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1.
Am J Geriatr Psychiatry ; 32(8): 1014-1027, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38521736

RESUMEN

OBJECTIVE: Converging evidence indicates that subjective cognitive decline (SCD) could be an early indicator of dementia. The hippocampus is the earliest affected region during the progression of cognitive impairment. However, little is known about whether and how acupuncture change the hippocampal structure and function of SCD individuals. METHODS: Here, we used multi-modal MRI to reveal the mechanism of acupuncture in treating SCD. Seventy-two older participants were randomized into acupuncture or sham acupuncture group and treated for 12 weeks. RESULTS: At the end of the intervention, compared to sham acupuncture, participants with acupuncture treatment showed improvement in composite Z score from multi-domain neuropsychological tests, as well as increased hippocampal volume and functional connectivity. Moreover, the greater white matter integrity of the fornix, which is the major output tract of the hippocampus, was shown in the acupuncture group. CONCLUSION: These findings suggest that acupuncture may improve the cognitive function of SCD individuals, and increase hippocampal volume on the regional level and enhance the structural and functional connectivity of hippocampus on the connective level.


Asunto(s)
Terapia por Acupuntura , Disfunción Cognitiva , Hipocampo , Imagen por Resonancia Magnética , Humanos , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/fisiopatología , Terapia por Acupuntura/métodos , Masculino , Femenino , Disfunción Cognitiva/terapia , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Anciano , Pruebas Neuropsicológicas , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Persona de Mediana Edad
2.
Psychol Med ; 54(10): 2403-2413, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38482853

RESUMEN

BACKGROUND: Growing evidence points to the pivotal role of vitamin D in the pathophysiology and treatment of major depressive disorder (MDD). However, there is a paucity of longitudinal research investigating the effects of vitamin D supplementation on the brain of MDD patients. METHODS: We conducted a double-blind randomized controlled trial in 46 MDD patients, who were randomly allocated into either VD (antidepressant medication + vitamin D supplementation) or NVD (antidepressant medication + placebos) groups. Data from diffusion tensor imaging, resting-state functional MRI, serum vitamin D concentration, and clinical symptoms were obtained at baseline and after an average of 7 months of intervention. RESULTS: Both VD and NVD groups showed significant improvement in depression and anxiety symptoms but with no significant differences between the two groups. However, a greater increase in serum vitamin D concentration was found to be associated with greater improvement in depression and anxiety symptoms in VD group. More importantly, neuroimaging data demonstrated disrupted white matter integrity of right inferior fronto-occipital fasciculus along with decreased functional connectivity between right frontoparietal and medial visual networks after intervention in NVD group, but no changes in VD group. CONCLUSIONS: These findings suggest that vitamin D supplementation as adjunctive therapy to antidepressants may not only contribute to improvement in clinical symptoms but also help preserve brain structural and functional connectivity in MDD patients.


Asunto(s)
Antidepresivos , Trastorno Depresivo Mayor , Suplementos Dietéticos , Imagen de Difusión Tensora , Imagen por Resonancia Magnética , Vitamina D , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/fisiopatología , Femenino , Masculino , Adulto , Método Doble Ciego , Antidepresivos/farmacología , Antidepresivos/administración & dosificación , Vitamina D/farmacología , Vitamina D/administración & dosificación , Vitamina D/sangre , Persona de Mediana Edad , Encéfalo/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Quimioterapia Combinada , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología
3.
Acta Neurochir (Wien) ; 165(6): 1675-1681, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37129683

RESUMEN

Peritumoral edema prevents fiber tracking from diffusion tensor imaging (DTI). A free-water correction may overcome this drawback, as illustrated in the case of a patient undergoing awake surgery for brain metastasis. The anatomical plausibility and accuracy of tractography with and without free-water correction were assessed with functional mapping and axono-cortical evoked-potentials (ACEPs) as reference methods. The results suggest a potential synergy between corrected DTI-based tractography and ACEPs to reliably identify and preserve white matter tracts during brain tumor surgery.


