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1.
Neuroimage ; 246: 118714, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34800665

RESUMEN

The mammalian striatum is comprised of intermingled tissue compartments, matrix and striosome. Though indistinguishable by routine histological techniques, matrix and striosome have distinct embryologic origins, afferent/efferent connections, surface protein expression, intra-striatal location, susceptibilities to injury, and functional roles in a range of animal behaviors. Distinguishing the compartments previously required post-mortem tissue and/or genetic manipulation; we aimed to identify matrix/striosome non-invasively in living humans. We used diffusion MRI (probabilistic tractography) to identify human striatal voxels with connectivity biased towards matrix-favoring or striosome-favoring regions (determined by prior animal tract-tracing studies). Segmented striatal compartments replicated the topological segregation and somatotopic organization identified in animal matrix/striosome studies. Of brain regions mapped in prior studies, our human brain data confirmed 93% of the compartment-selective structural connectivity demonstrated in animals. Test-retest assessment on repeat scans found a voxel classification error rate of 0.14%. Fractional anisotropy was significantly higher in matrix-like voxels, while mean diffusivity did not differ between the compartments. As mapped by the Talairach human brain atlas, 460 regions were significantly biased towards either matrix or striosome. Our method allows the study of striatal compartments in human health and disease, in vivo, for the first time.


Asunto(s)
Cuerpo Estriado/anatomía & histología , Cuerpo Estriado/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
2.
Phys Chem Chem Phys ; 23(16): 10006-10020, 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33870996

RESUMEN

Bismuth-containing borate glasses, xBi2O3-(1 - x)B2O3, were synthesized in the broad composition range 0.20 ≤ x ≤ 0.80 by melting in Pt crucibles and splat-quenching between two metal blocks. Infrared reflectance spectra, measured in the range 30-5000 cm-1, were transformed into absorption coefficient spectra and then deconvoluted into component bands to probe the glass structure as a function of composition. Integrated intensities of bands above 800 cm-1 were used in combination with mass and charge balance equations to quantify the short-range borate structure in terms of the molar fractions X4m, X4o, X3, X2, X1 and X0 for borate units BØ4-, BØ2O23-, BØ3, BØ2O-, BØO22- and BO33-, where Ø and O- denote bridging and non-bridging oxygen atoms. Borate tetrahedral units were found to be present in both the meta-borate, BØ4-, and ortho-borate, BØ2O23-, forms with BØ4- constituting the dominating tetrahedral species for 0.20 ≤ x ≤ 0.70. The BØ2O23- units prevail at higher Bi2O3 levels (x > 0.7), and coexist with their isomeric triangular borate species BO33- (BØ2O23- ⇌ BO33-). The present IR results for the total molar fraction of borate tetrahedral units, X4 = X4m + X4o, are in very good agreement with reported NMR results for the fraction of boron atoms in four-fold coordination, N4. Besides evaluating X4m and X4o, the present work reports also for the first time the fractions of all types of triangular borate species X3-n with n = 0, 1, 2 and 3. The IR region below 550 cm-1 was found to be dominated by the Bi-O vibrational activity in coexisting ionic (160-230 cm-1) and distorted BiO6 sites (330-365 cm-1 and 475-510 cm-1), a result reflecting the dual role of Bi2O3 as glass-modifier and glass-former oxide. The latter role dominates in glasses exceeding 60 mol% Bi2O3, and is consistent with the extended glass formation in the bismuth-borate system. The structural results were used to calculate the average number of bridging B-Ø bonds per boron center, the average Bi-O and B-O single bond energy, and the atomic packing density of the studied glasses. These properties vary approximately linearly with Bi2O3 content in the three regimes 0.2 ≤ x ≤ 0.4, 0.4 < x ≤ 0.6 and 0.6 < x ≤ 0.83, and contribute collectively to the composition dependence of glass transition temperature.

3.
Cereb Cortex ; 29(4): 1584-1593, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29701751

RESUMEN

Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field. Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4-27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.


