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1.
J Headache Pain ; 22(1): 75, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273945

RESUMO

BACKGROUND: To describe interictal brain structural and metabolic differences between patients with episodic migraine (EM), chronic migraine (CM) and healthy controls (HC). METHODS: This is an exploratory study including right-handed age-matched women with EM, CM and HC. On the same day, a sequential interictal scan was performed with 18FDG-PET and MRI. 3D T1-weighted images were segmented with FreeSurfer, normalized to a reference atlas and the mean values of metabolism, cortical thickness (CTh) and local gyrification index (IGI) were determined. Groups were compared using age-adjusted linear models, corrected for multiple comparisons. 18FDG-PET measurements between groups were also analysed adjusting by patient's age, CTh and lGI. The variables independently associated with diagnosis were obtained using a logistic regression analysis. RESULTS: Fifteen patients (8 EM, 7 CM) and 11 HC were included. Morphometric data showed an increased CTh in 6 frontal areas (L/R-Caudal Middle Frontal, L/R-Rostral Middle Frontal, L-Medial Orbitofrontal and L-Superior Frontal) in CM patients compared to HC without differences for IGI. The structural adjusted analysis in CM showed a statistically significantly hypometabolism in 9 frontal areas (L-Lateral Orbitofrontal, L/R-Medial Orbitofrontal, L-Frontal Superior, R-Frontal pole, R-Parts Triangularis, L/R-Paracentral and R-Precentral) and 7 temporal areas (L/R-Insula, L/R-Inferior temporal, L/R-Temporal pole and R-Banks superior temporal sulcus) compared to HC. EM patients presented intermediate metabolic values ​​between EM and HC (non-significant). CONCLUSIONS: CM patients showed frontotemporal hypometabolism and increased frontal cortical thickness when compared to HC that may explain some cognitive and behavioural pain-processing and sensory integration alterations in CM patients. Combined information from sequential or simultaneous PET and MRI could optimize the study of complex functional neurological disorders such as migraine.


Assuntos
Fluordesoxiglucose F18 , Transtornos de Enxaqueca , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Transtornos de Enxaqueca/diagnóstico por imagem , Tomografia por Emissão de Pósitrons
2.
Nat Protoc ; 16(7): 3241-3263, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34075229

RESUMO

Measurements of neuronal activity across brain areas are important for understanding the neural correlates of cognitive and motor processes such as attention, decision-making and action selection. However, techniques that allow cellular resolution measurements are expensive and require a high degree of technical expertise, which limits their broad use. Wide-field imaging of genetically encoded indicators is a high-throughput, cost-effective and flexible approach to measure activity of specific cell populations with high temporal resolution and a cortex-wide field of view. Here we outline our protocol for assembling a wide-field macroscope setup, performing surgery to prepare the intact skull and imaging neural activity chronically in behaving, transgenic mice. Further, we highlight a processing pipeline that leverages novel, cloud-based methods to analyze large-scale imaging datasets. The protocol targets laboratories that are seeking to build macroscopes, optimize surgical procedures for long-term chronic imaging and/or analyze cortex-wide neuronal recordings. The entire protocol, including steps for assembly and calibration of the macroscope, surgical preparation, imaging and data analysis, requires a total of 8 h. It is designed to be accessible to laboratories with limited expertise in imaging methods or interest in high-throughput imaging during behavior.


Assuntos
Comportamento Animal/fisiologia , Córtex Cerebral/citologia , Córtex Cerebral/diagnóstico por imagem , Imageamento Tridimensional/métodos , Animais , Artefatos , Hemodinâmica/fisiologia , Camundongos Transgênicos , Crânio/cirurgia
3.
Nat Commun ; 12(1): 3561, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117229

RESUMO

Active responses to stressors involve motor planning, execution, and feedback. Here we identify an insular cortex to BNST (insula→BNST) circuit recruited during restraint stress-induced active struggling that modulates affective behavior. We demonstrate that activity in this circuit tightly follows struggling behavioral events and that the size of the fluorescent sensor transient reports the duration of the struggle event, an effect that fades with repeated exposure to the homotypic stressor. Struggle events are associated with enhanced glutamatergic- and decreased GABAergic signaling in the insular cortex, indicating the involvement of a larger circuit. We delineate the afferent network for this pathway, identifying substantial input from motor- and premotor cortex, somatosensory cortex, and the amygdala. To begin to dissect these incoming signals, we examine the motor cortex input, and show that the cells projecting from motor regions to insular cortex are engaged shortly before struggle event onset. This study thus demonstrates a role for the insula→BNST pathway in monitoring struggling activity and regulating affective behavior.


