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Abstract: Previous studies using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) of the brain have found that a distributed parietal–frontal neuronal network is activated in normals during both auditory and visual oddball tasks. The common cortical regions in this network are inferior parietal lobule (IPL)/supramarginal gyrus (SMG), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). It is not clear whether the same network is activated by oddball tasks during somatosensory stimulation. The present study addressed this question by testing healthy adults as they performed a novel median-nerve oddball paradigm while undergoing magnetoencephalography (MEG). An automated multiple dipole analysis technique, the Multi-Start Spatio-Temporal (MSST) algorithm, localized multiple neuronal generators, and identified their time-courses. IPL/SMG, ACC, and DLPFC were reliably localized in the MEG median-nerve oddball responses, with IPL/SMG activation significantly preceding ACC and DLPFC activation. Thus, the same parietal–frontal neuronal network that shows activation during auditory and visual oddball tests is activated in a median-nerve oddball paradigm. Regions uniquely related to somatosensory oddball responses (e.g., primary and secondary somatosensory, dorsal premotor, primary motor, and supplementary motor areas) were also localized. Since the parietal–frontal network supports attentional allocation during performance of the task, this study may provide a novel method, as well as normative baseline data, for examining attention-related deficits in the somatosensory system of patients with neurological or psychiatric disorders. [Copyright &y& Elsevier]

The thalamus has a demonstrated role in language, particularly through its connectivity to frontal language cortices. A 59-year-old man with transient mixed aphasia following resection of a left-sided thalamic cavernous malformation is reported. No operative complications were encountered, and there was no surgical contact with cortical language areas. The patient recovered full language function within a week postoperatively. The role of thalamic nuclei in language processes and other reports of transient thalamic aphasia are reviewed. [ABSTRACT FROM AUTHOR]

Blast-related mild traumatic brain injury (bmTBI) often leads to long-term sequalae, but diagnostic approaches are lacking due to insufficient knowledge about the predominant pathophysiology. This study aimed to build a diagnostic model for future verification by applying machine-learning based support vector machine (SVM) modeling to diffusion tensor imaging (DTI) datasets to elucidate white-matter features that distinguish bmTBI from healthy controls (HC). Twenty subacute/chronic bmTBI and 19 HC combat-deployed personnel underwent DTI. Clinically relevant features for modeling were selected using tract-based analyses that identified group differences throughout white-matter tracts in five DTI metrics to elucidate the pathogenesis of injury. These features were then analyzed using SVM modeling with cross validation. Tract-based analyses revealed abnormally decreased radial diffusivity (RD), increased fractional anisotropy (FA) and axial/radial diffusivity ratio (AD/RD) in the bmTBI group, mostly in anterior tracts (29 features). SVM models showed that FA of the anterior/superior corona radiata and AD/RD of the corpus callosum and anterior limbs of the internal capsule (5 features) best distinguished bmTBI from HCs with 89% accuracy. This is the first application of SVM to identify prominent features of bmTBI solely based on DTI metrics in well-defined tracts, which if successfully validated could promote targeted treatment interventions. [ABSTRACT FROM AUTHOR]

A modified probabilistic neural network (PNN) for brain tissue segmentation with magnetic resonance imaging (MRI) is proposed. In this approach, covariance matrices are used to replace the singular smoothing factor in the PNN's kernel function, and weighting factors are added in the pattern of summation layer. This weighted probabilistic neural network (WPNN) classifier can account for partial volume effects, which exist commonly in MRI, not only in the final result stage, but also in the modeling process. It adopts the self-organizing map (SOM) neural network to overly segment the input MR image, and yield reference vectors necessary for probabilistic density function (pdf) estimation. A supervised "soft" labeling mechanism based on Bayesian rule is developed, so that weighting factors can be generated along with corresponding SOM reference vectors. Tissue classification results from various algorithms are compared, and the effectiveness and robustness of the proposed approach are demonstrated. [ABSTRACT FROM AUTHOR]

Abstract: Signal Space Separation (SSS) method is based on the solution of Laplace''s equation: expansion of the spherical harmonics. It has been realized and proved that the series of vector spherical harmonics solution can be split into two parts that are related to the MEG (magnetoencephalography) measurements: brain signals and external interferences. In practice, SSS has become an elegant and promising method to recover bio-magnetic signal and remove external disturbance in empirical MEG measurements. In the present study, we evaluate SSS comprehensively via computer simulation and real applications. We generate two types of interference sources: magnetic dipole and electric current dipole. We examine the suppression effect for interference signals, and the goodness of the reconstruction for the interested signal. The expansion order of vector spherical harmonics plays critical role in both signal reconstruction in the brain and external artifact reduction, this is studied thoroughly and demonstrated in this paper. Besides computer simulation, SSS method is also applied on real MEG data sets and the effectiveness is investigated. Finally, we give an objective conclusion of the advantage and limitation of SSS method, and assess its value in practical MEG measurements. [Copyright &y& Elsevier]

