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1.
Nat Commun ; 11(1): 4250, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843635

RESUMO

A mechanistic understanding of core cognitive processes, such as working memory, is crucial to addressing psychiatric symptoms in brain disorders. We propose a combined psychophysical and biophysical account of two symptomatologically related diseases, both linked to hypofunctional NMDARs: schizophrenia and autoimmune anti-NMDAR encephalitis. We first quantified shared working memory alterations in a delayed-response task. In both patient groups, we report a markedly reduced influence of previous stimuli on working memory contents, despite preserved memory precision. We then simulated this finding with NMDAR-dependent synaptic alterations in a microcircuit model of prefrontal cortex. Changes in cortical excitation destabilized within-trial memory maintenance and could not account for disrupted serial dependence in working memory. Rather, a quantitative fit between data and simulations supports alterations of an NMDAR-dependent memory mechanism operating on longer timescales, such as short-term potentiation.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Memória de Curto Prazo/fisiologia , Esquizofrenia/fisiopatologia , Sinapses/fisiologia , Adolescente , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Feminino , Humanos , Masculino , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Plasticidade Neuronal , Córtex Pré-Frontal/fisiopatologia , Receptores de N-Metil-D-Aspartato/fisiologia , Psicologia do Esquizofrênico , Adulto Jovem
2.
PLoS One ; 15(6): e0235046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579566

RESUMO

Post-ictal emergence of slow wave EEG (electroencephalogram) activity and burst-suppression has been associated with the therapeutic effects of the electroconvulsive therapy (ECT), indicating that mere "cerebral silence" may elicit antidepressant actions. Indeed, brief exposures to burst-suppressing anesthesia has been reported to elicit antidepressant effects in a subset of patients, and produce behavioral and molecular alterations, such as increased expression of brain-derived neurotrophic factor (BDNF), connected with antidepressant responses in rodents. Here, we have further tested the cerebral silence hypothesis by determining whether repeated exposures to isoflurane anesthesia reduce depressive-like symptoms or influence BDNF expression in male Wistar outbred rats (Crl:WI(Han)) subjected to chronic mild stress (CMS), a model which is responsive to repeated electroconvulsive shocks (ECS, a model of ECT). Stress-susceptible, stress-resilient, and unstressed rats were exposed to 5 doses of isoflurane over a 15-day time period, with administrations occurring every third day. Isoflurane dosing is known to reliably produce rapid EEG burst-suppression (4% induction, 2% maintenance; 15 min). Antidepressant and anxiolytic effects of isoflurane were assessed after the first, third, and fifth drug exposure by measuring sucrose consumption, as well as performance on the open field and the elevated plus maze tasks. Tissue samples from the medial prefrontal cortex and hippocampus were collected, and levels of BDNF (brain-derived neurotrophic factor) protein were assessed. We find that isoflurane anesthesia had no impact on the behavior of stress-resilient or anhedonic rats in selected tests; findings which were consistent-perhaps inherently related-with unchanged levels of BDNF.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo/prevenção & controle , Isoflurano/farmacologia , Estresse Psicológico/prevenção & controle , Anestésicos Inalatórios , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo/etiologia , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Eletroconvulsoterapia/métodos , Eletroencefalografia , Eletrochoque/efeitos adversos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Isoflurano/administração & dosagem , Masculino , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Ratos Wistar , Estresse Psicológico/etiologia , Estresse Psicológico/fisiopatologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-32479008

