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An otherwise healthy two-month-old female C57BL/6J mouse presented with a left-sided head tilt. Differential diagnoses included idiopathic necrotizing arteritis, bacterial otitis media/interna ( Pasteurella pneumotropica, Pseudomonas aeruginosa, Streptococcus sp., Mycoplasma pulmonis and Burkholderia gladioli), encephalitis, an abscess, neoplasia, a congenital malformation and an accidental or iatrogenic head trauma. Magnetic resonance imaging (MRI) revealed a large space-occupying right olfactory lobe intra-axial lesion with severe secondary left-sided subfalcine herniation. Following imaging, the animal was euthanized due to poor prognosis. Histopathologic examination revealed a unilateral, full-thickness bone defect at the base of the cribriform plate and nasal conchae dysplasia, resulting in the herniation of the olfactory bulb into the nasal cavity. There was also a left midline-shift of the frontal cortex and moderate catarrhal sinusitis in the left mandibular sinus. The MRI and histopathologic changes are consistent with a congenital malformation of the nasal cavity and frontal aspect of the skull known as an ethmoidal meningoencephalocele. Encephaloceles are rare abnormalities caused by herniation of contents of the brain through a defect in the skull which occur due to disruption of the neural tube closure at the level anterior neuropore or secondary to trauma, surgical complications, cleft palate or increased intracranial pressure. The etiology is incompletely understood but hypotheses include genetics, vitamin deficiency, teratogens, infectious agents and environmental factors. Ethmoidal encephaloceles have been reported in multiple species including humans but have not been reported previously in mice. There are multiple models for spontaneous and induced craniofacial malformation in mice, but none described for ethmoidal encephaloceles.

We propose a 2-dimensional cylindrical high-pass ladder (2D c-HPL) coil and exploit the added second dimension in a longitudinal direction to create a body-sized volume coil with a length of 91 cm for use in ultra-high-field (UHF) magnetic resonance imaging (MRI). Theory, circuit model, and in-silico results show that this architecture exhibits improved transmit field inhomogeneity (6.44%), decreased specific absorption rate (0.014 W/kg), and improved specific absorption rate (SAR) efficiency (0.59 μT/√W/kg). This could prove particularly useful for whole-body and spinal-cord imaging, among others, and could open up new pathways for clinical diagnostics in UHF MRI.

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., 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.

Purpose To quantify CSF transport kinetics and brain glymphatic distribution using MRI following intrathecal injection of gadolinium contrast in healthy adults. Subjects and methods Eight completely healthy volunteer subjects underwent intrathecal injection of gadolinium via image guided lumbar puncture and serial MRI's at six subsequent time points up to 11 h post-injection. Rate of enhancement and deposition were calculated for various regions and lobes of the brain. Results Normalized cranial data revealed that gadolinium in the intracranial CSF spaces peaked within 1–3 h and started to decrease at 7 h. In some regions of the brain parenchyma, such as the cerebral cortex and white matter, enhancement was increasing after 11 h. Differential rates of uptake between the parietal and frontal (p = 0.0003), cingulate (p = 0.002) and temporal (p = 0.018) lobes were shown as well as a several fold change between various cortical regions. Lastly, a linear regression comparing laterality between 35 cortical regions yielded (R2 = 0.90, p Conclusions Gadolinium enhancement after lumbar intrathecal injection demonstrated differential CSF flow and brain parenchymal penetration, which illustrated the distributory function of the glymphatic system.

See Boly and Laureys (doi:10.1093/brain/awy080) for a scientific commentary on this article.Patients with severe brain injury are difficult to assess and frequently subject to misdiagnosis. 'Cognitive motor dissociation' is a term used to describe a subset of such patients with preserved cognition as detected with neuroimaging methods but not evident in behavioural assessments. Unlike the locked-in state, cognitive motor dissociation after severe brain injury is prominently marked by concomitant injuries across the cerebrum in addition to limited or no motoric function. In the present study, we sought to characterize the EEG signals used as indicators of cognition in patients with disorders of consciousness and examine their reliability for potential future use to re-establish communication. We compared EEG-based assessments to the results of using similar methods with functional MRI. Using power spectral density analysis to detect EEG evidence of task performance (Two Group Test, P ≤ 0.05, with false discovery rate correction), we found evidence of the capacity to follow commands in 21 of 28 patients with severe brain injury and all 15 healthy individuals studied. We found substantial variability in the temporal and spatial characteristics of significant EEG signals among the patients in contrast to only modest variation in these domains across healthy controls; the majority of healthy controls showed suppression of either 8-12 Hz 'alpha' or 13-40 Hz 'beta' power during task performance, or both. Nine of the 21 patients with EEG evidence of command-following also demonstrated functional MRI evidence of command-following. Nine of the patients with command-following capacity demonstrated by EEG showed no behavioural evidence of a communication channel as detected by a standardized behavioural assessment, the Coma Recovery Scale - Revised. We further examined the potential contributions of fluctuations in arousal that appeared to co-vary with some patients' ability to reliably generate EEG signals in response to command. Five of nine patients with statistically indeterminate responses to one task tested showed a positive response after accounting for variations in overall background state (as visualized in the qualitative shape of the power spectrum) and grouping of trial runs with similar background state characteristics. Our findings reveal signal variations of EEG responses in patients with severe brain injuries and provide insight into the underlying physiology of cognitive motor dissociation. These results can help guide future efforts aimed at re-establishment of communication in such patients who will need customization for brain-computer interfaces.

