RESUMEN
This study aims to investigate the structural reorganization in the sensorimotor area of the brain in patients with gliomas, distinguishing between those with impaired and unimpaired strength. Using voxel-based morphometry (VBM) and region of interest (ROI) analysis, gray matter volumes (GMV) were compared in the contralesional primary motor gyrus, primary sensory gyrus, premotor area, bilateral supplementary motor area, and medial Brodmann area 8 (BA8). The results revealed that in patients with right hemisphere gliomas, the right medial BA8 volume was significantly larger in the impaired group than in the unimpaired group, with both groups exceeding the volume in 16 healthy controls (HCs). In patients with left hemisphere gliomas, the right supplementary motor area (SMA) was more pronounced in the impaired group compared to the unimpaired group, and both groups were greater than HCs. Additionally, the volumes of the right medial BA8 in both the impaired group were greater than HCs. Contralateral expansions in the gray matter of hand- and trunk-related cortices of the premotor area, precentral gyrus, and postcentral gyrus were observed compared to HCs. Furthermore, a negative correlation was found between hand Medical Research Council (MRC) score and volumes of the contralateral SMA and bilateral medial BA8. Notably, our findings reveal consistent results across both analytical approaches in identifying significant structural reorganizations within the sensorimotor cortex. These consistent findings underscore the adaptive neuroplastic responses to glioma presence, highlighting potential areas of interest for further neurosurgical planning and rehabilitation strategies.
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Neoplasias Encefálicas , Lateralidad Funcional , Glioma , Imagen por Resonancia Magnética , Corteza Sensoriomotora , Humanos , Masculino , Glioma/diagnóstico por imagen , Glioma/patología , Glioma/fisiopatología , Femenino , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/fisiopatología , Adulto , Persona de Mediana Edad , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/patología , Corteza Sensoriomotora/fisiopatología , Lateralidad Funcional/fisiología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Corteza Motora/diagnóstico por imagen , Corteza Motora/patología , Corteza Motora/fisiopatología , Mapeo Encefálico , Adulto JovenRESUMEN
Background. Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. Objective. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. Methods. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. Results. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Conclusions. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.
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Cuerpo Calloso/patología , Actividad Motora/fisiología , Tractos Piramidales/patología , Recuperación de la Función/fisiología , Corteza Sensoriomotora/patología , Accidente Cerebrovascular/patología , Sustancia Blanca/patología , Animales , Conducta Animal/fisiología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/fisiopatología , Imagen de Difusión Tensora , Modelos Animales de Enfermedad , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Tractos Piramidales/diagnóstico por imagen , Tractos Piramidales/fisiopatología , Ratas , Ratas Sprague-Dawley , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/fisiopatologíaRESUMEN
AIMS: To explore the novel linkage between a Western diet combining high saturated fat, sugar, and salt (HFSS) and neurological dysfunctions during aging as well as Metformin intervention, we assessed cerebral cortex abnormalities associated with sensory and motor dysfunctions and cellular and molecular insights in brains using HFSS-fed mice during aging. We also explored the effect of Metformin treatment on these mice. METHODS: C57BL/6 mice were fed with HFSS and treated with metformin from 20 to 22 months of age, resembling human aging from 56 to 68 years of age (an entry phase of the aged portion of lifespan). RESULTS: The motor and sensory cortexes in mice during aging after HFSS diet showed: (A) decreased motor-muscular and sensory functions; (B) reduced inflammation-resolving Arg-1+ microglia; (C) increased inflammatory iNOs+ microglia and TNFα levels; (D) enhanced abundance of amyloid-ß peptide and of phosphorylated Tau. Metformin attenuated these changes. CONCLUSION: A HFSS-combined diet caused motor-muscular and sensory dysfunctions, neuroinflammation, and neurodegeneration, whereas metformin counteracted these effects. Our findings show neuroinflammatory consequences of a HFSS diet in aging. Metformin curbs the HFSS-related neuroinflammation eliciting neuroprotection.
