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INTRODUCTION: In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. METHODS: In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. RESULTS: In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. DISCUSSION: WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. HIGHLIGHTS: White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.
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PURPOSE: The objective of this prospective, single-centre case series was to investigate feasibility, clinical outcomes, and neural correlates of non-invasive Neuromodulation-Induced Cortical Prehabilitation (NICP) before brain tumor surgery. Previous studies have shown that gross total resection is paramount to increase life expectancy but is counterbalanced by the need of preserving critical functional areas. NICP aims at expanding functional margins for extensive tumor resection without functional sequelae. Invasive NICP (intracranial neuromodulation) was effective but characterized by elevated costs and high rate of adverse events. Non-invasive NICP (transcranial neuromodulation) may represent a more feasible alternative. Nonetheless, up to this point, non-invasive NICP has been examined in only two case reports, yielding inconclusive findings. METHODS: Treatment sessions consisted of non-invasive neuromodulation, to transiently deactivate critical areas adjacent to the lesion, coupled with intensive functional training, to activate alternative nodes within the same functional network. Patients were evaluated pre-NICP, post-NICP, and at follow-up post-surgery. RESULTS: Ten patients performed the intervention. Feasibility criteria were met (retention, adherence, safety, and patient's satisfaction). Clinical outcomes showed overall stability and improvements in motor and executive function from pre- to post-NICP, and at follow-up. Relevant plasticity changes (increase in the distance between tumor and critical area) were observed when the neuromodulation target was guided by functional neuroimaging data. CONCLUSION: This is the first case series demonstrating feasibility of non-invasive NICP. Neural correlates indicate that neuroimaging-guided target selection may represent a valid strategy to leverage neuroplastic changes before neurosurgery. Further investigations are needed to confirm such preliminary findings.
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BACKGROUND AND OBJECTIVES: Cerebral hemorrhages are an exclusion criterion and potential adverse effect of antiamyloid agents. It is, therefore, critical to characterize the natural history of cerebral microbleeds in populations genetically predisposed to Alzheimer disease (AD), such as Down syndrome (DS). We aimed to assess microbleed emergence in adults with DS across the AD spectrum, defining their topography and associations with clinical variables, cognitive outcomes, and fluid and neuroimaging biomarkers. METHODS: This cross-sectional study included participants aged 18 years or older from the Down-Alzheimer Barcelona Neuroimaging Initiative and Sant Pau Initiative on Neurodegeneration with T1-weighted and susceptibility-weighted images. Participants underwent comprehensive assessments, including apolipoprotein E (APOE) genotyping; fluid and plasma determinations of beta-amyloid, tau, and neurofilament light; cognitive outcomes (Cambridge Cognitive Examination and modified Cued Recall Test); and vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia). We manually segmented microbleeds and characterized their topography. Associations between microbleed severity and AD biomarkers were explored using between-group comparisons (none vs 1 vs 2+) and multivariate linear models. RESULTS: We included 276 individuals with DS and 158 healthy euploid controls (mean age = 47.8 years, 50.92% female). Individuals with DS were more likely to have microbleeds than controls (20% vs 8.9%, p < 0.001), with more severe presentation (12% with 2+ vs 1.9%). Microbleeds increased with age (12% 20-30 years vs 60% > 60 years) and AD clinical stage (12.42% asymptomatic, 27.9% prodromal, 35.09% dementia) were more common in APOEε4 carriers (26% vs 18.3% noncarriers, p = 0.008), but not associated with vascular risk factors (p > 0.05). Microbleeds were predominantly posterior (cerebellum 33.66%; occipital 14.85%; temporal 21.29%) in participants with DS. Associations with microbleed severity were found for neuroimaging and fluid AD biomarkers, but only hippocampal volumes (standardized ß = -0.18 [-0.31, -0.06], p < 0.005) and CSF p-tau-181 concentrations (ß = 0.26 [0.12, 0.41], p < 0.005) survived regression controlling for age and disease stage, respectively. Microbleeds had limited effect on cognitive outcomes. DISCUSSION: In participants with DS, microbleeds present with a posterior, lobar predominance, are associated with disease severity, but do not affect cognitive performance. These results suggest an interplay between AD pathology and vascular lesions, implicating microbleeds as a risk factor limiting the use of antiamyloid agents in this population.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Hemorragia Cerebral , Síndrome de Down , Proteínas tau , Humanos , Síndrome de Down/líquido cefalorraquidiano , Síndrome de Down/complicações , Síndrome de Down/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/sangue , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Adulto , Imageamento por Ressonância Magnética , Idoso , Apolipoproteínas E/genética , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas de Neurofilamentos/sangueRESUMO
