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1.
PLoS One ; 15(1): e0228092, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978108

RESUMO

Early life exposure to air pollution poses a significant risk to brain development from direct exposure to toxicants or via indirect mechanisms involving the circulatory, pulmonary or gastrointestinal systems. In children, exposure to traffic related air pollution has been associated with adverse effects on cognitive, behavioral and psychomotor development. We aimed to determine whether childhood exposure to traffic related air pollution is associated with regional differences in brain volume and cortical thickness among children enrolled in a longitudinal cohort study of traffic related air pollution and child health. We used magnetic resonance imaging to obtain anatomical brain images from a nested subset of 12 year old participants characterized with either high or low levels of traffic related air pollution exposure during their first year of life. We employed voxel-based morphometry to examine group differences in regional brain volume, and with separate analyses, changes in cortical thickness. Smaller regional gray matter volumes were determined in the left pre- and post-central gyri, the cerebellum, and inferior parietal lobe of participants in the high traffic related air pollution exposure group relative to participants with low exposure. Reduced cortical thickness was observed in participants with high exposure relative to those with low exposure, primarily in sensorimotor regions of the brain including the pre- and post-central gyri and the paracentral lobule, but also within the frontal and limbic regions. These results suggest that significant childhood exposure to traffic related air pollution is associated with structural alterations in brain.


Assuntos
Poluição do Ar , Córtex Cerebral/patologia , Substância Cinzenta/patologia , Poluição Relacionada com o Tráfego , Adulto , Carbono/análise , Córtex Cerebral/diagnóstico por imagem , Criança , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão
2.
Environ Res ; 175: 71-78, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31103795

RESUMO

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry. OBJECTIVES: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS). METHODS: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myo-inositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels. RESULTS: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (ß = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (ß = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (ß = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels. CONCLUSIONS: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.


Assuntos
Ansiedade , Encéfalo , Inositol , Poluição Relacionada com o Tráfego , Adolescente , Ansiedade/etiologia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Inositol/análise , Espectroscopia de Ressonância Magnética , Masculino , Poluição Relacionada com o Tráfego/efeitos adversos
3.
Psychiatry Res Neuroimaging ; 286: 53-59, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30903953

RESUMO

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.


Assuntos
Transtorno da Compulsão Alimentar/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Inibidores da Captação de Dopamina/uso terapêutico , Dimesilato de Lisdexanfetamina/uso terapêutico , Rede Nervosa/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adulto , Transtorno da Compulsão Alimentar/diagnóstico por imagem , Transtorno da Compulsão Alimentar/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Inibidores da Captação de Dopamina/farmacologia , Feminino , Humanos , Dimesilato de Lisdexanfetamina/farmacologia , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Projetos Piloto , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Resultado do Tratamento
4.
Pediatr Blood Cancer ; 65(9): e27245, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29856521

RESUMO

BACKGROUND: Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. PROCEDURE: The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). RESULTS: Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. CONCLUSIONS: These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Deficiências da Aprendizagem/etiologia , Aprendizagem/efeitos da radiação , Transtornos da Memória/etiologia , Memória/efeitos da radiação , Dosagem Radioterapêutica , Adolescente , Antineoplásicos/uso terapêutico , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Terapia Combinada , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Hipocampo/efeitos da radiação , Humanos , Deficiências da Aprendizagem/psicologia , Imagem por Ressonância Magnética , Masculino , Transtornos da Memória/psicologia , Neuroimagem , Testes Neuropsicológicos , Tamanho do Órgão , Radioterapia Adjuvante/efeitos adversos , Eficiência Biológica Relativa , Carga Tumoral , Aprendizagem Verbal/efeitos da radiação
5.
Neurotoxicology ; 67: 1-26, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29634994