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Envejecimiento/efectos de los fármacos , Dieta de Carga de Carbohidratos/efectos adversos , Dieta Alta en Grasa/efectos adversos , Dieta Occidental/efectos adversos , Hipoglucemiantes/farmacología , Metformina/farmacología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Corteza Sensoriomotora/efectos de los fármacos , Cloruro de Sodio Dietético/efectos adversos , Anciano , Envejecimiento/patología , Envejecimiento/fisiología , Animales , Modelos Animales de Enfermedad , Humanos , Hipoglucemiantes/administración & dosificación , Masculino , Metformina/administración & dosificación , Ratones , Ratones Endogámicos C57BL , Enfermedades Neurodegenerativas/etiología , Enfermedades Neuroinflamatorias/etiología , Corteza Sensoriomotora/inmunología , Corteza Sensoriomotora/patología , Corteza Sensoriomotora/fisiopatologíaRESUMEN
Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro- and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term-equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3-4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole-brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel-based (FB) analysis to compute fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC) for each tract. Of 223 VPT infants with high-quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants.
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Parálisis Cerebral/diagnóstico por imagen , Parálisis Cerebral/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen de Difusión Tensora , Femenino , Humanos , Lactante , Recien Nacido Extremadamente Prematuro , Recién Nacido , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Estudios Prospectivos , Riesgo , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/patologíaRESUMEN
Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
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Tronco Encefálico/patología , Accidente Cerebrovascular Isquémico/patología , Corteza Sensoriomotora/patología , Tálamo/patología , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Mapeo Encefálico , Tronco Encefálico/irrigación sanguínea , Tronco Encefálico/diagnóstico por imagen , Revascularización Cerebral/métodos , Estudios de Cohortes , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Factores de Riesgo , Corteza Sensoriomotora/irrigación sanguínea , Corteza Sensoriomotora/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Factores Sexuales , Tálamo/irrigación sanguínea , Tálamo/diagnóstico por imagen , Resultado del TratamientoRESUMEN
The integrity of the structural cerebral cortex is disrupted after stroke either at the macroscopic or microscopic levels. Therefore, many attempts have been gathered to circumvent stroke-associated problems in the brain tissue. The current study was aimed to design an animal model of photochemical stroke using rose bengal (RB) plus laser irradiation (L) after 10, 15, and 20 min (´) and evaluate its effect on the cerebral tissue using unbiased stereological quantitative methods and morphometric histological analysis. Photochemical stroke was induced by intraperitoneal injection of RB dye and further activation through the exposure of the right sensorimotor cortex with the green laser radiation (100 mW; 532 nm). Mice were randomly allocated into 4 groups (each in 15) as follows: control (10 µg/gbw RB), RB + 10'L, RB + 15'L, and RB + 20'L. Target irradiation site was adjusted to 2 mm lateral to the bregma. Vernier caliper morphometric evaluation, cresyl violet staining, and unbiased stereological assays including Cavalier's principle and point counting techniques were used to monitor the pathological changes and lesion volume on days 1, 3, and 7 after the ischemia induction. Our data showed that the mean diameter of the lesion site and lesion infarct volume in the group RB + 20'L) was significantly increased relative to the other groups (P < 0.05). Notably, the lesion volume and diameter in the group RB + 15'L was larger compared with the group RB + 10'L and control mice (P < 0.05). Data showed an increased acute inflammatory response such as hyperemia and edema 3 days after ischemic induction while the intensity of acute changes and lesion volume were reduced and replaced with necrotic and chronic pathological changes including astrogliosis on day 7. It is concluded that the laser irradiation of RB-injected mice at a distinct time period could induce the magnificent degenerative effects on the cerebral cortex which is similar to the stroke condition.
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Procesos Fotoquímicos , Corteza Sensoriomotora/lesiones , Corteza Sensoriomotora/efectos de la radiación , Accidente Cerebrovascular/patología , Animales , Isquemia Encefálica/complicaciones , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Gliosis/complicaciones , Gliosis/patología , Masculino , Ratones , Corteza Sensoriomotora/patología , Accidente Cerebrovascular/complicacionesRESUMEN
To validate a simultaneous analysis tool for the brain and cervical cord embedded in the statistical parametric mapping (SPM) framework, we compared trauma-induced macro- and microstructural changes in spinal cord injury (SCI) patients to controls. The findings were compared with results obtained from existing processing tools that assess the brain and spinal cord separately. A probabilistic brain-spinal cord template (BSC) was generated using a generative semi-supervised modelling approach. The template was incorporated into the pre-processing pipeline of voxel-based morphometry and voxel-based quantification analyses in SPM. This approach was validated on T1-weighted scans and multiparameter maps, by assessing trauma-induced changes in SCI patients relative to controls and comparing the findings with the outcome from existing analytical tools. Consistency of the MRI measures was assessed using intraclass correlation coefficients (ICC). The SPM approach using the BSC template revealed trauma-induced changes across the sensorimotor system in the cord and brain in SCI patients. These changes were confirmed with established approaches covering brain or cord, separately. The ICC in the brain was high within regions of interest, such as the sensorimotor cortices, corticospinal tracts and thalamus. The simultaneous voxel-wise analysis of brain and cervical spinal cord was performed in a unique SPM-based framework incorporating pre-processing and statistical analysis in the same environment. Validation based on a SCI cohort demonstrated that the new processing approach based on the brain and cord is comparable to available processing tools, while offering the advantage of performing the analysis simultaneously across the neuraxis.
