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1.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(10): 111-120, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31793552

RESUMO

The high prevalence of anxiety disorders around the world leads to a high interest in the study of anxiety. At the moment, a lot of knowledge about the pathogenesis and therapy of anxiety disorders has been accumulated, which is well covered in modern domestic and world medical literature. It is known that many areas of the brain are involved in the modulation of anxiety, among which the amygdala is considered the key in the modulation of anxiety and fear. A large body of evidence supports the involvement of different neurotransmitter systems in the processes of anxiogenesis-anxiolysis (GABA, monoamines, glutamate, neuropeptides, neurosteroids). This article provides an analysis of methods of pharmacological impact on each of these systems, which serve to optimize the already known strategies of anxiolytic therapy.


Assuntos
Ansiolíticos , Transtornos de Ansiedade , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiopatologia , Ansiolíticos/uso terapêutico , Ansiedade , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/tratamento farmacológico , Medo , Humanos
2.
Neurochem Res ; 44(9): 2123-2138, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376053

RESUMO

Number of ligations made in the chronic constriction injury (CCI) neuropathic pain model has raised serious concerns. We compared behavioural responses, nerve morphology and expression of pain marker, c-fos among CCI models developed with one, two, three and four ligations. The numbers of ligation(s) on sciatic nerve shows no significant difference in displaying mechanical and cold allodynia, and mechanical and thermal hyperalgesia throughout 84 days. All groups underwent similar levels of nerve degeneration post-surgery. Similar c-fos level in brain cingulate cortex, parafascicular nuclei and amygdala were observed in all CCI models compared to sham-operated group. Therefore, number of ligations does not impact intensity of pain symptoms, pathogenesis and neuronal activation. A single ligation is sufficient to develop neuropathic pain, in contrast to the established model of four ligations. This study dissects and characterises the CCI model, ascertaining a more uniform animal model to surrogate actual neuropathic pain condition.


Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos ICR , Neuralgia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Tonsila do Cerebelo/fisiopatologia , Animais , Constrição Patológica/complicações , Giro do Cíngulo/metabolismo , Giro do Cíngulo/patologia , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/patologia , Ligadura , Masculino , Neuralgia/etiologia , Neuralgia/metabolismo , Neuralgia/patologia , Neuralgia/fisiopatologia , Medição da Dor , Proteínas Proto-Oncogênicas c-fos/metabolismo , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Neuropatia Ciática/etiologia , Neuropatia Ciática/metabolismo , Neuropatia Ciática/patologia , Neuropatia Ciática/fisiopatologia
3.
Soc Cogn Affect Neurosci ; 14(7): 769-775, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31309971

RESUMO

Previous research has linked sensation seeking with a heightened risk for drug abuse and other risk-taking behavior. As appetitive conditioning presents a model for the etiology and maintenance of addictive behavior, investigating sensation seeking in a classical conditioning paradigm might elucidate possible pathways toward addiction within this model. Furthermore, the theoretical concept underlying sensation seeking proposes a negative relationship between reward processing and sensation seeking in only moderately arousing situations, which has been neglected by previous research. This study aimed to investigate this inverse relationship in moderately stimulating situations entailing reward processing using functional magnetic resonance imaging. Subjects (N = 38) participated in a classical conditioning paradigm in which a neutral stimulus (CS+) was repeatedly paired with a monetary reward, while another neutral stimulus (CS-) was not. Imaging results revealed a negative relationship between sensation seeking and neural responses in the insula, amygdala and nucleus accumbens during the early phase and in the dorsal anterior cingulate cortex during the late phase of conditioning. These findings suggest reduced reward learning and consequently diminished processing of outcome expectancy in appetitive conditioning in subjects with high sensation seeking scores. The results are discussed with respect to clinical implications.


