2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2018
Studies that seek to predict the brain microstructure based on MRI require precise alignment of p... more Studies that seek to predict the brain microstructure based on MRI require precise alignment of processed brain histology slices to the corresponding 3D MRI data. However, achieving such alignment is a challenging problem, due to tissue distortions and the different contrasts seen in MRI and the processed tissue. Here we present a pipeline for aligning a histology volume to the MRI data of the tissue and to a stereotaxic brain atlas. To this end, we segment the volume of the brain from ex-vivo MRI data, align the MRI data obtained in the native space to an MRI stereotaxic template and create a 3D printed model (a mold or cradle) that precisely fits the brain. The pipeline then makes it possible to create grooves in the 3D model, for guiding blades for cutting slabs of tissue. Placing the brain in the brain-specific 3D printed model aligns the tissue to the MRI data by default. Aligning the MRI data to an MRI stereotaxic template makes it possible to section histology slices parallel...
<b>Content</b> This work is derived from the Alzheimer's Disease Neuroimaging Ini... more <b>Content</b> This work is derived from the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) and three samples from Montreal, Canada, as described in the following publications : Tam et al 2015, (https://dx.doi.org/10.3389/fnagi.2015.00242) ; Tam et al 2016, (https://doi.org/10.1016/j.dib.2016.11.036). It includes group brain parcellations for clusters generated from resting-state functional magnetic resonance images for 99 cognitively normal elderly persons and 129 patients with mild cognitive impairment. The parcellations have been generated using a method called bootstrap analysis of stable clusters (BASC, Bellec et al., 2010) and 8 resolutions of clusters (4, 6, 12, 22, 33, 65, 111, and 208 total bihemispheric parcels) were selected using a data-driven method called MSTEPS (Bellec, 2013). This work also includes parcellations that contain regions-of-interest (ROIs) that span only one hemisphere at 8 resolutions (10, 17, 30, 51, 77, 137, 199, and 322 total ROIs). It also includes maps illustrating uncorrected functional connectivity differences (t-maps) between patients and controls for four seeds/ROIs (superior medial frontal cortex, dorsomedial prefrontal cortex, striatum, middle temporal lobe). This release contains the following files: <b></b><b>README.md:</b> a text description of the release. <b></b><b>brain_parcellation_mcinet_basc_(sym,asym)_(#)clusters.(mnc,nii).gz:</b> 3D volumes (either in .mnc or .nii format) at 3 mm isotropic resolution, in the MNI non-linear 2009a space (http://www.bic.mni.mcgill.ca/ServicesAtlases/ICBM152NLin2009), at multiple resolutions of # clusters. Note that four versions of the templates are available, named with sym_mnc, asym_mnc, sym_nii or asym_nii. The mnc flavor contains files in the minc format, while the nii flavor has files in the nifti format. The asym flavor contains brain images that have been registered in the asymmetric version of the MNI brain template (reflecting that the brain is asymmetric), while with the sym flavor they have been registered in the [...]
Transcranial magnetic stimulation (TMS) involves the application of time-pulsed magnetic fields t... more Transcranial magnetic stimulation (TMS) involves the application of time-pulsed magnetic fields to cortical tissue through a coil positioned near the head. TMS is widely used for studying the mechanisms underlying perception and behaviour and is considered a potential therapeutic technique for various conditions. However, the application of TMS has been hindered by the lack of understanding of its mechanism of action. Here we studied the effects of three repetitive TMS (rTMS) paradigms on intra-cortical neuronal responses to oriented gratings in cat area 18. Each of stimulation protocols, including continuous theta-burst, intermittent theta-burst, and 15 Hz rTMS, consisted of 600 pulses. Application of continuous theta-burst and 15 Hz rTMS suppressed the action potential response to oriented grating stimuli for 1.5-6 minutes. In contrast, application of intermittent theta-burst stimulation was associated with enhancement of the action potential response ∼15 minutes following TMS. Ne...
IEEE Transactions on Instrumentation and Measurement, 2019
Electroencephalogram (EEG) signals are widely used to detect epileptic seizures in a patient's ne... more Electroencephalogram (EEG) signals are widely used to detect epileptic seizures in a patient's neuronal activity. Since visual inspection and interpretation of EEG signal are time-consuming and prone to errors, various computer-aided diagnostic (CAD) tools have been proposed. In this paper, we present a novel automated detection system to distinguish between intracranial EEG time courses with seizures and those that are seizure-free based on complexity measures. Specifically, the features used to characterize the EEG signals are estimates of multiscaling properties over a large spectrum measured by using the generalized Hurst exponent. We tested the capacity of these estimates to correctly classify seizure intervals using a publicly available data set. Using the k-nearest neighbor classifier and testing with tenfold cross validation, we achieved 100% accurate classification. Our proposed CAD system outperformed the existing state-of-the-art models. Moreover, our CAD system is not only accurate but also fast and simple to implement. Therefore, it can be used as an expert system to support a decision in clinical applications.
Parkinson's disease (PD) is a neurodegenerative disorder that causes severe motor and cognitive d... more Parkinson's disease (PD) is a neurodegenerative disorder that causes severe motor and cognitive dysfunctions. Several types of physiological signals can be analyzed to accurately detect PD by using machine learning methods. This work considers the diagnosis of PD based on voice patterns. In particular, we focus on assessing the performance of eight different pattern ranking techniques (also termed feature selection methods) when coupled with nonlinear support vector machine (SVM) to distinguish between PD patients and healthy control subjects. The parameters of the radial basis function kernel of the SVM classifier were optimized by using Bayesian optimization technique. Our results show that the receiver operating characteristic and the Wilcoxon-based ranking techniques provide the highest sensitivity and specificity.