RESUMO

Glutamatergic N-methyl-D-aspartate (NMDA) receptors have critical roles in several neurological and psychiatric diseases. Dizocilpine (MK-801) is a ligand at phencyclidine recognition sites that is associated with NMDA receptor-coupled cation channels, where it acts as a potent noncompetitive antagonist of central glutamate receptors. In this study, we investigate the effect of clozapine on MK-801-induced neurochemical and neurobehavioral alterations in the prefrontal cortex of mice. Acute administration of NMDA noncompetitive antagonist MK-801 impairs motor coordination, grip strength, and locomotor activity. Clozapine is the only medication that is indicated for treating refractory schizophrenia, due to its superior efficacy among all antipsychotic agents; however, its mechanism is not well understood. To understand its mechanism, we investigated the effects of clozapine on motor coordination, locomotor activity, and grip strength in mice against the NMDA receptor antagonist MK-801. MK-801 induced elevations in acetylcholinesterase (AChE) activity, monoamine oxidase (MAO) activity, and c-fos expression. The administration of clozapine inhibited the effects caused by MK-801 (0.2 mg/kg body weight). Motor coordination and grip strength paradigms that had been altered by MK-801 were restored by clozapine. Moreover, clozapine also ameliorated MK-801-induced elevation in AChE and MAO activity. Our immunostaining results demonstrated that clozapine treatment reduced overexpression of the neuronal activity marker c-fos in cortices of the brain. Results of the current study determine that clozapine ameliorated cognition in MK-801-treated mice via cholinergic and neural mechanisms. These findings show that clozapine possesses the potential to augment cognition in diseases such as schizophrenia.


Assuntos
Clozapina/farmacologia , Maleato de Dizocilpina/toxicidade , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Antagonistas da Serotonina/farmacologia , Animais , Antipsicóticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/toxicidade , Masculino , Camundongos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/induzido quimicamente
4.
PLoS One ; 15(5): e0233414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442205

RESUMO

INTRODUCTION: The effectiveness of repetitive transcranial Direct Current Stimulation (tDCS) on reducing smoking behaviour has been studied with mixed results. Smoking behaviour is influenced by affect and context, therefore we choose to use mobile ecological momentary assessments (EMA) to measure changes in smoking behaviour after tDCS. METHODS: In a randomized, placebo-controlled, between subject study, we applied tDCS bilaterally with the anodal electrode targeting the right DLPFC (https://clinicaltrials.gov/ct2/show/NCT03027687). Smokers were allocated to six sessions of either active tDCS (n = 35) or sham tDCS (n = 36) and received two sessions on three different days in one week. They were asked to keep track of their daily cigarette consumption, craving and affect in an application on their mobile phones for three months starting one week before the first tDCS session. RESULTS: Number of smoked cigarettes a day progressively decreased up to one week after the last tDCS session in both conditions. Active treatment had no additional effect on cigarette consumption, craving and affect. CONCLUSIONS: In this exploratory study, repetitive bilateral tDCS over the DLPFC had no effect on daily smoking behaviour. Future research needs to investigate how motivation to quit smoking and the number of tDCS sessions affect the efficacy of repetitive tDCS.


Assuntos
Fumar Cigarros/terapia , Prevenção do Hábito de Fumar/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Fumar Cigarros/fisiopatologia , Fumar Cigarros/psicologia , Fissura , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Córtex Pré-Frontal/fisiopatologia , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Adulto Jovem
5.
Medicine (Baltimore) ; 99(18): e19937, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358365

RESUMO

RATIONALE: We report a stroke patient who showed increased thalamocortical connectivity to the medial prefrontal cortex (mPFC) with recovery of impaired consciousness that was demonstrated on diffusion tensor tractography (DTT) of the ascending reticular activating system (ARAS). PATIENTS CONCERNS: A 48-year-old male patient underwent craniectomy and hematoma removal for spontaneous intracerebral hemorrhage in the right basal ganglia and thalamus. When he started rehabilitation at 5 weeks after onset he was in a vegetative state with a Coma Recovery Scale-Revised score of 6. DIAGNOSES: The patient was diagnosed spontaneous intracerebral hemorrhage in the right basal ganglia and thalamus. INTERVENTIONS: He underwent comprehensive rehabilitation including neurotropic durgs, transcranial direct current stimulation, and repetitive transcranial magnetic stimulation of the left prefrontal lobe (Brodmann area 10). OUTCOMES: After 5 weeks of rehabilitation, the patient had recovered to a nearly normal conscious state with a Coma Recovery Scale-Revised score of 22. On 10-week DTT, thickening of the lower dorsal ARAS was observed on both sides compared with 5-week DTT. Decreased neural connectivity to the left PFC was observed on 5-week DTT whereas decreased neural connectivity to the left PFC was increased on 10-week DTT, especially the mPFC. LESSONS: Increased thalamocortical connectivity to the mPFC was demonstrated in a stroke patient who showed concomitant recovery from a vegetative state to a nearly normal conscious state. The results suggest that the increased neural connectivity to the mPMC contributed to recovery of consciousness in this patient.


