Cardiovascular Ultrasound Predictors for Brain Alterations in Fetuses With Heart Disease: An Exploratory Review of the Literature.

OBJECTIVE: To identify cardiovascular ultrasound predictors for brain anomalies in fetuses with heart disease. METHODS: A literature search was performed in the following databases: MEDLINE through OVID, EMBASE, Cochrane Registry Center for Controlled Trials (CENTRAL), and LILACS, from their inception until May 2023. Clinical studies, cross-sectional studies, case-control studies, cohorts, and systematic reviews were included. Data extraction was performed, and the risk of bias was assessed using the QUADAS-2 tool. RESULTS: Among 2705 studies evaluated, after filtering information, 10 articles were selected that met the inclusion criteria. These studies noted the following outcomes: a decrease in fetal head circumference, changes in brain maturation measured in days, decreased depth of brain fissures, and a decrease in total brain volume. The studies show a statistically significant correlation with the presence of the following cardiovascular predictors: low or mixed oxygen content in the ascending aorta (p < 0.001), retrograde flow in the aortic arch (p < 0.001), lower z values of the MCA-PI (p < 0.05), higher UA-PI z values (p < 0.01), and lower CPR (p < 0.05). In addition, lower values of left ventricular flow (p < 0.01), ductus arteriosus (p < 0.0001), and combined cardiac output index (p < 0.01) were reported. CONCLUSIONS: This review describes the most relevant evidence correlating the effects of hemodynamic changes that lead to states of chronic hypoxia related to the aforementioned changes in the central nervous system.

Severe and unclassifiable tremor.

BACKGROUND: Patients often exhibit very severe or disabling forms of tremor that cannot be clearly characterized. OBJECTIVE: To present a series of 37 cases of tremor considered unclassifiable. Patients diagnosed with essential tremor according to criteria of the International Parkinson Disease and Movement Disorder Society (IPDMDS), who had been previously studied, were included as controls. All patients underwent a battery of tests between 2019 and 2022, which enabled us to compare them. METHODS: Relevant demographic and clinical information were collected. The following tools were applied: the Mini-Mental State Examination (MMSE); the Hospital Anxiety and Depression Scale (HADS); the Fahn-Tolosa-Marín Tremor Rating Scale (TRS); and the Quality of Life in Essential Tremor (QUEST). A simple brain magnetic resonance imaging (MRI) scan was performed for all patients. The categorical variables were compared using the Chi-squared test and the t-test with Fisher correction if appropriate, and the quantitative variables were compared through the two-tailed Student t-test. Values of p ≤ 0.01 were considered statistically significant. RESULTS: The cases presented higher scores on the anxiety and depression subscales of the HADS than the controls (p ≤ 0.006 and 0.000 respectively). In all domains of the TRS, the cases scored significantly higher, as well as in the QUEST. History of enolism was higher among the controls, and history of orthostasis and rest tremor was higher among the cases (p ≤ 0.000). Cerebellar atrophy was present in every patient in the case group, and in 24 subjects in the control group. Dystonia was observed in 7 subjects in the case group, and in none of the patients in the control group. CONCLUSION: There are patients with unclassifiable and extremely disabling tremors who respond poorly to the pharmacological therapy options.