A diet rich in salt is linked to an increased risk of cerebrovascular diseases and dementia, but it remains unclear how dietary salt harms the brain. We report that, in mice, excess dietary salt suppresses resting cerebral blood flow and endothelial function, leading to cognitive impairment. The effect depends on expansion of TH17 cells in the small intestine, resulting in a marked increase in plasma interleukin-17 (IL-17). Circulating IL-17, in turn, promotes endothelial dysfunction and cognitive impairment by the Rho kinase-dependent inhibitory phosphorylation of endothelial nitric oxide synthase and reduced nitric oxide production in cerebral endothelial cells. The findings reveal a new gut-brain axis linking dietary habits to cognitive impairment through a gut-initiated adaptive immune response compromising brain function via circulating IL-17. Thus, the TH17 cell-IL-17 pathway is a putative target to counter the deleterious brain effects induced by dietary salt and other diseases associated with TH17 polarization.

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.

Background Mechanisms underlying delayed orgasm (DO) are poorly understood; however, known effects of psychotropic medications on sexual function provides a rationale for aberrant central nervous system signaling as a cause. Aim To compare brain activation between men with normal orgasm and those with lifelong DO during sexual stimulation using brain fMRI algorithms. Methods 3 subjects with self-reported life-long DO and 6 normal controls were included in this study. The International Index of Erectile Function, Male Sexual Health Questionnaire, and self-reported time to orgasm were used to assess sexual function. Subjects underwent a 3-T fMRI study while viewing 3 video clips: a neutral control (NC), a positive emotional control (EC), and a sexual condition (SC). Each video sequence was repeated 5 times, with 50-second clips presented in a randomized fashion. fMRI data were analyzed in a block design manner to determine areas of differential brain activation between groups. The Allen Brain Atlas of gene expression in the human brain was used to identify signaling pathways in the areas of differential fMRI activation between the DO and control groups. Outcomes The primary outcome was differential activation of fMRI neural activation between groups. Results Analysis of differential activation in the SC compared with the NC and EC revealed increased activation in the right frontal operculum (P = .003), right prefrontal gyrus (P = .003), and inferior occipital gyrus (P = .003). Increased activation in the right fusiform gyrus of the occipital lobe and the right hippocampus (P = .0004) was seen in the DO group compared with controls. Using the Allen Atlas of Human Brain Expression, we identified corresponding neurotransmitter receptors to this region, including adenosine receptors, muscarinic and nicotinic cholinergic receptors, cannabinoid receptors, and dopamine receptors, among others. Clinical Implications Lifelong DO in men may be due to abnormal neurotransmitter signaling leading to poor progression of arousal due to aberrant processing of sexual cues. Identification of neurotransmitter pathways by fMRI will aid the development of pharmacotherapeutic agents. Strengths & Limitations Strengths of this study include the novel application of functional neuroimaging to investigate the pathogenesis of DO. Limitations include the small sample size, making this study exploratory in nature. Conclusion This study revealed differences in brain activation on visualization of sexual stimuli in men with a history of DO compared with controls. Identified regions are rich in numerous neurotransmitter receptor subtypes and may be amenable to pharmacologic targeting to identify novel therapies for these men.

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.