RESUMO

Childhood lead exposure has been correlated to acts of delinquency and criminal behavior; however, little research has been conducted to examine its potential long term influence on behavioral factors such as personality, specifically psychopathic personality. Neuroimaging studies have demonstrated that the effects of childhood lead exposure persist into adulthood, with structural abnormalities found in gray and white matter regions involved in behavioral decision making. The current study examined whether measurements of adult psychopathy were associated with neuroanatomical differences in structural brain volumes for a longitudinal cohort with measured childhood lead exposure. We hypothesized that increased total psychopathy scores and increased blood lead concentration at 78 months of age (PbB78) would be inversely associated with volumetric measures of gray and white matter brain structures responsible for executive and emotional processing. Analyses did not display a direct effect between total psychopathy score and gray matter volume; however, reduced white matter volume in the cerebellum and brain stem in relation to increased total psychopathy scores was observed. An interaction between sex and total psychopathy score was also detected. Females displayed increased gray matter volume in the frontal, temporal, and parietal lobes associated with increased total psychopathy score, but did not display any white matter volume differences. Males primarily displayed reductions in frontal gray and white matter brain volume in relation to increased total psychopathy scores. Additionally, reduced gray and white matter volume was associated with increased blood lead levels in the frontal lobes; reduced white matter volume was also observed in the parietal and temporal lobes. Females demonstrated gray and white matter volume loss associated with increased PbB78 values in the right temporal lobe, as well as reduced gray matter volume in the frontal lobe. Males displayed reduced white matter volumes associated with increased PbB78 values in the frontal, temporal, and parietal lobes. Comparison of the two primary models revealed a volumetric decrease in the white matter of the left prefrontal cortex associated with increased total psychopathy scores and increased blood lead concentration in males. The results of this study suggested that increased psychopathy scores in this cohort may be attributable to the neuroanatomical abnormalities observed and that childhood lead exposure may be influential to these outcomes.


Assuntos
Transtorno da Personalidade Antissocial/diagnóstico por imagem , Transtorno da Personalidade Antissocial/epidemiologia , Encéfalo/diagnóstico por imagem , Intoxicação do Sistema Nervoso por Chumbo na Infância/diagnóstico por imagem , Intoxicação do Sistema Nervoso por Chumbo na Infância/epidemiologia , Vigilância da População , Adulto , Transtorno da Personalidade Antissocial/psicologia , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imageamento Tridimensional/métodos , Lactente , Chumbo/efeitos adversos , Intoxicação do Sistema Nervoso por Chumbo na Infância/psicologia , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Tamanho do Órgão , Vigilância da População/métodos , Gravidez , Adulto Jovem
6.
Quant Imaging Med Surg ; 5(4): 511-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26435914

RESUMO

BACKGROUND: Childhood lead exposure has been linked to adult gray matter loss accompanied by changes in myelination and neurochemistry noninvasively revealed by magnetic resonance imaging (MRI) methods. However, the extent, duration and timing of lead exposure required to produce such imaging changes in humans are difficult to ascertain. METHODS: To determine if such changes are related to early exposure to low levels of lead, we treated mouse dams with 0, 3, or 30 ppm of lead acetate in drinking water for 2 months prior to mating through gestation until weaning of the offspring at post-natal day 21. Two male and two female pups from each litter were imaged at post-natal day 60. Volumetric, diffusion tensor imaging and magnetic resonance spectroscopy (MRS) measurements were obtained using a seven Tesla Bruker animal MRI scanner. RESULTS: Postnatal blood lead levels were identical between groups at the time of imaging. No effects of lead exposure were detected in the volumetric or MRS data. Mean diffusivity in the hippocampus showed significant effects of lead exposure and gender. CONCLUSIONS: These data suggest that low-level, gestational lead exposure in a mouse model produces minimal changes observed by MRI.

7.
Behav Brain Res ; 253: 32-41, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23850353

RESUMO

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50kHz USV emission. Rats emitted high levels of 22kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related to the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response.


