Source imaging of the cortical 10 Hz oscillations during cooling and warming in humans

Primary cold and warm afferent fibers show a robust overshoot in their firing during periods of temperature change, which subsides during tonic thermal stimulation. Our objective was to analyze cortical activation, on a scale of hundreds of milliseconds, occurring during the process of dynamic cooling and warming, based on an evaluation of the amplitude changes seen in 10 Hz electroencephalographic oscillations. Eleven right-handed subjects were exposed to innocuous cold ramp stimuli (from 32 degrees C to 22 degrees C, 10 degrees C/s) and warm ramp stimuli (32 degrees C to 42 degrees C, 10 degrees C/s) on the thenar region of their right palm, using a contact thermode. EEG was recorded from 111 scalp sites, and the 10 Hz current source densities were modeled using low-resolution electromagnetic tomography. During cooling, the earliest amplitude decreases of 10 Hz oscillations were seen in the contralateral posterior insula and secondary somatosensory cortex (SII), and the premotor cortex (PMC). During warming, the earliest events were only observed in the PMC and occurred approximately 0.7 s later than during cooling. Linear regression analysis between 10 Hz current source densities and temperature variations revealed cooling-sensitive activation in the bilateral posterior insula, PMC and the anterior cingulate cortex. During warming, the amplitude of 10 Hz oscillations in the PMC and posterior insula correlated with stimulus temperature. Dynamic thermal stimulation activates, in addition to the posterior insula and parietal operculum, the lateral PMC. The activation of the anterior cingulate cortex during cooling may aid in the anticipation of the cold temperature end-point and provide continuous evaluation of the thermal stimulus.     

The missing link: analogous human and primate cortical gamma oscillations

Recent animal studies highlighting the relationship between functional imaging signals and the underlying neuronal activity have revealed the potential capabilities of non-invasive methods. However, the valuable exchange of information between animal and human studies remains restricted by the limited evidence of direct physiological links between species. In this study we used magnetoencephalography (MEG) to investigate the occurrence of 30-70 Hz (gamma) oscillations in human visual cortex, induced by the presentation of visual stimuli of varying contrast. These oscillations, well described in the animal literature, were observed in retinotopically concordant locations of visual cortex and show striking similarity to those found in primate visual cortex using surgically implanted electrodes. The amplitude of the gamma oscillations increases linearly with stimulus contrast in strong correlation with the gamma oscillations found in the local field potential (LFP) of the macaque. We demonstrate that non-invasive magnetic field measurements of gamma oscillations in human visual cortex concur with invasive measures of activation in primate visual cortex, suggesting both a direct representation of underlying neuronal activity and a concurrence between human and primate cortical activity.     

Quantitative imaging of energy expenditure in human brain

Despite the essential role of the brain energy generated from ATP hydrolysis in supporting cortical neuronal activity and brain function, it is challenging to noninvasively image and directly quantify the energy expenditure in the human brain. In this study, we applied an advanced in vivo(31)P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMR(ATPase)) and creatine kinase (CMR(CK)), and to determine CMR(ATPase) and CMR(CK) in pure gray mater (GM) and white mater (WM), respectively. It was found that both ATPase and CK rates are three times higher in GM than WM; and CMR(CK) is seven times higher than CMR(ATPase) in GM and WM. Among the total brain ATP consumption in the human cortical GM and WM, 77% of them are used by GM in which approximately 96% is by neurons. A single cortical neuron utilizes approximately 4.7 billion ATPs per second in a resting human brain. This study demonstrates the unique utility of in vivo(31)P MRS imaging modality for direct imaging of brain energy generated from ATP hydrolysis, and provides new insights into the human brain energetics and its role in supporting neuronal activity and brain function.     

Wavelets and functional magnetic resonance imaging of the human brain

The discrete wavelet transform (DWT) is widely used for multiresolution analysis and decorrelation or "whitening" of nonstationary time series and spatial processes. Wavelets are naturally appropriate for analysis of biological data, such as functional magnetic resonance images of the human brain, which often demonstrate scale invariant or fractal properties. We provide a brief formal introduction to key properties of the DWT and review the growing literature on its application to fMRI. We focus on three applications in particular: (i) wavelet coefficient resampling or "wavestrapping" of 1-D time series, 2- to 3-D spatial maps and 4-D spatiotemporal processes; (ii) wavelet-based estimators for signal and noise parameters of time series regression models assuming the errors are fractional Gaussian noise (fGn); and (iii) wavelet shrinkage in frequentist and Bayesian frameworks to support multiresolution hypothesis testing on spatially extended statistic maps. We conclude that the wavelet domain is a rich source of new concepts and techniques to enhance the power of statistical analysis of human fMRI data.     

