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1.
J Clin Med ; 10(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34768590

RESUMO

(1) Background: Inflammation plays a pivotal role in atherosclerosis, and the association between chronic inflammatory states and ischemic heart disease (IHD) has been shown in several rheumatic diseases. Persistent inflammation might also be a risk factor for IHD in sarcoidosis patients. (2) Methods: Demographic and clinical data of 3750 sarcoidosis patients and 18,139 age- and sex-matched controls were retrieved from the database of Clalit Health Services, Israel's largest healthcare organization. Variables associated with IHD were assessed by a logistic regression model. To assess for variables that were related to increased risk of all-cause mortality, the Cox proportional hazards method was used, and a log-rank test was performed for survival analysis. (3) Results: Both groups were composed of 64% females with a median age of 56 years. An association between sarcoidosis and IHD was demonstrated by a multivariate analysis (adjusted odds ratio (OR) 1.5; 95% confidence interval (CI) 1.36-1.66). Long-term follow-up revealed increased mortality among sarcoidosis patients: 561 (15%) deaths compared to 1636 (9%) deaths among controls (p < 0.001). Survival analysis demonstrated that sarcoidosis patients were also at increased risk for all-cause mortality compared to controls (multivariate model, adjusted HR 1.93; 95% CI 1.76-2.13).

3.
N Engl J Med ; 385(16): 1474-1484, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34320281

RESUMO

BACKGROUND: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. METHODS: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. RESULTS: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. CONCLUSIONS: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.


Assuntos
Vacinas contra COVID-19 , COVID-19/epidemiologia , Pessoal de Saúde/estatística & dados numéricos , Adulto , Doenças Assintomáticas , COVID-19/diagnóstico , COVID-19/prevenção & controle , Teste de Ácido Nucleico para COVID-19 , Estudos de Casos e Controles , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Falha de Tratamento
4.
Nat Commun ; 11(1): 4047, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778724

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

5.
Nat Commun ; 11(1): 3192, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581214

RESUMO

Resolving approach-avoidance conflicts relies on encoding motivation outcomes and learning from past experiences. Accumulating evidence points to the role of the Medial Temporal Lobe (MTL) and Medial Prefrontal Cortex (mPFC) in these processes, but their differential contributions have not been convincingly deciphered in humans. We detect 310 neurons from mPFC and MTL from patients with epilepsy undergoing intracranial recordings and participating in a goal-conflict task where rewards and punishments could be controlled or not. mPFC neurons are more selective to punishments than rewards when controlled. However, only MTL firing following punishment is linked to a lower probability for subsequent approach behavior. mPFC response to punishment precedes a similar MTL response and affects subsequent behavior via an interaction with MTL firing. We thus propose a model where approach-avoidance conflict resolution in humans depends on outcome value tagging in mPFC neurons influencing encoding of such value in MTL to affect subsequent choice.


Assuntos
Comportamento de Escolha/fisiologia , Objetivos , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Lobo Temporal/fisiologia , Adolescente , Adulto , Idoso , Mapeamento Encefálico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Córtex Pré-Frontal/citologia , Punição , Tempo de Reação , Recompensa , Lobo Temporal/citologia , Adulto Jovem
6.
Rambam Maimonides Med J ; 11(1)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32017684

RESUMO

Chronic pain is a common complaint among patients, and rheumatic diseases are a common cause for chronic pain. Current pharmacological interventions for chronic pain are not always useful or safe enough for long-term use. Cannabis and cannabinoids are currently being studied due to their potential as analgesics. In this review we will discuss current literature regarding cannabinoids and cannabis as treatment for rheumatic diseases. Fibromyalgia is a prevalent rheumatic disease that causes diffuse pain, fatigue, and sleep disturbances. Treatment of this syndrome is symptomatic, and it has been suggested that cannabis and cannabinoids could potentially alleviate some of the symptoms associated with fibromyalgia. In this review we cite some of the evidence that supports this claim. However, data on long-term efficacy and safety of cannabinoid and cannabis use are still lacking. Cannabinoids and cannabis are commonly investigated as analgesic agents, but in recent years more evidence has accumulated on their potential immune-modulatory effect, supported by results in animal models of certain rheumatic diseases. While results that demonstrate the same effect in humans are still lacking, cannabinoids and cannabis remain potential drugs to alleviate the pain associated with rheumatic diseases, as they were shown to be safe and to cause limited adverse effects.

