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1.
Am J Vet Res ; 82(3): 230-236, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33629902

RESUMO

OBJECTIVE: To examine whether glucocorticoid (GC) administration alters hippocampal cerebral blood flow (CBF) or volume in dogs. ANIMALS: 6 clinically normal adult Beagles. PROCEDURES: Each dog underwent CT and MRI to measure the CBF in the hippocampus, basal ganglia, thalamus, and cerebral cortex and the volume of the hippocampus in each hemisphere of the brain before (day 0) and during (days 7 and 21) a 21-day treatment with prednisolone (1.0 mg/kg, PO, q 24 h) and famotidine (0.5 mg/kg, PO, q 12 h). Results for hippocampal volume, anesthesia-related variables, and semiquantitative measurements of CBF (hemisphere-specific ratios of the CBF in the hippocampus, basal ganglia, and thalamus relative to the CBF in the ipsilateral cerebral cortex and the left cerebral cortex CBF-to-right cerebral cortex CBF ratio) were compared across assessment time points (days 0, 7, and 21). RESULTS: The ratios of CBF in the right hippocampus and right thalamus to that in the right cerebral cortex on day 21 were significantly lower than those on day 0. No meaningful differences were detected in results for the hippocampal volume in either hemisphere or for the anesthesia-related variables across the 3 time points. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that GC administration reduced CBF in the hippocampus and thalamus in dogs of the present study, similar to that which occurs in humans. Research on GC-related brain alteration in dogs could potentially contribute to advancements in understanding Alzheimer disease in humans and neurodegenerative conditions in dogs.


Assuntos
Circulação Cerebrovascular , Prednisolona , Animais , Gânglios da Base/diagnóstico por imagem , Encéfalo , Cães , Hipocampo/diagnóstico por imagem , Tálamo/diagnóstico por imagem
2.
Nat Commun ; 11(1): 4686, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943633

RESUMO

Electrophysiology provides a direct readout of neuronal activity at a temporal precision only limited by the sampling rate. However, interrogating deep brain structures, implanting multiple targets or aiming at unusual angles still poses significant challenges for operators, and errors are only discovered by post-hoc histological reconstruction. Here, we propose a method combining the high-resolution information about bone landmarks provided by micro-CT scanning with the soft tissue contrast of the MRI, which allowed us to precisely localize electrodes and optic fibers in mice in vivo. This enables arbitrating the success of implantation directly after surgery with a precision comparable to gold standard histology. Adjustment of the recording depth with micro-drives or early termination of unsuccessful experiments saves many working hours, and fast 3-dimensional feedback helps surgeons avoid systematic errors. Increased aiming precision enables more precise targeting of small or deep brain nuclei and multiple targeting of specific cortical or hippocampal layers.


Assuntos
Encéfalo/diagnóstico por imagem , Eletrodos Implantados , Processamento de Imagem Assistida por Computador/métodos , Fibras Ópticas , Microtomografia por Raio-X/métodos , Animais , Comportamento Animal , Encéfalo/patologia , Mapeamento Encefálico , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/cirurgia , Técnicas Histológicas/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Silício , Técnicas Estereotáxicas
3.
Stroke ; 51(9): e183-e192, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32772680