Assuntos
Coma/fisiopatologia , Imagem de Tensor de Difusão/métodos , Estado Vegetativo Persistente/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Hemorragia Cerebral/complicações , Coma/diagnóstico por imagem , Coma/etiologia , Estado de Consciência , Craniotomia/métodos , Hematoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estado Vegetativo Persistente/diagnóstico por imagem , Estado Vegetativo Persistente/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Reabilitação do Acidente Vascular Cerebral/métodos
6.
PLoS One ; 15(5): e0232530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32384091

RESUMO

BACKGROUND: Clinical and animal studies have found that anxiety and depression are significantly more common after acute myocardial infarction (AMI). The medial prefrontal cortex (PFC) has a dual role: in higher brain functions and in cardiovascular control, making it a logical candidate for explaining the perceived bidirectional heart-brain connection. We used parallel Electrocardiography (ECG) and Electrocorticography (ECoG) registration to investigate AMI-induced changes in medial PFC bioelectrical activity in a rat model of AMI. MATERIALS AND METHODS: Adult male Wistar albino rats were used in the study. Gold-plated recording electrodes were implanted over the frontal cortex for ECoG recording. ECG was recorded via two holter electrodes attached on the skin of the back fixed in place by a jacket. Induction of AMI was performed by isoprenaline (150 mg/kg, i.p.). ECoG and ECG signals were registered at baseline, during 3 hours after isoprenaline administration and at 24 hours after isoprenaline administration. RESULTS: Significant increases of theta, alpha, and beta electroencephalographic (EEG) band power were observed in different time intervals after isoprenaline administration. Significant increase of theta band peak frequency was also observed during the first hour after isoprenaline administration. No statistically significant differences in band-power activity were found between the pre-isoprenaline measurements and 24 hours after administration. CONCLUSION: Our results demonstrate significant increases in EEG band power of alpha beta and theta bands during isoprenaline-induced AMI model. These are the first findings to connect heart damage during isoprenaline- induced AMI to disturbances in the cortical bioelectrical activity.


Assuntos
Isoproterenol/farmacologia , Infarto do Miocárdio/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Ondas Encefálicas/fisiologia , Modelos Animais de Doenças , Eletrocardiografia , Eletrocorticografia , Eletroencefalografia , Masculino , Infarto do Miocárdio/induzido quimicamente , Ratos , Ratos Wistar
7.
Nat Commun ; 11(1): 2329, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393757

RESUMO

Impaired cognitive functioning is a core feature of schizophrenia, and is hypothesized to be due to myelination as well as interneuron defects during adolescent prefrontal cortex (PFC) development. Here we report that in the apomorphine-susceptible (APO-SUS) rat model, which has schizophrenia-like features, a myelination defect occurred specifically in parvalbumin interneurons. The adult rats displayed medial PFC (mPFC)-dependent cognitive inflexibility, and a reduced number of mature oligodendrocytes and myelinated parvalbumin inhibitory axons in the mPFC. In the developing mPFC, we observed decreased myelin-related gene expression that persisted into adulthood. Environmental enrichment applied during adolescence restored parvalbumin interneuron hypomyelination as well as cognitive inflexibility. Collectively, these findings highlight that impairment of parvalbumin interneuron myelination is related to schizophrenia-relevant cognitive deficits.