INTRODUCTION: Early-onset Alzheimer's disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late-onset Alzheimer's disease (LOAD). We aim to determine the differences in the severity of neuropsychiatric symptoms and locus coeruleus (LC) integrity between EOAD and LOAD accounting for disease stage. METHODS: One hundred four subjects with AD diagnosis and 32 healthy controls were included. Participants underwent magnetic resonance imaging (MRI) to measure LC integrity, measures of noradrenaline levels in cerebrospinal fluid (CSF) and Neuropsychiatric Inventory (NPI). We analyzed LC-noradrenaline measurements and clinical and Alzheimer's disease (AD) biomarker associations. RESULTS: EOAD showed higher NPI scores, lower LC integrity, and similar levels of CSF noradrenaline compared to LOAD. Notably, EOAD exhibited lower LC integrity independently of disease stage. LC integrity negatively correlated with neuropsychiatric symptoms. Noradrenaline levels were increased in AD correlating with AD biomarkers. DISCUSSION: Decreased LC integrity negatively contributes to neuropsychiatric symptoms. The higher LC degeneration in EOAD compared to LOAD could explain the more severe neuropsychiatric symptoms in EOAD. HIGHLIGHTS: LC degeneration is greater in early-onset AD (EOAD) compared to late-onset AD. Tau-derived LC degeneration drives a higher severity of neuropsychiatric symptoms. EOAD harbors a more profound selective vulnerability of the LC system. LC degeneration is associated with an increase of cerebrospinal fluid noradrenaline levels in AD.
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Primary brain neoplasms are associated with elevated mortality and morbidity rates. Brain tumour surgery aims to achieve maximal tumour resection while minimizing damage to healthy brain tissue. Research on Neuromodulation Induced Cortical Prehabilitation (NICP) has highlighted the potential, before neurosurgery, of establishing new brain connections and transfer functional activity from one area of the brain to another. Nonetheless, the neural mechanisms underlying these processes, particularly in the context of space-occupying lesions, remain unclear. A patient with a left frontotemporoinsular tumour underwent a prehabilitation protocol providing 20 sessions of inhibitory non-invasive neuromodulation (rTMS and multichannel tDCS) over a language network coupled with intensive task training. Prehabilitation resulted in an increment of the distance between the tumour and the language network. Furthermore, enhanced functional connectivity within the language circuit was observed. The present innovative case-study exposed that inhibition of the functional network area surrounding the space-occupying lesion promotes a plastic change in the network's spatial organization, presumably through the establishment of novel functional pathways away from the lesion's site. While these outcomes are promising, prudence dictates the need for larger studies to confirm and generalize these findings.
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INTRODUCTION: A Mediterranean diet has positive effects on the brain in mid-older adults; however, there is scarce information on pregnant individuals. We aimed to evaluate the effect of a structured Mediterranean diet intervention on the cortical structure of the maternal brain during pregnancy. METHODS: This study was a secondary analysis of the IMPACT BCN, a randomized clinical trial with 1221 high-risk pregnant women randomly allocated into three groups at 19-23 weeks of gestation: Mediterranean diet intervention, a mindfulness-based stress reduction program, or usual care. Maternal brain magnetic resonance imaging was performed during the third trimester of pregnancy in a random subgroup of participants. For this study, data from the Mediterranean diet and usual groups were analyzed. Maternal dietary intake, adherence to the Mediterranean diet and metabolite biomarkers were evaluated using a food frequency questionnaire, a 17-item dietary screener and plasma/urine samples, respectively. RESULTS: The cluster-wise analysis showed that the Mediterranean diet group participants (n = 34) had significantly larger surface areas in the right precuneus (90%CI: <0.0001-0.0004, p < 0.001) and left superior parietal (90%CI: 0.026-0.033, p = 0.03) lobules compared to the usual care group participants (n = 37). A larger right precuneus area was associated with high improvements in adherence to the Mediterranean diet, a high intake of walnuts and high concentrations of urinary hydroxytyrosol. A larger left superior parietal area was associated with a high intake of walnuts and high concentrations of urinary hydroxytyrosol. CONCLUSIONS: The promotion of a Mediterranean diet during pregnancy has a significant effect on maternal brain structure.
