WorldWideScience

Sample records for corteza prefrontal medial

  1. Aprendiendo de las consecuencias de los actos: estudio electrofisiológico del hipocampo, corteza prefrontal y núcleo accumbens

    OpenAIRE

    Jurado Parras, María Teresa

    2012-01-01

    Programa de Doctorado en Neurociencias La presente Tesis Doctoral se ha centrado en el estudio del papel del hipocampo, la corteza prefrontal medial y el núcleo accumbens en la adquisición del condicionamiento instrumental, del aprendizaje por observación y de la ejecución de tareas instrumentales. Además, se ha estudiado la participación de las sinapsis CA3 ¿ CA1, CA1 ¿ corteza prefrontal medial, corteza prefrontal medial ¿ núcleo accumbens y núcleo accumbens ¿ corteza prefrontal medial e...

  2. Estudio de la asimetría interhemisférica en la corteza prefrontal dorsolateral de sujetos humanos

    Directory of Open Access Journals (Sweden)

    Hernán J. Pimienta J.

    2005-03-01

    Full Text Available Se presentan los resultados de un trabajo de investigación encaminado a establecer las diferencias entre los hemisferios cerebrales de la corteza prefrontal dorsolateral: áreas 46 laeral y 7 medial, de sujetos humanos.

  3. Ritmos circadianos y neurotransmisores : estudios en la corteza prefrontal de la rata

    OpenAIRE

    Márquez de Prado García, Blanca

    2004-01-01

    El objetivo de esta tesis doctoral fue el estudio los posibles ritmos circadianos de los neurotransmisores glutamato, GABA, dopamina y acetilcolina en la corteza prefrontal. Una vez descritos los ritmos circadianos de estos neurotransmisores en corteza prefrontal se estudió su regulación por cambios en el fotoperíodo y la melatonina. Se estudiaron también los efectos del envejecimiento sobre los ritmos circadianos neurotransmisores en corteza prefrontal, estriado y núcleo accumbens. Se realiz...

  4. Funciones de la corteza prefrontal ventromedial en la toma de decisiones emocionales

    Directory of Open Access Journals (Sweden)

    David Contreras

    2008-01-01

    Full Text Available La corteza prefrontal ventromedial (VMPFC ha sido implicada en la toma de decisiones emocionales debido a su posible participación en el aprendizaje de inversión afectivo, la propensión al riesgo y la impulsividad. Su especial entramado de conexiones con otras áreas de la corteza y con estructuras subcorticales como la amígdala justifican que pueda tener un papel de interfase entre cognición y emoción, y desempeñar una función fundamental en la regulación y el control del comportamiento. En este trabajo revisamos estudios realizados con la tarea de apuestas de Iowa, tareas de aprendizaje de inversión afectivo, tareas de apuestas con diferente varianza para medir la propensión al riesgo y tareas que introducen demora temporal de la recompensa para evaluar la impulsividad. Los datos obtenidos en esos trabajos con pacientes lesionados en la VMPFC o en otras áreas prefrontales y controles no lesionados, y datos conductuales y de actividad cerebral pueden interpretarse mejor si asumimos que la VMPFC está encargada de representar la expectativa de refuerzo. La representación de un reforzador esperado incluye la demora del reforzador, y la varianza de su magnitud.

  5. Implicación de la corteza prefrontal de la rata en la ejecución de una tarea de alternancia

    OpenAIRE

    Sañudo Peña, María Clara

    2011-01-01

    El planteamiento del presente trabajo consistió en la utilización de una tarea conductual para cuya correcta ejecución fuese imprescindible la integridad funcional de la corteza prefrontal de la rata, con el fin de estudiar la implicación de los distintos sistemas de neurotransmisores en la funcionalidad de dicho área cortical. Se plantearon los siguientes objetivos: En primer lugar, analizar el efecto que lesiones discretas o la inactivación reversible de diferentes áreas funcionales de la c...

  6. Anatomical segmentation of the human medial prefrontal cortex

    NARCIS (Netherlands)

    Corcoles-Parada, M.; Müller, N.C.J.; Ubero, M.; Serrano-Del-Pueblo, V.M.; Mansilla, F.; Marcos-Rabal, P.; Artacho-Perula, E.; Dresler, M.; Insausti, R.; Fernandez, G.; Munoz-Lopez, M.

    2017-01-01

    The medial prefrontal areas 32, 24, 14, and 25 (mPFC) form part of the limbic memory system, but little is known about their functional specialization in humans. To add anatomical precision to structural and functional magnetic resonance imaging (MRI) data, we aimed to identify these mPFC subareas

  7. Corteza prefrontal, amígdala y estrés: estudio de la noradrenalina, corticosterona y memoria aversiva en la rata

    OpenAIRE

    Ronzoni Blázquez, Giacomo

    2016-01-01

    La interacción funcional entre la corteza prefrontal (CPF) y la amígdala así como la activación del eje hipotálamo-hipófisis-adrenal (HHA) y la liberación de catecolaminas en áreas límbicas del cerebro, juegan un papel clave tanto en la regulación de la respuesta fisiológica a estrés como en respuestas mal-adaptativas a estrés. El procesamiento de la información emocional a largo plazo, es otro de los mecanismos que contribuyen a la capacidad de los individuos para adaptarse a situaciones de ...

  8. Medial prefrontal cortex role in recognition memory in rodents.

    Science.gov (United States)

    Morici, Juan Facundo; Bekinschtein, Pedro; Weisstaub, Noelia V

    2015-10-01

    The study of the neurobiology of recognition memory, defined by the integration of the different components of experiences that support recollection of past experiences have been a challenge for memory researches for many years. In the last twenty years, with the development of the spontaneous novel object recognition task and all its variants this has started to change. The features of recognition memory include a particular object or person ("what"), the context in which the experience took place, which can be the arena itself or the location within a particular arena ("where") and the particular time at which the event occurred ("when"). This definition instead of the historical anthropocentric one allows the study of this type of episodic memory in animal models. Some forms of recognition memory that require integration of different features recruit the medial prefrontal cortex. Focusing on findings from spontaneous recognition memory tasks performed by rodents, this review concentrates on the description of previous works that have examined the role that the medial prefrontal cortex has on the different steps of recognition memory. We conclude that this structure, independently of the task used, is required at different memory stages when the task cannot be solved by a single item strategy. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Transient medial prefrontal perturbation reduces false memory formation.

    Science.gov (United States)

    Berkers, Ruud M W J; van der Linden, Marieke; de Almeida, Rafael F; Müller, Nils C J; Bovy, Leonore; Dresler, Martin; Morris, Richard G M; Fernández, Guillén

    2017-03-01

    Knowledge extracted across previous experiences, or schemas, benefit encoding and retention of congruent information. However, they can also reduce specificity and augment memory for semantically related, but false information. A demonstration of the latter is given by the Deese-Roediger-McDermott (DRM) paradigm, where the studying of words that fit a common semantic schema are found to induce false memories for words that are congruent with the given schema, but were not studied. The medial prefrontal cortex (mPFC) has been ascribed the function of leveraging prior knowledge to influence encoding and retrieval, based on imaging and patient studies. Here, we used transcranial magnetic stimulation (TMS) to transiently perturb ongoing mPFC processing immediately before participants performed the DRM-task. We observed the predicted reduction in false recall of critical lures after mPFC perturbation, compared to two control groups, whereas veridical recall and recognition memory performance remained similar across groups. These data provide initial causal evidence for a role of the mPFC in biasing the assimilation of new memories and their consolidation as a function of prior knowledge. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Medial prefrontal cortex subserves diverse forms of self-reflection.

    Science.gov (United States)

    Jenkins, Adrianna C; Mitchell, Jason P

    2011-01-01

    The ability to think about oneself--to self--reflect--is one of the defining features of the human mind. Recent research has suggested that this ability may be subserved by a particular brain region: the medial prefrontal cortex (MPFC). However, although humans can contemplate a variety of different aspects of themselves, including their stable personality traits, current feelings, and physical attributes, no research has directly examined the extent to which these different forms of self-reflection are subserved by common mechanisms. To address this question, participants were scanned using functional magnetic resonance imaging (fMRI) while making judgments about their own personality traits, current mental states, and physical attributes as well as those of another person. Whereas some brain regions responded preferentially during only one form of self-reflection, a robust region of MPFC was engaged preferentially during self-reflection across all three types of judgment. These results suggest that--although dissociable--diverse forms of self-referential thought draw on a shared cognitive process subserved by MPFC.

  11. Anterior medial prefrontal cortex implements social priming of mimicry.

    Science.gov (United States)

    Wang, Yin; Hamilton, Antonia F de C

    2015-04-01

    The neural and cognitive mechanisms by which primed constructs can impact on social behavior are poorly understood. In the present study, we used functional magnetic resonance imaging (fMRI) to explore how scrambled sentence priming can impact on mimicry behavior. Sentences involving pro/antisocial events from a first/third-person point of view were presented in short blocks, followed by a reaction-time assessment of mimicry. Behavioral results showed that both prosociality and viewpoint impact on mimicry, and fMRI analysis showed this effect is implemented by anterior medial prefrontal cortex (amPFC). We suggest that social primes may subtly modulate processing in amPFC in a manner linked to the later behavior, and that this same region also implements the top-down control of mimicry responses. This priming may be linked to processing of self-schemas in amPFC. Our findings demonstrate how social priming can be studied with fMRI, and have important implications for our understanding of the underlying mechanisms of prime-to-behavior effects as well as for current theories in social psychology. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. Differential roles for medial prefrontal and medial temporal cortices in schema-dependent encoding: From congruent to incongruent

    OpenAIRE

    Kesteren, M.T.R. van; Beul, S.F.; Takashima, A.; Henson, R.N.; Ruiter, D.J.

    2013-01-01

    Information that is congruent with prior knowledge is generally remembered better than incongruent information. This effect of congruency on memory has been attributed to a facilitatory influence of activated schemas on memory encoding and consolidation processes, and hypothesised to reflect a shift between processing in medial temporal lobes (MTL) towards processing in medial prefrontal cortex (mPFC). To investigate this shift, we used functional magnetic resonance imaging (fMRI) to compare ...

  13. Considering healthiness promotes healthier choices but modulates medial prefrontal cortex differently in children compared with adults

    NARCIS (Netherlands)

    Meer, van Floor; Laan, van der Laura N.; Viergever, Max A.; Adan, Roger A.H.; Smeets, Paul A.M.

    2017-01-01

    Childhood obesity is a rising problem worldwide mainly caused by overconsumption, which is driven by food choices. In adults, food choices are based on a value signal encoded in the medial prefrontal cortex (mPFC). This signal is modulated by the dorsolateral prefrontal cortex (dlPFC), which is

  14. Fear Expression Suppresses Medial Prefrontal Cortical Firing in Rats.

    Directory of Open Access Journals (Sweden)

    Thomas F Giustino

    Full Text Available The medial prefrontal cortex (mPFC plays a crucial role in emotional learning and memory in rodents and humans. While many studies suggest a differential role for the prelimbic (PL and infralimbic (IL subdivisions of mPFC, few have considered the relationship between neural activity in these two brain regions recorded simultaneously in behaving animals. Importantly, how concurrent PL and IL activity relate to conditioned freezing behavior is largely unknown. Here we used single-unit recordings targeting PL and IL in awake, behaving rats during the acquisition and expression of conditioned fear. On Day 1, rats received either signaled or unsignaled footshocks in the recording chamber; an auditory conditioned stimulus (CS preceded signaled footshocks. Twenty-four hours later, animals were returned to the recording chamber (modified to create a novel context where they received 5 CS-alone trials. After fear conditioning, both signaled and unsignaled rats exhibited high levels of post-shock freezing that was associated with an enduring suppression of mPFC spontaneous firing, particularly in the IL of signaled rats. Twenty-four hours later, CS presentation produced differential conditioned freezing in signaled and unsignaled rats: freezing increased in rats that had received signaled shocks, but decreased in animals in the unsignaled condition (i.e., external inhibition. This group difference in CS-evoked freezing was mirrored in the spontaneous firing rate of neurons in both PL and IL. Interestingly, differences in PL and IL firing rate highly correlated with freezing levels. In other words, in the signaled group IL spontaneous rates were suppressed relative to PL, perhaps limiting IL-mediated suppression of fear and allowing PL activity to dominate performance, resulting in high levels of freezing. This was not observed in the unsignaled group, which exhibited low freezing. These data reveal that the activity of mPFC neurons is modulated by both

  15. Medial prefrontal cortex stimulation modulates the processing of conditioned fear

    Directory of Open Access Journals (Sweden)

    Anne eGuhn

    2014-02-01

    Full Text Available The extinction of conditioned fear is dependent on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC. In rats, high-frequency electrical mPFC stimulation was shown to improve extinction by a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects.Healthy volunteers received one-session of either active or sham repetitive transcranial magnetic stimulation (rTMS covering the mPFC while undergoing a two-day fear conditioning and extinction paradigm. rTMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS- was associated with an aversive scream (UCS. Immediate extinction learning (day 1 and extinction recall (day 2 were conducted without UCS delivery. Conditioned responses were assessed in a multimodal approach using fear-potentiated startle (FPS, skin conductance responses (SCR, functional near-infrared spectroscopy (fNIRS and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS which can be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy.

  16. Segregation of the human medial prefrontal cortex in social cognition

    Directory of Open Access Journals (Sweden)

    Danilo eBzdok

    2013-05-01

    Full Text Available While the human medial prefrontal cortex (mPFC is widely believed to be a key node of neural networks relevant for socio-emotional processing, its functional subspecialization is still poorly understood. We thus revisited the often assumed differentiation of the mPFC in social cognition along its ventral-dorsal axis. Our neuroinformatic analysis was based on a neuroimaging meta-analysis of perspective-taking that yielded two separate clusters in the ventral and dorsal mPFC, respectively. We determined each seed region’s brain-wide interaction pattern by two complementary measures of functional connectivity: co-activation across a wide range of neuroimaging studies archived in the BrainMap database and correlated signal fluctuations during unconstrained (resting cognition. Furthermore, we characterized the functions associated with these two regions using the BrainMap database. Across methods, the ventral mPFC was more strongly connected with the nucleus accumbens, hippocampus, posterior cingulate cortex, and retrosplenial cortex, while the dorsal mPFC was more strongly connected with the inferior frontal gyrus, temporo-parietal junction, and middle temporal gyrus. Further, the ventral mPFC was selectively associated with action execution, olfaction, and reward related tasks, while the dorsal mPFC was selectively associated with perspective-taking and episodic memory retrieval. The ventral mPFC is therefore predominantly involved in sensory-driven, approach/avoidance-modulating, and evaluation-related processing, whereas the dorsal mPFC is predominantly involved in internally driven, memory-informed, and metacognition-related processing in social cognition.

  17. Neuropsychiatric effects of neurodegeneration of the medial vs. lateral ventral prefrontal cortex in humans

    OpenAIRE

    Huey, Edward D.; Lee, Seonjoo; Brickman, Adam M.; Manoochehri, Masood; Griffith, Erica; Devanand, D.P.; Stern, Yaakov; Grafman, Jordan

    2015-01-01

    Animal evidence suggests that a brain network involving the medial and rostral ventral prefrontal cortex (PFC) is central for threat response and arousal and a network involving the lateral and caudal PFC plays an important role in reward learning and behavioral control. In this study, we contrasted the neuropsychiatric effects of degeneration of the medial versus lateral PFC in 43 patients with Frontotemporal dementia and 11 patients with Corticobasal Syndrome using MRI, the Neuropsychiatric...

  18. Electrophysiological evidence during episodic prospection implicates medial prefrontal and bilateral middle temporal gyrus.

    Science.gov (United States)

    Hsu, Chia-Fen; Sonuga-Barke, Edmund J S

    2016-08-01

    fMRI studies have implicated the medial prefrontal cortex and medial temporal lobe, components of the default mode network (DMN), in episodic prospection. This study compared quantitative EEG localized to these DMN regions during prospection and during resting and while waiting for rewards. EEG was recorded in twenty-two adults while they were asked to (i) envision future monetary episodes; (ii) wait for rewards and (iii) rest. Activation sources were localized to core DMN regions. EEG power and phase coherence were compared across conditions. Prospection, compared to resting and waiting, was associated with reduced power in the medial prefrontal gyrus and increased power in the bilateral medial temporal gyrus across frequency bands as well as greater phase synchrony between these regions in the delta band. The current quantitative EEG analysis confirms prior fMRI research suggesting that medial prefrontal and medial temporal gyrus interactions are central to the capacity for episodic prospection. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. tDCS of medial prefrontal cortex does not enhance interpersonal trust

    NARCIS (Netherlands)

    Colzato, L.S.; Sellaro, R.; van den Wildenberg, W.P.M.; Hommel, B.

    2015-01-01

    Interpersonal trust is an essential ingredient of many social relationships. Previous research has suggested that the medial Prefrontal Cortex (mPFC) may be a critical component in mediating the degree to which people trust others. Here we assessed the role of the mPFC in modulating interpersonal

  20. Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment

    NARCIS (Netherlands)

    van Harmelen, A.L.; van Tol, M.J.; Dalgleish, T.; van der Wee, N.J.A.; Veltman, D.J.; Aleman, A.; Spinhoven, P.; Penninx, B.W.J.H.; Elzinga, B.M.

    2014-01-01

    Childhood emotional maltreatment (CEM) has adverse effects on medial prefrontal cortex (mPFC) morphology, a structure that is crucial for cognitive functioning and (emotional) memory and which modulates the limbic system. In addition, CEM has been linked to amygdala hyperactivity during emotional

  1. Disruption of the Perineuronal Net in the Hippocampus or Medial Prefrontal Cortex Impairs Fear Conditioning

    Science.gov (United States)

    Hylin, Michael J.; Orsi, Sara A.; Moore, Anthony N.; Dash, Pramod K.

    2013-01-01

    The perineuronal net (PNN) surrounds neurons in the central nervous system and is thought to regulate developmental plasticity. A few studies have shown an involvement of the PNN in hippocampal plasticity and memory storage in adult animals. In addition to the hippocampus, plasticity in the medial prefrontal cortex (mPFC) has been demonstrated to…

  2. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

    Science.gov (United States)

    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  3. Gender moderates the association between dorsal medial prefrontal cortex volume and depressive symptoms in a subclinical sample.

    Science.gov (United States)

    Carlson, Joshua M; Depetro, Emily; Maxwell, Joshua; Harmon-Jones, Eddie; Hajcak, Greg

    2015-08-30

    Major depressive disorder is associated with lower medial prefrontal cortex volumes. The role that gender might play in moderating this relationship and what particular medial prefrontal cortex subregion(s) might be implicated is unclear. Magnetic resonance imaging was used to assess dorsal, ventral, and anterior cingulate regions of the medial prefrontal cortex in a normative sample of male and female adults. The Depression, Anxiety, and Stress Scale (DASS) was used to measure these three variables. Voxel-based morphometry was used to test for correlations between medial prefrontal gray matter volume and depressive traits. The dorsal medial frontal cortex was correlated with greater levels of depression, but not anxiety and stress. Gender moderates this effect: in males greater levels of depression were associated with lower dorsal medial prefrontal volumes, but in females no relationship was observed. The results indicate that even within a non-clinical sample, male participants with higher levels of depressive traits tend to have lower levels of gray matter volume in the dorsal medial prefrontal cortex. Our finding is consistent with low dorsal medial prefrontal volume contributing to the development of depression in males. Future longitudinal work is needed to substantiate this possibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression

    Directory of Open Access Journals (Sweden)

    Anders H. Andersen

    2015-01-01

    Full Text Available Parkinson’s disease (PD is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD patients. Participants included 18 ndPD patients (11 men, 7 women and 10 dPD patients (7 men, 3 women. Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN. DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

  5. The Role of Medial Prefrontal Cortex in Memory and Decision Making

    OpenAIRE

    Euston, David R.; Gruber, Aaron J.; McNaughton, Bruce L.

    2012-01-01

    Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time-scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, ...

  6. Reciprocal neural response within lateral and ventral medial prefrontal cortex during hot and cold reasoning.

    Science.gov (United States)

    Goel, Vinod; Dolan, Raymond J

    2003-12-01

    Logic is widely considered the basis of rationality. Logical choices, however, are often influenced by emotional responses, sometimes to our detriment, sometimes to our advantage. To understand the neural basis of emotionally neutral ("cold") and emotionally salient ("hot") reasoning we studied 19 volunteers using event-related fMRI, as they made logical judgments about arguments that varied in emotional saliency. Despite identical logical form and content categories across "hot" and "cold" reasoning conditions, lateral and ventral medial prefrontal cortex showed reciprocal response patterns as a function of emotional saliency of content. "Cold" reasoning trials resulted in enhanced activity in lateral/dorsal lateral prefrontal cortex (L/DLPFC) and suppression of activity in ventral medial prefrontal cortex (VMPFC). By contrast, "hot" reasoning trials resulted in enhanced activation in VMPFC and suppression of activation in L/DLPFC. This reciprocal engagement of L/DLPFC and VMPFC provides evidence for a dynamic neural system for reasoning, the configuration of which is strongly influenced by emotional saliency.

  7. Emotion regulation in spider phobia: role of the medial prefrontal cortex

    Science.gov (United States)

    Schäfer, Axel; Walter, Bertram; Stark, Rudolf; Vaitl, Dieter; Schienle, Anne

    2009-01-01

    Phobic responses are strong emotional reactions towards phobic objects, which can be described as a deficit in the automatic regulation of emotions. Difficulties in the voluntary cognitive control of these emotions suggest a further phobia-specific deficit in effortful emotion regulation mechanisms. The actual study is based on this emotion regulation conceptualization of specific phobias. The aim is to investigate the neural correlates of these two emotion regulation deficits in spider phobics. Sixteen spider phobic females participated in a functional magnetic resonance imaging (fMRI) study in which they were asked to voluntarily up- and down-regulate their emotions elicited by spider and generally aversive pictures with a reappraisal strategy. In line with the hypothesis concerning an automatic emotion regulation deficit, increased activity in the insula and reduced activity in the ventromedial prefrontal cortex was observed. Furthermore, phobia-specific effortful regulation within phobics was associated with altered activity in medial prefrontal cortex areas. Altogether, these results suggest that spider phobic subjects are indeed characterized by a deficit in the automatic as well as the effortful regulation of emotions elicited by phobic compared with aversive stimuli. These two forms of phobic emotion regulation deficits are associated with altered activity in different medial prefrontal cortex subregions. PMID:19398537

  8. Medial Prefrontal Cortex Activation Is Commonly Invoked by Reputation of Self and Romantic Partners

    Science.gov (United States)

    Kawamichi, Hiroaki; Sasaki, Akihiro T.; Matsunaga, Masahiro; Yoshihara, Kazufumi; Takahashi, Haruka K.; Tanabe, Hiroki C.; Sadato, Norihiro

    2013-01-01

    The reputation of others influences partner selection in human cooperative behaviors through verbal reputation representation. Although the way in which humans represent the verbal reputations of others is a pivotal issue for social neuroscience, the neural correlates underlying the representation of verbal reputations of others are unclear. Humans primarily depend on self-evaluation when assessing reputation of self. Likewise, humans might primarily depend on self-evaluation of others when representing their reputation. As interaction promotes the formation of more nuanced, individualized impressions of an interaction partner, humans tend to form self-evaluations of persons with whom they are intimate in their daily life. Thus, we hypothesized that the representation of reputation of others is modulated by intimacy due to one’s own evaluation formation of that person. To test this hypothesis, we conducted a functional magnetic resonance imaging experiment with 11 pairs of romantic partners while they viewed an evaluation of a target person (self, partner [intimate other], or stranger [non-intimate other]), made by other evaluators. When compared with strangers, viewing evaluations of self and partner activated overlapping regions in the medial prefrontal cortex. Verbal reputation of self-specific activation was found in the precuneus, which represents self-related processing. The data suggest that midline structures represent reputation of self. In addition, intimacy-modulated activation in the medial prefrontal cortex suggests that the verbal reputation of intimate others is represented similarly to reputation of self. These results suggest that the reputation representation in the medial prefrontal cortex is engaged by verbal reputation of self and intimate others stemming from both own and other evaluators’ judgments. PMID:24086409

  9. Bupropion Administration Increases Resting-State Functional Connectivity in Dorso-Medial Prefrontal Cortex.

    Science.gov (United States)

    Rzepa, Ewelina; Dean, Zola; McCabe, Ciara

    2017-06-01

    Patients on the selective serotonergic reuptake inhibitors like citalopram report emotional blunting. We showed previously that citalopram reduces resting-state functional connectivity in healthy volunteers in a number of brain regions, including the dorso-medial prefrontal cortex, which may be related to its clinical effects. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and is not reported to cause emotional blunting. However, how bupropion affects resting-state functional connectivity in healthy controls remains unknown. Using a within-subjects, repeated-measures, double-blind, crossover design, we examined 17 healthy volunteers (9 female, 8 male). Volunteers received 7 days of bupropion (150 mg/d) and 7 days of placebo treatment and underwent resting-state functional Magnetic Resonance Imaging. We selected seed regions in the salience network (amygdala and pregenual anterior cingulate cortex) and the central executive network (dorsal medial prefrontal cortex). Mood and anhedonia measures were also recorded and examined in relation to resting-state functional connectivity. Relative to placebo, bupropion increased resting-state functional connectivity in healthy volunteers between the dorsal medial prefrontal cortex seed region and the posterior cingulate cortex and the precuneus cortex, key parts of the default mode network. These results are opposite to that which we found with 7 days treatment of citalopram in healthy volunteers. These results reflect a different mechanism of action of bupropion compared with selective serotonergic reuptake inhibitors. These results help explain the apparent lack of emotional blunting caused by bupropion in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  10. Estudio comparativo del rendimiento de las funciones ejecutivas en la corteza prefrontal dorsolateral, orbitofrontal y frontomedial en adolescentes policonsumidores de sustancias psicoactivas, vinculados al sistema de responsabilidad penal en paralelo con adolescentes que no se encuentran bajo esta misma condición

    OpenAIRE

    Diego Alejandro Calle Sandoval; María Alexandra Cuéllar Arias; Paula Andrea Chede García; María Alejandra Quintero Bejarano; Diana Lucía Villamizar Herrera

    2017-01-01

    La presente investigación se realizó bajo una metodología cuantitativa comparativa y de corte transversal, la cual tuvo como objetivo la realización de un estudio del rendimiento de las funciones ejecutivas en la corteza prefrontal dorsolateral, orbitofrontal y frontomedial en adolescentes, entre los 14 y 18 años de edad, policonsumidores de sustancias psicoactivas (SPA) y vinculados al sistema de responsabilidad penal, en paralelo con adolescentes pertenecientes a una institución educativa q...

