Probabilistic Tractography Between Nucleus Accumbens and Other Reward-related Brain Areas in Malay Female Adolescents

@#Introduction: Studies show that adolescents are more reward sensitive compared to other age groups. The nucleus accumbens (NAcc) has been identified as a key brain area involved in reward through its connectivity to other reward-related brain areas. Our study aimed to characterise the white matter structural connectivity of nucleus accumbens with brain areas that are most often associated with reward in female adolescents. Methods: Fifteen healthy female Malay adolescents were recruited and underwent diffusion-weighted brain scanning. Two behaviour scales were also given to verify typical reward responsiveness. Then, probabilistic tractography and NAcc segmentation were performed on the data using FMRIB Software Library (FSL). Probabilistic tractography was performed to determine the relative connection probability of nucleus accumbens (NAcc) to areas shown to be associated with reward, namely amygdala, anterior cingulate cortex (ACC), medial orbitofrontal cortex (mOFC), hippocampus, ventrolateral prefrontal cortex (vlPFC) and dorsolateral prefrontal cortex (dlPFC). Connectivity-based segmentation of NAcc was performed to determine the spatial distribution of its connectivity with the target brain areas according to the highest connection probability. Results: The highest relative connection probability was found between NAcc to mOFC, while the NAcc parcellation showed the widest distribution of connection to mOFC compared to the other five targets on both sides of the brain. Conclusion: Our findings demonstrated the strongest structural connectivity and widest distribution between NAcc and mOFC compared with other brain areas related to reward. This study’s findings could be used as baseline to compare with people with atypical reward circuit problems.

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.

Divergent Projection Patterns Revealed by Reconstruction of Individual Neurons in Orbitofrontal Cortex / 神经科学通报·英文版

The orbitofrontal cortex (OFC) is involved in diverse brain functions via its extensive projections to multiple target regions. There is a growing understanding of the overall outputs of the OFC at the population level, but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare. Here, by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system (fMOST), we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons. We compared the whole-brain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer. We found cortical layer-dependent projections characterized by divergent patterns for information delivery. Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC, but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.

Impaired Parahippocampal Gyrus-Orbitofrontal Cortex Circuit Associated with Visuospatial Memory Deficit as a Potential Biomarker and Interventional Approach for Alzheimer Disease / 神经科学通报·英文版

The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

Executive function performance in patients with obesity: a systematic review / Desempeño en tareas de funcionamiento ejecutivo en pacientes con obesidad: una revisión sistemática

Abstract Executive dysfunction is associated with the inability to control aberrant behaviors, such as chronic overeating (Moore, Sabino, Koob, & Cottone, 2017). Obese individuals often report great difficulties controlling eating behaviors, despite a desire to successfully lose weight (Dohle, Diel, & Hofmann, 2018). However, current literature lacks a systematic review about the relationship between executive dysfunction and Obesity. The aim of this study is to present the most important findings about this matter. First, a bibliometric analysis shows the evolution of the topic. Then, the Tree of Science tool is used to show a chronological review that provides a general description of the roots and current perspectives of the state of literature. Finally, clustering analysis of the co-citation network was employed to identify the different perspectives of the topic. The main findings suggest four approaches: (1) effects of body mass index on executive functioning, (2) executive functioning in children with overweight and obesity, (3) physical activity for adult obesity and (4) structural and functional brain changes in obesity. Preliminary data state that in obesity, poor food choices may be associated with frontal cognitive impairments that contribute to reduced orbitofrontal cortex volume.