Assuntos
Condicionamento Clássico/fisiologia , Núcleo Accumbens/fisiologia , Sensação/fisiologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Feminino , Humanos , Aprendizagem/fisiologia , Imagem por Ressonância Magnética , Masculino , Recompensa , Adulto Jovem
4.
Depress Anxiety ; 36(7): 647-658, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31260599

RESUMO

BACKGROUND: Amygdala hyperreactivity to threat has been proposed to be a causal contributor to posttraumatic stress disorder (PTSD). However, emerging literature in healthy samples shows higher test-retest reliability for amygdala habituation (the change over time in response to repeated stimuli) than for its reactivity to threat. Amygdala habituation has received relatively little attention in relationship to PTSD, despite the key role of this region in the etiology of the disorder. Thus, we investigated habituation to repeated fearful face stimuli and PTSD, in a large sample of trauma exposed African American women. METHODS: African American women (N = 100) were recruited from a nonprofit hospital serving a largely low-income population with a high risk of trauma exposure. Participants underwent functional magnetic resonance imaging, passively viewing fearful and neutral face stimuli, and reported their history of trauma exposure and current PTSD symptoms. We examined associations between PTSD symptom severity and amygdala reactivity (fearful > neutral) and habituation (early > late) to fearful faces. Secondary analyses tested whether amygdala habituation to fearful faces mediated the association between childhood trauma and PTSD. RESULTS: PTSD symptom severity and PTSD status (based on self-report measure) were both positively associated with amygdala habituation to repeated fearful face stimuli. Whole-brain analysis showed that this association extended to the bilateral hippocampus and left fusiform gyrus. The association held when controlling for trauma history and depressive symptoms. Amygdala habituation to fearful faces partially mediated the association between childhood trauma severity and PTSD symptom severity. CONCLUSION: Individuals with greater PTSD symptom severity showed greater amygdala habituation to social threat cues (fearful faces), and greater habituation may partly explain the association between childhood trauma exposure and current PTSD symptoms. Further examination of the dynamics of the amygdala response to threat cues may lead to new insights in the understanding and treatment of stress-related disorders.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Medo/fisiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Mapeamento Encefálico , Criança , Sinais (Psicologia) , Expressão Facial , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
5.
Soc Cogn Affect Neurosci ; 14(6): 591-599, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31184751

RESUMO

Few studies have used matched affective paradigms to compare humans and non-human primates. In monkeys with amygdala lesions and youth with anxiety disorders, we examined cross-species pupillary responses during a saccade-based, affective attentional capture task. Given evidence of enhanced amygdala function in anxiety, we hypothesized that opposite patterns would emerge in lesioned monkeys and anxious participants. A total of 53 unmedicated youths (27 anxious, 26 healthy) and 8 adult male rhesus monkeys (Macaca mulatta) completed matched behavioral paradigms. Four monkeys received bilateral excitotoxic amygdala lesions and four served as unoperated controls. Compared to healthy youth, anxious youth exhibited increased pupillary constriction in response to emotional and non-emotional distractors (F(1,48) = 6.28, P = 0.02, η2p = 0.12). Pupillary response was associated significantly with anxiety symptoms severity (F(1,48) = 5.59, P = 0.02, η2p = 0.10). As hypothesized, lesioned monkeys exhibited the opposite pattern i.e. decreased pupillary constriction in response to distractors, compared to unoperated control monkeys (F(1,32) = 24.22, P < 0.001, η2 = 0.33). Amygdala lesioned monkeys and youth with anxiety disorders show opposite patterns of pupil constriction in the context of an affective distractor task. Such findings suggest the presence of altered amygdala circuitry functioning in anxiety. Future lesion and human neuroimaging work might examine the way in which specific amygdala sub-nuclei and downstream circuits mediate these effects.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Ansiedade/fisiopatologia , Atenção/fisiologia , Pupila/fisiologia , Adolescente , Animais , Ansiedade/diagnóstico , Transtornos de Ansiedade/diagnóstico , Criança , Emoções/fisiologia , Feminino , Humanos , Macaca mulatta , Masculino , Índice de Gravidade de Doença
6.
Nutrients ; 11(6)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174338