Diabetic retinopathy is a disease that can cause a loss of vision. An early and accurate diagnosi... more Diabetic retinopathy is a disease that can cause a loss of vision. An early and accurate diagnosis helps to improve treatment of the disease and prognosis. One of the earliest characteristics of diabetic retinopathy is the appearance of retinal hemorrhages. The purpose of this study is to design a fully automated system for the detection of hemorrhages in a retinal image. In the first stage of our proposed system, a retinal image is processed with variational mode decomposition (VMD) to obtain the first variational mode, which captures the high frequency components of the original image. In the second stage, four texture descriptors are extracted from the first variational mode. Finally, a classifier trained with all computed texture descriptors is used to distinguish between images of healthy and unhealthy retinas with hemorrhages. Experimental results showed evidence of the effectiveness of the proposed system for detection of hemorrhages in the retina, since a perfect detection rate was achieved. Our proposed system for detecting diabetic retinopathy is simple and easy to implement. It requires only short processing time, and it yields higher accuracy in comparison with previously proposed methods for detecting diabetic retinopathy.
We present group brain parcellations for clusters generated from resting-state functional magneti... more We present group brain parcellations for clusters generated from resting-state functional magnetic resonance images for 99 cognitively normal elderly persons and 129 patients with mild cognitive impairment, pooled from four independent datasets. The brain parcellations have been registered to both symmetric and asymmetric MNI brain templates and generated using a method called bootstrap analysis of stable clusters (BASC, Bellec et al., 2010). Eight resolutions of clusters were selected using a data-driven method called MSTEPS (Bellec, 2013). We present two variants of these parcellations. One variant contains bihemisphereic parcels (4, 6, 12, 22, 33, 65, 111, and 208 total parcels across eight resolutions). The second variant contains spatially connected regions of interest (ROIs) that span only one hemisphere (10, 17, 30, 51, 77, 199, and 322 total ROIs across eight resolutions). We also present maps illustrating functional connectivity differences between patients and controls for...
Background: It has been noticed that patients with Alzheimer's disease (AD) often show seizures [... more Background: It has been noticed that patients with Alzheimer's disease (AD) often show seizures [Hause et al, 1986], however the underlying pathomechanisms were not completely understood. Recently, frequent occurrence of seizures were also found in transgenic mice for AD model [Palop et al. 2007], and Bousche et al (2008) have demonstrated that clusters of neurons near amyloid plaques become hyperactive. Therefore, the objective of this study was to investigate relationships between cortical excitability and local amyloid deposition in humans using MEG and PiB-PET. To assess the cortical excitability in noninvasive manner, we measured somatosensory evoked magnetic field recovery (SEF-R) function to paired electric stimuli [Ugawa et al. 1991]. Methods: The participants were 7 AD, 12 mild cognitive impairment (MCI) and 33 cognitively normal (NC) volunteers. The study was approved by the Ethic Committee of National Center for Geriatrics and Gerontology and written informed consent was obtained from all of the participants. Five paired stimuli with different inter-stimulus intervals (ISIs ¼ 30, 60, 90, 120, 150 ms) were randomly administered to the left median nerve at the wrist. Magnetic responses were measured using a 306 channel system (Neuromag, Elekta). The paired stimuli elicited two primary responses (R1 and R2), and SEF-R value was calculated by dividing the magnitude of R2 by that of R1 in each ISI.
Amblyopia is a prevalent developmental visual disorder of childhood that typically persists in ad... more Amblyopia is a prevalent developmental visual disorder of childhood that typically persists in adults. Due to altered visual experience during critical periods of youth, the structure and function of adult visual cortex is abnormal. In addition to substantial deficits shown with task-based fMRI, previous studies have used resting state measures to demonstrate altered long-range connectivity in amblyopia. This is the first study in amblyopia to analyze connectivity between regions of interest that are smaller than a single cortical area and to apply partial correlation analysis to reduce network effects. We specifically assess short-range connectivity between retinotopically defined regions of interest within the occipital lobe of 8 subjects with amblyopia and 7 subjects with normal vision (aged 19-45). The representations of visual areas V1, V2, and V3 within each of the four quadrants of visual space were further subdivided into three regions based on maps of visual field eccentricity. Connectivity between pairs of all nine regions of interest in each quadrant was tested via correlation and partial correlation for both groups. Only the tests of partial correlation, i.e., correlation between time courses of two regions following the regression of time courses from all other regions, yielded significant differences between resting state functional connectivity in amblyopic and normal subjects. Subjects with amblyopia showed significantly higher partial correlation between para-foveal and more eccentric representations within V1, and this effect associated with poor acuity of the worse eye. In addition, we observed reduced correlation in amblyopic subjects between isoeccentricity regions in V1 and V2, and separately, between such regions in V2 and V3. We conclude that partial correlation-based connectivity is altered in an eccentricity-dependent pattern in visual field maps of amblyopic patients. Moreover, results are consistent with known clinical and psychophysical vision loss. More broadly, this provides evidence that abnormal cortical adaptations to disease may be better isolated with tests of partial correlation connectivity than with the regular correlation techniques that are currently widely used.