Resumen Las alteraciones en el funcionamiento ejecutivo están relacionadas con la incapacidad de controlar conductas como comer en exceso. Pacientes con diagnóstico de obesidad reportan dificultades para controlar las conductas alimentarias, a pesar del deseo de perder peso. Sin embargo, la literatura actual carece de una revisión sistemática sobre la relación entre las alteraciones del funcionamiento ejecutivo y la obesidad. El objetivo de este estudio es presentar los hallazgos más importantes sobre este tema. Primero, un análisis bibliométrico muestra la evolución del tema. Luego, desde la herramienta Tree of Science se presenta una revisión cronológica que proporciona una descripción general de estudios seminales y perspectivas actuales del estado de la literatura. Finalmente, se empleó el análisis de agrupamiento de la red de co-citaciones para identificar las diferentes perspectivas del tema. Los hallazgos sugieren cuatro perspectivas: (1) los efectos del índice de masa corporal en el funcionamiento ejecutivo, (2) el funcionamiento ejecutivo en niños con sobrepeso y obesidad, (3) la actividad física en adultos con obesidad y (4) los cambios cerebrales estructurales y funcionales en la obesidad. Los datos preliminares sugieren que, en la obesidad, la mala elección de alimentos puede asociarse con deficiencias cognitivas frontales que pueden ser el resultado de disminuciones en el volumen de la corteza orbitofrontal.

Promising Neuroimaging Biomarkers in Depression

The neuroimaging has been applied in the study of pathophysiology in major depressive disorder (MDD). In this review article, several kinds of methodologies of neuroimaging would be discussed to summarize the promising biomarkers in MDD. For the magnetic resonance imaging (MRI) and magnetoencephalography field, the literature review showed the potentially promising roles of frontal lobes, such as anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). In addition, the limbic regions, such as hippocampus and amygdala, might be the potentially promising biomarkers for MDD. The structures and functions of ACC, DLPFC, OFC, amygdala and hippocampus might be confirmed as the biomarkers for the prediction of antidepressant treatment responses and for the pathophysiology of MDD. The functions of cognitive control and emotion regulation of these regions might be crucial for the establishment of biomarkers. The near-infrared spectroscopy studies demonstrated that blood flow in the frontal lobe, such as the DLPFC and OFC, might be the biomarkers for the field of near-infrared spectroscopy. The electroencephalography also supported the promising role of frontal regions, such as the ACC, DLPFC and OFC in the biomarker exploration, especially for the sleep electroencephalogram to detect biomarkers in MDD. The positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in MDD demonstrated the promising biomarkers for the frontal and limbic regions, such as ACC, DLPFC and amygdala. However, additional findings in brainstem and midbrain were also found in PET and SPECT. The promising neuroimaging biomarkers of MDD seemed focused in the fronto-limbic regions.

The Glutamatergic Postrhinal Cortex-Ventrolateral Orbitofrontal Cortex Pathway Regulates Spatial Memory Retrieval / 神经科学通报·英文版

A deficit in spatial memory has been taken as an early predictor of Alzheimer's disease (AD) or mild cognitive impairment (MCI). The uncinate fasciculus (UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex (OFC) in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex (POR) and projecting to the ventrolateral orbitofrontal cortex (vlOFC) performs most of the functions of the UF in rodents. Although the literature suggests an association between spatial memory and the regions connected by the POR-vlOFC pathway, the function of the pathway in spatial memory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR-vlOFC pathway in mice. We determined that the POR-vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR-vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis: a visual rating study / Atrofia da massa cinzenta frontostriatal na esclerose lateral amiotrófica: um estudo de avaliação visual antes da publicação

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS. Objective: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS. Methods: 21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales. Results: Significantly higher atrophy ratings in the bilateral MOFC only in ALS patients versus controls was observed (p<.05). Patients with greater MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05). Conclusion: Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management.