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Encéfalo/diagnóstico por imagen , Médula Cervical/diagnóstico por imagen , Neuroimagen/métodos , Traumatismos de la Médula Espinal/diagnóstico por imagen , Adulto , Encéfalo/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen/normas , Tractos Piramidales/diagnóstico por imagen , Tractos Piramidales/patología , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/patología , Traumatismos de la Médula Espinal/patología , Tálamo/diagnóstico por imagen , Tálamo/patologíaRESUMEN
White matter fiber tracts demonstrate heterogeneous vulnerabilities to aging effects. Here, we estimated age-related differences in tract properties using UK Biobank diffusion magnetic resonance imaging data of 7167 47- to 76-year-old neurologically healthy people (3368 men and 3799 women). Tract properties in terms of generalized fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were sampled on 76 fiber tracts; for each tract, age-related differences were estimated by fitting these indices against age in a linear model. This cross-sectional study demonstrated 4 age-difference patterns. The dominant pattern was lower generalized fractional anisotropy and higher axial diffusivity, radial diffusivity, and mean diffusivity with age, constituting 45 of 76 tracts, mostly involving the association, projection, and commissure fibers connecting the prefrontal lobe. The other 3 patterns constituted only 14 tracts, with atypical age differences in diffusion indices, and mainly involved parietal, occipital, and temporal cortices. By analyzing the large volume of diffusion magnetic resonance imaging data available from the UK Biobank, the study has provided a detailed description of heterogeneous age-related differences in tract properties over the whole brain which generally supports the myelodegeneration hypothesis.
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Envejecimiento/patología , Imagen de Difusión por Resonancia Magnética , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Anciano , Anisotropía , Bancos de Muestras Biológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Degeneración Nerviosa , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/patología , Caracteres Sexuales , Reino Unido , Vías Visuales/diagnóstico por imagen , Vías Visuales/patologíaRESUMEN
Frequently reported neurotoxic sequelae of cancer treatment include cognitive deficits and sensorimotor abnormalities that have long-lasting negative effects on the quality of life of an increasing number of cancer survivors. The underlying mechanisms are not fully understood and there is no effective treatment. We show here that cisplatin treatment of mice not only caused cognitive dysfunction but also impaired sensorimotor function. These functional deficits are associated with reduced myelin density and complexity in the cingulate and sensorimotor cortex. At the ultrastructural level, myelin abnormalities were characterized by decompaction. We used this model to examine the effect of bexarotene, an agonist of the RXR-family of nuclear receptors. Administration of only five daily doses of bexarotene after completion of cisplatin treatment was sufficient to normalize myelin density and fiber coherency and to restore myelin compaction in cingulate and sensorimotor cortex. Functionally, bexarotene normalized performance of cisplatin-treated mice in tests for cognitive and sensorimotor function. RNAseq analysis identified the TR/RXR pathway as one of the top canonical pathways activated by administration of bexarotene to cisplatin-treated mice. Bexarotene also activated neuregulin and netrin pathways that are implicated in myelin formation/maintenance, synaptic function and axonal guidance. In conclusion, short term treatment with bexarotene is sufficient to reverse the adverse effects of cisplatin on white matter structure, cognitive function, and sensorimotor performance. These encouraging findings warrant further studies into potential clinical translation and the underlying mechanisms of bexarotene for chemobrain.