ANTECEDENTES: Os pacientes muitas vezes apresentam formas muito graves ou incapacitantes de tremor que não podem ser claramente caracterizadas. OBJETIVO: O objetivo deste trabalho foi apresentar uma série de 37 casos de tremor considerados inclassificáveis. Pacientes diagnosticados com tremor essencial de acordo com os critérios da International Parkinson Disease and Movement Disorder Society (IPDMDS), já estudados anteriormente, foram incluídos como controles. Todos os pacientes foram submetidos a exames entre 2019 e 2022 para permitir sua comparaç ão. MéTODOS: As informaç ões demográficas e clínicas relevantes foram coletadas. As seguintes ferramentas foram aplicadas: o Miniexame do Estado Mental (MEEM), a Escala Hospitalar de Ansiedade e Depressão (HADS, do inglês Hospital Anxiety and Depression Scale), a Escala de Avaliaç ão de Tremor de Fahn-Tolosa-Marín (TRS, do inglês Fahn-Tolosa-Marín Tremor Rating Scale) e a Qualidade de Vida em Tremor Essencial (QUEST, do inglês Quality of Life in Essential Tremor). Uma ressonância magnética simples do cérebro foi realizada em todos os pacientes. As variáveis categóricas foram comparadas pelo teste qui-quadrado e pelo teste t com correç ão de Fisher, se apropriado, enquanto as variáveis quantitativas foram comparadas por meio do teste t de Student bicaudal. Valores de p ≤ 0,01 foram considerados estatisticamente significativos. RESULTADOS: Os casos apresentaram pontuaç ões maiores nas subescalas de ansiedade e depressão do HADS do que os controles (p ≤ 0,006 e 0,000, respectivamente). Em todos os domínios do TRS, a pontuaç ão dos casos foi significativamente maior, assim como no QUEST. O histórico de enolismo foi maior entre os controles e o histórico de ortostase e tremor em repouso foi maior entre os casos (p ≤ 0,000). A atrofia cerebelar foi apresentada por todos os pacientes do grupo de casos e em 24 indivíduos do grupo de controle. A distonia foi observada em sete indivíduos do grupo de casos e em nenhum dos pacientes do grupo controle. CONCLUSãO: Há pacientes com tremores inclassificáveis e extremamente incapacitantes que respondem mal às opç ões terapêuticas farmacológicas.

Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol-SEPSIS-BRAIN.

INTRODUCTION: Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. METHODS: Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. ETHICS AND DISSEMINATION: The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. TRIAL REGISTRATION: Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

Toxic leukoencephalopathies.

Toxic-metabolic encephalopathies are a group of disorders in which an exogenous or endogenous substance leads to transient or permanent neuronal damage. It is an important cause of potentially reversible acute encephalopathy syndrome. The signs and symptoms of toxic encephalopathies may be relatively nonspecific, and toxicologic tests are not always widely available. Imaging plays a key role in determining the most probable diagnosis, pointing to the next steps of investigation, and providing prognostic information. In this chapter, we review the main acquired toxic-metabolic leukoencephalopathies, commenting on their pathophysiology, imaging patterns, and rationale for an adequate diagnosis in detail.

APIS: a paired CT-MRI dataset for ischemic stroke segmentation - methods and challenges.

Stroke, the second leading cause of mortality globally, predominantly results from ischemic conditions. Immediate attention and diagnosis, related to the characterization of brain lesions, play a crucial role in patient prognosis. Standard stroke protocols include an initial evaluation from a non-contrast CT to discriminate between hemorrhage and ischemia. However, non-contrast CTs lack sensitivity in detecting subtle ischemic changes in this phase. Alternatively, diffusion-weighted MRI studies provide enhanced capabilities, yet are constrained by limited availability and higher costs. Hence, we idealize new approaches that integrate ADC stroke lesion findings into CT, to enhance the analysis and accelerate stroke patient management. This study details a public challenge where scientists applied top computational strategies to delineate stroke lesions on CT scans, utilizing paired ADC information. Also, it constitutes the first effort to build a paired dataset with NCCT and ADC studies of acute ischemic stroke patients. Submitted algorithms were validated with respect to the references of two expert radiologists. The best achieved Dice score was 0.2 over a test study with 36 patient studies. Despite all the teams employing specialized deep learning tools, results reveal limitations of computational approaches to support the segmentation of small lesions with heterogeneous density.

Telomere length as a biomarker in multiple sclerosis.

BACKGROUND: Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS). OBJECTIVE: We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects. METHODS: Prospective 2-year study including two cohorts of young (18-35 years) and elderly (⩾50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay. RESULTS: Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration (p = 0.05), smoking (p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT (p = 0.00007), high-efficacy therapies (p = 0.001), brain lesion volume (BLV) (p = 0.011), and number of T2 lesions (p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm3 and white matter volume 1.78 cm3. CONCLUSION: LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS.