RESUMO

Few studies have investigated the underlying neural substrates of food addiction (FA) in humans using a recognised assessment tool. In addition, no studies have investigated subregions of the amygdala (basolateral (BLA) and central amygdala), which have been linked to reward-seeking behaviours, susceptibility to weight gain, and promoting appetitive behaviours, in the context of FA. This pilot study aimed to explore the association between FA symptoms and activation in the BLA and central amygdala via functional magnetic resonance imaging (fMRI), in response to visual food cues in fasted and fed states. Females (n = 12) aged 18-35 years completed two fMRI scans (fasted and fed) while viewing high-calorie food images and low-calorie food images. Food addiction symptoms were assessed using the Yale Food Addiction Scale. Associations between FA symptoms and activation of the BLA and central amygdala were tested using bilateral masks and small-volume correction procedures in multiple regression models, controlling for BMI. Participants were 24.1 ± 2.6 years, with mean BMI of 27.4 ± 5.0 kg/m2 and FA symptom score of 4.1 ± 2.2. A significant positive association was identified between FA symptoms and higher activation of the left BLA to high-calorie versus low-calorie foods in the fasted session, but not the fed session. There were no significant associations with the central amygdala in either session. This exploratory study provides pilot data to inform future studies investigating the neural mechanisms underlying FA.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Sinais (Psicologia) , Ingestão de Alimentos , Jejum , Comportamento Alimentar , Dependência de Alimentos/fisiopatologia , Hiperfagia/fisiopatologia , Adolescente , Adulto , Apetite , Índice de Massa Corporal , Ingestão de Energia , Feminino , Alimentos , Dependência de Alimentos/complicações , Dependência de Alimentos/psicologia , Humanos , Hiperfagia/etiologia , Hiperfagia/psicologia , Imagem por Ressonância Magnética , Projetos Piloto , Recompensa , Resposta de Saciedade , Ganho de Peso , Adulto Jovem
7.
Epileptic Disord ; 21(3): 252-264, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31225808

RESUMO

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) has been considered a subtype of TLE. We evaluated the epileptogenic zone in patients with TLE-AE, who underwent intracranial video-EEG (ivEEG) and/or intraoperative electrocorticography (ioECoG) as well as epilepsy surgery. Eleven patients with TLE-AE were enrolled and investigated based on seizure profile, volumetric MRI, the Wechsler Memory Scale-Revised (WMS-R), the location of seizure onset zone (SOZ) and irritative zone (IZ) based on ivEEG (n=8), the location of interictal epileptiform discharges (IEDs) based on ioECoG (11), surgical procedure, and seizure outcome. The mean age at seizure onset was 34.9 years (range: 23-57). The mean duration of seizures was 5.0 years (range: 1-10). The number of AEDs was 2.3 (range: 1-5). The mean seizure frequency was nine per month (range: 1-30/month). All patients presented with focal impaired awareness seizures with (n=9) and without (2) secondary generalized convulsions. Volumetric MRI analysis showed unilateral enlarged amygdala with statistical significance (p<0.01). None of the patients' hippocampi had any abnormality based on MRI. Pre-operative mean verbal, visual, and delayed recall scores based on the WMS-R were over 100. The SOZ and IZ were identified in both the amygdala and hippocampus in seven patients and in only the amygdala in one patient based on ivEEG. IEDs were identified in the hippocampus in six patients and in both the amygdala and hippocampus in four patients based on ioECoG. All 11 patients underwent anterior temporal lobectomy, including amygdala resection, with multiple hippocampal transections (dominant hemisphere: seven patients) and resection (non-dominant hemisphere: three patients). Nine (81.8%) of 11 patients achieved seizure freedom with a mean follow-up of 26 months (range: 12-47). Post-operative WMS-R results did not show any significant deterioration, with a mean follow-up of 15 months (range: 12-24). The resected amygdala showed no histopathological abnormality. The epileptogenic zone of TLE-AE involves both the amygdala and hippocampus. ivEEG may be needed to explore the SOZ in normal hippocampus in addition to enlarged amygdala. Amygdala resection and multiple hippocampal transections may control the epileptogenic limbic system and save memory function in patients with TLE-AE.


