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1.
Neuroimage ; 257: 119254, 2022 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-35490915

RESUMEN

The sources of inter- and intra-individual variability in age-related cognitive decline remain poorly understood. We examined the association between 20-year trajectories of cognitive decline and multimodal brain structure and morphology in older age. We used the Whitehall II Study, an extensively characterised cohort with 3T brain magnetic resonance images acquired at older age (mean age = 69.52 ± 4.9) and 5 repeated cognitive performance assessments between mid-life (mean age = 53.2 ±4.9 years) and late-life (mean age = 67.7 ± 4.9). Using non-negative matrix factorization, we identified 10 brain components integrating cortical thickness, surface area, fractional anisotropy, and mean and radial diffusivities. We observed two latent variables describing distinct brain-cognition associations. The first describes variations in 5 structural components associated with low mid-life performance across multiple cognitive domains, decline in reasoning, but maintenance of fluency abilities. The second describes variations in 6 structural components associated with low mid-life performance in fluency and memory, but retention of multiple abilities. Expression of latent variables predicts future cognition 3.2 years later (mean age = 70.87 ± 4.9). This data-driven approach highlights brain-cognition relationships wherein individuals degrees of cognitive decline and maintenance across diverse cognitive functions are both positively and negatively associated with markers of cortical structure.

2.
Transl Psychiatry ; 12(1): 202, 2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35562339

RESUMEN

Relatives of individuals with schizophrenia have a higher risk of developing the illness compared to the general population. Thus, youth at familial high risk (FHR) offer a unique opportunity to identify neuroimaging-based endophenotypes of psychosis. Previous studies have identified lower amygdalo-hippocampal volume in FHR, as well as lower verbal memory and emotion recognition. However, whether these phenotypes increase the risk of transition to psychosis remains unclear. To determine if individuals who develop psychosis have abnormal neurodevelopmental trajectories of the amygdala and hippocampus, we investigated longitudinal changes of these structures in a unique cohort of 82 youth FHR and 56 healthy controls during a 3-year period. Ten individuals from the FHR group converted to psychosis. Longitudinal changes were compared using linear mixed-effects models. Group differences in verbal memory and emotion recognition performance at baseline were also analyzed. Surface-based morphometry measures revealed variation in amygdalar shape (concave shape of the right dorsomedial region) in those who converted to psychosis. Significantly lower emotion recognition performance at baseline was observed in converters. Percent trial-to-trial transfer on the verbal learning task was also significantly impaired in FHR, independently of the conversion status. Our results identify abnormal shape development trajectories in the dorsomedial amygdala and lower emotion recognition abilities as phenotypes of transition to psychosis. Our findings illustrate potential markers for early identification of psychosis, aiding prevention efforts in youth at risk of schizophrenia.

3.
Brain Commun ; 4(2): fcac072, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35434622

RESUMEN

Alzheimer's disease is a progressive neurodegenerative disorder with a decades-long pre-symptomatic phase, substantiating the need for prodromal biomarker development and early intervention. To deconstruct the processes underlying disease progression and identify potential biomarkers, we used neuroimaging techniques with high translational potential to human clinical studies in the TgF344-AD rat model which recapitulates the full spectrum of Alzheimer's neuropathology (progressive amyloid deposition, tauopathy, frank neuronal loss, gliosis, and cognitive dysfunction). We employed longitudinal MRI and magnetic resonance spectroscopy in conjunction with behavioural testing to characterize multiple facets of disease pathology in male and female TgF344-AD rats (n = 26, 14M/12F) relative to wildtype littermates (n = 24, 12M/12F). Testing was performed at 4, 10, 16, and 18 months, covering much of the adult rat lifespan and multiple stages of disease progression. The TgF344-AD model demonstrated impaired spatial reference memory in the Barnes Maze by 4 months of age, followed by neurochemical abnormalities in the hippocampus by 10 months and major structural changes by 16 months. Specifically, TgF344-AD rats displayed increased total choline and lactate, and decreased total creatine, taurine, and N-acetylaspartate to myo-inositol ratio, dentate gyrus hypertrophy, and atrophy in the hippocampus, hypothalamus, and nucleus accumbens. Overall, these findings support the use of MRI and magnetic resonance spectroscopy for the development of non-invasive biomarkers of disease progression, clarify the timing of pathological feature presentation in this model, and contribute to the validation of the TgF344-AD rat as a highly relevant model for pre-clinical Alzheimer's disease research.