Transmission scanning acoustic imaging of human cortical bone and relation with the microstructure

OBJECTIVE: To investigate and compare the spatial distribution of velocity with that of the microstructural properties (dimension of the haversian canal, percentage of porosity) on cross section of cortical bone. DESIGN: Experimental investigations permitted to quantify variation of acoustic properties related with that of the microstructural properties. BACKGROUND: Transmission ultrasonic techniques have been used in vitro and in vivo to assess the elastic and acoustic properties of Human bone, but few investigated the relationship between their variation with that of the microstructure. METHODS: Two scanning techniques (in transmission with a focused transducer at 5 MHz and an environmental scanning electronic microscope at 20 KV) enabled to obtain the spatial distribution of relative acoustic velocities and the microstructural properties (pore size and porosity). RESULTS: Increase of the velocities is related with the decrease of pore size and porosity. Around the periphery of the sections, the velocities were found to be significantly lower in the posterior side with a significant increase along the length. Radial variations are correlated to the spatial distribution of the microstructure where the endocortical region is more porous compared to the periosteal region. CONCLUSION: Significant alterations of the microstructural properties of the cortical bone reflect small variation of velocity suggesting that the velocities are not so sensitive to microstructural changes. RELEVANCE: These results are of importance for the clinicians and researchers to get a better understanding (advantages and limitation) of the use of ultrasound technique to assess material and structural properties of cortical bone. Our study suggested that velocity could be an index of porosity. Then it would be of interest to improve the clinical assessment of bone quality by describing bone both by a mineralization index and a microstructural index.     

Three-dimensional quantitative magnetisation transfer imaging of the human brain

Quantitative magnetisation transfer (MT) analysis is based on a two-pool model of magnetisation transfer and allows important physical properties of the two proton pools to be assessed. A good signal-to-noise ratio (SNR) for the measured signal is essential in order to estimate reliably the parameters from a small number of samples, thus prompting the use of a sequence with high SNR, such as a three-dimensional spoiled gradient acquisition. Here, we show how full brain coverage can be accomplished efficiently, using a three-dimensional acquisition, in a clinically acceptable time, and without the use of large numbers of slice-selective radio-frequency pulses which could otherwise confound analysis. This acquisition was first compared in post mortem human brain tissue to established two-dimensional acquisition protocols with differing SNR levels and then used to collect data from six healthy subjects. Image data were fitted using the two pool model and showed negligible residual deviations. Quantitative results were assessed in several brain locations. Results were consistent with previous single-slice data, and parametric maps were of good quality. Further investigations are needed to interpret the regional variation of quantitative MT quantities.     

Postmortem MR imaging of formalin-fixed human brain

High-resolution postmortem neuroimaging of the brain can play a role in research programs by providing archival and reslicable images of brain specimens before permanent sectioning. These images can supplement evidence attained from both traditional neuropathological observations and in vivo neuroimaging. Differential brain tissue conspicuity, detectable with MRI, is determined by the density and mobility of water protons. Water content is about 70% in white matter, 80% in gray matter, and 99% in cerebrospinal fluid (CSF). To the extent that brain tissue contrast is determined by the number and microenvironment of water protons, timing parameters of MR image acquisition can interrogate this environment. Because the chemical environment of protons is different in living from dead tissue, optimal temporal imaging parameters, for example, for spin-echo imaging, commonly used for in vivo clinical and research study are different from those best for postmortem imaging. Here, we present a series of observations to identify relaxation times and optimal parameters for high-resolution structural imaging of formalin-fixed postmortem brain tissue using commercially available clinical scanners and protocols. Examples of high-resolution images and results from attempts at diffusion imaging are presented.     

How cortical neurons help us see: visual recognition in the human brain

Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us understand the computations performed by visual cortex.     