Assuntos
Tonsila do Cerebelo/patologia , Epilepsia Resistente a Medicamentos/patologia , Eletrocorticografia , Hipocampo/patologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Lobectomia Temporal Anterior/métodos , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Hipocampo/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Convulsões/fisiopatologia , Lobo Temporal/fisiopatologia
8.
Neuroimage ; 197: 493-501, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31077842

RESUMO

High levels of negative, and low levels of positive parenting behaviors can increase the risk of internalizing symptoms in children, but the mechanisms underlying this association are still unclear. One possibility is that parenting behaviors affect the neural correlates of emotion processing in children. Further, genetic variants relevant to the function of the hypothalamic-pituitary-adrenal (HPA) axis are thought to moderate the effect of early experiences on the brain circuits underlying emotion processing, particularly those involving the amygdala. However, no studies have investigated the interactive effect of parenting behaviors and HPA axis-related genes on amygdala activity and connectivity during emotion processing, and in turn internalizing symptoms in children. Participants comprised 80 children (46 females, mean age = 10.0 years) from the community. Observational measures of maternal behavior were collected during mother-child interactions. Children underwent functional magnetic resonance imaging while performing an implicit emotion-processing task, and mothers and children completed measures of child internalizing symptoms. Genetic risk was calculated using an HPA genetic risk score. HPA genetic risk score was indirectly associated with greater child self-reported depressive symptoms via increased amygdala-precuneus connectivity during the emotion-processing task, and interacted with negative maternal parenting behavior to predict increased connectivity between amygdala and superior frontal gyrus, anterior cingulate cortex and parietal cortex. HPA-related genetic variation appears to moderate the effect of negative maternal parenting behavior on the neural underpinnings of emotion processing in children, and may confer risk for depressive symptoms via modulation of amygdala connectivity.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Interação Gene-Ambiente , Comportamento Materno/psicologia , Relações Mãe-Filho/psicologia , Adulto , Criança , Depressão/etiologia , Depressão/fisiopatologia , Emoções , Feminino , Genótipo , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/fisiopatologia
9.
Depress Anxiety ; 36(8): 712-722, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31111629

RESUMO

OBJECTIVE: Amygdala-based network dysfunction has been found to be centrally implicated in major depressive disorder (MDD). However, relatively little is known about how different forms of effective or cognitive dysfunction are modulated in MDD. Therefore, in the current study, we aimed to examine the alteration of amygdala subregional networks in adult patients with MDD to explore whether different parts of the amygdala that are functionally connected to different regions contribute differently to the cerebral network mechanism of depression. METHODS: Resting-state fMRI scans were obtained from 70 medication-free adults with MDD and 70 age- and sex-matched healthy controls (HC). Functional connectivity maps of four distinct regions of the amygdala, including the amygdalostriatal transition area (AStr) and the basolateral (BLA), centromedial (CM) and superficial (SF) amygdala, were generated and compared between the two groups. RESULTS: Compared with HC, patients with MDD showed hypoconnectivity between the AStr/BLA and the orbitofrontal cortex (OFC), between the CM/SF and the brainstem/cerebellum, and within AStr/CM/SF-thalamic/striatal networks. Hyperconnectivity was observed between the left AStr/BLA and the fusiform gyrus. There was no difference in the gray matter volume of the amygdala or any of its subregions between the two groups. CONCLUSIONS: These findings suggest that amygdala subregional-network dysfunction in MDD is independent of structural changes and, more important, that hypoconnectivity and hyperconnectivity in different subregional networks may reflect imbalanced network function, which may modulate different forms of emotional and cognitive dysfunction in MDD.


