'resting state' cerebral metabolism. This technique made it possible to assess changes in metabolic activity in clinical applications, such as the study of severe brain injury and disorders of consciousness. Objective We assessed the possibility of creating functional MRI activity maps, which could estimate the relative levels of activity in FDG- PET cerebral metabolic maps. If no metabolic absolute measures can be extracted, our approach may still be of clinical use in centers without access to FDG- PET. It also overcomes the problem of recognizing individual networks of independent component selection in functional magnetic resonance imaging ( fMRI) resting state analysis. Methods We extracted resting state fMRI functional connectivity maps using independent component analysis and combined only components of neuronal origin. To assess neuronality of components a classification based on support vector machine ( SVM) was used. We compared the generated maps with the FDG- PET maps in 16 healthy controls, 11 vegetative state/unresponsive wakefulness syndrome patients and four locked-in patients. Results The results show a significant similarity with ρ = 0.75 ± 0.05 for healthy controls and ρ = 0.58 ± 0.09 for vegetative state/unresponsive wakefulness syndrome patients between the FDG- PET and the fMRI based maps. FDG- PET, fMRI neuronal maps, and the conjunction analysis show decreases in frontoparietal and medial regions in vegetative patients with respect to controls. Subsequent analysis in locked-in syndrome patients produced also consistent maps with healthy controls. Conclusions The constructed resting state fMRI functional connectivity map points toward the possibility for fMRI resting state to estimate relative levels of activity in a metabolic map. [ABSTRACT FROM AUTHOR]

Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for separating patients in a minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Among them, the auditory network was ranked the most highly. The regions of the auditory network which were more functionally connected in patients in minimally conscious state compared to vegetative state/unresponsive wakefulness syndrome encompassed bilateral auditory and visual cortices. Connectivity values in these three regions discriminated congruently 20 of 22 independently assessed patients. Our findings point to the significance of preserved abilities for multisensory integration and top-down processing in minimal consciousness seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics. [ABSTRACT FROM AUTHOR]

Objective Standard clinical characterization of patients with disorders of consciousness (DOC) relies on observation of motor output and may therefore lead to the misdiagnosis of vegetative state or minimally conscious state in patients with preserved cognition. We used conventional electroencephalographic (EEG) measures to assess a cohort of DOC patients with and without functional magnetic resonance imaging (fMRI)-based evidence of command-following, and correlated the findings with standard clinical behavioral evaluation and brain metabolic activity. Methods We enrolled 44 patients with severe brain injury. Behavioral diagnosis was established using standardized clinical assessments. Long-term EEG recordings were analyzed to determine wakeful background organization and presence of elements of sleep architecture. A subset of patients had fMRI testing of command-following using motor imagery paradigms (26 patients) and resting brain metabolism measurement using 18fluorodeoxyglucose positron emission tomography (31 patients). Results All 4 patients with fMRI evidence of covert command-following consistently demonstrated well-organized EEG background during wakefulness, spindling activity during sleep, and relative preservation of cortical metabolic activity. In the entire cohort, EEG organization and overall brain metabolism showed no significant association with bedside behavioral testing, except in a few cases when EEG was severely abnormal. Interpretation These findings suggest that conventional EEG is a simple strategy that complements behavioral and imaging characterization of DOC patients. Preservation of specific EEG features may be used to assess the likelihood of unrecognized cognitive abilities in severely brain-injured patients with very limited or no motor responses. Ann Neurol 2014;76:869-879 [ABSTRACT FROM AUTHOR]

Background Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains unknown. Abnormalities in two large-scale neuronal networks—the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)—are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response. Methods We used resting state functional magnetic resonance imaging to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a 5-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared with a cohort of 35 healthy control subjects. Results Before treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. Transcranial magnetic stimulation normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. Transcranial magnetic stimulation also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement. Conclusions Transcranial magnetic stimulation selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response. [ABSTRACT FROM AUTHOR]

Functional neuroimaging methods hold promise for the identification of cognitive function and communication capacity in some severely brain-injured patients who may not retain sufficient motor function to demonstrate their abilities. We studied seven severely brain-injured patients and a control group of 14 subjects using a novel hierarchical functional magnetic resonance imaging assessment utilizing mental imagery responses. Whereas the control group showed consistent and accurate (for communication) blood-oxygen-level-dependent responses without exception, the brain-injured subjects showed a wide variation in the correlation of blood-oxygen-level-dependent responses and overt behavioural responses. Specifically, the brain-injured subjects dissociated bedside and functional magnetic resonance imaging-based command following and communication capabilities. These observations reveal significant challenges in developing validated functional magnetic resonance imaging-based methods for clinical use and raise interesting questions about underlying brain function assayed using these methods in brain-injured subjects. [ABSTRACT FROM AUTHOR]

Mouse models are useful for studying genes involved in behavior, but whether they are relevant to human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy. [ABSTRACT FROM AUTHOR]

Abstract: Increasing the spatial resolution in functional Magnetic Resonance Imaging (fMRI) inherently lowers the signal-to-noise ratio (SNR). In order to still detect functionally significant activations in high-resolution images, spatial smoothing of the data is required. However, conventional non-adaptive smoothing comes with a reduced effective resolution, foiling the benefit of the higher acquisition resolution. We show how our recently proposed structural adaptive smoothing procedure for functional MRI data can improve signal detection of high-resolution fMRI experiments regardless of the lower SNR. The procedure is evaluated on human visual and sensory–motor mapping experiments. In these applications, the higher resolution could be fully utilized and high-resolution experiments were outperforming normal resolution experiments by means of both statistical significance and information content. [Copyright &y& Elsevier]