Asunto(s)
Neoplasias Encefálicas , Sustancia Blanca , Humanos , Imagen de Difusión Tensora/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/cirugía , Sustancia Blanca/patología , Vigilia , Agua , Mapeo Encefálico/métodos , Encéfalo/patología
4.
Acta Neurochir (Wien) ; 165(9): 2489-2500, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37199758

RESUMEN

BACKGROUND: Understanding the structural connectivity of white matter tracts (WMT) and their related functions is a prerequisite to implementing an "a la carte" "connectomic approach" to glioma surgery. However, accessible resources facilitating such an approach are lacking. Here we present an educational method that is readily accessible, simple, and reproducible that enables the visualization of WMTs on individual patient images via an atlas-based approach. METHODS: Our method uses the patient's own magnetic resonance imaging (MRI) images and consists of three main steps: data conversion, normalization, and visualization; these are accomplished using accessible software packages and WMT atlases. We implement our method on three common cases encountered in glioma surgery: a right supplementary motor area tumor, a left insular tumor, and a left temporal tumor. RESULTS: Using patient-specific perioperative MRIs with open-sourced and co-registered atlas-derived WMTs, we highlight the critical subnetworks requiring specific surgical monitoring identified intraoperatively using direct electrostimulation mapping with cognitive monitoring. The aim of this didactic method is to provide the neurosurgical oncology community with an accessible and ready-to-use educational tool, enabling neurosurgeons to improve their knowledge of WMTs and to better learn their oncologic cases, especially in glioma surgery using awake mapping. CONCLUSIONS: Taking no more than 3-5 min per patient and irrespective of their resource settings, we believe that this method will enable junior surgeons to develop an intuition, and a robust 3-dimensional imagery of WMT by regularly applying it to their cases both before and after surgery to develop an "a la carte" connectome-based perspective to glioma surgery.


Asunto(s)
Neoplasias Encefálicas , Conectoma , Glioma , Sustancia Blanca , Humanos , Conectoma/métodos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Procedimientos Neuroquirúrgicos/métodos , Glioma/diagnóstico por imagen , Glioma/cirugía , Glioma/patología , Sustancia Blanca/patología , Mapeo Encefálico/métodos , Encéfalo/cirugía
5.
Appetite ; 178: 106093, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35738483

RESUMEN

Tyrosine (tyr), the precursor of the neurotransmitter dopamine, is known to modulate cognitive functions including executive attention. Tyr supplementation is suggested to influence dopamine-modulated cognitive performance. However, results are inconclusive regarding the presence or strength and also the direction of the association between tyr and cognitive function. This pre-registered cross-sectional analysis investigates whether diet-associated serum tyr relates to executive attention performance, and whether this relationship is moderated by differences in white matter microstructure. 59 healthy, overweight, young to middle-aged adults (20 female sex/gender group, 28.3 ± 6.6 years, BMI: 27.3 ± 1.5 kg/m2) drawn from a longitudinal study reported dietary habits, donated blood and completed diffusion-weighted brain magnetic resonance imaging and the attention network test. Main analyses were performed using linear regressions and non-parametric voxel-wise inference testing. Confirmatory analyses did neither support an association between dietary and serum tyr nor a relationship between relative serum tyr/large neutral amino acids (LNAA) levels or white matter microstructure and executive attention performance. However, exploratory analyses revealed higher tyr intake, higher serum tyr and better executive attention performance in the male sex/gender group. In addition, older age was associated with higher dietary tyr intake and lower fractional anisotropy in a widespread cluster across the brain. Finally, a positive association between relative serum tyr/LNAA level and executive attention performance was found in the male sex/gender group when accounting for age effects. Our analysis advances the field of dopamine-modulated cognitive functions by revealing sex/gender and age differences which might be diet-related. Longitudinal or intervention studies and larger sample sizes are needed to provide more reliable evidence for links between tyr and executive attention.


Asunto(s)
Sustancia Blanca , Adulto , Encéfalo , Estudios Transversales , Dieta , Dopamina , Función Ejecutiva , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Sobrepeso/patología , Tirosina , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología
6.
Radiology ; 303(1): 141-150, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34981978

