Cigarette smoking is an addictive behavior. There are two learned emotional responses to smoking that may be particularly important for promoting addiction to smoking: the pleasure obtained from the airway sensory effects of smoking (airway sensory pleasure) and the urge to smoke that is elicited by environmental smoking cues (cue-induced urge). The ventromedial prefrontal cortex (VMPFC) has been implicated in a variety of learned emotional and motivational responses to drug-associated sensory cues. This project set out to address the role of the VMPFC and related areas in airway sensory pleasure and cue-induced urge, as well as the role of this region in promoting smoking behavior in real life, by examining the effects of focal lesions within the VMPFC and related areas in human cigarette smokers. It was found that lesions of the VMPFC itself were associated with a marked impairment of cue-induced urge in the laboratory, which was paralleled by a reported reduction in the difficulty of abstaining from smoking in real life. At the same time, VMPFC lesions led to a relative sparing of airway sensory pleasure in the laboratory, which was paralleled by no change in the enjoyment from smoking in real life. In addition, it was found that VMPFC lesions were not associated with changes in real-life measures of smoking dependence. It was found that lesions of the insula, a region that is functionally related to the VMPFC, were associated with an ability to quit smoking easily, immediately, without relapses and without a lasting urge to smoke. However, among patients with insula lesions who continued to smoke after lesion onset, there were no appreciable impairments of airway sensory pleasure or cue-induced urge. The results suggest that, while VMPFC lesions may disrupt cue-induced urges, they do not disrupt dependence upon smoking. This may be because VMPFC lesions spare more implicit motivational processes, such as "habits" and "incentive salience," that can drive smoking behavior in the absence of a conscious desire to smoke. The results also suggest that the insula functions in psychological processes that may contribute to the difficulty of quitting smoking.

There is a rich literature demonstrating that adults who stutter (AWS) demonstrate atypical functional brain activity during speech production. These differences can be characterized by increased activity in the right inferior frontal gyrus and premotor regions and decreased activity in the left inferior frontal gyrus, premotor area, and bilaterally in the superior temporal gyrus. The process of speech production requires motor movements first be planned and then executed. However, few studies have examined activity related to speech-motor planning independently from speech-motor execution. Additionally, due to methodological limitations, few investigations have examined functional brain activity in children who stutter (CWS). We hypothesized that AWS and CWS would demonstrate atypical brain activity related to both speech-motor planning and execution. Using Near Infrared Spectroscopy (fNIRS), we measured the change in oxygenated hemoglobin concentration (HbO) during speech-motor planning (repetition of nonwords with three repeated or different syllables) and speech-motor execution (covert/overt naming). Results indicated that both AWS and CWS demonstrated cortical activity that was atypical during speech-motor planning processes in the right inferior frontal gyrus and atypical speech-motor execution processes in the left inferior frontal gyrus. Deactivations in the left inferior frontal gyrus may reflect inefficient feedforward mechanisms for speech production. Inefficient feedforward mechanisms will likely result in more variable movements, for which larger feedback correction signals will be necessary. Overactivations in the right inferior frontal gyrus may reflect this increased correction. Additionally, AWS demonstrated atypical speech-motor planning activity in the right middle frontal gyrus, potentially related to the production of prosody. These results are presented within a theoretical framework of two competing theories of stuttering.