Assuntos
Aprendizagem da Esquiva , Comportamento Animal , Córtex Cerebral/fisiologia , Tonsila do Cerebelo , Animais , Encéfalo , Córtex Cerebral/diagnóstico por imagem , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios , Córtex Somatossensorial
4.
Medicine (Baltimore) ; 100(23): e26280, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115027

RESUMO

ABSTRACT: Despite lacking aphasia seen with left hemisphere (LH) infarcts involving the middle cerebral artery territory, right hemisphere (RH) strokes can result in significant difficulties in affective prosody. These impairments may be more difficult to identify but lead to significant communication problems.We determine if evaluation of singing can accurately identify stroke patients with cortical RH infarcts at risk for prosodic impairment who may benefit from rehabilitation.A prospective cohort of 36 patients evaluated with acute ischemic stroke was recruited. Participants underwent an experimental battery evaluating their singing, prosody comprehension, and prosody production. Singing samples were rated by 2 independent reviewers as subjectively "normal" or "abnormal," and analyzed for properties of the fundamental frequency. Relationships between infarct location, singing, and prosody performance were evaluated using t tests and chi-squared analysis.Eighty percent of participants with LH cortical strokes were unable to successfully complete any of the tasks due to severe aphasia. For the remainder, singing ratings corresponded to stroke location for 68% of patients. RH cortical strokes demonstrated a lower mean fundamental frequency while singing than those with subcortical infarcts (176.8 vs 130.4, P = 0.02). They also made more errors on tasks of prosody comprehension (28.6 vs 16.0, P < 0.001) and production (40.4 vs 18.4, P < 0.001).Patients with RH cortical infarcts are more likely to exhibit impaired prosody comprehension and production and demonstrate the poor variation of tone when singing compared to patients with subcortical infarcts. A simple singing screen is able to successfully identify patients with cortical lesions and potential prosodic deficits.


Assuntos
Córtex Cerebral , Infarto Cerebral , Canto/fisiologia , Inteligibilidade da Fala/fisiologia , Medida da Produção da Fala/métodos , Sintomas Afetivos/diagnóstico , Sintomas Afetivos/etiologia , Idoso , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Infarto Cerebral/diagnóstico , Infarto Cerebral/fisiopatologia , Infarto Cerebral/psicologia , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , AVC Isquêmico/diagnóstico , Masculino
5.
Arch Ital Biol ; 159(1): 3-20, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-34159573

RESUMO

Cortical thickness (CT) and local gyrification index (LGI) in psychotic disorders may show modifications that relate to clinical course. This observational study aimed to analyse such variables in patients with schizophrenia, compared to healthy controls (HCs). We compared CT and LGI of 18 patients with first-episode psychosis with that of 21 with multi-episode schizophrenia and 16 HCs. CT corrected for false-positive cases (Family-Wise Error Rate) showed a reduction in the multi-episode group compared to HCs in left temporal and parietal, and right temporal, parietal, occipital, and hippocampal cortices. Family-wise corrected LGI was increased in the left inferior and middle frontal cortices, and in the right fusiform gyrus, cingulate, lingual, and parahippocampal gyri in first onset patients compared to HCs. Increased LGI was absent from later stages of psychosis, suggesting that specific CT and LGI alterations may underlie different stages of illness.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Espessura Cortical do Cérebro , Córtex Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Transtornos Psicóticos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem
6.
Nat Commun ; 12(1): 3609, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127675

RESUMO

The insulo-opercular network functions critically not only in encoding taste, but also in guiding behavior based on anticipated food availability. However, there remains no direct measurement of insulo-opercular activity when humans anticipate taste. Here, we collect direct, intracranial recordings during a food task that elicits anticipatory and consummatory taste responses, and during ad libitum consumption of meals. While cue-specific high-frequency broadband (70-170 Hz) activity predominant in the left posterior insula is selective for taste-neutral cues, sparse cue-specific regions in the anterior insula are selective for palatable cues. Latency analysis reveals this insular activity is preceded by non-discriminatory activity in the frontal operculum. During ad libitum meal consumption, time-locked high-frequency broadband activity at the time of food intake discriminates food types and is associated with cue-specific activity during the task. These findings reveal spatiotemporally-specific activity in the human insulo-opercular cortex that underlies anticipatory evaluation of food across both controlled and naturalistic settings.