Functional MR imaging of the alert, behaving monkey is being used more and more often to detect a... more Functional MR imaging of the alert, behaving monkey is being used more and more often to detect activation patterns and guide electrophysiological research investigating the neural basis of behavior. Several labs have reported fMRI data from the awake monkey, but none of them has studied and systematically corrected the effects of monkeys' motion on fMRI time series. In this study, a significant refinement of acquisition and correction strategies is reported that can be used to minimize magnetic susceptibility artifacts induced by respiration and by jaw and body movement. Real-time acquisition of sensor signals (e.g., signals induced by jaw and body movement) and MR navigator data were combined to optimize fMRI signal-correction strategies. Within trials, the artifact-induced off-resonance changes were small and mainly reflected the effects of respiration; between trials, movements caused major changes of global frequency and shim (N 20 Hz/cm). Several methods were used to assess the stability of the fMRI series: k-space analysis (ddynamic intensity and off-resonance changes in k-spaceT, dubbed DICK and DORK) and image analysis using a Laplace operator and a center-of-mass metric. The variability between trials made it essential to correct for inter-trial variations. On the other hand, images were sufficiently stable with our approach to perform fMRI evaluations on single trials before averaging of trials. Different motion correction strategies were compared: DORK, McFLIRT (rigid body model with three translations and three rotations) and 2D image alignment based on a center-of-mass detection (in-plane translation). The latter yielded the best results and proved to be fast and robust for intra-and inter-trial alignment. Finally, fMRI in the behaving monkey was tested for spatial and temporal reproducibility on a trial-to-trial basis. Highly activated voxels also displayed good reproducibility between trials. On average, the BOLD amplitude response to a short 3-s visual stimulus was close to 2%.
Introduction Theoretical considerations as well as experimental studies have suggested that imagi... more Introduction Theoretical considerations as well as experimental studies have suggested that imaging at high fields is advantageous for fMRI. Specifically: 1) the signal to noise ratio (SNR) of the images is expected to increase; 2) the contrast to noise ratio (CNR) of the BOLD response is expected to increase; and 3) the specificity of BOLD response to the gray matter is expected to improve. The anticipated increase in SNR and CNR, and the decrease in signal from the blood vessels are supposed to bring about a high degree of reproducibility of the BOLD response at high field. In this study we have investigated the reproducibility of the BOLD response obtained from the human brain at high-resolution at 7 Tesla. Methods: fMRI Three healthy volunteers participated in this study. Imaging was performed at 7 Tesla (magnet: Magnex, console: Varian) using a quadrature RF surface coil (10x12 cm). A segmented gradient echo EPI sequence was used with the following parameters: matrix 128x128, F...
ABSTRACTFunctional MRI (fMRI) of the resting-state utilizes spontaneous fluctuations in metabolic... more ABSTRACTFunctional MRI (fMRI) of the resting-state utilizes spontaneous fluctuations in metabolic and hemodynamic signals to indirectly infer the underlying local changes in neuronal activity. For correct interpretation of spontaneous fluctuations and functional connectivity in the resting-state, it is important to characterize the neuronal mechanisms of fMRI in animal models. Animal studies of the evoked response and resting-state commonly use dexmedetomidine sedation. It has been demonstrated that dexmedetomidine combined with potent sensory stimuli is prone to inducing seizures in Sprague-Dawley (SD) rats.To characterize these seizures, here we combined optical imaging of intrinsic signals and cerebral blood flow with neurophysiological recordings. We characterize the susceptibility to seizures as a function of time from the beginning of dexmedetomidine administration. We show that these seizures are associated with spatially extensive high-amplitude cerebral blood flow and blood...
Wide-field Optical Imaging of Intrinsic Signals (OI-IS; Grinvald et al., 1986) is a method for im... more Wide-field Optical Imaging of Intrinsic Signals (OI-IS; Grinvald et al., 1986) is a method for imaging functional brain hemodynamic responses, mainly used to image activity from the surface of the cerebral cortex. It localizes small functional modules – such as cortical columns – with great spatial resolution and spatial specificity relative to the site of increases in neuronal activity. OI-IS is capable of imaging responses either through an intact or thinned skull or following a craniotomy. Therefore, it is minimally invasive, which makes it ideal for survival experiments. Here we describe OI-IS-based methods for guiding microinjections of optogenetics viral vectors in proximity to small functional modules (S1 barrels) of the cerebral cortex and for guiding the insertion of electrodes for electrophysiological recording into such modules. We validate our proposed methods by tissue processing of the cerebral barrel field area, revealing the track of the electrode in a predetermined ...
Abstract The majority of imaging studies looking at the functioning human brain rely on a techniq... more Abstract The majority of imaging studies looking at the functioning human brain rely on a technique appropriately called “functional magnetic resonance imaging” or fMRI. This method uses metabolic and hemodynamic responses to infer underlying changes in neural activity. Thus, the fMRI signal is an indirect measure of neural activity. This chapter unveils the nature of fMRI data and what this means for researchers.
