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BACKGROUND: Emotional dysregulation affects up to two-thirds of adult patients with attention-deficit/hyperactivity disorder (ADHD) and is increasingly seen as a core ADHD symptom that is clinically associated with greater functional impairment and psychiatric comorbidity. We sought to investigate emotional dysregulation in ADHD and explored its neural underpinnings. METHODS: We studied emotion induction and regulation in a clinical cohort of adult patients with ADHD before and after a stimulant challenge. We compared patients with age- and gender-matched healthy controls using behavioural, structural, and functional measures. We hypothesized that patients would demonstrate aberrant emotion processing compared with healthy controls, and sought to find whether this could be normalized by stimulant medication. RESULTS: Behaviourally, the ADHD group showed reduced emotion induction and regulation capacity. Brain imaging revealed abberant activation and deactivation patterns during emotion regulation, lower grey-matter volume in limbic and paralimbic areas, and greater grey-matter volume in visual and cerebellar areas, compared with healthy controls. The behavioural and functional deficits seen in emotion induction and regulation in the ADHD group were not normalized by stimulant medication. CONCLUSION: Patients with ADHD may have impaired emotion induction and emotion regulation capacity, but these deficits are not reversed by stimulant medication. These results have important clinical implications when assessing which aspects of emotional dysregulation are relevant for patients and if and how traditional ADHD pharmacotherapy affects emotion induction and emotion regulation.
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Trastorno por Déficit de Atención con Hiperactividad , Encéfalo , Estimulantes del Sistema Nervioso Central , Imagen por Resonancia Magnética , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Estimulantes del Sistema Nervioso Central/farmacología , Masculino , Femenino , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/efectos de los fármacos , Regulación Emocional/fisiología , Adulto Joven , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/efectos de los fármacos , Síntomas Afectivos/tratamiento farmacológico , Síntomas Afectivos/fisiopatología , Emociones/fisiología , Emociones/efectos de los fármacos , Estudios de Casos y Controles , Persona de Mediana EdadRESUMEN
LSD is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. This is the first study to follow the developmental changes in brain structure and function following LSD exposure in periadolescence. We hypothesized LSD given during a time of heightened neuroplasticity, particularly in the forebrain, would affect cognitive and emotional behavior and the associated underlying neuroanatomy and neurocircuitry. Female and male mice were given vehicle, single or multiple treatments of 3.3 µg of LSD by oral gavage starting on postnatal day 51. Between postnatal days 90-120 mice were imaged and tested for cognitive and motor behavior. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. Motor behavior and cognitive performance were unaffected by periadolescent exposure to LSD. Differences across experimental groups in brain volume for any of the 139 brain areas were few in number and not focused on any specific brain region. Multiple exposures to LSD significantly altered gray matter microarchitecture across much of the brain. These changes were primary associated with the thalamus, sensory and motor cortices, and basal ganglia. The forebrain olfactory system and prefrontal cortex and hindbrain cerebellum and brainstem were unaffected. The functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus was reduced with multidose LSD exposure. Does exposure to LSD in late adolescence have lasting effects on brain development? The bulk of our significant findings were seen through changes is DWI values across 74 brain areas in the multi-dose LSD group. The pronounced changes in indices of anisotropy across much of the brain would suggest altered gray matter microarchitecture and neuroplasticity. There was no evidence of LSD having consequential effects on cognitive or motor behavior when animal were evaluated as young adults 90-120 days of age. Neither were there any differences in the volume of specific brain areas between experimental conditions. The reduction in connectivity in forebrain white matter tracts with multidose LSD and consolidation around sensorimotor and hippocampal brain areas requires a battery of tests to understand the consequences of these changes on behavior.
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Encéfalo , Dietilamida del Ácido Lisérgico , Animales , Masculino , Femenino , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , Ratones , Dietilamida del Ácido Lisérgico/farmacología , Dietilamida del Ácido Lisérgico/administración & dosificación , Alucinógenos/administración & dosificación , Alucinógenos/farmacología , Cognición/efectos de los fármacos , Imagen por Resonancia Magnética , Plasticidad Neuronal/efectos de los fármacos , Administración Oral , Actividad Motora/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Sustancia Gris/efectos de los fármacos , Sustancia Gris/crecimiento & desarrollo , Sustancia Gris/diagnóstico por imagenRESUMEN
Coffee is a popular drink enjoyed around the world, and scientists are very interested in studying how it affects the human brain. This chapter looks at lots of different studies to understand how drinking coffee might change the brain and help protect it from neurodegenerative disorders especially like schizophrenia. With the help of available literature a link between the coffee mechanism and neurodegenerative disorders is established in this chapter. Researchers have found that drinking coffee can change the size of certain parts of the brain that control things like thinking and mood. Scientists also study how coffee's ingredients, especially caffeine, can change how the brain works. They think these changes could help protect the brain from diseases. This chapter focuses on how coffee might affect people with schizophrenia as hallucination is caused during and after excess consumption of caffeine. There's still a lot we don't know, but researchers are learning more by studying how different people's brains respond to coffee over time. Overall, this chapter shows that studying coffee and the brain could lead to new ways to help people with brain disorders. This study also draws ideas for future research and ways to help people stay healthy.