The ApoE4 allele is associated with increased risk of small vessel disease, which is a cause of vascular cognitive impairment. Here, we report that mice with targeted replacement (TR) of the ApoE gene with human ApoE4 have reduced neocortical cerebral blood flow compared to ApoE3-TR mice, an effect due to reduced vascular density rather than slowing of microvascular red blood cell flow. Furthermore, homeostatic mechanisms matching local delivery of blood flow to brain activity are impaired in ApoE4-TR mice. In a model of cerebral hypoperfusion, these cerebrovascular alterations exacerbate damage to the white matter of the corpus callosum and worsen cognitive dysfunction. Using 3-photon microscopy we found that the increased white matter damage is linked to an enhanced reduction of microvascular flow resulting in local hypoxia. Such alterations may be responsible for the increased susceptibility to hypoxic-ischemic lesions in the subcortical white matter of individuals carrying the ApoE4 allele.

PurposePreoperative 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 BOLD analysis.MethodsLocal 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). We derived a model based on coherence for analyzing BOLD fMRI that takes into account the altered hemodynamics adjacent to brain tumors.ResultsActivation maps computed using the coherence model were overall similar to standard activation maps. However, the coherence maps demonstrated clinically meaningful areas of activation that were not seen using the standard method in 12/16 cases. This included localization of language areas adjacent to brain tumors, where the coherence method results were confirmed by intra-operative direct cortical stimulation. Enhanced task response maps based on vasoreactivity mapping demonstrated more robust, anatomically-correct activation, in particular adjacent to tumors as compared to maps obtained without vasoreactivity information.ConclusionsThe present preliminary results demonstrate the principle that the neurovascular uncoupling known to affect the accuracy of BOLD fMRI adjacent to brain tumors may be, at least partially, overcome by incorporating an independent measurement of vasoreactivity into the BOLD analysis.

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.

Background and Purpose— Obstructive sleep apnea, a condition associated with chronic intermittent hypoxia (CIH), carries an increased risk of stroke. However, CIH has been reported to either increase or decrease brain injury in models of focal cerebral ischemia. The factors determining the differential effects of CIH on ischemic injury and their mechanisms remain unclear. Here, we tested the hypothesis that the intensity of the hypoxic challenge determines the protective or destructive nature of CIH by modulating mitochondrial resistance to injury. Methods— Male C57Bl/6J mice were exposed to CIH with 10% or 6% O 2 for ≤35 days and subjected to transient middle cerebral artery occlusion. Motor deficits and infarct volume were assessed 3 days later. Intraischemic cerebral blood flow was measured by laser-Doppler flowmetry and resting cerebral blood flow by arterial spin labeling MRI. Ca 2+ -induced mitochondrial depolarization and reactive oxygen species production were evaluated in isolated brain mitochondria. Results— We found that 10% CIH is neuroprotective, whereas 6% CIH exacerbates tissue damage. No differences in resting or intraischemic cerebral blood flow were observed between 6% and 10% CIH. However, 10% CIH reduced, whereas 6% CIH increased, mitochondrial reactive oxygen species production and susceptibility to Ca 2+ -induced depolarizations. Conclusions— The influence of CIH on the ischemic brain is dichotomous and can be attributed, in part, to changes in the mitochondrial susceptibility to injury. The findings highlight a previously unappreciated complexity in the effect of CIH on the brain, which needs to be considered in evaluating the neurological effect of conditions associated with cyclic hypoxia.

Songbirds spend much of their time learning, producing, and listening to complex vocal sequences we call songs. Songs are learned via cultural transmission, and singing, usually by males, has a strong impact on the behavioral state of the listeners, often promoting affiliation, pair bonding, or aggression. What is it in the acoustic structure of birdsong that makes it such a potent stimulus? We suggest that birdsong potency might be driven by principles similar to those that make music so effective in inducing emotional responses in humans: a combination of rhythms and pitches —and the transitions between acoustic states—affecting emotions through creating expectations, anticipations, tension, tension release, or surprise. Here we propose a framework for investigating how birdsong, like human music, employs the above “musical” features to affect the emotions of avian listeners. First we analyze songs of thrush nightingales (Luscinia luscinia) by examining their trajectories in terms of transitions in rhythm and pitch. These transitions show gradual escalations and graceful modifications, which are comparable to some aspects of human musicality. We then explore the feasibility of stripping such putative musical features from the songs and testing how this might affect patterns of auditory responses, focusing on fMRI data in songbirds that demonstrate the feasibility of such approaches. Finally, we explore ideas for investigating whether musical features of birdsong activate avian brains and affect avian behavior in manners comparable to music’s effects on humans. In conclusion, we suggest that birdsong research would benefit from current advances in music theory by attempting to identify structures that are designed to elicit listeners’ emotions and then testing for such effects experimentally. Birdsong research that takes into account the striking complexity of song structure in light of its more immediate function – to affect behavioral state in listeners – could provide a useful animal model for studying basic principles of music neuroscience in a system that is very accessible for investigation, and where developmental auditory and social experience can be tightly controlled.