4.
Proc Natl Acad Sci U S A ; 119(12): e2114545119, 2022 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-35286203

RESUMEN

Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental and psychiatric disorders. MIA-induced deficits in adolescent and adult offspring have been well characterized; however, less is known about the effects of MIA exposure on embryo development. To address this gap, we performed high-resolution ex vivo MRI to investigate the effects of early (gestational day [GD]9) and late (GD17) MIA exposure on embryo (GD18) brain structure. We identify striking neuroanatomical changes in the embryo brain, particularly in the late-exposed offspring. We further examined the putative neuroanatomical underpinnings of MIA timing in the hippocampus using electron microscopy and identified differential effects due to MIA timing. An increase in apoptotic cell density was observed in the GD9-exposed offspring, while an increase in the density of neurons and glia with ultrastructural features reflective of increased neuroinflammation and oxidative stress was observed in GD17-exposed offspring, particularly in females. Overall, our findings integrate imaging techniques across different scales to identify differential impact of MIA timing on the earliest stages of neurodevelopment.


Asunto(s)
Trastorno del Espectro Autista , Sistema Inmunológico , Efectos Tardíos de la Exposición Prenatal , Esquizofrenia , Adolescente , Animales , Encéfalo , Modelos Animales de Enfermedad , Femenino , Humanos , Sistema Inmunológico/fisiología , Inflamación , Imagen por Resonancia Magnética , Ratones , Embarazo
5.
J Psychiatry Neurosci ; 47(1): E1-E10, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35027443

RESUMEN

BACKGROUND: Abnormalities in the anterior cingulate cortex (ACC) are thought to play an important role in the pathophysiology of schizophrenia. Given regional variations in ACC structure, the present study aimed to examine ACC structural subdivisions and their relationships to treatment resistance and glutamatergic levels in schizophrenia. METHODS: This study included 100 patients with schizophrenia and 52 healthy controls from 2 cohorts. We applied non-negative matrix factorization to identify accurate and stable spatial components of ACC structure. Between groups, we compared ACC structural indices in each spatial component based on treatment resistance or response and tested relationships with ACC glutamate + glutamine levels. RESULTS: We detected reductions in cortical thickness and increases in mean diffusivity in the spatial components on the surface of the cingulate sulcus, especially in patients with treatment-resistant and clozapine-resistant schizophrenia. Notably, mean diffusivity in these components was higher in patients who did not respond to clozapine compared to those who did. Furthermore, these ACC structural alterations were related to elevated ACC glutamate + glutamine levels but not related to symptomatology or antipsychotic dose. LIMITATIONS: Sample sizes, cross-sectional findings and mixed antipsychotic status were limitations of this study. CONCLUSION: This study identified reproducible abnormalities in ACC structures in patients with treatment-resistant and clozapine-resistant schizophrenia. Given that these spatial components play a role in inhibitory control, the present study strengthens the notion that glutamate-related disinhibition is a common biological feature of treatment resistance in schizophrenia.


Asunto(s)
Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Clozapina/farmacología , Clozapina/uso terapéutico , Estudios Transversales , Ácido Glutámico , Glutamina , Giro del Cíngulo/diagnóstico por imagen , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico
6.
Brain Struct Funct ; 227(1): 407-419, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34657166

RESUMEN

Adult abilities in complex cognitive domains such as music appear to depend critically on the age at which training or experience begins, and relevant experience has greater long-term effects during periods of peak maturational change. Previous work has shown that early trained musicians (ET; < age 7) out-perform later-trained musicians (LT; > age 7) on tests of musical skill, and also have larger volumes of the ventral premotor cortex (vPMC) and smaller volumes of the cerebellum. These cortico-cerebellar networks mature and function in relation to one another, suggesting that early training may promote coordinated developmental plasticity. To test this hypothesis, we examined structural covariation between cerebellar volume and cortical thickness (CT) in sensorimotor regions in ET and LT musicians and non-musicians (NMs). Results show that ETs have smaller volumes in cerebellar lobules connected to sensorimotor cortices, while both musician groups had greater cortical thickness in right pre-supplementary motor area (SMA) and right PMC compared to NMs. Importantly, early musical training had a specific effect on structural covariance between the cerebellum and cortex: NMs showed negative correlations between left lobule VI and right pre-SMA and PMC, but this relationship was reduced in ET musicians. ETs instead showed a significant negative correlation between vermal IV and right pre-SMA and dPMC. Together, these results suggest that early musical training has differential impacts on the maturation of cortico-cerebellar networks important for optimizing sensorimotor performance. This conclusion is consistent with the hypothesis that connected brain regions interact during development to reciprocally influence brain and behavioral maturation.