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Antineoplásicos/farmacología , Bexaroteno/farmacología , Cisplatino/toxicidad , Cognición/efectos de los fármacos , Giro del Cíngulo/efectos de los fármacos , Vaina de Mielina/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Corteza Sensoriomotora/efectos de los fármacos , Animales , Antineoplásicos/toxicidad , Deterioro Cognitivo Relacionado con la Quimioterapia/metabolismo , Deterioro Cognitivo Relacionado con la Quimioterapia/patología , Deterioro Cognitivo Relacionado con la Quimioterapia/fisiopatología , Marcha/efectos de los fármacos , Perfilación de la Expresión Génica , Giro del Cíngulo/metabolismo , Giro del Cíngulo/patología , Giro del Cíngulo/fisiopatología , Ratones , Vaina de Mielina/metabolismo , Vaina de Mielina/patología , Vaina de Mielina/ultraestructura , Netrinas/efectos de los fármacos , Netrinas/genética , Netrinas/metabolismo , Neurregulinas/efectos de los fármacos , Neurregulinas/genética , Neurregulinas/metabolismo , Prueba de Campo Abierto , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Corteza Prefrontal/fisiopatología , RNA-Seq , Receptores X Retinoide/efectos de los fármacos , Receptores X Retinoide/genética , Receptores X Retinoide/metabolismo , Corteza Sensoriomotora/metabolismo , Corteza Sensoriomotora/patología , Corteza Sensoriomotora/fisiopatología , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/metabolismo , Sustancia Blanca/patologíaRESUMEN
INTRODUCTION: Hydrocephalus is a disorder in which the circulation of cerebrospinal fluid is altered in a manner that leads to its accumulation in the ventricles and subarachnoid space. Its impact on the neuronal density and networks in the overlying cerebral cortex in a time-dependent neonatal hydrocephalic process is largely unknown. We hypothesize that hydrocephalus will affect the cytoarchitecture of the cerebral cortical mantle of neonatal hydrocephalic mice, which will in turn modify sensorimotor processing and neurobehaviour. OBJECTIVE: The purpose of this study is to probe the effect of hydrocephalus on 3 developmental milestones (surface righting reflex, cliff avoidance reflex, and negative geotaxis) and on cortical neuronal densities in neonatal hydrocephalic mice. METHODS: Hydrocephalus was induced in 1-day-old mice by intracisternal injection of sterile kaolin suspension. The pups were tested for reflex development and sensorimotor ability using surface righting reflex (PND 5, 7, and 9), cliff avoidance (PND 6), and negative geotaxis (PND 10 and 12) prior to their sacrifice on PND 7, 14, and 21. Neuronal density and cortical thickness in the sensorimotor cortex were evaluated using atlas-based segmentation of the neocortex and boundary definition in 4-µm paraffin-embedded histological sections with hematoxylin and eosin as well as cresyl violet stains. RESULTS: Surface righting and cliff avoidance activities were significantly impaired in hydrocephalic pups but no statistically significant difference was observed in negative geotaxis in both experimental and control pups. The neuronal density of the sensorimotor cortex was significantly higher in hydrocephalic mice than in age-matched controls on PND 14 and 21 (373.20 ± 21.54 × 10-6 µm2 vs. 157.70 ± 21.88 × 10-6 µm2; 230.0 ± 44.1 × 10-6 µm2 vs. 129.60 ± 3.72 × 10-6 µm2, respectively; p < 0.05). This was accompanied by reduction in the cortical thickness (µm) in the hydrocephalic mice on PND 7 (2,409 ± 43.37 vs. 3,752 ± 65.74, p < 0.05), PND 14 (2,035 ± 322.10 vs. 4,273 ± 67.26, p < 0.05), and PND 21 (1,676 ± 33.90 vs. 4,945 ± 81.79, p < 0.05) compared to controls. CONCLUSION: In this murine model of neonatal hydrocephalus, the quantitative changes in the cortical neuronal population may play a role in the observed changes in neurobehavioural findings.
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Recuento de Células/métodos , Hidrocefalia/patología , Caolín/toxicidad , Trastornos del Neurodesarrollo/patología , Neuronas/patología , Corteza Sensoriomotora/patología , Animales , Animales Recién Nacidos , Hidrocefalia/inducido químicamente , Hidrocefalia/psicología , Ratones , Trastornos del Neurodesarrollo/inducido químicamente , Trastornos del Neurodesarrollo/psicología , Neuronas/efectos de los fármacos , Reflejo de Enderezamiento/efectos de los fármacos , Reflejo de Enderezamiento/fisiología , Corteza Sensoriomotora/efectos de los fármacos , Corteza Sensoriomotora/crecimiento & desarrolloRESUMEN
Mitochondrial respiratory chain integrity depends on a number of proteins encoded by nuclear and mitochondrial genomes. Mutations of such factors can result in isolated or combined respiratory chain deficits, some of which can induce abnormal morphology of the mitochondrial network or accumulation of intermediary metabolites. Consequently, affected patients are clinically heterogeneous, presenting with central nervous system, muscular, or neurodegenerative disorders. ATAD3A is a nuclear-encoded ATPase protein of the AAA+ family and has been localized to the inner mitochondrial membrane. Recently reported mutations or large deletions in the ATDA3A gene in patients have been shown to induce altered mitochondrial structure and function and abnormal cholesterol metabolism in a recessive or dominant manner. Here, we report two siblings presenting axonal sensory-motor neuropathy associated with neonatal cataract. Genetic analyses identified two novel mutations in ATAD3A; a point mutation and an intronic 15 bp deletion affecting splicing and leading to exon skipping. Biochemical analysis in patient cells and tissues showed abnormal function of the mitochondrial respiratory chain in muscle and abnormal mitochondrial cristae structure. These new cases underline the large spectrum of biochemical and clinical presentations of ATAD3A deficiency and the different modes of inheritance, making it an atypical mitochondrial disorder.