Background: Adolescence is a transition period from childhood to adulthood that is often characterized by emotional instability. This period is also a time of increased incidence of anxiety and depression, underscoring the importance of understanding biological substrates of behavioral and emotion regulation during adolescence. Developmental changes in the brain in concert with individual predispositions for anxiety might underlie the increased risk for poor outcomes reported during adolescence. We tested the hypothesis that difficulties in regulating behavior in emotional contexts in adolescents might be due to competition between heightened activity in subcortical emotional processing systems and immature top-down prefrontal systems. Individual differences in emotional reactivity might put some teens at greater risk during this sensitive transition in development. Methods: We examined the association between emotion regulation and frontoamygdala circuitry in 60 children, adolescents, and adults with an emotional go-nogo paradigm. We went beyond examining the magnitude of neural activity and focused on neural adaptation within this circuitry across time with functional magnetic resonance imaging. Results: Adolescents showed exaggerated amygdala activity relative to children and adults. This age-related difference decreased with repeated exposures to the stimuli, and individual differences in self-ratings of anxiety predicted the extent of adaptation or habituation in amygdala. Individuals with higher trait anxiety showed less habituation over repeated exposures. This failure to habituate was associated with less functional connectivity between ventral prefrontal cortex and amygdala. Conclusions: These findings suggest that exaggerated emotional reactivity during adolescence might increase the need for top-down control and put individuals with less control at greater risk for poor outcomes. [Copyright &y& Elsevier]

Abstract: Diffusion Tensor Imaging (DTI) data is characterized by a high noise level. Thus, estimation errors of quantities like anisotropy indices or the main diffusion direction used for fiber tracking are relatively large and may significantly confound the accuracy of DTI in clinical or neuroscience applications. Besides pulse sequence optimization, noise reduction by smoothing the data can be pursued as a complementary approach to increase the accuracy of DTI. Here, we suggest an anisotropic structural adaptive smoothing procedure, which is based on the Propagation–Separation method and preserves the structures seen in DTI and their different sizes and shapes. It is applied to artificial phantom data and a brain scan. We show that this method significantly improves the quality of the estimate of the diffusion tensor, by means of both bias and variance reduction, and hence enables one either to reduce the number of scans or to enhance the input for subsequent analysis such as fiber tracking. [Copyright &y& Elsevier]

Epilepsy is characterized by the spontaneous and unforeseeable occurrence of seizures, during which the perception or behavior of patients is disturbed. The predictability of these seizures would render novel therapeutic approaches possible. Several prediction methods have claimed to be able to predict seizures based on EEG recordings minutes in advance. However, the term seizure prediction is not unequivocally defined, different criteria to assess prediction methods exist, and only little attention has been paid to issues of sensitivity and false prediction rate. We introduce an assessment criterion called the seizure prediction characteristic that incorporates the assessment of sensitivity and false prediction rate. Within this framework, three nonlinear seizure prediction methods were evaluated on a large EEG data pool of 21 patients. Altogether, 582 h intracranial EEG data and 88 seizures were examined. With a rate of 1–3.6 false predictions per day, the “dynamical similarity index” achieves a sensitivity between 21 and 42%, which was the best result of the three methods. Sensitivity was between 18 and 31% for the extended, prospective version of the “accumulated energy” and between 13 and 30% for the “effective correlation dimension”. These results still are not sufficient for clinical applications. [Copyright &y& Elsevier]

Superconducting transformers are an important innovation for future power transmission and transportation systems. Powerful, lightweight, energy-saving and environmentally friendly they offer enormous benefits compared to their conventional counterparts. Siemens is developing a 1-MVA demonstrator transformer for laboratory testing, exhibiting innovative features like horizontal design, cabled-conductor windings and a closed cooling cycle with sub-cooled nitrogen. Being one of the most promising applications Siemens has started a programme towards the development of on-board transformers for electrical rail vehicles. This paper summarises world-wide efforts in the development of superconducting transformers and reports on the progress achieved at Siemens. [Copyright &y& Elsevier]

Summary Recent studies identify severely brain-injured patients with limited or no behavioral responses who successfully perform functional magnetic resonance imaging (fMRI) or electroencephalogram (EEG) mental imagery tasks [ 1–5 ]. Such tasks are cognitively demanding [ 1 ]; accordingly, recent studies support that fMRI command following in brain-injured patients associates with preserved cerebral metabolism and preserved sleep-wake EEG [ 5, 6 ]. We investigated the use of an EEG response that tracks the natural speech envelope (NSE) of spoken language [ 7–22 ] in healthy controls and brain-injured patients (vegetative state to emergence from minimally conscious state). As audition is typically preserved after brain injury, auditory paradigms may be preferred in searching for covert cognitive function [ 23–25 ]. NSE measures are obtained by cross-correlating EEG with the NSE. We compared NSE latencies and amplitudes with and without consideration of fMRI assessments. NSE latencies showed significant and progressive delay across diagnostic categories. Patients who could carry out fMRI-based mental imagery tasks showed no statistically significant difference in NSE latencies relative to healthy controls; this subgroup included patients without behavioral command following. The NSE may stratify patients with severe brain injuries and identify those patients demonstrating "cognitive motor dissociation" (CMD) [ 26 ] who show only covert evidence of command following utilizing neuroimaging or electrophysiological methods that demand high levels of cognitive function. Thus, the NSE is a passive measure that may provide a useful screening tool to improve detection of covert cognition with fMRI or other methods and improve stratification of patients with disorders of consciousness in research studies. Highlights • Latencies of the EEG response to the natural speech envelope were measured • Patients with disorders of consciousness showed progressive slowing of latencies • Patients capable of performing fMRI mental imagery tasks showed normal latencies • EEG speech envelope responses may help to identify cognitive motor dissociation Braiman et al. measure simultaneous EEG responses to the natural speech envelope in healthy controls and severely brain-injured patients. Latencies of EEG speech envelope responses stratify patients and identify a subgroup of patients capable of carrying out fMRI mental imagery tasks with latencies indistinguishable from those obtained in controls. [ABSTRACT FROM AUTHOR]