Words that deviate in their physical characteristics from their surrounding lead to enhanced recall memory, a pattern known as the Von Restorff effect. Furthermore, common (high frequency; HF) words are more likely to be recalled than uncommon (low frequency; LF) words when they occur in pure lists, while this pattern is reversed in mixed lists of both HF and LF words. This study investigated whether the Von Restorff effect and the reversal of word frequency effects in mixed lists, which may both be explained by enhanced perceived distinctiveness, are associated with common underlying brain processes. Event-related potentials (ERPs) were recorded while participants studied and subsequently recalled 70 word lists using rote memorization strategies. The three list types included (1) 14 regular-sized and one larger word, (2) 14 HF words and one LF word, or (3) 14 LF words and one HF word. The behavioral data showed a typical Von Restorff effect, a word frequency effect, as well as a reversal of the word frequency effect for LF words isolated in HF word lists ("LF isolates"). Larger words and LF isolates elicited a P300, an ERP component associated with subjective distinctiveness, whose amplitude was correlated with subsequent recall for both word types. This indicates that LF isolates were perceived as distinctive, and that this perceived distinctiveness aided subsequent recall in a similar way as for physically deviant words. Both larger words and LF isolates also elicited a left-lateralized slow wave which was larger for subsequently recalled than for not recalled words. This ERP component supposedly reflects item-to-item elaborative processes, indicating that such elaborative processes are enhanced when LF words occur in HF word list. HF words isolated in lists of LF words did not elicit comparable ERP subsequent memory effects. Rather, for these "HF isolates", the N400 was negatively correlated with subsequent recall, an ERP component that reflects semantic integration processes. We conclude that the reversal of the word frequency effect in mixed lists can be explained by a combination of enhanced subjective distinctiveness and enhanced inter-item elaborative processes for LF words that occur in lists of HF words.

MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search for other pathologies in depression that might yield clues for the development of better drug treatments. In this regard, a strong association has been found between oxidative stress and MDD. Our lab recently found increased DNA oxidation and elevated poly(ADP)ribose polymerase (PARP1) gene expression in the brain from donors that had MDD at the time of death. Besides DNA damage repair, PARP1 mediates several downstream inflammatory effects that may contribute to pathology in MDD. In fact, our lab has demonstrated that PARP-1 inhibition produces antidepressant-like effects in rodents, suggesting that PARP-1 inhibitors hold promise as a novel antidepressant drug. While our lab had previously demonstrated elevated PARP1 gene expression in the frontal cortex in MDD, whether PARP1 protein levels were also increased in depression had not been verified. My thesis research was performed to determine whether PARP1 protein expression was also elevated in the brain in MDD. I studied primarily the hippocampus because it is part of the limbic (mediating emotion) system of the brain and because previous research has shown numerous other pathologies in the hippocampus. My study was carried out simultaneously as others in our lab were measuring PARP1 protein levels in frontal cortex in MDD. This latter work was important since the lab’s previous work had observed elevated PARP1 gene expression in the frontal cortex, rather than in the hippocampus which was not previously studied. Hippocampal and frontal cortical brain sections were cut from frozen blocks of both MDD and psychiatrically normal control brain donors for these studies. PARP1 protein levels were estimated by assisted-imaging software. The findings herein demonstrate that levels of PARP1 immunoreactivity are significantly elevated in the frontal cortex of MDD donors as compared to control donors. However, there was no change in PARP1 immunoreactivity in the hippocampus in MDD.

<div> <div> <div> <p>Major depressive disorder (MDD) and risk for its development are characterized by reduced reactivity and flexibility to environmental demands. Frontal alpha asymmetry (FAA), heart rate variability (HRV), and salivary cortisol reactivity are each well-established indicators of regulation across neural, autonomic, and hypothalamic-pituitary-adrenal (HPA) physiological systems, respectively. Growing literature suggests that each of these processes is dysregulated in individuals with a history of MDD. However, patterns of dysregulation across these physiological systems and relative MDD risk are unknown. Moreover, these physiological regulatory patterns may extent beyond markers of MDD risk in adulthood to also capture the transmission of risk for MDD from parent to offspring. The following series of five studies investigated the pathophysiology of MDD and the permeability of risk across the lifespan. First, the pattern of dysregulation across physiological indices—representing neural, autonomic, and HPA functioning—in adults was examined with regard to depressive symptoms. Second, the associations amongst infant FAA, HRV, and cortisol reactivity and maternal depressive symptoms were assessed as potential early markers of depression risk. Third, mother-infant associations across physiological indices were investigated to assess direct intergenerational transmission of depression risk. Studies 4 and 5 further investigated pathophysiological functioning in mothers and infants within the context of comorbid anxiety and current depressive symptomatology versus lifetime MDD illness. Mothers and their 12-month-old infants (n = 35 dyads) completed resting- state and stressor tasks to assess regulatory patterns across neural, autonomic, and HPA systems, associations with MDD, and intergenerational transmission. In adults, results suggest that lifetime history of MDD is significantly associated with blunted cortisol reactivity; FAA and high- frequency HRV also demonstrated the same direction of associations. In infants, results demonstrated that maternal depressive symptoms, particularly current symptoms, relate to blunted physiological regulation in infants specifically for FAA and HRV indices. For mothers and infants, there was support for the direct intergenerational transmission of FAA and HRV indices. These intergenerational associations did not fully account for intergenerational risk of depression, as maternal physiological regulation and maternal depression were found to each significantly predict infant regulation as simultaneous predictors. Accounting for comorbid anxiety and examining current symptoms versus lifetime illness were essential to investigating associations amongst physiological functioning and depression. These patterns in conjunction with the literature suggest a developmental model to MDD pathophysiology that encompasses multiple theoretical frameworks. Future research is necessary to clarify regulatory patterns across physiological systems within individuals and across time with regard to MDD risk, onset, and course.</p></div></div></div>