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Encéfalo , Dieta Mediterrânea , Imageamento por Ressonância Magnética , Humanos , Feminino , Gravidez , Adulto , Encéfalo/diagnóstico por imagem , Atenção Plena , Biomarcadores/urina , Fenômenos Fisiológicos da Nutrição Materna , Terceiro Trimestre da GravidezRESUMO
Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI). BBB permeability in the whole brain (WB), gray matter (GM) and white matter (WM) was assessed with the parameter Ktrans. We used ambulatory blood pressure monitoring to measure 24-h systolic blood pressure (24-h SBP), diastolic blood pressure (24-h DBP), and pulse wave velocity (24-h PWV) both after stroke and following a 2-year follow-up. The differences between both measurements were calculated as Δ24-h SBP, Δ24-h DBP and Δ24-h PWV. DCE-MRI was acquired at a median (IQR) of 24 (19-27) months after stroke. Median age was 66.7 (9.7) years, and 24 (83%) patients were men. Median (IQR) Δ24-h PWV was 0.3 (-0.1, 0.5) m/s. WB-Ktrans, GM-Ktrans, and WM-Ktrans were associated with Δ24-h PWV (Spearman's, r [95% CI], WB 0.651 [0.363-0.839]; GM 0.657 [0.373-0.845], WM 0.530[0.197-0.777]) but not with Δ24-h SBP or Δ24-h DBP. These associations remained significant after adjustment with linear regression models, controlling for age, sex, body mass index, and Δ24-h SBP (b[95% CI], WB 0.725[0.384-1.127], GM 0.629 [0.316-1.369], WM 0.865 [0.455-0.892]) or Δ24-h DBP (b[95% CI], WM 0.707 [0.370-1.103], GM 0.643 [0.352-1.371], WM 0.772 [0.367-0.834]). Our results suggest that an increment on arterial stiffness in the months following a RSSI might increase BBB permeability.
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OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are complex clinical manifestations and misdiagnosis as status epilepticus remains high, entailing deleterious consequences for patients. Video-electroencephalography (vEEG) remains the gold-standard method for diagnosing PNES. However, time and economic constraints limit access to vEEG, and clinicians lack fast and reliable screening tools to assist in the differential diagnosis with epileptic seizures (ES). This study aimed to design and validate the PNES-DSC, a clinically based PNES diagnostic suspicion checklist with adequate sensitivity (Se) and specificity (Sp) to discriminate PNES from ES. METHODS: A cross-sectional study with 125 patients (n = 104 drug-resistant epilepsy; n = 21 PNES) admitted for a vEEG protocolised study of seizures. A preliminary PNES-DSC (16-item) was designed and used by expert raters blinded to the definitive diagnosis to evaluate the seizure video recordings for each patient. Cohen's kappa coefficient, leave-one-out cross-validation (LOOCV) and balance accuracy (BAC) comprised the main validation analysis. RESULTS: The final PNES-DSC is a 6-item checklist that requires only two to be present to confirm the suspicion of PNES. The LOOCV showed 71.4% BAC (Se = 45.2%; Sp = 97.6%) when the expert rater watched one seizure video recording and 83.4% BAC (Se = 69.6%; Sp = 97.2%) when the expert rater watched two seizure video recordings. CONCLUSION: The PNES-DSC is a straightforward checklist with adequate psychometric properties. With an integrative approach and appropriate patient history, the PNES-DSC can assist clinicians in expediting the final diagnosis of PNES when vEEG is limited. The PNES-DSC can also be used in the absence of patients, allowing clinicians to assess seizure recordings from smartphones.
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Lista de Checagem , Eletroencefalografia , Convulsões , Humanos , Adulto , Feminino , Diagnóstico Diferencial , Masculino , Estudos Transversais , Convulsões/diagnóstico , Eletroencefalografia/métodos , Pessoa de Meia-Idade , Gravação em Vídeo , Transtornos Psicofisiológicos/diagnóstico , Reprodutibilidade dos Testes , Adulto Jovem , Sensibilidade e Especificidade , Epilepsia/diagnóstico , Transtorno Conversivo/diagnóstico , Transtornos Somatoformes/diagnósticoRESUMO
BACKGROUND: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. METHODS: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. RESULTS: CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. DISCUSSION: In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. HIGHLIGHTS: This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.