Spontaneous recovery of brain function after severe brain injury may evolve over a long time period and is likely to involve both structural and functional reorganization of brain networks. We longitudinally tracked the recovery of communication in a patient with severe brain injury using multimodal brain imaging techniques and quantitative behavioral assessments measured at the bedside over a period of 2 years and 9 months (21 months after initial injury). Structural diffusion tensor imaging revealed changes in brain structure across interhemispheric connections and in local brain regions that support language and visuomotor function. These findings correlated with functional brain imaging using functional magnetic resonance imaging and positron emission tomography, which demonstrated increased language network recruitment in response to natural speech stimuli, graded increases in interhemispheric interactions of language-related frontal cortices, and increased cerebral metabolic activity in the language-dominant hemisphere. In addition, electrophysiological studies showed recovery of synchronization of sleep spindling activity. The observed changes suggest a specific mechanism for late recovery of communication after severe brain injury and provide support for the potential of activity-dependent structural and functional remodeling over long time periods.

BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene. Our hypothesis was that regional analysis of cortical brain degeneration may identify brain regions that are affected earliest and most severely by the disease. MATERIALS AND METHODS: Fifty-two high-resolution 3T MR imaging datasets were prospectively acquired on 38 subjects with CLN2. A retrospective cohort of 52 disease-free children served as a control population. The FreeSurfer software suite was used for calculation of cortical thickness. RESULTS: An increased rate of global cortical thinning in CLN2 versus control subjects was the primary finding in this study. Three distinct patterns were observed across brain regions. In the first, subjects with CLN2 exhibited differing rates of cortical thinning versus age. This was true in 22 and 26 of 34 regions in the left and right hemispheres, respectively, and was also clearly discernable when considering brain lobes as a whole and Brodmann regions. The second pattern exhibited a difference in thickness from healthy controls but with no discernable change with age (9 left hemispheres, 5 right hemispheres). In the third pattern, there was no difference in either the rate of cortical thinning or the mean cortical thickness between groups (3 left hemispheres, 3 right hemispheres). CONCLUSIONS: This study demonstrates that CLN2 causes differential rates of degeneration across the brain. Anatomic and functional regions that degenerate sooner and more severely than others compared with those in healthy controls may offer targets for directed therapies. The information gained may also provide neurobiologic insights regarding the mechanisms underlying disease progression.

BACKGROUND AND PURPOSE: LINCL is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene that encodes for tripeptidyl peptidase 1, a lysosomal enzyme necessary for the degradation of products of cellular metabolism. With the goal of developing quantitative noninvasive imaging biomarkers sensitive to disease progression, we evaluated a 5-component MR imaging metric and tested its correlation with a clinically derived disease-severity score. MATERIALS AND METHODS: MR imaging parameters were measured across the brain, including quantitative measures of the ADC, FA, nuclear spin-spin relaxation times (T2), volume percentage of CSF (%CSF), and NAA/Cr ratios. Thirty MR imaging datasets were prospectively acquired from 23 subjects with LINCL (2.5–8.4 years of age; 8 male/15 female). Whole-brain histograms were created, and the mode and mean values of the histograms were used to characterize disease severity. RESULTS: Correlation of single MR imaging parameters against the clinical disease-severity scale yielded linear regressions with R 2 ranging from 0.25 to 0.70. Combinations of the 5 biomarkers were evaluated by using PCA. The best combination included ADC, %CSF, and NAA/Cr ( R 2 = 0.76, P CONCLUSIONS: The multiparametric disease-severity score obtained from the combination of ADC, %CSF, and NAA/Cr whole-brain MR imaging techniques provided a robust measure of disease severity, which may be useful in clinical therapeutic trials of LINCL in which an objective assessment of therapeutic response is desired.