RESUMO

BACKGROUND AND PURPOSE: Brain atrophy can be regarded as an end-organ effect of cumulative cardiovascular risk factors. Accelerated brain atrophy is described following ischemic stroke, but it is not known whether atrophy rates vary over the poststroke period. Examining rates of brain atrophy allows the identification of potential therapeutic windows for interventions to prevent poststroke brain atrophy. METHODS: We charted total and regional brain volume and cortical thickness trajectories, comparing atrophy rates over 2 time periods in the first year after ischemic stroke: within 3 months (early period) and between 3 and 12 months (later period). Patients with first-ever or recurrent ischemic stroke were recruited from 3 Melbourne hospitals at 1 of 2 poststroke time points: within 6 weeks (baseline) or 3 months. Whole-brain 3T magnetic resonance imaging was performed at 3 time points: baseline, 3 months, and 12 months. Eighty-six stroke participants completed testing at baseline; 125 at 3 months (76 baseline follow-up plus 49 delayed recruitment); and 113 participants at 12 months. Their data were compared with 40 healthy control participants with identical testing. We examined 5 brain measures: hippocampal volume, thalamic volume, total brain and hemispheric brain volume, and cortical thickness. We tested whether brain atrophy rates differed between time points and groups. A linear mixed-effect model was used to compare brain structural changes, including age, sex, years of education, a composite cerebrovascular risk factor score, and total intracranial volume as covariates. RESULTS: Atrophy rates were greater in stroke than control participants. Ipsilesional hemispheric, hippocampal, and thalamic atrophy rates were 2 to 4 times greater in the early versus later period. CONCLUSIONS: Regional atrophy rates vary over the first year after stroke. Rapid brain volume loss in the first 3 months after stroke may represent a potential window for intervention. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02205424.


Assuntos
Atrofia , Isquemia Encefálica/patologia , Encéfalo/patologia , Acidente Vascular Cerebral/patologia , Adulto , Fatores Etários , Idoso , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Progressão da Doença , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores Sexuais , Acidente Vascular Cerebral/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Tálamo/patologia , Resultado do Tratamento
4.
Neurology ; 95(17): e2418-e2426, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32817185

RESUMO

OBJECTIVE: To test the hypothesis that in periventricular nodular heterotopia (PVNH) structure and function of cortical areas overlying the heterotopic gray matter are preferentially affected. METHODS: We studied a group of 40 patients with PVNH and normal-appearing cortex and compared their quantitative MRI markers of brain development, structure, and function to those of 43 age- and sex-matched healthy controls. Inspired by models of neocortical development suggesting that neuronal migration follows a curvilinear path to preserve topologic correspondence between the outer ventricular zone and the cortical surface, we computationally defined the overlying cortex using the Laplace equation and generated synthetic streamlines that link the ventricles, where nodules are located, and the neocortex. RESULTS: We found multilobar cortical thickening encompassing prefrontal, latero-basal temporal, and temporoparietal cortices largely corresponding with the PVNH group-averaged map of the overlying cortex, the latter colocalized with areas of abnormal function, as defined by resting-state fMRI. Patients also presented hippocampal functional hyperconnectivity and malrotation, the latter positively correlating with neocortical maldevelopment indexed by increased folding complexity of the parahippocampus. In clusters of thickness and curvature findings, there were no significant differences between unilateral and bilateral PVNH; contrasting brain-wide metrics between cohorts was also unrevealing. There was no relationship between imaging markers and disease duration except for positive correlation with functional anomalies. CONCLUSION: Our quantitative image analysis demonstrates widespread structural and functional alterations in PVNH with differential interaction with the overlying cortex and the hippocampus. Right hemispheric predominance may be explained by an early insult, likely genetically determined, on brain morphogenesis.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Heterotopia Nodular Periventricular/diagnóstico por imagem , Adulto , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Ventrículos Cerebrais/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Eletroencefalografia , Lateralidade Funcional , Substância Cinzenta/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Modelos Neurológicos , Imagem Multimodal , Neocórtex/crescimento & desenvolvimento , Giro Para-Hipocampal/diagnóstico por imagem , Fenótipo , Adulto Jovem
5.
Wien Klin Wochenschr ; 132(17-18): 542-544, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32778968

RESUMO

Acute encephalopathy is a rare complication of influenza, particularly in adults. We report the case of a 77-year-old woman presenting with complete anterograde and significant retrograde amnesia developing during an influenza B infection. Cranial magnetic resonance imaging (MRI) showed hippocampal lesions including restricted diffusion during the acute phase. Symptoms partially improved following treatment with intravenous methylprednisolone and immunoglobulins but an amnesic syndrome persisted. We discuss possible causes of neurological complications in influenza infections.