RESUMEN

Background MR spectroscopic imaging (MRSI) allows in vivo assessment of brain metabolism and is of special interest in multiple sclerosis (MS), where morphologic MRI cannot depict major parts of disease activity. Purpose To evaluate the ability of 7.0-T MRSI to depict and visualize pathologic alterations in the normal-appearing white matter (NAWM) and cortical gray matter (CGM) in participants with MS and to investigate their relation to disability. Materials and Methods Free-induction decay MRSI was performed at 7.0 T. Participants with MS and age- and sex-matched healthy controls were recruited prospectively between January 2016 and December 2017. Metabolic ratios were obtained in white matter lesions, NAWM, and CGM regions. Subgroup analysis for MS-related disability based on Expanded Disability Status Scale (EDSS) scores was performed using analysis of covariance. Partial correlations were applied to explore associations between metabolic ratios and disability. Results Sixty-five participants with MS (mean age ± standard deviation, 34 years ± 9; 34 women) and 20 age- and sex-matched healthy controls (mean age, 32 years ± 7; 11 women) were evaluated. Higher signal intensity of myo-inositol (mI) with and without reduced signal intensity of N-acetylaspartate (NAA) was visible on metabolic images in the NAWM of participants with MS. A higher ratio of mI to total creatine (tCr) was observed in the NAWM of the centrum semiovale of all MS subgroups, including participants without disability (marginal mean ± standard error, healthy controls: 0.78 ± 0.04; EDSS 0-1: 0.86 ± 0.03 [P = .02]; EDSS 1.5-3: 0.95 ± 0.04 [P < .001]; EDSS ≥3.5: 0.94 ± 0.04 [P = .001]). A lower ratio of NAA to tCr was found in MS subgroups with disabilities, both in their NAWM (marginal mean ± standard error, healthy controls: 1.46 ± 0.04; EDSS 1.5-3: 1.33 ± 0.03 [P = .03]; EDSS ≥3.5: 1.30 ± 0.04 [P = .01]) and CGM (marginal mean ± standard error, healthy controls: 1.42 ± 0.05; EDSS ≥3.5: 1.23 ± 0.05 [P = .006]). mI/NAA correlated with EDSS (NAWM of centrum semiovale: r = 0.47, P < .001; parietal NAWM: r = 0.43, P = .002; frontal NAWM: r = 0.34, P = .01; frontal CGM: r = 0.37, P = .004). Conclusion MR spectroscopic imaging at 7.0 T allowed in vivo visualization of multiple sclerosis pathologic findings not visible at T1- or T2-weighted MRI. Metabolic abnormalities in the normal-appearing white matter and cortical gray matter were associated with disability. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Barker in this issue.


Asunto(s)
Personas con Discapacidad , Esclerosis Múltiple , Sustancia Blanca , Adulto , Encéfalo/patología , Creatina/metabolismo , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Esclerosis Múltiple/patología , Receptores de Antígenos de Linfocitos T/metabolismo , Sustancia Blanca/patología
7.
Artículo en Inglés | MEDLINE | ID: mdl-34655804

RESUMEN

BACKGROUND: Thalamocortical white matter connectivity is disrupted in psychosis and is hypothesized to play a role in its etiology and associated cognitive impairment. Attenuated cognitive symptoms often begin in adolescence, during a critical phase of white matter and cognitive development. However, little is known about the development of thalamocortical white matter connectivity and its association with cognition. METHODS: This study characterized effects of age, sex, psychosis symptomatology, and cognition in thalamocortical networks in a large sample of youths (N = 1144, ages 8-22 years, 46% male) from the Philadelphia Neurodevelopmental Cohort, which included 316 typically developing youths, 330 youths on the psychosis spectrum, and 498 youths with other psychopathology. Probabilistic tractography was used to quantify percent total connectivity between the thalamus and six cortical regions and assess microstructural properties (i.e., fractional anisotropy) of thalamocortical white matter tracts. RESULTS: Overall, percent total connectivity of the thalamus was weakly associated with age and was not associated with psychopathology or cognition. In contrast, fractional anisotropy of all thalamocortical tracts increased significantly with age, was generally higher in males than females, and was lowest in youths on the psychosis spectrum. Fractional anisotropy of tracts linking the thalamus to prefrontal and posterior parietal cortices was related to better cognitive function across subjects. CONCLUSIONS: By characterizing the pattern of typical development and alterations in those at risk for psychotic disorders, this study provides a foundation for further conceptualization of thalamocortical white matter microstructure as a marker of neurodevelopment supporting cognition and an important risk marker for psychosis.


Asunto(s)
Trastornos Psicóticos , Sustancia Blanca , Adolescente , Adulto , Anisotropía , Niño , Cognición , Femenino , Humanos , Masculino , Tálamo , Sustancia Blanca/patología , Adulto Joven
8.
Commun Biol ; 4(1): 1413, 2021 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-34931059

RESUMEN

For over 150 years, the study of patients with acquired alexia has fueled research aimed at disentangling the neural system critical for reading. An unreached goal, however, relates to the determination of the fiber pathways that root the different visual and linguistic processes needed for accurate word reading. In a unique series of neurosurgical patients with a tumor close to the visual word form area, we combine direct electrostimulation and population-based streamline tractography to map the disconnectivity fingerprints characterizing dissociated forms of alexia. Comprehensive analyses of disconnectivity matrices establish similarities and dissimilarities in the disconnection patterns associated with pure, phonological and lexical-semantic alexia. While disconnections of the inferior longitudinal and posterior arcuate fasciculi are common to all alexia subtypes, disconnections of the long arcuate and vertical occipital fasciculi are specific to phonological and pure alexia, respectively. These findings provide a strong anatomical background for cognitive and neurocomputational models of reading.