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Café , Sustancia Gris , Humanos , Sustancia Gris/efectos de los fármacos , Sustancia Gris/patología , Neuroprotección/fisiología , Neuroprotección/efectos de los fármacos , Encéfalo/efectos de los fármacos , Cafeína/farmacología , Cafeína/administración & dosificación , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Animales , EsquizofreniaRESUMEN
BACKGROUND: Chronic overexposure to manganese (Mn) may result in neurotoxicity, which is characterized by motor and cognitive dysfunctions. This study aimed to utilize multivariate source-based morphometry (SBM) to explore the biomarkers for distinguishing Mn-exposed welders from healthy controls (HCs). METHODS: High-quality 3D T1-weighted MRI scans were obtained from 45 Mn-exposed full-time welders and 33 age-matched HCs in this study. After extracting gray matter structural covariation networks by SBM, multiple classic interaction linear models were applied to investigate distinct patterns in welders compared to HCs, and Z-transformed loading coefficients were compared between the two groups. A receiver operating characteristic (ROC) curve was used to identify potential biomarkers for distinguishing Mn-exposed welders from HCs. Additionally, we assessed the relationships between clinical features and gray matter volumes in the welders group. RESULTS: A total of 78 subjects (45 welders, mean age 46.23±4.93 years; 33 HCs, mean age 45.55±3.40 years) were evaluated. SBM identified five components that differed between the groups. These components displayed lower loading weights in the basal ganglia, thalamus, default mode network (including the lingual gyrus and precuneus), and temporal lobe network (including the temporal pole and parahippocampus), as well as higher loading weights in the sensorimotor network (including the supplementary motor cortex). ROC analysis identified the highest classification power in the thalamic network. CONCLUSIONS: Altered brain structures might be implicated in Mn overexposure-related disturbances in motivative modulation, cognitive control and information integration. These results encourage further studies that focus on the interaction mechanisms, including the basal ganglia network, thalamic network and default mode network. Our study identified potential neurobiological markers in Mn-exposed welders and illustrated the utility of a multivariate method of gray matter analysis.
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Biomarcadores , Sustancia Gris , Imagen por Resonancia Magnética , Manganeso , Exposición Profesional , Humanos , Sustancia Gris/efectos de los fármacos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Masculino , Persona de Mediana Edad , Manganeso/toxicidad , Adulto , Exposición Profesional/efectos adversos , Soldadura , Femenino , Intoxicación por Manganeso/patología , Intoxicación por Manganeso/diagnóstico por imagen , Obreros Metalúrgicos , Estudios de Casos y ControlesRESUMEN
MAO-A catalyzes the oxidative degradation of monoamines and is thus implicated in sex-specific neuroplastic processes that influence gray matter (GM) density (GMD) and microstructure (GMM). Given the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy (GHT) represent a valuable cohort to potentially investigate sex steroid-induced changes of GM and concomitant MAO-A density. Here, we investigated the effects of GHT over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men underwent two MRI scans in a longitudinal design. PET scans using [11C]harmine were performed before each MRI session in a subset of 35 individuals. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: pFWE+Bonferroni < 0.025). In terms of MAO-A distribution volume, no significant effects were found. Additionally, the sexual desire inventory (SDI) was applied to assess GHT-induced changes in sexual desire, showing an increase of SDI scores among transgender men. Changes in the GMD of the bilateral insula showed a moderate correlation to SDI scores (rho = - 0.62, pBonferroni = 0.047). The present results are indicative of a reliable influence of gender-affirming hormone therapy on 1) GMD and GMM following an interregional pattern and 2) sexual desire specifically among transgender men.