Asunto(s)
Corteza Motora , Música , Encéfalo , Mapeo Encefálico , Cerebelo/diagnóstico por imagen , Imagen por Resonancia Magnética
7.
Neuroimage ; 246: 118744, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34848302

RESUMEN

The striatum is a major subcortical connection hub that has been heavily implicated in a wide array of motor and cognitive functions. Here, we developed a normative multimodal, data-driven microstructural parcellation of the striatum using non-negative matrix factorization (NMF) based on multiple magnetic resonance imaging-based metrics (mean diffusivity, fractional anisotropy, and the ratio between T1- and T2-weighted structural scans) from the Human Connectome Project Young Adult dataset (n = 329 unrelated participants, age range: 22-35, F/M: 185/144). We further explored the biological and functional relationships of this parcellation by relating our findings to motor and cognitive performance in tasks known to involve the striatum as well as demographics. We identified 5 spatially distinct striatal components for each hemisphere. We also show the gain in component stability when using multimodal versus unimodal metrics. Our findings suggest distinct microstructural patterns in the human striatum that are largely symmetric and that relate mostly to age and sex. Our work also highlights the putative functional relevance of these striatal components to different designations based on a Neurosynth meta-analysis.


Asunto(s)
Cuerpo Estriado/anatomía & histología , Cuerpo Estriado/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Adulto , Conectoma , Femenino , Humanos , Masculino , Adulto Joven
8.
Neurobiol Aging ; 109: 216-228, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34775212

RESUMEN

Animal models are widely used to study the pathophysiology of disease and to evaluate the efficacy of novel interventions, crucial steps towards improving disease outcomes in humans. The Fischer 344 (F344) wildtype rat is a common experimental background strain for transgenic models of disease and is one of the most frequently used models in aging research. Despite frequency of use, characterization of agerelated neuroanatomical change has not been performed in the F344 rat. To this end, we present a comprehensive longitudinal examination of morphometric change in 73 brain regions and at a voxel-wise level during normative aging in vivo in a mixed-sexcohort of F344 rats. We identified the greatest vulnerability to aging within the cortex, caudoputamen, hindbrain, and internal capsule, while the influence of sex was strongest in the caudoputamen, hippocampus, nucleus accumbens, and thalamus, many of which are implicated in memory and motor control circuits frequently affected by aging and neurodegenerative disease. These findings provide a baseline for neuroanatomical changes associated with aging in male and female F344 rats, to which data from transgenic models or other background strains can be compared.


Asunto(s)
Envejecimiento/patología , Envejecimiento/fisiología , Encéfalo/patología , Encéfalo/fisiología , Caracteres Sexuales , Animales , Encéfalo/diagnóstico por imagen , Femenino , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Memoria , Modelos Animales , Neuroimagen , Ratas Endogámicas F344
9.
J Cereb Blood Flow Metab ; 42(5): 788-801, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34378436

RESUMEN

In vivo biomarker abnormalities provide measures to monitor therapeutic interventions targeting amyloid-ß pathology as well as its effects on downstream processes associated with Alzheimer's disease pathophysiology. Here, we applied an in vivo longitudinal study design combined with imaging and cerebrospinal fluid biomarkers, mirroring those used in human clinical trials to assess the efficacy of a novel brain-penetrating anti-amyloid fusion protein treatment in the McGill-R-Thy1-APP transgenic rat model. The bi-functional fusion protein consisted of a blood-brain barrier crossing single domain antibody (FC5) fused to an amyloid-ß oligomer-binding peptide (ABP) via Fc fragment of mouse IgG (FC5-mFc2a-ABP). A five-week treatment with FC5-mFc2a-ABP (loading dose of 30 mg/Kg/iv followed by 15 mg/Kg/week/iv for four weeks) substantially reduced brain amyloid-ß levels as measured by positron emission tomography and increased the cerebrospinal fluid amyloid-ß42/40 ratio. In addition, the 5-week treatment rectified the cerebrospinal fluid neurofilament light chain concentrations, resting-state functional connectivity, and hippocampal atrophy measured using magnetic resonance imaging. Finally, FC5-mFc2a-ABP (referred to as KG207-M) treatment did not induce amyloid-related imaging abnormalities such as microhemorrhage. Together, this study demonstrates the translational values of the designed preclinical studies for the assessment of novel therapies based on the clinical biomarkers providing tangible metrics for designing early-stage clinical trials.


Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Biomarcadores , Estudios Longitudinales , Ratones , Tomografía de Emisión de Positrones , Ratas
10.
Hum Brain Mapp ; 43(6): 1882-1894, 2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-34953011

RESUMEN

Progressive cortical volumetric loss following moderate-severe traumatic brain injury (TBI) has been observed; however, regionally specific changes in the structural determinants of cortical volume, namely, cortical thickness (CT) and cortical surface area (CSA), are unknown and may inform the patterns and neural substrates of neurodegeneration and plasticity following injury. We aimed to (a) assess differences in CT and CSA between TBI participants and controls in the early chronic stage post-injury, (b) describe longitudinal changes in cortical morphometry following TBI, and (c) examine how regional changes in CT and CSA are associated. We acquired magnetic resonance images for 67 participants with TBI at up to 4 time-points spanning 5 months to 7 years post-injury, and 18 controls at 2 time-points. In the early chronic stage, TBI participants displayed thinner cortices than controls, predominantly in frontal regions, but no CSA differences. Throughout the chronic period, TBI participants showed widespread CT reductions in posterior cingulate/precuneus regions and moderate CT increase in frontal regions. Additionally, CSA showed a significant decrease in the orbitofrontal cortex and circumscribed increase in posterior regions. No changes were identified in controls. Relationships between regional cortical changes in the same morphological measure revealed coordinated patterns within participants, whereas correlations between regions with CT and CSA change yielded bi-directional relationships. This suggests that these measures may be differentially affected by neurodegenerative mechanisms such as transneuronal degeneration following TBI and that degeneration may be localized to the depths of cortical sulci. These findings emphasize the importance of dissecting morphometric contributions to cortical volume change.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Adulto , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/patología , Giro del Cíngulo/patología , Humanos , Imagen por Resonancia Magnética , Corteza Prefrontal/patología
11.
Artículo en Inglés | MEDLINE | ID: mdl-34748864

RESUMEN

INTRODUCTION: Recent studies have observed that patients with treatment-resistant schizophrenia as well as patients with schizophrenia who do not respond within a medication trial exhibit excess activity of the glutamate system. In this study we sought to replicate the within-trial glutamate abnormality and to investigate the potential for structural differences and treatment-induced changes to improve identification of medication responders and non-responders. METHODS: We enrolled 48 medication-naïve patients in a 4-week trial of risperidone and classified them retrospectively into responders and non-responders using clinical criteria. Proton magnetic resonance spectroscopy and T1-weighted structural MRI were acquired pre- and post-treatment to quantify striatal glutamate levels and several measures of subcortical brain structure. RESULTS: Patients were classified as 29 responders and 19 non-responders. Striatal glutamate was higher in the non-responders than responders both pre- and post-treatment (F1,39 = 7.15, p = .01). Volumetric measures showed a significant group x time interaction (t = 5.163, <1%FDR), and group x time x glutamate interaction (t = 4.23, <15%FDR) were seen in several brain regions. Striatal volumes increased at trend level with treatment in both groups, and a positive association of striatal volumes with glutamate levels was seen in the non-responders. CONCLUSIONS: Combining anatomic measures with glutamate levels offers the potential to enhance classification of responders and non-responders to antipsychotic medications as well as to provide mechanistic understanding of the interplay between neuroanatomical and neurochemical changes induced by these medications. Ethical statement The study was approved by the Ethics and Scientific committees of the Instituto Nacional de Neurología y Neurocirugía in Mexico City. All participants over 18 years fully understood and signed the informed consent; in case the patient was under 18 years, informed consent was obtained from both parents. Participants did not receive a stipend.