Persistent homology reveals robustness loss in inhaled substance abuse rs-fMRI networks.

Analyzing functional brain activity through functional magnetic resonance imaging (fMRI) is commonly done using tools from graph theory for the analysis of the correlation matrices. A drawback of these methods is that the networks must be restricted to values of the weights of the edges within certain thresholds and there is no consensus about the best choice of such thresholds. Topological data analysis (TDA) is a recently-developed tool in algebraic topology which allows us to analyze networks through combinatorial spaces obtained from them, with the advantage that all the possible thresholds can be considered at once. In this paper we applied TDA, in particular persistent homology, to study correlation matrices from rs-fMRI, and through statistical analysis, we detected significant differences between the topological structures of adolescents with inhaled substance abuse disorder (ISAD) and healthy controls. We interpreted the topological differences as indicative of a loss of robustness in the functional brain networks of the ISAD population.

Analysis of brain activity for speech stimuli and child development of an infant with neurosyphilis: case report. / Análise da atividade cerebral para estímulos de fala e desenvolvimento infantil de um lactente com neurossífilis: relato de caso.

Neurosyphilis is an infection of the central nervous system caused by Treponema pallidum and may be symptomatic or asymptomatic in children with congenital syphilis. This study aims to describe the cortical activation pattern of a four-month-old infant with neurosyphilis using functional near-infrared spectroscopy (fNIRS). Born at term weighing 3,475 kg, she presented a Venereal Disease Research Laboratory (VDRL) test of 1:32 and changes in the cerebrospinal fluid test. She underwent treatment with crystalline penicillin for 10 days before discharge from the hospital. In the audiological evaluation, she presented normal tympanometry, otoacoustic emissions evoked by transient stimulus, brainstem auditory evoked potential with click stimulus at 80 and 30 dB nHL bilaterally. The Bayley III Scale was applied to assess language, cognition and motor development, showing delays in expressive language and broad motor skills. In the fNIRS acquisition, data were collected through 20 channels divided between the cerebral hemispheres. The /ba/ and /da/ stimuli were presented at 40 dB HL with the Psychopy software through a headphone. Data analysis used the MNE and MNE-NIRS toolboxes in the Spyder environment. The average by channel, ROI, and condition was exported for analysis. A similar theta coefficient was observed between the conditions and channels evaluated in both cerebral hemispheres, with a greater amplitude of oxyhemoglobin (HbO) being observed in the anterior position when compared to the posterior region of the temporal lobe. Therefore, this case report highlights the need to monitor the child development of babies with neurosyphilis.

A neurossífilis é uma infecção do sistema nervoso central causada pelo Treponema pallidum, podendo ser sintomática ou assintomática nas crianças com sífilis congênita. Este estudo visa descrever o padrão de ativação cortical de uma lactente de quatro meses com neurossífilis utilizando o funcional near-infrared spectroscopy (fNIRS). Nascida a termo com 3.475 Kg, apresentou teste Venereal Disease Research Laboratory (VDRL) de 1:32 e alteração no exame de líquor cefalorraquidiano. Realizou tratamento com penicilina cristalina por 10 dias antes da alta hospitalar. Na avaliação audiológica apresentou normalidade na timpanometria, emissões otoacústicas evocadas por estímulo transiente, potencial evocado auditivo de tronco encefálico com estímulo clique a 80 e 30 dB nNA bilateralmente. Foi aplicada a Escala Bayley III para a avaliação do desenvolvimento de linguagem, cognição e motor, apresentando atrasos na linguagem expressiva e no motor amplo. Na aquisição do fNIRS os dados foram coletados por 20 canais divididos entre os hemisférios cerebrais. Os estímulos /ba/ e /da/ foram apresentados a 40 dB NA com o auxílio do programa Psychopy por um fone de ouvido. A análise dos dados utilizou as toolboxes MNE e MNE-NIRS no ambiente Spyder. A média por canal, ROI e condição foi exportada para análise. Observou-se um coeficiente theta similar entre as condições e canais avaliados de ambos os hemisférios cerebrais, sendo observado maior amplitude da oxihemoglobina (HbO) na posição anterior quando comparados a região posterior do lobo temporal. Desta forma, este relato de caso evidencia a necessidade de monitoramento do desenvolvimento infantil de lactentes com neurossífilis.