There is increasing reliance on magnetic resonance imaging (MRI) techniques in both research and clinical settings. However, few standardized methods exist to permit comparative studies of brain pathology and function. To help facilitate these studies, we have created a detailed, MRI-based white matter atlas of the canine brain using diffusion tensor imaging. This technique, which relies on the movement properties of water, permits the creation of a three-dimensional diffusivity map of white matter brain regions that can be used to predict major axonal tracts. To generate an atlas of white matter tracts, thirty neurologically and clinically normal dogs underwent MRI imaging under anesthesia. High-resolution, three-dimensional T1-weighted sequences were collected and averaged to create a population average template. Diffusion-weighted imaging sequences were collected and used to generate diffusivity maps, which were then registered to the T1-weighted template. Using these diffusivity maps, individual white matter tracts-including association, projection, commissural, brainstem, olfactory, and cerebellar tracts-were identified with reference to previous canine brain atlas sources. To enable the use of this atlas, we created downloadable overlay files for each white matter tract identified using manual segmentation software. In addition, using diffusion tensor imaging tractography, we created tract files to delineate major projection pathways. This comprehensive white matter atlas serves as a standard reference to aid in the interpretation of quantitative changes in brain structure and function in clinical and research settings., Competing Interests: Paul A. Taylor and Daniel R. Glen were supported by the NIMH Intramural Research Programs (ZICMH002888) of the NIH (HHS, USA)., (© 2024 The Authors. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Background: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness., Methods: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R)., Results: Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands., Conclusions: Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Despite progress in diagnosis and therapy of heart failure (HF), etiology and risk stratification remain elusive in many patients., Methods: The My Biopsy HF Study (German clinical trials register number: DRKS22178) is a retrospective monocentric study investigating an all-comer population of patients with unexplained HF based on a thorough workup including endomyocardial biopsy (EMB)., Results: 655 patients (70.9% men, median age 55 [45/66] years) with non-ischemic, non-valvular HF were included in the analyses. 489 patients were diagnosed with HF with reduced ejection fraction (HFrEF), 52 patients with HF with mildly reduced ejection fraction (HFmrEF) and 114 patients with HF with preserved ejection fraction (HFpEF). After a median follow-up of 4.6 (2.5/6.6) years, 94 deaths were enumerated (HFrEF: 68; HFmrEF: 8; HFpEF: 18), equating to mortality rates of 3.3% and 11.6% for patients with HFrEF, 7.7% and 15.4% for patients with HFmrEF and 5.3% and 11.4% for patients with HFpEF after 1 and 5 years, respectively. In EMB, we detected a variety of putative etiologies of HF, including incidental cardiac amyloidosis (CA, 5.8%). In multivariate logistic regression analysis adjusting for age, sex and comorbidities only CA, age and NYHA functional class III + IV remained independently associated with all-cause mortality (CA: HR perui 3.13, 95% CI 1.5-6.51; p = 0.002)., Conclusions: In an all-comer population of patients presenting with HF of unknown etiology, incidental finding of CA stands out to be independently associated with all-cause mortality. Our findings suggest that prospective trials would be helpful to test the added value of a systematic and holistic work-up of HF of unknown etiology., (© 2024. The Author(s).)

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The corresponding author is the inventor of patent WO 2019/199960A1, awarded to Cornell University, that describes the method of hypersampling used in this work., (© 2024 The Author(s).)

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 ≥ 18% and ≥ 200% of the denoised images, respectively, imply efficient noise removal and visual quality enhancement. The structural similarity index (SSIM) of ≥ 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.

Southern giant pouched rats ( Cricetomys ansorgei ) are a small muroid species native to the sub-Saharan Africa. Their exceptionally developed olfactory system, trainability, and relatively small size makes them useful working animals for various applications in humanitarian work. At our institution, a breeding colony of Southern giant pouched rats is maintained to study their physiology and utility as scent detectors. This case report describes the occurrence of spontaneous pituitary neoplasms with distinct clinical presentations in 2 geriatric (approximately 7.5 y old) wild-caught female Southern giant pouched rats. The first pouched rat displayed vestibular deficits, including left-sided head tilt, ataxia, disorientation, and circling. MRI revealed a large, focal heterogeneous mass arising from the pituitary fossa. The second pouched rat presented with polyuria, polydipsia, and hyperglycemia but no neurologic signs. Examination after euthanasia revealed a prolactin (PRL)-expressing pituitary carcinoma and adenoma in the first and second pouched rat, respectively, associated with mammary hyperplasia in both animals. This is the first report of spontaneous PRL-producing pituitary tumors in Southern giant pouched rats.