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ATPasas Asociadas con Actividades Celulares Diversas/genética , Transporte de Electrón/genética , Proteínas de la Membrana/genética , Mitocondrias/genética , Enfermedades Mitocondriales/genética , Proteínas Mitocondriales/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Mitocondrias/patología , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/patología , Mutación/genética , Corteza Sensoriomotora/patología , HermanosRESUMEN
The sense of agency (SoA) refers to the perception that an action is the consequence of one's own intention. Studies exploring the SoA with neuroimaging techniques summarized the available data and confirmed a role of fronto-parietal areas and subcortical structures. However, these studies focused on specific regions of interest. We thus conducted a whole-brain meta-analysis to verify which regions emerge as significant for the SoA, specifically during motor execution. We performed a systematic search on PubMed, PsycINFO and Cochrane databases with the following inclusion criteria: studies investigating SoA with a visuo-motor task by means of neuroimaging in healthy subjects. We performed a quantitative, whole-brain, meta-analysis of neural correlates of the SoA based on the activation likelihood estimation. Of the 785 articles identified by our search, 22 studies met our inclusion criteria (169 foci, 295 subjects for decreased agency, and 58 foci, 165 subjects for normal agency). Neural correlates of decreased agency were the bilateral temporo-parietal junction (MNI: 50,-54,14; -44,-52,42; -48,-56,8). Normal agency showed no significant clusters of activation. This meta-analysis confirmed the key role of areas responsible for decreased SoA during motor control, whereas normal agency did not show a specific neural signature. This study sets the ground for future regions-of-interest analyses of neural correlates of SoA, as well as potential neuromodulation studies, which might be relevant in medical conditions presenting with abnormal SoA.
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Encéfalo/diagnóstico por imagen , Actividad Motora/fisiología , Autoimagen , Adolescente , Adulto , Encéfalo/fisiología , Femenino , Humanos , Intención , Masculino , Persona de Mediana Edad , Neuroimagen/métodos , Desempeño Psicomotor/fisiología , Autocontrol/psicología , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/patologíaRESUMEN
Graph theory and network modelling have been previously applied to characterize motor network structural topology in multiple sclerosis (MS). However, between-group differences disclosed by graph analysis might be primarily driven by discrepancy in density, which is likely to be reduced in pathologic conditions as a consequence of macroscopic damage and fibre loss that may result in less streamlines properly traced. In this work, we employed the convex optimization modelling for microstructure informed tractography (COMMIT) framework, which, given a tractogram, estimates the actual contribution (or weight) of each streamline in order to optimally explain the diffusion magnetic resonance imaging signal, filtering out those that are implausible or not necessary. Then, we analysed the topology of this 'COMMIT-weighted sensory-motor network' in MS accounting for network density. By comparing with standard connectivity analysis, we also tested if abnormalities in network topology are still identifiable when focusing on more 'quantitative' network properties. We found that topology differences identified with standard tractography in MS seem to be mainly driven by density, which, in turn, is strongly influenced by the presence of lesions. We were able to identify a significant difference in density but also in network global and local properties when accounting for density discrepancy. Therefore, we believe that COMMIT may help characterize the structural organization in pathological conditions, allowing a fair comparison of connectomes which considers discrepancies in network density. Moreover, discrepancy-corrected network properties are clinically meaningful and may help guide prognosis assessment and treatment choice.