Cytoarchitectural brain changes during normal aging remain poorly characterized, and it is unclear whether patterns of brain aging differ by sex. This study used restriction spectrum imaging to examine associations between age and brain microstructure in 147 community-dwelling participants (aged 56-99 years). Widespread associations with age in multiple diffusion compartments, including increased free water, decreased restricted and hindered diffusion, and reduced neurite complexity, were observed in the cortical gray matter, the white matter tracts, and the hippocampus. Age differences in cortical microstructure were largely independent of atrophy. Associations were mostly global, although foci of stronger effects emerged in the fornix, anterior thalamic radiation and commissural fibers, and the medial temporal, orbitofrontal, and occipital cortices. Age differences were stronger and more widespread for women than men, even after adjustment for education, hypertension, and body mass index. Restriction spectrum imaging may be a convenient, noninvasive tool for monitoring changes in diffusion properties that are thought to reflect reduced cellular fractions and neurite density or complexity, which occur with typical aging, and for detecting sex differences in patterns of brain aging. • We used RSI to assess associations between age and brain microstructure. • Age correlated with restricted, hindered and free diffusion in cortex and fibers. • Age-RSI associations were stronger and more widespread for women than for men. • Gray matter age-RSI associations persisted after controlling for cortical thickness. • Regional age-RSI associations emerged after adjusting for whole-brain RSI. [ABSTRACT FROM AUTHOR]

Visuospatial working memory impairments are common in Parkinson's disease (PD), yet the underlying neural mechanisms are poorly understood. The present study investigated abnormalities in context‐dependent functional connectivity of working memory hubs in PD. Cognitively normal PD and control participants underwent fMRI while performing a visuospatial working memory task. To identify sources of dysfunction, distraction, and load‐modulated connectivity were disentangled for encoding and retrieval phases of the task. Despite normal working memory performance in PD, two features of abnormal connectivity were observed, one due to a loss in normal context‐related connectivity and another related to upregulated connectivity of hubs for which the controls did not exhibit context‐dependent connectivity. During encoding, striatal‐prefrontal coupling was lost in PD, both during distraction and high memory loads. However, long‐range connectivity of prefrontal, medial temporal and occipital hubs was upregulated in a context‐specific manner. Memory retrieval was characterized by different aberrant connectivity patterns, wherein precuneus connectivity was upregulated during distraction, whereas prefrontal couplings were lost as memory load approached capacity limits. Features of abnormal functional connectivity in PD had pathological and compensatory influences as they correlated with poorer working memory or better visuospatial skills. The results offer new insights into working memory‐related signatures of aberrant cortico–cortical and corticostriatal functional connections, which may portend future declines in different facets of working memory. [ABSTRACT FROM AUTHOR]

Background: When patients present to emergency departments (EDs) with symptoms suspicious for ventriculoperitoneal shunt malfunction, evaluation often includes imaging of the shunt with both computed tomography (CT) of the head without contrast and a plain radiograph "shunt series" (SS). Recent literature has called into question the diagnostic value of the SS for the detection of ventriculoperitoneal shunt complications, suggesting that the plain radiographs provide redundant information and unnecessary exposure to radiation.Objective: The aim of our study was to assess the frequency of abnormal SS plain radiography and head CT in the evaluation of shunt malfunction in all adult ED patients and to measure the association of abnormalities on CT and SS with surgical intervention.Methods: We performed a retrospective chart review of all emergency department encounters at an urban level I trauma center between August 1, 2013 and October 3, 2018 in which an SS and head CT examination were performed within 24 h of each other. We described the results of imaging studies qualitatively and descriptive statistics were performed.Results: Positive findings on CT were significantly associated with the decision to proceed to surgery. Positive findings on SS, however, were not significantly associated with the decision to proceed to surgery.Conclusions: The potential information gained from SS and convenience of ordering simultaneously with head CT does not appear to outweigh the risk of increased radiation exposure to the patient, the additional costs of the study, and the potential delay in time to head CT. These findings support the initial use of head CT in evaluation of shunt malfunction. [ABSTRACT FROM AUTHOR]