RESUMO: A esclerose lateral amiotrófica (ELA) é caracterizada por alterações na substância cinzenta frontostriatal, semelhantes às da demência frontotemporal (DFT). No entanto, essas alterações geralmente são detectadas em nível de grupo, e as escalas simples de atrofia cortical por ressonância magnética visual (MRI) podem elucidar ainda mais as alterações frontostriatais na ELA. Objetivo: Investigar se as alterações frontostriatais são detectáveis usando escalas de classificação de atrofia MRI visuais simples aplicadas em um nível de paciente individual em ELA. Métodos: 21 pacientes com ELA e 17 controles foram recrutados e submetidos a uma ressonância magnética. Sub-regiões do córtex pré-frontal do córtex orbitofrontal medial (MOFC), córtex orbitofrontal lateral (LOFC) e córtex cingulado anterior (ACC), sub-regiões estriadas do núcleo caudado (NC) e nucleus accumbens (NAcc) foram classificadas usando escalas de atrofia de substância cinzenta visuais de Likert de 5 pontos. Resultados: Observações de atrofia significativamente maiores no MOFC bilateral em pacientes com ELA versus controles foram observadas apenas (p <0,05). Pacientes com maior atrofia do MOFC tiveram atrofia significativamente maior do CN (p <0,05) e LOFC (p <0,05). Conclusão: O uso de escalas de avaliação de atrofia visuais simples em um nível individual detecta de forma confiável déficits frontostriatais específicos para ELA, mostrando diferenças de atrofia MOFC com atrofia associada de CN e LOFC. Este é um método aplicável que pode ser usado para apoiar o diagnóstico e o gerenciamento clínico.

Spontaneous activity in medial orbitofrontal cortex correlates with trait anxiety in healthy male adults / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Medial orbitofrontal cortex (mOFC) abnormalities have been observed in various anxiety disorders. However, the relationship between mOFC activity and anxiety among the healthy population has not been fully examined. Here, we conducted a resting state functional magnetic resonance imaging (R-fMRI) study with 56 healthy male adults from the Nathan Kline Institute/Rockland Sample (NKI-RS) to examine the relationship between the fractional amplitude of low-frequency fluctuation (fALFF) signals and trait anxiety across the whole brain. A Louvain method for module detection based on graph theory was further employed in the automated functional subdivision to explore subregional correlates of trait anxiety. The results showed that trait anxiety was related to fALFF in the mOFC. Additionally, the resting-state functional connectivity (RSFC) between the right subregions of the mOFC and the precuneus was correlated with trait anxiety. These findings provided evidence about the involvement of the mOFC in anxiety processing among the healthy population.

Neural mechanism and evaluation of decision-making function in obsessive-compulsive disorder / 上海交通大学学报（医学版）

Obsessive-compulsive disorder (OCD) is a chronic,disabling,mental disorder,which has been linked to significant abnormalities in certain brain areas,including the orbital frontal cortex and the anterior cingulate cortex.Neuroimaging studies have also shown that brain areas related to the decision-making function include the orbital frontal cortex and the dorsal prefrontal lobes.Furthermore,the association between OCD and decision-making function has been consistently demonstrated from a neurobiological perspective.Clinically,impaired decision-making ability is commonly observed in OCD patients,and there is a correlation between OCD and abnormal decision function.Decision-making tasks are typically divided into two types,decision-making under risk and decision-making under ambiguity,with the former commonly evaluated using the Iowa Gambling Task (IGT) and the latter using the Game of Dice Task (GDT).In this article the neural mechanism and evaluation methods of decision making in OCD were reviewed.

Maturação Orbitofrontal, Marcadores Somáticos e Vulnerabilidade Precoce: para uma Hipótese Compreensiva de "Miopia Emocional" na Toxicodependência / Orbitofrontal Maturation, Somatic Markers and Early Vulnerability: A Comprehensive Hypothesis of "Emotional Myopia" in Drug Addiction

A hipótese de “miopia emocional” constitui uma reflexão teórica de compreensão da vulnerabilidade psicológica identificada em muitos toxicodependentes. Propõe-se uma cooperação, mas não incorporação, de níveis de conhecimento em torno dos determinantes do neurodesenvolvimento, de perspectivas psicanalíticas e de vinculação e de modelos psicobiológicos das toxicodependências. Salientam-se influências ambientais sobre as mudanças na morfologia cerebral, não apenas o trauma precoce ou a privação de cuidados, mas também as decorrentes de consumos abusivos como cernes de vulnerabilidade. Propõe-se que a hipótese Damasiana dos marcadores somáticos participe nessa formulação. A parca qualidade das interações precoces pode sustentar o desligamento afetivo progressivo, a hipomaturação do cérebro social, o incremento de um padrão alexitímico e a procura urgente de sensações, todos potenciais propiciadores da busca do prazer nas drogas.