Asunto(s)
Dislexia/patología , Lectura , Sustancia Blanca/patología , Adulto , Alexia Pura/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/patología , Adulto Joven
9.
J Inherit Metab Dis ; 44(6): 1434-1440, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34499753

RESUMEN

In the most common variant of childhood cerebral adrenoleukodystrophy (cALD), demyelinating brain lesions are distributed predominately in parieto-occipital white matter. Less frequently, lesions first develop in frontal white matter. This matched cohort study examined whether outcomes after standard treatment with hematopoietic cell transplantation (HCT) differ in patients with early stage frontal lesions as compared to parieto-occipital lesions. Retrospective chart review identified seven pediatric patients with frontal cALD lesions and MRI severity score < 10 who underwent a single HCT at our center between 1990 and 2019. Concurrent MRI, neurocognitive and psychiatric outcomes at last comprehensive follow-up (mean 1.2 years; range 0.5-2.1 years) were compared with a group of seven boys with the parieto-occipital variant matched on pre-HCT MRI severity score. Both groups showed similar rates of transplant complications and radiographic disease advancement. Neurocognitive outcomes were broadly similar, with more frequent working memory deficits among individuals with frontal lesions. Psychiatric problems (hyperactivity, aggression, and atypical behavior) were considerably more common and severe among patients with frontal lesions. Aligned with the critical role of the frontal lobes in emotional and behavioral regulation, functional disruption of self-regulation skills is widely observed among patients with frontal lesions. Comprehensive care for cALD should address needs for psychiatric care and management.


Asunto(s)
Adrenoleucodistrofia/cirugía , Enfermedades Desmielinizantes/etiología , Lóbulo Frontal/patología , Trasplante de Células Madre Hematopoyéticas , Trastornos Mentales/etiología , Sustancia Blanca/patología , Adolescente , Adrenoleucodistrofia/complicaciones , Adrenoleucodistrofia/diagnóstico por imagen , Niño , Preescolar , Enfermedades Desmielinizantes/diagnóstico por imagen , Emociones , Lóbulo Frontal/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Mentales/diagnóstico por imagen , Pruebas Neuropsicológicas , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Sustancia Blanca/diagnóstico por imagen
10.
Proc Natl Acad Sci U S A ; 118(21)2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-34011608

RESUMEN

Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation ("handshake"), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.


Asunto(s)
Corteza Cerebral/metabolismo , Cromatina/química , Cuerpo Calloso/metabolismo , Proteínas de Unión al ADN/genética , Mutación con Pérdida de Función , Tálamo/metabolismo , Factores de Transcripción/genética , Anomalías Múltiples/genética , Anomalías Múltiples/metabolismo , Anomalías Múltiples/patología , Animales , Corteza Cerebral/patología , Cromatina/metabolismo , Conectoma , Cuerpo Calloso/patología , Proteínas de Unión al ADN/deficiencia , Cara/anomalías , Cara/patología , Eliminación de Gen , Regulación de la Expresión Génica , Sustancia Gris/metabolismo , Sustancia Gris/patología , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/metabolismo , Deformidades Congénitas de la Mano/patología , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Discapacidad Intelectual/patología , Ratones , Ratones Transgénicos , Micrognatismo/genética , Micrognatismo/metabolismo , Micrognatismo/patología , Cuello/anomalías , Cuello/patología , Vías Nerviosas/metabolismo , Vías Nerviosas/patología , Neuronas/metabolismo , Neuronas/patología , Tálamo/patología , Factores de Transcripción/deficiencia , Vibrisas/metabolismo , Vibrisas/patología , Sustancia Blanca/metabolismo , Sustancia Blanca/patología
11.
Brain Struct Funct ; 226(2): 425-441, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33389045