  11. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

    Science.gov (United States)

    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects. Copyright © 2012 S. Karger AG, Basel.

  12. Functional heterogeneity of conflict, error, task-switching, and unexpectedness effects within medial prefrontal cortex.

    Science.gov (United States)

    Nee, Derek Evan; Kastner, Sabine; Brown, Joshua W

    2011-01-01

    The last decade has seen considerable discussion regarding a theoretical account of medial prefrontal cortex (mPFC) function with particular focus on the anterior cingulate cortex. The proposed theories have included conflict detection, error likelihood prediction, volatility monitoring, and several distinct theories of error detection. Arguments for and against particular theories often treat mPFC as functionally homogeneous, or at least nearly so, despite some evidence for distinct functional subregions. Here we used functional magnetic resonance imaging (fMRI) to simultaneously contrast multiple effects of error, conflict, and task-switching that have been individually construed in support of various theories. We found overlapping yet functionally distinct subregions of mPFC, with activations related to dominant error, conflict, and task-switching effects successively found along a rostral-ventral to caudal-dorsal gradient within medial prefrontal cortex. Activations in the rostral cingulate zone (RCZ) were strongly correlated with the unexpectedness of outcomes suggesting a role in outcome prediction and preparing control systems to deal with anticipated outcomes. The results as a whole support a resolution of some ongoing debates in that distinct theories may each pertain to corresponding distinct yet overlapping subregions of mPFC. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: A pilot study

    Institute of Scientific and Technical Information of China (English)

    Feng-Mei Fan; Shu-Ping Tan; Fu-De Yang; Yun-Long Tan; Yan-Li Zhao; Nan Chen; Bin-Bin Li

    2013-01-01

    People with schizophrenia exhibit impaired social cognitive functions,particularly emotion regulation.Abnormal activations of the ventral medial prefrontal cortex (vMPFC) during emotional tasks have been demonstrated in schizophrenia,suggesting its important role in emotion processing in patients.We used the resting-state functional connectivity approach,setting a functionally relevant region,the vMPFC,as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients.We found hypo-connectivity between the vMPFC and the medial frontal cortex,right middle temporal lobe (MTL),right hippocampus,parahippocampal cortex (PHC) and amygdala.Further,there was a decreased strength of the negative connectivity (or anticorrelation) between the vMPFC and the bilateral dorsal lateral prefrontal cortex (DLPFC) and pre-supplementary motor areas.Among these connectivity alterations,reduced vMPFCDLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale,while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients.These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia.The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.

  14. Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

    Science.gov (United States)

    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

    2018-02-01

    Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Differential roles for medial prefrontal and medial temporal cortices in schema-dependent encoding: from congruent to incongruent.

    Science.gov (United States)

    van Kesteren, Marlieke T R; Beul, Sarah F; Takashima, Atsuko; Henson, Richard N; Ruiter, Dirk J; Fernández, Guillén

    2013-10-01

    Information that is congruent with prior knowledge is generally remembered better than incongruent information. This effect of congruency on memory has been attributed to a facilitatory influence of activated schemas on memory encoding and consolidation processes, and hypothesised to reflect a shift between processing in medial temporal lobes (MTL) towards processing in medial prefrontal cortex (mPFC). To investigate this shift, we used functional magnetic resonance imaging (fMRI) to compare brain activity during paired-associate encoding across three levels of subjective congruency of the association with prior knowledge. Participants indicated how congruent they found an object-scene pair during scanning, and were tested on item and associative recognition memory for these associations one day later. Behaviourally, we found a monotonic increase in memory performance with increasing congruency for both item and associative memory. Moreover, as hypothesised, encoding-related activity in mPFC increased linearly with increasing congruency, whereas MTL showed the opposite pattern of increasing encoding-related activity with decreasing congruency. Additionally, mPFC showed increased functional connectivity with a region in the ventral visual stream, presumably related to the binding of visual representations. These results support predictions made by a recent neuroscientific framework concerning the effects of schema on memory. Specifically, our findings show that enhanced memory for more congruent information is mediated by the mPFC, which is hypothesised to guide integration of new information into a pre-existing schema represented in cortical areas, while memory for more incongruent information relies instead on automatic encoding of arbitrary associations by the MTL. © 2013 Elsevier Ltd. All rights reserved.

  16. The Role of the Rat Medial Prefrontal Cortex in Adapting to Changes in Instrumental Contingency

    Science.gov (United States)

    Coutureau, Etienne; Esclassan, Frederic; Di Scala, Georges; Marchand, Alain R.

    2012-01-01

    In order to select actions appropriate to current needs, a subject must identify relationships between actions and events. Control over the environment is determined by the degree to which action consequences can be predicted, as described by action-outcome contingencies – i.e. performing an action should affect the probability of the outcome. We evaluated in a first experiment adaptation to contingency changes in rats with neurotoxic lesions of the medial prefrontal cortex. Results indicate that this brain region is not critical to adjust instrumental responding to a negative contingency where the rats must refrain from pressing a lever, as this action prevents reward delivery. By contrast, this brain region is required to reduce responding in a non-contingent situation where the same number of rewards is freely delivered and actions do not affect the outcome any more. In a second experiment, we determined that this effect does not result from a different perception of temporal relationships between actions and outcomes since lesioned rats adapted normally to gradually increasing delays in reward delivery. These data indicate that the medial prefrontal cortex is not directly involved in evaluating the correlation between action-and reward-rates or in the perception of reward delays. The deficit in lesioned rats appears to consist of an abnormal response to the balance between contingent and non-contingent rewards. By highlighting the role of prefrontal regions in adapting to the causal status of actions, these data contribute to our understanding of the neural basis of choice tasks. PMID:22496747

  17. The role of the medial prefrontal cortex in the conditioning and extinction of fear

    Directory of Open Access Journals (Sweden)

    Thomas Francis Giustino

    2015-11-01

    Full Text Available Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD. As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL and infralimbic (IL subdivisions of the medial prefrontal cortex (mPFC regulate the expression and suppression of fear in rodents, respectively. Here we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.

  18. Medial prefrontal brain activation to anticipated reward and loss in obsessive-compulsive disorder.

    Science.gov (United States)

    Kaufmann, C; Beucke, J C; Preuße, F; Endrass, T; Schlagenhauf, F; Heinz, A; Juckel, G; Kathmann, N

    2013-01-01

    Obsessive-compulsive disorder (OCD) is associated with dysfunctional brain activity in several regions which are also involved in the processing of motivational stimuli. Processing of reward and punishment appears to be of special importance to understand clinical symptoms. There is evidence for higher sensitivity to punishment in patients with OCD which raises the question how avoidance of punishment relates to activity within the brain's reward circuitry. We employed the monetary incentive delay task paradigm optimized for modeling the anticipation phase of immediate reward and punishment, in the context of a cross-sectional event-related FMRI study comparing OCD patients and healthy control participants (n = 19 in each group). While overall behavioral performance was similar in both groups, patients showed increased activation upon anticipated losses in a medial and superior frontal cortex region extending into the cingulate cortex, and decreased activation upon anticipated rewards. No evidence was found for altered activation of dorsal or ventral striatal regions. Patients also showed more delayed responses for anticipated rewards than for anticipated losses whereas the reverse was true in healthy participants. The medial prefrontal cortex has been shown to implement a domain-general process comprising negative affect, pain and cognitive control. This process uses information about punishment to control aversively motivated actions by integrating signals arriving from subcortical regions. Our results support the notion that OCD is associated with altered sensitivity to anticipated rewards and losses in a medial prefrontal region whereas there is no significant aberrant activation in ventral or dorsal striatal brain regions during processing of reinforcement anticipation.

  19. Estudio comparativo del rendimiento de las funciones ejecutivas en la corteza prefrontal dorsolateral, orbitofrontal y frontomedial en adolescentes policonsumidores de sustancias psicoactivas, vinculados al sistema de responsabilidad penal en paralelo con adolescentes que no se encuentran bajo esta misma condición

    Directory of Open Access Journals (Sweden)

    Diego Alejandro Calle Sandoval

    2017-07-01

    Full Text Available La presente investigación se realizó bajo una metodología cuantitativa comparativa y de corte transversal, la cual tuvo como objetivo la realización de un estudio del rendimiento de las funciones ejecutivas en la corteza prefrontal dorsolateral, orbitofrontal y frontomedial en adolescentes, entre los 14 y 18 años de edad, policonsumidores de sustancias psicoactivas (SPA y vinculados al sistema de responsabilidad penal, en paralelo con adolescentes pertenecientes a una institución educativa que no se encuentran bajo esta misma condición; todos ellos del departamento del Quindío. A la población estudio se le aplicó una prueba neuropsicológica de funciones ejecutivas y lóbulos frontales (BANFE 2, cuyos resultados dan cuenta de que el grado de escolaridad –sea alto o inferior– no es un factor influyente en el rendimiento ejecutivo; además, evidencian diferencias significativas en el rendimiento de las funciones ejecutivas en la población bajo responsabilidad penal con antecedentes de policonsumo, encontrándose alteración en la corteza prefrontal dorsolateral, orbitofrontal y frontomedial, a diferencia de la población estudiantil que no cumple con esta condición.

  20. Dorsal medial prefrontal cortex contributes to conditioned taste aversion memory consolidation and retrieval.

    Science.gov (United States)

    Gonzalez, Maria Carolina; Villar, Maria Eugenia; Igaz, Lionel M; Viola, Haydée; Medina, Jorge H

    2015-12-01

    The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Hippocampal and ventral medial prefrontal activation during retrieval-mediated learning supports novel inference.

    Science.gov (United States)

    Zeithamova, Dagmar; Dominick, April L; Preston, Alison R

    2012-07-12

    Memory enables flexible use of past experience to inform new behaviors. Although leading theories hypothesize that this fundamental flexibility results from the formation of integrated memory networks relating multiple experiences, the neural mechanisms that support memory integration are not well understood. Here, we demonstrate that retrieval-mediated learning, whereby prior event details are reinstated during encoding of related experiences, supports participants' ability to infer relationships between distinct events that share content. Furthermore, we show that activation changes in a functionally coupled hippocampal and ventral medial prefrontal cortical circuit track the formation of integrated memories and successful inferential memory performance. These findings characterize the respective roles of these regions in retrieval-mediated learning processes that support relational memory network formation and inferential memory in the human brain. More broadly, these data reveal fundamental mechanisms through which memory representations are constructed into prospectively useful formats. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

    Science.gov (United States)

    Gonzalez, María C.; Kramar, Cecilia P.; Tomaiuolo, Micol; Katche, Cynthia; Weisstaub, Noelia; Cammarota, Martín; Medina, Jorge H.

    2014-01-01

    Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus. PMID:25506318

  3. Neuroanatomical Substrates of Rodent Social Behavior: The Medial Prefrontal Cortex and Its Projection Patterns

    Science.gov (United States)

    Ko, Jaewon

    2017-01-01

    Social behavior encompasses a number of distinctive and complex constructs that form the core elements of human imitative culture, mainly represented as either affiliative or antagonistic interactions with conspecifics. Traditionally considered in the realm of psychology, social behavior research has benefited from recent advancements in neuroscience that have accelerated identification of the neural systems, circuits, causative genes and molecular mechanisms that underlie distinct social cognitive traits. In this review article, I summarize recent findings regarding the neuroanatomical substrates of key social behaviors, focusing on results from experiments conducted in rodent models. In particular, I will review the role of the medial prefrontal cortex (mPFC) and downstream subcortical structures in controlling social behavior, and discuss pertinent future research perspectives. PMID:28659766

  4. Bidirectional control of social hierarchy by synaptic efficacy in medial prefrontal cortex.

    Science.gov (United States)

    Wang, Fei; Zhu, Jun; Zhu, Hong; Zhang, Qi; Lin, Zhanmin; Hu, Hailan

    2011-11-04

    Dominance hierarchy has a profound impact on animals' survival, health, and reproductive success, but its neural circuit mechanism is virtually unknown. We found that dominance ranking in mice is transitive, relatively stable, and highly correlates among multiple behavior measures. Recording from layer V pyramidal neurons of the medial prefrontal cortex (mPFC) showed higher strength of excitatory synaptic inputs in mice with higher ranking, as compared with their subordinate cage mates. Furthermore, molecular manipulations that resulted in an increase and decrease in the synaptic efficacy in dorsal mPFC neurons caused an upward and downward movement in the social rank, respectively. These results provide direct evidence for mPFC's involvement in social hierarchy and suggest that social rank is plastic and can be tuned by altering synaptic strength in mPFC pyramidal cells.

  5. Neural correlates of depth of strategic reasoning in medial prefrontal cortex

    Science.gov (United States)

    Coricelli, Giorgio; Nagel, Rosemarie

    2009-01-01

    We used functional MRI (fMRI) to investigate human mental processes in a competitive interactive setting—the “beauty contest” game. This game is well-suited for investigating whether and how a player's mental processing incorporates the thinking process of others in strategic reasoning. We apply a cognitive hierarchy model to classify subject's choices in the experimental game according to the degree of strategic reasoning so that we can identify the neural substrates of different levels of strategizing. According to this model, high-level reasoners expect the others to behave strategically, whereas low-level reasoners choose based on the expectation that others will choose randomly. The data show that high-level reasoning and a measure of strategic IQ (related to winning in the game) correlate with the neural activity in the medial prefrontal cortex, demonstrating its crucial role in successful mentalizing. This supports a cognitive hierarchy model of human brain and behavior. PMID:19470476

  6. Attention, emotion, and deactivation of default activity in inferior medial prefrontal cortex

    DEFF Research Database (Denmark)

    Geday, Jacob; Gjedde, Albert

    2008-01-01

    Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC...... with positron emission tomography (PET) of labeled water (H(15)2O) uptake in brain of 14 healthy subjects. The subjects performed either a less demanding or a more demanding task of attention while they watched neutral and emotive images of people in realistic indoor or outdoor situations. In the less demanding...... cortices, revealed significant activation in the fusiform gyrus, independently of the task. In contrast, we found no effect of emotional content in the IMPC, where emotions failed to override the effect of the task. The results are consistent with a role of the IMPC in the selection among competitive...

  7. The medial prefrontal cortex and memory of cue location in the rat.

    Science.gov (United States)

    Rawson, Tim; O'Kane, Michael; Talk, Andrew

    2010-01-01

    We developed a single-trial cue-location memory task in which rats experienced an auditory cue while exploring an environment. They then recalled and avoided the sound origination point after the cue was paired with shock in a separate context. Subjects with medial prefrontal cortical (mPFC) lesions made no such avoidance response, but both lesioned and control subjects avoided the cue itself when presented at test. A follow up assessment revealed no spatial learning impairment in either group. These findings suggest that the rodent mPFC is required for incidental learning or recollection of the location at which a discrete cue occurred, but is not required for cue recognition or for allocentric spatial memory. Copyright 2009 Elsevier Inc. All rights reserved.

  8. Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex.

    Science.gov (United States)

    Tada, Hirobumi; Miyazaki, Tomoyuki; Takemoto, Kiwamu; Takase, Kenkichi; Jitsuki, Susumu; Nakajima, Waki; Koide, Mayu; Yamamoto, Naoko; Komiya, Kasane; Suyama, Kumiko; Sano, Akane; Taguchi, Akiko; Takahashi, Takuya

    2016-10-25

    Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life.

  9. Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex

    Science.gov (United States)

    Tada, Hirobumi; Miyazaki, Tomoyuki; Takemoto, Kiwamu; Takase, Kenkichi; Jitsuki, Susumu; Nakajima, Waki; Koide, Mayu; Yamamoto, Naoko; Komiya, Kasane; Suyama, Kumiko; Sano, Akane; Taguchi, Akiko; Takahashi, Takuya

    2016-01-01

    Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life. PMID:27791080

  10. Role of the ventrolateral orbital cortex and medial prefrontal cortex in incentive downshift situations.

    Science.gov (United States)

    Ortega, Leonardo A; Glueck, Amanda C; Uhelski, Megan; Fuchs, Perry N; Papini, Mauricio R

    2013-05-01

    The present research evaluated the role of two prefrontal cortex areas, the ventrolateral orbital cortex (VLO) and the medial prefrontal cortex (mPFC), on two situations involving incentive downshifts, consummatory successive negative contrast (cSNC) with sucrose solutions and Pavlovian autoshaping following continuous vs. partial reinforcement with food pellets. Animals received electrolytic lesions and then were tested on cSNC, autoshaping, open-field activity, and sucrose sensitivity. Lesions of the VLO reduced suppression of consummatory behavior after the incentive downshift, but only during the first downshift trial, and also eliminated the enhancement of anticipatory behavior during partial reinforcement, relative to continuous reinforcement, in autoshaping. There was no evidence of specific effects of mPFC lesions on incentive downshifts. Open-field activity was also reduced by VLO lesions, but only in the central area, whereas mPFC lesions had no observable effects on activity. Animals with mPFC lesions exhibited decreased consumption of the lowest sucrose concentration, whereas no effects were observed in animals with VLO lesions. These results suggest that the VLO may exert nonassociative (i.e., motivational, emotional) influences on behavior in situations involving incentive downshifts. No clear role on incentive downshift was revealed by mPFC lesions. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Reversal of Cocaine-Associated Synaptic Plasticity in Medial Prefrontal Cortex Parallels Elimination of Memory Retrieval.

    Science.gov (United States)

    Otis, James M; Mueller, Devin

    2017-09-01

    Addiction is characterized by abnormalities in prefrontal cortex that are thought to allow drug-associated cues to drive compulsive drug seeking and taking. Identification and reversal of these pathologic neuroadaptations are therefore critical for treatment of addiction. Previous studies using rodents reveal that drugs of abuse cause dendritic spine plasticity in prelimbic medial prefrontal cortex (PL-mPFC) pyramidal neurons, a phenomenon that correlates with the strength of drug-associated memories in vivo. Thus, we hypothesized that cocaine-evoked plasticity in PL-mPFC may underlie cocaine-associated memory retrieval, and therefore disruption of this plasticity would prevent retrieval. Indeed, using patch clamp electrophysiology we find that cocaine place conditioning increases excitatory presynaptic and postsynaptic transmission in rat PL-mPFC pyramidal neurons. This was accounted for by increases in excitatory presynaptic release, paired-pulse facilitation, and increased AMPA receptor transmission. Noradrenergic signaling is known to maintain glutamatergic plasticity upon reactivation of modified circuits, and we therefore next determined whether inhibition of noradrenergic signaling during memory reactivation would reverse the cocaine-evoked plasticity and/or disrupt the cocaine-associated memory. We find that administration of the β-adrenergic receptor antagonist propranolol before memory retrieval, but not after (during memory reconsolidation), reverses the cocaine-evoked presynaptic and postsynaptic modifications in PL-mPFC and causes long-lasting memory impairments. Taken together, these data reveal that cocaine-evoked synaptic plasticity in PL-mPFC is reversible in vivo, and suggest a novel strategy that would allow normalization of prefrontal circuitry in addiction.

  12. Beyond the medial regions of prefrontal cortex in the regulation of fear and anxiety

    Directory of Open Access Journals (Sweden)

    Yoshiro eShiba

    2016-02-01

    Full Text Available Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC and orbitofrontal (OFC regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies.

  13. Anterior medial prefrontal cortex exhibits activation during task preparation but deactivation during task execution.

    Directory of Open Access Journals (Sweden)

    Hideya Koshino

    Full Text Available BACKGROUND: The anterior prefrontal cortex (PFC exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN, which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. METHODOLOGY/PRINCIPAL FINDINGS: Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition or to ignore them (No face memory condition, then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. CONCLUSIONS/SIGNIFICANCE: The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing.