Asunto(s)
Encéfalo/crecimiento & desarrollo , Longevidad/fisiología , Sustancia Blanca/crecimiento & desarrollo , Animales , Imagen de Difusión Tensora , Femenino , Macaca mulatta , Masculino , Modelos Neurológicos
4.
Mol Psychiatry ; 21(10): 1372-80, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26643541

RESUMEN

We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4-20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions-Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.


Asunto(s)
Aminopiridinas/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Piperazinas/administración & dosificación , Adulto , Aminopiridinas/farmacocinética , Biomarcadores Farmacológicos/sangre , Depresión/sangre , Depresión/tratamiento farmacológico , Depresión/metabolismo , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/metabolismo , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/farmacocinética , Escalas de Valoración Psiquiátrica , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Resultado del Tratamiento
5.
Hum Brain Mapp ; 35(8): 3841-56, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24382651

RESUMEN

Many studies have observed altered neurofunctional and structural organization in the aging brain. These observations from functional neuroimaging studies show a shift in brain activity from the posterior to the anterior regions with aging (PASA model), as well as a decrease in cortical thickness, which is more pronounced in the frontal lobe followed by the parietal, occipital, and temporal lobes (retrogenesis model). However, very little work has been done using diffusion MRI (dMRI) with respect to examining the structural tissue alterations underlying these neurofunctional changes in the gray matter. Thus, for the first time, we propose to examine gray matter changes using diffusion MRI in the context of aging. In this work, we propose a novel dMRI based measure of gray matter "heterogeneity" that elucidates these functional and structural models (PASA and retrogenesis) of aging from the viewpoint of diffusion MRI. In a cohort of 85 subjects (all males, ages 15-55 years), we show very high correlation between age and "heterogeneity" (a measure of structural layout of tissue in a region-of-interest) in specific brain regions. We examine gray matter alterations by grouping brain regions into anatomical lobes as well as functional zones. Our findings from dMRI data connects the functional and structural domains and confirms the "retrogenesis" hypothesis of gray matter alterations while lending support to the neurofunctional PASA model of aging in addition to showing the preservation of paralimbic areas during healthy aging.


Asunto(s)
Envejecimiento/patología , Encéfalo/patología , Sustancia Gris/patología , Adolescente , Adulto , Estudios de Cohortes , Imagen de Difusión por Resonancia Magnética , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Procesamiento de Señales Asistido por Computador , Adulto Joven
6.
Int J Clin Health Psychol ; 24(2): 100458, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38623146

RESUMEN

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

7.
Am J Med Genet B Neuropsychiatr Genet ; 162B(7): 604-35, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24132894

RESUMEN

In an effort to identify the developing abnormalities preceding psychosis, Dr. Ming T. Tsuang and colleagues at Harvard expanded Meehl's concept of "schizotaxia," and examined brain structure and function in families affected by schizophrenia (SZ). Here, we systematically review genetic (familial) high-risk (HR) studies of SZ using magnetic resonance imaging (MRI), examine how findings inform models of SZ etiology, and suggest directions for future research. Neuroimaging studies of youth at HR for SZ through the age of 30 were identified through a MEDLINE (PubMed) search. There is substantial evidence of gray matter volume abnormalities in youth at HR compared to controls, with an accelerated volume reduction over time in association with symptoms and cognitive deficits. In structural neuroimaging studies, prefrontal cortex (PFC) alterations were the most consistently reported finding in HR. There was also consistent evidence of smaller hippocampal volume. In functional studies, hyperactivity of the right PFC during performance of diverse tasks with common executive demands was consistently reported. The only longitudinal fMRI study to date revealed increasing left middle temporal activity in association with the emergence of psychotic symptoms. There was preliminary evidence of cerebellar and default mode network alterations in association with symptoms. Brain abnormalities in structure, function and neurochemistry are observed in the premorbid period in youth at HR for SZ. Future research should focus on the genetic and environmental contributions to these alterations, determine how early they emerge, and determine whether they can be partially or fully remediated by innovative treatments.