Asunto(s)
Cuerpo Estriado , Ácido Glutámico/metabolismo , Trastornos Psicóticos , Risperidona/administración & dosificación , Antagonistas de la Serotonina/administración & dosificación , Adulto , Encéfalo/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Espectroscopía de Protones por Resonancia Magnética , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/metabolismo , Estudios Retrospectivos , Risperidona/farmacología , /metabolismo , Antagonistas de la Serotonina/farmacología , Encuestas y Cuestionarios , Adulto Joven
12.
Neuroimage Clin ; 32: 102868, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34749289

RESUMEN

Prenatal exposure to maternal immune activation (MIA) is a risk factor for a variety of neurodevelopmental and psychiatric disorders. The timing of MIA-exposure has been shown to affect adolescent and adult offspring neurodevelopment, however, less is known about these effects in the neonatal period. To better understand the impact of MIA-exposure on neonatal brain development in a mouse model, we assess neonate communicative abilities with the ultrasonic vocalization task, followed by high-resolution ex vivo magnetic resonance imaging (MRI) on the neonatal (postnatal day 8) mouse brain. Early exposed offspring displayed decreased communicative ability, while brain anatomy appeared largely unaffected, apart from some subtle alterations. By integrating MRI and behavioural assays to investigate the effects of MIA-exposure on neonatal neurodevelopment we show that offspring neuroanatomy and behaviour are only subtly affected by both early and late exposure. This suggests that the deficits often observed in later stages of life may be dormant, not yet developed in the neonatal period, or not as easily detectable using a cross-sectional approach.


Asunto(s)
Efectos Tardíos de la Exposición Prenatal , Animales , Conducta Animal , Encéfalo/diagnóstico por imagen , Modelos Animales de Enfermedad , Femenino , Ratones , Embarazo
13.
Sci Rep ; 11(1): 21168, 2021 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-34707133

RESUMEN

The habenula is a small epithalamic structure with widespread connections to multiple cortical, subcortical and brainstem regions. It has been identified as the central structure modulating the reward value of social interactions, behavioral adaptation, sensory integration and circadian rhythm. Autism spectrum disorder (ASD) is characterized by social communication deficits, restricted interests, repetitive behaviors, and is frequently associated with altered sensory perception and mood and sleep disorders. The habenula is implicated in all these behaviors and results of preclinical studies suggest a possible involvement of the habenula in the pathophysiology of this disorder. Using anatomical magnetic resonance imaging and automated segmentation we show that the habenula is significantly enlarged in ASD subjects compared to controls across the entire age range studied (6-30 years). No differences were observed between sexes. Furthermore, support-vector machine modeling classified ASD with 85% accuracy (model using habenula volume, age and sex) and 64% accuracy in cross validation. The Social Responsiveness Scale (SRS) significantly differed between groups, however, it was not related to individual habenula volume. The present study is the first to provide evidence in human subjects of an involvement of the habenula in the pathophysiology of ASD.


Asunto(s)
Trastorno del Espectro Autista/diagnóstico por imagen , Habénula/diagnóstico por imagen , Adolescente , Adulto , Trastorno del Espectro Autista/patología , Niño , Femenino , Habénula/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Conducta Social , Máquina de Vectores de Soporte
15.
Artículo en Inglés | MEDLINE | ID: mdl-34557990

RESUMEN

Episodic memory ability relies on hippocampal-prefrontal connectivity. However, few studies have examined relationships between memory performance and white matter (WM) microstructure in hippocampal-prefrontal pathways in schizophrenia-spectrum disorder (SSDs). Here, we investigated these relationships in individuals with first-episode psychosis (FEP) and chronic schizophrenia-spectrum disorders (SSDs) using tractography analysis designed to interrogate the microstructure of WM tracts in the hippocampal-prefrontal pathway. Measures of WM microstructure (fractional anisotropy [FA], radial diffusivity [RD], and axial diffusivity [AD]) were obtained for 47 individuals with chronic SSDs, 28 FEP individuals, 52 older healthy controls, and 27 younger healthy controls. Tractography analysis was performed between the hippocampus and three targets involved in hippocampal-prefrontal connectivity (thalamus, amygdala, nucleus accumbens). Measures of WM microstructure were then examined in relation to episodic memory performance separately across each group. Both those with FEP and chronic SSDs demonstrated impaired episodic memory performance. However, abnormal WM microstructure was only observed in individuals with chronic SSDs. Abnormal WM microstructure in the hippocampal-thalamic pathway in the right hemisphere was associated with poorer memory performance in individuals with chronic SSDs. These findings suggest that disruptions in WM microstructure in the hippocampal-prefrontal pathway may contribute to memory impairments in individuals with chronic SSDs but not FEP.