The “emotional myopia” hypothesis is a theoretical reflection to increase the understanding of the psychological vulnerability showed by many drug addicts Instead of an incorporation, a cooperation is proposed of levels of knowledge on the determinants of the neurodevelopment, psychoanalytical and attachment perspectives and psychobiological models of drug addictions. Environmental inputs that change brain morphology are highlighted, not only early trauma or care deprivation but also others derived from the long-term use of drugs as the core of vulnerability. We propose that Damasio’s hypothesis of somatic markers forms part of this theoretical formulation. The low quality of early social interactions may support an increasing emotional disengagement, a poor maturation of the social brain, an increase of alexithymic patterns and novelty-seeking behaviours, all potential triggers for searching for pleasure in drugs.

Lesions of the orbitofrontal cortex do not affect the reinforcement omission effect in rats

The reinforcement omission effect (ROE), reflected by response rates that are higher after reinforcement omission than after reinforcement delivery, has been attributed to both motivational and attentional consequences of the surprising reinforcement omission. These processes depend on the operation of separate amygdala areas and their connections with other brain systems. The interaction between the amygdala and orbitofrontal cortex has been suggested to be important in the modulation of motivational processes. The present study sought to verify whether the mechanisms involved in the ROE depend on the integrity of the orbitofrontal cortex. Prior to acquisition training, rats received bilateral excitotoxic lesions of the orbitofrontal cortex or sham lesions. Following postoperative recovery, the rats were trained on a fixed-interval 12 s limited-hold 6 s signaled schedule of reinforcement. After the acquisition of stable performance, the training was changed from a 100% to 50% schedule of reinforcement. The results showed that rats in both groups exhibited the ROE, with no differences in performance between groups following nonreinforcement. These data do not support the hypothesis that the orbitofrontal cortex is included in the neural substrates related to ROE modulation. The results also showed no difference in response rates between groups in the periods that preceded and followed nonreinforcement. These findings confirm previous studies that showed that the ROE is not related to the facilitation of behavior induced by nonreinforcement...

Inteligencia para la alimentación: alimentación para la inteligencia / Intelligence for food: food for intelligence

Eating is a behavior oriented to get the energy necessary for the organism to survive and to contend with the demands of its environment. Food, besides of energy, provides structure and function, as amino acids are converted into structural or secretion proteins or enzymes. These proteins are synthesized following a strict genetic code. Variants in the genome happen frequently, but only those changes that result in a poor adaptive phenotype are well documented. There are other changes that may go unnoticed due to culture influence, and they may be seen as adaptive because they seem to favor individuals in the short-term. A child that overeats and becomes overweighed is culturally appreciated as a healthy child. However, systematic studies have shown that these feeding styles influenced by culture, in the long-term, result on an irreversible damage to the individual. Food selection also depends on the functioning of homeostatic and hedonistic systems. The homeostatic system involves the hypothalamus that includes nuclei that promote both appetite and satiety. The hedonic system is constituted by the ventral tegmental area and the nucleus accumbens. Stimulation of the ventral tegmental area induces the release of dopamine into the nucleus accumbens, making the individual to experience pleasure. This system also interacts with the hypothalamic systems that promote appetite. As it can be seen, food intake is regulated by diverse cerebral systems that are under the influence of one another. Failure in one of these systems may lead the subject to a compulsive, or defective, food intake. We have allowed media and mercantilist interests to govern our diet, instead of allowing our brain and its systems to do it. We should have psycoeducation as a priority in medicine to improve our capacity to select better quality food to eat, without compromising the pleasure of eating.