RESUMEN

The sagittal stratum (SS) is a large sheet-like structure where major axonal fiber tracts cross, though its anatomical delineations are still debated. Here we investigated the poorly studied anatomo-functional organization of the right SS using direct electrical stimulation (DES) in patients undergoing wide-awake surgery for a cerebral glioma. Seventeen patients were included. There were six males, the mean age was 38 years old. One patient underwent surgery twice. Fourteen patients were right-handed and one was ambidextrous. Behavior tasks were used to monitor online the patients' functions during DES, including visual and somesthetic processes, semantics, language, spatial and social cognition. Beyond the cortical DES, the mapping of axonal pathways evoked various functional responses. At the level of the core of the right SS, there were visual disturbances, visual hemi-agnosia, semantic paraphasia, left spatial neglect, confusion and comprehension difficulties, anomia, and mentalizing disturbances. At the level of the surrounding axonal pathways, there were left spatial neglect, anomia, vertigo, dysesthesia, and hearing disturbances. Our functionally defined three-dimensional map indicates that this complex region has a multilayered functional architecture, and supports an organization founded on two anatomical systems: a core system formed by the optic radiations, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus, and a peripheral one composed of surrounding or intersecting white matter tracts, including the superior longitudinal fasciculus/arcuate fasciculus, thalamocortical radiations, auditory radiations, and parieto-insular vestibular system. These results should prompt neurosurgeons to achieve awake DES mapping within the right SS because of the likelihood of causing multiple and irreversible structural disconnections.


Asunto(s)
Axones/fisiología , Red Nerviosa/patología , Sustancia Blanca/patología , Adulto , Mapeo Encefálico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/fisiopatología , Neoplasias Encefálicas/cirugía , Estimulación Eléctrica , Femenino , Glioma/patología , Glioma/fisiopatología , Glioma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Vigilia , Sustancia Blanca/fisiopatología
12.
Neuromolecular Med ; 23(3): 344-347, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33486699

RESUMEN

Following traumatic brain injury (TBI), increased production of reactive oxygen species (ROS) and the ensuing oxidative stress promotes the secondary brain damage that encompasses both grey matter and white matter. As this contributes to the long-term neurological deficits, decreasing oxidative stress during the acute period of TBI is beneficial. While NADPH oxidase (NOX2) is the major producer of ROS, transcription factor Nrf2 that induces antioxidant enzymes promotes efficient ROS disposal. We recently showed that treatment with an antioxidant drug combo of apocynin (NOX2 inhibitor) and TBHQ (Nrf2 activator) protects the grey matter in adult mice subjected to TBI. We currently show that this antioxidant combo therapy given at 2 h and 24 h after TBI also protects white matter in mouse brain. Thus, the better functional outcomes after TBI in the combo therapy treated mice might be due to a combination of sparing both grey matter and white matter. Hence, the antioxidant combo we tested is a potent therapeutic option for translation in future.


Asunto(s)
Acetofenonas/uso terapéutico , Antioxidantes/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Hidroquinonas/uso terapéutico , Sustancia Blanca/efectos de los fármacos , Acetofenonas/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Lesiones Traumáticas del Encéfalo/patología , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Sustancia Gris/efectos de los fármacos , Sustancia Gris/patología , Hidroquinonas/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , NADPH Oxidasa 2/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/agonistas , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Sustancia Blanca/patología
13.
Hum Brain Mapp ; 42(3): 753-765, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33098363

RESUMEN

This study aimed to explore brain structural and white matter microstructural reorganization in the early stage of tinnitus and identify brain alterations that contribute to its relief after 6 months of sound therapy. We studied 64 patients with idiopathic tinnitus, including 29 patients who were categorized into an effective group (EG) and 35 who were categorized into an ineffective group (IG) according to the 6-month follow-up improvement of the Tinnitus Handicap Inventory score, along with 63 healthy controls (HCs). All participants underwent structural and diffusion tensor imaging scanning on a 3-T magnetic resonance system. Differences in brain gray/white matter volume and white matter microstructure were evaluated using voxel-based morphometry analysis and tract-based spatial statistics among the three groups. Associations between brain reorganization and the improvement of tinnitus symptoms were also investigated. Compared with EG patients, IG patients experienced a significant gray matter volume decrease in the right middle frontal gyrus (MFG)/right precentral gyrus (PreCG). Meanwhile, both EG and IG patients showed significant changes (decrease or increase) in brain white matter integrity in the auditory-related or nonauditory-related white matter fiber tracts compared with HCs, while EG patients showed decreased axial diffusivity in the bilateral middle cerebellar peduncle (MCP) compared with IG patients. We combined the gray matter change of the MFG/PreCG and the white matter integrity of the bilateral MCP as an imaging indicator to evaluate the patient's prognosis and screen patients before treatment; this approach reached a sensitivity of 77.1% and a specificity of 82.8%. Our study suggests that there was a close relationship between brain reorganization and tinnitus improvement. The right MFG/PreCG and bilateral MCP may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and may be used to screen patients before sound therapy. These findings may provide new useful information that can lead to a better understanding of the tinnitus mechanism.