Assuntos
Cognição/fisiologia , Interneurônios/patologia , Bainha de Mielina/patologia , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Animais , Axônios/metabolismo , Axônios/ultraestrutura , Linhagem da Célula , Modelos Animais de Doenças , Neurônios GABAérgicos/metabolismo , Regulação da Expressão Gênica , Interneurônios/ultraestrutura , Aprendizagem , Bainha de Mielina/ultraestrutura , Oligodendroglia/patologia , Parvalbuminas/metabolismo , Córtex Pré-Frontal/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar
8.
Hum Genet ; 139(10): 1285-1297, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32385526

RESUMO

During the past decade, genetic studies of schizophrenia have become one of the most exciting and fast-moving areas. Hundreds of genes implicated in schizophrenia have been identified by genetic, epigenetic, and gene expression studies. However, how to systematically and efficiently use these published data to pinpoint the causal genes becomes a major challenge in schizophrenia research. Here, we release an updated version of a comprehensive database for schizophrenia research, SZDB2.0 ( www.szdb.org ), which accompanies significant data expansion and feature improvements, as well as functionality optimization. Compared with the first version (SZDB), the current database has the following updates: (1) We added the newly published genome-wide association study (GWAS) of schizophrenia from CLOZUK + PGC, which is the largest GWAS for schizophrenia; (2) We included a polygenic risk score calculator; (3) In the refined "Gene" module of SZDB2.0, we collated genetic, gene expression, methylation, and integrative results of all available schizophrenia studies; (4) In the "CNV (copy number variation)" module, we collated the results of all 77 CNV publications about schizophrenia; (5) We also updated other data, including gene expression quantitative trait loci (eQTL), transcript QTL, methylation QTL, and protein-protein interaction data, based on the information from the latest literatures. We optimized the query interface of SZDB2.0 for a better visualization and data retrieval. The updated SZDB2.0 will advance the research of schizophrenia.


Assuntos
Bases de Dados Genéticas , Epigênese Genética , Predisposição Genética para Doença , Herança Multifatorial , Locos de Características Quantitativas , Esquizofrenia/genética , Variações do Número de Cópias de DNA , Metilação de DNA , Ontologia Genética , Estudo de Associação Genômica Ampla , Humanos , Armazenamento e Recuperação da Informação/métodos , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Mapeamento de Interação de Proteínas , Risco , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia
9.
J Vis Exp ; (159)2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32421008

RESUMO

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and duration of the stressor; 2) type of cognitive function under study; and 3) timing of the stressor in relation to learning or executing the cognitive task. Furthermore, sex differences among the effects of stress on cognitive function have been widely documented. Described here is an adaptation of an automated operant strategy shifting paradigm to assess how variations in stress affect cognitive flexibility in male and female Sprague Dawley rats. Specifically, restraint stress is used before or after training in this operant-based task to examine how stress affects cognitive performance in both sexes. Particular brain areas associated with each task in this automated paradigm have been well-established (i.e., the medial prefrontal cortex and orbitofrontal cortex). This allows for targeted manipulations during the experiment or the assessment of particular genes and proteins in these regions upon completion of the paradigm. This paradigm also allows for the detection of different types of performance errors that occur after stress, each of which has defined neural substrates. Also identified are distinct sex differences in perseverative errors after a repeated restraint stress paradigm. The use of these techniques in a preclinical model may reveal how stress affects the brain and impairs cognition in psychiatric disorders, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), which display marked sex differences in prevalence.


