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1.
Adv Exp Med Biol ; 1305: 85-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834396

RESUMO

A leading goal in the field of biological psychiatry for depression is to find a promising diagnostic biomarker and selection of specific psychiatric treatment mode that is most likely to benefit patients with depression. Recent neuroimaging studies have characterized the pathophysiology of major depressive disorder (MDD) with functional and structural alterations in the neural circuitry involved in emotion or reward processing. Particularly, structural and functional magnetic resonance imaging (MRI) studies have reported that the brain structures deeply involved in emotion regulation or reward processing including the amygdala, prefrontal cortex (PFC), anterior cingulate cortex (ACC), ventral striatum, and hippocampus are key regions that provide useful information about diagnosis and treatment outcome prediction in MDD. For example, it has been consistently reported that elevated activity of the ACC is associated with better antidepressant response in patients with MDD. This chapter will discuss a growing body of evidence that suggests that diagnosis or prediction of outcome for specific treatment can be assisted by a neuroimaging-based biomarker in MDD.


Assuntos
Transtorno Depressivo Maior , Biomarcadores , Encéfalo/diagnóstico por imagem , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Imagem por Ressonância Magnética , Neuroimagem , Córtex Pré-Frontal
2.
Adv Exp Med Biol ; 1305: 333-349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834408

RESUMO

Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved technique for treating medication-resistant depression. Conventional rTMS includes high frequency (HF) to left dorsolateral prefrontal cortex (DLPFC) and low frequency to right DLPFC. However, not all depressed patients could benefit from standard rTMS protocols. Meta-analytical evidence indicated that there was an average response rate of 29.3% for patients receiving the most commonly adopted HF rTMS to the left DLPFC. Hence, newer forms of rTMS paradigms are warranted to improve antidepressant response and remission rate in patients with depression, especially those who are refractory to adequate antidepressant trials. In the current chapter, we review newer forms of rTMS paradigms and the content will cover standard theta burst stimulation (TBS), prolonged iTBS (piTBS), accelerated rTMS (aTMS), deep TMS (dTMS), priming TMS (pTMS), synchronized TMS (sTMS), and magnetic seizure therapy (MST).


Assuntos
Transtorno Depressivo Maior , Estimulação Magnética Transcraniana , Antidepressivos/uso terapêutico , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Córtex Pré-Frontal , Resultado do Tratamento
3.
Environ Health Prev Med ; 26(1): 34, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33706700

RESUMO

BACKGROUND: Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice. METHODS: Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method. RESULTS: The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1ß (IL-1ß) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice. CONCLUSIONS: These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.


Assuntos
Arsênico/toxicidade , Arsenitos/toxicidade , Poluentes Ambientais/toxicidade , Expressão Gênica/efeitos dos fármacos , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Comportamento Social , Compostos de Sódio/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Feminino , Marcadores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Córtex Pré-Frontal/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/psicologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serotonina/genética , Serotonina/metabolismo
4.
Neuron ; 109(6): 916-917, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33735614

RESUMO

In this issue of Neuron, Brincat et al. (2021) track in real time the working memory representations in prefrontal cortex of both hemispheres, as a saccade moves the remembered location from one hemifield to the other. They reveal a soft interhemispheric handover subserved by local rhythms and their interhemispheric synchronization.


Assuntos
Memória de Curto Prazo , Movimentos Sacádicos , Neurônios , Córtex Pré-Frontal
5.
Nihon Yakurigaku Zasshi ; 156(2): 62-65, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33642531