Assuntos
Córtex Cerebral/fisiologia , Alimentos , Percepção Gustatória/fisiologia , Paladar/fisiologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Sinais (Psicologia) , Eletroencefalografia , Fenômenos Eletrofisiológicos , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Neuroscience ; 467: 16-27, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34022325

RESUMO

Carotid stenosis is a major contributor to vascular dementia. Recent studies suggest that even clinically "asymptomatic" carotid stenosis is linked with cognitive decline and neuroimaging changes. Here we examined surface-based cortical morphometry, white matter hyperintensity (WMH), and multidomain cognitive performance in unilateral severe (>70% narrowing) asymptomatic carotid stenosis (SACS). We included 24 SACS patients (19 males/5 females; 64.25 ± 7.18 years) and 24 comorbidities-matched controls (19 males/5 females; 67.16 ± 6.10 years), and measured cortical thickness, sulcal depth, gyrification, cortical complexity, and WMH loads with structural MRI images. The SACS patients exhibited: (1) thinner cortex in bilateral somatosensory/motor, bilateral inferior frontal, bilateral fusiform, and left lateral temporal areas; (2) shallower sulci in left lateral temporal, parietal, insular and somatosensory/motor areas; (3) both hyper- and hypo-gyrification in lateral temporal and frontal cortices; (4) lower complexity (fractal dimension) in left insular and right superior temporal areas. Further association analyses showed that the cortical alterations were significantly correlated with verbal memory and WMH burden in SACS. These results suggest that SACS patients present a left-dominated damage tendency, especially in the Perisylvian cortices that span across several large-scale systems of somatosensory/motor and language. Our findings also provide cortical anatomy evidence for cognitive impairment in SACS, suggesting a neuroanatomical predisposition to dementia and cerebrovascular events.


Assuntos
Estenose das Carótidas , Substância Branca , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Cognição , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Substância Branca/diagnóstico por imagem
8.
Nat Commun ; 12(1): 2632, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976141

RESUMO

The neural systems supporting scene-perception and spatial-memory systems of the human brain are well-described. But how do these neural systems interact? Here, using fine-grained individual-subject fMRI, we report three cortical areas of the human brain, each lying immediately anterior to a region of the scene perception network in posterior cerebral cortex, that selectively activate when recalling familiar real-world locations. Despite their close proximity to the scene-perception areas, network analyses show that these regions constitute a distinct functional network that interfaces with spatial memory systems during naturalistic scene understanding. These "place-memory areas" offer a new framework for understanding how the brain implements memory-guided visual behaviors, including navigation.


Assuntos
Córtex Cerebral/fisiologia , Rememoração Mental/fisiologia , Memória Espacial/fisiologia , Navegação Espacial/fisiologia , Percepção Visual/fisiologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Adulto Jovem
9.
Nat Commun ; 12(1): 2909, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006833

RESUMO

The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals, we identify 55 lead single nucleotide polymorphisms (SNPs) within 42 genetic loci and 391 genes associated with volumes of the thalamus and its nuclei. In an independent validation sample (n = 5173) 53 out of the 55 lead SNPs of the discovery sample show the same effect direction (sign test, P = 8.6e-14). We map the genetic relationship between thalamic nuclei and 180 cerebral cortical areas and find overlapping genetic architectures consistent with thalamocortical connectivity. Pleiotropy analyses between thalamic volumes and ten psychiatric and neurological disorders reveal shared variants for all disorders. Together, these analyses identify genetic loci linked to thalamic nuclei and substantiate the emerging view of the thalamus having central roles in cortical functioning and common brain disorders.