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Sustancia Gris , Monoaminooxidasa , Tomografía de Emisión de Positrones , Personas Transgénero , Humanos , Sustancia Gris/efectos de los fármacos , Sustancia Gris/diagnóstico por imagen , Masculino , Adulto , Femenino , Monoaminooxidasa/sangre , Monoaminooxidasa/metabolismo , Adulto Joven , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estudios LongitudinalesRESUMEN
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability among individuals. Thus, this study aimed to explore a machine learning model based on the percentage of amplitude oscillations (PerAF) and gray matter volume (GMV) to predict the response to NSAIDs in migraine treatment. METHODS: Propensity score matching was adopted to match patients having migraine with response and nonresponse to NSAIDs, ensuring consistency in clinical characteristics and migraine-related features. Multimodal magnetic resonance imaging was employed to extract PerAF and GMV, followed by feature selection using the least absolute shrinkage and selection operator regression and recursive feature elimination algorithms. Multiple predictive models were constructed and the final model with the smallest predictive residuals was chosen. The model performance was evaluated using the area under the receiver operating characteristic (ROCAUC) curve, area under the precision-recall curve (PRAUC), balance accuracy (BACC), sensitivity, F1 score, positive predictive value (PPV), and negative predictive value (NPV). External validation was performed using a public database. Then, correlation analysis was performed between the neuroimaging predictors and clinical features in migraine. RESULTS: One hundred eighteen patients with migraine (59 responders and 59 non-responders) were enrolled. Six features (PerAF of left insula and left transverse temporal gyrus; and GMV of right superior frontal gyrus, left postcentral gyrus, right postcentral gyrus, and left precuneus) were observed. The random forest model with the lowest predictive residuals was selected and model metrics (ROCAUC, PRAUC, BACC, sensitivity, F1 score, PPV, and NPV) in the training and testing groups were 0.982, 0.983, 0.927, 0.976, 0.930, 0.889, and 0.973; and 0.711, 0.648, 0.639, 0.667,0.649, 0.632, and 0.647, respectively. The model metrics of external validation were 0.631, 0.651, 0.611, 0.808, 0.656, 0.553, and 0.706. Additionally, a significant positive correlation was found between the GMV of the left precuneus and attack time in non-responders. CONCLUSIONS: Our findings suggest the potential of multimodal neuroimaging features in predicting the efficacy of NSAIDs in migraine treatment and provide novel insights into the neural mechanisms underlying migraine and its optimized treatment strategy.
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Antiinflamatorios no Esteroideos , Sustancia Gris , Imagen por Resonancia Magnética , Trastornos Migrañosos , Neuroimagen , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/diagnóstico por imagen , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/administración & dosificación , Femenino , Adulto , Masculino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/efectos de los fármacos , Sustancia Gris/patología , Neuroimagen/métodos , Aprendizaje Automático , Persona de Mediana Edad , BiomarcadoresRESUMEN
This study aimed to assess associations between prenatal and postnatal exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) and gray matter volume of key regions of the brain reward circuit, namely the caudate nucleus, putamen, nucleus accumbens (nAcc), the amygdala, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC). Structural magnetic resonance imaging (MRI) was conducted in 77 Inuit adolescents (mean age = 18.39) from Nunavik, Canada, who also completed the Brief Sensation Seeking Scale (BSSS-4) and Sensation Seeking - 2 (SS-2), two self-report questionnaires evaluating the tendency toward sensation seeking, which is a proxy of reward-related behaviors. Exposures to Pb, Hg and PCBs were measured in cord blood at birth, in blood samples at 11 years old and at time of testing (18 years old). Multivariate linear regressions were corrected for multiple comparisons and adjusted for potential confounders, such as participants' sociodemographic characteristics and nutrient fish intake. Results showed that higher cord blood Pb levels predicted smaller gray matter volume in the bilateral nAcc, caudate nucleus, amygdala and OFC as well as in left ACC. A moderating effect of sex was identified, indicating that the Pb-related reduction in volume in the nAcc and caudate nucleus was more pronounced in female. Higher blood Hg levels at age 11 predicted smaller right amygdala independently of sex. No significant associations were found between blood PCBs levels at all three times of exposure. This study provides scientific support for the detrimental effects of prenatal Pb and childhood Hg blood concentrations on gray matter volume in key reward-related brain structures.
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Sustancia Gris , Inuk , Plomo , Imagen por Resonancia Magnética , Mercurio , Bifenilos Policlorados , Efectos Tardíos de la Exposición Prenatal , Recompensa , Humanos , Femenino , Sustancia Gris/efectos de los fármacos , Sustancia Gris/diagnóstico por imagen , Masculino , Bifenilos Policlorados/sangre , Bifenilos Policlorados/toxicidad , Bifenilos Policlorados/efectos adversos , Adolescente , Plomo/sangre , Plomo/toxicidad , Plomo/efectos adversos , Mercurio/sangre , Mercurio/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Contaminantes Ambientales/sangre , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/efectos adversos , Niño , Encéfalo/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Sangre Fetal/químicaRESUMEN
INTRODUCTION: Magnetic resonance imaging (MRI) based brain morphometric changes in unilateral 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model can be elucidated using voxel-based morphometry (VBM), study of alterations in gray matter volume and Machine Learning (ML) based analyses. METHODS: We investigated gray matter atrophy in 6-OHDA induced PD model as compared to sham control using statistical and ML based analysis. VBM and atlas-based volumetric analysis was carried out at regional level. Support vector machine (SVM)-based algorithms wherein features (volume) extracted from (a) each of the 150 brain regions (b) statistically significant features (only) and (c) volumes of each cluster identified after application of VBM (VBM_Vol) were used for training the decision model. The lesion of the 6-OHDA model was validated by estimating the net contralateral rotational behaviour by the injection of apomorphine drug and motor impairment was assessed by rotarod and open field test. RESULTS AND DISCUSSION: In PD, gray matter volume (GMV) atrophy was noted in bilateral cortical and subcortical brain regions, especially in the internal capsule, substantia nigra, midbrain, primary motor cortex and basal ganglia-thalamocortical circuits in comparison with sham control. Behavioural results revealed an impairment in motor performance. SVM analysis showed 100% classification accuracy, sensitivity and specificity at both 3 and 7 weeks using VBM_Vol. CONCLUSION: Unilateral 6-OHDA induced GMV changes in both hemispheres at 7th week may be associated with progression of the disease in the PD model. SVM based approaches provide an increased classification accuracy to elucidate GMV atrophy.