RESUMO

Exposure to stress induces alterations in synaptic functions, and increases the risk of stress-related psychiatric disorders, such as major depression and PTSD. To develop new treatments for stress-related psychiatric disorders, it is important to understand the effect of stress on the emotional circuits, such as prefrontal cortex (PFC), amygdala and other limbic regions. The orbitofrontal cortex (OFC, ventral subregion of the PFC) has important roles for processing of negative emotion and has recently been highlighted as a critical region in stress-related psychiatric disorders. However, mechanisms how stress affect OFC circuit and induce psychiatric symptoms were less understood. OFC sends dense projection to the amygdala, which is one of the key nodes for processing of negative emotion. Taken together, there is a possibility that stress affects the information processing in the OFC-amygdala pathway, and it underlies stress-induced emotional alteration. In this article, we introduce our research that examined effects of stress on the excitatory synaptic transmission from OFC to the basolateral nucleus of the amygdala (BLA) using optogenetic and whole-cell patch-clamp methods in mice.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Transtornos Mentais , Tonsila do Cerebelo , Animais , Camundongos , Córtex Pré-Frontal , Transmissão Sináptica
6.
Sheng Li Xue Bao ; 73(1): 10-16, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33665655

RESUMO

The aim of the present study was to observe the activation of microglia in the prefrontal cortex of type 1 diabetes mellitus (T1DM) mice, and the expression of the marker genes of the disease-associated microglia (DAM) associated with neurodegenerative diseases. Sixty healthy adult male C57BL/6J mice were randomly divided into two groups, normal control (CON) group and T1DM group. Streptozocin (STZ) was injected intraperitoneally to induce T1DM mice. The spatial learning and memory function of mice was detected by Morris water maze at the 8th week after the successful model establishment. The number and activation of microglia in the prefrontal cortex of mice were detected by immunofluorescence staining and Western blot. Changes in the mRNA level of several DAM molecular markers were detected by RT-FQ-PCR. The results showed that, compared with CON mice, the fasting blood glucose of T1DM mice increased significantly, while the body weight of T1DM mice decreased remarkably (P < 0.05). The escape latency of water maze in T1DM mice was longer than that in CON mice (P < 0.05). Compared with CON group, the Iba1 protein expression and the number of microglia in prefrontal cortex of T1DM group increased significantly (P < 0.05). In addition, the mRNA levels of several DAM markers in prefrontal cortex of T1DM group were increased significantly (P < 0.05). These results suggest that the microglia are activated and transformed to DAM type in the prefrontal cortex of T1DM mice.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Animais , Hipocampo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia , Córtex Pré-Frontal
7.
Nat Neurosci ; 24(3): 425-436, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33558695

RESUMO

We used the 10x Genomics Visium platform to define the spatial topography of gene expression in the six-layered human dorsolateral prefrontal cortex. We identified extensive layer-enriched expression signatures and refined associations to previous laminar markers. We overlaid our laminar expression signatures on large-scale single nucleus RNA-sequencing data, enhancing spatial annotation of expression-driven clusters. By integrating neuropsychiatric disorder gene sets, we showed differential layer-enriched expression of genes associated with schizophrenia and autism spectrum disorder, highlighting the clinical relevance of spatially defined expression. We then developed a data-driven framework to define unsupervised clusters in spatial transcriptomics data, which can be applied to other tissues or brain regions in which morphological architecture is not as well defined as cortical laminae. Last, we created a web application for the scientific community to explore these raw and summarized data to augment ongoing neuroscience and spatial transcriptomics research ( http://research.libd.org/spatialLIBD ).


Assuntos
Expressão Gênica , Córtex Pré-Frontal/metabolismo , Transcriptoma , Redes Reguladoras de Genes , Humanos
8.
Nat Commun ; 12(1): 1142, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602941

RESUMO

Negative symptoms in schizophrenia strongly contribute to poor functional outcomes, however its pathogenesis is still unclear. Here, we found that histamine H1 receptor (H1R) expression in basal forebrain (BF) cholinergic neurons was decreased in patients with schizophrenia having negative symptoms. Deletion of H1R gene in cholinergic neurons in mice resulted in functional deficiency of cholinergic projections from the BF to the prefrontal cortex and in the formation of sensorimotor gating deficit, social impairment and anhedonia-like behavior. These behavioral deficits can be rescued by re-expressing H1R or by chemogenetic activation of cholinergic neurons in the BF. Direct chemogenetic inhibition of BF cholinergic neurons produced such behavioral deficits and also increased the susceptibility to hyperlocomotion. Our results suggest that the H1R deficiency in BF cholinergic neurons is critical for sensorimotor gating deficit, social impairments and anhedonia-like behavior. This finding may help to understand the genetic and biochemical bases of negative symptoms in schizophrenia.