The sensitivity of fMRI in identification of eloquent cortical centers in the case of large infiltrative growing tumors and pronounced peritumoral edema may be reduced or significantly limited in some cases. The main cause is an attenuated Blood-Oxygen-Level-Dependent response (BOLD) caused by pathological vascular reactivity and subsequent neurovascular uncoupling of fMRI. In our study, we attempted to overcome these limitations and increase the sensitivity of this technique in identification of eloquent cortical areas adjacent to brain tumors by using vasoreactivity features of a breath-holding test and including these data in the BOLD analysis. Local vasoreactivity using a breath-holding paradigm with the same block design of both motor and speech tests was determined in 5 healthy volunteers and 3 patients in the preoperative period (two patients with high grade gliomas and one patient with single metastasis). A coherence-based model was developed for analysis of BOLD fMRI, which took into account altered hemodynamics in peritumoral zones. Obtained coherence maps demonstrated clinically more significant activation zones that were not seen with standard methods of fMRI processing. Thus, neurovascular uncoupling that is known to affect the accuracy of the BOLD fMRI response adjacent to brain tumors may be partially overcome by including an independent measurement of vasoreactivity using a breath-holding test in the BOLD analysis.Чувствительность предоперационных функциональных МРТ (фМРТ) может быть ограничена ослаблением BOLD-ответа (Blood-Oxygen-Level-Dependent), обусловленным патологической вазореактивностью и нейроваскулярным рассогласованием в злокачественных опухолях мозга и перитуморальной зоне. В нашем исследовании мы попытались преодолеть эти ограничения при помощи теста задержки дыхания и более точно локализовать функционально значимые зоны коры, расположенные рядом с опухолями мозга. Локальная вазореактивность с применением парадигмы задержки дыхания и аналогичным блоковым дизайном, как при моторных и речевых тестах, была определена у 5 здоровых добровольцев и 3 пациентов в предоперационном периоде (у 2 пациентов с глиомами высокой степени злокачественности и у 1 - с единичным метастазом). Была создана модель анализа BOLD фМРТ, основанная на когерентности, учитывающая измененную гемодинамику в перитуморальной зоне. Карты активации, вычисленные с применением когерентной модели, показали клинически значимые зоны активации, не выявлявшиеся при стандартных методах обработки фМРТ. Таким образом, нейроваскулярное рассогласование, оказывающее влияние на точность BOLD фМРТ-ответа вблизи опухолей мозга, может быть частично преодолено с помощью включения в BOLD-анализ независимого измерения вазореактивности при применении теста задержки дыхания. Исследования поддержаны грантом РФФИ #17-54-33018/17.

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.

An important problem of the analysis of fMRI experiments is to achieve some noise reduction of the data without blurring the shape of the activation areas. As a novel solution to this problem, the Propagation-Separation approach (PS), a structure adaptive smoothing method, has been proposed recently. PS adapts to different shapes of activation areas by generating a spatial structure corresponding to similarities and differences between time series in adjacent locations. In this paper we demonstrate how this method results in more accurate localization of brain activity. First, it is shown in numerical simulations that PS is superior over Gaussian smoothing with respect to the accurate description of the shape of activation clusters and and results in less false detections. Second, in a study of 37 presurgical planning cases we found that PS and Gaussian smoothing often yield different results, and we present examples showing aspects of the superiority of PS as applied to presurgical planning.

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.

BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (LINCL), a form of Batten disease, is a fatal neurodegenerative genetic disorder, diagnosed via DNA testing, that affects approximately 200 children in the United States at any one time. This study was conducted to evaluate whether quantitative data derived by diffusion-weighted MR imaging (DWI) techniques can supplement clinical disability scale information to provide a quantitative estimate of neurodegeneration, as well as disease progression and severity. MATERIALS AND METHODS: This study prospectively analyzed 32 DWI examinations from 18 patients having confirmed LINCL at various stages of disease. A whole-brain apparent diffusion coefficient (ADC) histogram was fitted with a dual Gaussian function combined with a function designed to model voxels containing a partial volume fraction of brain parenchyma versus CSF. Previously published whole-brain ADC values of age-matched control subjects were compared with those of the LINCL patients. Correlations were tested between the peak ADC of the fitted histogram and patient age, disease severity, and a CNS disability scale adapted for LINCL. RESULTS: ADC values assigned to brain parenchyma were higher than published ADC values for age-matched control subjects. ADC values between patients and control subjects began to differ at 5 years of age based on 95% confidence intervals. ADC values had a nearly equal correlation with patient age (R(2) = 0.71) and disease duration (R(2) = 0.68), whereas the correlation with the central nervous system disability scale (R(2) = 0.27) was much weaker. CONCLUSION: This study indicates that brain ADC values acquired using DWI may be used as an independent measure of disease severity and duration in LINCL.