ABSTRACTIn the mature CNS, netrin-1 is expressed by neurons and oligodendrocytes and implicated i... more ABSTRACTIn the mature CNS, netrin-1 is expressed by neurons and oligodendrocytes and implicated in the stability of axo-oligodendroglial paranodal junctions. Here we report that the netrin receptor UNC5B is highly expressed by mature oligodendrocytes and enriched at paranodes. We demonstrate that paranodes become disorganized following conditional deletion of UNC5B in oligodendrocytes, with disruption of the interface between glial loops and detachment of loops from the axon. As a result, Caspr1 and Kv1.1 disperse along the axon, internodes fail to lengthen and compact myelin periodicity is reduced. Paranodal and axoglial domain disorganization progressively worsens and a delay in motor learning develops in aged mice lacking oligodendroglial UNC5B. Altered glial loop ultrastructure and reduced levels of claudin-11 and JAM-C tight junction proteins support the conclusion that disruption of autotypic junctions between paranodal loops underlies paranode disorganization. Our findings re...
Functional MRI (fMRI) utilizes changes in metabolic and hemodynamic signals to indirectly infer t... more Functional MRI (fMRI) utilizes changes in metabolic and hemodynamic signals to indirectly infer the underlying local changes in neuronal activity. To investigate the mechanisms of fMRI responses, spontaneous fluctuations, and functional connectivity in the resting-state, it is important to pursue fMRI in animal models. Animal studies commonly use dexmedetomidine sedation. It has been demonstrated that potent sensory stimuli administered under dexmedetomidine are prone to inducing seizures in Sprague-Dawley (SD) rats. Here we combined optical imaging of intrinsic signals and cerebral blood flow with neurophysiological recordings to measure responses in rat area S1FL to electrical forepaw stimulation administered at 8 Hz. We show that the increased susceptibility to seizures starts no later than 1 h and ends no sooner than 3 h after initiating a continuous administration of dexmedetomidine. By administering different combinations of anesthetic and sedative agents, we demonstrate that dexmedetomidine is the sole agent necessary for the increased susceptibility to seizures. The increased susceptibility to seizures prevails under a combination of 0.3–0.5% isoflurane and dexmedetomidine anesthesia. The blood-oxygenation and cerebral blood flow responses to seizures induced by forepaw stimulation have a higher amplitude and a larger spatial extent relative to physiological responses to the same stimuli. The epileptic activity and the associated blood oxygenation and cerebral blood flow responses stretched beyond the stimulation period. We observed seizures in response to forepaw stimulation with 1–2 mA pulses administered at 8 Hz. In contrast, responses to stimuli administered at 4 Hz were seizure-free. We demonstrate that such seizures are generated not only in SD rats but also in Long-Evans rats, but not in C57BL6 mice stimulated with similar potent stimuli under dexmedetomidine sedation. We conclude that high-amplitude hemodynamic functional imaging responses evoked by peripheral stimulation in rats sedated with dexmedetomidine are possibly due to the induction of epileptic activity. Therefore, caution should be practiced in experiments that combine the administration of potent stimuli with dexmedetomidine sedation. We propose stimulation paradigms that elicit seizure-free, well detectable neurophysiological and hemodynamic responses in rats. We further conclude that the increased susceptibility to seizures under dexmedetomidine sedation is species dependent.
OBJECTIVE We introduce a novel animal model of somatosensory stimulation-induced reflex seizures ... more OBJECTIVE We introduce a novel animal model of somatosensory stimulation-induced reflex seizures which generates focal seizures without causing damage to the brain. METHODS Specifically, we electrically stimulated digits or forepaws of adult rats sedated with dexmedetomidine while imaging cerebral blood volume and recording neurophysiological activity in cortical area S1FL. For the recordings, we either inserted a linear probe into the D3 digit representation or we performed surface electrocorticography (ECoG) recordings. RESULTS Peripheral stimulation of a digit or the forepaw elicited seizures that were followed by a refractory period with decreased neuronal activity, or another seizure or normal response. LFP amplitudes in response to electrical pulses during the seizures (0.28 ± 0.03 mV) were higher than during normal evoked responses (0.25 ± 0.05 mV) and refractory periods (0.2 ± 0.08 mV). Seizures generated during the stimulation period showed prolonged after-discharges that were sustained for 20.9 ± 1.9 s following the cessation of the stimulus. High-frequency oscillations were observed prior to and during the seizures, with amplitudes higher than those associated with normal evoked responses. The seizures were initially focal. Optical imaging of the cerebral blood volume response showed that they propagated from the onset zone to adjacent cortical areas, beyond the S1FL representation of the stimulated digit or forepaw. The spatial extent during seizures was on average 1.74 times larger during the stimulation and 4.1 times following its cessation relative to normal evoked responses. Seizures were recorded not only by probes inserted into cortex but also with ECoG arrays (24.1 ± 5.8 seizures per rat) placed over the dura matter, indicating that the seizures were not induced by damage caused by inserting the probes to the cortex. Stimulation of the forepaw elicited more seizures (18.8 ± 8.5 seizures per rat) than stimulation of a digit (1.7 ± 0.7). Unlike rats sedated with dexmedetomidine, rats anesthetized with urethane showed no seizures, indicating that the seizures may depend on the use of the mild sedative dexmedetomidine. SIGNIFICANCE Our proposed animal model generates seizures induced by electrical sensory stimulation free of artifacts and brain damage. It can be used for studying the mechanisms underlying the generation and propagation of reflex seizures and for evaluating antiepileptic drugs.
