Search tips
Search criteria

Results 1-10 (10)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Distribution of Mesenchymal Stem Cells and Effects on Neuronal Survival and Axon Regeneration after Optic Nerve Crush and Cell Therapy 
PLoS ONE  2014;9(10):e110722.
Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC) injected into the vitreous body in a model of optic nerve injury. Adult (3–5 months old) Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1β expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime.
PMCID: PMC4210195  PMID: 25347773
Multiple sclerosis (Houndmills, Basingstoke, England)  2013;19(11):10.1177/1352458513498124.
We describe the acute presentation and the long-term evolution of recurrent tumefactive lesions (TLs) in a patient with relapsing-remitting multiple sclerosis.
Five TLs occurred at three separate timepoints over 12 years and these were followed by 73 serial magnetic resonance images.
TL evolution was described by means of magnetization transfer (MT) imaging and cerebrospinal fluid tissue specific imaging (TSI) over the period of the follow-up.
During the study period, the patient had three clinical relapses with only minimal disability progression. MT imaging demonstrated that only the peripheral portion of each TL reverted to pre-lesional MT ratios within six months post-enhancement.
Recurring TLs may present a similar pattern of recovery that may be associated with a long-term favorable clinical outcome.
PMCID: PMC3853337  PMID: 24062416
Multiple sclerosis; tumefactive lesion; magnetic resonance imaging; recovery; magnetization transfer imaging; tissue specific imaging
3.  White Matter Tract Damage in the Behavioral Variant of Frontotemporal and Corticobasal Dementia Syndromes 
PLoS ONE  2014;9(7):e102656.
The phenotypes of the behavioral variant of frontotemporal dementia and the corticobasal syndrome present considerable clinical and anatomical overlap. The respective patterns of white matter damage in these syndromes have not been directly contrasted. Beyond cortical involvement, damage to white matter pathways may critically contribute to both common and specific symptoms in both conditions. Here we assessed patients with the behavioral variant of frontotemporal dementia and corticobasal syndrome with whole-brain diffusion tensor imaging to identify the white matter networks underlying these pathologies. Twenty patients with the behavioral variant of frontotemporal dementia, 19 with corticobasal syndrome, and 15 healthy controls were enrolled in the study. Differences in tract integrity between (i) patients and controls, and (ii) patients with the corticobasal syndrome and the behavioral variant of frontotemporal dementia were assessed with whole brain tract-based spatial statistics and analyses of regions of interest. Behavioral variant of frontotemporal dementia and the corticobasal syndrome shared a pattern of bilaterally decreased white matter integrity in the anterior commissure, genu and body of the corpus callosum, corona radiata and in the long intrahemispheric association pathways. Patients with the behavioral variant of frontotemporal dementia showed greater damage to the uncinate fasciculus, genu of corpus callosum and forceps minor. In contrast, corticobasal syndrome patients had greater damage to the midbody of the corpus callosum and perirolandic corona radiata. Whereas several compact white matter pathways were damaged in both the behavioral variant of frontotemporal dementia and corticobasal syndrome, the distribution and degree of white matter damage differed between them. These findings concur with the distinctive clinical manifestations of these conditions and may improve the in vivo neuroanatomical and diagnostic characterization of these disorders.
PMCID: PMC4108323  PMID: 25054218
4.  Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD 
PLoS ONE  2014;9(2):e89129.
Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD.
PMCID: PMC3935853  PMID: 24586543
5.  Cellular scaling rules for the brain of afrotherians 
Quantitative analysis of the cellular composition of rodent, primate and eulipotyphlan brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in evolution in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of afrotherians, believed to be the first clade to radiate from the common eutherian ancestor. We find that afrotherians share non-neuronal scaling rules with rodents, primates and eulipotyphlans, as well as the coordinated scaling of numbers of neurons in the cerebral cortex and cerebellum. Afrotherians share with rodents and eulipotyphlans, but not with primates, the scaling of number of neurons in the cortex and in the cerebellum as a function of the number of neurons in the rest of the brain. Afrotheria also share with rodents and eulipotyphlans the neuronal scaling rules that apply to the cerebral cortex. Afrotherians share with rodents, but not with eulipotyphlans nor primates, the neuronal scaling rules that apply to the cerebellum. Importantly, the scaling of the folding index of the cerebral cortex with the number of neurons in the cerebral cortex is not shared by either afrotherians, rodents, or primates. The sharing of some neuronal scaling rules between afrotherians and rodents, and of some additional features with eulipotyphlans and primates, raise the interesting possibility that these shared characteristics applied to the common eutherian ancestor. In turn, the clade-specific characteristics that relate to the distribution of neurons along the surface of the cerebral cortex and to its degree of gyrification suggest that these characteristics compose an evolutionarily plastic suite of features that may have defined and distinguished mammalian groups in evolution.