Assuntos
Encéfalo/fisiopatologia , Cognição/fisiologia , Modelos Animais de Doenças , Deficiências da Aprendizagem/etiologia , Córtex Pré-Frontal/fisiopatologia , Reversão de Aprendizagem , Estresse Psicológico/complicações , Adaptação Psicológica , Animais , Comportamento Animal , Discriminação Psicológica , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
10.
Toxicol Appl Pharmacol ; 395: 114980, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32234516

RESUMO

Toluene can be intentionally misused by adolescents to experience psychoactive effects. Toluene has a complex mechanism of action and broad behavioral effects, among which memory impairment is reported consistently. We have previously reported that repeated toluene inhalation (8000 ppm) increases layer 5 prelimbic pyramidal cells' excitability in the medial prefrontal cortex (mPFC) of adolescent rats. Toluene also produces reactive oxygen species (ROS), which activate glial cells. Here, we tested the hypothesis that the anti-inflammatory agent minocycline would decrease toluene's effects because it inhibits NF-κB (nuclear factor enhancer of the kappa light chains of activated B cells) and reduces pro-inflammatory cytokine and ROS production. Our results show that minocycline (50 mg/kg, ip, for 10 days) prevents the hyperexcitability of mPFC neurons observed after repeated 8000 ppm toluene exposure (30 min/day, 2×/day for 10 days). Minocycline prevents toluene-induced hyperexcitability by a mechanism that averts the loss of the slow calcium-dependent potassium current, and normalizes mPFC neurons' firing frequency. These effects are accompanied by significant decreased expression of astrocytes and activated microglia in the mPFC, reduced NLRP3 inflammasome activation and mRNA expression levels of the pro-inflammatory cytokine interleukin 1ß (IL-1ß), as well as increased mRNA expression of the anti-inflammatory cytokine transforming growth factor ß (TGF-ß). Minocycline also prevents toluene-induced memory impairment in adolescent rats in the passive avoidance task and the temporal order memory test in which the mPFC plays a central role. These results show that neuroinflammation produces several effects of repeated toluene administration at high concentrations, and minocycline can significantly prevent them.


Assuntos
Anti-Inflamatórios/administração & dosagem , Transtornos da Memória/prevenção & controle , Minociclina/administração & dosagem , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Tolueno/toxicidade , Administração por Inalação , Animais , Expressão Gênica/efeitos dos fármacos , Abuso de Inalantes , Interleucina-1beta/genética , Masculino , Transtornos da Memória/induzido quimicamente , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Tolueno/administração & dosagem , Fator de Crescimento Transformador beta/genética
12.
Brain ; 143(4): 1261-1277, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236540

RESUMO

Frontotemporal dysconnectivity is a key pathology in schizophrenia. The specific nature of this dysconnectivity is unknown, but animal models imply dysfunctional theta phase coupling between hippocampus and medial prefrontal cortex (mPFC). We tested this hypothesis by examining neural dynamics in 18 participants with a schizophrenia diagnosis, both medicated and unmedicated; and 26 age, sex and IQ matched control subjects. All participants completed two tasks known to elicit hippocampal-prefrontal theta coupling: a spatial memory task (during magnetoencephalography) and a memory integration task. In addition, an overlapping group of 33 schizophrenia and 29 control subjects underwent PET to measure the availability of GABAARs expressing the α5 subunit (concentrated on hippocampal somatostatin interneurons). We demonstrate-in the spatial memory task, during memory recall-that theta power increases in left medial temporal lobe (mTL) are impaired in schizophrenia, as is theta phase coupling between mPFC and mTL. Importantly, the latter cannot be explained by theta power changes, head movement, antipsychotics, cannabis use, or IQ, and is not found in other frequency bands. Moreover, mPFC-mTL theta coupling correlated strongly with performance in controls, but not in subjects with schizophrenia, who were mildly impaired at the spatial memory task and no better than chance on the memory integration task. Finally, mTL regions showing reduced phase coupling in schizophrenia magnetoencephalography participants overlapped substantially with areas of diminished α5-GABAAR availability in the wider schizophrenia PET sample. These results indicate that mPFC-mTL dysconnectivity in schizophrenia is due to a loss of theta phase coupling, and imply α5-GABAARs (and the cells that express them) have a role in this process.