Carmustine wafers (Gliadel Wafer) are implanted at resection in some patients with high-grade gliomas. Studies suggest that proton magnetic resonance spectroscopic imaging ((1)H MRSI) demonstrates early changes predictive of future failure or response to systemic chemotherapy. This study explores (1)H MRSI as a means to assess peri-tumoral tissue response post-resection and Gliadel((R)) implantation in patients with high-grade gliomas. Pilot (1)H MRSI data are presented that demonstrate noninvasive, serial monitoring of metabolic changes at the tumor site following Gliadel implantation. Three patients with newly diagnosed glioblastoma multiforme (GBM) underwent MRI and (1)H MRSI at 3.0 Tesla prior to resection and at 3-5 andor =12 weeks post-operatively. Baseline MRS spectra of tumor tissue from all patients were characterized by marked increases of choline (CHO) and lactate (LAC), and a decrease of N-acetylaspartate (NAA), typical of GBM compared with normal contra-lateral brain tissue. Post-operatively, spectra were analyzed from the resection cavity and peri-tumoral regions and compared with normal tissue from the contra-lateral brain at baseline. In 2 of 3 patients, peri-tumoral NAA/CRE increased and CHO/NAA decreased compared to contra-lateral brain at 3-5 weeks compared with baseline following Gliadel therapy and surgery but prior to radiotherapy. This study indicates that (1)H MRSI has the ability to localize regions of heterogeneous response following Gliadel treatment. Although data are limited, these results suggest that metabolic indicators of outcome can be successfully monitored pre- and post-surgical resection and Gliadel implantation with (1)H MRSI. Additional study of patients receiving Gliadel Wafers using (1)H MRSI may serve to aid clinicians in assessing tumor regression and gauging efficacy of this chemotherapy treatment.

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 characteristicthat 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.

Background and Purpose— Level of consciousness is frequently assessed by command-following ability in the clinical setting. However, it is unclear what brain circuits are needed to follow commands. We sought to determine what networks differentiate command following from noncommand following patients after hemorrhagic stroke. Methods— Structural MRI, resting-state functional MRI, and electroencephalography were performed on 25 awake and unresponsive patients with acute intracerebral and subarachnoid hemorrhage. Structural injury was assessed via volumetric T1-weighted MRI analysis. Functional connectivity differences were analyzed against a template of standard resting-state networks. The default mode network (DMN) and the task-positive network were investigated using seed-based functional connectivity. Networks were interrogated by pairwise coherence of electroencephalograph leads in regions of interest defined by functional MRI. Results— Functional imaging of unresponsive patients identified significant differences in 6 of 16 standard resting-state networks. Significant voxels were found in premotor cortex, dorsal anterior cingulate gyrus, and supplementary motor area. Direct interrogation of the DMN and task-positive network revealed loss of connectivity between the DMN and the orbitofrontal cortex and new connections between the task-positive network and DMN. Coherence between electrodes corresponding to right executive network and visual networks was also decreased in unresponsive patients. Conclusions— Resting-state functional MRI and electroencephalography coherence data support a model in which multiple, chiefly frontal networks are required for command following. Loss of DMN anticorrelation with task-positive network may reflect a loss of inhibitory control of the DMN by motor-executive regions. Frontal networks should thus be a target for future investigations into the mechanism of responsiveness in the intensive care unit environment.

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.

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.

Cranioplasty following decompressive craniectomy is reported to result in improved blood flow, cerebral metabolism, and concomitant neurological recovery. We used multimodal functional imaging technology in a patient with marked neurological recovery after cranioplasty, specifically, imaging of functional MRI resting state networks, auditory responses, and cerebral metabolism before and after cranioplasty. Significant functional changes observed in the images correlated with the subject’s neurological recovery. Our results suggest a link between recovery of cerebral metabolism and intrinsic brain mechanisms of cerebral vascular integration and resting state networks identified with functional MRI following cranioplasty.

Functional Magnetic Resonance Imaging inherently involves noisy measurements and a severe multiple test problem. Smoothing is usually used to reduce the effective number of multiple comparisons and to locally integrate the signal and hence increase the signal-to-noise ratio. Here, we provide a new structural adaptive segmentation algorithm (AS) that naturally combines the signal detection with noise reduction in one procedure. Moreover, the new method is closely related to a recently proposed structural adaptive smoothing algorithm and preserves shape and spatial extent of activation areas without blurring their borders.