Asunto(s)
Corteza Cerebral/patología , Sustancia Gris/patología , Pedúnculo Cerebeloso Medio/patología , Neuroimagen/normas , Evaluación de Resultado en la Atención de Salud , Acúfeno/patología , Acúfeno/terapia , Sustancia Blanca/patología , Estimulación Acústica , Adulto , Corteza Cerebral/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Estudios de Seguimiento , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pedúnculo Cerebeloso Medio/diagnóstico por imagen , Sensibilidad y Especificidad , Acúfeno/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen
14.
J Cereb Blood Flow Metab ; 41(5): 1103-1118, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32791876

RESUMEN

Diffuse white matter (WM) disease is highly prevalent in elderly with cerebral small vessel disease (cSVD). In humans, cSVD such as cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease imposing a significant impediment for characterizing their distinct effects on WM. Here we studied the burden of age-related CAA pathology on WM disease in a novel transgenic rat model of CAA type 1 (rTg-DI). A cohort of rTg-DI and wild-type rats was scanned longitudinally using MRI for characterization of morphometry, cerebral microbleeds (CMB) and WM integrity. In rTg-DI rats, a distinct pattern of WM loss was observed at 9 M and 11 M. MRI also revealed manifestation of small CMB in thalamus at 6 M, which preceded WM loss and progressively enlarged until the moribund disease stage. Histology revealed myelin loss in the corpus callosum and thalamic CMB in all rTg-DI rats, the latter of which manifested in close proximity to occluded and calcified microvessels. The quantitation of CAA load in rTg-DI rats revealed that the most extensive microvascular Aß deposition occurred in the thalamus. For the first time using in vivo MRI, we show that CAA type 1 pathology alone is associated with a distinct pattern of WM loss.


Asunto(s)
Encéfalo/irrigación sanguínea , Angiopatía Amiloide Cerebral/patología , Hemorragia Cerebral/patología , Sustancia Blanca/patología , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Calcinosis/complicaciones , Estudios de Casos y Controles , Angiopatía Amiloide Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Cuerpo Calloso/patología , Imagen de Difusión Tensora/métodos , Modelos Animales de Enfermedad , Femenino , Carga Global de Enfermedades/estadística & datos numéricos , Imagen por Resonancia Magnética/métodos , Masculino , Microvasos/metabolismo , Microvasos/patología , Ratas , Ratas Transgénicas , Tálamo/patología , Sustancia Blanca/diagnóstico por imagen
15.
Mol Imaging Biol ; 23(1): 127-138, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32926288

RESUMEN

PURPOSE: Molecular imaging agents targeting butyrylcholinesterase (BChE) have shown promise in other neurodegenerative disorders and may have utility in detecting changes to normal appearing white matter in multiple sclerosis (MS). BChE activity is present in white matter and localizes to activated microglia associated with MS lesions. The purpose of this study was to further characterize changes in the cholinergic system in MS pathology, and to explore the utility of BChE radioligands as potential diagnostic and treatment monitoring agents in MS. PROCEDURE: Cortical and white matter lesions were identified using myelin staining, and lesions were classified based on microglial activation patterns. Adjacent brain sections were used for cholinesterase histochemistry and in vitro autoradiography using phenyl 4-[123I]-iodophenylcarbamate (123I-PIP), a previously described small-molecule cholinesterase-binding radioligand. RESULTS: BChE activity is positively correlated with microglial activation in white matter MS lesions. There is no alteration in cholinesterase activity in cortical MS lesions. 123I-PIP autoradiography revealed uptake of radioactivity in normal white matter, absence of radioactivity within demyelinated MS lesions, and variable uptake of radioactivity in adjacent normal-appearing white matter. CONCLUSIONS: BChE imaging agents have the potential to detect MS lesions and subtle pathology in normal-appearing white matter in postmortem MS brain tissue. The possibility of BChE imaging agents serving to supplement current diagnostic and treatment monitoring strategies should be evaluated.


Asunto(s)
Butirilcolinesterasa/metabolismo , Imagen Molecular , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/enzimología , Acetilcolinesterasa/metabolismo , Anciano , Autorradiografía , Estudios de Casos y Controles , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/patología , Fenilcarbamatos/química , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología
16.
Brain ; 144(1): 186-197, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33221873