  14. Medial prefrontal cortex and the adaptive regulation of reinforcement learning parameters.

    Science.gov (United States)

    Khamassi, Mehdi; Enel, Pierre; Dominey, Peter Ford; Procyk, Emmanuel

    2013-01-01

    Converging evidence suggest that the medial prefrontal cortex (MPFC) is involved in feedback categorization, performance monitoring, and task monitoring, and may contribute to the online regulation of reinforcement learning (RL) parameters that would affect decision-making processes in the lateral prefrontal cortex (LPFC). Previous neurophysiological experiments have shown MPFC activities encoding error likelihood, uncertainty, reward volatility, as well as neural responses categorizing different types of feedback, for instance, distinguishing between choice errors and execution errors. Rushworth and colleagues have proposed that the involvement of MPFC in tracking the volatility of the task could contribute to the regulation of one of RL parameters called the learning rate. We extend this hypothesis by proposing that MPFC could contribute to the regulation of other RL parameters such as the exploration rate and default action values in case of task shifts. Here, we analyze the sensitivity to RL parameters of behavioral performance in two monkey decision-making tasks, one with a deterministic reward schedule and the other with a stochastic one. We show that there exist optimal parameter values specific to each of these tasks, that need to be found for optimal performance and that are usually hand-tuned in computational models. In contrast, automatic online regulation of these parameters using some heuristics can help producing a good, although non-optimal, behavioral performance in each task. We finally describe our computational model of MPFC-LPFC interaction used for online regulation of the exploration rate and its application to a human-robot interaction scenario. There, unexpected uncertainties are produced by the human introducing cued task changes or by cheating. The model enables the robot to autonomously learn to reset exploration in response to such uncertain cues and events. The combined results provide concrete evidence specifying how prefrontal

  15. Norepinephrine regulates cocaine-primed reinstatement via α1-adrenergic receptors in the medial prefrontal cortex.

    Science.gov (United States)

    Schmidt, Karl T; Schroeder, Jason P; Foster, Stephanie L; Squires, Katherine; Smith, Brilee M; Pitts, Elizabeth G; Epstein, Michael P; Weinshenker, David

    2017-06-01

    Drug-primed reinstatement of cocaine seeking in rats is thought to reflect relapse-like behavior and is mediated by the integration of signals from mesocorticolimbic dopaminergic projections and corticostriatal glutamatergic innervation. Cocaine-primed reinstatement can also be attenuated by systemic administration of dopamine β-hydroxylase (DBH) inhibitors, which prevent norepinephrine (NE) synthesis, or by α1-adrenergic receptor (α1AR) antagonists, indicating functional modulation by the noradrenergic system. In the present study, we sought to further discern the role of NE in cocaine-seeking behavior by determining whether α1AR activation can induce reinstatement on its own or is sufficient to permit cocaine-primed reinstatement in the absence of all other AR signaling, and identifying the neuroanatomical substrate within the mesocorticolimbic reward system harboring the critical α1ARs. We found that while intracerebroventricular infusion of the α1AR agonist phenylephrine did not induce reinstatement on its own, it did overcome the blockade of cocaine-primed reinstatement by the DBH inhibitor nepicastat. Furthermore, administration of the α1AR antagonist terazosin in the medial prefrontal cortex (mPFC), but not the ventral tegmental area (VTA) or nucleus accumbens (NAc) shell, attenuated cocaine-primed reinstatement. Combined, these data indicate that α1AR activation in the mPFC is required for cocaine-primed reinstatement, and suggest that α1AR antagonists merit further investigation as pharmacotherapies for cocaine dependence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Cognitive behavioral therapy changes functional connectivity between medial prefrontal and anterior cingulate cortices.

    Science.gov (United States)

    Yoshimura, Shinpei; Okamoto, Yasumasa; Matsunaga, Miki; Onoda, Keiichi; Okada, Go; Kunisato, Yoshihiko; Yoshino, Atsuo; Ueda, Kazutaka; Suzuki, Shin-Ichi; Yamawaki, Shigeto

    2017-01-15

    Depression is characterized by negative self-cognition. Our previous study (Yoshimura et al. 2014) revealed changes in brain activity after cognitive behavioral therapy (CBT) for depression, but changes in functional connectivity were not assessed. This study included 29 depressive patients and 15 healthy control participants. Functional Magnetic Resonance Imaging was used to investigate possible CBT-related functional connectivity changes associated with negative emotional self-referential processing. Depressed and healthy participants (overlapping with our previous study, Yoshimura et al. 2014) were included. We defined a seed region (medial prefrontal cortex) and coupled region (ACC) based on our previous study, and we examined changes in MPFC-ACC functional connectivity from pretreatment to posttreatment. CBT was associated with reduced functional connectivity between the MPFC and ACC. Symptom change with CBT was positively correlated with change in MPFC-ACC functional connectivity. Patients received pharmacotherapy including antidepressant. The present sample size was quite small and more study is needed. Statistical threshold in fMRI analysis was relatively liberal. CBT for depression may disrupt MPFC-ACC connectivity, with associated improvements in depressive symptoms and dysfunctional cognition. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. The role of the medial prefrontal cortex in trace fear extinction

    Science.gov (United States)

    Kwapis, Janine L.; Jarome, Timothy J.

    2015-01-01

    The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that supports extinction of this memory has received very little attention. Recent research has indicated that trace fear extinction requires a different neural circuit than delay extinction; trace extinction requires the participation of the retrosplenial cortex, but not the amygdala, as noted in a previous study. Here, we tested the roles of the prelimbic and infralimbic regions of the medial prefrontal cortex in trace and delay fear extinction by blocking NMDA receptors during extinction learning. We found that the prelimbic cortex is necessary for trace, but not for delay fear extinction, whereas the infralimbic cortex is involved in both types of extinction. These results are consistent with the idea that trace fear associations require plasticity in multiple cortical areas for successful extinction. Further, the infralimbic cortex appears to play a role in extinction regardless of whether the animal was initially trained in trace or delay conditioning. Together, our results provide new information about how the neural circuits supporting trace and delay fear extinction differ. PMID:25512576

  18. Reversible online control of habitual behavior by optogenetic perturbation of medial prefrontal cortex

    Science.gov (United States)

    Smith, Kyle S.; Virkud, Arti; Deisseroth, Karl; Graybiel, Ann M.

    2012-01-01

    Habits tend to form slowly but, once formed, can have great stability. We probed these temporal characteristics of habitual behaviors by intervening optogenetically in forebrain habit circuits as rats performed well-ingrained habitual runs in a T-maze. We trained rats to perform a maze habit, confirmed the habitual behavior by devaluation tests, and then, during the maze runs (ca. 3 s), we disrupted population activity in a small region in the medial prefrontal cortex, the infralimbic cortex. In accordance with evidence that this region is necessary for the expression of habits, we found that this cortical disruption blocked habitual behavior. Notably, however, this blockade of habitual performance occurred on line, within an average of three trials (ca. 9 s of inhibition), and as soon as during the first trial (habit, and, simultaneously, the more recently acquired habit was blocked. These online changes occurred within an average of two trials (ca. 6 s of infralimbic inhibition). Measured changes in generalized performance ability and motivation to consume reward were unaffected. This immediate toggling between breaking old habits and returning to them demonstrates that even semiautomatic behaviors are under cortical control and that this control occurs online, second by second. These temporal characteristics define a framework for uncovering cellular transitions between fixed and flexible behaviors, and corresponding disturbances in pathologies. PMID:23112197

  19. Efficient learning mechanisms hold in the social domain and are implemented in the medial prefrontal cortex.

    Science.gov (United States)

    Seid-Fatemi, Azade; Tobler, Philippe N

    2015-05-01

    When we are learning to associate novel cues with outcomes, learning is more efficient if we take advantage of previously learned associations and thereby avoid redundant learning. The blocking effect represents this sort of efficiency mechanism and refers to the phenomenon in which a novel stimulus is blocked from learning when it is associated with a fully predicted outcome. Although there is sufficient evidence that this effect manifests itself when individuals learn about their own rewards, it remains unclear whether it also does when they learn about others' rewards. We employed behavioral and neuroimaging methods to address this question. We demonstrate that blocking does indeed occur in the social domain and it does so to a similar degree as observed in the individual domain. On the neural level, activations in the medial prefrontal cortex (mPFC) show a specific contribution to blocking and learning-related prediction errors in the social domain. These findings suggest that the efficiency principle that applies to reward learning in the individual domain also applies to that in the social domain, with the mPFC playing a central role in implementing it. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. An increase in tobacco craving is associated with enhanced medial prefrontal cortex network coupling.

    Directory of Open Access Journals (Sweden)

    Amy C Janes

    Full Text Available Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefrontal cortex (OMPFC network, which also included the subgenual anterior cingulate cortex (sgACC extending into the ventral striatum. Brain regions in the OMPFC network are not only implicated in addiction and reward, but, due to their rich anatomic interconnections, may serve as the site of integration across craving-related brain regions. Subjective craving and resting state fMRI were evaluated twice with an ∼1 hour delay between the scans. Cigarette craving was significantly increased at the end, relative to the beginning of the scan session. Enhanced craving was associated with heightened coupling between the OMPFC network and other cortical, limbic, striatal, and visceromotor brain regions that are both anatomically interconnected with the OMPFC, and have been implicated in addiction and craving. This is the first demonstration confirming that an increase in craving is associated with enhanced brain region interactions, which may play a role in the experience of craving.

  1. Different role of the ventral medial prefrontal cortex on modulation of innate and associative learned fear.

    Science.gov (United States)

    Lisboa, S F; Stecchini, M F; Corrêa, F M A; Guimarães, F S; Resstel, L B M

    2010-12-15

    Reversible inactivation of the ventral portion of medial prefrontal cortex (vMPFC) of the rat brain has been shown to induce anxiolytic-like effects in animal models based on associative learning. The role of this brain region in situations involving innate fear, however, is still poorly understood, with several contradictory results in the literature. The objective of the present work was to verify in male Wistar rats the effects of vMPFC administration of cobalt chloride (CoCl(2)), a selective inhibitor of synaptic activity, in rats submitted to two models based on innate fear, the elevated plus-maze (EPM) and light-dark box (LDB), comparing the results with those obtained in two models involving associative learning, the contextual fear conditioning (CFC) and Vogel conflict (VCT) tests. The results showed that, whereas CoCl(2) induced anxiolytic-like effects in the CFC and VCT tests, it enhanced anxiety in rats submitted to the EPM and LDB. Together these results indicate that the vMPFC plays an important but complex role in the modulation of defensive-related behaviors, which seems to depend on the nature of the anxiety/fear inducing stimuli. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. The world according to me: Personal relevance and the medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Anna eAbraham

    2013-07-01

    Full Text Available More than a decade of neuroimaging research has established that anterior and posterior cortical midline regions are consistently recruited during self-referential thinking. These regions are engaged under conditions of directed cognition, such as during explicit self-reference tasks, as well as during spontaneous cognition, such as under conditions of rest. One of the many issues that remain to be clarified regarding the relationship between self-referential thinking and cortical midline activity is the functional specificity of these regions with regard to the nature of self-representation and processing. The functional profile associated with the medial prefrontal cortex (mPFC is the focus of the current article. What is specifically explored is the idea that personal relevance or personal significance is a central factor that impacts how brain activity is modulated within this cortical midline region. The proactive, imaginative and predictive nature of function in the mPFC is examined by evaluating studies of spontaneously-directed cognition, which is triggered by stimulus associated personal relevance.

  3. Synaptic Modifications in the Medial Prefrontal Cortex in Susceptibility and Resilience to Stress

    Science.gov (United States)

    Wang, Minghui; Perova, Zinaida; Arenkiel, Benjamin R.

    2014-01-01

    When facing stress, most individuals are resilient whereas others are prone to developing mood disorders. The brain mechanisms underlying such divergent behavioral responses remain unclear. Here we used the learned helplessness procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a brain region highly implicated in both clinical and animal models of depression, in adaptive and maladaptive behavioral responses to stress. We found that uncontrollable and inescapable stress induced behavioral state-dependent changes in the excitatory synapses onto a subset of mPFC neurons: those that were activated during behavioral responses as indicated by their expression of the activity reporter c-Fos. Whereas synaptic potentiation was linked to learned helplessness, a depression-like behavior, synaptic weakening, was associated with resilience to stress. Notably, enhancing the activity of mPFC neurons using a chemical–genetic method was sufficient to convert the resilient behavior into helplessness. Our results provide direct evidence that mPFC dysfunction is linked to maladaptive behavioral responses to stress, and suggest that enhanced excitatory synaptic drive onto mPFC neurons may underlie the previously reported hyperactivity of this brain region in depression. PMID:24872553

  4. The medial prefrontal cortex: coordinator of autonomic, neuroendocrine and behavioural responses to stress.

    Science.gov (United States)

    McKlveen, J M; Myers, B; Herman, J P

    2015-06-01

    Responding to real or potential threats in the environment requires the coordination of autonomic, neuroendocrine and behavioural processes to promote adaptation and survival. These diverging systems necessitate input from the limbic forebrain to integrate and modulate functional output in accordance with contextual demand. In the present review, we discuss the potential role of the medial prefrontal cortex (mPFC) as a coordinator of behavioural and physiological stress responses across multiple temporal and contextual domains. Furthermore, we highlight converging evidence from rodent and human research indicating the necessity of the mPFC for modulating physiological energetic systems to mobilise or limit energetic resources as needed to ultimately promote behavioural adaptation in the face of stress. We review the literature indicating that glucocorticoids act as one of the primary messengers in the reallocation of energetic resources having profound effects locally within the mPFC, as well as shaping how the mPFC acts within a network of brain structures to modulate responses to stress. Finally, we discuss how both rodent and human studies point toward a critical role of the mPFC in the coordination of anticipatory responses to stress and why this distinction is an important one to make in stress neurobiology. © 2015 British Society for Neuroendocrinology.

  5. The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination.

    Science.gov (United States)

    Mair, Robert G; Miller, Rikki L A; Wormwood, Benjamin A; Francoeur, Miranda J; Onos, Kristen D; Gibson, Brett M

    2015-07-01

    Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The role of the medial prefrontal cortex in the play fighting of rats.

    Science.gov (United States)

    Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

    2009-12-01

    Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

  7. Association of familial risk for schizophrenia with thalamic and medial prefrontal functional connectivity during attentional control.

    Science.gov (United States)

    Antonucci, Linda A; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Romano, Raffaella; Quarto, Tiziana; Porcelli, Annamaria; Mancini, Marina; Di Giorgio, Annabella; Caforio, Grazia; Pergola, Giulio; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

    2016-05-01

    Anomalies in behavioral correlates of attentional processing and related brain activity are crucial correlates of schizophrenia and associated with familial risk for this brain disorder. However, it is not clear how brain functional connectivity during attentional processes is key for schizophrenia and linked with trait vs. state related variables. To address this issue, we investigated patterns of functional connections during attentional control in healthy siblings of patients with schizophrenia, who share with probands genetic features but not variables related to the state of the disorder. 356 controls, 55 patients with schizophrenia on stable treatment with antipsychotics and 40 healthy siblings of patients with this brain disorder underwent the Variable Attentional Control (VAC) task during fMRI. Independent Component Analysis (ICA) is allowed to identify independent components (IC) of BOLD signal recorded during task performance. Results indicated reduced connectivity strength in patients with schizophrenia as well as in their healthy siblings in left thalamus within an attentional control component and greater connectivity in right medial prefrontal cortex (PFC) within the so-called Default Mode Network (DMN) compared to healthy individuals. These results suggest a relationship between familial risk for schizophrenia and brain functional networks during attentional control, such that this biological phenotype may be considered a useful intermediate phenotype in order to link genes effects to aspects of the pathophysiology of this brain disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Perceived stress predicts altered reward and loss feedback processing in medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Michael T Treadway

    2013-05-01

    Full Text Available Stress is significant risk factor for the development of psychopathology, particularly symptoms related to reward processing. Importantly, individuals display marked variation in how they perceive and cope with stressful events, and such differences are strongly linked to risk for developing psychiatric symptoms following stress exposure. However, many questions remain regarding the neural architecture that underlies inter-subject variability in perceptions of stressors. Using functional magnetic resonance imaging (fMRI during a monetary incentive delay paradigm, we examined the effects of self-reported perceived stress levels on neural activity during reward anticipation and feedback in a sample of healthy individuals. We found that subjects reporting more uncontrollable and overwhelming stressors displayed blunted neural responses in medial prefrontal cortex (mPFC following feedback related to monetary gains as well monetary losses. This is consistent with preclinical models that implicate the mPFC as a key site of vulnerability to the noxious effects of uncontrollable stressors. Our data help translate these findings to humans, and elucidate some of the neural mechanisms that may underlie stress-linked risk for developing reward-related psychiatric symptoms.

  9. Protective role of curcumin against sulfite-induced structural changes in rats' medial prefrontal cortex.

    Science.gov (United States)

    Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied

    2015-08-01

    Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P curcumin had a protective role against the changes in the rats.

  10. The role of medial prefrontal cortex in memory and decision making.

    Science.gov (United States)

    Euston, David R; Gruber, Aaron J; McNaughton, Bruce L

    2012-12-20

    Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Laser technique for anatomical-functional study of the medial prefrontal cortex of the brain

    Science.gov (United States)

    Sanchez-Huerta, Laura; Hernandez, Adan; Ayala, Griselda; Marroquin, Javier; Silva, Adriana B.; Khotiaintsev, Konstantin S.; Svirid, Vladimir A.; Flores, Gonzalo; Khotiaintsev, Sergei N.

    1999-05-01

    The brain represents one of the most complex systems that we know yet. In its study, non-destructive methods -- in particular, behavioral studies play an important role. By alteration of brain functioning (e.g. by pharmacological means) and observation of consequent behavior changes an important information on brain organization and functioning is obtained. For inducing local alterations, permanent brain lesions are employed. However, for correct results this technique has to be quasi-non-destructive, i.e. not to affect the normal brain function. Hence, the lesions should be very small, accurate and applied precisely over the structure (e.g. the brain nucleus) of interest. These specifications are difficult to meet with the existing techniques for brain lesions -- specifically, neurotoxical, mechanical and electrical means because they result in too extensive damage. In this paper, we present new laser technique for quasi-non- destructive anatomical-functional mapping in vivo of the medial prefrontal cortex (MPFC) of the rat. The technique is based on producing of small-size, well-controlled laser- induced lesions over some areas of the MPFC. The anesthetized animals are subjected to stereotactic surgery and certain points of the MPFC are exposed the confined radiation of the 10 W cw CO2 laser. Subsequent behavioral changes observed in neonatal and adult animals as well as histological data prove effectiveness of this technology for anatomical- functional studies of the brain by areas, and as a treatment method for some pathologies.

  12. Humor Appreciation Involves Parametric and Synchronized Activity in the Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Iidaka, Tetsuya

    2017-12-01

    Humor perception is a ubiquitous phenomenon in human societies. In theories of humor perception, three factors, non-seriousness, social context, and incongruity, have been implicated in humor. In another theory, however, elaboration and reinterpretation of contexts are considered to play a role in eliciting humor. Although the neural correlates of humor appreciation have been investigated using neuroimaging methods, only a few studies have conducted such experiments under natural conditions. In the present study, two functional magnetic resonance imaging experiments, using a comedy movie as a stimulus, were conducted to investigate the neural correlates of humor under natural conditions. The subjects' brain activity was measured while watching and enjoying a movie. In experiment 1, a parametric analysis showed that the medial prefrontal cortex (MPFC) and hippocampus/amygdala had a positive relationship with the subjective rating of funniness. In experiment 2, intersubject correlation was analyzed to investigate synchronized activity across all participants. Signal synchronization that paralleled increased funniness ratings was observed in the MPFC and hippocampus. Thus, it appears that both parametric and synchronized activity in the MPFC and hippocampus are important during humor appreciation. The present study has revealed the brain regions that are predominantly involved in humor sensation under natural condition. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Contributions of the Hippocampus and Medial Prefrontal Cortex to Energy and Body Weight Regulation

    Science.gov (United States)

    Davidson, T. L.; Chan, Kinho; Jarrard, Leonard E.; Kanoski, Scott E.; Clegg, Deborah J.; Benoit, Stephen C.

    2008-01-01

    The effects of selective ibotenate lesions of the complete hippocampus (CHip), the hippocampal ventral pole (VP), or the medial prefrontal cortex (mPFC) in male rats were assessed on several measures related to energy regulation (i.e., body weight gain, food intake, body adiposity, metabolic activity general behavioral activity, conditioned appetitive responding). The testing conditions were designed to minimize the nonspecific debilitating effects of these surgeries on intake and body weight. Rats with CHip and VP lesions exhibited significantly greater weight gain and food intake compared to controls. Furthermore, CHip-lesioned rats, but not rats with VP lesions, showed elevated metabolic activity, general activity in the dark phase of the light-dark cycle, and greater conditioned appetitive behavior, compared to control rats without these brain lesions. In contrast, rats with mPFC lesions were not different from controls on any of these measures. These results indicate that hippocampal damage interferes with energy and body weight regulation, perhaps by disrupting higher-order learning and memory processes that contribute to the control of appetitive and consummatory behavior. PMID:18831000

  14. Astrocytic cytoskeletal atrophy in the medial prefrontal cortex of a triple transgenic mouse model of Alzheimer's disease

    Czech Academy of Sciences Publication Activity Database

    Kulijewicz-Nawrot, Magdaléna; Verkhratsky, Alexei; Chvátal, Alexandr; Syková, Eva; Rodríguez Arellano, Jose Julio

    2012-01-01

    Roč. 221, č. 3 (2012), s. 252-262 ISSN 0021-8782 R&D Projects: GA ČR GA305/08/1384; GA ČR GA309/09/1696; GA ČR GAP304/11/0184 Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : Alzheimer’s disease,, * astroglia * medial prefrontal cortex Subject RIV: FH - Neurology Impact factor: 2.357, year: 2012

  15. Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity.

    Science.gov (United States)

    Berkers, Ruud M W J; Klumpers, Floris; Fernández, Guillén

    2016-10-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to differences in (the risk for) affective disorders that are characterized by 'overgeneralized' emotional memories. Here, we investigate the neural underpinnings of individual differences in emotional associative memory. A large group of healthy male participants were scanned while encoding associations of face-photographs and written occupational identities that were of either neutral ('driver') or negative ('murderer') valence. Subsequently, memory was tested by prompting participants to retrieve the occupational identities corresponding to each face. Whereas in both valence categories a similar amount of faces was labeled correctly with 'neutral' and 'negative' identities, (gist memory), specific associations were found to be less accurately remembered when the occupational identity was negative compared to neutral (specific memory). This pattern of results suggests reduced memory specificity for associations containing a negatively valenced component. The encoding of these negative associations was paired with a selective increase in medial prefrontal cortex activity and medial prefrontal-hippocampal connectivity. Individual differences in valence-specific neural connectivity were predictive of valence-specific reduction of memory specificity. The relationship between loss of emotional memory specificity and medial prefrontal-hippocampal connectivity is in line with the hypothesized role of a medial prefrontal-hippocampal circuit in regulating memory specificity, and warrants further investigations in individuals displaying 'overgeneralized' emotional memories. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers.

    Science.gov (United States)

    Li, Xingbao; Sahlem, Gregory L; Badran, Bashar W; McTeague, Lisa M; Hanlon, Colleen A; Hartwell, Karen J; Henderson, Scott; George, Mark S

    2017-12-01

    Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue-elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub-cortical neural activity in non-treatment seeking nicotine-dependent participants. We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s-on, 10 s-off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session. A total of 11 non-treatment seeking nicotine-dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS. This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers. rTMS may exert its anti-craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788-794). © 2017 American Academy of Addiction Psychiatry.

  17. Lateral and medial prefrontal contributions to emotion generation by semantic elaboration during episodic encoding.

    Science.gov (United States)

    Kaneda, Takumi; Shigemune, Yayoi; Tsukiura, Takashi

    2017-02-01

    Memories for emotion-laden stimuli are remembered more accurately than those for neutral stimuli. Although this enhancement reflects stimulus-driven modulation of memory by emotions, functional neuroimaging evidence of the interacting mechanisms between emotions generated by intentional processes, such as semantic elaboration, and memory is scarce. The present fMRI study investigated how encoding-related activation is modulated by emotions generated during the process of semantic elaboration. During encoding with fMRI, healthy young adults viewed neutral (target) pictures either passively or with semantic elaboration. In semantic elaboration, participants imagined background stories related to the pictures. Encoding trials with semantic elaboration were subdivided into conditions in which participants imagined negative, positive, or neutral stories. One week later, memories for target pictures were tested. In behavioral results, memories for target pictures were significantly enhanced by semantic elaboration, compared to passive viewing, and the memory enhancement was more remarkable when negative or positive stories were imagined. fMRI results demonstrated that activations in the left inferior frontal gyrus and dorsal medial prefrontal cortex (dmPFC) were greater during the encoding of target pictures with semantic elaboration than those with passive viewing, and that these activations further increased during encoding with semantic elaboration of emotional stories than of neutral stories. Functional connectivity between the left inferior frontal gyrus and dmPFC/hippocampus during encoding significantly predicted retrieval accuracies of memories encoded with self-generated emotional stories. These findings suggest that networks including the left inferior frontal region, dmPFC, and hippocampus could contribute to the modulation of memories encoded with the emotion generation.