7.
Rheumatol Int ; 40(3): 465-470, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31630236

RESUMO

Ankylosing spondylitis (AS) and gout are common inflammatory arthropathies. It had been claimed previously that the two conditions rarely coexist. The aim of this study was to compare the prevalence of gout in a population of AS patients to its prevalence in the general population. To conduct this population-based case-control study, data of adult patients with a physician diagnosis of AS were retrieved from the database of the largest health-care provider organization in Israel, Clalit Health Services. For each patient with AS, five age- and sex-matched subjects without AS were randomly selected from the same database. Different parameters including the existence of gout, hypertension, body mass index, socioeconomic status, and smoking were evaluated in both the AS and the control groups. The study included 3763 patients with AS and 19,214 controls. The proportion of gout in the AS group was higher than in the control group: 73 subjects in the AS group had gout, while only 107 subjects in the non-AS group had gout (1.94% and 0.56%, respectively, OR 3.53, P < 0.001). Logistic regression adjusting for possible confounding variables found that AS was independently associated with gout (OR 1.41, P = 0.037). Our study suggests that gout is not less common in AS patients in comparison with the general population, and that it might even be more common in AS patients.


Assuntos
Gota/epidemiologia , Espondilite Anquilosante/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
8.
Neuromodulation ; 22(8): 884-893, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29741803

RESUMO

OBJECTIVES: Implicit regulation of emotions involves medial-prefrontal cortex (mPFC) regions exerting regulatory control over limbic structures. Diminished regulation relates to aberrant mPFC functionality and psychopathology. Establishing means of modulating mPFC functionality could benefit research on emotion and its dysregulation. Here, we tested the capacity of transcranial direct current stimulation (tDCS) targeting mPFC to modulate subjective emotional states by facilitating implicit emotion regulation. MATERIALS AND METHODS: Stimulation was applied concurrently with functional magnetic resonance imaging to validate its neurobehavioral effect. Sixteen participants were each scanned twice, counterbalancing active and sham tDCS application, while undergoing negative mood induction (clips featuring negative vs. neutral contents). Effects of stimulation on emotional experience were assessed using subjective and neural measures. RESULTS: Subjectively, active stimulation led to significant reduction in reported intensity of experienced emotions to negatively valenced (p = 0.005) clips but not to neutral clips (p > 0.99). Active stimulation further mitigated a rise in stress levels from pre- to post-induction (sham: p = 0.004; active: p = 0.15). Neurally, stimulation increased activation in mPFC regions associated with implicit emotion regulation (ventromedial-prefrontal cortex; subgenual anterior-cingulate cortex, sgACC), and in ventral striatum, a core limbic structure (all ps < 0.05). Stimulation also altered functional connectivity (assessed using whole-brain psycho-physiological interaction) between these regions, and with additional limbic regions. Stimulation-induced sgACC activation correlated with reported emotion intensity and depressive symptoms (rs > 0.64, ps < 0.018), suggesting individual differences in stimulation responsivity. CONCLUSIONS: Results of this study indicate the potential capacity of tDCS to facilitate brain activation in mPFC regions underlying implicit regulation of emotion and accordingly modulate subjective emotional experiences.


Assuntos
Estimulação Elétrica , Emoções/fisiologia , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/fisiologia , Estimulação Transcraniana por Corrente Contínua , Adulto , Afeto , Depressão/psicologia , Feminino , Humanos , Masculino , Vias Neurais , Estresse Psicológico/psicologia , Adulto Jovem
9.
Brain Imaging Behav ; 13(4): 1009-1020, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29971685

RESUMO

Disturbances in reward processing occur in Parkinson's disease (PD) however it is unclear whether these are solely drug-related. We applied an event-related fMRI gambling task to a group of non-manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene, in order to assess the reward network in an "at risk" population for future development of PD. Sixty-eight non-manifesting participants, 32 of which were non-manifesting non-carriers (NMNC), performed a gambling task which included defined intervals of anticipation and response to both reward and punishment in an fMRI setup. Behavior and cerebral activations were measured using both hypothesis driven and whole brain analysis. NMC demonstrated higher trait anxiety scores (p = 0.04) compared to NMNC. Lower activations were detected among NMC during risky anticipation in the left nucleus accumbens (NAcc) (p = 0.05) and during response to punishment in the right insula (p = 0.02), with higher activations among NMC during safe anticipation in the right insula (p = 0.02). Psycho-Physiological Interaction (PPI) analysis from the NAcc and insula revealed differential connectivity patterns. Whole brain analysis demonstrated divergent between-group activations in distributed cortical regions, bilateral caudate, left midbrain, when participants were required to press the response button upon making their next chosen move. Abnormal neural activity in both the reward and motor networks were detected in NMC indicating involvement of the ventral striatum regardless of medication use in "at risk" individuals for future development of PD.