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Atrofia , Sustancia Gris , Imagen por Resonancia Magnética , Oxidopamina , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/efectos de los fármacos , Atrofia/patología , Animales , Masculino , Modelos Animales de Enfermedad , Apomorfina/farmacología , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Máquina de Vectores de Soporte , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/diagnóstico por imagen , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/diagnóstico por imagenRESUMEN
Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chronic sleep restriction, CSR), and (2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. Thirty-six healthy adults participated in this double-blind, randomized, controlled study (age = 28.9 ± 5.2 y/; F:M = 15:21; habitual level of caffeine intake < 450 mg; 29 homozygous C/C allele carriers of rs5751876 of ADORA2A, an A2A adenosine receptor gene variant). Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We examined GM changes on the 2nd BL Day, 5th CSR Day, and REC Day using magnetic resonance imaging and voxel-based morphometry. Moreover, we used positron emission tomography with [18F]-CPFPX to quantify the baseline availability of A1 adenosine receptors (A1R) and its relation to the GM plasticity. The results from the voxel-wise multimodal whole-brain analysis on the Jacobian-modulated T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction effect between caffeine and CSR in four brain regions: (a) right temporal-occipital region, (b) right dorsomedial prefrontal cortex (DmPFC), (c) left dorsolateral prefrontal cortex (DLPFC), and (d) right thalamus. The post-hoc analyses on the signal intensity of these GM clusters indicated that, compared to BL, GM on the CSR day was increased in the DECAF group in all clusters but decreased in the thalamus, DmPFC, and DLPFC in the CAFF group. Furthermore, lower baseline subcortical A1R availability predicted a larger GM reduction in the CAFF group after CSR of all brain regions except for the thalamus. In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect thalamic GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors in CSR-induced GM plasticity are warranted.
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Cafeína , Sustancia Gris , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Receptor de Adenosina A1 , Privación de Sueño , Humanos , Cafeína/administración & dosificación , Cafeína/farmacología , Masculino , Adulto , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/metabolismo , Sustancia Gris/efectos de los fármacos , Sustancia Gris/patología , Receptor de Adenosina A1/metabolismo , Receptor de Adenosina A1/genética , Tomografía de Emisión de Positrones/métodos , Femenino , Imagen por Resonancia Magnética/métodos , Método Doble Ciego , Privación de Sueño/metabolismo , Privación de Sueño/diagnóstico por imagen , Adulto Joven , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2A/genéticaRESUMEN
Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = -0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = -12.73, pFDR = 0.048) and posterior (B = -17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity.
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Consumo de Bebidas Alcohólicas , Atrofia , Encéfalo , Sustancia Gris , Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Masculino , Anciano , Femenino , Estudios Longitudinales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/efectos de los fármacos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Sustancia Blanca/efectos de los fármacos , Anciano de 80 o más Años , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/efectos de los fármacos , Atrofia/patología , Envejecimiento/patología , Envejecimiento/fisiología , Consumo Excesivo de Bebidas Alcohólicas/patología , Consumo Excesivo de Bebidas Alcohólicas/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Tálamo/patología , Tálamo/efectos de los fármacos , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/efectos de los fármacos , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/patología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Cuerpo Calloso/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate the associations between prescription opioid exposures in community-dwelling older adults and gray and white matter structure by magnetic resonance imaging. METHODS: Secondary analysis was conducted of a prospective, longitudinal population-based cohort study employing cross-sectional imaging of older adult (≥65 years) enrollees between November 1, 2004, and December 31, 2017. Gray matter outcomes included cortical thickness in 41 structures and subcortical volumes in 6 structures. White matter outcomes included fractional anisotropy in 40 tracts and global white matter hyperintensity volumes. The primary exposure was prescription opioid availability expressed as the per-year rate of opioid days preceding magnetic resonance imaging, with a secondary exposure of per-year total morphine milligram equivalents (MME). Multivariable models assessed associations between opioid exposures and brain structures. RESULTS: The study included 2185 participants; median (interquartile range) age was 80 (75 to 85) years, 47% were women, and 1246 (57%) received opioids. No significant associations were found between opioids and gray matter. Increased opioid days and MME were associated with decreased white matter fractional anisotropy in 15 (38%) and 16 (40%) regions, respectively, including the corpus callosum, posterior thalamic radiation, and anterior limb of the internal capsule, among others. Opioid days and MME were also associated with greater white matter hyperintensity volume (1.02 [95% CI, 1.002 to 1.036; P=.029] and 1.01 [1.001 to 1.024; P=.032] increase in the geometric mean, respectively). CONCLUSION: The duration and dose of prescription opioids were associated with decreased white matter integrity but not with gray matter structure. Future studies with longitudinal imaging and clinical correlation are warranted to further evaluate these relationships.