Asunto(s)
Familia/psicología , Neuroimagen/métodos , Esquizofrenia/diagnóstico , Trastorno de la Personalidad Esquizotípica/diagnóstico , Predisposición Genética a la Enfermedad , Humanos , Red Nerviosa/fisiopatología , Esquizofrenia/genética , Esquizofrenia/fisiopatología , Trastorno de la Personalidad Esquizotípica/genética , Trastorno de la Personalidad Esquizotípica/fisiopatología
8.
AJNR Am J Neuroradiol ; 44(7): 768-775, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37348967

RESUMEN

BACKGROUND AND PURPOSE: While brain iron dysregulation has been observed in several neurodegenerative disorders, its association with the progressive neurodegeneration in Niemann-Pick type C is unknown. Systemic iron abnormalities have been reported in patients with Niemann-Pick type C and in animal models of Niemann-Pick type C. In this study, we examined brain iron using quantitative susceptibility mapping MR imaging in individuals with Niemann-Pick type C compared with healthy controls. MATERIALS AND METHODS: A cohort of 10 patients with adolescent- and adult-onset Niemann-Pick type C and 14 age- and sex-matched healthy controls underwent 7T brain MR imaging with T1 and quantitative susceptibility mapping acquisitions. A probing whole-brain voxelwise comparison of quantitative susceptibility mapping between groups was conducted. Mean quantitative susceptibility mapping in the ROIs (thalamus, hippocampus, putamen, caudate nucleus, and globus pallidus) was further compared. The correlations between regional volume, quantitative susceptibility mapping values, and clinical features, which included disease severity on the Iturriaga scale, cognitive function, and the Social and Occupational Functioning Assessment Scale, were explored as secondary analyses. RESULTS: We observed lower volume in the thalamus and voxel clusters of higher quantitative susceptibility mapping in the pulvinar nuclei bilaterally in patients with Niemann-Pick type C compared with the control group. In patients with Niemann-Pick type C, higher quantitative susceptibility mapping in the pulvinar nucleus clusters correlated with lower volume of the thalamus on both sides. Moreover, higher quantitative susceptibility mapping in the right pulvinar cluster was associated with greater disease severity. CONCLUSIONS: Our findings suggest iron deposition in the pulvinar nucleus in Niemann-Pick type C disease, which is associated with thalamic atrophy and disease severity. This preliminary evidence supports the link between iron and neurodegeneration in Niemann-Pick type C, in line with existing literature on other neurodegenerative disorders.


Asunto(s)
Hierro , Enfermedad de Niemann-Pick Tipo C , Humanos , Encéfalo/diagnóstico por imagen , Tálamo , Cognición , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico
10.
Methods ; 50(3): 166-77, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19577648

RESUMEN

Rhesus monkeys, whose typical lifespan can be as long as 30 years in the presence of veterinary care, undergo a cognitive decline as a function of age. While cortical neurons are largely preserved in the cerebral cortex, including primary motor and visual cortex as well as prefrontal association cortex there is marked breakdown of axonal myelin and an overall reduction in white matter predominantly in the frontal and temporal lobes. Whether the myelin breakdown is diffuse or specific to individual white matter fiber pathways is important to be known with certainty. To this end the delineation and quantification of specific frontotemporal fiber pathways within the frontal and temporal lobes is essential to determine which structures are altered and the extent to which these alterations correlate with behavioral findings. The capability of studying the living brain non-invasively with MRI opens up a new window in structural-functional and anatomic-clinical relationships allowing the integration of information derived from different scanning modalities in the same subject. For instance, for any particular voxel in the cerebrum we can obtain structural T1-, diffusion- and magnetization transfer- magnetic resonance imaging (MRI) based information. Moreover, it is thus possible to follow any observed changes longitudinally over time. These acquisitions of multidimensional data in the same individual within the same MRI experimental setting would enable the creation of a data base of integrated structural MRI-behavioral correlations for normal aging monkeys to elucidate the underlying neurobiological mechanisms of functional senescence in the aging non-human primate.