PMCID: PMC3925844  PMID: 24596544
evolution; glia-neuron ratio; numbers of neurons; cortical expansion; gyrification
6.  Real-Time fMRI Pattern Decoding and Neurofeedback Using FRIEND: An FSL-Integrated BCI Toolbox 
PLoS ONE  2013;8(12):e81658.
The demonstration that humans can learn to modulate their own brain activity based on feedback of neurophysiological signals opened up exciting opportunities for fundamental and applied neuroscience. Although EEG-based neurofeedback has been long employed both in experimental and clinical investigation, functional MRI (fMRI)-based neurofeedback emerged as a promising method, given its superior spatial resolution and ability to gauge deep cortical and subcortical brain regions. In combination with improved computational approaches, such as pattern recognition analysis (e.g., Support Vector Machines, SVM), fMRI neurofeedback and brain decoding represent key innovations in the field of neuromodulation and functional plasticity. Expansion in this field and its applications critically depend on the existence of freely available, integrated and user-friendly tools for the neuroimaging research community. Here, we introduce FRIEND, a graphic-oriented user-friendly interface package for fMRI neurofeedback and real-time multivoxel pattern decoding. The package integrates routines for image preprocessing in real-time, ROI-based feedback (single-ROI BOLD level and functional connectivity) and brain decoding-based feedback using SVM. FRIEND delivers an intuitive graphic interface with flexible processing pipelines involving optimized procedures embedding widely validated packages, such as FSL and libSVM. In addition, a user-defined visual neurofeedback module allows users to easily design and run fMRI neurofeedback experiments using ROI-based or multivariate classification approaches. FRIEND is open-source and free for non-commercial use. Processing tutorials and extensive documentation are available.
PMCID: PMC3847114  PMID: 24312569
7.  Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits 
Psychiatry research  2012;202(3):239-244.
Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult anti-social behaviour and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional MRI scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify.
PMCID: PMC3423593  PMID: 22819939
Psychopathic traits; conduct disorder; oppositional defiant disorder; diffusion tensor imaging; functional connectivity
8.  White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis 
Brain  2011;134(9):2642-2655.
Primary lateral sclerosis is a sporadic disorder characterized by slowly progressive corticospinal dysfunction. Primary lateral sclerosis differs from amyotrophic lateral sclerosis by its lack of lower motor neuron signs and long survival. Few pathological studies have been carried out on patients with primary lateral sclerosis, and the relationship between primary lateral sclerosis and amyotrophic lateral sclerosis remains uncertain. To detect in vivo structural differences between the two disorders, diffusion tensor imaging of white matter tracts was carried out in 19 patients with primary lateral sclerosis, 18 patients with amyotrophic lateral sclerosis and 19 age-matched controls. Fibre tracking was used to reconstruct the intracranial portion of the corticospinal tract and three regions of the corpus callosum: the genu, splenium and callosal fibres connecting the motor cortices. Both patient groups had reduced fractional anisotropy, a measure associated with axonal organization, and increased mean diffusivity of the reconstructed corticospinal and callosal motor fibres compared with controls, without changes in the genu or splenium. Voxelwise comparison of the whole brain white matter using tract-based spatial statistics confirmed the differences between patients and controls in the diffusion properties of the corticospinal tracts and motor fibres of the callosum. This analysis further revealed differences in the regional distribution of white matter alterations between the patient groups. In patients with amyotrophic lateral sclerosis, the greatest reduction in fractional anisotropy occurred in the distal portions of the intracranial corticospinal tract, consistent with a distal axonal degeneration. In patients with primary lateral sclerosis, the greatest loss of fractional anisotropy and mean diffusivity occurred in the subcortical white matter underlying the motor cortex, with reduced volume, suggesting tissue loss. Clinical measures of upper motor neuron dysfunction correlated with reductions in fractional anisotropy in the corticospinal tract in patients with amyotrophic lateral sclerosis and increased mean diffusivity and volume loss of the corticospinal tract in patients with primary lateral sclerosis. Changes in the diffusion properties of the motor fibres of the corpus callosum were strongly correlated with changes in corticospinal fibres in patients, but not in controls. These findings indicate that degeneration is not selective for corticospinal neurons, but affects callosal neurons within the motor cortex in motor neuron disorders.