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Analgésicos Opioides , Vida Independiente , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Anciano , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Anciano de 80 o más Años , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/efectos de los fármacos , Sustancia Gris/patología , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/efectos de los fármacos , Estudios Longitudinales , Estudios TransversalesRESUMEN
Aluminum (Al) is a low-toxic, accumulative substance with neurotoxicity properties that adversely affect human cognitive function. This study aimed to investigate the neurobiological mechanisms underlying cognitive impairment resulting from occupational Al exposure. Resting-state functional magnetic resonance imaging was conducted on 54 individuals with over 10 years of Al exposure. Al levels were measured, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Subsequently, the K-means clustering algorithm was employed to identify functional gray matter (GM) and white matter (WM) networks. Two-sample t-tests were conducted between the cognition impairment group and the control group. Al exhibited a negative correlation with MoCA scores. Participants with cognitive impairment demonstrated reduced functional connectivity (FC) between the middle cingulum network (WM1) and anterior cingulum network (WM2), as well as between the executive control network (WM6) and limbic network (WM10). Notably, decreased FCs were observed between the executive control network (GM5) and WM1, WM4, WM6, and WM10. Additionally, the FC of GM5-GM4 and WM1-WM2 negatively correlated with Trail Making Test Part A (TMT-A) scores. Prolonged Al accumulation detrimentally affects cognition, primarily attributable to executive control and limbic network disruptions.
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Aluminio , Disfunción Cognitiva , Sustancia Gris , Imagen por Resonancia Magnética , Exposición Profesional , Sustancia Blanca , Humanos , Sustancia Gris/efectos de los fármacos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Disfunción Cognitiva/inducido químicamente , Masculino , Persona de Mediana Edad , Femenino , Aluminio/toxicidad , Exposición Profesional/efectos adversos , Adulto , Red Nerviosa/efectos de los fármacos , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patología , Red Nerviosa/fisiopatología , AncianoRESUMEN
Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density. In addition, 88 SZ patients and 81 HCs were examined by resting-state functional MRI (rs-fMRI) at baseline and the patients were re-examined post-treatment to examine FC changes. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) were applied to measure psychiatric symptoms and cognitive impairments in SZ. SZ patients were then stratified into response and non-response groups according to PANSS score change (≥50 % decrease or <50 % decrease, respectively). The GM density of the right cingulate gyrus, WM density of the right superior frontal gyrus (SFG) plus 5 other WM tracts were reduced in the response group compared to the non-response group. The FC values between the right anterior cingulate and paracingulate gyrus and left thalamus were reduced in the entire SZ group (n = 88) after treatment, while FC between the right inferior temporal gyrus (ITG) and right medial superior frontal gyrus (SFGmed) was increased in the response group. There were no significant changes in regional FC among the non-response group after treatment and no correlations with symptom or cognition test scores. These findings suggest that the right SFG is a critical target of antipsychotic drugs and that WM density and FC alterations within this region could be used as potential indicators in predicting the treatment outcome of antipsychotics of SZ.