Assuntos
Encefalopatias , Influenza Humana , Idoso , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Imagem por Ressonância Magnética , Metilprednisolona/uso terapêutico
6.
Neurology ; 95(19): e2622-e2634, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-32732300

RESUMO

OBJECTIVE: To determine whether vascular and neurodegenerative factors influence cognition before clinically relevant Alzheimer disease pathology, we analyzed MRI measures and amyloid imaging in an ethnoracially diverse cohort of cognitively normal individuals older than 60 years. METHODS: Participants (n = 154; mean age 74.15 ± 6.94; 50% female; 54% Caucasian, 22.1% Hispanic, 14.9% African American) were recruited from the University of California, Davis Alzheimer's Disease Research Center, who were cognitively normal at baseline, time of PET, and MRI, and received yearly cognitive assessment for 6.23 ± 4.16 years. Mixed model regression with random slope and intercept was calculated for episodic memory and executive function, adjusting for age, sex, education, and ethnicity. RESULTS: Vascular burden score was associated with total white matter hyperintensity (WMH) volume (ß, 0.171; 95% confidence interval [CI], 0.024-0.318). WMH volume was associated with low baseline executive function (-0.115; -0.226 to -0.003) and rate of change in memory (-0.029; -0.045 to -0.012). Hippocampal volume was associated with the rate of change in memory (0.040; 0.021-0.059) and executive function (0.024; 0.008-0.039). Continuous measures of amyloid status influenced change in memory (-0.026; -0.044 to -0.008) and executive function (-0.033; -0.046 to -0.021) independently of MRI measures. CONCLUSION: Vascular brain injury and neurodegeneration are associated with baseline cognitive performance and the rate of longitudinal change independent of amyloid status among community-dwelling, ethnicity diverse cognitively normal individuals, supporting the role of vascular diseases as risk factors for later-life dementia.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Hipocampo/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Encéfalo/metabolismo , Cognição/fisiologia , Progressão da Doença , Função Executiva/fisiologia , Feminino , Hipocampo/patologia , Humanos , Vida Independente , Imagem por Ressonância Magnética , Masculino , Transtornos da Memória/fisiopatologia , Memória Episódica , Testes Neuropsicológicos , Tamanho do Órgão , Tomografia por Emissão de Pósitrons , Tiazóis , Substância Branca/patologia
7.
Nat Commun ; 11(1): 3318, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620879

RESUMO

Decision-making is guided by memories of option values. However, retrieving items from memory renders them malleable. Here, we show that merely retrieving values from memory and making a choice between options is sufficient both to induce changes to stimulus-reward associations in the hippocampus and to bias future decision-making. After allowing participants to make repeated choices between reward-conditioned stimuli, in the absence of any outcome, we observe that participants prefer stimuli they have previously chosen, and neglect previously unchosen stimuli, over otherwise identical-valued options. Using functional brain imaging, we show that decisions induce changes to hippocampal representations of stimulus-outcome associations. These changes are correlated with future decision biases. Our results indicate that choice-induced preference changes are partially driven by choice-induced modification of memory representations and suggest that merely making a choice - even without experiencing any outcomes - induces associative plasticity.


Assuntos
Comportamento de Escolha/fisiologia , Tomada de Decisões/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Adulto , Algoritmos , Viés , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Condicionamento Clássico/fisiologia , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Desempenho Psicomotor/fisiologia , Recompensa , Adulto Jovem
8.
BMC Neurol ; 20(1): 235, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513122