Niche-derived growth factors support self-renewal of mouse spermatogonial stem and progenitor cells through ERK MAPK signaling and other pathways. At the same time, dysregulated growth factor-dependent signaling has been associated with loss of stem cell activity and aberrant differentiation. We hypothesized that growth factor signaling through the ERK MAPK pathway in spermatogonial stem cells is tightly regulated within a narrow range through distinct intracellular negative feedback regulators. Evaluation of candidate extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK)-responsive genes known to dampen downstream signaling revealed robust induction of specific negative feedback regulators, including Spry4, in cultured mouse spermatogonial stem cells in response to glial cell line-derived neurotrophic factor or fibroblast growth factor 2. Undifferentiated spermatogonia in vivo exhibited high levels of Spry4 mRNA. Quantitative single-cell analysis of ERK MAPK signaling in spermatogonial stem cell cultures revealed both dynamic signaling patterns in response to growth factors and disruption of such effects when Spry4 was ablated, due to dysregulation of ERK MAPK downstream of RAS. Whereas negative feedback regulator expression decreased during differentiation, loss of Spry4 shifted cell fate toward early differentiation with concomitant loss of stem cell activity. Finally, a mouse Spry4 reporter line revealed that the adult spermatogonial stem cell population in vivo is demarcated by strong Spry4 promoter activity. Collectively, our data suggest that negative feedback-dependent regulation of ERK MAPK is critical for preservation of spermatogonial stem cell fate within the mammalian testis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Background: MRI T2 mapping has been proven to be sensitive to the level of blood oxygenation. We hypothesized that impaired exercise capacity in chronic heart failure is associated with a greater difference between right (RV) to left ventricular (LV) blood pool T2 relaxation times due to a higher level of peripheral blood desaturation, compared to patients with preserved exercise capacity and to healthy controls., Methods: Patients with chronic heart failure (n = 70) who had undergone both cardiac MRI (CMR) and a 6-min walk test (6MWT) were retrospectively identified. Propensity score matched healthy individuals (n = 35) served as control group. CMR analyses included cine acquisitions and T2 mapping to obtain blood pool T2 relaxation times of the RV and LV. Following common practice, age- and gender-adjusted nominal distances and respective percentiles were calculated for the 6MWT. The relationship between the RV/LV T2 blood pool ratio and the results from 6MWT were evaluated by Spearman's correlation coefficients and regression analyses. Inter-group differences were assessed by independent t-tests and univariate analysis of variance., Results: The RV/LV T2 ratio moderately correlated with the percentiles of nominal distances in the 6MWT (r = 0.66) while ejection fraction, end-diastolic and end-systolic volumes showed no correlation (r = 0.09, 0.07 and - 0.01, respectively). In addition, there were significant differences in the RV/LV T2 ratio between patients with and without significant post-exercise dyspnea (p = 0.001). Regression analyses showed that RV/LV T2 ratio was an independent predictor of the distance walked and the presence of post-exercise dyspnea (p < 0.001)., Conclusion: The proposed RV/LV T2 ratio, obtained by two simple measurements on a routinely acquired four-chamber T2 map, was superior to established parameters of cardiac function to predict exercise capacity and the presence of post-exercise dyspnea in patients with chronic heart failure., (© 2023. The Author(s).)

Assessing cognitive function-especially language processing-in severely brain-injured patients is critical for prognostication, care, and development of communication devices (e.g. brain-computer interfaces). In patients with diminished motor function, language processing has been probed using EEG measures of command-following in motor imagery tasks. While such tests eliminate the need for motor response, they require sustained attention. However, passive listening tasks, with an EEG response measure can reduce both motor and attentional demands. These considerations motivated the development of two assays of low-level language processing-identification of differential phoneme-class responses and tracking of the natural speech envelope. This cross-sectional study looks at a cohort of 26 severely brain-injured patient subjects and 10 healthy controls. Patients' level of function was assessed via the coma recovery scale-revised at the bedside. Patients were also tested for command-following via EEG and/or MRI assays of motor imagery. For the present investigation, EEG was recorded while presenting a 148 s audio clip of Alice in Wonderland . Time-locked EEG responses to phoneme classes were extracted and compared to determine a differential phoneme-class response. Tracking of the natural speech envelope was assessed from the same recordings by cross-correlating the EEG response with the speech envelope. In healthy controls, the dynamics of the two measures were temporally similar but spatially different: a central parieto-occipital component of differential phoneme-class response was absent in the natural speech envelope response. The differential phoneme-class response was present in all patient subjects, including the six classified as vegetative state/unresponsive wakefulness syndrome by behavioural assessment. However, patient subjects with evidence of language processing either by behavioural assessment or motor imagery tests had an early bilateral response in the first 50 ms that was lacking in patient subjects without any evidence of language processing. The natural speech envelope tracking response was also present in all patient subjects and responses in the first 100 ms distinguished patient subjects with evidence of language processing. Specifically, patient subjects with evidence of language processing had a more global response in the first 100 ms whereas those without evidence of language processing had a frontopolar response in that period. In summary, we developed two passive EEG-based methods to probe low-level language processing in severely brain-injured patients. In our cohort, both assays showed a difference between patient subjects with evidence of command-following and those with no evidence of command-following: a more prominent early bilateral response component., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Gram-negative bacteria are notoriously more resistant to antibiotics than Gram-positive bacteria, primarily due to the presence of the outer membrane and a plethora of active efflux pumps. However, the potency of antibiotics also varies dramatically between different Gram-negative pathogens, suggesting major mechanistic differences in how antibiotics penetrate permeability barriers. Two approaches are used broadly to analyze how permeability barriers affect intracellular accumulation of antibiotics. One compares the antibacterial activities of compounds, while the other measures the total intracellular concentrations of compounds in nongrowing cells, with both approaches using strains harboring wild-type or genetically modified efflux systems and permeability barriers. Whether the two assays provide similar mechanistic insights remains unclear. In this study, we analyzed the intracellular accumulation and antibacterial activities of antibiotics representative of major clinical classes in three Gram-negative pathogens of high clinical importance, Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. We found that both assays are informative about properties of permeability barriers, but there is no quantitative agreement between the assays. Our results show that the three pathogens differ dramatically in their permeability barriers, with the outer membrane playing the dominant role in E. coli and P. aeruginosa but efflux dominating in A. baumannii. However, even compounds of the same chemotype may use different permeation pathways depending on small chemical modifications. Accordingly, a classification analysis revealed limited conservation of molecular properties that define compound penetration into the three bacteria.