RESUMEN

The thalamus represents one of the first structures affected by neurodegenerative processes in multiple sclerosis. A greater thalamic volume reduction over time, on its CSF side, has been described in paediatric multiple sclerosis patients. However, its determinants and the underlying pathological changes, likely occurring before this phenomenon becomes measurable, have never been explored. Using a multiparametric magnetic resonance approach, we quantified, in vivo, the different processes that can involve the thalamus in terms of focal lesions, microstructural damage and atrophy in paediatric multiple sclerosis patients and their distribution according to the distance from CSF/thalamus interface and thalamus/white matter interface. In 70 paediatric multiple sclerosis patients and 26 age- and sex-matched healthy controls, we tested for differences in thalamic volume and quantitative MRI metrics-including fractional anisotropy, mean diffusivity and T1/T2-weighted ratio-in the whole thalamus and in thalamic white matter, globally and within concentric bands originating from CSF/thalamus interface. In paediatric multiple sclerosis patients, the relationship of thalamic abnormalities with cortical thickness and white matter lesions was also investigated. Compared to healthy controls, patients had significantly increased fractional anisotropy in whole thalamus (f2 = 0.145; P = 0.03), reduced fractional anisotropy (f2 = 0.219; P = 0.006) and increased mean diffusivity (f2 = 0.178; P = 0.009) in thalamic white matter and a trend towards a reduced thalamic volume (f2 = 0.027; P = 0.058). By segmenting the whole thalamus and thalamic white matter into concentric bands, in paediatric multiple sclerosis we detected significant fractional anisotropy abnormalities in bands nearest to CSF (f2 = 0.208; P = 0.002) and in those closest to white matter (f2 range = 0.183-0.369; P range = 0.010-0.046), while we found significant mean diffusivity (f2 range = 0.101-0.369; P range = 0.018-0.042) and T1/T2-weighted ratio (f2 = 0.773; P = 0.001) abnormalities in thalamic bands closest to CSF. The increase in fractional anisotropy and decrease in mean diffusivity detected at the CSF/thalamus interface correlated with cortical thickness reduction (r range = -0.27-0.34; P range = 0.004-0.028), whereas the increase in fractional anisotropy detected at the thalamus/white matter interface correlated with white matter lesion volumes (r range = 0.24-0.27; P range = 0.006-0.050). Globally, our results support the hypothesis of heterogeneous pathological processes, including retrograde degeneration from white matter lesions and CSF-mediated damage, leading to thalamic microstructural abnormalities, likely preceding macroscopic tissue loss. Assessing thalamic microstructural changes using a multiparametric magnetic resonance approach may represent a target to monitor the efficacy of neuroprotective strategies early in the disease course.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente/patología , Tálamo/patología , Adolescente , Anisotropía , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología
17.
Sci Rep ; 10(1): 19728, 2020 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-33184443

RESUMEN

The prefrontal lobe has been considered to be closely related to depression. This study examined the relationship between depression and three prefronto-thalamic tract (PF-TT) regions (the dorsolateral prefronto-thalamic tract [DLPF-TT], ventrolateral prefronto-thalamic tract [VLPF-TT], and the orbitofronto-thalamic tract [OF-TT]) in patients with mild traumatic brain injury (TBI), using diffusion tensor tractography (DTT). Thirty-seven patients with depression following mild TBI were recruited based on Beck Depression Inventory-II (BDI-II) scores. Thirty-one normal control subjects were also recruited. The three regions of the PF-TTs were reconstructed using probabilistic tractography and DTT parameters for each of the three PF-TT regions were determined. The tract volume of the DLPF-TT and OF-TT in the patient group showed a significant decrease compared to that of the control group (p < 0.05). The BDI-II score of the patient group showed a moderate negative correlation with the tract volume value of the right (r = - 0.33) and left (r = - 0.41) DLPF-TT (p < 0.05). On the other hand, no significant correlations were detected between the BDI-II score of the patient group and the values of the other DTT parameters values for the three PF-TT regions (p > 0.05). Using DTT, depression was found to be closely related to a DLPF-TT injury in patients with mild TBI. We believe that evaluation of the DLPF-TT using DTT would be helpful when assessing patients with depression following mild TBI. These results can provide useful information regarding the proper application of neuromodulation in the management of depression.


Asunto(s)
Conmoción Encefálica/complicaciones , Depresión/patología , Corteza Prefrontal/patología , Tálamo/patología , Sustancia Blanca/patología , Adolescente , Adulto , Anciano , Depresión/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/lesiones , Pronóstico , Tálamo/lesiones , Sustancia Blanca/lesiones , Adulto Joven
18.
Medicine (Baltimore) ; 99(48): e23176, 2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33235078