PMCID: PMC3170531  PMID: 21798965
diffusion tensor imaging; diffusion tensor tractography; motor neuron disorders; primary lateral sclerosis; corpus callosum
9.  Focal white matter changes in spasmodic dysphonia: a combined DTI and neuropathological study 
Brain : a journal of neurology  2007;131(Pt 2):447-459.
Spasmodic dysphonia (SD) is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although clinical symptoms of SD are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in SD patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes in SD and to target those brain regions for neuropathological examination. DTI showed rightsided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in the white matter along the corticobulbar/corticospinal tract in 20 SD patients compared to 20 healthy subjects. In addition, water diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus, and cerebellar white and gray matter in SD patients. These brain changes were substantiated with focal histopathological abnormalities presented as a loss of axonal density and myelin content in the right genu of the internal capsule and clusters of mineral depositions containing calcium, phosphorus and iron in the parenchyma and vessel walls of the posterior limb of the internal capsule, putamen, globus pallidus, and cerebellum in the postmortem brain tissue from one SD patient compared to three controls. The specificity of these brain abnormalities is confirmed by their localization limited only to the corticobulbar/corticospinal tract and its main input/output structures. We also found positive correlation between the diffusivity changes and clinical symptoms of SD (r = 0.509, p = 0.037). These brain abnormalities may alter the central control of voluntary voice production and, therefore, may underlie the pathophysiology of SD.
PMCID: PMC2376833  PMID: 18083751
laryngeal dystonia; corticobulbar tract; basal ganglia; neuroimaging; neuropathology
10.  Functional dissociation of ventral frontal and dorsomedial default mode network components during resting state and emotional autobiographical recall 
Human Brain Mapping  2013;35(7):3302-3313.
Humans spend a substantial share of their lives mind-wandering. This spontaneous thinking activity usually comprises autobiographical recall, emotional, and self-referential components. While neuroimaging studies have demonstrated that a specific brain “default mode network” (DMN) is consistently engaged by the “resting state” of the mind, the relative contribution of key cognitive components to DMN activity is still poorly understood. Here we used fMRI to investigate whether activity in neural components of the DMN can be differentially explained by active recall of relevant emotional autobiographical memories as compared with the resting state. Our study design combined emotional autobiographical memory, neutral memory and resting state conditions, separated by a serial subtraction control task. Shared patterns of activation in the DMN were observed in both emotional autobiographical and resting conditions, when compared with serial subtraction. Directly contrasting autobiographical and resting conditions demonstrated a striking dissociation within the DMN in that emotional autobiographical retrieval led to stronger activation of the dorsomedial core regions (medial prefrontal cortex, posterior cingulate cortex), whereas the resting state condition engaged a ventral frontal network (ventral striatum, subgenual and ventral anterior cingulate cortices) in addition to the IPL. Our results reveal an as yet unreported dissociation within the DMN. Whereas the dorsomedial component can be explained by emotional autobiographical memory, the ventral frontal one is predominantly associated with the resting state proper, possibly underlying fundamental motivational mechanisms engaged during spontaneous unconstrained ideation. Hum Brain Mapp 35:3302–3313, 2014. © 2013 Wiley Periodicals, Inc.
PMCID: PMC4216410  PMID: 25050426
fMRI; default mode; autobiographical memory; emotion; functional dissociation

Results 1-10 (10)