Eye-target synchronization is critical for effective smooth pursuit of a moving visual target. We apply the nonlinear dynamical technique of stochastic-phase synchronization to human visual pursuit of a moving target, in both normal and mild traumatic brain-injured (mTBI) patients. We observe significant fatigue effects in all subject populations, in which subjects synchronize better with the target during the first half of the trial than in the second half. The fatigue effect differed, however, between the normal and the mTBI populations and between old and young subpopulations of each group. In some cases, the younger (or=40 years old) normal subjects performed better than mTBI subjects and also better than older (40 years old) normal subjects. Our results, however, suggest that further studies will be necessary before a standard of "normal" smooth pursuit synchronization can be developed.

Background European citizens are increasingly being offered Internet health services. This study investigated patterns of health-related Internet use, its consequences, and citizens' expectations about their doctors' provision of e-health services. Methods Representative samples were obtained from the general populations in Norway, Denmark, Germany, Greece, Poland, Portugal and Latvia. The total sample consisted of 7934 respondents. Interviews were conducted by telephone. Results 44 % of the total sample, 71 % of the Internet users, had used the Internet for health purposes. Factors that positively affected the use of Internet for health purposes were youth, higher education, white-collar or no paid job, visits to the GP during the past year, long-term illness or disabilities, and a subjective assessment of one's own health as good. Women were the most active health users among those who were online. One in four of the respondents used the Internet to prepare for or follow up doctors' appointments. Feeling reassured after using the Internet for health purposes was twice as common as experiencing anxieties. When choosing a new doctor, more than a third of the sample rated the provision of e-health services as important. Conclusion The users of Internet health services differ from the general population when it comes to health and demographic variables. The most common way to use the Internet in health matters is to read information, second comes using the net to decide whether to see a doctor and to prepare for and follow up on doctors' appointments. Hence, health-related use of the Internet does affect patients' use of other health services, but it would appear to supplement rather than to replace other health services.

CO RR EC TE D P RO OF these abnormalities through motor tests. Homozyous mice performed poorly and showed no improvement on the inverted grip and rotarod tests. Together, these data suggest that the mice are impaired in their motor ability and strength, which may be due to gross accumulative manifestations in the brain. Additionally, they demonstrated increased stereotypic behavior in the open field test by entering the center zone less frequently and in categorized observation by spending more time chewing, but decreased stereotypic behavior in the marble burying test by burying fewer marbles. This study implicates particular sphingolipids in highly specific functions within the brain and a complex, but specific, system to regulate their expression. The detailed ceramide composition of the mouse brain illustrated in this study can serve as a reference point upon which brains from other neurological and storage disorders can be compared.

A novel two-dimensional ladder network resonator design is introduced for signal transmission and detection in magnetic resonance imaging. It is shown that planar structures consisting solely of inductively coupled elements have a high-pass eigenmode spectrum and exhibit eigenfunctions which can be used for magnetic resonance imaging, including quadrature operation. Two 5 times 5 element prototypes, a planar surface coil and a volume head coil, are presented to demonstrate the suitability of the design for imaging at 3.0 Tesla

We used diffusion tensor imaging (DTI) to study 2 patients with traumatic brain injury. The first patient recovered reliable expressive language after 19 years in a minimally conscious state (MCS); the second had remained in MCS for 6 years. Comparison of white matter integrity in the patients and 20 normal subjects using histograms of apparent diffusion constants and diffusion anisotropy identified widespread altered diffusivity and decreased anisotropy in the damaged white matter. These findings remained unchanged over an 18-month interval between 2 studies in the first patient. In addition, in this patient, we identified large, bilateral regions of posterior white matter with significantly increased anisotropy that reduced over 18 months. In contrast, notable increases in anisotropy within the midline cerebellar white matter in the second study correlated with marked clinical improvements in motor functions. This finding was further correlated with an increase in resting metabolism measured by PET in this subregion. Aberrant white matter structures were evident in the second patient's DTI images but were not clinically correlated. We propose that axonal regrowth may underlie these findings and provide a biological mechanism for late recovery. Our results are discussed in the context of recent experimental studies that support this inference.

This article reviews and discusses recent findings in functional MRI at 1.5 and 3.0 T magnetic field strengths, in research and clinical applications. Particular attention is paid to comparative studies and to an explanation of the physical and biological dependencies leading to potential gains and tradeoffs of functional scanning at magnets with a high field strength.