Assuntos
Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Imagem por Ressonância Magnética/métodos , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Adulto , Feminino , Humanos , Masculino
10.
Neuroimage Clin ; 22: 101802, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30991623

RESUMO

BACKGROUND: Previous studies presumed that the disturbed neurovascular coupling to be a critical risk factor of cognitive impairments in type 2 diabetes mellitus (T2DM), but distinct clinical manifestations were lacked. Consequently, we decided to investigate the neurovascular coupling in T2DM patients by exploring the MRI relationship between neuronal activity and the corresponding cerebral blood perfusion. METHODS: Degree centrality (DC) map and amplitude of low-frequency fluctuation (ALFF) map were used to represent neuronal activity. Cerebral blood flow (CBF) map was used to represent cerebral blood perfusion. Correlation coefficients were calculated to reflect the relationship between neuronal activity and cerebral blood perfusion. RESULTS: At the whole gray matter level, the manifestation of neurovascular coupling was investigated by using 4 neurovascular biomarkers. We compared these biomarkers and found no significant changes. However, at the brain region level, neurovascular biomarkers in T2DM patients were significantly decreased in 10 brain regions. ALFF-CBF in left hippocampus and fractional ALFF-CBF in left amygdala were positively associated with the executive function, while ALFF-CBF in right fusiform gyrus was negatively related to the executive function. The disease severity was negatively related to the memory and executive function. The longer duration of T2DM was related to the milder depression, which suggests T2DM-related depression may not be a physiological condition but be a psychological condition. CONCLUSION: Correlations between neuronal activity and cerebral perfusion maps may be a method for detecting neurovascular coupling abnormalities, which could be used for diagnosis in the future. Trial registry number: This study has been registered in ClinicalTrials.gov (NCT02420470) on April 2, 2015 and published on July 29, 2015.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Função Executiva/fisiologia , Neuroimagem Funcional/métodos , Substância Cinzenta/fisiopatologia , Hipocampo/fisiopatologia , Acoplamento Neurovascular/fisiologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Rememoração Mental/fisiologia , Pessoa de Meia-Idade
11.
Alcohol Alcohol ; 54(3): 209-215, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31008507

RESUMO

AIMS: Differences in DNA methylation of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression and predict brain functions in healthy individuals. This study investigated the association between SLC6A4 promoter methylation and threat-related amygdala activation in individuals with alcohol dependence (AD). METHODS: Methylation of the SLC6A4 promoter region was assessed using peripheral blood DNA from 45 individuals with AD and 45 healthy controls (HCs). All participants completed an emotional face matching task in a 3-T magnetic resonance imaging (MRI) scanner. RESULTS: Results did not reveal any association between SLC6A4 promoter methylation variation and threat-related amygdala activation in HCs or individuals with AD. Furthermore, methylation in the promoter region of SLC6A4 did not significantly differ between the groups. CONCLUSIONS: Our results do not replicate a previous finding that increased methylation in the promoter region of SLC6A4 is associated with threat-related amygdala activation in healthy individuals and further show that there is no such association in individuals with AD. Given that the number of imaging epigenetics studies on SLC6A4 is very limited to date, these inconsistent results indicate that future research is needed to clarify its association with amygdala reactivity in both healthy and clinical populations.


Assuntos
Alcoolismo/genética , Alcoolismo/fisiopatologia , Tonsila do Cerebelo/fisiopatologia , Metilação de DNA , Medo/fisiologia , Regiões Promotoras Genéticas , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Alcoolismo/psicologia , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
12.
Bipolar Disord ; 21(6): 503-513, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31025452

RESUMO

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.