Background: Mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members, Veterans, and civilians. However, few treatments are available for mTBI, partially because the mechanism of persistent mTBI deficits is not fully understood. Methods: We used magnetoencephalography (MEG) to investigate neuronal changes in individuals with mTBI following a passive neurofeedback-based treatment programme called IASIS. This programme involved applying low-intensity pulses using transcranial electrical stimulation (LIP-tES) with electroencephalography monitoring. Study participants included six individuals with mTBI and persistent post-concussive symptoms (PCS). MEG exams were performed at baseline and follow-up to evaluate the effect of IASIS on brain functioning. Results: At the baseline MEG exam, all participants had abnormal slow-waves. In the follow-up MEG exam, the participants showed significantly reduced abnormal slow-waves with an average reduction of 53.6 ± 24.6% in slow-wave total score. The participants also showed significant reduction of PCS scores after IASIS treatment, with an average reduction of 52.76 ± 26.4% in PCS total score. Conclusions: The present study demonstrates, for the first time, the neuroimaging-based documentation of the effect of LIP-tES treatment on brain functioning in mTBI. The mechanisms of LIP-tES treatment are discussed, with an emphasis on LIP-tES’s potentiation of the mTBI healing process. [ABSTRACT FROM PUBLISHER]

Blast mild traumatic brain injury (mTBI) is a leading cause of sustained impairment in military service members and veterans. However, the mechanism of persistent disability is not fully understood. The present study investigated disturbances in brain functioning in mTBI participants using a source-imaging-based approach to analyze functional connectivity (FC) from resting-state magnetoencephalography (rs-MEG). Study participants included 26 active-duty service members or veterans who had blast mTBI with persistent post-concussive symptoms, and 22 healthy control active-duty service members or veterans. The source time courses from regions of interest (ROIs) were used to compute ROI to whole-brain (ROI-global) FC for different frequency bands using two different measures: 1) time-lagged cross-correlation and 2) phase-lock synchrony. Compared with the controls, blast mTBI participants showed increased ROI-global FC in beta, gamma, and low-frequency bands, but not in the alpha band. Sources of abnormally increased FC included the: 1) prefrontal cortex (right ventromedial prefrontal cortex [vmPFC], right rostral anterior cingulate cortex [rACC]), and left ventrolateral and dorsolateral prefrontal cortex; 2) medial temporal lobe (bilateral parahippocampus, hippocampus, and amygdala); and 3) right putamen and cerebellum. In contrast, the blast mTBI group also showed decreased FC of the right frontal pole. Group differences were highly consistent across the two different FC measures. FC of the left ventrolateral prefrontal cortex correlated with executive functioning and processing speed in mTBI participants. Altogether, our findings of increased and decreased regionalpatterns of FC suggest that disturbances in intrinsic brain connectivity may be the result of multiple mechanisms, and are associated with cognitive sequelae of the injury. [ABSTRACT FROM AUTHOR]

Objective Localizing expressive language function has been challenging using the conventional magnetoencephalography (MEG) source modeling methods. The present MEG study presents a new accurate and precise approach in localizing the language areas using a high-resolution MEG source imaging method. Methods In 32 patients with brain tumors and/or epilepsies, an object-naming task was used to evoke MEG responses. Our Fast-VESTAL source imaging method was then applied to the MEG data in order to localize the brain areas evoked by the object-naming task. Results The Fast-VESTAL results showed that Broca’s area was accurately localized to the pars opercularis (BA 44) and/or the pars triangularis (BA 45) in all patients. Fast-VESTAL also accurately localized Wernicke’s area to the posterior aspect of the superior temporal gyri in BA 22, as well as several additional brain areas. Furthermore, we found that the latency of the main peak of the response in Wernicke’s area was significantly earlier than that of Broca’s area. Conclusion In all patients, Fast-VESTAL analysis established accurate and precise localizations of Broca’s area, as well as other language areas. The responses in Wernicke’s area were also shown to significantly precede those of Broca’s area. Significance The present study demonstrates that using Fast-VESTAL, MEG can serve as an accurate and reliable functional imaging tool for presurgical mapping of language functions in patients with brain tumors and/or epilepsies. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) is common in the United States, accounting for as many as 75-80% of all TBIs. It is recognized as a significant public health concern, but there are ongoing controversies regarding the etiology of persistent symptoms post-mTBI. This constellation of nonspecific symptoms is referred to as postconcussive syndrome (PCS). The present study combined results from magnetoencephalography (MEG) and cognitive assessment to examine group differences and relationships between brain activity and cognitive performance in 31 military and civilian individuals with a history of mTBI+PCS and 33 matched healthy control subjects. An operator-free analysis was used for MEG data to increase reliability of the technique. Subjects completed a comprehensive neuropsychological assessment, and measures of abnormal slow-wave activity from MEG were collected. Results demonstrated significant group differences on measures of executive functioning and processing speed. In addition, significant correlations between slow-wave activity on MEG and patterns of cognitive functioning were found in cortical areas, consistent with cognitive impairments on exams. Results provide more objective evidence that there may be subtle changes to the neurobiological integrity of the brain that can be detected by MEG. Further, these findings suggest that these abnormalities are associated with cognitive outcomes and may account, at least in part, for long-term PCS in those who have sustained an mTBI. [ABSTRACT FROM AUTHOR]

Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI. [ABSTRACT FROM AUTHOR]

Background The use of noncontrast head computed tomography (CT) has become commonplace in the emergency department (ED) as a means of screening for a wide variety of pathologies. Approximately 1 in 14 ED patients receives a head CT scan, and analyzing and interpreting this high volume of images in a timely manner is a daily challenge. Objectives Minimizing interpretation error is of paramount importance in the context of life-threatening and time-sensitive diagnoses. Therefore, it is prudent for the physician to recognize particular pitfalls in head CT interpretation and establish search patterns and practices that minimize such errors. In this article, we discuss a collection of common ED cases with easily missed findings, and identify time-effective practices and patterns to minimize interpretation error. Discussion There are numerous reasons for false-negative interpretations, including, but not limited to, incomplete or misleading clinical history, failure to review prior studies, suboptimal windowing and leveling, and failure to utilize multiple anatomic views via multi-planar reconstructions and scout views. We illustrate this in four specific clinical scenarios: stroke, trauma, headache, and altered mental status. Conclusion Accurate and timely interpretation in the emergent setting is a daily challenge for emergency physicians. Knowledge of easily overlooked yet critical findings is a first step in minimizing interpretation error. [ABSTRACT FROM AUTHOR]

This study investigated the ability of individuals with Parkinson's disease (PD) to synthesize temporal information across the senses, namely audition and vision. Auditory signals (A) are perceived as lasting longer than visual signals (V) when they are compared together, since attention is captured and sustained more easily than for visual information. We used the audiovisual illusion to probe for disturbances in brain networks that govern the resolution of time in two intersensory conditions that putatively differ in their attention demands. PD patients and controls judged the relative duration of successively presented pairs of unimodal (AA, VV) and crossmodal (VA, AV) signals whilst undergoing fMRI. There were four main findings. First, underestimation of time was exaggerated in PD when timing depended on controlled attention (AV), where as subtle deficits were found when audition dominated and attention was more easily sustained (VA). Second, group differences in regional activation were observed only for the AV-unimodal comparison, where the PD group failed tomodulate basal ganglia, anterior insula, and inferior cerebellum activity in accord with the timing condition. Third, the intersensory timing conditions were dissociated by patterns of abnormal functional connectivity. When intersensory timing emphasized controlled attention, patients showed weakened connectivity of the cortico-thalamus-basal ganglia (CTBG) circuit and the anterior insula with widespread cortical regions, yet enhanced cerebellar connectivity. When audition dominated intersensory timing, patients showed enhanced connectivity of CTBG elements, the anterior insula, and the cerebellum with the caudate tail and frontal cortex. Fourth, abnormal connectivity measures showed excellent sensitivity and specificity in accurately classifying subjects. The results demonstrate that intersensory timing deficits in PD were well characterized by context-dependent patterns of functional connectivity within a presumed core timing system(CTBG) and a ventral attention hub (anterior insula), and enhanced cerebellar connectivity irrespective of the hypothesized attention demands of timing. [ABSTRACT FROM AUTHOR]

Purpose: Working memory (WM) represents the brain’s ability to maintain information in a readily available state for short periods of time. This study examines the resting-state cortical activity patterns that are most associated with performance on a difficult working-memory task. Methods: Magnetoencephalographic (MEG) band-passed (delta/theta (1–7 Hz), alpha (8–13 Hz), beta (14–30 Hz)) and sensor based regional power was collected in a population of adult men (18–28 yrs, n = 24) in both an eyes-closed and eyes-open resting state. The normalized power within each resting state condition as well as the normalized change in power between eyes closed and open (zECO) were correlated with performance on a WM task. The regional and band-limited measures that were most associated with performance were then combined using singular value decomposition (SVD) to determine the degree to which zECO power was associated with performance on the three-back verbal WM task. Results: Changes in power from eyes closed to open revealed a significant decrease in power in all band-widths that was most pronounced in the posterior brain regions (delta/theta band). zECO right posterior frontal and parietal cortex delta/theta power were found to be inversely correlated with three-back working memory performance. The SVD evaluation of the most correlated zECO metrics then provided a singular measure that was highly correlated with three-back performance (r = −0.73, p<0.0001). Conclusion: Our results indicate that there is an association between WM performance and changes in resting-state power (right posterior frontal and parietal delta/theta power). Moreover, an SVD of the most associated zECO measures produces a composite resting-state metric of regional neural oscillatory power that has an improved association with WM performance. To our knowledge, this is the first investigation that has found that changes in resting state electromagnetic neural patterns are highly associated with verbal working memory performance. [ABSTRACT FROM AUTHOR]