Subcortical Aphasia: An Update.

PURPOSE OF REVIEW: This review aims to rediscuss the leading theories concerning the role of basal ganglia and the thalamus in the genesis of aphasic symptoms in the absence of gross anatomical lesions in cortical language areas as assessed by conventional neuroimaging studies. RECENT FINDINGS: New concepts in language processing and modern neuroimaging techniques have enabled some progress in resolving the impasse between the current dominant theories: (a) direct and specific linguistic processing and (b) subcortical structures as processing relays in domain-general functions. Of particular interest are studies of connectivity based on functional magnetic resonance imaging (MRI) and tractography that highlight the impact of white matter pathway lesions on aphasia development and recovery. Connectivity studies have put into evidence the central role of the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), and uncinate fasciculus (UF) in the genesis of aphasia. Regarding the thalamus, its involvement in lexical-semantic processing through modulation of the frontal cortex is becoming increasingly apparent.

Directed brain interactions over time: A resting-state EEG comparison between schizophrenia and healthy individuals.

Understanding the neurophysiological mechanisms of schizophrenia (SZ) is one of the challenges of neuroscience. Many anatomical and functional studies have pointed to problems in brain connectivity in SZ individuals. However, little is known about the relationships between specific brain regions and impairments in brain connectivity in SZ individuals. Herein we propose a new approach using time-varying graphs and the motif synchronization method to build dynamic brain functional networks (BFNs). Dynamic BFNs were constructed from resting-state electroencephalography (rs-EEG) of 14 schizophrenia (SZ) individuals and 14 healthy controls (HCs). BFNs were evaluated based on the percentage of synchronization importance between a pair of regions (considering external and internal interactions) over time. We found differences in the directed interaction between brain regions in SZ individuals compared to the control group. Our method revealed low bilaterally directed interactions between the temporal lobes in SZ individuals compared to HCs, indicating a potential link between altered brain connectivity and the characteristic symptoms of schizophrenia. From a clinical perspective, these results shed light on developing new therapeutic approaches targeting these specific neural interactions that are altered in individuals with SZ. This knowledge allows the application of better interventions focused on restoring or compensating for interrupted connectivity patterns.

Educational disparities in brain health and dementia across Latin America and the United States.

BACKGROUND: Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown. METHODS: A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type. RESULTS: Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions. DISCUSSION: The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research. HIGHLIGHTS: Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions.

In Vivo Neural Tract Tracing Procedures: Unravelling Neural Hodology Using Fluorescent and Non-fluorescent Neural Tract Tracers, Optogenetic Approach, and Diffusion Tensor Neurotractography Protocols.

Fluorescent and non-fluorescent neural tract tracers enable the investigation of neural pathways in both peripheral and central nervous systems in laboratory animals demonstrating images with high resolution and great anatomic precision. Anterograde and retrograde viral tracers are important cutting-edge tools for neuroanatomical mapping. The optogenetic consists of an advanced alternative for in vivo neural tract tracing procedures, fundamentally considering the possibility to dissect and modulate pathways either exciting or inhibiting neural circuits in laboratory animals. The neurotractography by diffusion tensor imaging in vivo procedures enables the study of neural pathways in humans with reasonable accuracy. Here we describe the procedure of classical anatomic neural tract tracing and modern optogenetic technique performed in anima vili in addition to different diffusion tensor neurotractography performed in anima nobili.