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Imagen de Difusión por Resonancia Magnética/métodos , Sustancia Gris/patología , Esclerosis Múltiple Crónica Progresiva/patología , Red Nerviosa/patología , Corteza Prefrontal/patología , Corteza Sensoriomotora/patología , Adulto , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Corteza Sensoriomotora/diagnóstico por imagenRESUMEN
Dipeptidyl peptidase-4 inhibitors (or gliptins), a class of antidiabetic drugs, have recently been shown to have protective actions in the central nervous system. Their cellular and molecular mechanisms responsible for these effects are largely unknown. In the present study, two structurally different gliptins, sitagliptin and vildagliptin, were examined for their therapeutic actions in a controlled cortical impact (CCI) model of moderate traumatic brain injury (TBI) in mice. Early post-CCI treatment with sitagliptin, but not vildagliptin, significantly reduced body asymmetry, locomotor hyperactivity, and brain lesion volume. Sitagliptin attenuated post-CCI microglial deramification in the ipsilateral dorsolateral (DL) striatum, while vildagliptin had no effect. Sitagliptin also reduced striatal expression of galectin-3 and monocyte chemoattractant protein 1(MCP-1), and increased the cortical and striatal levels of the anti-inflammatory cytokine IL-10 on the ipsilateral side. These data support a differential protective effect of sitagliptin against TBI, possibly mediated by an anti-inflammatory effect in striatum to preserve connective network. Both sitagliptin and vildagliptin produced similar increases of active glucagon-like peptide-1 (GLP-1) in blood and brain. Increasing active GLP-1 may not be the sole molecular mechanisms for the neurotherapeutic effect of sitagliptin in TBI.
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Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Fármacos Neuroprotectores/farmacología , Corteza Sensoriomotora/efectos de los fármacos , Corteza Sensoriomotora/lesiones , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Quimiocina CCL2/metabolismo , Modelos Animales de Enfermedad , Galectina 3/metabolismo , Péptido 1 Similar al Glucagón/sangre , Péptido 1 Similar al Glucagón/metabolismo , Interleucina-10 , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/patología , Corteza Sensoriomotora/patología , Fosfato de Sitagliptina/farmacología , Vildagliptina/farmacología , Corteza Visual/efectos de los fármacos , Corteza Visual/patologíaRESUMEN
Importance: Developmental coordination disorder (DCD) is a motor impairment that significantly interferes with activities of daily living. Little is known about the cause of DCD and how it develops, making it difficult to understand why children with DCD struggle in learning motor skills and to determine the best intervention to optimize function. Objective: To characterize white matter differences using diffusion tensor imaging in children with and without DCD. Design, Setting, and Participants: This cross-sectional study collected diffusion tensor imaging data at BC Children's Hospital Research Institute in Vancouver, British Columbia, Canada, from September 2014 to January 2017. Using a sample of convenience, children with DCD and children without DCD aged 8 to 12 years underwent magnetic resonance imaging. Data analysis was conducted from January 2017 to January 2020. Main Outcomes and Measures: The main outcome measures were diffusion parameters, including fractional anisotropy and mean, axial, and radial diffusivity, which are thought to provide an indirect measure of white matter microstructure. Tract-based spatial statistics, a voxelwise statistical analysis of diffusion parameters, were conducted using a 2-group comparison design matrix with age and attention as covariates. Results: Thirty children without DCD (mean [SD] age, 9.9 [1.4] years; 21 [70%] boys) and 31 children with DCD (mean [SD] age, 10.1 [1.2] years; 26 [84%] boys) were included in the study. Compared with children without DCD, children with DCD were characterized by significantly lower fractional anisotropy and axial diffusivity in regions of white matter pathways associated with motor and sensorimotor processing, including the corticospinal tract (fractional anisotropy: mean [SD], 0.54 [0.03] vs 0.51 [0.03]; P < .001; axial diffusivity: mean [SD], 0.13 [0.98] vs 0.12 [0.46]; P = .01), posterior thalamic radiation at the retrolenticular part of the internal capsule (axial diffusivity: mean [SD], 0.14 [0.57] vs 0.14 [0.44]; P = .01), and cerebellar pathways (eg, superior cerebellar peduncle, fractional anisotropy: mean [SD], 0.49 [0.05] vs 0.46 [0.03]; P = .03; axial diffusivity: mean [SD], 0.14 [0.66] vs 0.14 [0.63]; P = .009). There were no significant differences in mean diffusivity and radial diffusivity between children with and without DCD. Conclusions and Relevance: These findings suggest that children with DCD show significant brain differences in motor and sensorimotor white matter pathways compared with children without DCD. The pattern of diffusion parameters in children with DCD suggests that axonal development may be disrupted in this neurodevelopmental disorder.