Background Damage to the right parietal lobe has long been associated with various disorders of body image. The authors have recently suggested that an unusual behavioural condition in which otherwise rational individuals desire the amputation of a healthy limb might also arise from right parietal dysfunction. Methods Four subjects who desired the amputation of healthy legs (two right, one left and one, at first, bilateral and then left only) were recruited and underwent magnetoencephalography (MEG) scans during tactile stimulation of sites above and below the desired amputation line. Regions of interest (ROIs) in each hemisphere (superior parietal lobule (SPL), inferior parietal lobule, S1, M1, insula, premotor cortex and precuneus) were defined using FreeSurfer software. Results Analysis of average MEG activity across the 40e140 ms post-stimulation timeframe was carried out using an unpaired t test. This revealed significantly reduced activation only in the right SPL ROI for the subjects' affected legs when compared with both subjects' unaffected legs and that of controls. Conclusions The right SPL is a cortical area that appears ideally placed to unify disparate sensory inputs to create a coherent sense of having a body. The authors propose that inadequate activation of the right SPL leads to the unnatural situation in which the sufferers can feel the limb in question being touched without it actually incorporating into their body image, with a resulting desire for amputation. The authors introduce the term 'xenomelia' as a more appropriate name than apotemnophilia or body integrity identity disorder, for what appears to be an unrecognised right parietal lobe syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Beamformer spatial filters are commonly used to explore the active neuronal sources underlying magnetoencephalography (MEG) recordings at low signal-to-noise ratio (SNR). Conventional beamformer techniques are successful in localizing uncorrelated neuronal sources under poor SNR conditions. However, the spatial and temporal features from conventional beamformer reconstructions suffer when sources are correlated, which is a common and important property of real neuronal networks. Dual-beamformer techniques, originally developed by Brookes et al. to deal with this limitation, successfully localize highly-correlated sources and determine their orientations and weightings, but their performance degrades at low correlations. They also lack the capability to produce individual time courses and therefore cannot quantify source correlation. In this paper, we present an enhanced formulation of our earlier dual-core beamformer (DCBF) approach that reconstructs individual source time courses and their correlations. Through computer simulations, we show that the enhanced DCBF (eDCBF) consistently and accurately models dual-source activity regardless of the correlation strength. Simulations also show that a multi-core extension of eDCBF effectively handles the presence of additional correlated sources. In a human auditory task, we further demonstrate that eDCBF accurately reconstructs left and right auditory temporal responses and their correlations. Spatial resolution and source localization strategies corresponding to different measures within the eDCBF framework are also discussed. In summary, eDCBF accurately reconstructs source spatio-temporal behavior, providing a means for characterizing complex neuronal networks and their communication. [Copyright &y& Elsevier]

Background: Parkinson's disease (PD) disrupts temporal processing but the neuronal sources of deficits and their response to dopamine (DA) therapy are not understood. Though the striatum and DA transmission are thought to be essential for timekeeping potential working memory (WM) and executive problems could also disrupt timing. Methodology/Findings: The present study addressed these issues by testing controls and PD volunteers 'on' and 'off' DA therapy as they underwent fMRI while performing a time-perception task. To distinguish systems associated with abnormalities in temporal and non-temporal processes we separated brain activity during encoding and decision-making phases of a trial. Whereas both phases involved timekeeping the encoding and decision phases emphasized WM and executive processes respectively. The methods enabled exploration of both the amplitude and temporal dynamics of neural activity. First we found that time-perception deficits were associated with striatal cortical and cerebellar dysfunction. Unlike studies of timed movement our results could not be attributed to traditional roles of the striatum and cerebellum in movement. Second for the first time we identified temporal and non-temporal sources of impaired time perception. Striatal dysfunction was found during both phases consistent with its role in timekeeping. Activation was also abnormal in a WM network (middle-frontal and parietal cortex lateral cerebellum) during encoding and a network that modulates executive and memory functions (parahippocampus posterior cingulate) during decision making. Third, hypoactivation typified neuronal dysfunction in PD but was sometimes characterized by abnormal temporal dynamics (e.g., lagged prolonged) that were not due to longer response times. Finally DA therapy did not alleviate timing deficits. Conclusions/Significance: Our findings indicate that impaired timing in PD arises from nigrostriatal and mesocortical dysfunction in systems that mediate temporal and non-temporal control-processes. However time perception impairments were not improved by DA treatment likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity. [ABSTRACT FROM AUTHOR]