Patients recovering from COVID-19 who presented with anosmia during their acute episode have behavioral, functional, and structural brain alterations.

Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r = - 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up.

Contributions of neuroimaging in central poststroke pain: a review.

BACKGROUND: Central neuropathic poststroke pain (CNPSP) affects up to 12% of patients with stroke in general and up to 18% of patients with sensory deficits. This pain syndrome is often incapacitating and refractory to treatment. Brain computed tomography and magnetic resonance imaging (MRI) are widely used methods in the evaluation of CNPSP. OBJECTIVE: The present study aims to review the role of neuroimaging methods in CNPSP. METHODS: We performed a literature review of the main clinical aspects of CNPSP and the contribution of neuroimaging methods to study its pathophysiology, commonly damaged brain sites, and possible differential diagnoses. Lastly, we briefly mention how neuroimaging can contribute to the non-pharmacological CNPSP treatment. Additionally, we used a series of MRI from our institution to illustrate this review. RESULTS: Imaging has been used to explain CNPSP pathogenesis based on spinothalamic pathway damage and connectome dysfunction. Imaging locations associated with CNPSP include the brainstem (mainly the dorsolateral medulla), thalamus (especially the ventral posterolateral/ventral posteromedial nuclei), cortical areas such as the posterior insula and the parietal operculum, and, more recently, the thalamocortical white matter in the posterior limb of the internal capsule. Imaging also brings the prospect of helping search for new targets for non-pharmacological treatments for CNPSP. Other neuropathic pain causes identified by imaging include syringomyelia, multiple sclerosis, and herniated intervertebral disc. CONCLUSION: Imaging is a valuable tool in the complimentary evaluation of CNPSP patients in clinical and research scenarios.

ANTECEDENTES: A dor neuropática central pós-acidente vascular cerebral (DNPAVC) afeta até 12% dos pacientes com AVC em geral e até 18% dos pacientes com déficits sensoriais. Essa síndrome dolorosa costuma ser incapacitante e refratária ao tratamento. A tomografia computadorizada e a ressonância magnética do cérebro são métodos amplamente utilizados na avaliação da DNPAVC. OBJETIVO: Este estudo tem como objetivo revisar o papel dos métodos de neuroimagem na DNPAVC. MéTODOS: Realizamos uma revisão da literatura sobre os principais aspectos clínicos da DNPAVC e a contribuição dos métodos de neuroimagem para estudar a fisiopatologia da DNPAVC, locais cerebrais comumente lesados na DNPAVC e possíveis diagnósticos diferenciais. Por fim, mencionamos brevemente como a neuroimagem pode contribuir no tratamento não farmacológico da DNPAVC. Além disso, utilizamos uma série de imagens de ressonância magnética da nossa instituição para ilustrar esta revisão. RESULTADOS: Os exames de imagem têm sido usados para explicar a patogênese da DNPAVC com base no dano da via espinotalâmica e na disfunção do conectoma. Os locais de imagem associados à DNPAVC incluem o tronco cerebral (principalmente o bulbo dorsolateral), o tálamo (especialmente os núcleos ventral posterolateral/ventral posteromedial), áreas corticais como a ínsula posterior e o opérculo parietal e, mais recentemente, a substância branca tálamo-cortical no membro posterior da cápsula interna. Os exames de imagem também trazem a perspectiva de auxiliar na busca de novos alvos para tratamentos não farmacológicos para DNPAVC. Outras causas de dor neuropática identificadas por exames de imagem incluem siringomielia, esclerose múltipla e hérnia de disco intervertebral. CONCLUSãO: Os exames de imagem são uma ferramenta valiosa na avaliação complementar de pacientes com DNPAVC em cenários clínicos e de pesquisa.

Omics-derived biological modules reflect metabolic brain changes in Alzheimer's disease.