  18. Decreased medial prefrontal cortex activation during self-referential processing in bipolar mania.

    Science.gov (United States)

    Herold, Dorrit; Usnich, Tatiana; Spengler, Stephanie; Sajonz, Bastian; Bauer, Michael; Bermpohl, Felix

    2017-09-01

    Patients with bipolar disorder in mania exhibit symptoms pointing towards altered self-referential processing, such as decreased self-focus, flight of ideas and high distractibility. In depression, the opposite pattern of symptoms has been connected to increased activation of medial prefrontal cortex (mPFC) during self-referential processing. In this study, we hypothesized that (1) patients with mania will exhibit decreased activation in the mPFC during self-referential processing and (2) will be more alexithymic and that levels of alexithymia will correlate negatively with mPFC activation. The neural response to standardized pictures was compared in 14 patients with bipolar I disorder in mania to 14 healthy controls using blood oxygen level dependent contrast magnetic resonance imaging. Participants were asked to indicate with button press during the scanning session for each picture whether the pictures personally related to them or not. Toronto alexithymia scale (TAS) scores were recorded from all participants. In the group analysis, patients with mania exhibited decreased activation in a predefined region of interest in the mPFC during self-referential processing compared to healthy controls. Patients with mania showed significantly higher levels of alexithymia, attributable to difficulties in identifying and describing emotions. Activation in the mPFC correlated negatively with levels of alexithymia. Results presented here should be replicated in a larger group, potentially including unmedicated patients. The finding of decreased mPFC activation during self-referential processing in mania may reflect decreased self-focus and high distractibility. Support for this view comes from the negative correlation between higher alexithymia scores and decreased mPFC activation. These findings represent an opposite clinical and neuroimaging pattern to findings in depression. Copyright © 2017. Published by Elsevier B.V.

  19. Strategic neuronal encoding in medial prefrontal cortex of spatial working memory in the T-maze.

    Science.gov (United States)

    Yang, Yang; Mailman, Richard B

    2018-05-02

    Strategic neuronal encoding in the medial prefrontal cortex (mPFC) of the rat was correlated with spatial working memory (sWM) assessed by behavior in the T-maze. Neurons increased their firing rate around choice, with the increase largely occurring before choice as a prospective encode of behavior. This could be classified as sensitive-to-spatial information or sensitive-to-choice outcome. The sensitivity-to-spatial choice was defined by distinct firing rate changes before left- or right-choice. The percentage of left-choice sensitive neurons was not different from the percentage of right-choice sensitive neurons. There was also location-related neuronal activity in which neurons fired at distinct rates when rats were in a left- or right-location. More neurons were sensitive to left-location, as most of them were recorded from rats preferring to enter the right-location. The sensitivity to outcome was defined by a distinct firing rate around correct or error choice. Significantly more neurons were sensitive to error outcome, and, among these, more preferred to encode prospectively, increasing firing in advance of an error outcome. Similar to single neuron activity, the mPFC enhanced its neuronal network as measured by the oscillation of local field potential. The maximum power of oscillation was around choice, and occurred slightly earlier before error versus before correct outcome. Thus, sWM modulation in the mPFC includes not only spatial, but also outcome-related inputs, and neuronal ensembles monitor behavioral outcome to make strategic adjustments ensuring successful task performance. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Hippocampal-medial prefrontal circuit supports memory updating during learning and post-encoding rest

    Science.gov (United States)

    Schlichting, Margaret L.; Preston, Alison R.

    2015-01-01

    Learning occurs in the context of existing memories. Encountering new information that relates to prior knowledge may trigger integration, whereby established memories are updated to incorporate new content. Here, we provide a critical test of recent theories suggesting hippocampal (HPC) and medial prefrontal (MPFC) involvement in integration, both during and immediately following encoding. Human participants with established memories for a set of initial (AB) associations underwent fMRI scanning during passive rest and encoding of new related (BC) and unrelated (XY) pairs. We show that HPC-MPFC functional coupling during learning was more predictive of trial-by-trial memory for associations related to prior knowledge relative to unrelated associations. Moreover, the degree to which HPC-MPFC functional coupling was enhanced following overlapping encoding was related to memory integration behavior across participants. We observed a dissociation between anterior and posterior MPFC, with integration signatures during post-encoding rest specifically in the posterior subregion. These results highlight the persistence of integration signatures into post-encoding periods, indicating continued processing of interrelated memories during rest. We also interrogated the coherence of white matter tracts to assess the hypothesis that integration behavior would be related to the integrity of the underlying anatomical pathways. Consistent with our predictions, more coherent HPC-MPFC white matter structure was associated with better performance across participants. This HPC-MPFC circuit also interacted with content-sensitive visual cortex during learning and rest, consistent with reinstatement of prior knowledge to enable updating. These results show that the HPC-MPFC circuit supports on- and offline integration of new content into memory. PMID:26608407

  1. Increased neuronal firing in resting and sleep in areas of the macaque medial prefrontal cortex.

    Science.gov (United States)

    Gabbott, Paul L; Rolls, Edmund T

    2013-06-01

    The medial prefrontal cortex (mPFC) of humans and macaques is an integral part of the default mode network and is a brain region that shows increased activation in the resting state. A previous paper from our laboratory reported significantly increased firing rates of neurons in the macaque subgenual cingulate cortex, Brodmann area (BA) 25, during disengagement from a task and also during slow wave sleep [E.T. Rolls et al. (2003) J. Neurophysiology, 90, 134-142]. Here we report the finding that there are neurons in other areas of mPFC that also increase their firing rates during disengagement from a task, drowsiness and eye-closure. During the neurophysiological recording of single mPFC cells (n = 249) in BAs 9, 10, 13 m, 14c, 24b and especially pregenual area 32, populations of neurons were identified whose firing rates altered significantly with eye-closure compared with eye-opening. Three types of neuron were identified: Type 1 cells (28.1% of the total population) significantly increased (mean + 329%; P ≪ 0.01) their average firing rate with eye-closure, from 3.1 spikes/s when awake to 10.2 spikes/s when asleep; Type 2 cells (6.0%) significantly decreased (mean -68%; P areas of mPFC, implicated in the anterior default mode network, there is a substantial population of neurons that significantly increase their firing rates during periods of eye-closure. Such neurons may be part of an interconnected network of distributed brain regions that are more active during periods of relaxed wakefulness than during attention-demanding tasks. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  2. The medial prefrontal cortex is involved in spatial memory retrieval under partial-cue conditions.

    Science.gov (United States)

    Jo, Yong Sang; Park, Eun Hye; Kim, Il Hwan; Park, Soon Kwon; Kim, Hyun; Kim, Hyun Taek; Choi, June-Seek

    2007-12-05

    Brain circuits involved in pattern completion, or retrieval of memory from fragmented cues, were investigated. Using different versions of the Morris water maze, we explored the roles of the CA3 subregion of the hippocampus and the medial prefrontal cortex (mPFC) in spatial memory retrieval under various conditions. In a hidden platform task, both CA3 and mPFC lesions disrupted memory retrieval under partial-cue, but not under full-cue, conditions. For a delayed matching-to-place task, CA3 lesions produced a deficit in both forming and recalling spatial working memory regardless of extramaze cue conditions. In contrast, damage to mPFC impaired memory retrieval only when a fraction of cues was available. To corroborate the lesion study, we examined the expression of the immediate early gene c-fos in mPFC and the hippocampus. After training of spatial reference memory in full-cue conditions for 6 d, the same training procedure in the absence of all cues except one increased the number of Fos-immunoreactive cells in mPFC and CA3. Furthermore, mPFC inactivation with muscimol, a GABA agonist, blocked memory retrieval in the degraded-cue environment. However, mPFC-lesioned animals initially trained in a single-cue environment had no difficulty in retrieving spatial memory when the number of cues was increased, demonstrating that contextual change per se did not impair the behavioral performance of the mPFC-lesioned animals. Together, these findings strongly suggest that pattern completion requires interactions between mPFC and the hippocampus, in which mPFC plays significant roles in retrieving spatial information maintained in the hippocampus for efficient navigation.

  3. Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment.

    Science.gov (United States)

    van Harmelen, Anne-Laura; van Tol, Marie-José; Dalgleish, Tim; van der Wee, Nic J A; Veltman, Dick J; Aleman, André; Spinhoven, Philip; Penninx, Brenda W J H; Elzinga, Bernet M

    2014-12-01

    Childhood emotional maltreatment (CEM) has adverse effects on medial prefrontal cortex (mPFC) morphology, a structure that is crucial for cognitive functioning and (emotional) memory and which modulates the limbic system. In addition, CEM has been linked to amygdala hyperactivity during emotional face processing. However, no study has yet investigated the functional neural correlates of neutral and emotional memory in adults reporting CEM. Using functional magnetic resonance imaging, we investigated CEM-related differential activations in mPFC during the encoding and recognition of positive, negative and neutral words. The sample (N = 194) consisted of patients with depression and/or anxiety disorders and healthy controls (HC) reporting CEM (n = 96) and patients and HC reporting no abuse (n = 98). We found a consistent pattern of mPFC hypoactivation during encoding and recognition of positive, negative and neutral words in individuals reporting CEM. These results were not explained by psychopathology or severity of depression or anxiety symptoms, or by gender, level of neuroticism, parental psychopathology, negative life events, antidepressant use or decreased mPFC volume in the CEM group. These findings indicate mPFC hypoactivity in individuals reporting CEM during emotional and neutral memory encoding and recognition. Our findings suggest that CEM may increase individuals' risk to the development of psychopathology on differential levels of processing in the brain; blunted mPFC activation during higher order processing and enhanced amygdala activation during automatic/lower order emotion processing. These findings are vital in understanding the long-term consequences of CEM. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  4. The role of medial prefrontal cortex in extinction and reinstatement of alcohol-seeking in rats.

    Science.gov (United States)

    Willcocks, Andrea L; McNally, Gavan P

    2013-01-01

    The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer-seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug-seeking. Rather, they support the view that PL is important for retrieval of drug-seeking contingency information and that the use of contextual information is enhanced with IL manipulation. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  5. Effects of neonatal inferior prefrontal and medial temporal lesions on learning the rule for delayed nonmatching-to-sample.

    Science.gov (United States)

    Málková, L; Bachevalier, J; Webster, M; Mishkin, M

    2000-01-01

    The ability of rhesus monkeys to master the rule for delayed nonmatching-to-sample (DNMS) has a protracted ontogenetic development, reaching adult levels of proficiency around 4 to 5 years of age (Bachevalier, 1990). To test the possibility that this slow development could be due, at least in part, to immaturity of the prefrontal component of a temporo-prefrontal circuit important for DNMS rule learning (Kowalska, Bachevalier, & Mishkin, 1991; Weinstein, Saunders, & Mishkin, 1988), monkeys with neonatal lesions of the inferior prefrontal convexity were compared on DNMS with both normal controls and animals given neonatal lesions of the medial temporal lobe. Consistent with our previous results (Bachevalier & Mishkin, 1994; Málková, Mishkin, & Bachevalier, 1995), the neonatal medial temporal lesions led to marked impairment in rule learning (as well as in recognition memory with long delays and list lengths) at both 3 months and 2 years of age. By contrast, the neonatal inferior convexity lesions yielded no impairment in rule-learning at 3 months and only a mild impairment at 2 years, a finding that also contrasts sharply with the marked effects of the same lesion made in adulthood. This pattern of sparing closely resembles the one found earlier after neonatal lesions to the cortical visual area TE (Bachevalier & Mishkin, 1994; Málková et al., 1995). The functional sparing at 3 months probably reflects the fact that the temporo-prefrontal circuit is nonfunctional at this early age, resulting in a total dependency on medial temporal contributions to rule learning. With further development, however, this circuit begins to provide a supplementary route for learning.

  6. Effects of medial prefrontal cortex lesions in rats on the what-where-when memory of a fear conditioning event.

    Science.gov (United States)

    Li, Jay-Shake; Hsiao, Kun-Yuan; Chen, Wei-Min

    2011-03-17

    Previous animal studies have defined the ability to remember the details of what, where, and when of an event as an episodic-like memory to be used to model episodic memory in humans. Numerous findings indicate that the hippocampal-frontal cortical circuitry plays a major part in its neural mechanism. Researchers have intensively studied roles of diverse hippocampus sub-regions using animal models. By contrast, the impact of prefrontal cortex lesions on episodic-like memory in animals is still unknown. Here we show that Wistar rats with bilateral medial prefrontal cortex lesions failed to use the temporal-contextual information to retrieve memory of a fear-conditioning event, indicating impairments in their episodic-like memory. Subsequent experiments excluded alternative interpretations that the manipulation impaired the fear-conditioning per se, or interfered with the sensory preconditioning process. We concluded that damages in this area might impair temporal information processing, or interfere with integrating temporal and contextual elements of fear-conditioning events to form a conjunctive entity. These findings can help understand how the medial prefrontal cortex contributes to episodic-like memory. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Modulation of medial prefrontal cortical activity using in vivo recordings and optogenetics

    Directory of Open Access Journals (Sweden)

    Ji Guangchen

    2012-10-01

    Full Text Available Abstract Background The medial prefrontal cortex (mPFC serves major executive functions. mPFC output to subcortical brain areas such as the amygdala controls emotional processing and plays an important role in fear extinction. Impaired mPFC function correlates with extinction deficits in anxiety disorders such as PTSD and with cognitive decision-making deficits in neuropsychiatric disorders and persistent pain. Controlling mPFC output is a desirable therapeutic goal in neuropsychiatric disorders but functional differences of cell types (pyramidal cells and interneurons and regions (infralimbic and prelimbic represent a challenge. This electrophysiological study used optogenetics for the cell- and region-specific modulation of mPFC pyramidal output in the intact anesthetized animal. Results Extracellular single-unit recordings were made from infralimbic (IL pyramidal cells, IL interneurons and prelimbic (PL pyramidal cells 2–3 weeks after intra-IL injection of a viral vector encoding channel rhodopsin 2 (ChR2 under the control of the CaMKII promoter (rAAV5/CaMKIIa-ChR2(H134R-EYFP or a control vector that lacked the ChR2 sequence (rAAV5/CaMKIIa-EYFP. Optical stimulation with laser-generated blue light pulses delivered through an optical fiber to the IL increased spontaneous and evoked action potential firing of ChR2 expressing IL pyramidal cells but had no effect on IL interneurons that were distinguished from pyramidal cells based on their higher firing rate and shorter spike duration. Optical activation of IL pyramidal cells also inhibited PL pyramidal cells, suggesting that IL output controls PL output. The effects were light intensity-dependent and reversible. Confocal microscopy confirmed ChR2-EYFP or control vector expression in mPFC pyramidal cells but not in GABAergic cells. Conclusions The novelty of our study is the analysis of optogenetic effects on background and evoked activity of defined cell types in different mPFC regions. The

  8. Laminar and Cellular Distribution of Monoamine Receptors in Rat Medial Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Noemí Santana

    2017-09-01

    Full Text Available The prefrontal cortex (PFC is deeply involved in higher brain functions, many of which are altered in psychiatric conditions. The PFC exerts a top-down control of most cortical and subcortical areas through descending pathways and is densely innervated by axons emerging from the brainstem monoamine cell groups, namely, the dorsal and median raphe nuclei (DR and MnR, respectively, the ventral tegmental area and the locus coeruleus (LC. In turn, the activity of these cell groups is tightly controlled by afferent pathways arising from layer V PFC pyramidal neurons. The reciprocal connectivity between PFC and monoamine cell groups is of interest to study the pathophysiology and treatment of severe psychiatric disorders, such as major depression and schizophrenia, inasmuch as antidepressant and antipsychotic drugs target monoamine receptors/transporters expressed in these areas. Here we review previous reports examining the presence of monoamine receptors in pyramidal and GABAergic neurons of the PFC using double in situ hybridization. Additionally, we present new data on the quantitative layer distribution (layers I, II–III, V, and VI of monoamine receptor-expressing cells in the cingulate (Cg, prelimbic (PrL and infralimbic (IL subfields of the medial PFC (mPFC. The receptors examined include serotonin 5-HT1A, 5-HT2A, 5-HT2C, and 5-HT3, dopamine D1 and D2 receptors, and α1A-, α1B-, and α1D-adrenoceptors. With the exception of 5-HT3 receptors, selectively expressed by layers I–III GABA interneurons, the rest of monoamine receptors are widely expressed by pyramidal and GABAergic neurons in intermediate and deep layers of mPFC (5-HT2C receptors are also expressed in layer I. This complex distribution suggests that monoamines may modulate the communications between PFC and cortical/subcortical areas through the activation of receptors expressed by neurons in intermediate (e.g., 5-HT1A, 5-HT2A, α1D-adrenoceptors, dopamine D1 receptors and deep

  9. Mechanisms Underlying Serotonergic Excitation of Callosal Projection Neurons in the Mouse Medial Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Emily K. Stephens

    2018-01-01

    Full Text Available Serotonin (5-HT selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current, or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs. However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of serotonergic excitation in commissural/callosal (COM projection neurons, a subpopulation of pyramidal neurons that exhibits 2A-dependent excitation in response to 5-HT. In baseline conditions, 5-HT enhanced the rate of action potential generation in COM neurons experiencing suprathreshold somatic current injection. This serotonergic excitation was occluded by activation of muscarinic acetylcholine (ACh receptors, confirming that 5-HT acts via the same Gq-signaling cascades engaged by ACh. Like ACh, 5-HT promoted the generation of calcium-dependent ADPs following spike trains. However, calcium was not necessary for serotonergic excitation, as responses to 5-HT were enhanced (by >100%, rather than reduced, by chelation of intracellular calcium with 10 mM BAPTA. This suggests intracellular calcium negatively regulates additional ionic conductances gated by 2A receptors. Removal of extracellular calcium had no effect when intracellular calcium signaling was intact, but suppressed 5-HT response amplitudes, by about 50%, when BAPTA was included in patch pipettes. This suggests that 2A excitation involves activation of a non-specific cation conductance that is both calcium-sensitive and calcium-permeable. M-current suppression was found to be a third

  10. Deactivation of medial prefrontal and posterior cingulate cortex in anxiety disorders

    International Nuclear Information System (INIS)

    Zhao Xiaohu; Wang Peijun; Dong Ningxin; Li Chunbo; Wu Wenyuan; Hu Zhenghui; Tang Xiaowei

    2007-01-01

    Objective: We used blood oxygenation level dependent-functional MR imaging (BOLD- fMRI) to explore the characteristics of deactivation patterns in patients with anxiety disorders and the underlying neural mechanism of this disease. Methods: Ten patients and ten healthy controls participated the experiments. All subjects performed the trait portion of the State-Trait anxiety Inventory (STAI-T) prior to the fMRI scans. The subjects underwent noninvasive functional magnetic resonance imaging while listening actively to emotionally neutral words alternating with no words (experiment 1) and threat related-words alternating with emotionally neutral words (experiment2). During fMRI scanning, subjects were instructed to closely listen to each stimuli word and to silently make a judgment of the word's valence. Data were analyzed with statistical parametric mapping (SPM 99). Individual and group analysis were conducted. Results: Mean STAI-T score was significantly higher for patients group than that of controls (58 ± 8 for patients group and 33 ± 5 for controls, t=8.3, P<0.01). Our fMRI data revealed sets of deactivation brain regions in Experiment for patients and healthy controls, however, the deactivation can be found in experiment 2 only for patients. Interestingly, all the observed deactivation patterns were similar. The related areas compromise medial prefrontal cortex(BA 10, BA 24/32), posterior cingulate (BA 31/30) and Bilateral inferior parietal cortex (MPFC) (BA 39/40), which nearly overlapping with the organized default model network. Further more, the mean t values in the MPFC area (BA 24/32) was significantly higher for control group than that of patient (5.1 controls and 4.2 for patients, t=4.8, P=0.006), conversely, the mean t values in the posterior cingulate cortex(PCC) area was significantly higher for patients l than that of controls (4.9 controls and 5.8 for patients, t=2.4, P=0.026). Conclusion: Our observations suggest that the default model network

  11. Medial prefrontal cortex involvement in the expression of extinction and ABA renewal of instrumental behavior for a food reinforcer.

    Science.gov (United States)

    Eddy, Meghan C; Todd, Travis P; Bouton, Mark E; Green, John T

    2016-02-01

    Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of

  12. The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal-thalamus-hippocampus network.

    Science.gov (United States)

    Thielen, Jan-Willem; Hong, Donghyun; Rohani Rankouhi, Seyedmorteza; Wiltfang, Jens; Fernández, Guillén; Norris, David G; Tendolkar, Indira

    2018-06-01

    The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long-term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans. By using MRS, we measured mPFC γ-aminobutyric acid (GABA) and glutamate/glutamine (GLx) concentrations before and after volunteers memorized face-name association. We demonstrate that mPFC GLx but not GABA levels increased during the memory task, which appeared to be related to memory performance. Regarding functional connectivity, we used the subsequent memory paradigm and found that the GLx increase was associated with stronger mPFC connectivity to thalamus and hippocampus for associations subsequently recognized with high confidence as opposed to subsequently recognized with low confidence/forgotten. Taken together, we provide new evidence for an mPFC involvement in episodic memory by showing a memory-related increase in mPFC excitatory neurotransmitter levels that was associated with better memory and stronger memory-related functional connectivity in a medial prefrontal-thalamus-hippocampus network. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  13. The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

    Science.gov (United States)

    Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

    2015-01-01

    The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

  14. The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    2007-01-01

    Full Text Available Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

  15. Activity in inferior parietal and medial prefrontal cortex signals the accumulation of evidence in a probability learning task.

    Directory of Open Access Journals (Sweden)

    Mathieu d'Acremont

    Full Text Available In an uncertain environment, probabilities are key to predicting future events and making adaptive choices. However, little is known about how humans learn such probabilities and where and how they are encoded in the brain, especially when they concern more than two outcomes. During functional magnetic resonance imaging (fMRI, young adults learned the probabilities of uncertain stimuli through repetitive sampling. Stimuli represented payoffs and participants had to predict their occurrence to maximize their earnings. Choices indicated loss and risk aversion but unbiased estimation of probabilities. BOLD response in medial prefrontal cortex and angular gyri increased linearly with the probability of the currently observed stimulus, untainted by its value. Connectivity analyses during rest and task revealed that these regions belonged to the default mode network. The activation of past outcomes in memory is evoked as a possible mechanism to explain the engagement of the default mode network in probability learning. A BOLD response relating to value was detected only at decision time, mainly in striatum. It is concluded that activity in inferior parietal and medial prefrontal cortex reflects the amount of evidence accumulated in favor of competing and uncertain outcomes.

  16. Partial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Tariq Waseem Chohan

    2014-09-01

    Full Text Available Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1 and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET and wild-type (WT mice using [3H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV and the dentate gyrus (DG of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex.

  17. Inducible nitric oxide inhibitors block NMDA antagonist-stimulated motoric behaviors and medial prefrontal cortical glutamate efflux

    Directory of Open Access Journals (Sweden)

    Hadley C Bergstrom

    2015-12-01

    Full Text Available Nitric oxide (NO plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS for studying the neurobehavioral effects of noncompetitive NMDA-antagonist stimulants such as dizocilpine (MK-801 and phencyclidine (PCP. This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS aminoguanidine (AG and (--epigallocatechin-3-gallate (EGCG in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG or vehicle prior to receiving NMDA antagonists MK-801, PCP or a conventional psychostimulant (cocaine and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated medial prefrontal cortical glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in green tea and chocolate may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia.

  18. Memory retrieval in response to partial cues requires NMDA receptor-dependent neurotransmission in the medial prefrontal cortex.