Asunto(s)
Imagen de Difusión Tensora , Trastornos de la Destreza Motora/patología , Sustancia Blanca/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Colombia Británica , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Trastornos de la Destreza Motora/diagnóstico por imagen , Trastornos de la Destreza Motora/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/patología , Corteza Sensoriomotora/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiopatologíaRESUMEN
There is ongoing debate regarding the role that sensorimotor regions play in conceptual processing, with embodied theories supporting their direct involvement in processing verbs describing body part movements. Patient lesion studies examining a causal role for sensorimotor activation in conceptual task performance have suffered the caveat of lesions being largely diffuse and extensive beyond sensorimotor cortices. The current study addresses this limitation in reporting on 20 pre-operative neurosurgical patients with focal lesion to the pre- and post-central area corresponding to somatotopic representations. Patients were presented with a battery of neuropsychological tests and experimental tasks tapping into motor imagery and verbal conceptual verb processing in addition to neurophysiological measures including DTI, fMRI, and MEP being measured. Results indicated that left tumor patients who presented with a lesion at or near somatotopic hand representations performed significantly worse on the mental rotation hand task and that performance correlated with MEP amplitudes in the upper limb motor region. Furthermore, performance on tasks of verbal processing was within the normal range. Taken together, while our results evidence the involvement of the motor system in motor imagery processes, they do not support the embodied view that sensorimotor regions are necessary to tasks of action verb processing.
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Neoplasias Encefálicas/patología , Glioma/patología , Corteza Sensoriomotora/diagnóstico por imagen , Conducta Verbal/fisiología , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Potenciales Evocados Motores , Femenino , Lateralidad Funcional , Glioma/diagnóstico por imagen , Glioma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Periodo Preoperatorio , Desempeño Psicomotor/fisiología , Tiempo de Reacción , Corteza Sensoriomotora/patología , Adulto JovenRESUMEN
Brain tumors are generally associated with cognitive changes. Little is known about cognition in patients with meningioma - a lesion that usually shifts and compresses the brain parenchyma with a low probability of infiltrate it. We investigated the cognitive functioning in a consecutive series of 46 patients with a meningioma in the sensorimotor area in the left (LH, N = 27) or in the right (RH, N = 19) hemisphere. All the patients underwent a pre-operative neuropsychological assessment and structural MRI. Clinical symptoms varied between LH and RH meningioma patients. Impaired performance was seen in naming (19.23% noun and 35% verb naming), short-term (18.18%) and working (14.24%) memory in the LH group, and in visuo-spatial tasks (25% neglect, 21.42% visuospatial planning) in the RH group. Both groups were impaired on a sensorimotor mental imagery task (LH, 66.66% of the LH 70% of the RH meningioma patients), while only the RH meningioma group was impaired on the visuo-spatial mental imagery task. The lesion MRI maximum overlap occurred in the postcentral and paracentral lobules. Edema was maximally localized on the left superior longitudinal fasciculus and the superior part of the right superior corona radiata. We found that only the meningioma mass, and not the edema, is a predictive variable in determining patients' performance. Patients with meningioma could present with cognitive alterations at pre-surgical evaluation even if the meningioma occurs in sensorimotor areas. In the present series, a large meningioma vs. a large edema is more relevant for cognitive performance.
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Edema Encefálico/patología , Disfunción Cognitiva/fisiopatología , Neoplasias Meníngeas/patología , Meningioma/patología , Corteza Sensoriomotora/patología , Sustancia Blanca/patología , Adulto , Anciano , Disfunción Cognitiva/etiología , Femenino , Humanos , Imaginación/fisiología , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/diagnóstico , Meningioma/complicaciones , Meningioma/diagnóstico por imagen , Persona de Mediana Edad , Pruebas Neuropsicológicas , Corteza Sensoriomotora/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND: Photothrombosis is a minimally invasive method for induction of cortical ischemia. However, different ways of applying some methods to assess photothrombosis-induced damage need to be developed. NEW METHODS: We applied the tongue protrusion test and H&E staining of brain sections to detect ischemic damage after photothrombosis. Evaluation of the local status of the BBB using Evans blue dye was proposed. We also assessed the sensitivity of the grid-walk test. Moreover, we examined the interchangeability of MRI and TTC staining to measure lesion volume. RESULTS: We evaluated ischemic outcomes at 24â¯h after photothrombosis in mice. The tongue protrusion test did not reveal impairments of the neurological status whereas the grid-walk test showed the high sensitivity. Using histological techniques, we determined the reduction in the number of neurons with normal morphology in the penumbra. 3D reconstruction of the brain, which reflected Evans blue dye distribution in the nervous tissue, revealed BBB disruption in areas remote from the ischemic core. We also showed the strong correlation between damage volumes assessed by MRI and TTC staining. COMPARISON WITH EXISTING METHODS: The present work demonstrates the efficacy of the classical histological approach and TTC staining that are more affordable than MRI and immunohistochemical methods. Detection of 3D distribution of Evans blue dye in the brain in contrast to its total extraction reveals BBB damage in details. CONCLUSIONS: We proposed the simple methods for describing the severity of brain ischemia at the cellular and whole organism levels without significant labor and financial expenditures.