RESUMO

BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy, which is frequently characterized by hippocampal sclerosis (HS). Accumulating studies have suggested widespread cortico-cortical connections related to MTLE. The role of subcortical structures involved in general epilepsy has been extensively investigated, but it is still limited in MTLE. Our purpose was to determine the specific morphological correlation between sclerotic hippocampal and thalamic sub-regions, using quantitative analysis, in MTLE. METHODS: In this study, 23 MTLE patients with unilateral hippocampal sclerosis and 24 healthy controls were examined with three-dimensional T1 MRI. Volume quantitative analysis in the hippocampus and thalamus was conducted and group-related volumetric difference was assessed. Moreover, vertex analysis was further performed using automated software to delineate detailed morphological patterns of the hippocampus and thalamus. The correlation was used to examine whether there is a relationship between volume changes of two subcortical structures and clinical characteristics. RESULTS: The patients had a significant volume decrease in the sclerotic hippocampus (p < 0.001). Compared to controls, obvious atrophic patterns were observed in the bilateral hippocampus in MTLE (p < 0.05). Only small patches of shrinkage were noted in the bilateral thalamus (p < 0.05). Moreover, the volume change of the hippocampus had a significant positive correlation with that of the thalamus (P < 0.001). Intriguingly, volume changes of the hippocampus and thalamus were correlated with the duration of epilepsy (hippocampus: P = 0.024; thalamus: P = 0.022). However, only volume changes of thalamus possibly differentiated between two prognostic groups in patients (P = 0.026). CONCLUSIONS: We demonstrated the morphological characteristics of the hippocampus and thalamus in MTLE, providing new insights into the interrelated mechanisms between the hippocampus and thalamus, which have potential clinical significance for refining neuromodulated targets.


Assuntos
Epilepsia do Lobo Temporal , Hipocampo , Tálamo , Adolescente , Adulto , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose , Tálamo/diagnóstico por imagem , Tálamo/patologia , Adulto Jovem
9.
Neurology ; 95(2): e206-e212, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32532848

RESUMO

OBJECTIVE: To analyze how the evidence of hippocampal diffusion-weighted imaging (DWI) lesions may support the clinical diagnosis of transient global amnesia (TGA). METHODS: In this retrospective observational study, 390 consecutive patients with isolated TGA were analyzed, who were evaluated at our institution between July 1999 and August 2018. The size, location, and number of lesions and time-dependent lesion detectability were examined. The incidence of DWI lesions was reviewed with regard to different levels of clinical diagnostic certainty upon presentation to the emergency department. RESULTS: Hippocampal DWI lesions were detected in 272 (70.6%) patients with TGA, with a mean of 1.05 ± 0.98 (range 0-6) and a mean lesion size of 4.01 ± 1.22 mm (range 1.7-8.6 mm). In the subgroups of lower diagnostic certainty (amnesia witnessed by layperson or self-reported amnestic gap), DWI was helpful in supporting the diagnosis of TGA in 76 (69.1%) patients. In 187 patients with information about the exact onset, DWI lesions were analyzed in relation to latency between onset and MRI. Lesions could be detected at all time points and up to 6 days after symptom onset in individual patients; the highest rate of DWI-positive MRI (93%) was in the 12-24 hours time window. CONCLUSION: MRI findings can support the diagnosis of TGA and may be particularly valuable in situations of low clinical certainty. DWI-ideally performed with a minimum delay of 20 hours after onset-should therefore be considered a useful adjunct to the diagnosis of TGA.


Assuntos
Amnésia Global Transitória/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amnésia Global Transitória/diagnóstico , Amnésia Global Transitória/psicologia , Bases de Dados Factuais , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Retrospectivos
10.
AJNR Am J Neuroradiol ; 41(6): 987-993, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32522839

RESUMO

BACKGROUND AND PURPOSE: Automated volumetry of the hippocampus is considered useful to assist the diagnosis of hippocampal sclerosis in temporal lobe epilepsy. However, voxel-based morphometry is rarely used for individual subjects because of high rates of false-positives. We investigated whether an approach with high dimensional warping to the template and nonparametric statistics would be useful to detect hippocampal atrophy in patients with hippocampal sclerosis. MATERIALS AND METHODS: We performed single-subject voxel-based morphometry with nonparametric statistics within the framework of Statistical Parametric Mapping to compare MRI from 26 well-characterized patients with temporal lobe epilepsy individually against a group of 110 healthy controls. The following statistical threshold was used: P < .05 corrected for multiple comparisons with family-wise error over the region of interest right and left hippocampus. RESULTS: The sensitivity for the detection of atrophy related to hippocampal sclerosis was 0.92 (95% CI, 0.67-0.99) for the right hippocampus and 0.60 (0.31-0.83) for the left, and the specificity for volume changes was 0.98 (0.93-0.99). All clusters of decreased hippocampal volumes were correctly lateralized to the seizure focus. Hippocampal volume decrease was in accordance with neuronal cell loss on histology reports. CONCLUSIONS: Nonparametric voxel-based morphometry is sensitive and specific for hippocampal atrophy in patients with mesial temporal lobe epilepsy and may be useful in clinical practice.