Assuntos
Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologia , Ritmo Teta/fisiologia , Adulto , Feminino , Humanos , Magnetoencefalografia , Masculino , Vias Neurais/metabolismo , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/metabolismo , Receptores de GABA-A/metabolismo , Esquizofrenia/metabolismo , Lobo Temporal/metabolismo
13.
Neuron ; 106(6): 992-1008.e9, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32320644

RESUMO

Astrocytes play essential roles in brain function by supporting synaptic connectivity and associated circuits. How these roles are regulated by transcription factors is unknown. Moreover, there is emerging evidence that astrocytes exhibit regional heterogeneity, and the mechanisms controlling this diversity remain nascent. Here, we show that conditional deletion of the transcription factor nuclear factor I-A (NFIA) in astrocytes in the adult brain results in region-specific alterations in morphology and physiology that are mediated by selective DNA binding. Disruptions in astrocyte function following loss of NFIA are most pronounced in the hippocampus, manifested by impaired interactions with neurons, coupled with diminution of learning and memory behaviors. These changes in hippocampal astrocytes did not affect basal neuronal properties but specifically inhibited synaptic plasticity, which is regulated by NFIA in astrocytes through calcium-dependent mechanisms. Together, our studies reveal region-specific transcriptional dependencies for astrocytes and identify astrocytic NFIA as a key transcriptional regulator of hippocampal circuits.


Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , Cálcio/metabolismo , Regulação da Expressão Gênica , Aprendizagem/fisiologia , Fatores de Transcrição NFI/genética , Animais , Astrócitos/fisiologia , Encéfalo/citologia , Encéfalo/fisiopatologia , Tronco Encefálico/citologia , Tronco Encefálico/metabolismo , Tronco Encefálico/fisiopatologia , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/fisiopatologia , Hipocampo/citologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Potenciação de Longa Duração/fisiologia , Memória/fisiologia , Camundongos , Camundongos Knockout , Vias Neurais , Plasticidade Neuronal , Neurônios , Bulbo Olfatório/citologia , Bulbo Olfatório/metabolismo , Bulbo Olfatório/fisiopatologia , Técnicas de Patch-Clamp , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Memória Espacial/fisiologia
14.
Psychiatry Res Neuroimaging ; 299: 111062, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32278278

RESUMO

Posttraumatic Stress Disorder (PTSD) is a debilitating condition often associated with difficulty in emotion regulation, including reappraising negative emotions. This study assessed neural mechanisms associated with emotion regulation in veterans prior to and following treatment for PTSD. Participants with PTSD and combat exposed controls (CC) completed diagnostic evaluation and underwent fMRI scanning while completing Emotion Regulation Task (ERT) and Emotional Faces Assessment Task (EFAT). Participants with PTSD were randomly assigned to Prolonged Exposure plus placebo (PE+PLB), Sertraline plus enhanced medication management (SERT+EMM), or PE plus SERT (PE+SERT) and repeated diagnostic evaluation and MRI scanning following treatment. The amygdala, dmPFC, and dlPFC were examined as regions of interest. On ERT, veterans with PTSD showed significantly less dmPFC activation than CCs during reappraisal vs emotional maintenance. Within the PTSD group, results demonstrated a significant association between less activation in the dmPFC during emotion reappraisal vs maintenance trials before treatment and greater reductions in symptoms from pre- to post-treatment. During the EFAT, there were no group differences between participants with PTSD and CCs in brain activation, and no relationships between brain function and PTSD symptoms. These findings suggest that less emotional reactivity might potentially reflect less need for recruitment of prefrontal regions when reappraising negative emotion, and is an individual factor associated with better treatment outcome.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Emoções/fisiologia , Córtex Pré-Frontal/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Sertralina/uso terapêutico , Resultado do Tratamento , Veteranos/psicologia
15.
Am J Psychiatry ; 177(8): 716-726, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32252538

RESUMO

OBJECTIVE: New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression. METHODS: Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. RESULTS: One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects. CONCLUSIONS: SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.


