Investigating the role of Prefrontal Neurons in cognitive tasks through Fiber Photometry and Adapted Barnes Maze Protocols

The medial prefrontal cortex (mPFC) is essential in the execution of cognitive tasks, however very little is known on how these neurons are modulated during specific tasks and which subtype of neurons are responsible for so. Therego, with the intention of addressing this issue, we recorded mPFC gabaergic and glutamatergic activation patterns through fiber photometry (FIP) in mice, while simultaneously performing the Barnes Maze (BM) cognitive task (4 day behavioral trial). In addition, an altered structural and procedural protocol for BM was validated in this study due to necessary modifications allowing FIP and BM to happen simultaneously. A successful protocol validation was followed by our preliminary results, which showed that both glutamatergic and gabaergic neurons presented significant change in activation intensity and number of events in specific contexts throughout the task days. In addition, when stratified and crossed with BM performance parameters, such as latency to complete tasks and adopted strategy, glutamatergic and gabaergic neurons presented a significant decline in both activation patterns and number of activation events throughout the days. This data suggest not only an important role of glutamatergic and gabaergic mPFC neurons in learning, memory and decision making, but also that activation patterns of each of these groups may serve as markers for cognitive progression and/or dysfunction. KEY-WORDS: Memory, Learning, Decision Making, Medial Prefrontal Cortex (mPFC), Fiber Photometry (FIP), Barnes Maze (BM), Glutamatergic, Gabaergic, Neuronal Activity, Neuronal Activation Patterns, Neuronal Dynamics.

O córtex pré-frontal medial (mPFC) é essencial na execução de tarefas cognitivas, no entanto, pouco se sabe sobre como esses neurônios são modulados durante tarefas específicas e qual subtipo de neurônios é responsável por isso. Portanto, com a intenção de abordar essa questão, registramos os padrões de ativação de neurônios gabaérgicos e glutamatérgicos do mPFC por meio de fotometria de fibra (FIP) em camundongos, enquanto realizávamos simultaneamente a tarefa cognitiva do Labirinto de Barnes (BM) (ensaio comportamental de 4 dias). Além disso, um protocolo estrutural e procedimental alterado para o BM foi validado neste estudo devido a modificações necessárias que permitiram a realização simultânea de FIP e BM. Uma validação bem-sucedida do protocolo foi seguida pelos nossos resultados preliminares, que mostraram que tanto os neurônios glutamatérgicos quanto os gabaérgicos apresentaram mudanças significativas na intensidade de ativação e no número de eventos em contextos específicos ao longo dos dias da tarefa. Além disso, quando estratificados e cruzados com parâmetros de desempenho do BM, como latência para completar as tarefas e estratégia adotada, os neurônios glutamatérgicos e gabaérgicos apresentaram uma diminuição significativa nos padrões de ativação e no número de eventos de ativação ao longo dos dias. Esses dados sugerem não apenas um papel importante dos neurônios glutamatérgicos e gabaérgicos do mPFC na aprendizagem, memória e tomada de decisões, mas também que os padrões de ativação de cada um desses grupos podem servir como marcadores de progressão e/ou disfunção cognitiva. PALAVRAS-CHAVE: Memória, Aprendizagem, Tomada de Decisões, Córtex Pré-Frontal Medial (mPFC), Fotometria de Fibra (FIP), Labirinto de Barnes (BM), Glutamatérgico, Gabaérgico, Atividade Neuronal, Padrões de Ativação Neuronal, Dinâmica Neuronal.

Agressividade e psicopatia: um estudo comparativo entre detentos e adolescentes / Aggression and psychopathy: a comparative study between prisoners and adolescents / Agresividad y psicopatía: un estudio comparativo entre prisionesros y adolescentes

A agressividade e a psicopatia estão relacionadas com o funcionamento do córtex pré-frontal (CPF), cuja maturação leva aproximadamente 21 anos. Assim, objetivou-se identificar a existência de diferenças entre um grupo de adolescentes, com no máximo 20 anos de idade, e um grupo de detentos no tocante ao nível de agressividade e psicopatia. Para tanto, contou-se com a participação de 48 detentos do sexo masculino, com idade média de 34,6 (DP = 8,68) e 48 adolescentes do sexo masculino, com idade média de 17,75 (DP = 1,15). Os participantes responderam ao Questionário de Agressão de Buss-Perry, a Levenson Self-Report Psychopathy scale (LSRS) e a um questionário sociodemográfico. Os resultados dos testes Mann-Whitney e teste t de student indicaram a existência de diferenças significativas apenas para a psicopatia secundária, sendo mais característica em detentos. Os achados foram discutidos considerando a relação do desenvolvimento do CPF com fatores ambientais