Assuntos
Neurônios Colinérgicos/metabolismo , Receptores Histamínicos H1/metabolismo , Filtro Sensorial , Comportamento Social , Anedonia/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Colina O-Acetiltransferase/metabolismo , Disfunção Cognitiva/complicações , Maleato de Dizocilpina/farmacologia , Feminino , Integrases/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Esquizofrenia/patologia
9.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540803

RESUMO

Distinct from ovarian estradiol, the steroid hormone 17ß-estradiol (E2) is produced in the brain and is involved in numerous functions, particularly acting as a neurosteroid. However, the physiological role of E2 and the mechanism of its effects are not well known. In hippocampal slices, 17ß-estradiol has been found to cause a modest increase in fast glutamatergic transmission; because some of these effects are rapid and acute, they might be mediated by membrane-associated receptors via nongenomic action. Moreover, activation of membrane estrogen receptors can rapidly modulate neuron function in a sex-specific manner. To further investigate the neurological role of E2, we examined the effect of E2, as an estrogen receptor (ER) agonist, on synaptic transmission in slices of the prefrontal cortex (PFC) and hippocampus in both male and female mice. Whole-cell recordings of spontaneous excitatory postsynaptic currents (sEPSC) in the PFC showed that E2 acts as a neuromodulator in glutamatergic transmission in the PFC in both sexes, but often in a cell-specific manner. The sEPSC amplitude and/or frequency responded to E2 in three ways, namely by significantly increasing, decreasing or having no response. Additional experiments using an agonist selective for ERß, diarylpropionitrile (DPN) showed that in males the sEPSC and spontaneous inhibitory postsynaptic currents sIPSC responses were similar to their E2 responses, but in females the estrogen receptor ß (ERß) agonist DPN did not influence excitatory transmission in the PFC. In contrast, in the hippocampus of both sexes E2 potentiated the gluatmatergic synaptic transmission in a subset of hippocampal cells. These data indicate that activation of E2 targeting probably a estrogen subtypes or different downstream signaling affect synaptic transmission in the brain PFC and hippocampus between males versus females mice.


Assuntos
Estradiol/farmacologia , Receptor alfa de Estrogênio/fisiologia , Hipocampo/metabolismo , Córtex Pré-Frontal/metabolismo , Transmissão Sináptica/fisiologia , Animais , Receptor alfa de Estrogênio/agonistas , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Feminino , GABAérgicos/farmacologia , Hipocampo/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Cinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nitrilos/farmacologia , Técnicas de Patch-Clamp , Córtex Pré-Frontal/efeitos dos fármacos , Propionatos/farmacologia , Caracteres Sexuais , Transmissão Sináptica/efeitos dos fármacos
10.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540617