Assuntos
Encefalopatias/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Tálamo/metabolismo , Encefalopatias/classificação , Mapeamento Encefálico/métodos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Loci Gênicos/genética , Genoma Humano/genética , Humanos , Desequilíbrio de Ligação , Imageamento por Ressonância Magnética/métodos , Transtornos Mentais/classificação , Transtornos Mentais/genética , Locos de Características Quantitativas/genética , Núcleos Talâmicos/diagnóstico por imagem , Núcleos Talâmicos/metabolismo , Tálamo/diagnóstico por imagem
10.
Nat Commun ; 12(1): 2930, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006884

RESUMO

The neural mechanisms underlying conscious recognition remain unclear, particularly the roles played by the prefrontal cortex, deactivated brain areas and subcortical regions. We investigated neural activity during conscious object recognition using 7 Tesla fMRI while human participants viewed object images presented at liminal contrasts. Here, we show both recognized and unrecognized images recruit widely distributed cortical and subcortical regions; however, recognized images elicit enhanced activation of visual, frontoparietal, and subcortical networks and stronger deactivation of the default-mode network. For recognized images, object category information can be decoded from all of the involved cortical networks but not from subcortical regions. Phase-scrambled images trigger strong involvement of inferior frontal junction, anterior cingulate cortex and default-mode network, implicating these regions in inferential processing under increased uncertainty. Our results indicate that content-specific activity in both activated and deactivated cortical networks and non-content-specific subcortical activity support conscious recognition.


Assuntos
Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Estado de Consciência/fisiologia , Reconhecimento Psicológico/fisiologia , Córtex Visual/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Estimulação Luminosa/métodos , Córtex Visual/diagnóstico por imagem , Adulto Jovem
11.
Brain Topogr ; 34(4): 430-441, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34008053

RESUMO

The cortical thickness has been used as a biomarker to assess different cerebral conditions and to detect alterations in the cortical mantle. In this work, we compare methods from the FreeSurfer software, the Computational Anatomy Toolbox (CAT12), a Laplacian approach and a new method here proposed, based on the Euclidean Distance Transform (EDT), and its corresponding computational phantom designed to validate the calculation algorithm. At region of interest (ROI) level, within- and inter-method comparisons were carried out with a test-retest analysis, in a subset comprising 21 healthy subjects taken from the Multi-Modal MRI Reproducibility Resource (MMRR) dataset. From the Minimal Interval Resonance Imaging in Alzheimer's Disease (MIRIAD) data, classification methods were compared in their performance to detect cortical thickness differences between 23 healthy controls (HC) and 45 subjects with Alzheimer's disease (AD). The validation of the proposed EDT-based method showed a more accurate and precise distance measurement as voxel resolution increased. For the within-method comparisons, mean test-retest measures (percentages differences/intraclass correlation/Pearson correlation) were similar for FreeSurfer (1.80%/0.90/0.95), CAT12 (1.91%/0.83/0.91), Laplacian (1.27%/0.89/0.95) and EDT (2.20%/0.88/0.94). Inter-method correlations showed moderate to strong values (R > 0.77) and, in the AD comparison study, all methods were able to detect cortical alterations between groups. Surface- and voxel-based methods have advantages and drawbacks regarding computational demands and measurement precision, while thickness definition was mainly associated to the cortical thickness absolute differences among methods. However, for each method, measurements were reliable, followed similar trends along the cortex and allowed detection of cortical atrophies between HC and patients with AD.


Assuntos
Doença de Alzheimer , Processamento de Imagem Assistida por Computador , Doença de Alzheimer/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes
12.
J Affect Disord ; 290: 316-323, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34020206

RESUMO

BACKGROUND: Memory control (MC) ability is critical for people's mental and physical health. Previous research had conceptually demonstrated that MC ability has close relationship with reappraisal. However, experimental evidence supporting the relationship was limited. Thus, in the present study, we investigated how MC and reappraisal are linked, both in behavior and in the brain. METHODS: The habitual use of reappraisal was assessed by Emotion Regulation Questionnaire, and memory control ability was measured through directed forgetting task. Resting-state functional magnetic resonance imaging was used to test the seed-based functional connectivity in 181 healthy subjects. RESULTS: Behavioral results revealed that more frequent reappraisal was associated with an enhanced ability to control negative memories. Resting-state seed-based functional connectivity showed that habitual use of reappraisal was positively related to the strength of functional connectivity between the right ventrolateral prefrontal cortex (VLPFC) and right insula. Most importantly, this functional connectivity mediated the effect of habitual use of reappraisal on control over negative memories. LIMITATIONS: Present results mainly showed the habitual use of reappraisal was related with MC ability in negative items. Future study could further explore the relationship between MC ability of different categories of negative emotional memories and other kinds of ER strategies. CONCLUSIONS: Our results support the notion that reappraisal provides opportunities for individuals to practice and enhance inhibitory control-a relationship underpinned by connectivity between the right VLPFC and right insula.