Lack of a body-sized, bore-mounted, radiofrequency (RF) body coil for ultrahigh field (UHF) magnetic resonance imaging (MRI) is one of the major drawbacks of UHF, hampering the clinical potential of the technology. Transmit field (B 1 ) nonuniformity and low specific absorption rate (SAR) efficiencies in UHF MRI are two challenges to be overcome. To address these problems, and ultimately provide a pathway for the full clinical potential of the modality, we have designed and simulated two-dimensional cylindrical high-pass ladder (2D c-HPL) architectures for clinical bore-size dimensions, and demonstrated a simplified proof of concept with a head-sized prototype at 7 T. A new dispersion relation has been derived and electromagnetic simulations were used to verify coil modes. The coefficient of variation (CV) for brain, cerebellum, heart, and prostate tissues after B 1 + shimming in silico is reported and compared with previous works. Three prototypes were designed in simulation: a head-sized, body-sized, and long body-sized coil. The head-sized coil showed a CV of 12.3%, a B 1 + efficiency of 1.33 μT/√W, and a SAR efficiency of 2.14 μT/√(W/kg) for brain simulations. The body-sized 2D c-HPL coil was compared with same-sized transverse electromagnetic (TEM) and birdcage coils in silico with a four-port circularly polarized mode excitation. Improved B 1 + uniformity (26.9%) and SAR efficiency (16% and 50% better than birdcage and TEM coils, respectively) in spherical phantoms was observed. We achieved a CV of 12.3%, 4.9%, 16.7%, and 2.8% for the brain, cerebellum, heart, and prostate, respectively. Preliminary imaging results for the head-sized coil show good agreement between simulation and experiment. Extending the 1D birdcage coil concept to 2D c-HPLs provides improved B 1 + uniformity and SAR efficiency., (© 2022 John Wiley & Sons, Ltd.)

Background and Objectives: Following severe brain injury, up to 16% of adults showing no clinical signs of cognitive function nonetheless have preserved cognitive capacities detectable via neuroimaging and neurophysiology; this has been designated cognitive-motor dissociation (CMD). Pediatric medicine lacks both practice guidelines for identifying covert cognition and epidemiologic data regarding CMD prevalence., Methods: We applied a diverse battery of neuroimaging and neurophysiologic tests to evaluate 2 adolescents (aged 15 and 18 years) who had shown no clinical evidence of preserved cognitive function following brain injury at age 9 and 13 years, respectively. Clinical evaluations were consistent with minimally conscious state (minus) and vegetative state, respectively., Results: Both participants' EEG, and 1 participant's fMRI, provided evidence that they could understand commands and make consistent voluntary decisions to follow them. Both participants' EEG demonstrated larger-than-expected responses to auditory stimuli and intact semantic processing of words in context., Discussion: These converging lines of evidence lead us to conclude that both participants had preserved cognitive function dissociated from their motor output. Throughout the 5+ years since injury, communication attempts and therapy had remained uninformed by such objective evidence of their cognitive abilities. Proper diagnosis of CMD is an ethical imperative. Children with covert cognition reflect a vulnerable and isolated population; the methods outlined here provide a first step in identifying such persons to advance efforts to alleviate their condition., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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× 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× acceleration (equivalent to 11× 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.

Resting state functional connectivity magnetic resonance imaging (fMRI) is a tool for investigating human brain organization. Here we identify, visually and algorithmically, two prevalent influences on fMRI signals during 440 h of resting state scans in 440 healthy young adults, both caused by deviations from normal breathing which we term deep breaths and bursts. The two respiratory patterns have distinct influences on fMRI signals and signal covariance, distinct timescales, distinct cardiovascular correlates, and distinct tendencies to manifest by sex. Deep breaths are not sex-biased. Bursts, which are serial taperings of respiratory depth typically spanning minutes at a time, are more common in males. Bursts share features of chemoreflex-driven clinical breathing patterns that also occur primarily in males, with notable neurological, psychiatric, medical, and lifespan associations. These results identify common breathing patterns in healthy young adults with distinct influences on functional connectivity and an ability to differentially influence resting state fMRI studies.

Objective: It is well established that long-term hypothyroidism is associated with cognitive deficits. Based on recent literature, we hypothesized that pharmacologically induced euthyroidism would lead to improved cognitive performance compared to a hypothyroid state., Methods: We analyzed data from 14 nondepressed thyroidectomized female patients after differentiated thyroid carcinoma during hypothyroidism (due to a four-week withdrawal of thyroid hormone, T1) and euthyroidism brought about by substitution with L-thyroxine (T2). At both measurement points, patients completed a cognitive test battery as our dependent measure and Beck’s Depression Inventory to control depressive states., Results: A Wilcoxon signed-rank tests revealed a significant improvement in the Rey–Osterrieth complex figure test (cognitive reproduction), Z = −3.183, p = 0.001, and the D2 concentration score, Z = −1.992, p = 0.046 in euthyroidism compared to hypothyroidism., Conclusions: Our results confirm that hormone replacement therapy with L-thyroxine promotes cognitive reproduction and concentration in thyroidectomized female patients after differentiated thyroid carcinoma.