2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2018
Studies that seek to predict the brain microstructure based on MRI require precise alignment of p... more Studies that seek to predict the brain microstructure based on MRI require precise alignment of processed brain histology slices to the corresponding 3D MRI data. However, achieving such alignment is a challenging problem, due to tissue distortions and the different contrasts seen in MRI and the processed tissue. Here we present a pipeline for aligning a histology volume to the MRI data of the tissue and to a stereotaxic brain atlas. To this end, we segment the volume of the brain from ex-vivo MRI data, align the MRI data obtained in the native space to an MRI stereotaxic template and create a 3D printed model (a mold or cradle) that precisely fits the brain. The pipeline then makes it possible to create grooves in the 3D model, for guiding blades for cutting slabs of tissue. Placing the brain in the brain-specific 3D printed model aligns the tissue to the MRI data by default. Aligning the MRI data to an MRI stereotaxic template makes it possible to section histology slices parallel...
<b>Content</b> This work is derived from the Alzheimer's Disease Neuroimaging Ini... more <b>Content</b> This work is derived from the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) and three samples from Montreal, Canada, as described in the following publications : Tam et al 2015, (https://dx.doi.org/10.3389/fnagi.2015.00242) ; Tam et al 2016, (https://doi.org/10.1016/j.dib.2016.11.036). It includes group brain parcellations for clusters generated from resting-state functional magnetic resonance images for 99 cognitively normal elderly persons and 129 patients with mild cognitive impairment. The parcellations have been generated using a method called bootstrap analysis of stable clusters (BASC, Bellec et al., 2010) and 8 resolutions of clusters (4, 6, 12, 22, 33, 65, 111, and 208 total bihemispheric parcels) were selected using a data-driven method called MSTEPS (Bellec, 2013). This work also includes parcellations that contain regions-of-interest (ROIs) that span only one hemisphere at 8 resolutions (10, 17, 30, 51, 77, 137, 199, and 322 total ROIs). It also includes maps illustrating uncorrected functional connectivity differences (t-maps) between patients and controls for four seeds/ROIs (superior medial frontal cortex, dorsomedial prefrontal cortex, striatum, middle temporal lobe). This release contains the following files: <b></b><b>README.md:</b> a text description of the release. <b></b><b>brain_parcellation_mcinet_basc_(sym,asym)_(#)clusters.(mnc,nii).gz:</b> 3D volumes (either in .mnc or .nii format) at 3 mm isotropic resolution, in the MNI non-linear 2009a space (http://www.bic.mni.mcgill.ca/ServicesAtlases/ICBM152NLin2009), at multiple resolutions of # clusters. Note that four versions of the templates are available, named with sym_mnc, asym_mnc, sym_nii or asym_nii. The mnc flavor contains files in the minc format, while the nii flavor has files in the nifti format. The asym flavor contains brain images that have been registered in the asymmetric version of the MNI brain template (reflecting that the brain is asymmetric), while with the sym flavor they have been registered in the [...]
Transcranial magnetic stimulation (TMS) involves the application of time-pulsed magnetic fields t... more Transcranial magnetic stimulation (TMS) involves the application of time-pulsed magnetic fields to cortical tissue through a coil positioned near the head. TMS is widely used for studying the mechanisms underlying perception and behaviour and is considered a potential therapeutic technique for various conditions. However, the application of TMS has been hindered by the lack of understanding of its mechanism of action. Here we studied the effects of three repetitive TMS (rTMS) paradigms on intra-cortical neuronal responses to oriented gratings in cat area 18. Each of stimulation protocols, including continuous theta-burst, intermittent theta-burst, and 15 Hz rTMS, consisted of 600 pulses. Application of continuous theta-burst and 15 Hz rTMS suppressed the action potential response to oriented grating stimuli for 1.5-6 minutes. In contrast, application of intermittent theta-burst stimulation was associated with enhancement of the action potential response ∼15 minutes following TMS. Ne...
IEEE Transactions on Instrumentation and Measurement, 2019
Electroencephalogram (EEG) signals are widely used to detect epileptic seizures in a patient's ne... more Electroencephalogram (EEG) signals are widely used to detect epileptic seizures in a patient's neuronal activity. Since visual inspection and interpretation of EEG signal are time-consuming and prone to errors, various computer-aided diagnostic (CAD) tools have been proposed. In this paper, we present a novel automated detection system to distinguish between intracranial EEG time courses with seizures and those that are seizure-free based on complexity measures. Specifically, the features used to characterize the EEG signals are estimates of multiscaling properties over a large spectrum measured by using the generalized Hurst exponent. We tested the capacity of these estimates to correctly classify seizure intervals using a publicly available data set. Using the k-nearest neighbor classifier and testing with tenfold cross validation, we achieved 100% accurate classification. Our proposed CAD system outperformed the existing state-of-the-art models. Moreover, our CAD system is not only accurate but also fast and simple to implement. Therefore, it can be used as an expert system to support a decision in clinical applications.
Parkinson's disease (PD) is a neurodegenerative disorder that causes severe motor and cognitive d... more Parkinson's disease (PD) is a neurodegenerative disorder that causes severe motor and cognitive dysfunctions. Several types of physiological signals can be analyzed to accurately detect PD by using machine learning methods. This work considers the diagnosis of PD based on voice patterns. In particular, we focus on assessing the performance of eight different pattern ranking techniques (also termed feature selection methods) when coupled with nonlinear support vector machine (SVM) to distinguish between PD patients and healthy control subjects. The parameters of the radial basis function kernel of the SVM classifier were optimized by using Bayesian optimization technique. Our results show that the receiver operating characteristic and the Wilcoxon-based ranking techniques provide the highest sensitivity and specificity.