INTRODUCTION: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive. METHODS: Here, we integrated [18F]FDG-PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel-wise linear regression analysis. RESULTS: Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG-PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak-t(223) = 4.86, P value < 0.001) and zinc-finger-related regulatory units (peak-t(223) = 3.90, P value < 0.001). DISCUSSION: By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity-associated genes and zinc-finger-related regulatory units are highly associated with brain metabolic changes in AD. HIGHLIGHTS: We conducted an integrated analysis of system-based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) at the voxel level in Alzheimer's disease (AD). The biological process of serine/threonine kinase activity was the most associated with [18F]FDG-PET in the AD brain. Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG-PET. Zinc-finger transcription factor targets were associated with AD brain [18F]FDG-PET metabolism.

Comparison of baseline correction algorithms for in vivo 1H-MRS.

Proton MRS is used clinically to collect localized, quantitative metabolic data from living tissues. However, the presence of baselines in the spectra complicates accurate MRS data quantification. The occurrence of baselines is not specific to short-echo-time MRS data. In short-echo-time MRS, the baseline consists typically of a dominating macromolecular (MM) part, and can, depending on B0 shimming, poor voxel placement, and/or localization sequences, also contain broad water and lipid resonance components, indicated by broad components (BCs). In long-echo-time MRS, the MM part is usually much smaller, but BCs may still be present. The sum of MM and BCs is denoted by the baseline. Many algorithms have been proposed over the years to tackle these artefacts. A first approach is to identify the baseline itself in a preprocessing step, and a second approach is to model the baseline in the quantification of the MRS data themselves. This paper gives an overview of baseline handling algorithms and also proposes a new algorithm for baseline correction. A subset of suitable baseline removal algorithms were tested on in vivo MRSI data (semi-LASER at TE = 40 ms) and compared with the new algorithm. The baselines in all datasets were removed using the different methods and subsequently fitted using spectrIm-QMRS with a TDFDFit fitting model that contained only a metabolite basis set and lacked a baseline model. The same spectra were also fitted using a spectrIm-QMRS model that explicitly models the metabolites and the baseline of the spectrum. The quantification results of the latter quantification were regarded as ground truth. The fit quality number (FQN) was used to assess baseline removal effectiveness, and correlations between metabolite peak areas and ground truth models were also examined. The results show a competitive performance of our new proposed algorithm, underscoring its automatic approach and efficiency. Nevertheless, none of the tested baseline correction methods achieved FQNs as good as the ground truth model. All separately applied baseline correction methods introduce a bias in the observed metabolite peak areas. We conclude that all baseline correction methods tested, when applied as a separate preprocessing step, yield poorer FQNs and biased quantification results. While they may enhance visual display, they are not advisable for use before spectral fitting.

Feasibility and success of a non-sedated brain MRI training protocol in 7-year-old children from rural and semi-rural Colombia.

BACKGROUND: Brain magnetic resonance imaging (MRI) is a crucial tool for clinical evaluation of the brain and neuroscience research. Obtaining successful non-sedated MRI in children who live in resource-limited settings may be an additional challenge. OBJECTIVE: To present a feasibility study of a novel, low-cost MRI training protocol used in a clinical research study in a rural/semi-rural region of Colombia and to examine neurodevelopmental factors associated with successful scans. MATERIALS AND METHODS: Fifty-seven typically developing Colombian children underwent a training protocol and non-sedated brain MRI at age 7. Group training utilized a customized booklet, an MRI toy set, and a simple mock scanner. Children attended MRI visits in small groups of two to three. Resting-state functional and structural images were acquired on a 1.5-Tesla scanner with a protocol duration of 30-40 minutes. MRI success was defined as the completion of all sequences and no more than mild motion artifact. Associations between the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Movement Assessment Battery for Children (MABC), Behavioral Rating Inventory of Executive Function (BRIEF), Child Behavior Checklist (CBCL), and Adaptive Behavior Assessment System (ABAS) scores and MRI success were analyzed. RESULTS: Mean (SD) age at first MRI attempt was 7.2 (0.2) years (median 7.2 years, interquartile range 7.1-7.3 years). Twenty-six (45.6%) participants were male. Fifty-one (89.5%) children were successful across two attempts; 44 (77.2%) were successful on their first attempt. Six (10.5%) were unsuccessful due to refusal or excessive motion. Age, sex, and scores across all neurodevelopmental assessments (MABC, TVIP, ABAS, BRIEF, CBCL, NIH Toolbox Flanker, NIH Toolbox Pattern Comparison, WPPSI) were not associated with likelihood of MRI success (P=0.18, 0.19, 0.38, 0.92, 0.84, 0.80, 1.00, 0.16, 0.75, 0.86, respectively). CONCLUSION: This cohort of children from a rural/semi-rural region of Colombia demonstrated comparable MRI success rates to other published cohorts after completing a low-cost MRI familiarization training protocol suitable for low-resource settings. Achieving non-sedated MRI success in children in low-resource and international settings is important for the continuing diversification of pediatric research studies.