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Antipsicóticos , Imagen por Resonancia Magnética , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/patología , Esquizofrenia/fisiopatología , Masculino , Femenino , Adulto , Imagen por Resonancia Magnética/métodos , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/efectos de los fármacos , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/patología , Persona de Mediana Edad , Resultado del Tratamiento , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adulto Joven , Neuroimagen/métodos , BiomarcadoresRESUMEN
BACKGROUND: Loss of brain gray matter fractional volume predicts multiple sclerosis (MS) progression and is associated with worsening physical and cognitive symptoms. Within deep gray matter, thalamic damage is evident in early stages of MS and correlates with physical and cognitive impairment. Natalizumab is a highly effective treatment that reduces disease progression and the number of inflammatory lesions in patients with relapsing-remitting MS (RRMS). OBJECTIVE: To evaluate the effect of natalizumab on gray matter and thalamic atrophy. METHODS: A combination of deep learning-based image segmentation and data augmentation was applied to MRI data from the AFFIRM trial. RESULTS: This post hoc analysis identified a reduction of 64.3% (p = 0.0044) and 64.3% (p = 0.0030) in mean percentage gray matter volume loss from baseline at treatment years 1 and 2, respectively, in patients treated with natalizumab versus placebo. The reduction in thalamic fraction volume loss from baseline with natalizumab versus placebo was 57.0% at year 2 (p < 0.0001) and 41.2% at year 1 (p = 0.0147). Similar findings resulted from analyses of absolute gray matter and thalamic fraction volume loss. CONCLUSION: These analyses represent the first placebo-controlled evidence supporting a role for natalizumab treatment in mitigating gray matter and thalamic fraction atrophy among patients with RRMS. CLINICALTRIALS.GOV IDENTIFIER: NCT00027300URL: https://clinicaltrials.gov/ct2/show/NCT00027300.
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Atrofia , Sustancia Gris , Factores Inmunológicos , Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente , Natalizumab , Tálamo , Humanos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Natalizumab/farmacología , Natalizumab/uso terapéutico , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/efectos de los fármacos , Adulto , Tálamo/patología , Tálamo/diagnóstico por imagen , Tálamo/efectos de los fármacos , Masculino , Femenino , Factores Inmunológicos/farmacología , Atrofia/patología , Persona de Mediana Edad , Aprendizaje ProfundoRESUMEN
Mild mesial temporal lobe epilepsy (MTLE) patients may remain untreated for a considerable time after disease onset or achieve seizure control with a single anti-seizures medication (ASM). Thus, they represent an optimal population to investigate whether ASMs might have influence on brain structure. We consecutively enrolled 56 mild MTLE patients (22/56 untreated, 34/56 on-monotherapy) and 58 healthy controls, matched for age and gender. All subjects underwent 3T-brain MRI, using FreeSurfer for automated morphometry. Differences in gray matter were assessed using one-way Analysis of Covariance (ANCOVA), adjusting for age, disease duration and intracranial volume. No significant change was observed between treated and untreated patients. We observed a significant reduction in cortical thickness of left inferior parietal, inferior temporal, middle temporal gyri, and right inferior parietal gyrus, temporal pole in monotherapy patients compared to healthy controls, as well as an increase in left isthmus of cingulate gyrus in untreated MTLE subjects compared to controls. Surface and subcortical volumes analysis revealed no differences among groups. Our study demonstrated no substantial morphological abnormalities between untreated mild MTLE patients and those undergoing monotherapy. Although exploratory, these results may reassure about safety of commonly used drugs and their marginal role in influencing neuroimaging results. PLAIN LANGUAGE SUMMARY: This study investigated the following question: can medications against epileptic seizures have an effect on brain structure in mild mesial temporal lobe? Preliminary results from our analyses suggest not, as we did not find any difference in brain gray matter between untreated patients and those treated with a single anti-seizures medication. On the other hand, epilepsy patients presented cortical thinning compared to healthy controls in several regions of the temporal and parietal lobes, in line with previous studies investigating the disease.
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Anticonvulsivantes , Epilepsia del Lóbulo Temporal , Imagen por Resonancia Magnética , Humanos , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Femenino , Masculino , Anticonvulsivantes/uso terapéutico , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Adulto Joven , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/efectos de los fármacos , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología , Lóbulo Temporal/efectos de los fármacosRESUMEN
This study aimed to evaluate the effect of intrathecal (IT) recombinant human arylsulfatase A (rhASA) on magnetic resonance imaging (MRI)-assessed brain tissue changes in children with metachromatic leukodystrophy (MLD). In total, 510 MRI scans were collected from 12 intravenous (IV) rhASA-treated children with MLD, 24 IT rhASA-treated children with MLD, 32 children with untreated MLD, and 156 normally developing children. Linear mixed models were fitted to analyze the time courses of gray matter (GM) volume and fractional anisotropy (FA) in the posterior limb of the internal capsule. Time courses for demyelination load and FA in the centrum semiovale were visualized using locally estimated scatterplot smoothing regression curves. All assessed imaging parameters demonstrated structural evidence of neurological deterioration in children with MLD. GM volume was significantly lower at follow-up (median duration, 104 weeks) in IV rhASA-treated versus IT rhASA-treated children. GM volume decline over time was steeper in children receiving low-dose (10 or 30 mg) versus high-dose (100 mg) IT rhASA. Similar effects were observed for demyelination. FA in the posterior limb of the internal capsule showed a higher trend over time in IT rhASA-treated versus children with untreated MLD, but FA parameters were not different between children receiving the low doses versus those receiving the high dose. GM volume in IT rhASA-treated children showed a strong positive correlation with 88-item Gross Motor Function Measure score over time. In some children with MLD, IT administration of high-dose rhASA may delay neurological deterioration (assessed using MRI), offering potential therapeutic benefit.