Aggression and psychopathy are prefrontal cortex (PFC) activity-related and the maturation of this region takes approximately 21 years. Our aim was to assess differences in aggression and psychopathy levels between an adolescent group (máx age 20) and a prisoner group. It counted with a sample of 48 male prisoners mean aged 34,6 (SD = 3.66) and 48 male adolescents mean aged 17,75 (SD = 1.5). The participants answered the Buss-Perry Aggression Questionnaire; the Levenson Levenson Self-Report Psychopathy Scale (LSRS) and a demographic questionnaire. The Mann-Whitney test and the Student's t-test results shown significant differences only for secondary psychopathy, which was higher in the prisoner group. Our findings were discussed considering the relationship between the PFC development and external factors

La agresividad y la psicopatía están relacionadas con el funcionamiento de la corteza prefrontal (CPF), cuya maduración tarda aproximadamente 21 años. Por lo tanto, el objetivo era identificar la existencia de diferencias entre un grupo de adolescentes, con un máximo de 20 años de edad, y un grupo de prisioneros, con respecto al nivel de agresión y psicopatía. Para ello, participaron del estudio 48 prisioneros de sexo masculino, con una edad promedio de 34,6 (DE = 8,68) y 48 adolescentes de sexo masculino, con una edad promedio de 17,75 (DE = 1,15). Los participantes respondieron al Cuestionario de Agresión de Buss-Perry, al Levenson Self-Report Psychopathy scale ­ LSRS y a un cuetionario sociodemográfico. Los resultados de los testes de Mann-Whitney y de t de Student indicaron diferencias significativas solo para la psicopatía secundaria, siendo más característicos en los prisioneros. Los hallazgos se discutieron como base en la relación del desarrollo de la CPF con factores ambientales

La depresión con ideas suicidas presenta disfunciones corticales prefrontales que favorecen significativamente el intento suicida / Depression with suicidal ideas presents prefrontal cortical dysfunctions that significantly favor suicidal intent

Se realiza una revisión de estudios de resonancia magnética integral y funcional, así como estudios bioquímicos en pacientes con y sin ideas suicidas. Estos estudios en pacientes con alto riesgo de suicidio presentan una disminución de volúmenes corticales en la corteza prefrontal dorso y ventrolateral. Lo importante de estos estudios es que resultan de la comparación con pacientes deprimidos con bajo riesgo de suicidio. Los estudios de resonancia magnética funcional mostraron una hipofuncionalidad del lóbulo prefrontal en los pacientes depresivos con ideas suicidas severas, que se observa como una disminución del flujo sanguíneo cerebral en las áreas lateral y ventral. Se observa una disminución del metabolismo de serotonina, en clara relación con la severidad de las ideas de muerte, también con un foco en la región lateroventral prefrontal. Dado que las funciones de la corteza prefrontal afirman al individuo en su perspectiva vital, disfunciones como las descritas debilitan la coordinación y organización del apego a la vida, quedando, por el contrario, la posibilidad de la búsqueda de la muerte. Se concluye que los pacientes depresivos con ideas suicidas tienen una alta vulnerabilidad para el intento de suicidio por la afectación de las zonas prefrontales.

A review of functional integral magnetic resonance and biochemical data from patients with and without suicidal ideation is presented. Patients with high suicidal risk show a decrease in cortical volume in ventrolateral and dorsal prefrontal cortex. These studies are compared to those of depressed patients with low suicidal risk. Functional magnetic resonance in depressed patients with severe suicidal ideation show an hypo functional prefrontal lobe, seen as a decrease in blood flow in lateral and ventral areas. There is a decrease in serotonin metabolism, clearly related to the severity of suicidal ideation, also in ventrolateral prefrontal cortex. As prefrontal cortex functions enhance vital perspectives, such dysfunctions weaken coordination and organization of attachment to life, making search for death a possibility. Authors conclude that depressed patients with suicidal ideation have a high vulnerability for suicidal intent due to changes in prefrontal areas.