16.
Eur J Neurol ; 28(12): 4153-4166, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34487400

RESUMEN

BACKGROUND AND PURPOSE: In an era of individualized multiple sclerosis (MS) patient management, biomarkers for accurate prediction of future clinical outcomes are needed. We aimed to evaluate the potential of short-term magnetic resonance imaging (MRI) atrophy measures and serum neurofilament light chain (sNfL) as predictors of the dynamics of disability accumulation in relapse-onset MS. METHODS: Brain gray and white matter, thalamic, striatal, pallidal and cervical spinal cord volumes, and lesion load were measured over three available time points (mean time span 2.24 ± 0.70 years) for 183 patients (140 relapsing-remitting [RRMS] and 43 secondary-progressive MS (SPMS); 123 female, age 46.4 ± 11.0 years; disease duration 15.7 ± 9.3 years), and their respective annual changes were calculated. Baseline sNfL was also measured at the third available time point for each patient. Subsequently, patients underwent annual clinical examinations over 5.4 ± 3.7 years including Expanded Disability Status Scale (EDSS) scoring, the nine-hole peg test and the timed 25-foot walk test. RESULTS: Higher annual spinal cord atrophy rates and lesion load increase predicted higher future EDSS score worsening over time in SPMS. Lower baseline thalamic volumes predicted higher walking speed worsening over time in RRMS. Lower baseline gray matter, as well as higher white matter and spinal cord atrophy rates, lesion load increase, baseline striatal volumes and baseline sNfL, predicted higher future hand dexterity worsening over time. All models showed reasonable to high prediction accuracy. CONCLUSION: This study demonstrates the capability of short-term MRI metrics to accurately predict future dynamics of disability progression in a real-world relapse-onset MS cohort. The present study represents a step towards the utilization of structural MRI measurements in patient care.


Asunto(s)
Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Atrofia/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Esclerosis Múltiple Crónica Progresiva/diagnóstico por imagen , Esclerosis Múltiple Crónica Progresiva/patología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología
17.
Neuroimage Clin ; 31: 102771, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34359014

RESUMEN

Men and women tend to differ in the age of first alcohol consumption, transition into disordered drinking, and the prevalence of alcohol use disorder. Here, we use a unique longitudinal dataset to test for potentially predispositonal sex-biases in brain organization prior to initial alcohol exposure. Our study combines measures of subcortical morphometry gathered in alcohol naive individuals during childhood (mean age: 9.43 years, SD = 2.06) with self-report measures of alcohol use in the same individuals an average of 17 years later (N = 81, 46 males, 35 females). We observe that pediatric amygdala and hippocampus volume both show sex-biased relationships with adult drinking. Specifically, females show a stronger association between subcortical volumetric reductions in childhood and peak drinking in adulthood as compared to males. Detailed analysis of subcortical shape localizes these effects to the rostro-medial hippocampus and basolateral amygdala subnuclei. In contrast, we did not observe sex-specific associations between striatal anatomy and peak alcohol consumption. These results are consistent with a model in which organization of the amygdala and hippocampus in childhood is more relevant for subsequent patterns of peak alcohol use in females as compared to males. Differential neuroanatomical precursors of alcohol use in males and females could provide a potential developmental basis for well recognized sex-differences in alcohol use behaviors.. Thus, our findings not only indicate that brain correlates of human alcohol consumption are manifest long before alcohol initiation, but that some of these correlates are not equivalent between males and females.