<p>NR 20140805</p>

No description available.

Schizophrenia postmortem brain is characterized by γ aminobutyric acid downregulation and by decreased dendritic spine density in frontal cortex. Protracted L-methionine treatment exacerbates schizophrenia symptoms, and our earlier work (Tremolizzo et al. and Dong et al.) has shown that L-methionine decreases reelin and GAD67 transcription in mice which is prevented by co-administration of valproate. In this study, we observed a decrease in spine density following L-methionine treatment, which was prevented by co-administration of valproate. Together with our earlier findings conducted under the same experimental conditions, we suggest that downregulation of spine density in L-methionine-treated mice may be because of the decreased expression of reelin and that valproate may prevent spine downregulation by inhibiting the methylation induced decrease in reelin.

Objetivo: Evaluar la preferencia de dos diseños de etiquetado frontal en productos industrializados (octógono vs semáforo-GDA). Material y métodos: Estudio descriptivo transversal en usuarios de mercados de Lima Metropolitana (Chorrillos, Breña, La Victoria y La Molina). Se utilizó una encuesta previamente validada que constó de 4 preguntas basadas en láminas con cada etiquetado nutricional: ¿Cuál de los productos le parece más saludable?”, “¿Por qué escogió este?”, “¿Cuál de las dos etiquetas le parece más fácil de entender?” y “¿Cuál de los dos etiquetados le gusta más?”. Los datos se presentan en porcentajes y medianas (rango intercuartil) y las diferencias entre los grupos se evaluaron con la prueba exacta de Fisher (datos categóricos). Los datos se analizaron en el programa Stata v15. Resultados: Se encuestaron 93 usuarios, el Semáforo-GDA fue elegido como el etiquetado más saludable (74.3%) y el que más les gustó (69.9%); sin embargo, el octógono fue el que les pareció más fácil de entender (58.4%). La mayoría de los usuarios consideró el semáforo como más saludable debido a que “tiene más verde en la etiqueta”, lo que podría confundir la finalidad de la advertencia nutricional, minimizando el impacto del símbolo rojo y/o amarillo por tenerlos en menor cantidad de éstos. Conclusiones: Los participantes mencionaron que el octógono era más sencillo y fácil de leer; los símbolos verdes del semáforo-GDA podrían influir en que el producto se perciba como más saludable. / Objective: To evaluate the preference of two designs of frontal labeling in industrialized products (octagon vs traffic light-GDA). Material and methods: Cross-sectional descriptive study in market users of Metropolitan Lima (Chorrillos, Breña, La Victoria and La Molina). We used a previously validated survey that consisted of 4 questions: “Which of the products do you find most healthy?", "Why did you choose this one?", "Which of the two labels do you find easiest to understand?", and "Which of the two labeled do you like the most?". The data are presented in percentages and median (interquartile range) and the differences between the groups were evaluated with Fisher's exact test (categorical data). The data was analyzed in the Stata v15 program. Results: 93 users were surveyed, the traffic light-GDA was chosen as the healthiest label (74.3%) and the one they liked the most (69.9%); however, the octagon was the one that seemed easier to understand (58.4%). The majority of users considered the traffic light-GDA as healthier because it "has more green on the label". Conclusions: Participants mentioned that the octagon was simpler and easier to read; the green symbols of the traffic light-GDA could influence that the product is perceived as healthier. Which could confuse the purpose of the nutritional warning, minimizing the impact of the red and/or yellow symbol by having them in less quantity than these. / Trabajo de investigación