We compared the acute effect of typical (haloperidol) and atypical (aripiprazole, clozapine, olanzapine) antipsychotic drugs (APDs) on spontaneous electrophysiological activity of in vitro neuronal networks cultured on microelectrode arrays (MEAs). Network burst analysis revealed a "regularizing" effect of all APDs at therapeutic concentrations, i.e., an increase of network-wide temporal synchronization. At supratherapeutic concentrations, all APDs but olanzapine mediated a decrease of burst and spike rates, burst duration, number of spikes in bursts, and network synchrony. The rank order of potency of APDs was: haloperidol > aripiprazole > clozapine > olanzapine (no suppression). Disruption of network function was not due to enhanced cell death as assessed by trypan blue staining. APDs promoted distinct concentration-dependent alterations yielding acute effect fingerprints of the tested compounds. These effects were rather characteristic for individual compounds than distinctive for typical vs. atypical APDs. Thus, this dichotomy may be of value in distinguishing clinical features but has no apparent basis on the network or local circuitry level.

Purpose: Preoperative functional MRI (fMRI) is limited by a muted BOLD response caused by abnormal vasoreactivity and resultant neurovascular uncoupling adjacent to malignant brain tumors. We propose to overcome this limitation and more accurately identify eloquent areas adjacent to brain tumors by independently assessing vasoreactivity using breath-holding and incorporating these data into the fMRI analysis., Methods: Local vasoreactivity using a breath-holding paradigm with the same timing as the functional motor and language tasks was determined in 16 patients (9 glioblastomas, 1 anaplastic astrocytoma, 5 low grade astrocytomas, and 1 metastasis) and 6 healthy control subjects. We derived an fMRI model based on an observed vaso-task response dependency that takes into account the altered hemodynamics adjacent to brain tumors., Results: In both healthy controls and brain tumor subjects, we found a statistical dependency between breath-hold and task BOLD response. In tumor subjects, activation maps that take into account this vaso-task dependency demonstrated clinically meaningful areas of activation that were not seen using the task-only analysis in about half of the cases studied. This included localization of language areas adjacent to brain tumors., Conclusions: The present preliminary results demonstrate that neurovascular uncoupling known to affect the accuracy of BOLD fMRI adjacent to brain tumors may be, at least partially, overcome by incorporating an observed vaso-task dependency in the BOLD signal analysis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The neuropeptide oxytocin (OT) is known to be an important modulator of social cognition. It has been shown that lower OT plasma concentrations are linked to impairments in social cognition. Studies have also shown that intranasal OT may enhance social-cognitive abilities in healthy subjects. We hypothesize that, besides baseline OT concentrations, the reactivity of the OT system may have an important role in social-cognitive functioning of individuals. In the present study, we explored if an emotional challenge paradigm is suitable to elicit OT release into plasma to make the reactivity of the OT system measurable. Therefore, 20 healthy male volunteers watched an emotional film clip, showing another person in pain during a severe dentist's treatment, while blood draws were conducted pre and post challenge. OT concentrations in plasma were measured by ELISA after solid phase extraction from plasma. OT plasma concentrations at baseline were significantly negatively correlated to an empathetic rating of our film clip and to measures of emotional empathy for positive and negative emotions, whereas the difference between post-challenge value and baseline was significantly positively correlated with the latter measures. Our data thus show that a short emotional video can be successfully employed as a challenge paradigm for eliciting an increase of peripheral OT in healthy male subjects. Calculating the relative OT change post- vs. pre-challenge may give a measure of OT reactivity. The combination of low peripheral OT at baseline with high OT reactivity may be a psychoendocrine trait that is linked to higher emotional functioning.

A filter with delay-induced negative group delay is presented. The filter consists of multiple time-delayed feedback terms, which lead to a negative group delay for frequencies in the baseband. It can be used for the real-time prediction of band-limited signals. The filter is universal as it does not rely on a specific model of the signal. Specifically, as long as the signal to be predicted is band-limited with a known cutoff frequency, the filter predicts the signal in real time up to a prediction horizon that depends on the cutoff frequency. How signal prediction arises from the negative group delay of the filter is worked out in detail. Its properties, including stability, are derived analytically and demonstrated by numerical simulations. For chaotic systems, the filter is predictive during phases of high predictability.

A method to upsample insufficiently sampled experimental time series of pseudo-periodic signals is proposed. The result is an estimate of the pseudo-periodic cycle underlying the signal. This "hypersampling" requires a sufficiently sampled reference signal that defines the pseudo-periodic dynamics. The time series and reference signal are combined by projecting the time series values to the analytic phase of the reference signal. The resulting estimate of the pseudo-periodic cycle has a considerably higher effective sampling rate than the time series. The procedure is applied to time series of MRI images of the human brain. As a result, the effective sampling rate could be increased by three orders of magnitude. This allows for capturing the waveforms of the very fast cerebral pulse waves traversing the brain. Hypersampling is numerically compared to the more commonly used retrospective gating. An outlook regarding EEG and optical recordings of brain activity as the reference signal is provided., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Disclosure TV has received grant support from Bristol-Myers Squibb. IV has served on the speakers’ bureaux of Bristol-Myers Squibb (New York, NY), Eli Lilly (Indianapolis, IN), and GlaxoSmithKline (London, UK). GG has served as a consultant for Allergan, Boehringer Ingelheim, Eli Lilly, Janssen-Cilag, Lundbeck, Ono Pharmaceuticals, Otsuka, Recordati, Roche, Servier, and Takeda, and served on the speakers’ bureaux of Eli Lilly, Janssen Cilag, Lundbeck, Neuraxpharm, Otsuka, Roche, Servier, and Trommsdorff. He has received grant support from Boehringer Ingelheim and Roche, and is cofounder of Pharma Image and Brainfoods GmbH. The other authors report no conflicts of interest in this work.