Asunto(s)
Envejecimiento , Conducta Animal/fisiología , Imagen de Difusión Tensora/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Animales , Mapeo Encefálico/métodos , Cerebro/patología , Diencéfalo/patología , Macaca mulatta , Fibras Nerviosas Mielínicas/patología , Vías Nerviosas/patología
11.
Andrologia ; 43(5): 353-7, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21806650

RESUMEN

Men with Down syndrome are considered as infertile although the causes of infertility are not known in detail yet. Although this constitutes a general rule there are three confirmed cases of parenting by fathers with Down syndrome. Many investigators have addressed the causes of infertility and their studies indicate that the causes may be hormonal deficits, morphological alterations of the gonads, abnormal spermatogenesis, psychological and social factors related to the mental retardation. It is obvious that the extra chromosome 21 has a detrimental direct and indirect effect on the reproductive capacity of the affected male patient. But the definite cause of the insufficient and inadequate spermatogenesis remains to be discovered.


Asunto(s)
Síndrome de Down/fisiopatología , Infertilidad Masculina/etiología , Síndrome de Down/complicaciones , Síndrome de Down/genética , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/psicología , Masculino
12.
Histochem Cell Biol ; 132(2): 159-67, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19387680

RESUMEN

Pinopodes represent the morphological and integrins, the biomolecular markers of endometrial receptivity. We studied using scanning electron microscopy, the expression of pinopodes on tubal samples and their corresponding endometria, from 21 women of reproductive age (7 from proliferative phase, 7 from day LH +5 and 7 from day LH +7). In addition, we examined the immunohistochemical staining of integrins alpha v beta 3, alpha v beta 5 and their ligands, fibronectin (FN) and osteopontin (OPN) in the same tubal epithelium samples. Pinopodes were detected on the tubal epithelium exclusively during day LH +7, coincident with their formation in the endometrium and synchronous to alpha v beta 3 sharp increase in the oviduct epithelium, suggesting a regulation similar to the endometrium. In contrast, alpha v beta 5, FN and OPN remained unchanged during the cycle. These results show for the first time the formation of pinopodes in the tubal epithelium at the time of endometrial receptivity and correlate it with the upregulation of the intact dimmer alpha v beta 3 in the tubes.


Asunto(s)
Implantación del Embrión , Endometrio/fisiología , Trompas Uterinas/fisiología , Integrina alfaVbeta3/biosíntesis , Adulto , Biomarcadores/análisis , Biomarcadores/metabolismo , Endometrio/citología , Endometrio/metabolismo , Epitelio/metabolismo , Epitelio/fisiología , Trompas Uterinas/citología , Trompas Uterinas/metabolismo , Femenino , Fibronectinas/análisis , Fibronectinas/biosíntesis , Humanos , Inmunohistoquímica , Integrina alfaVbeta3/análisis , Persona de Mediana Edad , Osteopontina/análisis , Osteopontina/biosíntesis , Receptores de Vitronectina/análisis , Receptores de Vitronectina/biosíntesis
13.
Acta Neurol Scand ; 120(3): 198-203, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19154532

RESUMEN

AIM: To assess the significance of the second lumbrical-interosseous latency (2LI-DML) comparison in the diagnosis of carpal tunnel syndrome (CTS). PATIENTS AND METHODS: We examined 150 consecutive hands of patients referred with suspected CTS, using the 2LI-DML test and other standard measures of median nerve function. Correlations of the 2LI-DML test with standard tests were computed. RESULTS: Hundred and four hands were electrophysiologically confirmed to have CTS. The 2LI-DML test was abnormal in 99/104 (95.2%) hands with CTS with a mean value of 1.54 +/- 1.12 ms. Among the other measures, the orthodromic median-ulnar palmar velocity comparison was the most frequently abnormal test (95/104 hands, 91.3%), followed by the double-peak morphology of orthodromic sensory action potential from digit 4 (94/104, 90.4%). The 2LI-DML test significantly correlated, either positively or negatively, with all other standard tests. CONCLUSION: The 2LI-DML comparison is highly sensitive in diagnosing CTS, even in mild cases in which standard tests fail to detect abnormalities.