Assuntos
Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Neuroimagem/métodos , Adulto , Atrofia/diagnóstico por imagem , Atrofia/patologia , Feminino , Humanos , Imageamento Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
11.
PLoS One ; 15(6): e0233670, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492020

RESUMO

AIMS: Smaller hippocampal volumes are among the most consistently reported neuroimaging findings in schizophrenia. However, little is known about hippocampal volumes in people who report psychotic experiences. This study investigated differences in hippocampal volume between young people without formal diagnoses who report psychotic experiences (PEs) and those who do not report such experiences. This study also investigated if any differences persisted over two years. METHODS: A nested case-control study of 25 adolescents (mean age 13.5 years) with reported PEs and 25 matched controls (mean age 13.36 years) without PEs were drawn from a sample of 100 local schoolchildren. High-resolution T1-weighted anatomical imaging and subsequent automated cortical segmentation (Freesurfer 6.0) was undertaken to determine total hippocampal volumes. Comprehensive semi-structured clinical interviews were also performed including information on PEs, mental diagnoses and early life stress (bullying). Participants were invited for a second scan at two years. RESULTS: 19 adolescents with PEs and 19 controls completed both scans. Hippocampal volumes were bilaterally lower in the PE group compared to the controls with moderate effects sizes both at baseline [left hippocampus p = 0.024 d = 0.736, right hippocampus p = 0.018, d = 0.738] and at 2 year follow up [left hippocampus p = 0.027 d = 0.702, right = 0.048 d = 0.659] throughout. These differences survived adjustment for co-morbid mental disorders and early life stress. CONCLUSIONS: Psychotic experiences are associated with total hippocampal volume loss in young people and this volume loss appears to be independent of possible confounders such as co-morbid disorders and early life stress.


Assuntos
Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Adolescente , Bullying , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Tamanho do Órgão
12.
Am J Cardiol ; 129: 102-108, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32576368

RESUMO

Evidence on the relations between heart rate, brain morphology, and cognition is limited. We examined the associations of resting heart rate (RHR), visit-to-visit heart rate variation (VVHRV), brain volumes and cognitive impairment. The study sample consisted of postmenopausal women enrolled in the Women's Health Initiative Memory Study and its ancillary MRI sub-studies (WHIMS-MRI 1 and WHIMS-MRI 2) without a history of cardiovascular disease, including 493 with one and 299 women with 2 brain magnetic resonance imaging (MRI) scans. HR readings were acquired annually starting from baseline visit (1996-1998). RHR was calculated as the mean and VVHRV as standard deviation of all available HR readings. Brain MRI scans were performed between 2005 and 2006 (WHIMS-MRI 1), and approximately 5 years later (WHIMS-MRI 2). Cognitive impairment was defined as incident mild cognitive impairment or probable dementia until December 30, 2017. An elevated RHR was associated with greater brain lesion volumes at the first MRI exam (7.86 cm3 [6.48, 9.24] vs 4.78 cm3 [3.39, 6.17], p-value <0.0001) and with significant increases in lesion volumes between brain MRI exams (6.20 cm3 [4.81, 7.59] vs 4.28 cm3 [2.84, 5.73], p-value = 0.0168). Larger ischemic lesion volumes were associated with a higher risk for cognitive impairment (Hazard Ratio [95% confidence interval], 2.02 [1.18, 3.47], p-value = 0.0109). Neither RHR nor VVHRV were related to cognitive impairment. In sensitivity analyses, we additionally included women with a history of cardiovascular disease to the study sample. The main results were consistent to those without a history of cardiovascular disease. In conclusion, these findings show an association between elevated RHR and ischemic brain lesions, probably due to underlying subclinical disease processes.