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Encéfalo , Cerebrósido Sulfatasa , Inyecciones Espinales , Leucodistrofia Metacromática , Imagen por Resonancia Magnética , Humanos , Leucodistrofia Metacromática/tratamiento farmacológico , Leucodistrofia Metacromática/diagnóstico por imagen , Cerebrósido Sulfatasa/administración & dosificación , Cerebrósido Sulfatasa/genética , Masculino , Femenino , Niño , Imagen por Resonancia Magnética/métodos , Preescolar , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Adolescente , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/efectos de los fármacosRESUMEN
INTRODUCTION: Ocrelizumab (OCR) and Fingolimod (FGL) are two high-efficacy treatments in multiple sclerosis which, besides their strong anti-inflammatory activity, may limit neurodegeneration. AIM: To compare the effect of OCR and FGL on clinical and MRI endpoints. METHODS: 95 relapsing-remitting patients (57 OCR, 38 FGL) clinically followed for 36 months underwent a 3-Tesla MRI at baseline and after 24 months. The annualized relapse rate, EDSS, new cortical/white matter lesions and regional cortical and deep grey matter volume loss were evaluated. RESULTS: OCR reduced the relapse rate from 0.48 to 0.04, FGL from 0.32 to 0.05 (both p < 0.001). Compared to FGL, OCR-group experienced fewer new white matter lesions (12% vs 32%, p = 0.005), no differences in new cortical lesions, lower deep grey matter volume loss (- 0.12% vs - 0.66%; p = 0.002, Cohen's d = 0.54), lower global cortical thickness change (- 0.45% vs - 0.70%; p = 0.036; d = 0.42) and reduced cortical thinning/volume loss in several regions of interests, including those of parietal gyrus (d-range = 0.65-0.71), frontal gyrus (d-range = 0.47-0.60), cingulate (d-range = 0.41-0.72), insula (d = 0.36), cerebellum (cortex d = 0.72, white matter d = 0.44), putamen (d = 0.35) and thalamus (d = 0.31). The effect on some regional thickness changes was confirmed in patients without focal lesions. CONCLUSIONS: When compared with FGL, patients receiving OCR showed greater suppression of focal MRI lesions accumulation and lower cortical and deep grey matter volume loss.
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Anticuerpos Monoclonales Humanizados , Clorhidrato de Fingolimod , Sustancia Gris , Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente , Humanos , Femenino , Masculino , Adulto , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Sustancia Gris/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Persona de Mediana Edad , Clorhidrato de Fingolimod/farmacología , Clorhidrato de Fingolimod/uso terapéutico , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/efectos de los fármacos , Moduladores de los Receptores de fosfatos y esfingosina 1/farmacología , Factores Inmunológicos/farmacología , Factores Inmunológicos/administración & dosificación , Estudios de SeguimientoRESUMEN
BACKGROUND AND PURPOSE: Cerebral gray matter (GM) atrophy is a proposed measure of neuroprotection in multiple sclerosis (MS). Glatiramer acetate (GA) limits clinical relapses, MRI lesions, and whole brain atrophy in relapsing-remitting MS (RRMS). The effect of GA on GM atrophy remains unclear. We assessed GM atrophy in patients with RRMS starting GA therapy in comparison to a cohort of patients with clinically benign RRMS (BMS). DESIGN/METHODS: We studied 14 patients at GA start [age (mean ± SD) 44.2 ± 7.0 years, disease duration (DD) 7.2 ± 6.4 years, Expanded Disability Status Scale score (EDSS) (median,IQR) 1.0,2.0] and 6 patients with BMS [age 43.0 ± 6.1 years, DD 18.1 ± 8.4 years, EDSS 0.5,1.0]. Brain MRI was obtained at baseline and one year later (both groups) and two years later in all patients in the GA group except one who was lost to follow-up. Semi-automated algorithms assessed cerebral T2 hyperintense lesion volume (T2LV), white matter fraction (WMF), GM fraction (GMF), and brain parenchymal fraction (BPF). The exact Wilcoxon-Mann-Whitney test compared the groups. The Wilcoxon signed rank test assessed longitudinal changes within groups. RESULTS: During the first year, MRI changes did not differ significantly between groups (p > 0.15). Within the BMS group, WMF and BPF decreased during the first year (p = 0.03). Within the GA group, there was no significant change in MRI measures during each annual period (p > 0.05). Over two years, the GA group had a significant increase in T2LV and decrease in WMF (p < 0.05), while GMF and BPF remained stable (p > 0.05). MRI changes in brain volumes (GMF or WMF) in the first year in the GA group were not significantly different from those in the BMS group (p > 0.5). CONCLUSIONS: In this pilot study with a small sample size, patients with RRMS started on GA did not show significant GM or whole brain atrophy over 2 years, resembling MS patients with a clinically benign disease course.