Posibles mecanismos de acción de la terapia electroconvulsiva en esquizofrenia: revisión de la evidencia disponible en investigación con seres humanos / A review about the putative mechanisms of action of electroconvulsive therapy in schizophrenia in human research

Electroconvulsive therapy (ECT) has multiple uses in psychiatry, but its mechanisms of action (MA) in patients with schizophrenia (PS) are poorly understood. We synthesize and discuss the available evidence in this regard. We conducted a search for primary human studies and systematic reviews searching MA of ECT in PS published in PubMed/Medline, SciELO, PsycInfo, and the Cochrane Library, including 24 articles. Genetic findings are scarce and inconsistent. At the molecular level, the dopaminergic and GABAergic role stands out. The increase in brain derived neurotrophic factor (BDNF) after ECT, is a predictor of positive clinical outcomes, while the change in N-acetyl aspartate levels would demonstrate a neuroprotective role for ECT. This intervention would improve inflammatory and oxidative parameters, thereby resulting in a symptomatic improvement. ECT is associated with an increase in functional connectivity in the thalamus, right putamen, prefrontal cortex and left precuneus, structures that play a role in the neural default mode network. A decrease in connectivity between the thalamus and the sensory cortex and an enhanced functional connectivity of the right thalamus to right putamen along with a clinical improvement have been reported after ECT. Moreover a volumetric increase in hippocampus and insula has been reported after ECT. These changes could be associated with the biochemical pathophysiology of schizophrenia. Most of the included studies are observational or quasi-experimental, with small sample sizes. However, they show simultaneous changes at different neurobiological levels, with a pathophysiological and clinical correlation. We propose that the research on ECT should be carried out from neurobiological dimensions, but with a clinical perspective.

High efficiency of left superior frontal gyrus and the symptom features of major depressive disorder / 中南大学学报(医学版)

OBJECTIVES@#Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment.@*METHODS@#Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki).@*RESULTS@#Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment.@*CONCLUSIONS@#There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.

Patterns of diversification and phylogenetic structure in the dorsolateral head musculature of Neotropical electric eels (Ostariophysi: Gymnotiformes), with a myological synonymy

The present study offers a broad comparative analysis of the dorsolateral head musculature in the Gymnotiformes, with detailed descriptions and illustrations of the dorsolateral head muscles of 83 species representing combined all valid genera. Results permit a detailed assessment of primary homologies and taxonomically-relevant variation across the order. This provides the basis for a myological synonymy, which organizes 33 previously proposed names for 15 recognized muscles. Morphological variation derived from dorsolateral head musculature was coded into 56 characters. When analyzed in isolation, that set of characters results in Gymnotidae as the sister group of remaining gymnotiforms, and all other currently recognized families as monophyletic groups. In a second analysis, myological characters were concatenated with other previously proposed characters into a phenotypic matrix. Results of that analysis reveal new myological synapomorphies for nearly all taxonomic categories within Gymnotiformes. A Partitioned Bremer Support (PBS) was used to asses the significance of comparative myology in elucidating phylogenetic relationships. PBS values show strongly non-uniform distributions on the tree, with positive scores skewed towards more inclusive taxa, and negative PBS values concentrated on less inclusive clades. Our results provide background for future studies on biomechanical constraints evolved in the early stages of gymnotiform evolution.(AU)

O presente estudo fornece uma ampla análise comparativa da musculatura dorsolateral da cabeça dos Gymnotiformes, com descrições detalhadas e ilustrações dos músculos dorsolaterais da cabeça de 83 espécies representando quase todos os gêneros válidos. Resultados permitem uma avaliação das homologias primárias e da variação taxonomicamente relevante na ordem. Isto fornece a base para uma sinonímia da nomenclatura miológica que organiza 33 nomes previamente propostos para os 15 músculos reconhecidos. As variações morfológicas da musculatura dorsolateral da cabeça foram codificadas em 56 caracteres. Este conjunto de dados foi inicialmente analisado isoladamente, resultando em Gymnotidae como grupo-irmão dos demais Gymnotiformes; e todas as famílias como grupos monofiléticos. Numa segunda análise, os caracteres musculares foram concatenados com uma matriz fenotípica previamente proposta compondo uma ampla matriz morfológica combinada. Os resultados desta análise revelaram novas sinapomorfias miológicas para todas as categorias taxonômicas em Gymnotiformes. O Suporte de Bremer Particionado (SBP) foi implementado para acessar a influência da miologia em elucidar os relacionamentos filogenéticos. Os valores de SBP exibem uma distribuição não uniforme na árvore, com indicadores positivos para agrupamentos mais inclusivos e valores negativos de SBP em clados menos inclusivos. Nossos resultados fornecem subsídios para investigações futuras sobre as restrições biomecânicas envolvidas nos estágios inicias da evolução dos Gymnotiformes.(AU)