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Doença de Alzheimer , Síndrome de Down , Imageamento por Ressonância Magnética , Humanos , Síndrome de Down/patologia , Síndrome de Down/complicações , Síndrome de Down/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Adulto , Idoso , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/patologia , Prevalência , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/patologia , Angiopatia Amiloide Cerebral/complicações , Fatores de Risco , Córtex Cerebral/patologia , Córtex Cerebral/diagnóstico por imagemRESUMO
BACKGROUND: Evidence regarding cortical atrophy patterns in Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-pRBD) remains scarce. Cortical mean diffusivity (cMD), as a novel imaging biomarker highly sensitive to detecting cortical microstructural changes in different neurodegenerative diseases, has not been investigated in PD-pRBD yet. OBJECTIVES: The aim was to investigate cMD as a sensitive measure to identify subtle cortical microstructural changes in PD-pRBD and its relationship with cortical thickness (CTh). METHODS: Twenty-two PD-pRBD, 31 PD without probable RBD (PD-nonpRBD), and 28 healthy controls (HC) were assessed using 3D T1-weighted and diffusion-weighted magnetic resonance imaging on a 3-T scanner and neuropsychological testing. Measures of cortical brain changes were obtained through cMD and CTh. Two-class group comparisons of a general linear model were performed (P < 0.05). Cohen's d effect size for both approaches was computed. RESULTS: PD-pRBD patients showed higher cMD than PD-nonpRBD patients in the left superior temporal, superior frontal, and precentral gyri, precuneus cortex, as well as in the right middle frontal and postcentral gyri and paracentral lobule (d > 0.8), whereas CTh did not detect significant differences. PD-pRBD patients also showed increased bilateral posterior cMD in comparison with HCs (d > 0.8). These results partially overlapped with CTh results (0.5 < d < 0.8). PD-nonpRBD patients showed no differences in cMD when compared with HCs but showed cortical thinning in the left fusiform gyrus and lateral occipital cortex bilaterally (d > 0.5). CONCLUSIONS: cMD may be more sensitive than CTh displaying significant cortico-structural differences between PD subgroups, indicating this imaging biomarker's utility in studying early cortical changes in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Córtex Cerebral , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Transtorno do Comportamento do Sono REM/patologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética/métodos , Atrofia/patologia , Testes NeuropsicológicosRESUMO
White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.
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Imagem de Tensor de Difusão , Aprendizado de Máquina , Transtorno Obsessivo-Compulsivo , Substância Branca , Humanos , Substância Branca/patologia , Substância Branca/diagnóstico por imagem , Masculino , Feminino , Adulto , Imagem de Tensor de Difusão/métodos , Criança , Adolescente , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group. METHODS: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. RESULTS: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( η ρ max 2 = .05) and longer epilepsy duration ( η ρ max 2 = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. SIGNIFICANCE: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.
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Epilepsia do Lobo Temporal , Síndromes Epilépticas , Adulto , Humanos , Epilepsia do Lobo Temporal/complicações , Fenitoína , Estudos Transversais , Síndromes Epilépticas/complicações , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Convulsões/complicações , Imageamento por Ressonância Magnética/métodos , Atrofia/patologiaRESUMO
BACKGROUND AND OBJECTIVE: Alzheimer's disease (AD) and frontotemporal dementia (FTD) show different patterns of cortical thickness (CTh) loss compared with healthy controls (HC), even though there is relevant heterogeneity between individuals suffering from each of these diseases. Thus, we developed CTh models to study individual variability in AD, FTD, and HC. METHODS: We used the baseline CTh measures of 379 participants obtained from the structural MRI processed with FreeSurfer. A total of 169 AD patients (63 ± 9 years, 65 men), 88 FTD patients (64 ± 9 years, 43 men), and 122 HC (62 ± 10 years, 47 men) were studied. We fitted region-wise temporal models of CTh using Support Vector Regression. Then, we studied associations of individual deviations from the model with cerebrospinal fluid levels of neurofilament light chain (NfL) and 14-3-3 protein and Mini-Mental State Examination (MMSE). Furthermore, we used real longitudinal data from 144 participants to test model predictivity. RESULTS: We defined CTh spatiotemporal models for each group with a reliable fit. Individual deviation correlated with MMSE for AD and with NfL for FTD. AD patients with higher deviations from the trend presented higher MMSE values. In FTD, lower NfL levels were associated with higher deviations from the CTh prediction. For AD and HC, we could predict longitudinal visits with the presented model trained with baseline data. For FTD, the longitudinal visits had more variability. CONCLUSION: We highlight the value of CTh models for studying AD and FTD longitudinal changes and variability and their relationships with cognitive features and biomarkers.