En neuro-oncologie pédiatrique, les études neurocognitives et neuropsychologiques sur les tumeurs hémisphériques (sus-tentorielles) sont plus rares que celles sur les tumeurs de la fosse postérieure (sous-tentorielles), bénignes (notamment l’astrocytome pilocytique du cervelet) ou malignes (en particulier, le médulloblastome qui est la tumeur maligne la plus fréquente chez l’enfant). A l’heure actuelle il n’existe pas, à notre connaissance, de séries publiées de cas d’enfants traités pour tumeur frontale, bénigne ou maligne et même les descriptions isolées d’un seul cas restent rares (Daigneault, S & al, 1997 ; Anderson, S.W, 2000). Il existe des séries de cas de tumeur frontale chez l’adulte (Roca & al, 2010 ; Yong-Gao & al, 2012). Il existe par contre une littérature importante porte sur le devenir et les séquelles des enfants traités pour une tumeur de la fosse postérieure. En effet, les progrès thérapeutiques ont amélioré les taux de survie, et plusieurs équipes ont examinés l’impact de différents facteurs (essentiellement mais pas exclusivement médicaux : topographie lésionnelle, âge d’apparition de la tumeur, nature des traitements et complications, etc., mais aussi niveau d’éducation des parents, etc.) sur les séquelles motrices et cognitives, le devenir et la qualité de vie de ces enfants et adolescents. Entre septembre 2010 et septembre 2011, 21 patients âgés entre 8 ans 3 mois et 27 ans 10 mois au moment de l’évaluation neuropsychologique ont été inclus dans cette étude. L’évaluation neuropsychologique, réalisée en deux temps, incluait des tests (tests papier-crayon et épreuves écologiques) évaluant l’efficience intellectuelle, des fonctions exécutives, d’attention, et de théorie de l’esprit. 44 patients contrôles ont été appariés en âge, sexe et NSC (niveau socio-économique) au groupe de patients. Au niveau statistique d’importantes différences sont relevées, notamment, dans les épreuves de reconnaissance d’expressions faciales émotionnelles. Il s’agit de la 1ère étude qui évalue les fonctions cognitives et affectives dans un groupe de patients ayant été traités dans l’enfance pour une tumeur frontale bénigne ou maligne. / Frontal lesions in children and adolescents have been mainly explored in traumatic brain injury (TBI). Other frontal lobe pathologies such as frontal lobe epilepsy (FLE), frontal focal lobe lesion, such as brain tumours or frontal focal lobe pathologies, can explain sequelae after frontal lobe pathologies. In the literature only two cases studies exist on benign frontal lobe tumour in children. To our knowledge there is no study group of frontal lobe tumours in children. Between September 2010 and September 2011, we observed 21 patients treated for benign/malign tumours. We examined 22 young patients aged between 8.3 years and 27.10 years old, all treated for benign or malign frontal tumour in Gustave Roussy’s Institute (in case of malign tumour) or Necker Enfants-Malades (in case of malign tumour). Treatment of this patients depended on benign or malign tumour. A total of 44 controls subjects were enrolled in study. All children and adolescents had neuropsychological tests, such as executive function tests (planning, mental flexibility, attention, working memory tasks) and measure or theory of mind tests such as face recognition test (TOM). All children were seen twice. Main differences are observed in facial recognition test between patients with malign and benign tumours and control subjects. IQ in not affected when tumours are benign, and most children obtain normal performances in executive tests. This is a first study with comprehensive neuropsychological assessment of children and adolescents with frontal lobe tumours. Findings have to be compared with classical studies of frontal lobe lesions in adults. Results suggest that many children treated for frontal lobe tumours do not present the classical dysexecutive syndrome and major behavioural changes as described in adults. However most of them present deficits in facial recognition of emotions and gesture imitations deficits.