Assuntos
Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Doença de Parkinson/genética , Adulto , Antecipação Psicológica/fisiologia , Encéfalo/fisiologia , Córtex Cerebral/metabolismo , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mutação , Núcleo Accumbens/metabolismo , Doença de Parkinson/fisiopatologia , Recompensa , Estriado Ventral/metabolismo
10.
Harefuah ; 157(2): 108-111, 2018 Feb.
Artigo em Hebraico | MEDLINE | ID: mdl-29484867

RESUMO

INTRODUCTION: Pain is one of the most common symptoms among cancer patients, and particularly in those who suffer from metastatic or terminal disease. There is great importance in delivering good pain management to these patients in order to alleviate their suffering, improve their functional status and their overall quality of life. In most cases, pain management is based on pharmacotherapy with opioids and other medications. However, there are selected patients for whom pharmacotherapy does not achieve acceptable pain relief or is associated with marked side effects. These patients, who suffer from refractory cancer pain, may benefit from neurosurgical procedures selectively intervening in different locations along the pain signaling pathways. This article summarizes several of these neurosurgical procedures: percutaneous cordotomy for unilateral pain, punctuate midline myelotomy for visceral pain and stereotactic cingulotomy for diffuse pain syndromes. This article demonstrates the use of careful patient selection by an interdisciplinary team which is critical for the success of these procedures. The team consists of palliative care specialists, pain specialists and a neurosurgeon. These neurosurgical interventions are presented through representative clinical cases, followed by a discussion of the clinical considerations that guided the choice of the therapeutic approach for each case.


Assuntos
Dor do Câncer/terapia , Cordotomia/métodos , Dor Intratável/terapia , Dor do Câncer/cirurgia , Humanos , Neoplasias , Dor Intratável/cirurgia , Cuidados Paliativos , Qualidade de Vida
11.
Neuroimage ; 163: 244-263, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28939433

RESUMO

Major methodological advancements have been recently made in the field of neural decoding, which is concerned with the reconstruction of mental content from neuroimaging measures. However, in the absence of a large-scale examination of the validity of the decoding models across subjects and content, the extent to which these models can be generalized is not clear. This study addresses the challenge of producing generalizable decoding models, which allow the reconstruction of perceived audiovisual features from human magnetic resonance imaging (fMRI) data without prior training of the algorithm on the decoded content. We applied an adapted version of kernel ridge regression combined with temporal optimization on data acquired during film viewing (234 runs) to generate standardized brain models for sound loudness, speech presence, perceived motion, face-to-frame ratio, lightness, and color brightness. The prediction accuracies were tested on data collected from different subjects watching other movies mainly in another scanner. Substantial and significant (QFDR<0.05) correlations between the reconstructed and the original descriptors were found for the first three features (loudness, speech, and motion) in all of the 9 test movies (R¯=0.62, R¯ = 0.60, R¯ = 0.60, respectively) with high reproducibility of the predictors across subjects. The face ratio model produced significant correlations in 7 out of 8 movies (R¯=0.56). The lightness and brightness models did not show robustness (R¯=0.23, R¯ = 0). Further analysis of additional data (95 runs) indicated that loudness reconstruction veridicality can consistently reveal relevant group differences in musical experience. The findings point to the validity and generalizability of our loudness, speech, motion, and face ratio models for complex cinematic stimuli (as well as for music in the case of loudness). While future research should further validate these models using controlled stimuli and explore the feasibility of extracting more complex models via this method, the reliability of our results indicates the potential usefulness of the approach and the resulting models in basic scientific and diagnostic contexts.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Humanos
12.
PLoS One ; 12(7): e0180740, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28700619

RESUMO

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.