Assuntos
Isquemia Encefálica/epidemiologia , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Frequência Cardíaca/fisiologia , Idoso , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Demência/diagnóstico por imagem , Terapia de Reposição de Estrogênios , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Tamanho do Órgão , Pós-Menopausa , Modelos de Riscos Proporcionais , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
14.
Nat Commun ; 11(1): 3143, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561719

RESUMO

Topoisomerase 3ß (Top3ß) is the only dual-activity topoisomerase in animals that can change topology for both DNA and RNA, and facilitate transcription on DNA and translation on mRNAs. Top3ß mutations have been linked to schizophrenia, autism, epilepsy, and cognitive impairment. Here we show that Top3ß knockout mice exhibit behavioural phenotypes related to psychiatric disorders and cognitive impairment. The mice also display impairments in hippocampal neurogenesis and synaptic plasticity. Notably, the brains of the mutant mice exhibit impaired global neuronal activity-dependent transcription in response to fear conditioning stress, and the affected genes include many with known neuronal functions. Our data suggest that Top3ß is essential for normal brain function, and that defective neuronal activity-dependent transcription may be a mechanism by which Top3ß deletion causes cognitive impairment and psychiatric disorders.


Assuntos
Disfunção Cognitiva/genética , DNA Topoisomerases Tipo I/genética , Transtornos Mentais/genética , Neurogênese/genética , Plasticidade Neuronal/genética , Animais , Técnicas de Observação do Comportamento , Comportamento Animal , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Feminino , Hipocampo/citologia , Hipocampo/diagnóstico por imagem , Hipocampo/crescimento & desenvolvimento , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/patologia , Camundongos , Camundongos Knockout , Neurônios/patologia , Técnicas Estereotáxicas , Potenciais Sinápticos/genética , Transcrição Genética/fisiologia
15.
J Clin Neurosci ; 78: 327-332, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32593622

RESUMO

Using magnetic resonance imaging to determine neuropathology in autism spectrum disorders, we report findings on the volume of the amygdala and hippocampus in autistic children. The volumes of amygdala, hippocampus and total brain were obtained by volbrain and their volumes were measured in young people (6.5-27.0 years of age) that comes from ABIDE dataset. Although there was no significant difference in total brain capacity between groups, autistic children (6.5-12.0 years of age) had larger right and left absolute and relative amygdala volumes than the control group. There was no difference in amygdala volume between adolescence (13-19 years old) and adults (20-27 years old). Interestingly, the volume of the amygdala in typical developing children increased significantly from 6.5 to 27 years of age. Thus, amygdala in children with autism was initially small, but no age-related increases were observed in normal developing children. The right absolute hippocampal volume of autistic patients was also larger than that of normal adults, but not after controlling the total brain volume. These cross-sectional findings suggest that abnormal patterns of hippocampal and amygdala development continue into adolescence in autistic patients.


Assuntos
Tonsila do Cerebelo/crescimento & desenvolvimento , Transtorno Autístico/diagnóstico por imagem , Hipocampo/crescimento & desenvolvimento , Imagem por Ressonância Magnética/métodos , Adolescente , Adulto , Fatores Etários , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/patologia , Transtorno Autístico/patologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Criança , Estudos Transversais , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Tamanho do Órgão , Adulto Jovem
16.
Proc Natl Acad Sci U S A ; 117(25): 14503-14511, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513712

RESUMO

The nanoscale co-organization of neurotransmitter receptors facing presynaptic release sites is a fundamental determinant of their coactivation and of synaptic physiology. At excitatory synapses, how endogenous AMPARs, NMDARs, and mGluRs are co-organized inside the synapse and their respective activation during glutamate release are still unclear. Combining single-molecule superresolution microscopy, electrophysiology, and modeling, we determined the average quantity of each glutamate receptor type, their nanoscale organization, and their respective activation. We observed that NMDARs form a unique cluster mainly at the center of the PSD, while AMPARs segregate in clusters surrounding the NMDARs. mGluR5 presents a different organization and is homogenously dispersed at the synaptic surface. From these results, we build a model predicting the synaptic transmission properties of a unitary synapse, allowing better understanding of synaptic physiology.