Primary lateral sclerosis associated with PSEN1 Pro284Leu variant in a Colombian family: Clinical and neuropathological features.

INTRODUCTION: This study investigates primary lateral sclerosis (PLS) as a rare manifestation of the presenilin 1 (PSEN1) NM_000021 c.851C > T p.Pro284Leu variant in three siblings of a Colombian family, outlining its clinical and neuropathological features and their relationship to Alzheimer's disease (AD). METHODS: Data were gathered using clinical evaluations, next-generation genetic sequencing, magnetic resonance imaging, biomarker analysis, and neuropathological examination. RESULTS: Carriers of the PSEN1 Pro284Leu variant exhibited classic PLS symptoms, including unilateral onset and bulbar syndromes, along with cognitive decline. Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter. DISCUSSION: Our findings suggest an overlap between PLS and AD pathology in PSEN1 variant carriers. Results support considering PLS when diagnosing AD-related motor syndromes and including PSEN1 evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS-AD relationship, informing future treatments and clinical trials. HIGHLIGHTS: Pathogenic variants in presenilin 1 (PSEN1) can manifest as hereditary primary lateral sclerosis PSEN1 Pro284Leu carriers present motor, cognitive, and behavioral alterations  Cases had corticospinal tract microgliosis and severe Aß pathology in motor cortex  There was no evidence of amyloid deposition in the spinal cord white matter  All the neuropathology images are available for online visualization  Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts.

Greater Neighborhood Disadvantage Is Associated with Alterations in Fetal Functional Brain Network Structure.

OBJECTIVE: To determine the association between neighborhood disadvantage (ND) and functional brain development of in utero fetuses. STUDY DESIGN: We conducted an observational study using Social Vulnerability Index (SVI) scores to assess the impact of ND on a prospectively recruited sample of healthy pregnant women from Washington, DC. Using 79 functional magnetic resonance imaging scans from 68 healthy pregnancies at a mean gestational age of 33.12 weeks, we characterized the overall functional brain network structure using a graph metric approach. We used linear mixed effects models to assess the relationship between SVI and gestational age on 5 graph metrics, adjusting for multiple scans. RESULTS: Exposure to greater ND was associated with less well integrated functional brain networks, as observed by longer characteristic path lengths and diminished global efficiency (GE), as well as diminished small world propensity (SWP). Across gestational ages, however, the association between SVI and network integration diminished to a negligible relationship in the third trimester. Conversely, SWP was significant across pregnancy, but the relationship changed such that there was a negative association with SWP earlier in the second trimester that inverted around the transition to the third trimester to a positive association. CONCLUSIONS: These data directly connect ND and altered functional brain maturation in fetuses. Our results suggest that, even before birth, proximity to environmental stressors in the wider neighborhood environment are associated with altered brain development.

Regional-based static and dynamic alterations in Alzheimer disease: a longitudinal study.