Assuntos
Mapeamento Encefálico , Córtex Cerebral , Córtex Cerebral/diagnóstico por imagem , Emoções , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem
13.
Neurology ; 96(23): e2874-e2884, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33910940

RESUMO

OBJECTIVES: To test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism. METHODS: We included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations. RESULTS: Severity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters. CONCLUSIONS: These results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops.


Assuntos
Sintomas Comportamentais , Cerebelo , Disfunção Cognitiva , Rede Nervosa , Doença de Parkinson , Adulto , Idoso , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/metabolismo , Gânglios da Base/fisiopatologia , Sintomas Comportamentais/diagnóstico por imagem , Sintomas Comportamentais/etiologia , Sintomas Comportamentais/metabolismo , Sintomas Comportamentais/fisiopatologia , Cerebelo/diagnóstico por imagem , Cerebelo/metabolismo , Cerebelo/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/metabolismo , Rede Nervosa/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Tomografia por Emissão de Pósitrons , Análise de Componente Principal , Tálamo/diagnóstico por imagem , Tálamo/metabolismo , Tálamo/fisiopatologia
14.
Brain ; 144(4): 1263-1276, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1169654

RESUMO

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.


Assuntos
COVID-19/metabolismo , Córtex Cerebral/metabolismo , Disfunção Cognitiva/metabolismo , Glucose/metabolismo , Testes de Estado Mental e Demência , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico por imagem , COVID-19/psicologia , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos
15.
Brain ; 144(4): 1263-1276, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33822001

RESUMO

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.


Assuntos
COVID-19/metabolismo , Córtex Cerebral/metabolismo , Disfunção Cognitiva/metabolismo , Glucose/metabolismo , Testes de Estado Mental e Demência , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico por imagem , COVID-19/psicologia , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/psicologia , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos
16.
Nat Commun ; 12(1): 2430, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893294

RESUMO

Knowledge about the relevance of environmental features can guide stimulus processing. However, it remains unclear how processing is adjusted when feature relevance is uncertain. We hypothesized that (a) heightened uncertainty would shift cortical networks from a rhythmic, selective processing-oriented state toward an asynchronous ("excited") state that boosts sensitivity to all stimulus features, and that (b) the thalamus provides a subcortical nexus for such uncertainty-related shifts. Here, we had young adults attend to varying numbers of task-relevant features during EEG and fMRI acquisition to test these hypotheses. Behavioral modeling and electrophysiological signatures revealed that greater uncertainty lowered the rate of evidence accumulation for individual stimulus features, shifted the cortex from a rhythmic to an asynchronous/excited regime, and heightened neuromodulatory arousal. Crucially, this unified constellation of within-person effects was dominantly reflected in the uncertainty-driven upregulation of thalamic activity. We argue that neuromodulatory processes involving the thalamus play a central role in how the brain modulates neural excitability in the face of momentary uncertainty.


Assuntos
Córtex Cerebral/fisiologia , Percepção/fisiologia , Tálamo/fisiologia , Incerteza , Adolescente , Adulto , Algoritmos , Córtex Cerebral/diagnóstico por imagem , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Modelos Neurológicos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Tálamo/diagnóstico por imagem , Adulto Jovem
17.
Nat Med ; 27(5): 871-881, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33927414

RESUMO

Alzheimer's disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These 'subtypes' were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of 'typical AD' and a revisiting of tau pathological staging.