RESUMO

Methamphetamine (MA) is a highly addictive psychomotor stimulant drug. In recent years, MA use has increased exponentially on a global scale, with the number of MA-involved deaths reaching epidemic proportions. There is no approved pharmacotherapy for treating MA use disorder, and we know relatively little regarding the neurobiological determinants of vulnerability to this disease. Extracellular signal-regulated kinase (ERK) is an important signaling molecule implicated in the long-lasting neuroadaptations purported to underlie the development of substance use disorders, but the role for this kinase in the propensity to develop addiction, particularly MA use disorder, is uncharacterized. In a previous MA-induced place-conditioning study of C57BL/6J mice, we characterized mice as MA-preferring, -neutral, or -avoiding and collected tissue from the medial prefrontal cortex (mPFC). Using immunoblotting, we determined that elevated phosphorylated ERK expression within the medial prefrontal cortex (mPFC) is a biochemical correlate of the affective valence of MA in a population of C57BL/6J mice. We confirmed the functional relevance for mPFC ERK activation for MA-induced place-preference via site-directed infusion of the MEK inhibitor U0126. By contrast, ERK inhibition did not have any effect upon MA-induced locomotion or its sensitization upon repeated MA treatment. Through studies of transgenic mice with alanine point mutations on T1123/S1126 of mGlu5 that disrupt ERK-dependent phosphorylation of the receptor, we discovered that ERK-dependent mGlu5 phosphorylation normally suppresses MA-induced conditioned place-preference (MA-CPP), but is necessary for this drug's reinforcing properties. If relevant to humans, the present results implicate individual differences in the capacity of MA-associated cues/contexts to hyper-activate ERK signaling within mPFC in MA Use Disorder vulnerability and pose mGlu5 as one ERK-directed target contributing to the propensity to seek out and take MA.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Metanfetamina/farmacologia , Transtornos Relacionados com Narcóticos/metabolismo , Córtex Pré-Frontal/metabolismo , Receptor de Glutamato Metabotrópico 5/metabolismo , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Relacionados com Narcóticos/psicologia , Fosforilação , Córtex Pré-Frontal/efeitos dos fármacos , Processamento de Proteína Pós-Traducional , Receptor de Glutamato Metabotrópico 5/química , Reforço Psicológico , Recompensa
11.
Neuron ; 109(6): 1055-1066.e4, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33561399

RESUMO

Visual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered location from one hemifield to the other. Before the shift, spike rates and oscillatory power showed clear signatures of memory laterality. After the shift, the lateralization inverted, consistent with transfer of the memory trace from one hemisphere to the other. Transferred traces initially used different neural ensembles from feedforward-induced ones, but they converged at the end of the delay. Around the time of transfer, synchrony between the two prefrontal hemispheres peaked in theta and beta frequencies, with a directionality consistent with memory trace transfer. This illustrates how dynamics between the two cortical hemispheres can stitch together WM traces across visual hemifields.


Assuntos
Lateralidade Funcional/fisiologia , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/fisiologia , Percepção Visual/fisiologia , Animais , Feminino , Macaca mulatta , Masculino
12.
Zhen Ci Yan Jiu ; 46(1): 8-13, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33559419

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) and "Sanyinjiao"(SP6) on conditioned place preference (CPP) and activation of glutamatergic neurons in the ventromedial prefrontal cortex (VMPFC) of morphine-addiction rats, so as to explore its mechanisms underlying detoxification. METHODS: Thirty male SD rats were randomly and equally divided into control, model and EA groups. The rats with acquisition of morphine-induced CPP received intraperitoneal injection of morphine (10 mg/kg) in the morphine-paired chamber, once daily for 3 consecutive days, and those of the control group received intraperitoneal injection of the same dose of normal saline in saline-paired chamber. Thirty minutes before CPP acquisition training, EA (2 Hz/100 Hz, 0.5 to 1.0 mA) was applied to ST36 and SP6 for 20 min every day. The double-labeled neurons of Fos/vesicular glutamate transporter 2 (VGLUT2) in the VMPFC were detected by using fluorescent immunohistochemistry. The discharges of the VMPFC neurons were recorded by using a multi-channel microarray electrophysiological system, followed by performing a z-score standardized processing. The ratio of firing rate frequency of rats in the morphine-paired chamber/saline-paired chamber was calculated, and further statistical analysis was conducted on the data based on the standardized z-scores. The neuronal firing characteristic of glutamatergic neuron is low frequency and wide wave. RESULTS: Compared with the control group, the score of morphine-induced CPP and numbers of Fos, VGLUT2-positive and Fos-VGLUT2 double-labeled positive cells were significantly increased in the model group (P<0.01,P<0.05). After EA and in comparison with the model group, the morphine CPP score and numbers of Fos, VGLUT2-positive and Fos-VGLUT2 double-labeled cells were significantly reduced in the EA group (P<0.01,P<0.05). The ratio of firing rate of the VMPFC neurons in the preference chamber and the percentage of inhibitory neurons as well as the z-score were considerably lower in the EA group than in the model group (P<0.001). CONCLUSION: EA can suppress morphine-induced seeking behavior in rats, which may be related to its inhibitory effect on glutamatergic neurons in the VMPFC.