基于螺旋成像的人脑认知功能研究

目前,人脑认知功能研究广泛使用平面回波成像（EPI）来快速扫描全脑。然而,EPI采用笛卡尔轨迹覆盖k空间,其读出持续时间较长,对运动的敏感性高。该文介绍另外一种快速成像技术--螺旋成像（spiral imaging）。Spiral用阿基米德或类似轨迹覆盖k空间,其读出持续时间短,对运动的敏感性低。Spiral有望突破EPI在脑认知功能研究中的瓶颈,具体表现为内、外螺旋（spiral-in/out）能够在减少磁敏感性脑区信号衰减的同时增加磁敏感性均匀脑区的信噪比,变化密度螺旋（variable density spiral）可以在保持信噪比的条件下实现单次激发Spiral的高时空分辨扫描。     

The spatiotemporal pattern of auditory cortical responses during verbal hallucinations

Functional magnetic resonance imaging (fMRI) studies can provide insight into the neural correlates of hallucinations. Commonly, such studies require self-reports about the timing of the hallucination events. While many studies have found activity in higher-order sensory cortical areas, only a few have demonstrated activity of the primary auditory cortex during auditory verbal hallucinations. In this case, using self-reports as a model of brain activity may not be sensitive enough to capture all neurophysiological signals related to hallucinations. We used spatial independent component analysis (sICA) to extract the activity patterns associated with auditory verbal hallucinations in six schizophrenia patients. SICA decomposes the functional data set into a set of spatial maps without the use of any input function. The resulting activity patterns from auditory and sensorimotor components were further analyzed in a single-subject fashion using a visualization tool that allows for easy inspection of the variability of regional brain responses. We found bilateral auditory cortex activity, including Heschl's gyrus, during hallucinations of one patient, and unilateral auditory cortex activity in two more patients. The associated time courses showed a large variability in the shape, amplitude, and time of onset relative to the self-reports. However, the average of the time courses during hallucinations showed a clear association with this clinical phenomenon. We suggest that detection of this activity may be facilitated by examining hallucination epochs of sufficient length, in combination with a data-driven approach.     

Mapping single-trial EEG records on the cortical surface through a spatiotemporal modality

Event-related potentials (ERPs) induced by visual perception and cognitive tasks have been extensively studied in neuropsychological experiments. ERP activities time-locked to stimulus presentation and task performance are often observed separately at individual scalp channels based on averaged time series across epochs and experimental subjects. An analysis using averaged EEG dynamics could discount information regarding interdependency between ongoing EEG and salient ERP features. Advanced tools such as independent component analysis (ICA) have been developed for decomposing collections of single-trial EEG records into separate features. Those features (or independent components) can then be mapped onto the cortical surface using source localization algorithms to visualize brain activation maps and to study between-subject consistency. In this study, we propose a statistical framework for estimating the time course of spatiotemporally independent EEG components simultaneously with their cortical distributions. Within this framework, we implemented Bayesian spatiotemporal analysis for imaging the sources of EEG features on the cortical surface. The framework allows researchers to include prior knowledge regarding spatial locations as well as spatiotemporal independence of different EEG sources. The use of the Electromagnetic Spatiotemporal ICA (EMSICA) method is illustrated by mapping event-related EEG dynamics induced by events in a visual two-back continuous performance task. The proposed method successfully identified several interesting components with plausible corresponding cortical activation topographies, including processes contributing to the late positive complex (LPC) located in central parietal, frontal midline, and anterior cingulate cortex, to atypical mu rhythms associated with the precentral gyrus, and to the central posterior alpha activity in the precuneus.     

Prospective and retrospective motion correction in diffusion magnetic resonance imaging of the human brain

Diffusion-weighting in magnetic resonance imaging (MRI) increases the sensitivity to molecular Brownian motion, providing insight in the micro-environment of the underlying tissue types and structures. At the same time, the diffusion weighting renders the scans sensitive to other motion, including bulk patient motion. Typically, several image volumes are needed to extract diffusion information, inducing also inter-volume motion susceptibility. Bulk motion is more likely during long acquisitions, as they appear in diffusion tensor, diffusion spectrum and q-ball imaging. Image registration methods are successfully used to correct for bulk motion in other MRI time series, but their performance in diffusion-weighted MRI is limited since diffusion weighting introduces strong signal and contrast changes between serial image volumes.In this work, we combine the capability of free induction decay (FID) navigators, providing information on object motion, with image registration methodology to prospectively - or optionally retrospectively - correct for motion in diffusion imaging of the human brain. Eight healthy subjects were instructed to perform small-scale voluntary head motion during clinical diffusion tensor imaging acquisitions.The implemented motion detection based on FID navigator signals is processed in real-time and provided an excellent detection performance of voluntary motion patterns even at a sub-millimetre scale (sensitivity ≥ 92%, specificity > 98%). Motion detection triggered an additional image volume acquisition with b = 0 s/mm² which was subsequently co-registered to a reference volume. In the prospective correction scenario, the calculated motion-parameters were applied to perform a real-time update of the gradient coordinate system to correct for the head movement.Quantitative analysis revealed that the motion correction implementation is capable to correct head motion in diffusion-weighted MRI to a level comparable to scans without voluntary head motion. The results indicate the potential of this method to improve image quality in diffusion-weighted MRI, a concept that can also be applied when highest diffusion weightings are performed.     