Abstract: The “Dual-Core Beamformer” (DCBF) is a new lead-field based MEG inverse-modeling technique designed for localizing highly correlated networks from noisy MEG data. Conventional beamformer techniques are successful in localizing neuronal sources that are uncorrelated under poor signal-to-noise ratio (SNR) conditions. However, they fail to reconstruct multiple highly correlated sources. Though previously published dual-beamformer techniques can successfully localize multiple correlated sources, they are computationally expensive and impractical, requiring a priori information. The DCBF is able to automatically calculate optimal amplitude-weighting and dipole orientation for reconstruction, greatly reducing the computational cost of the dual-beamformer technique. Paired with a modified Powell algorithm, the DCBF can quickly identify multiple sets of correlated sources contributing to the MEG signal. Through computer simulations, we show that the DCBF quickly and accurately reconstructs source locations and their time-courses under widely varying SNR, degrees of correlation, and source strengths. Simulations also show that the DCBF identifies multiple simultaneously active correlated networks. Additionally, DCBF performance was tested using MEG data in humans. In an auditory task, the DCBF localized and reconstructed highly correlated left and right auditory responses. In a median-nerve stimulation task, the DCBF identified multiple meaningful networks of activation without any a priori information. Altogether, our results indicate that the DCBF is an effective and valuable tool for reconstructing correlated networks of neural activity from MEG recordings. [ABSTRACT FROM AUTHOR]

The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions. [ABSTRACT FROM AUTHOR]

Abstract: The ability of magnetoencephalography (MEG) to accurately localize neuronal currents and obtain tangential components of the source is largely due to MEG''s insensitivity to the conductivity profile of the head tissues. However, MEG cannot reliably detect the radial component of the neuronal current. In contrast, the localization accuracy of electroencephalography (EEG) is not as good as MEG, but EEG can detect both the tangential and radial components of the source. In the present study, we investigated the conductivity dependence in a new approach that combines MEG and EEG to accurately obtain, not only the location and tangential components, but also the radial component of the source. In this approach, the source location and tangential components are obtained from MEG alone, and optimal conductivity values of the EEG model are estimated by best-fitting EEG signal, while precisely matching the tangential components of the source in EEG and MEG. Then, the radial components are obtained from EEG using the previously estimated optimal conductivity values. Computer simulations testing this integrated approach demonstrated two main findings. First, there are well-organized optimal combinations of the conductivity values that provide an accurate fit to the combined MEG and EEG data. Second, the radial component, in addition to the location and tangential components, can be obtained with high accuracy without needing to know the precise conductivity profile of the head. We then demonstrated that this new approach performed reliably in an analysis of the 20-ms component from human somatosensory responses elicited by electric median-nerve stimulation. [Copyright &y& Elsevier]

The orienting of attention to different locations in space is fundamental to most organisms and occurs in all sensory modalities. Orienting has been extensively studied in vision, but to date, few studies have investigated neuronal networks underlying automatic orienting of attention and inhibition of return to auditory signals. In the current experiment, functional magnetic resonance imaging and behavioral data were collected while healthy volunteers performed an auditory orienting task in which a monaurally presented tone pip (cue) correctly or incorrectly cued the location of a target tone pip. The stimulus onset asynchrony (SOA) between the cue and target was 100 or 800 msec. Behavioral results were consistent with previous studies showing that valid auditory cues produced facilitation at the short SOA and inhibition of return at the long SOA. Functional results indicated that the reorienting of attention (100 msec SOA) and inhibition of return (800 msec SOA) were mediated by both common and distinct neuronal structures. Both attention mechanisms commonly activated a network consisting of fronto-oculomotor areas, the left postcentral gyrus, right premotor area, and bilateral tonsil of the cerebellum. Several distinct areas of frontal and parietal activation were identified for the reorienting condition, whereas the right inferior parietal lobule was the only structure uniquely associated with inhibition of return. [ABSTRACT FROM AUTHOR]