Neurovascular coupling analysis of working memory based on electroencephalography and functional near-infrared spectroscopy / 生物医学工程学杂志

Working memory is an important foundation for advanced cognitive function. The paper combines the spatiotemporal advantages of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to explore the neurovascular coupling mechanism of working memory. In the data analysis, the convolution matrix of time series of different trials in EEG data and hemodynamic response function (HRF) and the blood oxygen change matrix of fNIRS are extracted as the coupling characteristics. Then, canonical correlation analysis (CCA) is used to calculate the cross correlation between the two modal features. The results show that CCA algorithm can extract the similar change trend of related components between trials, and fNIRS activation of frontal pole region and dorsolateral prefrontal lobe are correlated with the delta, theta, and alpha rhythms of EEG data. This study reveals the mechanism of neurovascular coupling of working memory, and provides a new method for fusion of EEG data and fNIRS data.

Effects of transcranial magneto-acoustic electrical stimulation on calcium signals in prefrontal nerve clusters / 生物医学工程学杂志

Transcranial magneto-acoustic electrical stimulation (TMAES) is a novel method of brain nerve regulation and research, which uses induction current generated by the coupling of ultrasound and magnetic field to regulate neural electrical activity in different brain regions. As the second special envoy of nerve signal, calcium plays a key role in nerve signal transmission. In order to investigate the effect of TMAES on prefrontal cortex electrical activity, 15 mice were divided into control group, ultrasound stimulation (TUS) group and TMAES group. The TMAES group received 2.6 W/cm 2 and 0.3 T of magnetic induction intensity, the TUS group received only ultrasound stimulation, and the control group received no ultrasound and magnetic field for one week. The calcium ion concentration in the prefrontal cortex of mice was recorded in real time by optical fiber photometric detection technology. The new object recognition experiment was conducted to compare the behavioral differences and the time-frequency distribution of calcium signal in each group. The results showed that the mean value of calcium transient signal in the TMAES group was (4.84 ± 0.11)% within 10 s after the stimulation, which was higher than that in the TUS group (4.40 ± 0.10)% and the control group (4.22 ± 0.08)%, and the waveform of calcium transient signal was slower, suggesting that calcium metabolism was faster. The main energy band of the TMAES group was 0-20 Hz, that of the TUS group was 0-12 Hz and that of the control group was 0-8 Hz. The cognitive index was 0.71 in the TMAES group, 0.63 in the TUS group, and 0.58 in the control group, indicating that both ultrasonic and magneto-acoustic stimulation could improve the cognitive ability of mice, but the effect of the TMAES group was better than that of the TUS group. These results suggest that TMAES can change the calcium homeostasis of prefrontal cortex nerve clusters, regulate the discharge activity of prefrontal nerve clusters, and promote cognitive function. The results of this study provide data support and reference for further exploration of the deep neural mechanism of TMAES.

Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats / 中国应用生理学杂志

Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P＜0.01), the level of MT were decreased significantly (P＜0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P＜0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P＜0.01), and the level of ROS was increased significantly (P＜0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P＜0.01, P＜0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P＜0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.

Mechanism of valproic acid-induced dendritic spine and synaptic impairment in the prefrontal cortex for causing core autistic symptoms in mice / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism of valproic acid (VPA) -induced impairment of the dendritic spines and synapses in the prefrontal cortex (PFC) for causing core symptoms of autism spectrum disorder (ASD) in mice.@*METHODS@#Female C57 mice were subjected to injections of saline or VPA on gestational days 10 and 12, and the male offspring mice in the two groups were used as the normal control group and ASD model group (n=10), respectively. Another 20 male mice with fetal exposure to VPA were randomized into two groups for stereotactic injection of DMSO or Wortmannin into the PFC (n=10). Open field test, juvenile play test and 3-chamber test were used to evaluate autistic behaviors of the mice. The density of dendrite spines in the PFC was observed with Golgi staining. Western blotting and immunofluorescence staining were used to detect the expressions of p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and the synaptic proteins PSD95, p-Syn, and Syn in the PFC of the mice.@*RESULTS@#Compared with the normal control mice, the mice with fetal exposure to VPA exhibited obvious autism-like behaviors with significantly decreased density of total, mushroom and stubby dendritic spines (P < 0.05) and increased filopodia dendritic spines (P < 0.05) in the PFC. The VPA-exposed mice also showed significantly increased expressions of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR (P < 0.01) and lowered expressions of PSD95 and p-Syn/Syn in the PFC (P < 0.05 or 0.001). Wortmannin injection into the PFC obviously improved the ASD-like phenotype and dendritic spine development, down-regulated PI3K/Akt/mTOR signaling pathway and up-regulated the synaptic proteins in VPA-exposed mice.@*CONCLUSION@#In male mice with fetal exposure to VPA, excessive activation of PI3K/Akt/mTOR signaling pathway and decreased expressions of the synaptic proteins PSD95 and p-Syn cause dendritic spine damage and synaptic development disturbance in the PFC, which eventually leads to ASD-like phenotype.