fMRI resting state networks define distinct modes of long-distance interactions in the human brain

Functional magnetic resonance imaging (fMRI) studies of the human brain have suggested that low-frequency fluctuations in resting fMRI data collected using blood oxygen level dependent (BOLD) contrast correspond to functionally relevant resting state networks (RSNs). Whether the fluctuations of resting fMRI signal in RSNs are a direct consequence of neocortical neuronal activity or are low-frequency artifacts due to other physiological processes (e.g., autonomically driven fluctuations in cerebral blood flow) is uncertain. In order to investigate further these fluctuations, we have characterized their spatial and temporal properties using probabilistic independent component analysis (PICA), a robust approach to RSN identification. Here, we provide evidence that: i. RSNs are not caused by signal artifacts due to low sampling rate (aliasing); ii. they are localized primarily to the cerebral cortex; iii. similar RSNs also can be identified in perfusion fMRI data; and iv. at least 5 distinct RSN patterns are reproducible across different subjects. The RSNs appear to reflect "default" interactions related to functional networks related to those recruited by specific types of cognitive processes. RSNs are a major source of non-modeled signal in BOLD fMRI data, so a full understanding of their dynamics will improve the interpretation of functional brain imaging studies more generally. Because RSNs reflect interactions in cognitively relevant functional networks, they offer a new approach to the characterization of state changes with pathology and the effects of drugs.     

Laser Doppler imaging for intraoperative human brain mapping

The identification and accurate location of centers of brain activity are vital both in neuro-surgery and brain research. This study aimed to provide a non-invasive, non-contact, accurate, rapid and user-friendly means of producing functional images intraoperatively. To this end a full field Laser Doppler imager was developed and integrated within the surgical microscope and perfusion images of the cortical surface were acquired during awake surgery whilst the patient performed a predetermined task. The regions of brain activity showed a clear signal (10–20% with respect to the baseline) related to the stimulation protocol which lead to intraoperative functional brain maps of strong statistical significance and which correlate well with the preoperative fMRI and intraoperative cortical electro-stimulation. These initial results achieved with a prototype device and wavelet based regressor analysis (the hemodynamic response function being derived from MRI applications) demonstrate the feasibility of LDI as an appropriate technique for intraoperative functional brain imaging.     

A multimodal brain imaging study of repetition suppression in the human visual cortex

Repetition suppression (RS) relates to a reduced neuronal response to a stimulus that is repeated. This phenomenon has been observed in the visual ventral stream and other sensory modalities, suggesting that it is a common feature of neuronal processing. Whilst a number of different models have been suggested to explain the underlying neural mechanisms of RS, they are difficult to test due to variety in paradigm design and the limited resolution of different measuring modalities. This study combined information from different modalities using the same paradigm across the same subjects, in an attempt to create a clearer link between fMRI, magnetoencephalography (MEG) and behaviour data, and thus better understand the underlying mechanism of neuronal RS. We used an oriented Gabor patch stimulus separated by two possible interstimulus intervals of 200 or 600 ms and two possible orientation combinations: the second patch was consistently vertical combined with the first patch which was either horizontal (DIFF) or vertical (SAME). For the 200 -ms condition only, behavioural data showed a statistically significant impairment in subjects' ability to discern the direction of tilt at the SAME condition compared to the DIFF condition; fMRI showed suppression of the BOLD response, and MEG showed suppression of the peak amplitude. A significant correlation between the suppressed BOLD and MEG signals confirm the neuronal origin of the BOLD suppression effect. Measurements from the 3 modalities suggest that neuronal RS in the visual cortex in the current orientation-driven paradigm can be best explained by an overall reduction in the size of the response of all neurons (fatigue model) or a reduction in the number of neurons responding (sharpening model).     