Comer es una conducta dirigida a conseguir la energía para llevar a cabo las funciones que mantienen al organismo y le permiten contender contra las demandas del medio. Debido a que nuestro organismo evolucionó dentro de un ambiente con escasez de alimentos, los genes que nos adaptaron al medio fueron los que promueven el almacenamiento y optimización de los nutrientes, así como aquellos que promueven la habilidad de generar estrategias de cacería y otras conductas orientadas a ese objetivo. Estos mecanismos fisiológicos y bioquímicos incluyen una amplia variedad de genes, desde aquellos que codifican para enzimas que almacenan el glucógeno hasta enzimas que sintetizan o degradan a los neurotransmisores. Diversos sistemas cerebrales regulan la ingestión del alimento: El homeostásico involucra al hipotálamo lateral como promotor de la ingestión de alimento por medio de neuronas orexinérgicas y MCHérgicas, al núcleo arcuato que sintetiza y libera neuropéptido Y y al péptido relacionado al gen agouti y como promotor de la saciedad a través de la POMC y del CART. Diferentes hormonas y proteínas hipotalámicas participan en la función del sistema hedónico compuesto por el área ventral tegmental y el núcleo accumbens, produciéndose un diálogo entre los sistemas homeostásico y hedónico. Otros sistemas cerebrales que participan son la amígdala y el lóbulo de la ínsula que promueven la selección de los alimentos con base en la experiencia. La corteza prefrontal participa en la preferencia por los alimentos y la toma de decisiones tales como qué, cuándo y dónde comer. Es importante reconocer que los sistemas neuroquímicos que regulan la ingestión del alimento también participan en funciones cognitivas y que la falla en estos sistemas afecta la forma en que el individuo elige su alimentación y, a su vez, el estado cognitivo del sujeto. Por lo tanto, la psicoeducación para regular los hábitos alimenticios debe ser una prioridad en el campo de la medicina.

Disruption of Orbitofronto-Striatal Functional Connectivity Underlies Maladaptive Persistent Behaviors in Alcohol-Dependent Patients

OBJECTIVE: Alcohol dependence is characterized by persistent alcohol-seeking despite negative consequences. Previous studies suggest that maladaptive persistent behaviors reflect alcohol-induced brain changes that cause alterations in the cortico-striatal-limbic circuit. METHODS: Twenty one alcohol dependent patients and 24 age-matched healthy controls performed a decision-making task during functional MRI. We defined the medial orbitofrontal cortex (mOFC) as a region-of-interest and performed seed-based functional connectivity analysis. RESULTS: Healthy controls were more flexible in adapting an alternative behavioral strategy, which correlated with stronger mOFC-dorsal striatum functional connectivity. In contrast, alcohol dependent patients persisted to the first established behavioral strategy. The mOFC-dorsal striatum functional connectivity was impaired in the alcohol-dependent patients, but increased in correlation with the duration of abstinence. CONCLUSION: Our findings support that the disruption of the mOFC-striatal circuitry contribute to the maldaptive persistent behaviors in alcohol dependent patients.

The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings / O envolvimento do cortex orbitofrontal em transtornos psiquiátricos: uma atualização dos achados de neuroimagens

OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC) in the pathophysiology of the most prevalent psychiatric disorders (PD). METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was done up to July 2011. DISCUSSION: Structural and functional OFC abnormalities have been reported in many PD, namely schizophrenia, mood disorders, anxiety disorders, personality disorders and drug addiction. Structural magnetic resonance imaging studies have reported reduced OFC volume in patients with schizophrenia, mood disorders, PTSD, panic disorder, cluster B personality disorders and drug addiction. Furthermore, functional magnetic resonance imaging studies using cognitive paradigms have shown impaired OFC activity in all PD listed above. CONCLUSION: Neuroimaging studies have observed an important OFC involvement in a number of PD. However, future studies are clearly needed to characterize the specific role of OFC on each PD as well as understanding its role in both normal and pathological behavior, mood regulation and cognitive functioning.