    Science.gov (United States)

    Jo, Yong Sang; Choi, June-Seek

    2014-03-01

    The medial prefrontal cortex (mPFC) has been suggested to play a crucial role in retrieving detailed contextual information about a previous learning episode in response to a single retrieval cue. However, few studies investigated the neurochemical mechanisms that mediate the prefrontal retrieval process. In the current study, we examined whether N-methyl-D-aspartate receptors (NMDARs) in the mPFC were necessary for retrieval of a well-learned spatial location on the basis of partial or degraded spatial cues. Rats were initially trained to find a hidden platform in the Morris water maze using four extramaze cues in the surrounding environment. Their retrieval performance was subsequently tested under different cue conditions. Infusions of DL-2-amino-5-phosphonovaleric acid (APV), a NMDAR antagonist, significantly disrupted memory retrieval when three of the original cues were removed. By contrast, APV injections into the mPFC did not affect animals' retrieval performance when the original cues were presented or when three novels landmarks were added alongside the original cues. These results indicate that prefrontal NMDARs are required for memory retrieval when allocentric spatial information is degraded. NMDAR-dependent neurotransmission in the mPFC may facilitate an active retrieval process to reactivate complete contextual representations associated with partial retrieval cues. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Lateral Orbitofrontal Cortical Modulation on the Medial Prefrontal Cortex-Amygdala Pathway: Differential Regulation of Intra-Amygdala GABAA and GABAB Receptors.

    Science.gov (United States)

    Chang, Chun-Hui

    2017-07-01

    The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex and lateral orbitofrontal cortex. Earlier studies have shown that lateral orbitofrontal cortex activation exerts an inhibitory gating on medial prefrontal cortex-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process. In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to medial prefrontal cortex activation, tested lateral orbitofrontal cortex gating at different delays (lateral orbitofrontal cortex-medial prefrontal cortex delays: 25, 50, 100, 250, 500, and 1000 milliseconds), and examined differential contribution of GABAA and GABAB receptors with iontophoresis. Relative to baseline, lateral orbitofrontal cortex stimulation exerted an inhibitory modulatory gating on the medial prefrontal cortex-amygdala pathway and was effective up to a long delay of 500 ms (long-delay latencies at 100, 250, and 500 milliseconds). Moreover, blockade of intra-amygdala GABAA receptors with bicuculline abolished the lateral orbitofrontal cortex inhibitory gating at both short- (25 milliseconds) and long-delay (100 milliseconds) intervals, while blockade of GABAB receptors with saclofen reversed the inhibitory gating at long delay (100 milliseconds) only. Among the majority of the neurons examined (8 of 9), inactivation of either GABAA or GABAB receptors during baseline did not change evoked probability per se, suggesting that local feed-forward inhibitory mechanism is pathway specific. Our results suggest that the effect of lateral orbitofrontal cortex inhibitory modulatory gating was effective up to 500 milliseconds and that intra-amygdala GABAA and GABAB receptors differentially modulate the short- and long-delay lateral orbitofrontal cortex inhibitory gating on the medial prefrontal cortex-amygdala pathway. © The Author 2017

  20. Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex

    Science.gov (United States)

    Aoyama, Yuki; Toriumi, Kazuya; Mouri, Akihiro; Hattori, Tomoya; Ueda, Eriko; Shimato, Akane; Sakakibara, Nami; Soh, Yuka; Mamiya, Takayoshi; Nagai, Taku; Kim, Hyoung-Chun; Hiramatsu, Masayuki; Nabeshima, Toshitaka; Yamada, Kiyofumi

    2016-01-01

    Cigarette smoking during pregnancy is associated with various disabilities in the offspring such as attention deficit/hyperactivity disorder, learning disabilities, and persistent anxiety. We have reported that nicotine exposure in female mice during pregnancy, in particular from embryonic day 14 (E14) to postnatal day 0 (P0), induces long-lasting behavioral deficits in offspring. However, the mechanism by which prenatal nicotine exposure (PNE) affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that PNE disrupted the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and subventricular zones. In addition, using a cumulative 5-bromo-2′-deoxyuridine labeling assay, we evaluated the rate of cell cycle progression causing the impairment of neuronal progenitor proliferation, and uncovered anomalous cell cycle kinetics in mice with PNE. Accordingly, the density of glutamatergic neurons in the medial prefrontal cortex (medial PFC) was reduced, implying glutamatergic dysregulation. Mice with PNE exhibited behavioral impairments in attentional function and behavioral flexibility in adulthood, and the deficits were ameliorated by microinjection of D-cycloserine into the PFC. Collectively, our findings suggest that PNE affects the proliferation and maturation of progenitor cells to glutamatergic neuron during neurodevelopment in the medial PFC, which may be associated with cognitive deficits in the offspring. PMID:26105135

  1. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure

    DEFF Research Database (Denmark)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo

    2017-01-01

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT2A receptor (5-HT2AR) dependent. Here, we further investigated how blockade of 5-HT2ARs in mice exposed to a novel open-field...... of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5 mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time...... spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin...

  2. Medial prefrontal aberrations in major depressive disorder revealed by cytoarchitectonically informed voxel-based morphometry

    Science.gov (United States)

    Bludau, Sebastian; Bzdok, Danilo; Gruber, Oliver; Kohn, Nils; Riedl, Valentin; Sorg, Christian; Palomero-Gallagher, Nicola; Müller, Veronika I.; Hoffstaedter, Felix; Amunts, Katrin; Eickhoff, Simon B.

    2017-01-01

    Objective The heterogeneous human frontal pole has been identified as a node in the dysfunctional network of major depressive disorder. The contribution of the medial (socio-affective) versus lateral (cognitive) frontal pole to major depression pathogenesis is currently unclear. The present study performs morphometric comparison of the microstructurally informed subdivisions of human frontal pole between depressed patients and controls using both uni- and multivariate statistics. Methods Multi-site voxel- and region-based morphometric MRI analysis of 73 depressed patients and 73 matched controls without psychiatric history. Frontal pole volume was first compared between depressed patients and controls by subdivision-wise classical morphometric analysis. In a second approach, frontal pole volume was compared by subdivision-naive multivariate searchlight analysis based on support vector machines. Results Subdivision-wise morphometric analysis found a significantly smaller medial frontal pole in depressed patients with a negative correlation of disease severity and duration. Histologically uninformed multivariate voxel-wise statistics provided converging evidence for structural aberrations specific to the microstructurally defined medial area of the frontal pole in depressed patients. Conclusions Across disparate methods, we demonstrated subregion specificity in the left medial frontal pole volume in depressed patients. Indeed, the frontal pole was shown to structurally and functionally connect to other key regions in major depression pathology like the anterior cingulate cortex and the amygdala via the uncinate fasciculus. Present and previous findings consolidate the left medial portion of the frontal pole as particularly altered in major depression. PMID:26621569

  3. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure.

    Science.gov (United States)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo; Rydbirk, Rasmus; Olesen, Mikkel Vestergaard; Hay-Schmidt, Anders; Pakkenberg, Bente; Aznar, Susana

    2017-05-30

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT 2A receptor (5-HT 2A R) dependent. Here, we further investigated how blockade of 5-HT 2A Rs in mice exposed to a novel open-field arena affects medial PFC activation and basolateral amygdala (BLA) reactivity. We used c-Fos immunoreactivity (IR) as a marker of neuronal activation and stereological quantification for obtaining the total number of c-Fos-IR neurons as a measure of regional activation. We further examined the impact of 5-HT 2A R blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin-treated animals, upholding its involvement in modulating averseness. Ketanserin did not affect the number of activated striatal-projecting BLA neurons (measured by number of Cholera Toxin b (CTb) retrograde labelled neurons also being c-Fos-IR) following CTb injection in the ventral striatum. These results support a role of 5-HT 2A R activation in modulating mPFC and BLA activation during exposure to a novel environment, which may be interrelated. Conversely, 5-HT 2A R blockade does not seem to affect the amygdala-striatal projection. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The Medial Prefrontal Cortex Is Critical for Memory Retrieval and Resolving Interference

    Science.gov (United States)

    Peters, Gregory J.; David, Christopher N.; Marcus, Madison D.; Smith, David M.

    2013-01-01

    The prefrontal cortex (PFC) is known to be critically involved in strategy switching, attentional set shifting, and inhibition of prepotent responses. A central feature of this kind of behavioral flexibility is the ability to resolve conflicting response tendencies, suggesting a general role of the PFC in resolving interference. If so, the PFC…

  5. Lateral, Not Medial, Prefrontal Cortex Contributes to Punishment and Aversive Instrumental Learning

    Science.gov (United States)

    Jean-Richard-dit-Bressel , Philip; McNally, Gavan P.

    2016-01-01

    Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral…

  6. Nicotinic acetylcholine receptor β2-subunits in the medial prefrontal cortex control attention

    NARCIS (Netherlands)

    Guillem, K.; Bloem, B.; Poorthuis, R.B.; Loos, M.; Smit, A.B.; Maskos, U.; Spijker, S.; Mansvelder, H.D.

    2011-01-01

    More than one-third of all people are estimated to experience mild to severe cognitive impairment as they age. Acetylcholine (ACh) levels in the brain diminish with aging, and nicotinic ACh receptor (nAChR) stimulation is known to enhance cognitive performance. The prefrontal cortex (PFC) is

  7. Anticipatory activity in rat medial prefrontal cortex during a working memory task

    Institute of Scientific and Technical Information of China (English)

    Wenwen Bai; Tiaotiao Liu; Hu Yi; Shuangyan Li; Xin Tian

    2012-01-01

    Objective Working memory is a key cognitive function in which the prefrontal cortex plays a crucial role.This study aimed to show the firing patterns of a neuronal population in the prefrontal cortex of the rat in a working memory task and to explore how a neuronal ensemble encodes a working memory event.Methods Sprague-Dawley rats were trained in a Y-maze until they reached an 80% correct rate in a working memory task.Then a 16-channel microelectrode array was implanted in the prefrontal cortex.After recovery,neuronal population activity was recorded during the task,using the Cerebus data-acquisition system.Spatio-temporal trains of action potentials were obtained from the original neuronal population signals.Results During the Y-maze working memory task,some neurons showed significantly increased firing rates and evident neuronal ensemble activity.Moreover,the anticipatory activity was associated with the delayed alternate choice of the upcoming movement.In correct trials,the averaged pre-event firing rate (10.86 ± 1.82 spikes/bin) was higher than the post-event rate (8.17 ± 1.15 spikes/bin) (P <0.05).However,in incorrect trials,the rates did not differ.Conclusion The results indicate that the anticipatory activity of a neuronal ensemble in the prefrontal cortex may play a role in encoding working memory events.

  8. Inactivation of the dorsal hippocampus or the medial prefrontal cortex impairs retrieval but has differential effect on spatial memory reconsolidation.

    Science.gov (United States)

    Rossato, Janine I; Köhler, Cristiano A; Radiske, Andressa; Bevilaqua, Lia R M; Cammarota, Martín

    2015-11-01

    Active memories can incorporate new information through reconsolidation. However, the notion that memory retrieval is necessary for reconsolidation has been recently challenged. Non-reinforced retrieval induces hippocampus and medial prefrontal cortex (mPFC)-dependent reconsolidation of spatial memory in the Morris water maze (MWM). We found that the effect of protein synthesis inhibition on this process is abolished when retrieval of the learned spatial preference is hindered through mPFC inactivation but not when it is blocked by deactivation of dorsal CA1. Our results do not fully agree with the hypothesis that retrieval is unneeded for reconsolidation. Instead, they support the idea that a hierarchic interaction between the hippocampus and the mPFC controls spatial memory in the MWM, and indicate that this cortex is sufficient to retrieve the information essential to reconsolidate the spatial memory trace, even when the hippocampus is inactivated. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

    Science.gov (United States)

    Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

    2016-10-01

    Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

  10. Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Maximiliano Rapanelli

    Full Text Available Circuit modification associated with learning and memory involves multiple events, including the addition and remotion of newborn cells trough adulthood. Adult neurogenesis and gliogenesis were mainly described in models of voluntary exercise, enriched environments, spatial learning and memory task; nevertheless, it is unknown whether it is a common mechanism among different learning paradigms, like reward dependent tasks. Therefore, we evaluated cell proliferation, neurogenesis, astrogliogenesis, survival and neuronal maturation in the medial prefrontal cortex (mPFC and the hippocampus (HIPP during learning an operant conditioning task. This was performed by using endogenous markers of cell proliferation, and a bromodeoxiuridine (BrdU injection schedule in two different phases of learning. Learning an operant conditioning is divided in two phases: a first phase when animals were considered incompletely trained (IT, animals that were learning the task when they performed between 50% and 65% of the responses, and a second phase when animals were considered trained (Tr, animals that completely learned the task when they reached 100% of the responses with a latency time lower than 5 seconds. We found that learning an operant conditioning task promoted cell proliferation in both phases of learning in the mPFC and HIPP. Additionally, the results presented showed that astrogliogenesis was induced in the medial prefrontal cortex (mPFC in both phases, however, the first phase promoted survival of these new born astrocytes. On the other hand, an increased number of new born immature neurons was observed in the HIPP only in the first phase of learning, whereas, decreased values were observed in the second phase. Finally, we found that neuronal maturation was induced only during the first phase. This study shows for the first time that learning a reward-dependent task, like the operant conditioning, promotes neurogenesis, astrogliogenesis, survival and

  11. Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Hauser, Tobias U; Iannaccone, Reto; Ball, Juliane; Mathys, Christoph; Brandeis, Daniel; Walitza, Susanne; Brem, Silvia

    2014-10-01

    Attention-deficit/hyperactivity disorder (ADHD) has been associated with deficient decision making and learning. Models of ADHD have suggested that these deficits could be caused by impaired reward prediction errors (RPEs). Reward prediction errors are signals that indicate violations of expectations and are known to be encoded by the dopaminergic system. However, the precise learning and decision-making deficits and their neurobiological correlates in ADHD are not well known. To determine the impaired decision-making and learning mechanisms in juvenile ADHD using advanced computational models, as well as the related neural RPE processes using multimodal neuroimaging. Twenty adolescents with ADHD and 20 healthy adolescents serving as controls (aged 12-16 years) were examined using a probabilistic reversal learning task while simultaneous functional magnetic resonance imaging and electroencephalogram were recorded. Learning and decision making were investigated by contrasting a hierarchical Bayesian model with an advanced reinforcement learning model and by comparing the model parameters. The neural correlates of RPEs were studied in functional magnetic resonance imaging and electroencephalogram. Adolescents with ADHD showed more simplistic learning as reflected by the reinforcement learning model (exceedance probability, Px = .92) and had increased exploratory behavior compared with healthy controls (mean [SD] decision steepness parameter β: ADHD, 4.83 [2.97]; controls, 6.04 [2.53]; P = .02). The functional magnetic resonance imaging analysis revealed impaired RPE processing in the medial prefrontal cortex during cue as well as during outcome presentation (P decision making and learning mechanisms in adolescents with ADHD are driven by impaired RPE processing in the medial prefrontal cortex. This novel, combined approach furthers the understanding of the pathomechanisms in ADHD and may advance treatment strategies.

  12. Regionally Selective Requirement for D[subscript 1]/D[subscript 5] Dopaminergic Neurotransmission in the Medial Prefrontal Cortex in Object-in-Place Associative Recognition Memory

    Science.gov (United States)

    Savalli, Giorgia; Bashir, Zafar I.; Warburton, E. Clea

    2015-01-01

    Object-in-place (OiP) memory is critical for remembering the location in which an object was last encountered and depends conjointly on the medial prefrontal cortex, perirhinal cortex, and hippocampus. Here we examined the role of dopamine D[subscript 1]/D[subscript 5] receptor neurotransmission within these brain regions for OiP memory. Bilateral…

  13. The flexible use of multiple cue relationships in spatial navigation : A comparison of water maze performance following hippocampal, medial septal, prefrontal cortex, or posterior parietal cortex lesions

    NARCIS (Netherlands)

    Compton, DM; Griffith, HR; McDaniel, WF; Foster, RA; Davis, BK

    Rats prepared with lesions of the prefrontal cortex, posterior parietal cortex, hippocampus, or medial septal area were tested for acquisition of a number of variations of the open-field water maze using a version of place learning assessment described by Eichenbaum, Stewart, and Morris (1991).

  14. Protein malnutrition during gestation and early life decreases neuronal size in the medial prefrontal cortex of post-pubertal rats

    Directory of Open Access Journals (Sweden)

    Roelf J. Cruz-Rizzolo

    2017-12-01

    Full Text Available Retrospective studies in human populations indicate that protein deprivation during pregnancy and early life (early protein malnutrition, EPM is associated with cognitive impairments, learning disabilities and may represent a risk factor for the late onset of some psychiatric disorders, fundamentally schizophrenia, a condition where the prefrontal cortex plays an important role. The purpose of this study was to analyze whether EPM affects structural aspects of the rat medial prefrontal cortex (mPFC, such as cortical volume, neuronal density and neuronal soma size, which seem altered in patients with schizophrenia. For this, a rat model of EPM (5% casein from conception to postnatal day 60 was adopted and the rat mPFC volume, total number of neurons and average neuronal volume were evaluated on postnatal day 60 (post-pubertal animals by histo- and immunohistochemical techniques using unbiased stereological analysis. EPM did not alter the number of NeuN+ neurons in the rat mPFC. However, a very significant decrease in mPFC volume and average neuronal size was observed in malnourished rats. Although the present study does not establish causal relationships between malnutrition and schizophrenia, our results may indicate a similar structural phenomenon in these two situations.

  15. Cell-Type Specific Changes in Glial Morphology and Glucocorticoid Expression During Stress and Aging in the Medial Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Thomas E. Chan

    2018-05-01

    Full Text Available Repeated exposure to stressors is known to produce large-scale remodeling of neurons within the prefrontal cortex (PFC. Recent work suggests stress-related forms of structural plasticity can interact with aging to drive distinct patterns of pyramidal cell morphological changes. However, little is known about how other cellular components within PFC might be affected by these challenges. Here, we examined the effects of stress exposure and aging on medial prefrontal cortical glial subpopulations. Interestingly, we found no changes in glial morphology with stress exposure but a profound morphological change with aging. Furthermore, we found an upregulation of non-nuclear glucocorticoid receptors (GR with aging, while nuclear levels remained largely unaffected. Both changes are selective for microglia, with no stress or aging effect found in astrocytes. Lastly, we show that the changes found within microglia inversely correlated with the density of dendritic spines on layer III pyramidal cells. These findings suggest microglia play a selective role in synaptic health within the aging brain.

  16. Single unit activity in the medial prefrontal cortex during Pavlovian heart rate conditioning: Effects of peripheral autonomic blockade.

    Science.gov (United States)

    Powell, D A; Ginsberg, Jay P

    2005-11-01

    Electrical activity was recorded from single neurons in the medial prefrontal cortex of rabbits during differential Pavlovian heart rate (HR) conditioning. A heterogeneous population of cells were found, some of which showed CS-evoked increases and others CS-evoked decreases in discharge, while some cells were biphasic. A subset of cells also showed trial-related changes in discharge that were related to acquisition of the HR discrimination between the reinforced CS+ and non-reinforced CS-. Administration of the peripheral cholinergic antagonist, methylscopolamine, and the andrenergic antagonist, atenolol, either increased or decreased maintained baseline activity of many cells, but had little or no effect on the CS-evoked activity of these cells. Waveform changes also did not result from administration of these drugs. This finding suggests that CS-evoked mPFC activity is not being driven by cardiac afferent input to CNS cardiac control centers. Previous studies have shown that ibotenic acid lesions of this area greatly decreases the magnitude of decelerative heart rate conditioned responses; the latter finding, plus the results of the present study, suggest that processing of CS/US contingencies by the prefrontal cortex contributes to the acquisition of autonomic changes during Pavlovian conditioning.

  17. Medial prefrontal cortex lesions impair decision-making on a rodent gambling task: reversal by D1 receptor antagonist administration.

    Science.gov (United States)

    Paine, Tracie A; Asinof, Samuel K; Diehl, Geoffrey W; Frackman, Anna; Leffler, Joseph

    2013-04-15

    Decision-making is a complex cognitive process that is impaired in a number of psychiatric disorders. In the laboratory, decision-making is frequently assessed using "gambling" tasks that are designed to simulate real-life decisions in terms of uncertainty, reward and punishment. Here, we investigate whether lesions of the medial prefrontal cortex (PFC) cause impairments in decision-making using a rodent gambling task (rGT). In this task, rats have to decide between 1 of 4 possible options: 2 options are considered "advantageous" and lead to greater net rewards (food pellets) than the other 2 "disadvantageous" options. Once rats attained stable levels of performance on the rGT they underwent sham or excitoxic lesions of the medial PFC and were allowed to recover for 1 week. Following recovery, rats were retrained for 5 days and then the effects of a dopamine D1-like receptor antagonist (SCH23390) or a D2-like receptor antagonist (haloperidol) on performance were assessed. Lesioned rats exhibited impaired decision-making: they made fewer advantageous choices and chose the most optimal choice less frequently than did sham-operated rats. Administration of SCH23390 (0.03 mg/kg), but not haloperidol (0.015-0.03 mg/kg) attenuated the lesion-induced decision-making deficit. These results indicate that the medial PFC is important for decision-making and that excessive signaling at D1 receptors may contribute to decision-making impairments. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Effects of disrupting medial prefrontal cortex GABA transmission on decision-making in a rodent gambling task.

    Science.gov (United States)

    Paine, T A; O'Hara, A; Plaut, B; Lowes, D C

    2015-05-01

    Decision-making is a complex cognitive process that is mediated, in part, by subregions of the medial prefrontal cortex (PFC). Decision-making is impaired in a number of psychiatric conditions including schizophrenia. Notably, people with schizophrenia exhibit reductions in GABA function in the same PFC areas that are implicated in decision-making. For example, expression of the GABA-synthesizing enzyme GAD67 is reduced in the dorsolateral PFC of people with schizophrenia. The goal of this experiment was to determine whether disrupting cortical GABA transmission impairs decision-making using a rodent gambling task (rGT). Rats were trained on the rGT until they reached stable performance and then were implanted with guide cannulae aimed at the medial PFC. Following recovery, the effects of intra-PFC infusions of the GABAA receptor antagonist bicuculline methiodide (BMI) or the GABA synthesis inhibitor L-allylglycine (LAG) on performance on the rGT were assessed. Intracortical infusions of BMI (25 ng/μl/side), but not LAG (10 μg/μl/side), altered decision-making. Following BMI infusions, rats made fewer advantageous choices. Follow-up experiments suggested that the change in decision-making was due to a change in the sensitivity to the punishments, rather than a change in the sensitivity to reward magnitudes, associated with each outcome. LAG infusions increased premature responding, a measure of response inhibition, but did not affect decision-making. Blocking GABAA receptors, but not inhibiting cortical GABA synthesis, within the medial PFC affects decision-making in the rGT. These data provide proof-of-concept evidence that disruptions in GABA transmission can contribute to the decision-making deficits in schizophrenia.

  19. THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

    Science.gov (United States)

    Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

    2018-03-01

    Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

  20. Nonlinear responses within the medial prefrontal cortex reveal when specific implicit information influences economic decision making.

    Science.gov (United States)

    Deppe, Michael; Schwindt, Wolfram; Kugel, Harald; Plassmann, Hilke; Kenning, Peter

    2005-04-01

    The authors used functional magnetic resonance imaging (fMRI) to investigate how individual economic decisions are influenced by implicit memory contributions. Twenty-two participants were asked to make binary decisions between different brands of sensorily nearly undistinguishable consumer goods. Changes of brain activity comparing decisions in the presence or absence of a specific target brand were detected by fMRI. Only when the tar get brand was the participant's favorite one did the authors find reduced activation in the dorsolateral prefrontal, posterior parietal, and occipital cortices and the left premotor area (Brodmann areas [BA] 9, 46, 7/19, and 6). Simultaneously, activity was increased in the inferior precuneus and posterior cingulate (BA 7), right superior frontal gyrus (BA 10), right supramarginal gyrus (BA 40), and, most pronounced, in the ventromedial prefrontal cortex (BA 10). For products mainly distinguishable by brand information, the authors revealed a nonlinear winner-take-all effect for a participant's favorite brand characterized, on one hand, by reduced activation in brain areas associated with working memory and reasoning and, on the other hand, increased activation in areas involved in processing of emotions and self-reflections during decision making.