Functional cortical changes in patients with multiple sclerosis and nonspecific findings on conventional magnetic resonance imaging scans of the brain

Recent functional magnetic resonance imaging (fMRI) work has suggested that cortical reorganisation might have an adaptive role in limiting the clinical impact of multiple sclerosis (MS) structural damage. In this study, we investigated whether, in patients with MS, the presence and extent of structural damage of the normal-appearing brain tissue are associated with the extent of the movement-associated pattern of cortical activations. Using fMRI and a general search method, we assessed the patterns of brain activations associated with simple motor tasks in 12 right-handed patients with clinically definite MS and nonspecific T2-weighted abnormalities on conventional MRI scans of the brain and compared them with those from 12 sex- and age-matched right- handed healthy controls. Also investigated were the extent to which the fMRI changes correlated with normal-appearing white matter and grey matter (GM) pathology, measured using diffusion tensor MRI. When performing the simple motor task with the dominant hand, MS patients had more significant activations of the ipsilateral supplementary motor area (SMA), the ipsilateral superior frontal sulcus, the contralateral superior temporal gyrus, and the thalamus than controls. On the contrary, healthy subjects showed more significant activations of the medial part of the contralateral parieto-occipital fissure and the ipsilateral primary sensorimotor cortex (SMC) than patients with MS. In patients with MS, the relative activation of the ipsilateral SMA was correlated with the peak height (r = -0.88, P < 0.001) and position (r = 0.87, P < 0.001) of the GM mean diffusivity histogram. This study shows that cortical reorganisation occurs over a rather distributed sensorimotor network even in patients with MS and nonspecific abnormalities on conventional brain MRI scans. This suggests that, in patients with MS, an increased recruitment of movement-associated cortical network can be elicited by the presence of normal-appearing tissue pathology, which is independent of macroscopic T2-weighted abnormalities.     

Optimizing tissue clearing and imaging methods for human brain tissue

ObjectivesTo identify optimum sample conditions for human brains, we compared the clearing efficiency, antibody staining efficiency, and artifacts between fresh and cadaver samples.MethodsFresh and cadaver samples were cleared using X-CLARITY™. Clearing efficiency and artifact levels were calculated using ImageJ, and antibody staining efficiency was evaluated after confocal microscopy imaging. Three staining methods were compared: 4-day staining (4DS), 11-day staining (11DS), and 4-day staining with a commercial kit (4DS-C). The optimum staining method was then selected by evaluating staining time, depth, method complexity, contamination, and cost.ResultsFresh samples outperformed cadaver samples in terms of the time and quality of clearing, artifacts, and 4′,6-diamidino-2-phenylindole (DAPI) staining efficiency, but had a glial fibrillary acidic protein (GFAP) staining efficiency that was similar to that of cadaver samples. The penetration depth and DAPI staining improved in fresh samples as the incubation period lengthened. 4DS-C was the best method, with the deepest penetration. Human brain images containing blood vessels, cell nuclei, and astrocytes were visualized three-dimensionally. The chemical dye staining depth reached 800 µm and immunostaining depth exceeded 200 µm in 4 days.ConclusionsWe present optimized sample preparation and staining protocols for the visualization of three-dimensional macrostructure in the human brain.     

NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain

This paper introduces neurite orientation dispersion and density imaging (NODDI), a practical diffusion MRI technique for estimating the microstructural complexity of dendrites and axons in vivo on clinical MRI scanners. Such indices of neurites relate more directly to and provide more specific markers of brain tissue microstructure than standard indices from diffusion tensor imaging, such as fractional anisotropy (FA). Mapping these indices over the whole brain on clinical scanners presents new opportunities for understanding brain development and disorders. The proposed technique enables such mapping by combining a three-compartment tissue model with a two-shell high-angular-resolution diffusion imaging (HARDI) protocol optimized for clinical feasibility. An index of orientation dispersion is defined to characterize angular variation of neurites. We evaluate the method both in simulation and on a live human brain using a clinical 3T scanner. Results demonstrate that NODDI provides sensible neurite density and orientation dispersion estimates, thereby disentangling two key contributing factors to FA and enabling the analysis of each factor individually. We additionally show that while orientation dispersion can be estimated with just a single HARDI shell, neurite density requires at least two shells and can be estimated more accurately with the optimized two-shell protocol than with alternative two-shell protocols. The optimized protocol takes about 30 min to acquire, making it feasible for inclusion in a typical clinical setting. We further show that sampling fewer orientations in each shell can reduce the acquisition time to just 10 min with minimal impact on the accuracy of the estimates. This demonstrates the feasibility of NODDI even for the most time-sensitive clinical applications, such as neonatal and dementia imaging.