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Barrera Hematoencefálica/fisiopatología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patología , Colorantes , Trombosis Intracraneal/complicaciones , Imagen por Resonancia Magnética , Actividad Motora/fisiología , Corteza Sensoriomotora/patología , Coloración y Etiquetado , Animales , Conducta Animal/fisiología , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/etiología , Modelos Animales de Enfermedad , Eosina Amarillenta-(YS) , Hematoxilina , Imagen por Resonancia Magnética/economía , Imagen por Resonancia Magnética/normas , Masculino , Ratones , Ratones Endogámicos BALB C , Corteza Sensoriomotora/diagnóstico por imagen , Coloración y Etiquetado/economía , Coloración y Etiquetado/métodos , Coloración y Etiquetado/normas , Sales de Tetrazolio , Caminata/fisiologíaRESUMEN
C-Jun N-terminal kinase (JNK) is a pivotal MAPK (mitogen-activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK-IN-8 in ischemic stroke and the mechanisms underlying of JNK-IN-8 about neuroprotection are not well understood. In this work, male rats were treated with JNK-IN-8 after transient middle cerebral artery occlusion, and then the modified improved neurological function score (mNSS), the foot-fault test (FFT), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) levels were assessed. We found that JNK-IN-8-treated rats with MCAO exerted an observable melioration in space learning as tested by the improved mNSS, and showed sensorimotor functional recovery as measured by the FFT. JNK-IN-8 also played anti-inflammatory roles as indicated through decreased activation of microglia and decreased IL-6, IL-1ß, and TNF-α expression. Furthermore, JNK-IN-8 suppressed the activation of JNK and nuclear factor-κB (NF-κB) signaling as indicated by the decreased level of phosphorylated-JNK and p65. All data demonstrate that JNK-IN-8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF-κB and is a promising agent for the prevention of ischemic brain injury.
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Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Fármacos Neuroprotectores/farmacología , Animales , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Lesiones Traumáticas del Encéfalo/patología , Células Cultivadas , Hipoxia-Isquemia Encefálica/patología , Inflamación/tratamiento farmacológico , Interleucina-1beta/análisis , Interleucina-6/análisis , Accidente Cerebrovascular Isquémico/patología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Aprendizaje/efectos de los fármacos , Masculino , Microglía/metabolismo , Arteria Cerebral Media/patología , Neuroprotección/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Corteza Sensoriomotora/efectos de los fármacos , Corteza Sensoriomotora/patología , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
BACKGROUND: Gray matter (GM) atrophy in brain is one of the best predictors of long-term disability in multiple sclerosis (MS), and recent findings have revealed that localized GM atrophy is associated with clinical disabilities. GM atrophy associated with each disability mapped to a distinct brain region, revealing a disability-specific atlas (DSA) of GM loss. OBJECTIVE: To uncover the mechanisms underlying the development of localized GM atrophy. METHODS: We used voxel-based morphometry (VBM) to evaluate localized GM atrophy and Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY) to evaluate specific pathologies in mice with experimental autoimmune encephalomyelitis (EAE). RESULTS: We observed extensive GM atrophy throughout the cerebral cortex, with additional foci in the thalamus and caudoputamen, in mice with EAE compared to normal controls. Next, we generated pathology-specific atlases (PSAs), voxelwise mappings of the correlation between specific pathologies and localized GM atrophy. Interestingly, axonal damage (end-bulbs and ovoids) in the spinal cord strongly correlated with GM atrophy in the sensorimotor cortex of the brain. CONCLUSION: The combination of VBM with CLARITY in EAE can localize GM atrophy in brain that is associated with a specific pathology in spinal cord, revealing a PSA of GM loss.