  1. Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources

    Science.gov (United States)

    Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

    2014-01-01

    Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts—for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts. PMID:23460073

  2. Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources.

    Science.gov (United States)

    Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

    2014-05-01

    Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts--for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts.

  3. Different involvement of medial prefrontal cortex and dorso-lateral striatum in automatic and controlled processing of a future conditioned stimulus.

    Science.gov (United States)

    Pérez-Díaz, Francisco; Díaz, Estrella; Sánchez, Natividad; Vargas, Juan Pedro; Pearce, John M; López, Juan Carlos

    2017-01-01

    Recent studies support the idea that stimulus processing in latent inhibition can vary during the course of preexposure. Controlled attentional mechanisms are said to be important in the early stages of preexposure, while in later stages animals adopt automatic processing of the stimulus to be used for conditioning. Given this distinction, it is possible that both types of processing are governed by different neural systems, affecting differentially the retrieval of information about the stimulus. In the present study we tested if a lesion to the dorso-lateral striatum or to the medial prefrontal cortex has a selective effect on exposure to the future conditioned stimulus (CS). With this aim, animals received different amounts of exposure to the future CS. The results showed that a lesion to the medial prefrontal cortex enhanced latent inhibition in animals receiving limited preexposure to the CS, but had no effect in animals receiving extended preexposure to the CS. The lesion of the dorso-lateral striatum produced a decrease in latent inhibition, but only in animals with an extended exposure to the future conditioned stimulus. These results suggest that the dorsal striatum and medial prefrontal cortex play essential roles in controlled and automatic processes. Automatic attentional processes appear to be impaired by a lesion to the dorso-lateral striatum and facilitated by a lesion to the prefrontal cortex.

  4. Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study.

    Science.gov (United States)

    Abend, Rany; Sar-El, Roy; Gonen, Tal; Jalon, Itamar; Vaisvaser, Sharon; Bar-Haim, Yair; Hendler, Talma

    2018-05-09

    Implicit regulation of emotions involves medial-prefrontal cortex (mPFC) regions exerting regulatory control over limbic structures. Diminished regulation relates to aberrant mPFC functionality and psychopathology. Establishing means of modulating mPFC functionality could benefit research on emotion and its dysregulation. Here, we tested the capacity of transcranial direct current stimulation (tDCS) targeting mPFC to modulate subjective emotional states by facilitating implicit emotion regulation. Stimulation was applied concurrently with functional magnetic resonance imaging to validate its neurobehavioral effect. Sixteen participants were each scanned twice, counterbalancing active and sham tDCS application, while undergoing negative mood induction (clips featuring negative vs. neutral contents). Effects of stimulation on emotional experience were assessed using subjective and neural measures. Subjectively, active stimulation led to significant reduction in reported intensity of experienced emotions to negatively valenced (p = 0.005) clips but not to neutral clips (p > 0.99). Active stimulation further mitigated a rise in stress levels from pre- to post-induction (sham: p = 0.004; active: p = 0.15). Neurally, stimulation increased activation in mPFC regions associated with implicit emotion regulation (ventromedial-prefrontal cortex; subgenual anterior-cingulate cortex, sgACC), and in ventral striatum, a core limbic structure (all ps  0.64, ps < 0.018), suggesting individual differences in stimulation responsivity. Results of this study indicate the potential capacity of tDCS to facilitate brain activation in mPFC regions underlying implicit regulation of emotion and accordingly modulate subjective emotional experiences. © 2018 International Neuromodulation Society.

  5. Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder.

    Science.gov (United States)

    Morey, Rajendra A; Haswell, Courtney C; Hooper, Stephen R; De Bellis, Michael D

    2016-02-01

    Posttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment.

  6. Medial prefrontal cortex: genes linked to bipolar disorder and schizophrenia have altered expression in the highly social maternal phenotype

    Directory of Open Access Journals (Sweden)

    Brian E Eisinger

    2014-04-01

    Full Text Available The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for postpartum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for postpartum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC, a region implicated in both maternal behavior and psychiatric disorders. Postpartum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET, we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets and bipolar disorder (BPD, 3 of 3 sets. In contrast to previous studies of maternal lateral septum and medial preoptic area, enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets. Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7, glutamate metabotropic receptor 3 (Grm3, platelet derived growth factor, beta polypeptide (Pdgfrb, and nuclear receptor subfamily 1, group D, member 1 (Nr1d1. RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1 and proenkephalin (Penk. Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for postpartum psychosis with aspects of schizophrenia and BPD.

  7. Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Diana Martinez

    2018-03-01

    Full Text Available BackgroundPrevious studies have shown that repetitive transcranial magnetic stimulation (rTMS to the dorsolateral prefrontal cortex may serve as a potential treatment for cocaine use disorder (CUD, which remains a public health problem that is refractory to treatment. The goal of this pilot study was to investigate the effect of rTMS on cocaine self-administration in the laboratory. In the self-administration sessions, CUD participants chose between cocaine and an alternative reinforcer (money in order to directly measure cocaine-seeking behavior. The rTMS was delivered with the H7 coil, which provides stimulation to the medial prefrontal cortex (mPFC and anterior cingulate cortex (ACC. These brain regions were targeted based on previous imaging studies demonstrating alterations in their activation and connectivity in CUD.MethodsVolunteers with CUD were admitted to an inpatient unit for the entire study and assigned to one of three rTMS groups: high frequency (10 Hz, low frequency (1 Hz, and sham. Six participants were included in each group and the rTMS was delivered on weekdays for 3 weeks. The cocaine self-administration sessions were performed at three time points: at baseline (pre-TMS, session 1, after 4 days of rTMS (session 2, and after 13 days of rTMS (session 3. During each self-administration session, the outcome measure was the number of choices for cocaine.ResultsThe results showed a significant group by time effect (p = 0.02, where the choices for cocaine decreased between sessions 2 and 3 in the high frequency group. There was no effect of rTMS on cocaine self-administration in the low frequency or sham groups.ConclusionTaken in the context of the existing literature, these results contribute to the data showing that high frequency rTMS to the prefrontal cortex may serve as a potential treatment for CUD.

  8. Posttraumatic stress disorder: the role of medial prefrontal cortex and amygdala.

    Science.gov (United States)

    Koenigs, Michael; Grafman, Jordan

    2009-10-01

    Posttraumatic stress disorder (PTSD) is characterized by recurrent distressing memories of an emotionally traumatic event. In this review, the authors present neuroscientific data highlighting the function of two brain areas--the amygdala and ventromedial prefrontal cortex (vmPFC)--in PTSD and related emotional processes. A convergent body of human and nonhuman studies suggests that the amygdala mediates the acquisition and expression of conditioned fear and the enhancement of emotional memory, whereas the vmPFC mediates the extinction of conditioned fear and the volitional regulation of negative emotion. It has been theorized that the vmPFC exerts inhibition on the amygdala, and that a defect in this inhibition could account for the symptoms of PTSD. This theory is supported by functional imaging studies of PTSD patients, who exhibit hypoactivity in the vmPFC but hyperactivity in the amygdala. A recent study of brain-injured and trauma-exposed combat veterans confirms that amygdala damage reduces the likelihood of developing PTSD. But contrary to the prediction of the top-down inhibition model, vmPFC damage also reduces the likelihood of developing PTSD. The putative roles of the amygdala and the vmPFC in the pathophysiology of PTSD, as well as implications for potential treatments, are discussed in light of these results.

  9. Contributions of the Medial Prefrontal Cortex to Social Influence in Economic Decision-Making.

    Science.gov (United States)

    Apps, M A J; Ramnani, N

    2017-09-01

    Economic decisions are guided by highly subjective reward valuations (SVs). Often these SVs are over-ridden when individuals conform to social norms. Yet, the neural mechanisms that underpin the distinct processing of such normative reward valuations (NVs) are poorly understood. The dorsomedial and ventromedial portions of the prefrontal cortex (dmPFC/vmPFC) are putatively key regions for processing social and economic information respectively. However, the contribution of these regions to economic decisions guided by social norms is unclear. Using functional magnetic resonance imaging and computational modeling we examine the neural mechanisms underlying the processing of SVs and NVs. Subjects (n = 15) indicated either their own economic preferences or made similar choices based on a social norm-learnt during a training session. We found that that the vmPFC and dmPFC make dissociable contributions to the processing of SV and NV. Regions of the dmPFC processed "only" the value of rewards when making normative choices. In contrast, we identify a novel mechanism in the vmPFC for the coding of value. This region signaled both subjective and normative valuations, but activity was scaled positively for SV and negatively for NV. These results highlight some of the key mechanisms that underpin conformity and social influence in economic decision-making. © The Author 2017. Published by Oxford University Press.

  10. Medial prefrontal-perirhinal cortical communication is necessary for flexible response selection.

    Science.gov (United States)

    Hernandez, Abbi R; Reasor, Jordan E; Truckenbrod, Leah M; Lubke, Katelyn N; Johnson, Sarah A; Bizon, Jennifer L; Maurer, Andrew P; Burke, Sara N

    2017-01-01

    The ability to use information from the physical world to update behavioral strategies is critical for survival across species. The prefrontal cortex (PFC) supports behavioral flexibility; however, exactly how this brain structure interacts with sensory association cortical areas to facilitate the adaptation of response selection remains unknown. Given the role of the perirhinal cortex (PER) in higher-order perception and associative memory, the current study evaluated whether PFC-PER circuits are critical for the ability to perform biconditional object discriminations when the rule for selecting the rewarded object shifted depending on the animal's spatial location in a 2-arm maze. Following acquisition to criterion performance on an object-place paired association task, pharmacological blockade of communication between the PFC and PER significantly disrupted performance. Specifically, the PFC-PER disconnection caused rats to regress to a response bias of selecting an object on a particular side regardless of its identity. Importantly, the PFC-PER disconnection did not interfere with the capacity to perform object-only or location-only discriminations, which do not require the animal to update a response rule across trials. These findings are consistent with a critical role for PFC-PER circuits in rule shifting and the effective updating of a response rule across spatial locations. Published by Elsevier Inc.

  11. Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex.

    Science.gov (United States)

    Littlefield, Melissa M; Dietz, Martin J; Fitzgerald, Des; Knudsen, Kasper J; Tonks, James

    2015-01-01

    "Truth" has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person's mental state, a phenomenon known as Theory of Mind. Using a novel ecological paradigm, we examined blood oxygenation level dependent (BOLD) responses during social and simple truth telling. Participants (n = 27) were randomly divided into two competing teams. Post-competition, each participant was scanned while evaluating performances from in-group and out-group members. Participants were asked to be honest and were told that their evaluations would be made public. We found increased BOLD responses in the medial prefrontal cortex, bilateral anterior insula and precuneus when participants were asked to tell social truths compared to simple truths about another person. At the behavioral level, participants were slower at responding to social compared to simple questions about another person. These findings suggest that telling the truth is a nuanced cognitive operation that is dependent on the degree of mentalizing. Importantly, we show that the cortical regions engaged by truth telling show a distinct pattern when the task requires social reasoning.

  12. Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons.

    Science.gov (United States)

    Ładno, W; Gawlak, M; Szulczyk, P; Nurowska, E

    2017-06-15

    TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α 1 , α 2 , β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β 1 but not of α 1 - and α 2 -adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Neurobiological foundations of multisensory processing integration in people with autism spectrum disorders: The role of the medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Sonia eMartínez-Sanchis

    2014-12-01

    Full Text Available This review aims to relate the sensory processing problems in people with Autism spectrum disorders (ASD, especially Multisensory interaction (MSI, to the role of the medial prefrontal cortex (mPFC by exploring neuroanatomical findings; brain connectivity and Default Network (DN; global or locally directed attention; and temporal multisensory binding. The mPFC is part of the brain’s DN, which is deactivated when attention is focused on a particular task and activated on rest when spontaneous cognition emerges. In those with ASD, it is hypoactive and the higher the social impairment the greater the atypical activity. With an immature DN, cross-modal integration is impaired, resulting in a collection of disconnected fragments instead of a coherent global perception. The deficit in MSI may lie in the temporal synchronization of neural networks. The time interval in which the stimulation of one sensory channel could influence another would be higher, preventing integration in the typical shorter time range. Thus, the underconnectivity between distant brain areas would be involved in top-down information processes (relying on global integration of data from different sources and would enhance low level perception processes such as over focused attention to sensory details.

  14. The medial prefrontal cortex and nucleus accumbens mediate the motivation for voluntary wheel running in the rat.

    Science.gov (United States)

    Basso, Julia C; Morrell, Joan I

    2015-08-01

    Voluntary wheel running in rats provides a preclinical model of exercise motivation in humans. We hypothesized that rats run because this activity has positive incentive salience in both the acquisition and habitual stages of wheel running and that gender differences might be present. Additionally, we sought to determine which forebrain regions are essential for the motivational processes underlying wheel running in rats. The motivation for voluntary wheel running in male and female Sprague-Dawley rats was investigated during the acquisition (Days 1-7) and habitual phases (after Day 21) of running using conditioned place preference (CPP) and the reinstatement (rebound) response after forced abstinence, respectively. Both genders displayed a strong CPP for the acquisition phase and a strong rebound response to wheel deprivation during the habitual phase, suggesting that both phases of wheel running are rewarding for both sexes. Female rats showed a 1.5 times greater rebound response than males to wheel deprivation in the habitual phase of running, while during the acquisition phase, no gender differences in CPP were found. We transiently inactivated the medial prefrontal cortex (mPFC) or the nucleus accumbens (NA), hypothesizing that because these regions are involved in the acquisition and reinstatement of self-administration of both natural and pharmacological stimuli, they might also serve a role in the motivation to wheel run. Inactivation of either structure decreased the rebound response in the habitual phase of running, demonstrating that these structures are involved in the motivation for this behavior. (c) 2015 APA, all rights reserved).

  15. Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the rat medial prefrontal cortex

    KAUST Repository

    Virtanen, Mari A.; Lacoh, Claudia Marvine; Fiumelli, Hubert; Kosel, Markus; Tyagarajan, Shiva; de Roo, Mathias; Vutskits, Laszlo

    2018-01-01

    Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons. Using this technique and focusing on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto these cells between postnatal days 10 and 20. While the spatial distribution of gephyrin clusters was not affected by the distance from the cell body at postnatal day 10, we found that distal dendritic segments appeared to have a higher gephyrin density at later developmental stages. We also show a transient increase around postnatal day 20 in the percentage of spines that are carrying a gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the precise spatial arrangement of synaptic inputs is an important determinant of neuronal responses, we believe that the method described in this work may allow a better understanding of how inhibition settles together with excitation, and serve as basics for further modelling studies focusing on the geometry of dendritic inhibition during development.

  16. Interaction between the medial prefrontal cortex and hippocampal CA1 area is essential for episodic-like memory in rats.

    Science.gov (United States)

    Chao, Owen Y; Nikolaus, Susanne; Lira Brandão, Marcus; Huston, Joseph P; de Souza Silva, Maria A

    2017-05-01

    The interplay between medial prefrontal cortex (mPFC) and hippocampus, particularly the hippocampal CA3 area, is critical for episodic memory. To what extent the mPFC also interacts with the hippocampus CA1 subregion still requires elucidation. To investigate this issue, male rats received unilateral N-methyl- D -aspartate lesions of the mPFC together with unilateral lesions of the hippocampal CA1 area, either in the same (control) or in the opposite hemispheres (disconnection). They underwent an episodic-like memory test, combining what-where-when information, and separate tests for novel object preference (what), object place preference (where) and temporal order memory (when). Compared to controls, the disconnected mPFC-CA1 rats exhibited disrupted episodic-like memory with an impaired integration of the what-where-when elements. Both groups showed intact memories for what and when, while only the control group showed intact memory for where. These findings suggest that the functional interaction of the mPFC-CA1 circuit is crucial for the processing of episodic memory and, in particular, for the integration of the spatial memory component. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Oxytocin in the medial prefrontal cortex regulates maternal care, maternal aggression and anxiety during the postpartum period

    Science.gov (United States)

    Sabihi, Sara; Dong, Shirley M.; Durosko, Nicole E.; Leuner, Benedetta

    2014-01-01

    The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiety. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum, but not virgin, females. In addition, OTR blockade in the postpartum mPFC impaired maternal care behaviors and enhanced maternal aggression. Overall, these results suggest that OT in the mPFC modulates maternal care and aggression, as well as anxiety-like behavior, during the postpartum period. Although the relationship among these behaviors is complicated and further investigation is required to refine our understanding of OT actions in the maternal mPFC, these data nonetheless provide new insights into neural circuitry of OT-mediated postpartum behaviors. PMID:25147513

  18. Role of medial prefrontal cortex serotonin 2A receptors in the control of retrieval of recognition memory in rats.

    Science.gov (United States)

    Bekinschtein, Pedro; Renner, Maria Constanza; Gonzalez, Maria Carolina; Weisstaub, Noelia

    2013-10-02

    Often, retrieval cues are not uniquely related to one specific memory, which could lead to memory interference. Controlling interference is particularly important during episodic memory retrieval or when remembering specific events in a spatiotemporal context. Despite a clear involvement of prefrontal cortex (PFC) in episodic memory in human studies, information regarding the mechanisms and neurotransmitter systems in PFC involved in memory is scarce. Although the serotoninergic system has been linked to PFC functionality and modulation, its role in memory processing is poorly understood. We hypothesized that the serotoninergic system in PFC, in particular the 5-HT2A receptor (5-HT2AR) could have a role in the control of memory retrieval. In this work we used different versions of the object recognition task in rats to study the role of the serotoninergic modulation in the medial PFC (mPFC) in memory retrieval. We found that blockade of 5-HT2AR in mPFC affects retrieval of an object in context memory in a spontaneous novelty preference task, while sparing single-item recognition memory. We also determined that 5-HT2ARs in mPFC are required for hippocampal-mPFC interaction during retrieval of this type of memory, suggesting that the mPFC controls the expression of memory traces stored in the hippocampus biasing retrieval to the most relevant one.

  19. Shift in the intrinsic excitability of medial prefrontal cortex neurons following training in impulse control and cued-responding tasks.

    Directory of Open Access Journals (Sweden)

    Scott J Hayton

    Full Text Available Impulse control is an executive process that allows animals to inhibit their actions until an appropriate time. Previously, we reported that learning a simple response inhibition task increases AMPA currents at excitatory synapses in the prelimbic region of the medial prefrontal cortex (mPFC. Here, we examined whether modifications to intrinsic excitability occurred alongside the synaptic changes. To that end, we trained rats to obtain a food reward in a response inhibition task by withhold responding on a lever until they were signaled to respond. We then measured excitability, using whole-cell patch clamp recordings in brain slices, by quantifying action potentials generated by the injection of depolarizing current steps. Training in this task depressed the excitability of layer V pyramidal neurons of the prelimbic, but not infralimbic, region of the mPFC relative to behavioral controls. This decrease in maximum spiking frequency was significantly correlated with performance on the final session of the task. This change in intrinsic excitability may represent a homeostatic mechanism counterbalancing increased excitatory synaptic inputs onto those neurons in trained rats. Interestingly, subjects trained with a cue that predicted imminent reward availability had increased excitability in infralimbic, but not the prelimbic, pyramidal neurons. This dissociation suggests that both prelimbic and infralimbic neurons are involved in directing action, but specialized for different types of information, inhibitory or anticipatory, respectively.

  20. Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

    Directory of Open Access Journals (Sweden)

    Chun-Lei Zhang

    Full Text Available Methylphenidate (MPH, commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD. Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC. To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+ increase, but does not require PKA and extracellular Ca(2+ influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

  1. Transcranial direct current stimulation of the medial prefrontal cortex modulates the propensity to help in costly helping behavior.

    Science.gov (United States)

    Liao, Chong; Wu, Song; Luo, Yue-Jia; Guan, Qing; Cui, Fang

    2018-05-01

    Social decision-making engages traditional decision-making processes (e.g. valuation), as well as social cognition processes (e.g. inferring the affective and mental states of another person). Neuroimaging and neuro-stimulation studies have suggested the involvement of the medial prefrontal cortex (mPFC) in a variety of social decision-making tasks. Yet no study has investigated the effect of the cortical excitability of mPFC in the decision-making of costly helping behavior. Here, we used tDCS to demonstrate the causal relationship between the cortical excitability of mPFC and costly helping decision-making. Subjects assigned to the anodal, cathodal and sham groups were required to decide whether they would like to cost their own money to relieve another subject (a confederate actually) from painful electrical shocks with a certain probability of success. Results showed that the subjects receiving anodal stimulation acted more prosaically than the subjects receiving cathodal stimulation. And this effect was only significant when the probability of success was high. We proposed that tDCS induced modulation of the cortical excitability, targeting the mPFC, can affect the prosocial propensity in costly helping behavior, and the possible underlying mechanisms were discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Repeated Blockade of NMDA Receptors during Adolescence Impairs Reversal Learning and Disrupts GABAergic Interneurons in Rat Medial Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Jitao eLi

    2016-03-01

    Full Text Available Adolescence is of particular significance to schizophrenia, since psychosis onset typically occurs in this critical period. Based on the N-methyl-D-aspartate (NMDA receptor hypofunction hypothesis of schizophrenia, in this study, we investigated whether and how repeated NMDA receptor blockade during adolescence would affect GABAergic interneurons in rat medial prefrontal cortex (mPFC and mPFC-mediated cognitive functions. Specifically, adolescent rats were subjected to intraperitoneal administration of MK-801 (0.1, 0.2, 0.4 mg/kg, a non-competitive NMDA receptor antagonist, for 14 days and then tested for reference memory and reversal learning in the water maze. The density of parvabumin (PV-, calbindin (CB- and calretinin (CR-positive neurons in mPFC were analyzed at either 24 hours or 7 days after drug cessation. We found that MK-801 treatment delayed reversal learning in the water maze without affecting initial acquisition. Strikingly, MK-801 treatment also significantly reduced the density of PV+ and CB+ neurons, and this effect persisted for 7 days after drug cessation at the dose of 0.2 mg/kg. We further demonstrated that the reduction in PV+ and CB+ neuron densities was ascribed to a downregulation of the expression levels of PV and CB, but not to neuronal death. These results parallel the behavioral and neuropathological changes of schizophrenia and provide evidence that adolescent NMDA receptors antagonism offers a useful tool for unraveling the etiology of the disease.

  3. Prenatal alcohol exposure modifies glucocorticoid receptor subcellular distribution in the medial prefrontal cortex and impairs frontal cortex-dependent learning.

    Directory of Open Access Journals (Sweden)

    Andrea M Allan

    Full Text Available Prenatal alcohol exposure (PAE has been shown to impair learning, memory and executive functioning in children. Perseveration, or the failure to respond adaptively to changing contingencies, is a hallmark on neurobehavioral assessment tasks for human fetal alcohol spectrum disorder (FASD. Adaptive responding is predominantly a product of the medial prefrontal cortex (mPFC and is regulated by corticosteroids. In our mouse model of PAE we recently reported deficits in hippocampal formation-dependent learning and memory and a dysregulation of hippocampal formation glucocorticoid receptor (GR subcellular distribution. Here, we examined the effect of PAE on frontal cortical-dependent behavior, as well as mPFC GR subcellular distribution and the levels of regulators of intracellular GR transport. PAE mice displayed significantly reduced response flexibility in a Y-maze reversal learning task. While the levels of total nuclear GR were reduced in PAE mPFC, levels of GR phosphorylated at serines 203, 211 and 226 were not significantly changed. Cytosolic, but not nuclear, MR levels were elevated in the PAE mPFC. The levels of critical GR trafficking proteins, FKBP51, Hsp90, cyclophilin 40, dynamitin and dynein intermediate chain, were altered in PAE mice, in favor of the exclusion of GR from the nucleus, indicating dysregulation of GR trafficking. Our findings suggest that there may be a link between a deficit in GR nuclear localization and frontal cortical learning deficits in prenatal alcohol-exposed mice.