Abstract: Minimum L1-norm solutions have been used by many investigators to analyze MEG responses because they provide high spatial resolution images. However, conventional minimum L1-norm approaches suffer from instability in spatial construction, and poor smoothness of the reconstructed source time-courses. Activity commonly “jumps” from one grid point to (usually) the neighboring grid points. Equivalently, the time-course of one specific grid point can show substantial “spiky-looking” discontinuity. In the present study, we present a new vector-based spatial–temporal analysis using a L1-minimum-norm (VESTAL). This approach is based on a principle of MEG physics: the magnetic waveforms in sensor-space are linear functions of the source time-courses in the imaging-space. Our computer simulations showed that VESTAL provides good reconstruction of the source amplitude and orientation, with high stability and resolution in both the spatial and temporal domains. “Spiky-looking” discontinuity was not observed in the source time-courses. Importantly, the simulations also showed that VESTAL can resolve sources that are 100% correlated. We then examined the performance of VESTAL in the analysis of human median-nerve MEG responses. The results demonstrated that this method easily distinguishes sources very spatially close to each other, including individual primary somatosensory areas (BA 1, 2, 3b), primary motor area (BA 4), and other regions in the somatosensory system (e.g., BA 5, 7, SII, SMA, and temporal–parietal junction) with high temporal stability and resolution. VESTAL''s potential for obtaining information on source extent was also examined. [Copyright &y& Elsevier]

A novel hybrid algorithm for the tissue segmentation of brain magnetic resonance images is proposed. The core of the algorithm is a probabilistic neural network (PNN) in which weighting factors are added to the summation layer, such that partial volume effects can be taken into account in the modeling process. The mean vectors for the probability density function estimation and the corresponding weighting factors are generated by a hierarchical scheme involving a self-organizing map neural network and an expectation maximization algorithm. Unlike conventional PNN, this approach circumvents the need for training sets. Tissue segmentation results from various algorithms are compared and the effectiveness and robustness of the proposed approach are demonstrated. [ABSTRACT FROM AUTHOR]

A novel hybrid algorithm for the tissue segmentation of brain magnetic resonance images is proposed. The core of the algorithm is a probabilistic neural network (PNN) in which weighting factors are added to the summation layer, such that partial volume effects can be taken into account in the modeling process. The mean vectors for the probability density function estimation and the corresponding weighting factors are generated by a hierarchical scheme involving a self-organizing map neural network and an expectation maximization algorithm. Unlike conventional PNN, this approach circumvents the need for training sets. Tissue segmentation results from various algorithms are compared and the effectiveness and robustness of the proposed approach are demonstrated. [ABSTRACT FROM AUTHOR]

Despite numerous studies in which hippocampal abnormalities were found, schizophrenia patients' hippocampal neural activity has not been systematically evaluated on a specific hippocampal-dependent task. The transverse-patterning task (TP) is sensitive to the relational mnemonic capabilities of the hippocampus. Ten schizophrenia patients and 10 controls performed TP and control tasks that are not hippocampal dependent. As predicted, patients displayed a behavioral impairment in TP and not in control tasks. Magnetoencephalography showed controls activating right hippocampus during TP performance. Patients showed more bilateral or left hippocampal activation during TP, and greater left lateralization was associated with better performance on TP. Patients' abnormal hippocampal lateralization may play a role in the hippocampal-dependent behavioral deficit. [ABSTRACT FROM AUTHOR]

Abstract: Auditory response profiles for a group of ten healthy young and ten healthy elderly subjects, evoked by implicit memory and delayed verbal recognition tasks, were evaluated to determine if effects of stimulus repetition could be identified in the superior temporal gyrus (STG) and prefrontal cortical regions. We hypothesized that effects of stimulus repetition should occur both early in time and at early levels of the nervous system (STG) followed by later effects in prefrontal regions. Magnetoencephalographic (MEG) responses were recorded using a whole-head MEG system and automated, multi-start analysis methods were applied to the data in order to characterize the temporal response profiles from distributed but focal, cortical regions engaged in memory-related tasks. The findings revealed a main effect of age for early activity (∼50 ms) in STG which appeared to be nonspecific for Old/New words and an Age × Task interaction for late activity (∼100–800 ms) in STG which was specific to Old/New words. Although the behavioral performance measures did not reveal traditional effects of response priming, the MEG measures did reveal a reduction in amplitude with stimulus repetition in young subjects. The elderly did not reveal a reduction in amplitude concomitant with stimulus repetition for either the global attributes of words or for specific Old/New words. Long duration effects of stimulus repetition noted in the present study raise the possibility that results from sensory gating, mismatch negativity and P300 paradigms may represent a continuum of stimulus repetition effects. Two of these paradigms evoke greater enhancement to novel or infrequent stimuli, or rather, greater reduction of amplitude with repetition. [Copyright &y& Elsevier]

The article presents information on the consequences of overdoses of olanzapine. It reports that typical antipsychotics are a relatively new group of medications for the management of psychosis. Currently approved medications of this category include clozapine, risperidone, quetiapine, and olanzapine. Overdoses can lead to deaths. The American Association of Poison Control Centers Toxic Exposure Surveillance System reported the number of deaths associated with olanzapine to be six in 2000, 10 in 2001, and 10 in 2002. The article presents a case history of a 62-year-old married man who had a long and clear history of bipolar affective disorder with features of obsessive compulsion, and was treated by psychiatrists for more than 10 years.