OBJETIVO: Relatar estudos de neuroimagens estruturais e funcionais explorando o papel potencial do córtex orbitofrontal (COF) na fisiopatologia dos transtornos psiquiátricos (TP) mais prevalentes. MÉTODO: Foi realizada uma revisão não sistemática da literatura no MEDLINE, usando como parâmetros os seguintes termos: "córtex orbitofrontal", "esquizofrenia", "transtorno bipolar", "depressão maior", "transtornos ansiosos", "transtornos de personalidade" e "dependência a drogas". A pesquisa eletrônica foi feita até julho de 2011. DISCUSSÃO: Foram relatadas anormalidades estruturais e funcionais do COF em muitos TP, particularmente esquizofrenia, transtornos afetivos, transtornos ansiosos, transtornos de personalidade e dependência a drogas. Estudos de aquisição de imagens estruturais por ressonância magnética relataram a redução do volume do COF em pacientes portadores de esquizofrenia, transtornos afetivos, TEPT, transtorno do pânico, transtornos de personalidade do grupo B e dependência a drogas. Além disso, estudos de aquisição de imagens funcionais por ressonância magnética empregando paradigmas cognitivos demonstraram alterações na atividade do COF em todos os TP anteriormente relacionados. CONCLUSÃO: Estudos de neuroimagens observaram um envolvimento importante do COF em vários TP. Entretanto, estudos futuros são claramente necessários para caracterizar o papel específico do COF em cada TP, assim como para a compreensão de seu papel tanto no comportamento normal como no patológico, na regulação do humor e no funcionamento cognitivo.

Transcriptional Mechanisms of Drug Addiction

Regulation of gene expression is considered a plausible mechanism of drug addiction given the stability of behavioral abnormalities that define an addicted state. Numerous transcription factors, proteins that bind to regulatory regions of specific genes and thereby control levels of their expression, have been implicated in the addiction process over the past decade or two. Here we review the growing evidence for the role played by several prominent transcription factors, including a Fos family protein (DeltaFosB), cAMP response element binding protein (CREB), and nuclear factor kappa B (NFkappaB), among several others, in drug addiction. As will be seen, each factor displays very different regulation by drugs of abuse within the brain's reward circuitry, and in turn mediates distinct aspects of the addiction phenotype. Current efforts are geared toward understanding the range of target genes through which these transcription factors produce their functional effects and the underlying molecular mechanisms involved. This work promises to reveal fundamentally new insight into the molecular basis of addiction, which will contribute to improved diagnostic tests and therapeutics for addictive disorders.

Empathy and Mood Awareness Reflected in the Resting-State Brain Metabolic Activity in the Patients with Schizophrenia and Normal Subjects

OBJECTIVES: Empathy has been conceptualized as the ability of emotional resonance and perspective-taking. Emotional awareness has been proposed as the basis of empathy. In this study we examined the relationship between empathy and mood awareness and their neural correlates in resting-state activity in normal controls and patients with schizophrenia. METHODS: Empathy and mood awareness scale scores were compared between 29 patients with schizophrenia and 21 normal controls by voxel-based t-tests and voxel-based correlation analyses of resting-state 18F-FDG PET images. RESULTS: Empathy and mood labeling scale scores were significantly decreased in schizophrenic patients. Mood monitoring was positively correlated with empathy score in normal controls, but not in schizophrenic patients. In normal controls, empathy was positively correlated with resting-state activities in the intraparietal sulcus and mood monitoring was positively correlated with the temporal pole, frontopolar cortex, inferior temporal gyrus, entorhinal cortex and the subgenual prefrontal cortex resting activities. The orbitofrontal cortex resting activity was positively correlated with mood monitoring-related subgenual prefrontal cortex activity in the normal controls. Patients with schizophrenia showed decreased orbitofrontal resting activity and loss of its correlations with mood monitoring-related regional activities. CONCLUSION: This study showed that alteration in the resting-state activity in schizophrenia may reflect dysfunctional empathy and distorted characteristic of emotional awareness. However, the resting-state activity may not reflect the relationship between emotional awareness and empathy.