The purpose of this study is to determine the effects of high cumulative doses of ultra-small paramagnetic iron oxide (USPIO) used in neuroimaging studies. We intravenously administered 8 mg/kg of 2 USPIO compounds daily for 4 wk to male Sprague-Dawley rats (Crl:SD). Multiecho gradient-echo MRI, serum iron levels, and histology were performed at the end of dosing and after a 7-d washout period. R2* maps and quantitative susceptibility maps (QSM) were generated from multiecho gradient-echo data. R2* maps and QSM showed iron accumulation in brain ventricles on MR images acquired at the 4- and 5-wk time points. Estimates from QSM data showed ventricular iron concentration was equal to or higher than serum iron concentration. Histologic analysis revealed choroid plexus hemosiderosis and midbrain vacuolation, without iron deposition in brain parenchyma. Serum iron levels increased with administration of both compounds, and a 7-d washout period effectively reduced serum iron levels of one but not both of the compounds. High cumulative doses from multiple, frequent administrations of USPIO can lead to iron deposition in brain ventricles, resulting in persistent signal loss on T2*-weighted images. Techniques such as QSM are helpful in quantifying iron biodistribution in this situation.

We analyze the pulsatile signal component of dynamic echo planar imaging data from the brain by modeling the dependence between local temporal and spatial signal variability. The resulting magnetic resonance advection imaging maps depict the location of major arteries. Color direction maps allow for visualization of the direction of blood vessels. The potential significance of magnetic resonance advection imaging maps is demonstrated on a functional magnetic resonance imaging data set of 19 healthy subjects. A comparison with the here introduced pulse coherence maps, in which the echo planar imaging signal is correlated with a cardiac pulse signal, shows that the magnetic resonance advection imaging approach results in a better spatial definition without the need for a pulse reference. In addition, it is shown that magnetic resonance advection imaging velocities can be estimates of pulse wave velocities if certain requirements are met, which are specified. Although for this application magnetic resonance advection imaging velocities are not quantitative estimates of pulse wave velocities, they clearly depict local pulsatile dynamics. Magnetic resonance advection imaging can be applied to existing dynamic echo planar imaging data sets with sufficient spatiotemporal resolution. It is discussed whether magnetic resonance advection imaging might have the potential to evolve into a biomarker for the health of the cerebrovascular system.

Biomarkers have transformed modern medicine but remain largely elusive in psychiatry, partly because there is a weak correspondence between diagnostic labels and their neurobiological substrates. Like other neuropsychiatric disorders, depression is not a unitary disease, but rather a heterogeneous syndrome that encompasses varied, co-occurring symptoms and divergent responses to treatment. By using functional magnetic resonance imaging (fMRI) in a large multisite sample (n = 1,188), we show here that patients with depression can be subdivided into four neurophysiological subtypes ('biotypes') defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks. Clustering patients on this basis enabled the development of diagnostic classifiers (biomarkers) with high (82-93%) sensitivity and specificity for depression subtypes in multisite validation (n = 711) and out-of-sample replication (n = 477) data sets. These biotypes cannot be differentiated solely on the basis of clinical features, but they are associated with differing clinical-symptom profiles. They also predict responsiveness to transcranial magnetic stimulation therapy (n = 154). Our results define novel subtypes of depression that transcend current diagnostic boundaries and may be useful for identifying the individuals who are most likely to benefit from targeted neurostimulation therapies.

We propose that feedback-delayed manual tracking performance is limited by fundamental constraints imposed by the physics of negative group delay. To test this hypothesis, the results of an experiment in which subjects demonstrate both reactive and predictive dynamics are modeled by a linear system with delay-induced negative group delay. Although one of the simplest real-time predictors conceivable, this model explains key components of experimental observations. Most notably, it explains the observation that prediction time linearly increases with feedback delay, up to a certain point when tracking performance deteriorates. It also explains the transition from reactive to predictive behavior with increasing feedback delay. The model contains only one free parameter, the feedback gain, which has been fixed by comparison with one set of experimental observations for the reactive case. Our model provides quantitative predictions that can be tested in further experiments.