RESUMEN

Magnetic resonance imaging (MRI) can be a tool that allows the observation of structural injury patterns after cooling. The aim of this study was to determine the early pattern of brain injury in the MRIs of infants with hypoxic ischemic encephalopathy (HIE) after cooling and to search for any clinical factors related to abnormal MRI findings.The study retrospectively recruited 118 infants who were treated with therapeutic hypothermia (TH) between 2013 and 2016.Forty-three patients had normal brain MRI, and 75 had abnormal brain MRI findings. The TH-treated infants with abnormal brain MRI readings showed significantly more clinical seizures and the use of additional antiepileptic drugs (AEDs) than the normal MRI group. As a long-term outcome, more lesions in the basal ganglia and thalamus, posterior limb of internal capsule, or severe white matter lesions were associated with abnormal neurodevelopmental outcomes at 18 to 24 months of age.A higher frequency of clinical seizures and AED use were related to abnormal brain injury on MRI. A significant risk for poor long-term outcomes was found in the abnormal brain MRI group.


Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Hipotermia Inducida/métodos , Hipoxia-Isquemia Encefálica/terapia , Convulsiones/epidemiología , Anticonvulsivantes/uso terapéutico , Ganglios Basales/patología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/estadística & datos numéricos , Femenino , Humanos , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Lactante , Cápsula Interna/patología , Masculino , Trastornos del Neurodesarrollo/epidemiología , Evaluación de Resultado en la Atención de Salud , Pronóstico , República de Corea/epidemiología , Estudios Retrospectivos , Convulsiones/tratamiento farmacológico , Tálamo/patología , Sustancia Blanca/patología
19.
Hum Brain Mapp ; 41(15): 4431-4441, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-32657510

RESUMEN

Deficits in information processing speed (IPS) are among the earliest and most prominent cognitive manifestations in mild traumatic brain injury (mTBI). We investigated the impact of white matter fiber location on IPS outcome in an individual basis assessment. A total of 112 acute mild TBI with all CT negative underwent brain DTI and blood sampling for inflammation cytokines within 7 days postinjury and 72 age- and sex matched healthy controls with same assessments were enrolled. IPS outcome was assessed by the trail making test at 6-12 month postinjury in mild TBI. Fractional anisotropy (FA) features were extracted using a novel lesion-load analytical strategy to capture spatially heterogeneous white matter injuries and minimize implicit assumptions of uniform injury across diverse clinical presentations. Acute mild TBI exhibited a general pattern of increased and decreased FA in specific white matter tracts. The power of acute FA measures to identify patients developing IPS deficits with 92% accuracy and further improved to 96% accuracy by adding inflammation cytokines. The classifiers predicted individual's IPS and working memory ratings (r = .74 and .80, respectively, p < .001). The thalamo-cortical circuits and commissural tracts projecting or connecting frontal regions became important predictors. This prognostic model was also verified by an independent replicate sample. Our findings highlighted damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in mild TBI.


Asunto(s)
Conmoción Encefálica/patología , Conmoción Encefálica/fisiopatología , Corteza Cerebral/patología , Disfunción Cognitiva/fisiopatología , Imagen de Difusión Tensora , Tiempo de Reacción/fisiología , Tálamo/patología , Sustancia Blanca/patología , Adulto , Conmoción Encefálica/complicaciones , Corteza Cerebral/diagnóstico por imagen , Disfunción Cognitiva/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Tálamo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto Joven
20.
Curr Opin Neurol ; 33(4): 422-429, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32657883

RESUMEN

PURPOSE OF REVIEW: Ultra-high field 7 T MRI has multiple applications for the in vivo characterization of the heterogeneous aspects underlying multiple sclerosis including the identification of cortical lesions, characterization of the different types of white matter plaques, evaluation of structures difficult to assess with conventional MRI (thalamus, cerebellum, spinal cord, meninges). RECENT FINDINGS: The sensitivity of cortical lesion detection at 7 T is twice than at lower field MRI, especially for subpial lesions, the most common cortical lesion type in multiple sclerosis. Cortical lesion load accrual is independent of that in the white matter and predicts disability progression.Seven Tesla MRI provides details on tissue microstructure that can be used to improve white matter lesion characterization. These include the presence of a central vein, whose identification can be used to improve multiple sclerosis diagnosis, or the appearance of an iron-rich paramagnetic rim on susceptibility-weighted images, which corresponds to iron-rich microglia at the periphery of slow expanding lesions. Improvements in cerebellar and spinal cord tissue delineation and lesion characterization have also been demonstrated. SUMMARY: Imaging at 7 T allows assessing more comprehensively the complementary pathophysiological aspects of multiple sclerosis, opening up novel perspectives for clinical and therapeutics evaluation.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Médula Espinal/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Progresión de la Enfermedad , Humanos , Esclerosis Múltiple/patología , Médula Espinal/patología , Sustancia Blanca/patología
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