Abordaje interhemisférico contralateral transfalcino para resección de empendimoma supratentorial extraventricular: presentación de caso y análisis de literatura / Contralateral Transfalcine Interhemispheric Approach for Resection of Extraventricular Supratentorial Empendymoma: Case Presentation and Literature Analysis

Introducción: los ependimomas supratentoriales extraventriculares son una entidad sumamente infrecuente, solo 45 casos han sido reportados en la literatura. La mayoría de los ependimomas se localizan a nivel infratentorial e intraventricular, solo en un grupo pequeño de casos no presentan continuidad con el sistema ventricular. El objetivo de este trabajo es describir y presentar el caso de un tumor inusual, cuya importancia radica en la baja prevalencia de casos reportados en la literatura y en la particularidad del abordaje quirúrgico seleccionado. Descripción del caso: paciente de sexo masculino, de 16 años de edad, con diagnóstico de lesión ocupante de espacio sólida-quística, a nivel frontal izquierdo, entre el giro frontal superior y giro del cíngulo. Se optó por realizar un abordaje interhemisférico contralateral transfalcino, logrando la resección total de la lesión tumoral. Se obtuvo el diagnóstico histopatológico de ependimoma Grado II según clasificación de la OMS. Discusión: en base a la información analizada en los diferentes artículos, los hallazgos imagenológicos y anatomopatológicos del caso presentado coinciden con lo relatado en la literatura acerca de los ependimomas supratentoriales extraventricualres. Es imprescindible la utilización de técnicas de inmunohistoquímica para la correcta tipificación del tumor ya que las características del mismo son fácilmente confundibles con otras entidades y su correcta graduación tiene implicancias pronósticas y terapéuticas. Conclusión: los ependimomas supratentoriales extraventricualares son neoplasias sumamente inusuales. La resección quirúrgica es considerada el tratamiento de primera línea para mejorar el pronóstico y la sobrevida. El abordaje interhemisférico contralateral transfalcino nos permitió lograr la exéresis total de la lesión tumoral, favoreciéndonos un adecuado ángulo de trabajo y reduciendo así la transgresión del parénquima cerebral

ntroduction: extraventricular supratentorial ependymomas are an extremely rare entity, only 45 cases have been reported in the literature. Most ependymomas are located at the infratentorial and intraventricular level, only in a small group of cases don ́t present continuity with the ventricular system. The aim of this paper is to describe and to present the case of an unusual tumor, the importance lies in the low prevalence of cases reported in the literature and in the particularity of the selected surgical approach. Case description: a 16-year-old male patient with a diagnosis of a solid-cystic space-occupying lesion, at the left frontal level, between the superior frontal gyrus and the cingulate gyrus, measuring 40mm x 50mm x 60mm. A contralateral transfalcine interhemispheric approach was chosen, achieving total resection of the lesion. The histopathological diagnosis of Grade II ependymoma was obtained according to WHO. Discussion: based on the information analyzed in the different articles, the imaging and pathological findings of the case presented coincide with what is reported in the literature about supratentorial extraventricular ependymomas. The use of immunohistochemical techniques is essential for the correct typing of the tumor since its characteristics are easily confused with other entities and its correct graduation has prognostic and therapeutic implications Conclusion: extraventricular supratentorial ependymomas are extremely rare neoplasms. Surgical resection is considered the first-line treatment to improve prognosis and survival. The contralateral transfalcine interhemispheric approach allowed us to achieve a total resection of the lesion, favoring an adequate working angle and thus reducing the transgression of the brain parenchyma