Diabetic retinopathy is a disease that can cause a loss of vision. An early and accurate diagnosi... more Diabetic retinopathy is a disease that can cause a loss of vision. An early and accurate diagnosis helps to improve treatment of the disease and prognosis. One of the earliest characteristics of diabetic retinopathy is the appearance of retinal hemorrhages. The purpose of this study is to design a fully automated system for the detection of hemorrhages in a retinal image. In the first stage of our proposed system, a retinal image is processed with variational mode decomposition (VMD) to obtain the first variational mode, which captures the high frequency components of the original image. In the second stage, four texture descriptors are extracted from the first variational mode. Finally, a classifier trained with all computed texture descriptors is used to distinguish between images of healthy and unhealthy retinas with hemorrhages. Experimental results showed evidence of the effectiveness of the proposed system for detection of hemorrhages in the retina, since a perfect detection rate was achieved. Our proposed system for detecting diabetic retinopathy is simple and easy to implement. It requires only short processing time, and it yields higher accuracy in comparison with previously proposed methods for detecting diabetic retinopathy.
We present group brain parcellations for clusters generated from resting-state functional magneti... more We present group brain parcellations for clusters generated from resting-state functional magnetic resonance images for 99 cognitively normal elderly persons and 129 patients with mild cognitive impairment, pooled from four independent datasets. The brain parcellations have been registered to both symmetric and asymmetric MNI brain templates and generated using a method called bootstrap analysis of stable clusters (BASC, Bellec et al., 2010). Eight resolutions of clusters were selected using a data-driven method called MSTEPS (Bellec, 2013). We present two variants of these parcellations. One variant contains bihemisphereic parcels (4, 6, 12, 22, 33, 65, 111, and 208 total parcels across eight resolutions). The second variant contains spatially connected regions of interest (ROIs) that span only one hemisphere (10, 17, 30, 51, 77, 199, and 322 total ROIs across eight resolutions). We also present maps illustrating functional connectivity differences between patients and controls for...
Background: It has been noticed that patients with Alzheimer's disease (AD) often show seizures [... more Background: It has been noticed that patients with Alzheimer's disease (AD) often show seizures [Hause et al, 1986], however the underlying pathomechanisms were not completely understood. Recently, frequent occurrence of seizures were also found in transgenic mice for AD model [Palop et al. 2007], and Bousche et al (2008) have demonstrated that clusters of neurons near amyloid plaques become hyperactive. Therefore, the objective of this study was to investigate relationships between cortical excitability and local amyloid deposition in humans using MEG and PiB-PET. To assess the cortical excitability in noninvasive manner, we measured somatosensory evoked magnetic field recovery (SEF-R) function to paired electric stimuli [Ugawa et al. 1991]. Methods: The participants were 7 AD, 12 mild cognitive impairment (MCI) and 33 cognitively normal (NC) volunteers. The study was approved by the Ethic Committee of National Center for Geriatrics and Gerontology and written informed consent was obtained from all of the participants. Five paired stimuli with different inter-stimulus intervals (ISIs ¼ 30, 60, 90, 120, 150 ms) were randomly administered to the left median nerve at the wrist. Magnetic responses were measured using a 306 channel system (Neuromag, Elekta). The paired stimuli elicited two primary responses (R1 and R2), and SEF-R value was calculated by dividing the magnitude of R2 by that of R1 in each ISI.
Amblyopia is a prevalent developmental visual disorder of childhood that typically persists in ad... more Amblyopia is a prevalent developmental visual disorder of childhood that typically persists in adults. Due to altered visual experience during critical periods of youth, the structure and function of adult visual cortex is abnormal. In addition to substantial deficits shown with task-based fMRI, previous studies have used resting state measures to demonstrate altered long-range connectivity in amblyopia. This is the first study in amblyopia to analyze connectivity between regions of interest that are smaller than a single cortical area and to apply partial correlation analysis to reduce network effects. We specifically assess short-range connectivity between retinotopically defined regions of interest within the occipital lobe of 8 subjects with amblyopia and 7 subjects with normal vision (aged 19-45). The representations of visual areas V1, V2, and V3 within each of the four quadrants of visual space were further subdivided into three regions based on maps of visual field eccentricity. Connectivity between pairs of all nine regions of interest in each quadrant was tested via correlation and partial correlation for both groups. Only the tests of partial correlation, i.e., correlation between time courses of two regions following the regression of time courses from all other regions, yielded significant differences between resting state functional connectivity in amblyopic and normal subjects. Subjects with amblyopia showed significantly higher partial correlation between para-foveal and more eccentric representations within V1, and this effect associated with poor acuity of the worse eye. In addition, we observed reduced correlation in amblyopic subjects between isoeccentricity regions in V1 and V2, and separately, between such regions in V2 and V3. We conclude that partial correlation-based connectivity is altered in an eccentricity-dependent pattern in visual field maps of amblyopic patients. Moreover, results are consistent with known clinical and psychophysical vision loss. More broadly, this provides evidence that abnormal cortical adaptations to disease may be better isolated with tests of partial correlation connectivity than with the regular correlation techniques that are currently widely used.