Assuntos
Modelos Neurológicos , Neurônios/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/fisiologia , Animais , Células Cultivadas , Embrião de Mamíferos , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/citologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Microscopia Intravital , Neurônios/ultraestrutura , Técnicas de Patch-Clamp , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Imagem Individual de Molécula
17.
Psychiatry Res Neuroimaging ; 301: 111087, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32413812

RESUMO

Childhood maltreatment has long lasting impacts on neural development of the hippocampus, which is important for learning and memory. The present study aimed to assess the effects of a mindfulness based intervention on hippocampal morphometry and episodic memory in this population. We administered MRI, psychological questionnaires and an episodic memory task to 21 participants (5 males) before and after a mindfulness-based behavioral intervention, compared to 21 participants (7 males) on the waiting list. Changes in Gray Matter Volume (GMV) in bilateral hippocampi were analyzed with Voxel-Based Morphometry (VBM). One cluster was identified in the right hippocampus with a group by time interaction effect that consisted of 130 contiguous voxels but fell short of significance with full FDR correction (p = 0.077). GMV in this cluster increased by 0.76% in the mindfulness group and decreased by 0.78% in the control group. Within the mindfulness group, changes in hippocampal GMV were negatively associated with changes in perceived stress and depression severity and positively associated with enhancement in performance accuracy on the episodic memory task. Findings from this pilot study suggest that a mindfulness-based intervention may lead to an increase in partial hippocampal GMV with associated symptom reduction and improvement in episodic memory.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Hipocampo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Atenção Plena , Adulto , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Memória Episódica , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
18.
Ann Neurol ; 88(1): 170-182, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32379905

RESUMO

OBJECTIVE: Cognitive problems, especially disturbances in episodic memory, and hippocampal sclerosis are common in temporal lobe epilepsy (TLE), but little is known about the relationship of hippocampal morphology with memory. We aimed to relate hippocampal surface-shape patterns to verbal and visual learning. METHODS: We analyzed hippocampal surface shapes on high-resolution magnetic resonance images and the Adult Memory and Information Processing Battery in 145 unilateral refractory TLE patients undergoing epilepsy surgery, a validation set of 55 unilateral refractory TLE patients, and 39 age- and sex-matched healthy volunteers. RESULTS: Both left TLE (LTLE) and right TLE (RTLE) patients had lower verbal (LTLE 44 ± 11; RTLE 45 ± 10) and visual learning (LTLE 34 ± 8, RTLE 30 ± 8) scores than healthy controls (verbal 58 ± 8, visual 39 ± 6; p < 0.001). Verbal learning was more impaired the greater the atrophy of the left superolateral hippocampal head. In contrast, visual memory was worse with greater bilateral inferomedial hippocampal atrophy. Postsurgical verbal memory decline was more common in LTLE than in RTLE (reliable change index in LTLE 27% vs RTLE 7%, p = 0.006), whereas there were no differences in postsurgical visual memory decline between those groups. Preoperative atrophy of the left hippocampal tail predicted postsurgical verbal memory decline. INTERPRETATION: Memory deficits in TLE are associated with specific morphological alterations of the hippocampus, which could help stratify TLE patients into those at high versus low risk of presurgical or postsurgical memory deficits. This knowledge could improve planning and prognosis of selective epilepsy surgery and neuropsychological counseling in TLE. ANN NEUROL 2020 ANN NEUROL 2020;88:170-182.