Asunto(s)
Síndrome del Túnel Carpiano/diagnóstico , Electrodiagnóstico , Potenciales de Acción/fisiología , Adulto , Anciano , Análisis de Varianza , Síndrome del Túnel Carpiano/fisiopatología , Femenino , Humanos , Masculino , Nervio Mediano/fisiopatología , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Sensibilidad y Especificidad
14.
Am J Med Genet B Neuropsychiatr Genet ; 150B(6): 762-81, 2009 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-19388013

RESUMEN

Brain derived neurotrophic factor (BDNF) regulates neural development and synaptic transmission. We have tested the hypothesis that functional variation in the BDNF gene (Val66Met polymorphism, rs6265) affects brain reward circuitry encoding human judgment and decision-making regarding relative preference. We quantified relative preference among faces with emotional expressions (angry, fearful, sad, neutral, and happy) by a keypress procedure performed offline to measure effort traded for viewing time. Keypress-based relative preferences across the ensemble of faces were mirrored significantly by fMRI signal in the orbitofrontal cortex, amygdala, and hippocampus when passively viewing these faces. For these three brain regions, there was also a statistically significant group difference by BDNF genotype in the fMRI responses to the emotional expressions. In comparison with Val/Met heterozygotes, Val/Val individuals preferentially sought exposure to positive emotions (e.g., happy faces) and had stronger regional fMRI activation to aversive stimuli (e.g., angry, fearful, and sad faces). BDNF genotype accounted for approximately 30% of the variance in fMRI signal that mirrors keypress responses to these stimuli. This study demonstrates that functional allelic variation in BDNF modulates human brain circuits processing reward/aversion information and relative preference transactions.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Toma de Decisiones , Emociones/fisiología , Expresión Facial , Recompensa , Adulto , Amígdala del Cerebelo/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Femenino , Lóbulo Frontal/fisiología , Genotipo , Hipocampo/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Polimorfismo Genético
15.
Brain Imaging Behav ; 13(2): 472-481, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29667043

RESUMEN

The "cognitive dysmetria" hypothesis suggests that impairments in cognition and behavior in patients with schizophrenia can be explained by disruptions in the cortico-cerebellar-thalamic-cortical circuit. In this study we examine thalamo-cortical connections in patients with first-episode schizophrenia (FESZ). White matter pathways are investigated that connect the thalamus with three frontal cortex regions including the anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), and lateral oribitofrontal cortex (LOFC). We use a novel method of two-tensor tractography in 26 patients with FESZ compared to 31 healthy controls (HC), who did not differ on age, sex, or education. Dependent measures were fractional anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD). Subjects were also assessed using clinical functioning measures including the Global Assessment of Functioning (GAF) Scale, the Global Social Functioning Scale (GF: Social), and the Global Role Functioning Scale (GF: Role). FESZ patients showed decreased FA in the right thalamus-right ACC and right-thalamus-right LOFC pathways compared to healthy controls (HCs). In the right thalamus-right VLPFC tract, we found decreased FA and increased RD in the FESZ group compared to HCs. After correcting for multiple comparisons, reductions in FA in the right thalamus- right ACC and the right thalamus- right VLPC tracts remained significant. Moreover, reductions in FA were significantly associated with lower global functioning scores as well as lower social and role functioning scores. We report the first diffusion tensor imaging study of white matter pathways connecting the thalamus to three frontal regions. Findings of white matter alterations and clinical associations in the thalamic-cortical component of the cortico-cerebellar-thalamic-cortical circuit in patients with FESZ support the cognitive dysmetria hypothesis and further suggest the possible involvement of myelin sheath pathology and axonal membrane disruption in the pathogenesis of the disorder.