Functional MR imaging of the alert, behaving monkey is being used more and more often to detect a... more Functional MR imaging of the alert, behaving monkey is being used more and more often to detect activation patterns and guide electrophysiological research investigating the neural basis of behavior. Several labs have reported fMRI data from the awake monkey, but none of them has studied and systematically corrected the effects of monkeys' motion on fMRI time series. In this study, a significant refinement of acquisition and correction strategies is reported that can be used to minimize magnetic susceptibility artifacts induced by respiration and by jaw and body movement. Real-time acquisition of sensor signals (e.g., signals induced by jaw and body movement) and MR navigator data were combined to optimize fMRI signal-correction strategies. Within trials, the artifact-induced off-resonance changes were small and mainly reflected the effects of respiration; between trials, movements caused major changes of global frequency and shim (N 20 Hz/cm). Several methods were used to assess the stability of the fMRI series: k-space analysis (ddynamic intensity and off-resonance changes in k-spaceT, dubbed DICK and DORK) and image analysis using a Laplace operator and a center-of-mass metric. The variability between trials made it essential to correct for inter-trial variations. On the other hand, images were sufficiently stable with our approach to perform fMRI evaluations on single trials before averaging of trials. Different motion correction strategies were compared: DORK, McFLIRT (rigid body model with three translations and three rotations) and 2D image alignment based on a center-of-mass detection (in-plane translation). The latter yielded the best results and proved to be fast and robust for intra-and inter-trial alignment. Finally, fMRI in the behaving monkey was tested for spatial and temporal reproducibility on a trial-to-trial basis. Highly activated voxels also displayed good reproducibility between trials. On average, the BOLD amplitude response to a short 3-s visual stimulus was close to 2%.
Introduction Theoretical considerations as well as experimental studies have suggested that imagi... more Introduction Theoretical considerations as well as experimental studies have suggested that imaging at high fields is advantageous for fMRI. Specifically: 1) the signal to noise ratio (SNR) of the images is expected to increase; 2) the contrast to noise ratio (CNR) of the BOLD response is expected to increase; and 3) the specificity of BOLD response to the gray matter is expected to improve. The anticipated increase in SNR and CNR, and the decrease in signal from the blood vessels are supposed to bring about a high degree of reproducibility of the BOLD response at high field. In this study we have investigated the reproducibility of the BOLD response obtained from the human brain at high-resolution at 7 Tesla. Methods: fMRI Three healthy volunteers participated in this study. Imaging was performed at 7 Tesla (magnet: Magnex, console: Varian) using a quadrature RF surface coil (10x12 cm). A segmented gradient echo EPI sequence was used with the following parameters: matrix 128x128, F...
ABSTRACTFunctional MRI (fMRI) of the resting-state utilizes spontaneous fluctuations in metabolic... more ABSTRACTFunctional MRI (fMRI) of the resting-state utilizes spontaneous fluctuations in metabolic and hemodynamic signals to indirectly infer the underlying local changes in neuronal activity. For correct interpretation of spontaneous fluctuations and functional connectivity in the resting-state, it is important to characterize the neuronal mechanisms of fMRI in animal models. Animal studies of the evoked response and resting-state commonly use dexmedetomidine sedation. It has been demonstrated that dexmedetomidine combined with potent sensory stimuli is prone to inducing seizures in Sprague-Dawley (SD) rats.To characterize these seizures, here we combined optical imaging of intrinsic signals and cerebral blood flow with neurophysiological recordings. We characterize the susceptibility to seizures as a function of time from the beginning of dexmedetomidine administration. We show that these seizures are associated with spatially extensive high-amplitude cerebral blood flow and blood...
Wide-field Optical Imaging of Intrinsic Signals (OI-IS; Grinvald et al., 1986) is a method for im... more Wide-field Optical Imaging of Intrinsic Signals (OI-IS; Grinvald et al., 1986) is a method for imaging functional brain hemodynamic responses, mainly used to image activity from the surface of the cerebral cortex. It localizes small functional modules – such as cortical columns – with great spatial resolution and spatial specificity relative to the site of increases in neuronal activity. OI-IS is capable of imaging responses either through an intact or thinned skull or following a craniotomy. Therefore, it is minimally invasive, which makes it ideal for survival experiments. Here we describe OI-IS-based methods for guiding microinjections of optogenetics viral vectors in proximity to small functional modules (S1 barrels) of the cerebral cortex and for guiding the insertion of electrodes for electrophysiological recording into such modules. We validate our proposed methods by tissue processing of the cerebral barrel field area, revealing the track of the electrode in a predetermined ...
Abstract The majority of imaging studies looking at the functioning human brain rely on a techniq... more Abstract The majority of imaging studies looking at the functioning human brain rely on a technique appropriately called “functional magnetic resonance imaging” or fMRI. This method uses metabolic and hemodynamic responses to infer underlying changes in neural activity. Thus, the fMRI signal is an indirect measure of neural activity. This chapter unveils the nature of fMRI data and what this means for researchers.