Evaluation of structural changes in orbitofrontal cortex in relation to medication overuse in migraine patients: a diffusion tensor imaging study / Avaliação das mudanças estruturais no córtex orbitofrontal em relação ao uso excessivo de medicamentos em pacientes com migrânea: um estudo de imagem por tensor de difusão

Abstract Background: Migraine is a prevalent neurological disease that leads to severe headaches. Moreover, it is the commonest among the primary headaches that cause medication overuse headache (MOH). The orbitofrontal cortex (OFC) is one of the structures most associated with medication overuse. Objective: To determine microstructural changes in the OFC among migraine patients who developed MOH, through the diffusion tensor imaging (DTI) technique. Methods: Fifty-eight patients who had been diagnosed with migraine based on the Classification of Headache Disorders (ICHD-III-B) were included in the study. Patients were sub-classified into two groups, with and without MOH, based on the MOH criteria of ICHD-III-B. DTI was applied to each patient. The OFC fractional anisotropy (FA), and apparent diffusion coefficient (ADC) values of the two groups were compared. Results: The mean age of all the patients was 35.98±7.92 years (range: 18-65), and 84.5% (n=49) of them were female. The two groups, with MOH (n=25) and without (n=33), were alike in terms of age, gender, family history, migraine with or without aura and duration of illness. It was found that there was a significant difference in FA values of the left OFC between the two groups (0.32±0.01 versus 0.29±0.01; p=0.04). Conclusions: An association was found between MOH and changes to OFC microstructure. Determination of neuropathology and factors associated with medication overuse among migraine patients is crucial in terms of identifying the at-risk patient population and improving proper treatment strategies specific to these patients.

RESUMO Introdução: A migrânea é uma doença neurológica prevalente que causa fortes dores de cabeça. Além disso, é a mais comum entre as cefaleias primárias que causam cefaleia por uso excessivo de medicamentos (CUEM). O córtex orbitofrontal (OF) é uma das estruturas mais associadas ao uso excessivo de medicamentos. Objetivo: Determinar alterações microestruturais no córtex OF em pacientes com migrânea que desenvolveram CUEM, por meio da técnica de imagem por tensor de difusão (ITD). Métodos: Cinquenta e oito pacientes com diagnóstico de migrânea, com base na Classificação das Cefaleias (ICHD-III-B), foram incluídos no estudo. Os pacientes foram subclassificados em dois grupos, com e sem CUEM, com base nos critérios de CUEM da ICHD-III-B. A ITD foi aplicada a cada paciente. Os valores de anisotropia fracionada OFC (AF) e coeficiente de difusão aparente (CDA) dos dois grupos foram comparados. Resultados: A média de idade de todos os pacientes foi de 35,98±7,92 anos (variação: 18‒65), sendo 84,5% (n=49) do sexo feminino. Os dois grupos, com CUEM (n=25) e sem (n=33), são semelhantes em termos de idade, sexo, história familiar, migrânea com ou sem aura e duração da doença. Verificou-se que houve diferença significativa nos valores de AF do córtex OF esquerdo entre os dois grupos (0,32±0,01 versus 0,29±0,01; p=0,04). Conclusões: Foi encontrada associação entre o CUEM e as alterações na microestrutura do córtex OF. A determinação da neuropatologia e dos fatores associados ao uso excessivo de medicamentos entre pacientes com migrânea é crucial para identificar a população de pacientes em risco e melhorar as estratégias de tratamento adequadas específicas para esses pacientes.

Improvement in borderline personality disorder symptomatology after repetitive transcranial magnetic stimulation of the dorsomedial prefrontal cortex: preliminary results

Objective: Current treatment for borderline personality disorder (BPD) involves psychological and pharmacological interventions. However, neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) may positively affect BPD symptomatology. The objective of this study was to evaluate the clinical and neuropsychological effects of rTMS on the dorsomedial prefrontal cortex (DMPFC) in BPD patients. Methods: Fourteen patients with BPD were randomized into two groups (active vs. sham) for 15 sessions of rTMS on the DMPFC. Clinical effects were measured using the Borderline Symptoms List (BSL), Clinical Global Impression Scale for BPD (CGI-BPD), Borderline Evaluation of Severity over Time (BEST), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Barratt's Impulsiveness Scale (BIS). Neuropsychological effects were determined by a Stop-Signal Task (SST), the Wisconsin Card-Sorting Test (WCST), and the Iowa Gambling Test (IGT). Results: Within-group comparison showed significant differences (p < 0.05) in CGI-BPD (total score and six of nine psychopathologic domains), BEST, HDRS, HARS, and IGT scores for active modality. Conclusion: The 5 Hz-DMPFC rTMS technique was well tolerated and lessened the severity of BPD symptomatology, especially abandonment, affective issues, interpersonal relationships, suicidal behavior, anger, and paranoid ideation. Cognitive improvement was seen in decision-making. Additional studies are needed to fully evaluate the effects of rTMS on BPD symptomatology. Clinical Trial Registration: NCT03832777.