Assuntos
Eletroacupuntura , Pontos de Acupuntura , Animais , Masculino , Morfina , Neurônios , Córtex Pré-Frontal , Ratos , Ratos Sprague-Dawley
13.
Zhen Ci Yan Jiu ; 46(1): 52-7, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33559426

RESUMO

OBJECTIVE: To observe the effect of acupuncture on the expression of proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), microglia marker ion calcium adaptor protein (Iba-1) and triggering receptor expressed on myeloid cells 2 (TREM2) in the prefrontal cortex of chronic stress-induced depression rats, so as to explore its antidepressant mechanism. METHODS: Thirty-two SD rats were randomly divided into normal control, model, acupuncture and fluoxetine groups, with 8 rats in each group. The depression model was established by using chronic mild unpredictable stress methods for 6 weeks. Manual acupuncture stimulation was applied to "Baihui" (GV20) and "Yintang" (GV29) for 10 min before modeling for 6 weeks. Fluoxetine (10 mg/kg, 1 mg/mL) was given to rats of the fluoxetine group by gavage before stress stimulation, once every day for 6 weeks. The open field test was used to evaluate the behavioral changes of rats. The contents of IL-1ß, IL-6 in the prefrontal cortex were determined by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to determine the expression of Iba-1 in the prefrontal cortex. The TREM2 gene expression in the prefrontal cortex was determined by real time fluorescent quantitative polymerase chain reaction (RT-PCR). RESULTS: After modeling, the crossing numbers and rearing times were significantly decreased in the model group relevant to the control group (P<0.05). After the treatment, the crossing numbers were significantly increased in the acupuncture and fluoxetine groups (P<0.05), while the rearing times in the acupuncture group were significantly increased (P<0.05). Compared with the control group, the contents of IL-1ß, IL-6 and the expression of Iba-1 positive cells in the prefrontal cortex were significantly increased in the model group (P<0.05), while the expression of TREM2 gene in the prefrontal cortex was significantly decreased (P<0.05). After the treatment, the increased levels of IL-1ß, IL-6 and Iba-1 positive cells and the decreased TREM2 gene expression were considerably reversed in both acupuncture and fluoxetine groups compared with the model group (P<0.05). CONCLUSION: Acupuncture intervention plays a positive role in anti-depression in rats, which may be related to its effects in inhibiting the activation of microglia, reducing the expression of proinflammatory cytokines, and increasing TREM2 expression in the prefrontal cortex.


Assuntos
Terapia por Acupuntura , Depressão , Animais , Depressão/genética , Depressão/terapia , Hipocampo , Microglia , Córtex Pré-Frontal , Ratos , Ratos Sprague-Dawley
14.
Nat Commun ; 12(1): 894, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563989

RESUMO

Prefrontal cortex is critical for cognition. Although much is known about the representation of cognitive variables in the prefrontal cortex, much less is known about the spatio-temporal neural dynamics that underlie cognitive operations. In the present study, we examined information timing and flow across the lateral prefrontal cortex (LPFC), while monkeys carried out a two-armed bandit reinforcement learning task in which they had to learn to select rewarding actions or rewarding objects. When we analyzed signals independently within subregions of the LPFC, we found a task-specific, caudo-rostral gradient in the strength and timing of signals related to chosen objects and chosen actions. In addition, when we characterized information flow among subregions, we found that information flow from action to object representations was stronger from the dorsal to ventral LPFC, and information flow from object to action representations was stronger from the ventral to dorsal LPFC. The object to action effects were more pronounced in object blocks, and also reflected learning specifically in these blocks. These results suggest anatomical segregation followed by the rapid integration of information within the LPFC.