ABSTRACTIn the mature CNS, netrin-1 is expressed by neurons and oligodendrocytes and implicated i... more ABSTRACTIn the mature CNS, netrin-1 is expressed by neurons and oligodendrocytes and implicated in the stability of axo-oligodendroglial paranodal junctions. Here we report that the netrin receptor UNC5B is highly expressed by mature oligodendrocytes and enriched at paranodes. We demonstrate that paranodes become disorganized following conditional deletion of UNC5B in oligodendrocytes, with disruption of the interface between glial loops and detachment of loops from the axon. As a result, Caspr1 and Kv1.1 disperse along the axon, internodes fail to lengthen and compact myelin periodicity is reduced. Paranodal and axoglial domain disorganization progressively worsens and a delay in motor learning develops in aged mice lacking oligodendroglial UNC5B. Altered glial loop ultrastructure and reduced levels of claudin-11 and JAM-C tight junction proteins support the conclusion that disruption of autotypic junctions between paranodal loops underlies paranode disorganization. Our findings re...
Functional MRI (fMRI) utilizes changes in metabolic and hemodynamic signals to indirectly infer t... more Functional MRI (fMRI) utilizes changes in metabolic and hemodynamic signals to indirectly infer the underlying local changes in neuronal activity. To investigate the mechanisms of fMRI responses, spontaneous fluctuations, and functional connectivity in the resting-state, it is important to pursue fMRI in animal models. Animal studies commonly use dexmedetomidine sedation. It has been demonstrated that potent sensory stimuli administered under dexmedetomidine are prone to inducing seizures in Sprague-Dawley (SD) rats. Here we combined optical imaging of intrinsic signals and cerebral blood flow with neurophysiological recordings to measure responses in rat area S1FL to electrical forepaw stimulation administered at 8 Hz. We show that the increased susceptibility to seizures starts no later than 1 h and ends no sooner than 3 h after initiating a continuous administration of dexmedetomidine. By administering different combinations of anesthetic and sedative agents, we demonstrate that dexmedetomidine is the sole agent necessary for the increased susceptibility to seizures. The increased susceptibility to seizures prevails under a combination of 0.3–0.5% isoflurane and dexmedetomidine anesthesia. The blood-oxygenation and cerebral blood flow responses to seizures induced by forepaw stimulation have a higher amplitude and a larger spatial extent relative to physiological responses to the same stimuli. The epileptic activity and the associated blood oxygenation and cerebral blood flow responses stretched beyond the stimulation period. We observed seizures in response to forepaw stimulation with 1–2 mA pulses administered at 8 Hz. In contrast, responses to stimuli administered at 4 Hz were seizure-free. We demonstrate that such seizures are generated not only in SD rats but also in Long-Evans rats, but not in C57BL6 mice stimulated with similar potent stimuli under dexmedetomidine sedation. We conclude that high-amplitude hemodynamic functional imaging responses evoked by peripheral stimulation in rats sedated with dexmedetomidine are possibly due to the induction of epileptic activity. Therefore, caution should be practiced in experiments that combine the administration of potent stimuli with dexmedetomidine sedation. We propose stimulation paradigms that elicit seizure-free, well detectable neurophysiological and hemodynamic responses in rats. We further conclude that the increased susceptibility to seizures under dexmedetomidine sedation is species dependent.
OBJECTIVE We introduce a novel animal model of somatosensory stimulation-induced reflex seizures ... more OBJECTIVE We introduce a novel animal model of somatosensory stimulation-induced reflex seizures which generates focal seizures without causing damage to the brain. METHODS Specifically, we electrically stimulated digits or forepaws of adult rats sedated with dexmedetomidine while imaging cerebral blood volume and recording neurophysiological activity in cortical area S1FL. For the recordings, we either inserted a linear probe into the D3 digit representation or we performed surface electrocorticography (ECoG) recordings. RESULTS Peripheral stimulation of a digit or the forepaw elicited seizures that were followed by a refractory period with decreased neuronal activity, or another seizure or normal response. LFP amplitudes in response to electrical pulses during the seizures (0.28 ± 0.03 mV) were higher than during normal evoked responses (0.25 ± 0.05 mV) and refractory periods (0.2 ± 0.08 mV). Seizures generated during the stimulation period showed prolonged after-discharges that were sustained for 20.9 ± 1.9 s following the cessation of the stimulus. High-frequency oscillations were observed prior to and during the seizures, with amplitudes higher than those associated with normal evoked responses. The seizures were initially focal. Optical imaging of the cerebral blood volume response showed that they propagated from the onset zone to adjacent cortical areas, beyond the S1FL representation of the stimulated digit or forepaw. The spatial extent during seizures was on average 1.74 times larger during the stimulation and 4.1 times following its cessation relative to normal evoked responses. Seizures were recorded not only by probes inserted into cortex but also with ECoG arrays (24.1 ± 5.8 seizures per rat) placed over the dura matter, indicating that the seizures were not induced by damage caused by inserting the probes to the cortex. Stimulation of the forepaw elicited more seizures (18.8 ± 8.5 seizures per rat) than stimulation of a digit (1.7 ± 0.7). Unlike rats sedated with dexmedetomidine, rats anesthetized with urethane showed no seizures, indicating that the seizures may depend on the use of the mild sedative dexmedetomidine. SIGNIFICANCE Our proposed animal model generates seizures induced by electrical sensory stimulation free of artifacts and brain damage. It can be used for studying the mechanisms underlying the generation and propagation of reflex seizures and for evaluating antiepileptic drugs.
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Papers by Amir Shmuel