Assuntos
Afeto/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Atenção/fisiologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Emoções/fisiologia , Feminino , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Tálamo/fisiopatologia
13.
J Autism Dev Disord ; 49(6): 2605-2611, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30972653

RESUMO

Prior studies have emphasized the contribution of aberrant amygdala structure and function in social aspects of autism. However, it remains largely unknown whether amygdala dysfunction directly impairs visual attention and exploration as has been observed in people with autism spectrum disorders (ASD). Here, gaze patterns were directly compared between a rare amygdala lesion patient and adults with ASD when they freely viewed static images of complex natural scenes. The amygdala lesion patient showed a gaze pattern that was more similar to controls rather than that of the ASD group, which was independent of image content (social vs. objects) or complexity. This finding was further corroborated by analysis of temporal aspects of the gaze patterns and semantic category analysis. Together, the present results suggest that abnormal visual exploration observed in people with ASD is not likely primarily attributed to the amygdala.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Adulto , Atenção , Feminino , Fixação Ocular , Humanos , Masculino
14.
Transl Psychiatry ; 9(1): 132, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967545

RESUMO

Schizophrenia is a severe and highly heritable disorder. Dystrobrevin-binding protein 1 (DTNBP1), also known as dysbindin-1, has been implicated in the pathophysiology of schizophrenia. Specifically, dysbindin-1 mRNA and protein expression are decreased in the brains of subjects with this disorder. Mice lacking dysbinidn-1 also display behavioral phenotypes similar to those observed in schizophrenic patients. However, it remains unknown whether deletion of dysbindin-1 impacts functions of the amygdala, a brain region that is critical for emotional processing, which is disrupted in patients with schizophrenia. Here, we show that dysbindin-1 is expressed in both excitatory and inhibitory neurons of the basolateral amygdala (BLA). Deletion of dysbindin-1 in male mice (Dys-/-) impaired cued and context-dependent threat memory, without changes in measures of anxiety. The behavioral deficits observed in Dys-/- mice were associated with perturbations in the BLA, including the enhancement of GABAergic inhibition of pyramidal neurons, increased numbers of parvalbumin interneurons, and morphological abnormalities of dendritic spines on pyramidal neurons. Our findings highlight an important role for dysbindin-1 in the regulation of amygdalar function and indicate that enhanced inhibition of BLA pyramidal neuron activity may contribute to the weakened threat memory expression observed in Dys-/- mice.


Assuntos
Tonsila do Cerebelo/metabolismo , Disbindina/genética , Deleção de Genes , Consolidação da Memória , Esquizofrenia/genética , Tonsila do Cerebelo/fisiopatologia , Animais , Comportamento Animal , Sinais (Psicologia) , Feminino , Interneurônios/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Piramidais/metabolismo
15.
Biol Psychol ; 145: 198-210, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30935991

RESUMO

Previous studies have reported altered fear circuitry function during fear conditioning in highly anxious individuals and in adults with a history of severe childhood adversity; less is known regarding younger populations and more common forms of adversity. We investigated fear circuitry functioning in healthy youths with histories of high (HH) or low (LH) chronic harsh parenting and high (HA) or low (LA) anxiety levels. 84 youths aged 13-16 performed an fMRI fear conditioning task. HH displayed decreased selective medial temporal lobe deactivations to CS+> CS- relative to LH. In addition, we found less amygdala-insula connectivity in HH vs LH. Interestingly, we observed distinct patterns of anxiety differences in amygdala-rostral ACC connectivity and subjective fear ratings depending on harsh parenting levels, suggesting a history of harsh parenting is linked with unique neural and behavioral anxious manifestations, which are different from anxiety manifestations in a context of low adversity.


Assuntos
Ansiedade/fisiopatologia , Ansiedade/psicologia , Medo/fisiologia , Poder Familiar/psicologia , Adolescente , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Medo/psicologia , Feminino , Voluntários Saudáveis , Humanos , Imagem por Ressonância Magnética , Masculino , Análise e Desempenho de Tarefas , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia
16.
Neuron ; 102(1): 60-74, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30946827

RESUMO

Threat processing is central to understanding debilitating fear- and trauma-related disorders such as posttraumatic stress disorder (PTSD). Progress has been made in understanding the neural circuits underlying the "engram" of threat or fear memory formation that complements a decades-old appreciation of the neurobiology of fear and threat involving hub structures such as the amygdala. In this review, we examine key recent findings, as well as integrate the importance of hormonal and physiological approaches, to provide a broader perspective of how bodily systems engaged in threat responses may interact with amygdala-based circuits in the encoding and updating of threat-related memory. Understanding how trauma-related memories are encoded and updated throughout the brain and the body will ultimately lead to novel biologically-driven approaches for treatment and prevention.