Assuntos
Doença de Alzheimer/patologia , Córtex Cerebral/patologia , Disfunção Cognitiva/patologia , Proteínas tau/metabolismo , Idoso , Doença de Alzheimer/classificação , Carbolinas/farmacologia , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Neuroimagem/métodos , Fenótipo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Análise Espaço-Temporal
18.
J Affect Disord ; 287: 380-386, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33836366

RESUMO

BACKGROUND: Adolescents are at increased risk of developing major depressive disorder (MDD) than many other age groups. Although the neural correlates of MDD in adults have been studied prospectively, such adolescent depression studies are mainly cross-sectional. We extracted data regarding the relationship between cortical thickness and later development of adolescent MDD from a national community study that uses an accelerated longitudinal design to examine the psychological, environmental, and neural differences related to drinking and brain development. METHODS: 692 subjects (age 12-21 years; 50% female) without a history of MDD were assessed with structural neuroimaging at baseline. We compared those 101 subjects who transitioned to MDD by 1-year follow-up to those who remained non-depressed over the same time period. FreeSurfer's autosegmentation process estimated vertex-wide cortical thicknesses and its Query, Design, Estimate, Contrast (Qdec) application investigated cortical thickness between those who later developed MDD and those who remained without MDD (Monte Carlo corrected for multiple comparisons, vertex-wise cluster threshold of 1.3, p < 0.01). RESULTS: Those who transitioned in the next year to MDD had, at baseline, thinner cortices in the superior frontal cortex, precentral and postcentral regions, and superior temporal cortex, above and beyond effects attributable to age and sex. No cortical thickness sex differences or sex-by-depression interactions were observed. LIMITATIONS: A larger sample size could improve statistical power and future investigations will be needed to confirm our results. CONCLUSIONS: Thinner cortices over frontal and temporal regions may be linked to enhanced vulnerability for future depression during the adolescent-young adulthood transition.


Assuntos
Transtorno Depressivo Maior , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Criança , Estudos Transversais , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Adulto Jovem
19.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808700

RESUMO

The prevalence of obesity has increased rapidly in recent years and has put a huge burden on healthcare worldwide. Obesity is associated with an increased risk for many comorbidities, such as cardiovascular diseases, type 2 diabetes and hypertension. The hypothalamus is a key brain region involved in the regulation of food intake and energy expenditure. Research on experimental animals has shown neuronal loss, as well as microglial activation in the hypothalamus, due to dietary-induced obesity. Microglia, the resident immune cells in the brain, are responsible for maintaining the brain homeostasis and, thus, providing an optimal environment for neuronal function. Interestingly, in obesity, microglial cells not only get activated in the hypothalamus but in other brain regions as well. Obesity is also highly associated with changes in hippocampal function, which could ultimately result in cognitive decline and dementia. Moreover, changes have also been reported in the striatum and cortex. Microglial heterogeneity is still poorly understood, not only in the context of brain region but, also, age and sex. This review will provide an overview of the currently available data on the phenotypic differences of microglial innate immunity in obesity, dependent on brain region, sex and age.


Assuntos
Variação Biológica da População , Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Microglia/metabolismo , Obesidade/diagnóstico por imagem , Fatores Etários , Animais , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Humanos , Hipotálamo/diagnóstico por imagem , Hipotálamo/metabolismo , Fatores Sexuais
20.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799851

RESUMO

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR5 expression provide conflicting findings about the nature of dysregulation of cerebral mGluR5 pathways in subtypes of ASD. The demonstration of reduced mGluR5 expression throughout the living brains of men with fragile X syndrome (FXS), the most common known single-gene cause of ASD, provides a clue to examine mGluR5 expression in ASD. We aimed to (A) compare and contrast mGluR5 expression in idiopathic autism spectrum disorder (IASD), FXS, and typical development (TD) and (B) show the value of positron emission tomography (PET) for the application of precision medicine for the diagnosis and treatment of individuals with IASD, FXS, and related conditions. Two teams of investigators independently administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a novel, specific mGluR5 PET ligand to quantitatively measure the density and the distribution of mGluR5s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR5 expression was significantly increased in the cortical regions of participants with IASD and significantly reduced in all regions of men with FXS. These results suggest the feasibility of this protocol as a valuable tool to measure mGluR5 expression in clinical trials of individuals with IASD and FXS and related conditions.


Assuntos
Transtorno do Espectro Autista/metabolismo , Córtex Cerebral/metabolismo , Síndrome do Cromossomo X Frágil/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Adolescente , Adulto , Animais , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/genética , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Córtex Cerebral/diagnóstico por imagem , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico por imagem , Síndrome do Cromossomo X Frágil/genética , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tomografia por Emissão de Pósitrons/métodos , Receptor de Glutamato Metabotrópico 5/genética , Adulto Jovem
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