Assuntos
Comportamento de Escolha/fisiologia , Córtex Pré-Frontal/fisiologia , Recompensa , Animais , Mapeamento Encefálico , Aprendizagem , Macaca , Modelos Neurológicos , Neurônios/fisiologia , Córtex Pré-Frontal/citologia , Tempo de Reação/fisiologia , Reforço Psicológico
15.
J Vis Exp ; (167)2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33522512

RESUMO

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that changes the likelihood of neuronal firing through modulation of neural resting membranes. Compared to other techniques, tDCS is relatively safe, cost-effective, and can be administered while individuals are engaged in controlled, specific cognitive processes. This latter point is important as tDCS may predominantly affect intrinsically active neural regions. In an effort to test tDCS as a potential treatment for psychiatric illness, the protocol described here outlines a novel procedure that allows the simultaneous application of tDCS during exposure to trauma-related cues using virtual reality (tDCS+VR) for veterans with posttraumatic stress disorder (NCT03372460). In this double-blind protocol, participants are assigned to either receive 2 mA tDCS, or sham stimulation, for 25 minutes while passively watching three 8-minute standardized virtual reality drives through Iraq or Afghanistan, with virtual reality events increasing in intensity during each drive. Participants undergo six sessions of tDCS+VR over the course of 2-3 weeks, and psychophysiology (skin conductance reactivity) is measured throughout each session. This allows testing for within and between session changes in hyperarousal to virtual reality events and adjunctive effects of tDCS. Stimulation is delivered through a built-in rechargeable battery-driven tDCS device using a 1 (anode) x 1 (cathode) unilateral electrode set-up. Each electrode is placed in a 3 x 3 cm (current density 2.22 A/m2) reusable sponge pocket saturated with 0.9% normal saline. Sponges with electrodes are attached to the participant's skull using a rubber headband with the electrodes placed such that they target regions within the ventromedial prefrontal cortex. The virtual reality headset is placed over the tDCS montage in such a way as to avoid electrode interference.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Realidade Virtual , Adolescente , Adulto , Idoso , Método Duplo-Cego , Eletrodos , Feminino , Resposta Galvânica da Pele , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiologia , Transtornos de Estresse Pós-Traumáticos/terapia , Estimulação Transcraniana por Corrente Contínua/psicologia
16.
Nat Commun ; 12(1): 1103, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597516

RESUMO

Neurons in some sensory areas reflect the content of working memory (WM) in their spiking activity. However, this spiking activity is seldom related to behavioral performance. We studied the responses of inferotemporal (IT) neurons, which exhibit object-selective activity, along with Frontal Eye Field (FEF) neurons, which exhibit spatially selective activity, during the delay period of an object WM task. Unlike the spiking activity and local field potentials (LFPs) within these areas, which were poor predictors of behavioral performance, the phase-locking of IT spikes and LFPs with the beta band of FEF LFPs robustly predicted successful WM maintenance. In addition, IT neurons exhibited greater object-selective persistent activity when their spikes were locked to the phase of FEF LFPs. These results reveal that the coordination between prefrontal and temporal cortex predicts the successful maintenance of visual information during WM.


Assuntos
Macaca mulatta/fisiologia , Memória de Curto Prazo/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Lobo Temporal/fisiologia , Potenciais de Ação/fisiologia , Algoritmos , Animais , Lobo Frontal/citologia , Lobo Frontal/fisiologia , Masculino , Modelos Neurológicos , Estimulação Luminosa , Córtex Pré-Frontal/citologia , Lobo Temporal/citologia
17.
Ecotoxicol Environ Saf ; 212: 112000, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33550075