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Doença de Alzheimer , Demência Frontotemporal , Masculino , Humanos , Doença de Alzheimer/diagnóstico , Demência Frontotemporal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Testes de Estado Mental e Demência , Biomarcadores/líquido cefalorraquidianoRESUMO
BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.
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Transtorno da Conduta , Comportamento Problema , Masculino , Criança , Adolescente , Humanos , Transtorno da Conduta/diagnóstico por imagem , Agressão/psicologia , Emoções , Encéfalo/diagnóstico por imagemRESUMO
Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed (d=0.42). Maximum volume loss was observed in the corpus medullare (dmax=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (dmax= 0.47), Crus I/II (dmax= 0.39), VIIIA (dmax=0.45) and VIIIB (dmax=0.40). Earlier age at seizure onset (ηρ2max=0.05) and longer epilepsy duration (ηρ2max=0.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy.
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Introduction: Neurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy. Methods and analysis: Patients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery. Ethics and dissemination: Ethics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses. Clinical trial registration: ClinicalTrials.gov, identifier NCT05844605.
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BACKGROUND: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and infant neurodevelopment. OBJECTIVE: This study aimed to investigate if structured lifestyle interventions involving a Mediterranean diet or mindfulness-based stress reduction during pregnancy are associated with differences in fetal and neonatal brain development. STUDY DESIGN: This was a secondary analysis of the randomized clinical trial Improving Mothers for a Better Prenatal Care Trial Barcelona that was conducted in Barcelona, Spain, from 2017 to 2020. Participants with singleton pregnancies were randomly allocated into 3 groups, namely Mediterranean diet intervention, stress reduction program, or usual care. Participants in the Mediterranean diet group received monthly individual sessions and free provision of extra-virgin olive oil and walnuts. Pregnant women in the stress reduction group underwent an 8-week mindfulness-based stress reduction program adapted for pregnancy. Magnetic resonance imaging of 90 fetal brains was performed at 36 to 39 weeks of gestation and the Neonatal Neurobehavioral Assessment Scale was completed for 692 newborns at 1 to 3 months. Fetal outcomes were the total brain volume and lobular or regional volumes obtained from a 3-dimensional reconstruction and semiautomatic segmentation of magnetic resonance images. Neonatal outcomes were the 6 clusters scores of the Neonatal Neurobehavioral Assessment Scale. Multiple regression analyses were conducted to assess the association between the interventions and the fetal and neonatal outcomes. RESULTS: When compared with the usual care group, the offspring exposed to a maternal Mediterranean diet had a larger total fetal brain volume (mean, 284.11 cm3; standard deviation, 23.92 cm3 vs 294.01 cm3; standard deviation, 26.29 cm3; P=.04), corpus callosum (mean, 1.16 cm3; standard deviation, 0.19 cm3 vs 1.26 cm3; standard deviation, 0.22 cm3; P=.03), and right frontal lobe (44.20; standard deviation, 4.09 cm3 vs 46.60; standard deviation, 4.69 cm3; P=.02) volumes based on magnetic resonance imaging measures and higher scores in the Neonatal Neurobehavioral Assessment Scale clusters of autonomic stability (mean, 7.4; standard deviation, 0.9 vs 7.6; standard deviation, 0.7; P=.04), social interaction (mean, 7.5; standard deviation, 1.5 vs 7.8; standard deviation, 1.3; P=.03), and range of state (mean, 4.3; standard deviation, 1.3 vs 4.5; standard deviation, 1.0; P=.04). When compared with the usual care group, offspring from the stress reduction group had larger fetal left anterior cingulate gyri volume (1.63; standard deviation, 0.32 m3 vs 1.79; standard deviation, 0.30 cm3; P=.03) based on magnetic resonance imaging and higher scores in the Neonatal Neurobehavioral Assessment Scale for regulation of state (mean, 6.0; standard deviation, 1.8 vs 6.5; standard deviation, 1.5; P<.01). CONCLUSION: Maternal structured lifestyle interventions involving the promotion of a Mediterranean diet or stress reduction during pregnancy were associated with changes in fetal and neonatal brain development.