Assuntos
Encéfalo/fisiopatologia , Medo/fisiologia , Memória/fisiologia , Trauma Psicológico/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estresse Psicológico/fisiopatologia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiologia , Tonsila do Cerebelo/fisiopatologia , Encéfalo/metabolismo , Encéfalo/fisiologia , Núcleo Central da Amígdala/fisiologia , Núcleo Central da Amígdala/fisiopatologia , Hormônio Liberador da Corticotropina/metabolismo , Medo/psicologia , Glucocorticoides/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Humanos , Hipotálamo/metabolismo , Hipotálamo/fisiologia , Hipotálamo/fisiopatologia , Interneurônios/metabolismo , Interneurônios/fisiologia , Trauma Psicológico/metabolismo , Trauma Psicológico/psicologia , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Tálamo/metabolismo , Tálamo/fisiologia , Tálamo/fisiopatologia
17.
Transl Psychiatry ; 9(1): 121, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30923309

RESUMO

Individuals with clinical anxiety demonstrate an attention bias toward threatening information, which is thought to be partially driven by heightened amygdala activity to perceived threat. Attention Bias Modification (ABM) is a computer-based treatment that trains attention toward neutral stimuli and away from threatening stimuli. Alterations in initial processing of threat have been linked to ABM responses, but the impact of protracted processing in the aftermath of neutral and threatening information on ABM outcomes has not been well studied. Our study tested whether sustained activity in the amygdala, which occurred after neutral and threatening stimuli had been removed, could predict which individuals would respond well to ABM. Unmedicated anxious individuals underwent a baseline fMRI assessment during performance of a task sensitive to protracted emotional processing. Afterward, they were randomized to complete eight sessions of ABM (n = 38) or a sham training (n = 19). ABM patients who displayed greater sustained bilateral amygdalar response in the aftermath of neutral stimuli displayed the least improvement in self-reported (but not clinician-rated) vigilance symptoms. In contrast, amygdalar response did not predict improvement in sham patients. Results suggest that in certain anxious individuals, the amygdala may have a robust protracted response even to subjectively neutral cues, which could make these individuals a poor fit for ABM because of its focus on repeatedly retraining attention toward neutral cues. Findings may help elucidate neural mechanisms of ABM and promote the identification of a subset of anxious patients who would be good candidates for this intervention.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/terapia , Atenção/fisiologia , Terapia Cognitivo-Comportamental/métodos , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Transtornos de Ansiedade/psicologia , Sinais (Psicologia) , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Autorrelato , Resultado do Tratamento , Adulto Jovem
18.
Nat Commun ; 10(1): 971, 2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30814498

RESUMO

The hippocampus and amygdala are key brain structures of the medial temporal lobe, involved in cognitive and emotional processes as well as pathological states such as epilepsy. Despite their importance, it is still unclear whether their  neural activity can be recorded non-invasively. Here, using simultaneous intracerebral and magnetoencephalography (MEG) recordings in patients with focal drug-resistant epilepsy, we demonstrate a direct contribution of amygdala and hippocampal activity to surface MEG recordings. In particular, a method of blind source separation, independent component analysis, enabled activity arising from large neocortical networks to be disentangled from that of deeper structures, whose amplitude at the surface was small but significant. This finding is highly relevant for our understanding of hippocampal and amygdala brain activity as it implies that their activity could potentially be measured non-invasively.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Epilepsias Parciais/fisiopatologia , Hipocampo/fisiopatologia , Magnetoencefalografia/métodos , Adulto , Tonsila do Cerebelo/patologia , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/métodos , Eletroencefalografia/estatística & dados numéricos , Epilepsias Parciais/patologia , Feminino , Hipocampo/patologia , Humanos , Imagem Tridimensional , Magnetoencefalografia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Modelos Anatômicos , Modelos Neurológicos , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Adulto Jovem
19.
Mol Brain ; 12(1): 25, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922409