RESUMO

Perinatal exposure to polybrominated diphenyl ethers (PBDEs) may be a potential risk factor for autism spectrum disorders (ASD). BDE-47 is one of the most common PBDEs and poses serious health hazards on the central nervous system (CNS). However, effects of perinatal exposure to BDE-47 on social behaviors and the potential mechanisms are largely unexplored. Thus, we aimed to investigate whether BDE-47 exposure during gestation and lactation led to autistic-like behaviors in offspring rats in the present study. Valproic acid (VPA), which is widely used to establish animal model of ASD, was also adopted to induce autistic-like behaviors. A battery of tests was conducted to evaluate social and repetitive behaviors in offspring rats. We found that perinatal exposure to BDE-47 caused mild autistic-like behaviors in offspring, which were similar but less severe to those observed in pups maternally exposed to VPA. Moreover, perinatal exposure to BDE-47 aggravated the autistic-like behaviors in pups maternally exposed to VPA. Abnormal dendritic development is known to be deeply associated with autistic-like behaviors. Golgi-Cox staining was used to observe the morphological characteristics of dendrites in the prefrontal cortex of pups. We found perinatal exposure to BDE-47 reduced dendritic length and complexity of branching pattern, and spine density in the offspring prefrontal cortex, which may contribute to autistic-like behaviors observed in the present study. Perinatal exposure to BDE-47 also exacerbated the impairments of dendritic development in pups maternally exposed to VPA. Besides, our study also provided the evidence that the inhibition of BDNF-CREB signaling, a key regulator of dendritic development, may be involved in the dendritic impairments induced by perinatal exposure to BDE-47 and/or VPA, and the consequent autistic-like behaviors.


Assuntos
Transtorno do Espectro Autista/induzido quimicamente , Dendritos/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Éteres Difenil Halogenados/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ácido Valproico/toxicidade , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Idade Gestacional , Lactação , Masculino , Córtex Pré-Frontal/efeitos dos fármacos , Gravidez , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Comportamento Social
18.
Medicine (Baltimore) ; 100(4): e24319, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530222

RESUMO

RATIONALE: Several brain structures, including the orbital prefrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, amygdala, and anterior cingulate cortex, are considered key structures in the neural circuitry underlying emotion regulation. We report on a patient showing behavior changes and degeneration of core neural tracts for emotional regulation following traumatic brain injury (TBI). PATIENT CONCERNS: A 51-year-old male patient suffered an in-car accident. The patient lost consciousness for approximately 30 days, and his Glasgow Coma Scale score was 3. He underwent stereotactic drainage for traumatic intraventricular and intracerebral hemorrhages. At approximately 6.5-year after onset, he began to show disinhibition behaviors such as shouting with anger, which worsened over time. At approximately 8-year after onset, he showed severe depression signs and disinhibition, including violence. DIAGNOSES: The patient who showed delayed-onset behavioral changes (disinhibition and depression). INTERVENTIONS: Diffusion tensor imaging data were acquired at 3 months and 8 years after TBI onset. OUTCOMES: The patient showed degeneration of core neural tracts for emotional regulation that was associated with delayed behavioral changes following TBI. On both 3-month and 8-year diffusion tensor tractographies (DTTs), the right dorsolateral prefronto-thalamic tract, ventrolateral prefronto-thalamic tract, orbital prefronto-thalamic tract, uncinate fasciculus, and both cinguli were reconstructed whereas other neural tracts were not reconstructed. Compared with the 3-month DTT, all reconstructed neural tracts on the 8-year DTT were narrow, except for the left cingulum, which showed new transcallosal fibers between both anterior cingula. The fractional anisotropy and tract volume of all reconstructed neural tracts were lower on the 8-year DTT than the 3-month DTT, except for the tract volume of left cingulum. LESSONS: The evaluation of dorsolateral, ventrolateral, and orbital prefronto-thalamic tract, uncinate fasciculus, and cingulum using follow-up DTTs is useful when a patient with TBI shows delayed-onset behavioral problems.