Asunto(s)
Imagen de Difusión Tensora/métodos , Procesamiento de Imagen Asistido por Computador , Esquizofrenia/patología , Tálamo/patología , Sustancia Blanca/patología , Adulto , Anisotropía , Encéfalo/patología , Estudios Transversales , Femenino , Giro del Cíngulo/patología , Humanos , Masculino , Corteza Prefrontal/patología , Adulto Joven
16.
Neuron ; 19(3): 591-611, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9331351

RESUMEN

We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, ventral tegmentum, and pons and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pons, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.


Asunto(s)
Mapeo Encefálico , Cocaína/farmacología , Emociones/efectos de los fármacos , Narcóticos/farmacología , Núcleo Accumbens/efectos de los fármacos , Trastornos Relacionados con Sustancias/fisiopatología , Adulto , Ganglios Basales/efectos de los fármacos , Ganglios Basales/fisiología , Conducta/efectos de los fármacos , Emociones/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Núcleo Accumbens/fisiología , Reproducibilidad de los Resultados , Cloruro de Sodio/farmacología , Trastornos Relacionados con Sustancias/diagnóstico , Lóbulo Temporal/efectos de los fármacos , Lóbulo Temporal/fisiología
17.
Acta Neurol Scand ; 118(4): 209-17, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18336627

RESUMEN

OBJECTIVES: We review and discuss the pathogenesis, epidemiology, diagnosis as well as recent advances in the treatment of NMO. We also highlight areas of future research. METHODS: A review was carried out on reports drawn from MEDLINE until 2007. RESULTS: Neuromyelitis optica (NMO) is a relative uncommon demyelinating disease of the central nervous system (CNS) that preferentially affects the optic nerves and spinal cord. NMO follows an unpredictable course, being either monophasic or relapsing. The relapsing form of NMO primarily affects women with onset varying from childhood to adults in their 40s or elderly. Until recently, NMO was considered to be a variant of multiple sclerosis. However, in contrast to multiple sclerosis, NMO attacks are not mediated by T cells but rather by B cells and NMO-immunoglobulin G antibodies that target aquaporin-4. Humoral immune mechanisms, including complement activation plays an important role in the pathogenesis of NMO. At present, parenteral corticosteroids are widely employed as first-line treatment of optic neuritis and myelitis attacks, whereas therapeutic plasmapheresis is applied in the case of corticosteroids failure. Various strategies for the prevention of NMO relapses have been employed in small case series with modest activity. CONCLUSION: Recent advances in the clinical, neuroimaging, laboratory and pathological hallmarks have established that NMO is a distinct demyelinating disease of the CNS.


Asunto(s)
Neuromielitis Óptica , Humanos , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/patología , Neuromielitis Óptica/terapia
18.
Biol Psychol ; 79(1): 126-36, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18423838

RESUMEN

Several genes of the dopaminergic and glutamatergic neurotransmitter systems have been found to be associated with alcohol disease and related intermediate phenotypes. Here, we evaluated genetic variants of the catechol-O-methyltransferase (COMT) and the metabotropic glutamate receptor 3 (mGluR3) genes in alcohol-dependent patients and their association with volumetric measurements of brain structures. By combined analysis of imaging data and genotyping results, large numbers of variables are produced that overstrain conventional statistical methods based on tests for group differences. Limitations in assessment of epistatic effects and multiple testing problems are encountered. Therefore, we introduce a novel method for detecting associations between a set of genetic markers and phenotypical measurements based on machine learning techniques. Hippocampal volume was found to be associated with epistatic effects of the COMT-mGluR3 genes in alcohol-dependent patients but not in controls. These data are in line with prior studies supporting a role for dopamine-glutamate interaction in modulation of alcohol disease.