RESUMO

Posttraumatic stress disorder is developed by exposure to a threatening and/or a horrifying event and characterized by the presence of anxiety, hyperarousal, avoidance, and sleep abnormality for a prolonged period of time. To elucidate the potential molecular mechanisms, we constructed a mouse model by electric foot shock followed by situational reminders and performed transcriptome analysis in brain tissues. The stressed mice acquired anxiety-like behavior after 2 weeks and exaggerated startle response after 4 weeks. Avoidance latency and freezing behavior were sustained up to 5 weeks post stress and abnormal static behavior was observed during the sleep period. RNA sequencing was performed in two of the emotional regulatory regions, anterior cingulate cortex and amygdala, at 2 and 5 weeks post stress. More than 1000 differentially expressed genes were identified at 2 weeks in both regions. The number of the regulated genes remained constant in amygdala at 5 weeks post stress, whereas those in anterior cingulate cortex were plummeted. Although synaptic remodeling and endocrine system were the most enriched signaling pathways in both anterior cingulate cortex and amygdala, the individual gene expression profile was regulated in a region- and time-dependent manner. In addition, several genes associated with PTSD involved in Hypothalamic-Pituitary-Adrenal axis were differentially regulated. These findings suggested that global gene expression profile was dynamically regulated in accordance with the disease development stage, and therefore targeting the distinct signaling molecules in different region and development stage might be critical for effective treatment to PTSD.


Assuntos
Tonsila do Cerebelo/metabolismo , Regulação da Expressão Gênica , Giro do Cíngulo/metabolismo , Transtornos de Estresse Pós-Traumáticos/genética , Tonsila do Cerebelo/fisiopatologia , Animais , Ansiedade/complicações , Ansiedade/genética , Ansiedade/fisiopatologia , Nível de Alerta/genética , Aprendizagem da Esquiva , Comportamento Animal , Modelos Animais de Doenças , Reação de Congelamento Cataléptica , Perfilação da Expressão Gênica , Ontologia Genética , Giro do Cíngulo/fisiopatologia , Imobilização , Masculino , Aprendizagem em Labirinto , Memória , Camundongos Endogâmicos C57BL , Tempo de Reação/genética , Reflexo de Sobressalto , Sono , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Fatores de Tempo
20.
Bipolar Disord ; 21(4): 309-320, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30851221

RESUMO

OBJECTIVES: Little is known about potential differences in the pathophysiology of bipolar disorder (BD) across development. The present study aimed to characterize age-related neural mechanisms of BD. METHODS: Youths and adults with and without BD (N = 108, age range = 9.8-55.9 years) completed an emotional face labeling task during fMRI acquisition. We leveraged three different fMRI analytic tools to identify age-related neural mechanisms of BD, investigating (a) change in neural responses over the course of the task, (b) neural activation averaged across the entire task, and (c) amygdala functional connectivity. RESULTS: We found converging Age Group × Diagnosis patterns across all three analytic methods. Compared to healthy youths vs adults, youths vs adults with BD show an altered pattern in response to repeated presentation of emotional faces in medial prefrontal, amygdala, and temporoparietal regions, as well as amygdala-temporoparietal connectivity. Specifically, medial prefrontal and lingual activation decreases over the course of repeated emotional face presentations in healthy youths vs adults but increases in youths with BD compared to adults with BD. Moreover, youths vs adults with BD show less medial prefrontal activation and amygdala-temporoparietal junction connectivity averaged over the task, but this difference is not found for healthy youths vs adults. CONCLUSION: Although longitudinal confirmation and replication will be necessary, these findings suggest that neural development may be aberrant in BD and that some neural mechanisms mediating BD may differ in adults vs children with the illness.


Assuntos
Conectoma/métodos , Emoções/fisiologia , Expressão Facial , Fatores Etários , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Transtorno Bipolar/psicologia , Criança , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
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