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Sustancia Gris , Esclerosis Múltiple Recurrente-Remitente , Adulto , Humanos , Persona de Mediana Edad , Atrofia/tratamiento farmacológico , Atrofia/patología , Encéfalo/efectos de los fármacos , Encéfalo/patología , Acetato de Glatiramer/uso terapéutico , Acetato de Glatiramer/farmacología , Factor de Maduración de la Glia/farmacología , Sustancia Gris/efectos de los fármacos , Sustancia Gris/patología , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/patología , Proyectos PilotoRESUMEN
Melatonin has shown promising neuroprotective effects due to its anti-oxidant, anti-inflammatory and anti-apoptotic properties, making it a candidate drug for translation to humans in conditions that compromise the developing brain. Our study aimed to explore the impact of prenatal melatonin in an inflammatory/infectious context on GABAergic neurons and on oligodendrocytes (OLs), key cells involved in the encephalopathy of prematurity. An inflammatory/infectious agent (LPS, 300 µg/kg) was injected intraperitoneally (i.p.) to pregnant Wistar rats at gestational day 19 and 20. Melatonin (5 mg/kg) was injected i.p. following the same schedule. Immunostainings focusing on GABAergic neurons, OL lineage and myelination were performed on pup brain sections. Melatonin succeeded in preventing the LPS-induced decrease of GABAergic neurons within the retrospenial cortex, and sustainably promoted GABAergic neurons within the dentate gyrus in the inflammatory/infectious context. However, melatonin did not effectively prevent the LPS-induced alterations on OLs and myelination. Therefore, we demonstrated that melatonin partially prevented the deleterious effects of LPS according to the cell type. The timing of exposure related to the cell maturation stage is likely to be critical to achieve an efficient action of melatonin. Furthermore, it can be speculated that melatonin exerts a modest protective effect on extremely preterm infant brains.
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Encéfalo/efectos de los fármacos , Encéfalo/embriología , Corioamnionitis/patología , Melatonina/farmacología , Neurogénesis/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Animales Recién Nacidos , Antiinflamatorios/farmacología , Corioamnionitis/etiología , Corioamnionitis/metabolismo , Corioamnionitis/prevención & control , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/metabolismo , Sustancia Gris/efectos de los fármacos , Sustancia Gris/metabolismo , Sustancia Gris/patología , Lipopolisacáridos/efectos adversos , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , Embarazo , RatasRESUMEN
BACKGROUND: Chronic alcohol consumption is associated with structural brain changes and increased inflammatory signaling throughout the brain and body. Increased inflammation in the brain has been associated with structural damage. Recent studies have also shown that neurofilament light polypeptide (NfL) is released into the systemic circulation following neuronal damage. Although NfL has thus been proposed as a biomarker for neurodegenerative diseases, its connection to alcohol use disorder has not been explored. For this secondary data analysis, we proposed a conceptual model linking alcohol consumption, the pro-inflammatory cytokine IL-6, brain structure, and NfL in heavy drinking participants. METHODS: Of the 182 individuals enrolled in this study, 81 participants had usable data on gray matter (GM) thickness and 80 had usable data on white matter (WM) diffusivity. A subset of participants had NfL (n = 78) and IL-6 (n = 117) data. An estimate of GM thickness was extracted from middle frontal brain regions using FreeSurfer. Estimated mean WM diffusivity values were extracted from Tract Based Spatial Statistics. NfL and IL-6 were measured in blood. Regression models were used to test individual linkages in the conceptual model. Based on significant regression results, we created a simplified conceptual model, which we tested using path analysis. RESULTS: In regressions, negative relationships emerged between GM and both drinks per drinking day (DPDD) (p = 0.018) and NfL (p = 0.004). A positive relationship emerged between WM diffusivity and DPDD (p = 0.033). IL-6 was not significantly associated with alcohol use, GM or WM. The final path model demonstrated adequate fit to the data and showed significant, negative associations between DPDD and middle frontal gyrus (MFG) thickness, and between MFG thickness and NfL, but the association between DPDD and NfL was not significant. CONCLUSIONS: This is the first study to show that heavy drinking is associated with lower GM thickness and higher WM diffusivity and that lower GM thickness is associated with higher circulating NfL. The analyses also show that the effects of drinking do not involve the pro-inflammatory cytokine IL-6.