Nicotinic acetylcholine receptor (nAChR) subtypes containing the α4 subunit, particularly α4β2 nAChRs, play an important role in cognitive functioning. The impact of the smoking cessation aid varenicline, a selective partial α4β2 nAChR agonist, on (1) changes of central protein and mRNA expression of this receptor and (2) on memory deficits in a mouse model of cognitive impairment was investigated. Protein and mRNA expression of both the α4 and β2 receptor subunits in mouse brain endothelial and hippocampal cells as well as hippocampus and neocortex tissues were determined by western blot and realtime PCR, respectively. The β2 antibody showed low specificity, though. Tissues were examined following a 2-week oral treatment with various doses of varenicline (0.01, 0.1, 1, 3 mg/kg/day) or vehicle. In addition, episodic memory of mice was assessed following this treatment with an object recognition task using (1) normal mice and (2) animals with anticholinergic-induced memory impairment (i.p. injection of 0.5 mg/kg scopolamine). Varenicline dose-dependently increased protein expression of both the α4 and β2 subunit in cell cultures and brain tissues, respectively, but had no effect on mRNA expression of both subunits. Scopolamine injection induced a significant reduction of object memory in vehicle-treated mice. By contrast, cognitive performance was not altered by scopolamine in varenicline-treated mice. In conclusion, a 2-week oral treatment with varenicline prevented memory impairment in the scopolamine mouse model. In parallel, protein, but not mRNA expression was upregulated, suggesting a posttranscriptional mechanism. Our findings suggest a beneficial effect of varenicline on cognitive dysfunction., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The leaky integrator, the basis for many neuronal models, possesses a negative group delay when a time-delayed recurrent inhibition is added to it. By means of this delay, the leaky integrator becomes a predictor for some frequency components of the input signal. The prediction properties are derived analytically, and an application to a local field potential is provided.

In many social animals, early exposure to conspecific stimuli is critical for the development of accurate species recognition. Obligate brood parasitic songbirds, however, forego parental care and young are raised by heterospecific hosts in the absence of conspecific stimuli. Having evolved from non-parasitic, parental ancestors, how brood parasites recognize their own species remains unclear. In parental songbirds (e.g. zebra finch Taeniopygia guttata), the primary and secondary auditory forebrain areas are known to be critical in the differential processing of conspecific vs. heterospecific songs. Here we demonstrate that the same auditory brain regions underlie song discrimination in adult brood parasitic pin-tailed whydahs (Vidua macroura), a close relative of the zebra finch lineage. Similar to zebra finches, whydahs showed stronger behavioral responses during conspecific vs. heterospecific song and tone pips as well as increased neural responses within the auditory forebrain, as measured by both functional magnetic resonance imaging (fMRI) and immediate early gene (IEG) expression. Given parallel behavioral and neuroanatomical patterns of song discrimination, our results suggest that the evolutionary transition to brood parasitism from parental songbirds likely involved an "evolutionary tinkering" of existing proximate mechanisms, rather than the wholesale reworking of the neural substrates of species recognition., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The mildly invasive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging technique to measure 'resting state' cerebral metabolism. This technique made it possible to assess changes in metabolic activity in clinical applications, such as the study of severe brain injury and disorders of consciousness., Objective: We assessed the possibility of creating functional MRI activity maps, which could estimate the relative levels of activity in FDG-PET cerebral metabolic maps. If no metabolic absolute measures can be extracted, our approach may still be of clinical use in centers without access to FDG-PET. It also overcomes the problem of recognizing individual networks of independent component selection in functional magnetic resonance imaging (fMRI) resting state analysis., Methods: We extracted resting state fMRI functional connectivity maps using independent component analysis and combined only components of neuronal origin. To assess neuronality of components a classification based on support vector machine (SVM) was used. We compared the generated maps with the FDG-PET maps in 16 healthy controls, 11 vegetative state/unresponsive wakefulness syndrome patients and four locked-in patients., Results: The results show a significant similarity with ρ = 0.75 ± 0.05 for healthy controls and ρ = 0.58 ± 0.09 for vegetative state/unresponsive wakefulness syndrome patients between the FDG-PET and the fMRI based maps. FDG-PET, fMRI neuronal maps, and the conjunction analysis show decreases in frontoparietal and medial regions in vegetative patients with respect to controls. Subsequent analysis in locked-in syndrome patients produced also consistent maps with healthy controls., Conclusions: The constructed resting state fMRI functional connectivity map points toward the possibility for fMRI resting state to estimate relative levels of activity in a metabolic map.

Background: Hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity in survivors. Therapeutic hypothermia (TH) is the only available intervention, but the protection is incomplete. Preclinical studies of HIE/TH in the rodent have relied on the postnatal day (P) 7 rat whose brain approximates a 32-36 wk gestation infant, less relevant for these studies. We propose that HIE and TH in the term-equivalent P10 rat will be more translational., Methods: P10-11 rat pups were subjected to unilateral hypoxia-ischemia (HI) and 4 h recovery in normothermic (N) or hypothermic (TH) conditions. Brain damage was assessed longitudinally at 24 h, 2 wk, and 12 wk. Motor function was assessed with the beam walk; recognition memory was measured by novel object recognition., Results: Neuroprotection with TH was apparent at 2 and 12 wk in both moderately and severely damaged animals. TH improved motor function in moderate, but not severe, damage. Impaired object recognition occurred with severe damage with no evidence of protection of TH., Conclusion: This adaptation of the immature rat model of HI provides a reproducible platform to further study HIE/TH in which individual animals are followed up longitudinally to provide a useful translational preclinical model.

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.

We present a method for local estimation of the signal-dependent noise level in magnetic resonance images. The procedure uses a multi-scale approach to adaptively infer on local neighborhoods with similar data distribution. It exploits a maximum-likelihood estimator for the local noise level. The validity of the method was evaluated on repeated diffusion data of a phantom and simulated data using T1-data corrupted with artificial noise. Simulation results were compared with a recently proposed estimate. The method was also applied to a high-resolution diffusion dataset to obtain improved diffusion model estimation results and to demonstrate its usefulness in methods for enhancing diffusion data., (Copyright © 2014 Elsevier B.V. All rights reserved.)