Assuntos
Epilepsia do Lobo Temporal/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Transtornos da Memória/diagnóstico por imagem , Memória Episódica , Adulto , Mapeamento Encefálico , Epilepsia do Lobo Temporal/complicações , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tamanho do Órgão/fisiologia
19.
Neuropsychology ; 34(5): 578-590, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32352829

RESUMO

OBJECTIVE: Presurgical memory functional MRI (fMRI) mapping for temporal lobe epilepsy surgery is important because of the excision of structures in the temporal lobe (e.g., hippocampus) that are relevant for intact memory. Although the American Academy of Neurology recommends the use of fMRI for presurgical mapping of epilepsy of verbal and nonverbal memory to predict memory outcome, there are still no specific recommendations about which tests to use. In the current study, we evaluate the potential for clinical utility of two established neuropsychological tests of memory adapted into the fMRI setting. METHOD: We used the Verbal Paired Associates (VPA) for assessment of verbal memory and the Object Learning and Location (OLL) task for assessment of visuospatial memory. To confirm that these tasks engage the hippocampus, we examined their neural underpinning and patterns of laterality in 20 healthy volunteers (mean age = 26.35). RESULTS: During fMRI of the VPA task of verbal memory, we found a strong left-lateralized posterior hippocampal activation. Remembering the location of objects in the OLL task of visuospatial memory elicited right-lateralized hippocampal activation. CONCLUSIONS: These findings demonstrate the utility of the VPA and OLL tests to delineate domain-specific activity and laterality and, as such, may provide supportive evidence to strengthen links between presurgical neuropsychological assessment and memory fMRI mapping for epilepsy surgery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Lateralidade Funcional/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Adulto , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Adulto Jovem
20.
Neurology ; 94(23): e2424-e2435, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32358221

RESUMO

OBJECTIVE: To determine the predictive power of white matter neuronal networks (i.e., structural connectomes [SCs]) in discriminating memory-impaired patients with temporal lobe epilepsy (TLE) from those with normal memory. METHODS: T1- and diffusion MRI (dMRI), clinical variables, and neuropsychological measures of verbal memory were available for 81 patients with TLE. Prediction of memory impairment was performed with a tree-based classifier (XGBoost) for 4 models: (1) a clinical model including demographic and clinical features, (2) a hippocampal volume (HCV) model, (3) a tract model including 5 temporal lobe white matter association tracts derived from a dMRI atlas, and (4) an SC model based on dMRI. SCs were derived by extracting cortical-cortical connections from a temporal lobe subnetwork with probabilistic tractography. Principal component (PC) analysis was then applied to reduce the dimensionality of the SC, yielding 10 PCs. Multimodal models were also tested combining SCs and tracts with HCV. Each model was trained on 48 patients from 1 epilepsy center and tested on 33 patients from a different center. RESULTS: Multimodal models that included the SC + HCV model yielded the highest classification accuracy (81%; 0.90 sensitivity; 0.67 specificity), outperforming the clinical model (61%; p < 0.001) and HCV model (66%; p < 0.001). In addition, the unimodal SC model (76% accuracy) and tract model (73% accuracy) outperformed the clinical model (p < 0.001) and HCV model (p < 0.001) for classifying patients with TLE with and without memory impairment. Furthermore, the SC identified that short-range temporal-temporal connections were important contributors to memory performance. CONCLUSION: SCs and tract-based models are stronger predictors of memory impairment in TLE than HCVs and clinical variables. However, SCs may provide additional information about local cortical-cortical connectivity contributing to memory that is not captured in large association tracts.


Assuntos
Conectoma , Epilepsia do Lobo Temporal/psicologia , Transtornos da Memória/etiologia , Adulto , Anisotropia , Área Sob a Curva , Imagem de Tensor de Difusão , Escolaridade , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/patologia , Pessoa de Meia-Idade , Modelos Neurológicos , Testes Neuropsicológicos , Tamanho do Órgão , Análise de Componente Principal , Curva ROC , Sensibilidade e Especificidade , Aprendizagem Verbal/fisiologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
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