Assuntos
Mapeamento Encefálico/métodos , Idioma , Monitorização Intraoperatória/métodos , Adulto , Estimulação Elétrica , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Resultado do Tratamento
13.
Stereotact Funct Neurosurg ; 95(6): 400-408, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29316566

RESUMO

BACKGROUND: Stereotactic anterior cingulotomy has been used in the treatment of patients suffering from refractory oncological pain due to its effects on pain perception. However, the optimal targets as well as suitable candidates and outcome measures have not been well defined. We report our initial experience in the ablation of 2 cingulotomy targets on each side and the use of the Brief Pain Inventory (BPI) as a perioperative assessment tool. METHODS: A retrospective review of all patients who underwent stereotactic anterior cingulotomy in our Department between November 2015 and February 2017 was performed. All patients had advanced metastatic cancer with limited prognosis and suffered from intractable oncological pain. RESULTS: Thirteen patients (10 women and 3 men) underwent 14 cingulotomy procedures. Their mean age was 54 ± 14 years. All patients reported substantial pain relief immediately after the operation. Out of the 6 preoperatively bedridden patients, 3 started ambulating shortly after. At the 1-month follow-up, the mean preoperative Visual Analogue Scale score decreased from 9 ± 0.9 to 4 ± 2.7 (p = 0.003). Mean BPI pain severity and interference scores decreased from levels of 29 ± 4 and 55 ± 12 to 16 ± 12 (p = 0.028) and 37 ± 15 (p = 0.043), respectively. During the 1- and 3-month follow-up visits, 9/11 patients (82%) and 5/7 patients (71%) available for follow-up reported substantial pain relief. No patient reported worsening of pain during the study period. Neuropsychological analyses of 6 patients showed stable cognitive functions with a mild nonsignificant decline in focused attention and executive functions. Adverse events included transient confusion or mild apathy in 5 patients (38%) lasting 1-4 weeks. CONCLUSIONS: Our initial experience indicates that double stereotactic cingulotomy is safe and effective in alleviating refractory oncological pain.


Assuntos
Dor do Câncer/cirurgia , Giro do Cíngulo/cirurgia , Manejo da Dor/métodos , Dor Intratável/cirurgia , Psicocirurgia/métodos , Técnicas Estereotáxicas , Adulto , Idoso , Dor do Câncer/diagnóstico por imagem , Cognição/fisiologia , Feminino , Seguimentos , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Dor Intratável/diagnóstico por imagem , Estudos Retrospectivos
14.
World Neurosurg ; 99: 674-679, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28034812

RESUMO

BACKGROUND: Despite selection process before awake-craniotomy, some patients experience an unexpected decline in language functions in the operating room (OR), compared with their baseline evaluation, which may impair their functional monitoring. To investigate this phenomenon we prospectively compared language function the day before surgery and on entrance to the OR. METHODS: Data were collected prospectively from consecutive patients undergoing awake-craniotomy with intraoperative cortical mapping for resection of gliomas affecting language areas. Language functions of 79 patients were evaluated and compared 1-2 days before surgery and after entering the OR. Changes in functional linguistic performance were analyzed with respect to demographic, clinical, and pathologic characteristics. RESULTS: There was a significant decline in language function, beyond sedation effect, after entering the OR, (from median/interquartile range: 0.94/0.72-0.98 to median/interquartile range: 0.86/0.51-0.94; Z = -7.19, P < 0.001). Univariate analyses revealed that this decline was related to age, preoperative Karnofsky Performance Scale, tumor location, tumor pathology, and preexisting language deficits. Multivariate stepwise regression identified tumor pathology and the presence of preoperative language deficit as significant independent predictors for this functional decline. CONCLUSIONS: Patients undergoing awake-craniotomy may experience a substantial decline in language functioning after entering the OR. Tumor grade and the presence of preoperative language deficits were significant risk factors for this phenomenon, suggesting a possible relation between cognitive reserve, psychobehavioral coping abilities and histologic features of a tumor involving language areas. Capturing and identifying this unique population of patients who are prone to experience such language decline may improve our ability in the future to select patients eligible for awake-craniotomy.


Assuntos
Neoplasias Encefálicas/cirurgia , Craniotomia , Glioma/cirurgia , Idioma , Adaptação Psicológica , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/psicologia , Reserva Cognitiva , Feminino , Glioma/patologia , Glioma/psicologia , Humanos , Monitorização Neurofisiológica Intraoperatória , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Adulto Jovem
15.
Psychoneuroendocrinology ; 76: 77-83, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27889465

RESUMO

Interpersonal space is a nonverbal indicator of affiliation and closeness. In this study we investigated the effects of oxytocin (OT), a neuropeptide known for its social role in humans, on interpersonal space. In a double blind placebo controlled study we measured the effect of intranasal OT on the personal distance preferences of different familiar (friend) and unfamiliar (stranger) protagonists. Behavioral results showed that participants preferred to be closer to a friend than to a stranger. Intranasal OT was associated with an overall distancing effect, but this effect was significant for the stranger and not for the friend. The imaging results showed interactions between treatment (OT, placebo) and protagonist (friend, stranger) in regions that mediate social behavior including the dorsomedial prefrontal cortex (dmPFC), a region associated with the mentalizing system. Specifically, OT increased activity in the dmPFC when a friend approached the participants but not when a stranger approached. The results indicate that the effect of OT on interpersonal space greatly depends on the participant's relationship with the protagonist. This supports the social salience theory, according to which OT increases the salience of social cues depending on the context.