Assuntos
Transtorno Depressivo Resistente a Tratamento , Giro do Cíngulo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Adulto , Protocolos Clínicos , Cognição , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/fisiopatologia , Transtorno Depressivo Resistente a Tratamento/terapia , Feminino , Neuroimagem Funcional/métodos , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Monitorização Fisiológica/métodos , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Indução de Remissão/métodos
16.
Psychiatry Res Neuroimaging ; 298: 111047, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32114310

RESUMO

Electroacupuncture (EA) is a safe method for treating obesity; however, its underlying neural mechanisms remain unclear. We employed resting-state-functional-magnetic-resonance-imaging (RS-fMRI) and amplitude-of-low-frequency-fluctuation (ALFF) to investigate acute/long-term effects of EA on brain activity and resting-state-functional-connectivity (RSFC) in overweight/obesity subjects who received real/Sham stimulation. For acute effects, 26 and 19 overweight/obesity subjects were included in EA and Sham groups respectively. There were significant time effects on ALFF in the right insula (INS) and left dorsolateral-prefrontal-cortex (DLPFC) due to decreases/increases in INS/DLPFC in both groups. There were weaker positive RSFC between INS and supplementary-motor-area (SMA)/right DLPFC and weaker negative RSFC between INS and precuneus (PCUN); stronger negative RSFC between DLPFC and dorsomedial-prefrontal-cortex (DMPFC) in both groups. For long-term study, body-mass-index (BMI) had significant reduction in EA (n = 17) and Sham (15) groups; EA had higher BMI reduction than in Sham. There were significant time effects on ALFF in right ventrolateral-prefrontal-cortex (VLPFC) due to significant increases in EA group, and stronger positive RSFC between VLPFC and orbitofrontal-cortex and negative RSFC between VLPFC and left thalamus (THA) in both groups after long-term treatment. These findings suggest that changes in resting-activity and RSFC implicated in inhibitory-control, gastric-motility and satiety-control are associated with EA-induced weight-loss.


Assuntos
Córtex Cerebral/fisiopatologia , Conectoma , Eletroacupuntura , Avaliação de Resultados em Cuidados de Saúde , Sobrepeso/fisiopatologia , Sobrepeso/terapia , Tálamo/fisiopatologia , Perda de Peso , Adulto , Córtex Cerebral/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Obesidade/diagnóstico por imagem , Obesidade/fisiopatologia , Obesidade/terapia , Sobrepeso/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Tálamo/diagnóstico por imagem
17.
J Headache Pain ; 21(1): 29, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188423

RESUMO

BACKGROUND: The increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10-30 headache days/month). METHODS: We prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥50% reduction of baseline headache days and poor outcome was defined as reduction < 50% or frequency increase. Voxel-based morphometry was used to study gray matter volume (GMV), and structural covariance was used to investigate structural connectivity. RESULTS: Among 56 patients with HFM, 37 had good outcome and 19 poor outcome. Compared to the healthy controls (n = 37), patients with poor outcome had decreased GMV over the left posterior cingulate gyrus, and increased GMV over the bilateral cerebellum and the right precentral gyrus. Further, patients with poor outcome had greater GMV over the right and the left cerebella compared to patients with good outcome, and the GMVs of the cerebella were correlated to 2-year headache frequencies (right: r = 0.38, P = 0.005; left: r = 0.35, P = 0.009). Structural connectivity were increased between the cerebellum and the cuneus, the calcarine cortex, and the temporal lobe, respectively, in patients with poor outcome, and was decreased between the cerebellum and the prefrontal cortex in patients with poor outcome. The structural covariance integrities between the right cerebellum and the right cuneus were correlated to 2-year headache frequencies (r = 0.36, P = 0.008). CONCLUSIONS: Structural volume and connectivity changes of the cerebellum may underlie headache persistence in patients with HFM.