Assuntos
Lesões Encefálicas Traumáticas/psicologia , Regulação Emocional , Degeneração Neural/psicologia , Acidentes de Trânsito , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Depressão/diagnóstico por imagem , Depressão/etiologia , Imagem de Tensor de Difusão , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/lesões , Humanos , Inibição Psicológica , Masculino , Pessoa de Meia-Idade , Degeneração Neural/diagnóstico por imagem , Degeneração Neural/etiologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/lesões , Técnicas de Rastreamento Neuroanatômico , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/lesões , Tálamo/diagnóstico por imagem , Tálamo/lesões , /lesões
19.
Nat Commun ; 12(1): 904, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568654

RESUMO

In a dynamic world, it is essential to decide when to leave an exploited resource. Such patch-leaving decisions involve balancing the cost of moving against the gain expected from the alternative patch. This contrasts with value-guided decisions that typically involve maximizing reward by selecting the current best option. Patterns of neuronal activity pertaining to patch-leaving decisions have been reported in dorsal anterior cingulate cortex (dACC), whereas competition via mutual inhibition in ventromedial prefrontal cortex (vmPFC) is thought to underlie value-guided choice. Here, we show that the balance between cortical excitation and inhibition (E/I balance), measured by the ratio of GABA and glutamate concentrations, plays a dissociable role for the two kinds of decisions. Patch-leaving decision behaviour relates to E/I balance in dACC. In contrast, value-guided decision-making relates to E/I balance in vmPFC. These results support mechanistic accounts of value-guided choice and provide evidence for a role of dACC E/I balance in patch-leaving decisions.


Assuntos
Tomada de Decisões , Giro do Cíngulo/fisiologia , Adulto , Excitabilidade Cortical , Feminino , Ácido Glutâmico/análise , Ácido Glutâmico/metabolismo , Giro do Cíngulo/química , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Inibição Neural , Córtex Pré-Frontal , Adulto Jovem , Ácido gama-Aminobutírico/análise , Ácido gama-Aminobutírico/metabolismo
20.
Aerosp Med Hum Perform ; 92(2): 75-82, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33468287

RESUMO

BACKGROUND: Ischemic hypoxia induced by suprathreshold G-force loading can adversely affect vision, cognition, and lead to loss of consciousness (LOC). The purpose of this study was to determine whether reductions in cerebral oxygenation, caused by subthreshold G-forces (up to 4 Gz and of limited durations that do not lead to LOC), would affect visual perception and working memory performance.METHODS: Sixteen subjects performed visual perception and working memory tasks both before and during Gz exposures (1, 2.2, 3, 4 with leg pressurization, 4 with leg and abdomen pressurization) within a human-use centrifuge.RESULTS: As measured using near-infrared spectroscopy, blood oxygenation over medial prefrontal cortex was similar in the 1 and 2.2 Gz conditions, but was reduced to a similar extent in the 3 and 4 Gz conditions. In parallel, visual perception accuracy was reduced in the 3 and 4 Gz conditions, with no difference between the 3 and 4 Gz conditions. No change in reaction time was seen. Conversely, neither accuracy nor reaction time changes were observed for the visual working memory task.DISCUSSION: These results indicate that although visual working memory is not affected, the ability to visually discriminate between stimuli is reduced at G-forces as low as 3 and 4 Gz. This may have important ramifications for pilots who are routinely subjected to such forces.Croft RJ, Klegrd R, Tribukait A, Taylor NAS, Eiken O. Effects of acceleration-induced reductions in retinal and cerebral oxygenation on human performance. Aerosp Med Hum Perform. 2021; 92(2):7582.


Assuntos
Aceleração , Memória de Curto Prazo , Oxigênio/sangue , Córtex Pré-Frontal/irrigação sanguínea , Vasos Retinianos , Percepção Visual , Adulto , Medicina Aeroespacial , Feminino , Voluntários Saudáveis , Humanos , Masculino , Espectroscopia de Luz Próxima ao Infravermelho , Suécia , Análise e Desempenho de Tarefas
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