Data from functional magnetic resonance imaging (fMRI) consist of time series of brain images that are characterized by a low signal-to-noise ratio. In order to reduce noise and to improve signal detection, the fMRI data are spatially smoothed. However, the common application of a Gaussian filter does this at the cost of loss of information on spatial extent and shape of the activation area. We suggest to use the propagation-separation procedures introduced by Polzehl, J., Spokoiny, V. (2006). Propagation-separation approach for local likelihood estimation. Probab. Theory Relat. Fields, in print. instead. We show that this significantly improves the information on the spatial extent and shape of the activation region with similar results for the noise reduction. To complete the statistical analysis, signal detection is based on thresholds defined by random field theory. Effects of adaptive and non-adaptive smoothing are illustrated by artificial examples and an analysis of experimental data.

We propose a quantitative model for human smooth pursuit tracking of a continuously moving visual target which is based on synchronization of an internal expectancy model of the target position coupled to the retinal target signal. The model predictions are tested in a smooth circular pursuit eye tracking experiment with transient target blanking of variable duration. In subjects with a high tracking accuracy, the model accounts for smooth pursuit and repeatedly reproduces quantitatively characteristic patterns of the eye dynamics during target blanking. In its simplest form, the model has only one free parameter, a coupling constant. An extended model with a second parameter, a time delay or memory term, accounts for predictive smooth pursuit eye movements which advance the target. The model constitutes an example of synchronization of a complex biological system with perceived sensory signals.

Epilepsy is characterized by the sudden occurrence of seizures disturbing the perception or behavior of epileptic patients. Several prediction methods have claimed to be able to predict seizures based on EEG-recordings minutes in advance, which opens up new approaches to treat the disease. However, the term seizure prediction is not unequivocally defined and different assessment criteria for prediction methods exist which impedes the comparison between methods. Moreover, only little attention is paid to the dependency between sensitivity and false prediction rate. We address these shortcomings and introduce a terminology and assessment criterion for seizure prediction methods based on statistical and clinical considerations: the seizure prediction characteristic.

The main intention of this contribution is to discuss different nonlinear approaches to heart rate and blood pressure variability analysis for a better understanding of the cardiovascular regulation. We investigate measures of complexity which are based on symbolic dynamics, renormalised entropy and the finite time growth rates. The dual sequence method to estimate the baroreflex sensitivity and the maximal correlation method to estimate the nonlinear coupling between time series are employed for analysing bivariate data. The latter appears to be a suitable method to estimate the strength of the nonlinear coupling and the coupling direction. Heart rate and blood pressure data from clinical pilot studies and from very large clinical studies are analysed. We demonstrate that parameters from nonlinear dynamics are useful for risk stratification after myocardial infarction, for the prediction of life-threatening cardiac events even in short time series, and for modelling the relationship between heart rate and blood pressure regulation. These findings could be of importance for clinical diagnostics, in algorithms for risk stratification, and for therapeutic and preventive tools of next generation implantable cardioverter defibrillators.

Objective: To assess whether 1) repetitive transcranial magnetic stimulation (rTMS) can ameliorate aphasia in Alzheimer9s disease (AD) patients and 2) whether there are changes in activation patterns in relevant cortical areas using functional brain imaging subsequent to rTMS. Background Among the earliest manifestations of AD are deficits in language that significantly impair patients9 quality of life. Currently approved agents for slowing progression of AD do not target aphasia. Studies have demonstrated beneficial effects of rTMS in improving cognition and language deficits in patients with neurological disorders. rTMS may be a potential therapeutic tool to help improve aphasia in AD patients. Design/Methods: Eleven AD patients with aphasia underwent 4 sessions of rTMS applied to the dorsolateral prefrontal cortex at a frequency of 10-15 Hz over two weeks. They underwent standardized cognitive tests at baseline, immediately after completing the course of rTMS, and 4-weeks after the last rTMS treatment. All patients underwent concomitant functional MRI (fMRI) scans at the time of the tests while performing cognitive paradigms in the scanner. Results: All patients completed the cognitive portions of the study. Three patients could not tolerate imaging and therefore did not complete the imaging portion of the study. There was improvement in verbal and non-verbal agility on testing that was seen 4-weeks post-treatment relative to baseline (p Conclusions: These preliminary results suggest that rTMS may serve as an effective adjunctive treatment for aphasia found in AD patients. Further research using control stimulation is needed. Disclosure: Dr. Devi has nothing to disclose. Dr. Levine has nothing to disclose. Dr. Voss has nothing to disclose. Dr. de Boisblanc has nothing to disclose. Dr. Heier has nothing to disclose. Dr. Halper has nothing to disclose.