  4. Serotonin 2a Receptor and serotonin 1a receptor interact within the medial prefrontal cortex during recognition memory in mice

    Directory of Open Access Journals (Sweden)

    Juan Facundo Morici

    2015-12-01

    Full Text Available Episodic memory, can be defined as the memory for unique events. The serotonergic system one of the main neuromodulatory systems in the brain appears to play a role in it. The serotonin 2a receptor (5-HT2aR one of the principal post-synaptic receptors for 5-HT in the brain, is involved in neuropsychiatric and neurological disorders associated with memory deficits. Recognition memory can be defined as the ability to recognize if a particular event or item was previously encountered and is thus considered, under certain conditions, a form of episodic memory. As human data suggest that a constitutively decrease of 5-HT2A signaling might affect episodic memory performance we decided to compare the performance of mice with disrupted 5-HT2aR signaling (htr2a -/- with wild type (htr2a+/+ littermates in different recognition memory and working memory tasks that differed in the level of proactive interference. We found that ablation of 5-HT2aR signaling throughout development produces a deficit in tasks that cannot be solved by single item strategy suggesting that 5-HT2aR signaling is involved in interference resolution. We also found that in the absence of 5-HT2aR signaling serotonin has a deleterious effect on recognition memory retrieval through the activation of 5-HT1aR in the medial prefrontal cortex.

  5. Effects of the mode of re-socialization after juvenile social isolation on medial prefrontal cortex myelination and function.

    Science.gov (United States)

    Makinodan, Manabu; Ikawa, Daisuke; Yamamuro, Kazuhiko; Yamashita, Yasunori; Toritsuka, Michihiro; Kimoto, Sohei; Yamauchi, Takahira; Okumura, Kazuki; Komori, Takashi; Fukami, Shin-Ichi; Yoshino, Hiroki; Kanba, Shigenobu; Wanaka, Akio; Kishimoto, Toshifumi

    2017-07-14

    Social isolation is an important factor in the development of psychiatric disorders. It is necessary to develop an effective psychological treatment, such as cognitive rehabilitation, for children who have already suffered from social isolation, such as neglect and social rejection. We used socially isolated mice to validate whether elaborate re-socialization after juvenile social isolation can restore hypomyelination in the medial prefrontal cortex (mPFC) and the attendant functions manifested in socially isolated mice. While mice who underwent re-socialization with socially isolated mice after juvenile social isolation (Re-IS mice) demonstrated less mPFC activity during exposure to a strange mouse, as well as thinner myelin in the mPFC than controls, mice who underwent re-socialization with socially housed mice after juvenile social isolation (Re-SH mice) caught up with the controls in terms of most mPFC functions, as well as myelination. Moreover, social interaction of Re-IS mice was reduced as compared to controls, but Re-SH mice showed an amount of social interaction comparable to that of controls. These results suggest that the mode of re-socialization after juvenile social isolation has significant effects on myelination in the mPFC and the attendant functions in mice, indicating the importance of appropriate psychosocial intervention after social isolation.

  6. Theta synchronization between medial prefrontal cortex and cerebellum is associated with adaptive performance of associative learning behavior

    Science.gov (United States)

    Chen, Hao; Wang, Yi-jie; Yang, Li; Sui, Jian-feng; Hu, Zhi-an; Hu, Bo

    2016-01-01

    Associative learning is thought to require coordinated activities among distributed brain regions. For example, to direct behavior appropriately, the medial prefrontal cortex (mPFC) must encode and maintain sensory information and then interact with the cerebellum during trace eyeblink conditioning (TEBC), a commonly-used associative learning model. However, the mechanisms by which these two distant areas interact remain elusive. By simultaneously recording local field potential (LFP) signals from the mPFC and the cerebellum in guinea pigs undergoing TEBC, we found that theta-frequency (5.0–12.0 Hz) oscillations in the mPFC and the cerebellum became strongly synchronized following presentation of auditory conditioned stimulus. Intriguingly, the conditioned eyeblink response (CR) with adaptive timing occurred preferentially in the trials where mPFC-cerebellum theta coherence was stronger. Moreover, both the mPFC-cerebellum theta coherence and the adaptive CR performance were impaired after the disruption of endogenous orexins in the cerebellum. Finally, association of the mPFC -cerebellum theta coherence with adaptive CR performance was time-limited occurring in the early stage of associative learning. These findings suggest that the mPFC and the cerebellum may act together to contribute to the adaptive performance of associative learning behavior by means of theta synchronization. PMID:26879632

  7. Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the rat medial prefrontal cortex

    KAUST Repository

    Virtanen, Mari A.

    2018-01-10

    Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons. Using this technique and focusing on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto these cells between postnatal days 10 and 20. While the spatial distribution of gephyrin clusters was not affected by the distance from the cell body at postnatal day 10, we found that distal dendritic segments appeared to have a higher gephyrin density at later developmental stages. We also show a transient increase around postnatal day 20 in the percentage of spines that are carrying a gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the precise spatial arrangement of synaptic inputs is an important determinant of neuronal responses, we believe that the method described in this work may allow a better understanding of how inhibition settles together with excitation, and serve as basics for further modelling studies focusing on the geometry of dendritic inhibition during development.

  8. Glutamate concentration in the medial prefrontal cortex predicts resting-state cortical-subcortical functional connectivity in humans.

    Directory of Open Access Journals (Sweden)

    Niall W Duncan

    Full Text Available Communication between cortical and subcortical regions is integral to a wide range of psychological processes and has been implicated in a number of psychiatric conditions. Studies in animals have provided insight into the biochemical and connectivity processes underlying such communication. However, to date no experiments that link these factors in humans in vivo have been carried out. To investigate the role of glutamate in individual differences in communication between the cortex--specifically the medial prefrontal cortex (mPFC--and subcortical regions in humans, a combination of resting-state fMRI, DTI and MRS was performed. The subcortical target regions were the nucleus accumbens (NAc, dorsomedial thalamus (DMT, and periaqueductal grey (PAG. It was found that functional connectivity between the mPFC and each of the NAc and DMT was positively correlated with mPFC glutamate concentrations, whilst functional connectivity between the mPFC and PAG was negatively correlated with glutamate concentration. The correlations involving mPFC glutamate and FC between the mPFC and each of the DMT and PAG were mirrored by correlations with structural connectivity, providing evidence that the glutamatergic relationship may, in part, be due to direct connectivity. These results are in agreement with existing results from animal studies and may have relevance for MDD and schizophrenia.

  9. Self-distancing improves interpersonal perceptions and behavior by decreasing medial prefrontal cortex activity during the provision of criticism.

    Science.gov (United States)

    Leitner, Jordan B; Ayduk, Ozlem; Mendoza-Denton, Rodolfo; Magerman, Adam; Amey, Rachel; Kross, Ethan; Forbes, Chad E

    2017-04-01

    Previous research suggests that people show increased self-referential processing when they provide criticism to others, and that this self-referential processing can have negative effects on interpersonal perceptions and behavior. The current research hypothesized that adopting a self-distanced perspective (i.e. thinking about a situation from a non-first person point of view), as compared with a typical self-immersed perspective (i.e. thinking about a situation from a first-person point of view), would reduce self-referential processing during the provision of criticism, and in turn improve interpersonal perceptions and behavior. We tested this hypothesis in an interracial context since research suggests that self-referential processing plays a role in damaging interracial relations. White participants prepared for mentorship from a self-immersed or self-distanced perspective. They then conveyed negative and positive evaluations to a Black mentee while electroencephalogram (EEG) was recorded. Source analysis revealed that priming a self-distanced (vs self-immersed) perspective predicted decreased activity in regions linked to self-referential processing (medial prefrontal cortex; MPFC) when providing negative evaluations. This decreased MPFC activity during negative evaluations, in turn, predicted verbal feedback that was perceived to be more positive, warm and helpful. Results suggest that self-distancing can improve interpersonal perceptions and behavior by decreasing self-referential processing during the provision of criticism. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  10. Glutamate and GABA contributions to medial prefrontal cortical activity to emotion: implications for mood disorders.

    Science.gov (United States)

    Stan, Ana D; Schirda, Claudiu V; Bertocci, Michele A; Bebko, Genna M; Kronhaus, Dina M; Aslam, Haris A; LaBarbara, Eduard J; Tanase, Costin; Lockovich, Jeanette C; Pollock, Myrna H; Stiffler, Richelle S; Phillips, Mary L

    2014-09-30

    The dorsomedial prefrontal cortex (MdPFC) and anterior cingulate cortices (ACC) play a critical role in implicit emotion regulation; however the understanding of the specific neurotransmitters that mediate such role is lacking. In this study, we examined relationships between MdPFC concentrations of two neurotransmitters, glutamate and γ-amino butyric acid (GABA), and BOLD activity in ACC during performance of an implicit facial emotion-processing task. Twenty healthy volunteers, aged 20-35 years, were scanned while performing an implicit facial emotion-processing task, whereby presented facial expressions changed from neutral to one of the four emotions: happy, anger, fear, or sad. Glutamate concentrations were measured before and after the emotion-processing task in right MdPFC using magnetic resonance spectroscopy (MRS). GABA concentrations were measured in bilateral MdPFC after the emotion-processing task. Multiple regression models were run to determine the relative contribution of glutamate and GABA concentration, age, and gender to BOLD signal in ACC to each of the four emotions. Multiple regression analyses revealed a significant negative correlation between MdPFC GABA concentration and BOLD signal in subgenual ACC (psad versus shape contrast. For the anger versus shape contrast, there was a significant negative correlation between age and BOLD signal in pregenual ACC (p<0.05, corrected) and a positive correlation between MdPFC glutamate concentration (pre-task) and BOLD signal in pregenual ACC (p<0.05, corrected). Our findings are the first to provide insight into relationships between MdPFC neurotransmitter concentrations and ACC BOLD signal, and could further understanding of molecular mechanisms underlying emotion processing in healthy and mood-disordered individuals. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the medial prefrontal cortex is triggered by the expression of Fos protein in guinea pigs

    OpenAIRE

    ZHENG, YA-JUAN; DONG, YU-CHEN; ZHU, CHAO; ZHAO, MEI-SHENG

    2016-01-01

    Eyelid conditioning, including delay eyelid conditioning and trace eyelid conditioning, has been used extensively to study neural structures and mechanisms of learning and memory as a form of associative learning. In the present study, microcurrent electrical stimulation was used to stimulate the medial prefrontal cortex (mPFC) to induce delay eyelid conditioning in guinea pigs. The acquisition rate and relative latency of the conditioned eyelid response (CR) and the startle eyelid response (...

  12. GluN2B-containing NMDA receptors and AMPA receptors in medial prefrontal cortex are necessary for odor span in rats

    Directory of Open Access Journals (Sweden)

    Don A Davies

    2013-12-01

    Full Text Available Working memory is a type of short-term memory involved in the maintenance and manipulation of information essential for complex cognition. While memory span capacity has been extensively studied in humans as a measure of working memory, it has received considerably less attention in rodents. Our aim was to examine the role of the NMDA and AMPA glutamate receptors in odor span capacity using systemic injections or infusions of receptor antagonists into the medial prefrontal cortex. Long Evans rats were trained on a well-characterized odor span task. Initially, rats were trained to dig for a food reward in sand followed by training on a non-match to sample discrimination using sand scented with household spices. The rats were then required to perform a serial delayed non-match to sample procedure which was their odor span. Systemic injection of the broad spectrum NMDA receptor antagonist CPP (10 mg/kg or the GluN2B-selective antagonist Ro25-6981 (10 mg/kg but not 6 mg/kg significantly reduced odor span capacity. Infusions of the GluN2B- selective antagonist Ro25-6981 (2.5 µg/hemisphere into medial prefrontal cortex reduced span capacity, an effect that was nearly significant (p = 0.069. Infusions of the AMPA receptor antagonist CNQX (1.25 µg/hemisphere into medial prefrontal cortex reduced span capacity and latency for the rats to make a choice in the task. These results demonstrate span capacity in rats depends on ionotropic glutamate receptor activation in the medial prefrontal cortex. Further understanding of the circuitry underlying span capacity may aid in the novel therapeutic drug development for persons with working memory impairments as a result of disorders such as schizophrenia and Alzheimer’s disease.

  13. Opposite effective connectivity in the posterior cingulate and medial prefrontal cortex between first-episode schizophrenic patients with suicide risk and healthy controls.

    Directory of Open Access Journals (Sweden)

    Huiran Zhang

    Full Text Available OBJECTIVE: The schizophrenic patients with high suicide risk are characterized by depression, better cognitive function, and prominent positive symptoms. However, the neurobiological basis of suicide attempts in schizophrenia is not clear. The suicide in schizophrenia is implicated in the defects in emotional process and decision-making, which are associated with prefrontal-cingulate circuit. In order to explore the possible neurobiological basis of suicide in schizophrenia, we investigated the correlation of prefrontal-cingulate circuit with suicide risk in schizophrenia via dynamic casual modelling. METHOD: Participants were 33 first-episode schizophrenic patients comprising of a high suicide risk group (N = 14 and a low suicide risk group (N = 19. A comparison group of healthy controls (N = 15 were matched for age, gender and education. N-back tasking functional magnetic resonance imaging data was collected. RESULTS: Compared with healthy controls group, the two patients groups showed decreased task-related suppression during 2-back task state versus baseline state in the left posterior cingulate and medial prefrontal cortex; the hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex existed in both schizophrenic patients groups, but hypo-connectivity in the opposite direction only existed in the schizophrenic patients group with high suicide risk. CONCLUSIONS: The hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex may suggest that the abnormal effective connectivity was associated with risk for schizophrenia. The hypo-connectivity in the opposite direction may represent a possible correlate of increased vulnerability to suicide attempt.

  14. Functional deficit in the medial prefrontal cortex during a language comprehension task in patients with schizophrenia.

    Science.gov (United States)

    Dollfus, Sonia; Razafimandimby, Annick; Maiza, Olivier; Lebain, Pierrick; Brazo, Perrine; Beaucousin, Virginie; Lecardeur, Laurent; Delamillieure, Pascal; Mazoyer, Bernard; Tzourio-Mazoyer, Nathalie

    2008-02-01

    We and others have observed that patients with schizophrenia commonly presented a reduced left recruitment in language semantic brain regions. However, most studies include patients with leftward and rightward lateralizations for language. We investigated whether a cohort comprised purely of patients with typical lateralization (leftward) presented a reduced left recruitment in semantic regions during a language comprehension task. The goal was to reduce the inter-subject variability and thus improve the resolution for studying functional abnormalities in the language network. Twenty-three patients with schizophrenia (DSM-IV) were matched with healthy subjects in age, sex, level of education and handedness. All patients exhibited leftward lateralization for language. Functional MRI was performed as subjects listened to a story comprising characters and social interactions. Functional MRI signal variations were analyzed individually and compared among groups. Although no differences were observed in the recruitment of the semantic language network, patients with schizophrenia presented significantly lower signal variations compared to controls in the medial part of the left superior frontal gyrus (MF1) (x=-6, y=58, z=20; Z(score)=5.6; pTheory of Mind (ToM) network. Only 5 of the 23 patients (21.7%) and 21 of the 23 (91.3%) control subjects demonstrated a positive signal variation in this area. A left functional deficit was observed in a core region of the ToM network in patients with schizophrenia and typical lateralizations for language. This functional defect could represent a neural basis for impaired social interaction and communication in patients with schizophrenia.

  15. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

    2016-03-15

    Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Interaction of basolateral amygdala, ventral hippocampus and medial prefrontal cortex regulates the consolidation and extinction of social fear.

    Science.gov (United States)

    Qi, Chu-Chu; Wang, Qing-Jun; Ma, Xue-Zhu; Chen, Hai-Chao; Gao, Li-Ping; Yin, Jie; Jing, Yu-Hong

    2018-03-19

    Following a social defeat, the balanced establishment and extinction of aversive information is a beneficial strategy for individual survival. Abnormal establishment or extinction is implicated in the development of mental disorders. This study investigated the time course of the establishment and extinction of aversive information from acute social defeat and the temporal responsiveness of the basolateral amygdala (BLA), ventral hippocampus (vHIP) and medial prefrontal cortex (mPFC) in this process. Mouse models of acute social defeat were established by using the resident-intruder paradigm. To evaluate the engram of social defeat, the intruder mice were placed into the novel context at designated time to test the social behavior. Furthermore, responses of BLA, vHIP and mPFC were investigated by analyzing the expression of immediate early genes, such as zif268, arc, and c-fos. The results showed after an aggressive attack, aversive memory was maintained for approximately 7 days before gradually diminishing. The establishment and maintenance of aversive stimulation were consistently accompanied by BLA activity. By contrast, vHIP and mPFC response was inhibited from this process. Additionally, injecting muscimol (Mus), a GABA receptor agonist, into the BLA alleviated the freezing behavior and social fear and avoidance. Simultaneously, Mus treatment decreased the zif268 and arc expression in BLA, but it increased their expression in vHIP. Our data support and extend earlier findings that implicate BLA, vHIP and mPFC in social defeat. The time courses of the establishment and extinction of social defeat are particularly consistent with the contrasting BLA and vHIP responses involved in this process.

  17. Differential effects of beta-adrenergic receptor blockade in the medial prefrontal cortex during aversive and incidental taste memory formation.

    Science.gov (United States)

    Reyes-López, J; Nuñez-Jaramillo, L; Morán-Guel, E; Miranda, M I

    2010-08-11

    The medial prefrontal cortex (mPFC) is a brain area crucial for memory, attention, and decision making. Specifically, the noradrenergic system in this cortex is involved in aversive learning, as well as in the retrieval of these memories. Some evidence suggests that this area has an important role during taste memory, particularly during conditioned taste aversion (CTA), a model of aversive memory. Despite some previous evidence, there is scarce information about the role of adrenergic receptors in the mPFC during formation of aversive taste memory and appetitive/incidental taste memory. The goal of this research was to evaluate the role of mPFC beta-adrenergic receptors during CTA acquisition/consolidation or CTA retrieval, as well as during incidental taste memory formation using the model of latent inhibition of CTA. The results showed that infusions in the mPFC of the beta-adrenergic antagonist propranolol before CTA acquisition impaired both short- and long-term aversive taste memory formation, and also that propranolol infusions before the memory test impaired CTA retrieval. However, propranolol infusions before pre-exposure to the taste during the latent inhibition procedure had no effect on incidental taste memory acquisition or consolidation. These data indicate that beta-adrenergic receptors in the mPFC have different functions during taste memory formation: they have an important role during aversive taste association as well as during aversive retrieval but not during incidental taste memory formation. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. β-Adrenoceptor Blockade in the Basolateral Amygdala, But Not the Medial Prefrontal Cortex, Rescues the Immediate Extinction Deficit.

    Science.gov (United States)

    Giustino, Thomas F; Seemann, Jocelyn R; Acca, Gillian M; Goode, Travis D; Fitzgerald, Paul J; Maren, Stephen

    2017-12-01

    Early psychological interventions, such as exposure therapy, rely on extinction learning to reduce the development of stress- and trauma-related disorders. However, recent research suggests that extinction often fails to reduce fear when administered soon after trauma. This immediate extinction deficit (IED) may be due to stress-induced dysregulation of neural circuits involved in extinction learning. We have shown that systemic β-adrenoceptor blockade with propranolol rescues the IED, but impairs delayed extinction. Here we sought to determine the neural locus of these effects. Rats underwent auditory fear conditioning and then received either immediate (30 min) or delayed (24 h) extinction training. We used bilateral intracranial infusions of propranolol into either the infralimbic division of the medial prefrontal cortex (mPFC) or the basolateral amygdala (BLA) to examine the effects of β-adrenoceptor blockade on immediate and delayed extinction learning. Interestingly, intra-BLA, but not intra-mPFC, propranolol rescued the IED; animals receiving intra-BLA propranolol prior to immediate extinction showed less spontaneous recovery of fear during extinction retrieval. Importantly, this was not due to impaired consolidation of the conditioning memory. In contrast, neither intra-BLA nor intra-mPFC propranolol affected delayed extinction learning. Overall, these data contribute to a growing literature suggesting dissociable roles for key nodes in the fear extinction circuit depending on the timing of extinction relative to conditioning. These data also suggest that heightened noradrenergic activity in the BLA underlies stress-induced extinction deficits. Propranolol may be a useful adjunct to behavioral therapeutic interventions in recently traumatized individuals who are at risk for developing trauma-related disorders.

  19. Behavioral control blunts reactions to contemporaneous and future adverse events: Medial prefrontal cortex plasticity and a corticostriatal network

    Directory of Open Access Journals (Sweden)

    Steven F. Maier

    2015-01-01

    Full Text Available It has been known for many years that the ability to exert behavioral control over an adverse event blunts the behavioral and neurochemical impact of the event. More recently, it has become clear that the experience of behavioral control over adverse events also produces enduring changes that reduce the effects of subsequent negative events, even if they are uncontrollable and quite different from the original event controlled. This review focuses on the mechanism by which control both limits the impact of the stressor being experienced and produces enduring, trans-situational “immunization”. The evidence will suggest that control is detected by a corticostriatal circuit involving the ventral medial prefrontal cortex (mPFC and the posterior dorsomedial striatum (DMS. Once control is detected, other mPFC neurons that project to stress-responsive brainstem (dorsal raphe nucleus, DRN and limbic (amygdala structures exert top–down inhibitory control over the activation of these structures that is produced by the adverse event. These structures, such as the DRN and amygdala, in turn regulate the proximate mediators of the behavioral and physiological responses produced by adverse events, and so control blunts these responses. Importantly, the joint occurrence of control and adverse events seems to produce enduring plastic changes in the top–down inhibitory mPFC system such that this system is now activated by later adverse events even if they are uncontrollable, thereby reducing the impact of these events. Other issues are discussed that include a whether other processes such as safety signals and exercise, that lead to resistance/resilience, also use the mPFC circuitry or do so in other ways; b whether control has similar effects and neural mediation in humans, and c the relationship of this work to clinical phenomena.

  20. Altered structure and function in the hippocampus and medial prefrontal cortex in patients with burning mouth syndrome.

    Science.gov (United States)

    Khan, Shariq A; Keaser, Michael L; Meiller, Timothy F; Seminowicz, David A

    2014-08-01

    Burning mouth syndrome (BMS) is a debilitating, idiopathic chronic pain condition. For many BMS patients, burning oral pain begins in late morning and becomes more intense throughout the day, peaking by late afternoon or evening. We investigated brain gray matter volume (GMV) with voxel-based morphometry (VBM), white matter fractional anisotropy (FA) with diffusion tensor imaging (DTI), and functional connectivity in resting state functional MRI (rsfMRI) in a tightly screened, homogeneous sample of 9 female, postmenopausal/perimenopausal BMS patients and 9 matched healthy control subjects. Patients underwent 2 scanning sessions in the same day: in the morning, when ongoing pain/burning was low, and in the afternoon, when pain/burning was significantly higher. Patients had increased GMV and lower FA in the hippocampus (Hc), and decreased GMV in the medial prefrontal cortex (mPFC). rsfMRI revealed altered connectivity patterns in different states of pain/burning, with increased connectivity between mPFC (a node in the default mode network) and anterior cingulate cortex, occipital cortex, ventromedial PFC, and bilateral Hc/amygdala in the afternoon compared with the morning session. Furthermore, mPFC-Hc connectivity was higher in BMS patients than control subjects for the afternoon but not the morning session. mPFC-Hc connectivity was related to Beck depression inventory scores both between groups and between burning states within patients, suggesting that depression and anxiety partially explain pain-related brain dysfunction in BMS. Overall, we provide multiple lines of evidence supporting aberrant structure and function in the mPFC and Hc, and implicate a circuit involving the mPFC and Hc in regulating mood and depressive symptoms in BMS. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory

    Directory of Open Access Journals (Sweden)

    Amy L Griffin

    2015-03-01

    Full Text Available Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC. Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a variety of working memory tasks. Therefore, it is likely that hippocampal-mPFC oscillatory synchrony is modulated by RE activity. This article will review the anatomical connections between the hippocampus, mPFC and RE along with the behavioral studies that have investigated the effects of RE disruption on working memory task performance. The article will conclude with suggestions for future directions aimed at identifying the specific role of the RE in regulating functional interactions between the hippocampus and the PFC and investigating the degree to which these interactions contribute to spatial working memory.