Assuntos
Relações Interpessoais , Neurotransmissores/farmacologia , Ocitocina , Espaço Pessoal , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Comportamento Social , Teoria da Mente/fisiologia , Adolescente , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Neurotransmissores/administração & dosagem , Ocitocina/administração & dosagem , Ocitocina/farmacologia , Ocitocina/fisiologia , Adulto Jovem
16.
Ann Surg Oncol ; 24(3): 794-800, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27766560

RESUMO

BACKGROUND: The extent of tumor resection (EOTR) calculated by enhanced T1 changes in glioblastomas has been previously reported to predict survival. However, fluid-attenuated inversion recovery (FLAIR) volume may better represent tumor burden. In this study, we report the first assessment of the dynamics of FLAIR volume changes over time as a predictive variable for post-resection overall survival (OS). METHODS: Contemporary data from 103 consecutive patients with complete imaging and clinical data who underwent resection of newly diagnosed glioblastoma followed by the Stupp protocol between 2010 and 2013 were analyzed. Clinical, radiographic, and outcome parameters were retrieved for each patient, including magnetic resonance imaging (MRI)-based volumetric tumor analysis before, immediately after, and 3 months post-surgery. RESULTS: OS rate was 17.6 months. A significant incremental OS advantage was noted, with as little as 85 % T1-weighted gadolinium-enhanced (T1Gd)-EOTR measured on contrast-enhanced MRI. Pre- and immediate postoperative FLAIR-based EOTR was not predictive of OS; however, abnormal FLAIR volume measured 3 months post-surgery correlated significantly with outcome when FLAIR residual tumor volume (RTV) was <19.3 cm3 and <46 % of baseline volume (p < 0.0001 for both). Age and isocitrate dehydrogenase (IDH)-1 mutation were predictive of OS (p < 0.0001, Cox proportional hazards). CONCLUSIONS: OS correlated with the immediate postoperative T1Gd-EOTR measured by enhanced T1 MRI, but not by FLAIR volume. Diminished abnormal FLAIR volume at 3 months post-surgery was associated with OS benefit when FLAIR-RTV was <19.3 cm3 or <46 % of baseline. These threshold values provide a new radiological variable that can be used for prediction of OS in patients with glioblastoma immediately after completion of standard chemoradiation.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Imagem de Difusão por Ressonância Magnética/métodos , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Fatores Etários , Idoso , Neoplasias Encefálicas/patologia , Meios de Contraste , Feminino , Gadolínio , Glioblastoma/patologia , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
17.
Hum Brain Mapp ; 37(12): 4654-4672, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27477592

RESUMO

We introduce a novel method for delineating context-dependent functional brain networks whose connectivity dynamics are synchronized with the occurrence of a specific psychophysiological process of interest. In this method of context-related network dynamics analysis (CRNDA), a continuous psychophysiological index serves as a reference for clustering the whole-brain into functional networks. We applied CRNDA to fMRI data recorded during the viewing of a sadness-inducing film clip. The method reliably demarcated networks in which temporal patterns of connectivity related to the time series of reported emotional intensity. Our work successfully replicated the link between network connectivity and emotion rating in an independent sample group for seven of the networks. The demarcated networks have clear common functional denominators. Three of these networks overlap with distinct empathy-related networks, previously identified in distinct sets of studies. The other networks are related to sensorimotor processing, language, attention, and working memory. The results indicate that CRNDA, a data-driven method for network clustering that is sensitive to transient connectivity patterns, can productively and reliably demarcate networks that follow psychologically meaningful processes. Hum Brain Mapp 37:4654-4672, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Emoções/fisiologia , Imageamento por Ressonância Magnética , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Filmes Cinematográficos , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Psicofisiologia , Autorrelato
18.
Cogn Affect Behav Neurosci ; 16(4): 709-23, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27142636