Asunto(s)
Alcoholismo , Amígdala del Cerebelo , Adulto , Consumo de Bebidas Alcohólicas , Amígdala del Cerebelo/diagnóstico por imagen , Niño , Femenino , Estudios de Seguimiento , Hipocampo , Humanos , Masculino
18.
Schizophr Bull ; 47(6): 1706-1717, 2021 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-34254147

RESUMEN

OBJECTIVE: Brain-based Biotypes for psychotic disorders have been developed as part of the B-SNIP consortium to create neurobiologically distinct subgroups within idiopathic psychosis, independent from traditional phenomenological diagnostic methods. In the current study, we aimed to validate the Biotype model by assessing differences in volume and shape of the amygdala and hippocampus contrasting traditional clinical diagnoses with Biotype classification. METHODS: A total of 811 participants from 6 sites were included: probands with schizophrenia (n = 199), schizoaffective disorder (n = 122), psychotic bipolar disorder with psychosis (n = 160), and healthy controls (n = 330). Biotype classification, previously developed using cognitive and electrophysiological data and K-means clustering, was used to categorize psychosis probands into 3 Biotypes, with Biotype-1 (B-1) showing reduced neural salience and severe cognitive impairment. MAGeT-Brain segmentation was used to determine amygdala and hippocampal volumetric data and shape deformations. RESULTS: When using Biotype classification, B-1 showed the strongest reductions in amygdala-hippocampal volume and the most widespread shape abnormalities. Using clinical diagnosis, probands with schizophrenia and schizoaffective disorder showed the most significant reductions of amygdala and hippocampal volumes and the most abnormal hippocampal shape compared with healthy controls. Biotype classification provided the strongest neuroanatomical differences compared with conventional DSM diagnoses, with the best discrimination seen using bilateral amygdala and right hippocampal volumes in B-1. CONCLUSION: These findings characterize amygdala and hippocampal volumetric and shape abnormalities across the psychosis spectrum. Grouping individuals by Biotype showed greater between-group discrimination, suggesting a promising approach and a favorable target for characterizing biological heterogeneity across the psychosis spectrum.


Asunto(s)
Amígdala del Cerebelo/patología , Trastorno Bipolar/diagnóstico , Disfunción Cognitiva/diagnóstico , Hipocampo/patología , Trastornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Adulto , Trastorno Bipolar/clasificación , Trastorno Bipolar/patología , Trastorno Bipolar/fisiopatología , Análisis por Conglomerados , Disfunción Cognitiva/clasificación , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/clasificación , Trastornos Psicóticos/patología , Trastornos Psicóticos/fisiopatología , Esquizofrenia/clasificación , Esquizofrenia/patología , Esquizofrenia/fisiopatología
19.
Neurobiol Aging ; 106: 153-168, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34280848

RESUMEN

The study of the hippocampus across the healthy adult lifespan has rendered inconsistent findings. While volumetric measurements have often been a popular technique for analysis, more advanced morphometric techniques have demonstrated compelling results that highlight the importance and improved specificity of shape-based measures. Here, the MAGeT Brain algorithm was applied on 134 healthy individuals aged 18-81 years old to extract hippocampal subfield volumes and hippocampal shape measurements, namely: local surface area (SA) and displacement. We used linear-, second- or third-order natural splines to examine the relationships between hippocampal measures and age. In addition, partial least squares analyses were performed to relate volume and shape measurements with cognitive and demographic information. Volumetric results indicated a relative preservation of the right cornus ammonis 1 with age and a global volume reduction linked with older age, female sex, lower levels of education and cognitive performance. Vertex-wise analysis demonstrated an SA preservation in the anterior hippocampus with a peak during the sixth decade, while the posterior hippocampal SA gradually decreased across lifespan. Overall, SA decrease was linked to older age, female sex and, to a lesser extent lower levels of education and cognitive performance. Outward displacement in the lateral hippocampus and inward displacement in the medial hippocampus were enlarged with older age, lower levels of cognition and education, indicating an accentuation of the hippocampal "C" shape with age. Taken together, our findings suggest that vertex-wise analyses have higher spatial specifity and that sex, education, and cognition are implicated in the differential impact of age on hippocampal subregions throughout its anteroposterior and medial-lateral axes. This article is part of the Virtual Special Issue titled COGNITIVE NEU- ROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.


Asunto(s)
Cognición/fisiología , Envejecimiento Saludable/patología , Envejecimiento Saludable/psicología , Hipocampo/patología , Hipocampo/fisiología , Longevidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Caracteres Sexuales , Adulto Joven
20.
Neuroimage ; 238: 118172, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34082116

RESUMEN

Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices ("Prisma Upgrade protocol") and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence ("vNav protocol"). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT and amygdala, globus pallidus, hippocampus, and striatum volumes, were observed. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement.


Asunto(s)
Grosor de la Corteza Cerebral , Encéfalo/diagnóstico por imagen , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Proyectos de Investigación
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