BACKGROUND: Alzheimer disease (AD) leads to cognitive decline and alters functional connectivity (FC) in key brain regions. Resting-state functional magnetic resonance imaging (rs-fMRI) assesses these changes using static-FC for overall correlation and dynamic-FC for temporal variability. OBJECTIVE: In AD, there is altered FC compared to normal conditions. The present study investigates possible region-specific functional abnormalities occurring longitudinally over 1 year. Our aim is to evaluate the potential usefulness of the static and dynamic approaches in identifying biomarkers of AD progression. METHODS: The study involved 15 AD and 20 healthy participants from the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) database, tracked over 2 visits within 1 year. Using constrained-independent component analysis, we assessed FC changes across 80-regions of interest in AD over the year, examining both static and dynamic conditions. RESULTS: The average regional FC decreased in AD compared to healthy subjects at baseline and after 1 year. The dynamic condition identifies similarities with a few additional changes in the FC compared to the static condition. In both analyses, the baseline assessment revealed reduced connectivity between the following regions: right-middle-occipital and left-superior-occipital, left-hippocampus and right-postcentral, left-lingual and left-fusiform, and precuneus and left-thalamus. Additionally, increased connectivity was found between the left-superior-occipital and precuneus regions. In the 1-year AD assessment, increased connectivity was noted between the right-superior-temporal-pole and right-insular, right-hippocampus and left-caudate, right-middle-occipital and right-superior-temporal-pole, and posterior-cingulate-cortex and middle-temporal-pole regions. CONCLUSION: Significant changes were observed at baseline in the frontal, occipital, and core basal-ganglia regions, progressing towards the temporal lobe and subcortical regions in the following year. After 1 year, we observed the aforementioned region-specific neurological differences in AD, significantly aiding diagnosis and disease tracking.

ANTECEDENTES: A doença de Alzheimer (DA) leva ao declínio cognitivo e altera a conectividade funcional (CF) em regiões-chave do cérebro. A ressonância magnética funcional em estado de repouso (rs-fMRI) avalia essas alterações usando CF estática para correlação geral e CF dinâmica para variabilidade temporal. OBJETIVO: Na DA, há CF alterada em relação às condições normais. O presente estudo investiga possíveis anormalidades funcionais específicas da região que ocorrem longitudinalmente ao longo de um ano. Nosso objetivo é avaliar a utilidade potencial das abordagens estáticas e dinâmicas na identificação de biomarcadores da progressão da DA. MéTODOS: O estudo envolveu 15 participantes com DA e 20 participantes saudáveis do banco de dados da Iniciativa de Neuroimagem da Doença de Alzheimer 2 (ADNI2), rastreados em duas visitas no período de um ano. Usando análise de componentes independentes e restritos, avaliamos as mudanças de CF em 80 regiões de interesse na DA ao longo do ano, examinando condições estáticas e dinâmicas. RESULTADOS: A CF regional média diminuiu na DA em comparação com indivíduos saudáveis no início do estudo e após um ano. A condição dinâmica identifica semelhanças com algumas alterações adicionais na CF em comparação com a condição estática. Em ambas as análises, a avaliação inicial revelou conectividade reduzida entre as seguintes regiões: occipital médio direito e occipital superior esquerdo, hipocampo esquerdo e pós-central direito, lingual esquerdo e fusiforme esquerdo, e precuneus e tálamo esquerdo. Além disso, foi encontrada maior conectividade entre as regiões occipital superior esquerda e precuneus. Na avaliação de DA de um ano, foi observada conectividade aumentada entre o polo temporal superior direito e o insular direito, o hipocampo direito e o caudado esquerdo, occipital médio direito e o polo temporal superior direito, e regiões posteriores do córtex cingulado e do polo temporal médio. CONCLUSãO: Mudanças significativas foram observadas no início do estudo nas regiões frontal, occipital e dos gânglios basais centrais, progredindo em direção ao lobo temporal e regiões subcorticais no ano seguinte. Após um ano, observamos as diferenças neurológicas específicas da região acima mencionadas na DA, auxiliando significativamente no diagnóstico e no rastreamento da doença.