Assuntos
Reflexo de Sobressalto/fisiologia , Filtro Sensorial/fisiologia , Vocalização Animal/fisiologia , Estimulação Acústica , Animais , Cruzamento , Interpretação Estatística de Dados , Emoções/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Esquema de Reforço
8.
Arthritis Rheum ; 65(8): 2190-200, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23666759

RESUMO

OBJECTIVE: To use structural magnetic resonance imaging (MRI) to characterize changes in gray matter and white matter volumes between patients with childhood-onset systemic lupus erythematosus (SLE) and matched controls, between patients with childhood-onset SLE with and those without neurocognitive deficit, and in relation to disease duration and treatment with steroids. METHODS: Twenty-two patients with childhood-onset SLE and 19 healthy controls underwent high-resolution structural MRI. Probability density maps for gray matter and white matter were compared between groups. RESULTS: Neuropsychological testing confirmed the presence of neurocognitive deficit in 8 patients with childhood-onset SLE. Multiple brain regions had reduced gray matter volume in the patients with childhood- onset SLE with neurocognitive deficit versus controls or patients with childhood-onset SLE without neurocognitive deficit. Neither disease duration nor cumulative oral or intravenous steroid doses accounted for decreases in gray matter. White matter volume was also reduced in patients with childhood-onset SLE with neurocognitive deficit, and the reduction was positively associated with both disease duration and cumulative oral steroid dose. Conversely, higher cumulative intravenous steroid doses were associated with higher white matter volumes. CONCLUSION: Neurocognitive deficit in patients with childhood-onset SLE is associated with multifocal decreases in both gray and white matter volumes. Since only white matter volume changes are related to disease duration and cumulative oral steroid use, this may suggest that gray and white matter alterations relate to different underlying mechanisms. Further work is needed to understand the relationship between gray and white matter alterations in childhood-onset SLE, whether the underlying mechanisms relate to immunologic, vascular, or other causes, and whether the changes are reversible or preventable. Likewise, the protective properties of intravenous steroids in maintaining white matter volumes require confirmation in larger cohorts.


Assuntos
Encéfalo/patologia , Transtornos Cognitivos/patologia , Lúpus Eritematoso Sistêmico/patologia , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Amielínicas/patologia , Administração Oral , Adolescente , Idade de Início , Anti-Hipertensivos/uso terapêutico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Comorbidade , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Illinois/epidemiologia , Imunossupressores/uso terapêutico , Injeções Intravenosas , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Imagem por Ressonância Magnética , Masculino , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Amielínicas/efeitos dos fármacos , Testes Neuropsicológicos , Ohio/epidemiologia , Escalas de Graduação Psiquiátrica
9.
Stress ; 12(3): 250-8, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18951246

RESUMO

Exposure to prenatal stress (PNS) has been shown to induce a set of psychological and behavioral changes in developing offspring. We used the rodent model to investigate whether PNS produces changes in the ability of the pup to express social motivation. We used a set of behavioral tasks including monitoring ultrasonic vocalizations after isolation, a conditioned place preference, and a novel and familiar odor approach test. Pregnant Long-Evans rats were exposed to an unpredictable, variable stressor twice daily during the third week of gestation. Isolation vocalizations were assessed on postnatal day (PND) 10. Pup affinity for the dam was evaluated on PND 15. Typically, pups display a selective preference for an odor-paired environment only after the odor has been associated with the dam. This previous association produces a positive conditioned stimulus (CS). Normally, pups exposed to a neutral CS (odor paired with cotton balls) do not form this place preference. Results indicate that PNS exposed pups had significantly increased distress vocalizations and an equal preference for the positive and neutral conditioned stimuli. This type of alteration in forming early preferences could be detrimental because of decreases in the specificity of social learning and an impaired responsiveness in social relationships.


Assuntos
Motivação , Efeitos Tardios da Exposição Pré-Natal , Estresse Psicológico/psicologia , Vocalização Animal/fisiologia , Animais , Condicionamento Clássico , Feminino , Odorantes , Gravidez , Ratos , Ratos Long-Evans , Restrição Física , Isolamento Social
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