RESUMO

Recent theoretical and empirical work has highlighted the role of domain-general, large-scale brain networks in generating emotional experiences. These networks are hypothesized to process aspects of emotional experiences that are not unique to a specific emotional category (e.g., "sadness," "happiness"), but rather that generalize across categories. In this article, we examined the dynamic interactions (i.e., changing cohesiveness) between specific domain-general networks across time while participants experienced various instances of sadness, fear, and anger. We used a novel method for probing the network connectivity dynamics between two salience networks and three amygdala-based networks. We hypothesized, and found, that the functional connectivity between these networks covaried with the intensity of different emotional experiences. Stronger connectivity between the dorsal salience network and the medial amygdala network was associated with more intense ratings of emotional experience across six different instances of the three emotion categories examined. Also, stronger connectivity between the dorsal salience network and the ventrolateral amygdala network was associated with more intense ratings of emotional experience across five out of the six different instances. Our findings demonstrate that a variety of emotional experiences are associated with dynamic interactions of domain-general neural systems.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Emoções/fisiologia , Modelos Neurológicos , Vias Neurais/fisiologia , Dinâmica não Linear , Adulto , Análise de Variância , Encéfalo/diagnóstico por imagem , Feminino , Lateralidade Funcional , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Estimulação Luminosa , Adulto Jovem
19.
Soc Cogn Affect Neurosci ; 11(6): 961-72, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26833917

RESUMO

Goal conflict situations, involving the simultaneous presence of reward and punishment, occur commonly in real life, and reflect well-known individual differences in the behavioral tendency to approach or avoid. However, despite accumulating neural depiction of motivational processing, the investigation of naturalistic approach behavior and its interplay with individual tendencies is remarkably lacking. We developed a novel ecological interactive scenario which triggers motivational behavior under high or low goal conflict conditions. Fifty-five healthy subjects played the game during a functional magnetic resonance imaging scan. A machine-learning approach was applied to classify approach/avoidance behaviors during the game. To achieve an independent measure of individual tendencies, an integrative profile was composed from three established theoretical models. Results demonstrated that approach under high relative to low conflict involved increased activity in the ventral tegmental area (VTA), peri-aquaductal gray, ventral striatum (VS) and precuneus. Notably, only VS and VTA activations during high conflict discriminated between approach/avoidance personality profiles, suggesting that the relationship between individual personality and naturalistic motivational tendencies is uniquely associated with the mesostriatal pathway. VTA-VS further demonstrated stronger coupling during high vs low conflict. These findings are the first to unravel the multilevel relationship among personality profile, approach tendencies in naturalistic set-up and their underlying neural manifestation, thus enabling new avenues for investigating approach-related psychopathologies.


Assuntos
Mapeamento Encefálico/métodos , Conflito Psicológico , Objetivos , Personalidade/fisiologia , Estriado Ventral/fisiologia , Área Tegmentar Ventral/fisiologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto Jovem
20.
J Neurosurg ; 125(2): 481-93, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26722848

RESUMO

OBJECTIVE Providing a reliable assessment of language lateralization is an important task to be performed prior to neurosurgery in patients with epilepsy. Over the last decade, functional MRI (fMRI) has emerged as a useful noninvasive tool for language lateralization, supplementing or replacing traditional invasive methods. In standard practice, fMRI-based language lateralization is assessed qualitatively by visual inspection of fMRI maps at a specific chosen activation threshold. The purpose of this study was to develop and evaluate a new computational technique for providing the probability of each patient to be left, right, or bilateral dominant in language processing. METHODS In 76 patients with epilepsy, a language lateralization index was calculated using the verb-generation fMRI task over a wide range of activation thresholds (from a permissive threshold, analyzing all brain regions, to a harsh threshold, analyzing only the strongest activations). The data were classified using a probabilistic logistic regression method. RESULTS Concordant results between fMRI and Wada lateralization were observed in 89% of patients. Bilateral and right-dominant groups showed similar fMRI lateralization patterns differentiating them from the left-dominant group but still allowing classification in 82% of patients. CONCLUSIONS These findings present the utility of a semi-supervised probabilistic learning approach for presurgical language-dominance mapping, which may be extended to other cognitive domains such as memory and attention.


Assuntos
Epilepsia Resistente a Medicamentos/fisiopatologia , Lateralidade Funcional , Idioma , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Adolescente , Adulto , Criança , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Adulto Jovem
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