Asunto(s)
Alcoholismo/metabolismo , Alcoholismo/patología , Dopamina/fisiología , Ácido Glutámico/fisiología , Hipocampo/metabolismo , Hipocampo/patología , Adulto , Alelos , Catecol O-Metiltransferasa/genética , Femenino , Variación Genética , Genotipo , Humanos , Procesamiento de Imagen Asistido por Computador , Potenciación a Largo Plazo , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Escalas de Valoración Psiquiátrica , Receptores de Glutamato Metabotrópico/genética
19.
Int J Gynaecol Obstet ; 97(1): 6-9, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17313949

RESUMEN

OBJECTIVE: To compare 3-dimentional hysterosonography (3-DHS) and diagnostic hysteroscopy for the evaluation of intrauterine lesions. METHODS: In this prospective study 124 women with suspected intrauterine abnormality on 2-D ultrasonography or on hysterosalpingography were scheduled to undergo hysteroscopy, 3-DHS, and 3-D power Doppler (3-DPD) examination. However, 3-DHS could not be performed in 3 of the women because of cervical stenosis. The sensitivity and specificity of 3-DHS and 3-DPD were compared with those of hysteroscopy. RESULTS: Of the 121 women found to have an intracavitary abnormality, 20 had polyps, 11 had myomas, 2 had Müllerian duct anomalies, and 6 had synechiae on hysteroscopy. There was agreement between hysteroscopy and 3-DHS in 19 of the polyp cases, 11 of the myoma cases, 2 of the Müllerian anomaly cases, and 4 of the synechiae cases. Examination with 3-DHS and 3-DPD reached a sensitivity of 91.9% and specificity of 98.8%, with a positive predictive value of 97.1% and a negative predictive value of 96.5%, respectively. CONCLUSIONS: Examination with 3-DHS and 3-DPD both allows for accurate assessment of intrauterine abnormalities.


Asunto(s)
Histeroscopía , Imagenología Tridimensional , Enfermedades Uterinas/diagnóstico , Útero/diagnóstico por imagen , Aborto Habitual/diagnóstico por imagen , Adulto , Femenino , Humanos , Leiomioma/diagnóstico , Leiomioma/diagnóstico por imagen , Menorragia/diagnóstico por imagen , Persona de Mediana Edad , Sensibilidad y Especificidad , Ultrasonografía Doppler/métodos , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/diagnóstico por imagen
20.
Eur J Gynaecol Oncol ; 28(1): 39-42, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17375704

RESUMEN

AIM: To compare 3-D hysterosonography (3-DHS) and diagnostic hysteroscopy in women with abnormal uterine bleeding. MATERIALS AND METHODS: Of 248 women with abnormal uterine bleeding who were referred to our department, 3-D hysterosonography and hysteroscopy were performed in 242 women and the results were estimated. In six women 3-DHS could not performed because of cervical stenosis. Sensitivity and specificity of 3-DHS compared to those of hysteroscopy. RESULTS: From the 242 women who underwent examination, we found 30 patients with polyps, 22 with myomas, four with mullerian anomalies, ten with endometrial cancer, 12 with adhesions and 165 with a normal uterine cavity. There was agreement between the two methods in 28 cases of polyps, 22 cases of myomas, four cases of mullerian anomalies, ten cases of endometrial cancer, eight cases of adhesions and in 165 cases of normal endometrium. The sensitivity and specificity of 3D hysterosonography was 93.5% and 99.4%, respectively, with a positive prognostic value (PPV) of 98.6% and a negative prognostic value (NPV) of 97%. The sensitivity and specificity of hysteroscopy was 98.7% and 99.4%, respectively, with a PPV of 98.7% and a NPV of 99.4%. CONCLUSIONS: Three-D hysterosonography accurately assessed intrauterine pathology.


Asunto(s)
Endosonografía/métodos , Histeroscopía/métodos , Enfermedades Uterinas/diagnóstico por imagen , Hemorragia Uterina/diagnóstico por imagen , Adulto , Hiperplasia Endometrial/diagnóstico por imagen , Neoplasias Endometriales/diagnóstico por imagen , Endometrio/diagnóstico por imagen , Femenino , Humanos , Leiomioma/diagnóstico por imagen , Persona de Mediana Edad , Pólipos/diagnóstico por imagen , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Enfermedades Uterinas/complicaciones , Hemorragia Uterina/etiología , Neoplasias Uterinas/diagnóstico por imagen
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