Our perception of time depends on multiple psychological processes that allow us to anticipate events. In this study, we used event-related functional magnetic resonance imaging (fMRI) to differentiate neural systems involved in formulating representations of time from processes associated with making decisions about their duration. A time perception task consisting of two randomly presented standard intervals was used to ensure that intervals were encoded on each trial and to enhance memory requirements. During the encoding phase of a trial, activation was observed in the right caudate nucleus, right inferior parietal cortex and left cerebellum. Activation in these regions correlated with timing sensitivity (coefficient of variation). In contrast, encoding-related activity in the right parahippocampus and hippocampus correlated with the bisection point and right precuneus activation was associated with a measure of memory distortion. Decision processes were studied by examining brain activation during the decision phase of a trial that was associated with the difficulty of interval discriminations. Activation in the right parahippocampus was greater for easier than harder discriminations. In contrast, activation was greater for harder than easier discriminations in systems involved in working memory (left middle-frontal and parietal cortex) and auditory rehearsal (left inferior-frontal and superior-temporal cortex). Activity in the auditory rehearsal network correlated with memory distortion. Our results support the independence of systems that mediate interval encoding and decision processes. The results also suggest that distortions in memory for time may be due to strategic processing in cortical systems involved in either encoding or rehearsal. [Copyright &y& Elsevier]

The role of motor activity ipsilateral to movement remains a matter of debate, due in part to discrepancies among studies in the localization of this activity, when observed, and uncertainty about its time course. The present study used magnetoencephalography (MEG) to investigate the spatial localization and temporal dynamics of contralateral and ipsilateral motor activity during the preparation of unilateral finger movements. Eight right-handed normal subjects carried out self-paced finger-lifting movements with either their dominant or nondominant hand during MEG recordings. The Multi-Start Spatial Temporal multi-dipole method was used to analyze MEG responses recorded during the movement preparation and early execution stage (−800 msec to +30 msec) of movement. Three sources were localized consistently, including a source in the contralateral primary motor area (M1) and in the supplementary motor area (SMA). A third source ipsilateral to movement was located significantly anterior, inferior, and lateral to M1, in the premotor area (PMA) (Brodmann area [BA] 6). Peak latency of the SMA and the ipsilateral PMA sources significantly preceded the peak latency of the contralateral M1 source by 60 msec and 52 msec, respectively. Peak dipole strengths of both the SMA and ipsilateral PMA sources were significantly weaker than was the contralateral M1 source, but did not differ from each other. Altogether, the results indicated that the ipsilateral motor activity was associated with premotor function, rather than activity in M1. The time courses of activation in SMA and ipsilateral PMA were consistent with their purported roles in planning movements. Hum. Brain Mapp. 23:26-39, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT. Background. One-third of children diagnosed with autism spectrum disorders (ASDs) are reported to have had normal early development followed by an autistic regression between the ages of 2 and 3 years. This clinical profile partly parallels that seen in Landau-Kleffner syndrome (LKS), an acquired language disorder (aphasia) believed to be caused by epileptiform activity. Given the additional observation that one-third of autistic children experience one or more seizures by adolescence, epileptiform activity may play a causal role in some cases of autism. Objective. To compare and contrast patterns of epileptiform activity in children with autistic regressions versus classic LKS to determine if there is neurobiological overlap between these conditions. It was hypothesized that many children with regressive ASDs would show epileptiform activity in a multifocal pattern that includes the same brain regions implicated in LKS. Design. Magnetoencephalography (MEG), a noninvasive method for identifying zones of abnormal brain electrophysiology, was used to evaluate patterns of epileptiform activity during stage III sleep in 6 children with classic LKS and 50 children with regressive ASDs with onset between 20 and 36 months of age (16 with autism and 34 with pervasive developmental disorder-not otherwise specified). Whereas 5 of the 6 children with LKS had been previously diagnosed with complex-partial seizures, a clinical seizure disorder had been diagnosed for only 15 of the 50 ASD children. However, all the children in this study had been reported to occasionally demonstrate unusual behaviors (eg, rapid blinking, holding of the hands to the ears, unprovoked crying episodes, and/or brief staring spells) which, if exhibited by a normal child, might be interpreted as indicative of a subclinical epileptiform condition. MEG data were compared with simultaneously recorded electroencephalography (EEG) data, and with data from previous 1-hour and/or 24-hour clinical... [ABSTRACT FROM AUTHOR]