Mild poikilocapnic hypoxia increases very low frequency haemoglobin oxygenation oscillations in prefrontal cortex

BACKGROUND: The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO2), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO2 from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m2, age 30.8 ± 13.4 years). RESULTS: We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema. CONCLUSIONS: Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO2 and SAS width monitoring might be beneficial for patients with acute lung disease.

Electroacupuncture suppresses glucose metabolism and GLUT-3 expression in medial prefrontal cortical in rats with neuropathic pain

BACKGROUND: Accumulating evidence has demonstrated that the electroacupuncture (EA) stimulation could effectively alleviate neuropathic pain. The medial prefrontal cortex (mPFC) is a vital part of the cortical representation of pain in the brain, and its glucose metabolism is mostly affected in the progression of pain. However, the central mechanism of EA analgesia remains unclear. METHODS: Fifty-four male SD rats were equally randomized into sham surgery (Sham) group, chronic constriction injury (CCI) group and EA stimulation (EA) group. The CCI model, involving ligature of the right sciatic nerve, was established in all animals except the Sham group. EA stimulation was applied on the right side acupoints of Huantiao (GB30) and Yanglingquan (GB34) in the EA group. Paw withdrawal threshold (PWT) and paw thermal withdrawal latency (PWL) were measured. The 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) was used to evaluate glucose metabolism changes in the mPFC. The expression of glucose transporter 3 (GLUT-3) in the mPFC was determined by immune histochemistry and ELISA. RESULTS: Comparing with CCI groups, EA treatment was obviously reversed CCI-induced mechanical allodynia (P < 0.01), thermal hyperalgesia (P < 0.01) and the increase of glucose metabolism in the left mPFC (P < 0.05). Furthermore, EA treatment significantly decreased the protein expression of GLUT-3 in the left mPFC (P < 0.01). CONCLUSIONS: Our results indicate that EA analgesia effect may be related to suppressing the glucose metabolism and GLUT-3 expression in the mPFC. This study could provide a potential insight into the central mechanisms involved in the analgesic effect of EA.

Effects of maternal exposure to arsenic on social behavior and related gene expression in F2 male mice

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-1β (IL-1β) 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.

Changes in microglia number and Iba1 expression level in the prefrontal cortex of type 1 diabetic mice / 生理学报

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.

The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction / 神经科学通报·英文版

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca

Research on the influence of mixed emotional factors on false memory based on brain functional network / 生物医学工程学杂志

Analyzing the influence of mixed emotional factors on false memory through brain function network is helpful to further explore the nature of brain memory. In this study, Deese-Roediger-Mc-Dermott (DRM) paradigm electroencephalogram (EEG) experiment was designed with mixed emotional memory materials, and different kinds of music were used to induce positive, calm and negative emotions of three groups of subjects. For the obtained false memory EEG signals, standardized low resolution brain electromagnetic tomography algorithm (sLORETA) was applied in the source localization, and then the functional network of cerebral cortex was built and analyzed. The results show that the positive group has the most false memories [(83.3 ± 6.8)%], the prefrontal lobe and left temporal lobe are activated, and the degree of activation and the density of brain network are significantly larger than those of the calm group and the negative group. In the calm group, the posterior prefrontal lobe and temporal lobe are activated, and the collectivization degree and the information transmission rate of brain network are larger than those of the positive and negative groups. The negative group has the least false memories [(73.3 ± 2.2)%], and the prefrontal lobe and right temporal lobe are activated. The brain network is the sparsest in the negative group, the degree of centralization is significantly larger than that of the calm group, but the collectivization degree and the information transmission rate of brain network are smaller than the positive group. The results show that the brain is stimulated by positive emotions, so more brain resources are used to memorize and associate words, which increases false memory. The activity of the brain is inhibited by negative emotions, which hinders the brain's memory and association of words and reduces false memory.