Assuntos
Cerebelo/fisiopatologia , Substância Cinzenta/fisiopatologia , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/fisiopatologia , Adulto , Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Progressão da Doença , Feminino , Giro do Cíngulo/fisiopatologia , Cefaleia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia , Prognóstico , Qualidade de Vida , Adulto Jovem
18.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32161644

RESUMO

Even apparently simple choices, like selecting a dessert in a pastry shop, involve options characterized by multiple motivationally relevant attributes. Neuroeconomic research suggests that the human brain may track the subjective value of such options, allowing disparate reward-predictive information to be compared in a common currency. However, the brain mechanisms involved in identifying value-predictive features and combining these to assess the value of each decision option remain unclear. Here, we review recent evidence from studies of multi-attribute decision-making in people with focal frontal lobe damage and in healthy people undergoing functional magnetic resonance imaging. This work suggests that ventromedial and lateral prefrontal cortex and orbitofrontal cortex are important for forming value judgments under conditions of complexity. We discuss studies supporting the involvement of these regions in selecting among and evaluating option attributes during value judgment and decision-making and when learning from reward feedback. These findings are consistent with roles for these regions in guiding value construction. They argue for a more nuanced understanding of how ventral and lateral prefrontal cortex contribute to discovering and recognizing value, processes that are required under the complex conditions typical of many everyday decisions.


Assuntos
Tomada de Decisões , Lobo Frontal/fisiologia , Lobo Frontal/fisiopatologia , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/fisiopatologia , Lobo Frontal/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Recompensa
19.
Psychiatry Res Neuroimaging ; 299: 111059, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32135406

RESUMO

This study explored imaging predictors of electroconvulsive therapy (ECT) outcome in schizophrenia patients based on pre-treatment functional connectivity (FC) within regions with strong ECT electric fields distribution. Forty-seven patients received standard antipsychotic drugs combined with ECT as well as two brain imaging sessions. Regions of interest (ROI) with strong electric field distribution were determined by ECT simulation. Using baseline functional connectivity between ROIs, a model was constructed to predict the percentage reduction of Positive and Negative Syndrome Scale (PANSS) scores. The strong electric fields were distributed in the orbital prefrontal lobe, medial temporal lobe, and other parts of the temporal lobe. Ten functional connectivity features within the electric field distribution areas showed a predictive ability for ECT outcome. The correlation coefficient between the predictive and real values of cross-validation was 0.7165. Among the predictive features, ECT induced a significant decrease in functional connectivity between the right amygdala and the left hippocampus. These results suggest that pretreatment functional connectivity patterns in brain regions with strong electric field distributions during ECT could be potential predictors of the efficacy of ECT augmentation in schizophrenia. These findings may help to improve individualized clinical treatment in the future.


Assuntos
Antipsicóticos/uso terapêutico , Eletroconvulsoterapia/métodos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/terapia , Adulto , Encéfalo/fisiopatologia , Feminino , Hipocampo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologia
20.
Brain Topogr ; 33(2): 275-283, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32056031

RESUMO

"Remind-to-Move" (RTM) has been developed and used as a new treatment for rehabilitation of upper extremity functions in patients with hemiplegia. This study aimed to investigate the cortical activation patterns using functional near-infrared spectroscopic topography for patients with chronic stroke receiving RTM by comparing with their healthy counterparts. Twelve patients with right hemispheric stroke and 15 healthy adults participated in this study. All participants were instructed to completed three experimental conditions-RTM, Move without reminding (Sham), and Remind with No-move (RNoM). In patients with stroke, RTM elicited higher level of activation than the Sham in the contralateral somatosensory association cortex, primary motor cortex, primary somatosensory cortex and the dorsolateral prefrontal cortex, which has been found in healthy participants. However, effects of RTM were robust and more widely distributed in healthy participants, comparing to patients with stroke, comparatively RNoM showed no significant higher activation than the baseline in those areas in both populations. RTM enhances the recruitment of contralateral primary motor cortex and this effect appears to be associated with increased attention allocation towards moving hands upon tactile stimulation in the form of vibration. The RTM treatment is useful to patients with stroke.


Assuntos
Córtex Motor/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Feminino , Mãos , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho , Vibração
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