  2. The temporal structure of resting-state brain activity in the medial prefrontal cortex predicts self-consciousness.

    Science.gov (United States)

    Huang, Zirui; Obara, Natsuho; Davis, Henry Hap; Pokorny, Johanna; Northoff, Georg

    2016-02-01

    Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called "rest-self overlap" remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self-Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting-state activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder.

    Science.gov (United States)

    Meier, Timothy B; Drevets, Wayne C; Wurfel, Brent E; Ford, Bart N; Morris, Harvey M; Victor, Teresa A; Bodurka, Jerzy; Teague, T Kent; Dantzer, Robert; Savitz, Jonathan

    2016-03-01

    Reductions in gray matter volume of the medial prefrontal cortex (mPFC), especially the rostral and subgenual anterior cingulate cortex (rACC, sgACC) are a widely reported finding in major depressive disorder (MDD). Inflammatory mediators, which are elevated in a subgroup of patients with MDD, activate the kynurenine metabolic pathway and increase production of neuroactive metabolites such as kynurenic acid (KynA), 3-hydroxykynurenine (3HK) and quinolinic acid (QA) which influence neuroplasticity. It is not known whether the alterations in brain structure and function observed in major depressive disorders are due to the direct effect of inflammatory mediators or the effects of neurotoxic kynurenine metabolites. Here, using partial posterior predictive distribution mediation analysis, we tested whether the serum concentrations of kynurenine pathway metabolites mediated reductions in cortical thickness in mPFC regions in MDD. Further, we tested whether any association between C-reactive protein (CRP) and cortical thickness would be mediated by kynurenine pathway metabolites. Seventy-three unmedicated subjects who met DSM-IV-TR criteria for MDD and 91 healthy controls (HC) completed MRI scanning using a pulse sequence optimized for tissue contrast resolution. Automated cortical parcellation was performed using the PALS-B12 Brodmann area atlas as implemented in FreeSurfer in order to compare the cortical thickness and cortical area of six PFC regions: Brodmann areas (BA) 9, 10, 11, 24, 25, and 32. Serum concentrations of kynurenine pathway metabolites were determined by high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) detection, while high-sensitivity CRP concentration was measured immunoturbidimetrically. Compared with HCs, the MDD group showed a reduction in cortical thickness of the right BA24 (pdepressive episodes displayed thinner cortex in BA32 (pmediated the relationship between diagnosis and cortical thickness of right BA32

  4. Perceived life stress exposure modulates reward-related medial prefrontal cortex responses to acute stress in depression.

    Science.gov (United States)

    Kumar, Poornima; Slavich, George M; Berghorst, Lisa H; Treadway, Michael T; Brooks, Nancy H; Dutra, Sunny J; Greve, Douglas N; O'Donovan, Aoife; Bleil, Maria E; Maninger, Nicole; Pizzagalli, Diego A

    2015-07-15

    Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI. Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r=0.79, p=0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r=0.79) and no-stress (r=-0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC gray matter, but functional findings remained robust while accounting for structural differences. Small sample size, which warrants replication. Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats.

    Science.gov (United States)

    Sabihi, Sara; Durosko, Nicole E; Dong, Shirley M; Leuner, Benedetta

    2014-07-01

    The neuropeptide oxytocin (OT) is anxiolytic in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a target where OT acts to diminish anxiety. To investigate this possibility, female rats were administered OT bilaterally into the prelimbic (PL) region of the mPFC and anxiety-like behavior assessed. In addition, to determine if the effects of OT on anxiety-like behavior are sex dependent and to evaluate the specificity of OT, male and female anxiety-like behavior was tested following delivery of either OT or the closely related neuropeptide arginine vasopressin (AVP) into the PL mPFC. Finally, the importance of endogenous OT in the regulation of anxiety-like behavior was examined in male and female rats that received PL infusions of an OT receptor antagonist (OTR-A). Overall, even though males and females showed some differences in their baseline levels of anxiety-like behavior, OT in the PL region of the mPFC decreased anxiety regardless of sex. In contrast, neither AVP nor an OTR-A affected anxiety-like behavior in males or females. Together, these findings suggest that although endogenous OT in the PL region of the mPFC does not influence anxiety, the PL mPFC is a site where exogenous OT may act to attenuate anxiety-related behavior independent of sex. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

    Science.gov (United States)

    Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M; Mair, Robert G

    2017-01-01

    The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

  7. Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high-frequency heart rate variability.

    Science.gov (United States)

    Jennings, J Richard; Sheu, Lei K; Kuan, Dora C-H; Manuck, Stephen B; Gianaros, Peter J

    2016-04-01

    Resting high-frequency heart rate variability (HF-HRV) relates to cardiac vagal control and predicts individual differences in health and longevity, but its functional neural correlates are not well defined. The medial prefrontal cortex (mPFC) encompasses visceral control regions that are components of intrinsic networks of the brain, particularly the default mode network (DMN) and the salience network (SN). Might individual differences in resting HF-HRV covary with resting state neural activity in the DMN and SN, particularly within the mPFC? This question was addressed using fMRI data from an eyes-open, 5-min rest period during which echoplanar brain imaging yielded BOLD time series. Independent component analysis yielded functional connectivity estimates defining the DMN and SN. HF-HRV was measured in a rest period outside of the scanner. Midlife (52% female) adults were assessed in two studies (Study 1, N = 107; Study 2, N = 112). Neither overall DMN nor SN connectivity strength was related to HF-HRV. However, HF-HRV related to connectivity of one region within mPFC shared by the DMN and SN, namely, the perigenual anterior cingulate cortex, an area with connectivity to other regions involved in autonomic control. In sum, HF-HRV does not seem directly related to global resting state activity of intrinsic brain networks, but rather to more localized connectivity. A mPFC region was of particular interest as connectivity related to HF-HRV was shared by the DMN and SN. These findings may indicate a functional basis for the coordination of autonomic cardiac control with engagement and disengagement from the environment. © 2015 Society for Psychophysiological Research.

  8. Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients.

    Science.gov (United States)

    Carmi, Lior; Alyagon, Uri; Barnea-Ygael, Noam; Zohar, Joseph; Dar, Reuven; Zangen, Abraham

    Obsessive Compulsive Disorder (OCD) is a chronic and disabling disorder with poor response to pharmacological treatments. Converging evidences suggest that OCD patients suffer from dysfunction of the cortico-striato-thalamo-cortical (CSTC) circuit, including in the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC). To examine whether modulation of mPFC-ACC activity by deep transcranial magnetic stimulation (DTMS) affects OCD symptoms. Treatment resistant OCD participants were treated with either high-frequency (HF; 20 Hz), low-frequency (LF; 1 Hz), or sham DTMS of the mPFC and ACC for five weeks, in a double-blinded manner. All treatments were administered following symptoms provocation, and EEG measurements during a Stroop task were acquired to examine changes in error-related activity. Clinical response to treatment was determined using the Yale-Brown-Obsessive-Compulsive Scale (YBOCS). Interim analysis revealed that YBOCS scores were significantly improved following HF (n = 7), but not LF stimulation (n = 8), compared to sham (n = 8), and thus recruitment for the LF group was terminated. Following completion of the study, the response rate in the HF group (n = 18) was significantly higher than that of the sham group (n = 15) for at least one month following the end of the treatment. Notably, the clinical response in the HF group correlated with increased Error Related Negativity (ERN) in the Stroop task, an electrophysiological component that is attributed to ACC activity. HF DTMS over the mPFC-ACC alleviates OCD symptoms and may be used as a novel therapeutic intervention. Notwithstanding alternative explanations, this may stem from DTMS ability to directly modify ACC activity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Organización celular del área 10 de la corteza orbitofrontal del ser humano

    OpenAIRE

    Hernán J. Pimienta J.; John Umbarila Prieto

    2005-01-01

    La región orbital del área 10 de la corteza cerebral del humano se relaciona con la disociación de la atención, la introspección, la monitorización individuo-ambiente y la memoria prospectiva.  Los estudios imaginológicos funcionales han identificado asimetrías en la actividad prefrontal.  Los correlatos celulares de estas asimetrías son desconocidos.

  10. Organización celular del área 10 de la corteza orbitofrontal del ser humano

    Directory of Open Access Journals (Sweden)

    Hernán J. Pimienta J.

    2005-03-01

    Full Text Available La región orbital del área 10 de la corteza cerebral del humano se relaciona con la disociación de la atención, la introspección, la monitorización individuo-ambiente y la memoria prospectiva.  Los estudios imaginológicos funcionales han identificado asimetrías en la actividad prefrontal.  Los correlatos celulares de estas asimetrías son desconocidos.

  11. Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex.

    Science.gov (United States)

    Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Frau, Roberto; Gessa, Gian L

    2015-10-01

    Disulfiram has been claimed to be useful in cocaine addiction therapy, its efficacy being attributed to dopamine-beta-hydroxylase (DBH) inhibition. Our previous results indicate that disulfiram and the selective DBH inhibitor nepicastat increase extracellular dopamine (DA) in the rat medial prefrontal cortex (mPFC), and markedly potentiated cocaine-induced increase. Concomitantly, in rats with cocaine self-administration history, cocaine-seeking behavior induced by drug priming was prevented, probably through overstimulation of D1 receptors due to the DA increase. The present research was aimed at studying the neurochemical mechanisms originating the enhanced DA release. Noradrenergic system ablation was attained by intracerebroventricular (i.c.v.) administration of the neurotoxin anti-DBH-saporin (aDBH-sap). DA, noradrenaline (NA), and DOPAC were assessed by HPLC after ex vivo tissue extraction or in vivo microdialysis. Control and denervated rats were subjected to microdialysis in the mPFC and caudate nucleus to evaluate the effect of nepicastat-cocaine combination on extracellular DA levels and their regulation by α2-adrenoceptors. Fifteen days after neurotoxin or its vehicle administration, tissue and extracellular NA were reduced to less than 2% the control value, while extracellular DA was increased by approximately 100%. In control rats, nepicastat given alone and in combination with cocaine increased extracellular DA by about 250% and 1100%, respectively. In denervated rats, nepicastat slightly affected extracellular DA, while in combination with cocaine increased extracellular DA by 250%. No differences were found in the caudate nucleus. Clonidine almost totally reversed the extracellular DA elevation produced by nepicastat-cocaine combination, while it was ineffective in denervated rats. This research shows that the increase of extracellular DA produced by nepicastat alone or in combination with cocaine was prevented by noradrenergic denervation. The

  12. Habitual 'sleep credit' is associated with greater grey matter volume of the medial prefrontal cortex, higher emotional intelligence and better mental health.

    Science.gov (United States)

    Weber, Mareen; Webb, Christian A; Deldonno, Sophie R; Kipman, Maia; Schwab, Zachary J; Weiner, Melissa R; Killgore, William D S

    2013-10-01

    In modern society, people often fail to obtain the amount of sleep that experts recommend for good health and performance. Insufficient sleep can lead to degraded cognitive performance and alterations in emotional functioning. However, most people also acknowledge that on a regular basis they obtain more sleep than they subjectively perceive they need at a minimum to stave off performance decrements, a construct we describe as subjective 'sleep credit'. Few people would contest the notion that getting more sleep is better, but data on both behavioural and neuroanatomical correlates of 'sleep credit' are surprisingly limited. We conducted a voxel-based morphometric study to assess cerebral grey matter correlates of habitually sleeping more than one's subjective requirements. We further tested whether these structural correlates are associated with perceived emotional intelligence and indices of psychopathology while controlling for age, gender, and total intracranial volume. In a sample of 55 healthy adults aged 18-45 years (28 males, 27 females), whole-brain multiple regression showed that habitual subjective 'sleep credit' was correlated positively with grey matter volume within regions of the left medial prefrontal cortex and right orbitofrontal gyrus. Volumes were extracted and regressed against self-report emotion and psychopathology indices. Only grey matter volume of the medial prefrontal cortex cluster correlated with greater emotional intelligence and lower scores on several indices of psychopathology. Findings converge with previous evidence of the role of the medial prefrontal cortex in the relationship between sleep and emotional functioning, and suggest that behaviour and brain structure vary with habitual 'sleep credit'. © 2013 European Sleep Research Society.

  13. Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity.

    Science.gov (United States)

    Calcagno, E; Canetta, A; Guzzetti, S; Cervo, L; Invernizzi, R W

    2007-11-01

    We used the microdialysis technique to compare basal extracellular serotonin (5-HT) and the response to citalopram in different strains of mice with functionally different allelic forms of tryptophan hydroxylase-2 (TPH-2), the rate-limiting enzyme in brain 5-HT synthesis. DBA/2J, DBA/2N and BALB/c mice carrying the 1473G allele of TPH-2 had less dialysate 5-HT in the medial prefrontal cortex and dorsal hippocampus (DH) (20-40% reduction) than C57BL/6J and C57BL/6N mice carrying the 1473C allele. Extracellular 5-HT estimated by the zero-net flux method confirmed the result of conventional microdialysis. Citalopram, 1.25, 5 and 20 mg/kg, dose-dependently raised extracellular 5-HT in the medial prefrontal cortex of C57BL/6J mice, with maximum effect at 5 mg/kg, but had significantly less effect in DBA/2J and BALB/c mice and in the DH of DBA/2J mice. A tryptophan (TRP) load enhanced basal extracellular 5-HT in the medial prefrontal cortex of DBA/2J mice but did not affect citalopram's ability to raise cortical and hippocampal extracellular 5-HT. The impairment of 5-HT synthesis quite likely accounts for the reduction of basal 5-HT and the citalopram-induced rise in mice carrying the mutated enzyme. These findings might explain why DBA/2 and BALB/c mice do not respond to citalopram in the forced swimming test. Although TRP could be a useful strategy to improve the antidepressant effect of citalopram (Cervo et al. 2005), particularly in subjects with low 5-HT synthesis, the contribution of serotonergic and non-serotonergic mechanisms to TRP's effect remains to be elucidated.

  14. Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic Acid animal model of autism

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

    2008-01-01

    of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions...

  15. Rostro-caudal and dorso-ventral gradients in medial and lateral prefrontal cortex during cognitive control of affective and cognitive interference.

    Science.gov (United States)

    Rahm, Christoffer; Liberg, Benny; Wiberg-Kristoffersen, Maria; Aspelin, Peter; Msghina, Mussie

    2013-04-01

    Characterizing the anatomical substrates of major brain functions such as cognition and emotion is of utmost importance to the ongoing efforts of understanding the nature of psychiatric ailments and their potential treatment. The aim of our study was to investigate how the brain handles affective and cognitive interferences on cognitive processes. Functional magnetic resonance imaging investigation was performed on healthy individuals, comparing the brain oxygenation level dependent activation patterns during affective and cognitive counting Stroop tasks. The affective Stroop task activated rostral parts of medial prefrontal cortex (PFC) and rostral and ventral parts of lateral PFC, while cognitive Stroop activated caudal parts of medial PFC and caudal and dorsal parts of lateral PFC. Our findings suggest that the brain may handle affective and cognitive interference on cognitive processes differentially, with affective interference preferentially activating rostral and ventral PFC networks and cognitive interference activating caudal and dorsal PFC networks. © 2013 The Authors. Scandinavian Journal of Psychology © 2013 The Scandinavian Psychological Associations.

  16. Hyper-Connectivity and Hyper-Plasticity in the Medial Prefrontal Cortex in the Valproic Acid Animal Model of Autism

    OpenAIRE

    Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

    2008-01-01

    The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. Th...

  17. The medial prefrontal cortex-lateral entorhinal cortex circuit is essential for episodic-like memory and associative object-recognition.

    Science.gov (United States)

    Chao, Owen Y; Huston, Joseph P; Li, Jay-Shake; Wang, An-Li; de Souza Silva, Maria A

    2016-05-01

    The prefrontal cortex directly projects to the lateral entorhinal cortex (LEC), an important substrate for engaging item-associated information and relaying the information to the hippocampus. Here we ask to what extent the communication between the prefrontal cortex and LEC is critically involved in the processing of episodic-like memory. We applied a disconnection procedure to test whether the interaction between the medial prefrontal cortex (mPFC) and LEC is essential for the expression of recognition memory. It was found that male rats that received unilateral NMDA lesions of the mPFC and LEC in the same hemisphere, exhibited intact episodic-like (what-where-when) and object-recognition memories. When these lesions were placed in the opposite hemispheres (disconnection), episodic-like and associative memories for object identity, location and context were impaired. However, the disconnection did not impair the components of episodic memory, namely memory for novel object (what), object place (where) and temporal order (when), per se. Thus, the present findings suggest that the mPFC and LEC are a critical part of a neural circuit that underlies episodic-like and associative object-recognition memory. © 2015 Wiley Periodicals, Inc.

  18. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

    International Nuclear Information System (INIS)

    Asensio, S.; Goldstein, R.; Romero, M.J.; Romero, F.J.; Wong, C.T.; Alia-Klein, N.; Tomasi, D.; Wang, G.-J.; Telang, F.; Volkow, N.D.; Goldstein, R.Z.

    2010-01-01

    Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with ( 11 C)raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

  19. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

    Energy Technology Data Exchange (ETDEWEB)

    Asensio, S.; Goldstein, R.; Asensio, S.; Romero, M.J.; Romero, F.J.; Wong, C.T.; Alia-Klein, N.; Tomasi, D.; Wang, G.-J.; Telang, F..; Volkow, N.D.; Goldstein, R.Z.

    2010-05-01

    Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [{sup 11}C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

  20. Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism

    Directory of Open Access Journals (Sweden)

    Tania Rinaldi

    2008-10-01

    Full Text Available The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. These excitatory connections are more plastic displaying enhanced long-term potentiation of the strength of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions in the brain, and stands in contrast to the hypo-functionality that is normally proposed in this region to explain some of the autistic symptoms. We propose that a number of deficits in autism such as sociability, attention, multi-tasking and repetitive behaviours, should be re-interpreted in the light of a hyper-functional prefrontal cortex.

  1. Blockade of IP[subscript 3]-Mediated SK Channel Signaling in the Rat Medial Prefrontal Cortex Improves Spatial Working Memory

    Science.gov (United States)

    Brennan, Avis R.; Dolinsky, Beth; Vu, Mai-Anh T.; Stanley, Marion; Yeckel, Mark F.; Arnsten, Amy F. T.

    2008-01-01

    Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP[subscript 3]-PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP[subscript 3] receptor (IP[subscript…

  2. Sex differences in social interaction behaviors in rats are mediated by extracellular signal-regulated kinase 2 expression in the medial prefrontal cortex

    Science.gov (United States)

    Carrier, Nicole; Kabbaj, Mohamed

    2012-01-01

    Considerable sex differences occur in the incidence and prevalence of anxiety disorders where women are more anxious than men, particularly in situations where social interaction is required. In preclinical studies, the social interaction test represents a valid animal model to study sex differences in social anxiety. Indeed, female rats engage less in conspecific interactions than their male counterparts, which are behaviors indicative of higher social anxiety in female rats. In this work, we implicated extracellular signal regulated kinase 2 (ERK2) in the medial prefrontal cortex (mPFC) in mediating social interaction. Indeed, female rats’ had lower ERK2 expression compared to male rats, and overexpression of ERK2 in the mPFC increases their social interaction to the level seen in their male counterparts. These data indicate that the sexually dimorphic expression of ERK2 mediates social anxiety-like behaviors. PMID:22521590

  3. The Medial Temporal Lobe and the Left Inferior Prefrontal Cortex Jointly Support Interference Resolution in Verbal Working Memory

    Science.gov (United States)

    Oztekin, Ilke; Curtis, Clayton E.; McElree, Brian

    2009-01-01

    During working memory retrieval, proactive interference (PI) can be induced by semantic similarity and episodic familiarity. Here, we used fMRI to test hypotheses about the role of the left inferior frontal gyrus (LIFG) and the medial temporal lobe (MTL) regions in successful resolution of PI. Participants studied six-word lists and responded to a…

  4. Inactivating the infralimbic but not prelimbic medial prefrontal cortex facilitates the extinction of appetitive Pavlovian conditioning in Long-Evans rats.

    Science.gov (United States)

    Mendoza, J; Sanio, C; Chaudhri, N

    2015-02-01

    The infralimbic medial prefrontal cortex (IL) has been posited as a common node in distinct neural circuits that mediate the extinction of appetitive and aversive conditioning. However, appetitive extinction is typically assessed using instrumental conditioning procedures, whereas the extinction of aversive conditioning is customarily studied using Pavlovian assays. The role of the IL in the extinction of appetitive Pavlovian conditioning remains underexplored. We investigated the involvement of the IL and prelimbic medial prefrontal cortex (PrL) in appetitive extinction in Pavlovian and instrumental conditioning assays in male, Long-Evans rats. Following acquisition, a gamma-aminobutyric acid agonist solution (0.03 nmol muscimol; 0.3 nmol baclofen; 0.3 μl/side) was bilaterally microinfused into the IL or PrL to pharmacologically inactivate each region before the first extinction session. Compared to saline, PrL inactivation did not affect the acquisition of extinction or the recall of extinction memory 24-h later. IL inactivation caused a more rapid extinction of Pavlovian conditioning, but had no effect on the extinction of instrumental conditioning or extinction recall. IL inactivation during a Pavlovian conditioning session in which conditioned stimulus (CS) trials were paired with sucrose did not affect CS-elicited behaviour, but increased responding during intervals that did not contain the CS. The same manipulation did not impact lever pressing for sucrose. These findings suggest that the IL may normally maintain Pavlovian conditioned responding when an anticipated appetitive CS is unexpectedly withheld, and that this region has distinct roles in the expression of Pavlovian conditioning when an appetitive unconditioned stimulus is either presented or omitted. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex.

    Science.gov (United States)

    Ventura, R; Pascucci, T; Catania, M V; Musumeci, S A; Puglisi-Allegra, S

    2004-09-01

    Fragile X syndrome is an X-linked form of mental retardation including, among others, symptoms such as stereotypic behaviour, hyperactivity, hyperarousal, and cognitive deficits. We hypothesized that hyperactivity and/or compromised attentional, cognitive functions may lead to impaired performance in cognitive tasks in Fmr1 knockout mice, the most widely used animal model of fragile X syndrome, and suggested that psychostimulant treatment may improve performance by acting on one or both components. Since hyperactivity and cognitive functions have been suggested to depend on striatal and prefrontal cortex dopaminergic dysfunction, we assessed whether amphetamine produced beneficial, positive effects by acting on dopaminergic corticostriatal systems. Our results show that Fmr1 knockout mice are not able to discriminate between a familiar object and a novel one in the object recognition test, thus showing a clear-cut cognitive impairment that, to date, has been difficult to demonstrate in other cognitive tasks. Amphetamine improved performance of Fmr1 knockout mice, leading to enhanced ability to discriminate novel versus familiar objects, without significantly affecting locomotor activity. In agreement with behavioural data, amphetamine produced a greater increase in dopamine release in the prefrontal cortex of Fmr1 knockout compared with the wild-type mice, while a weak striatal dopaminergic response was observed in Fmr1 knockout mice. Our data support the view that the psychostimulant ameliorates performance in Fmr1 knockout mice by improving merely cognitive functions through its action on prefrontal cortical dopamine, irrespective of its action on motor hyperactivity. These results indicate that prefrontal cortical dopamine plays a major role in cognitive impairments characterizing Fmr1 knockout mice, thus pointing to an important aetiological factor in the fragile X syndrome.

  6. Removing the effect of response time on brain activity reveals developmental differences in conflict processing in the posterior medial prefrontal cortex.

    Science.gov (United States)

    Carp, Joshua; Fitzgerald, Kate Dimond; Taylor, Stephan F; Weissman, Daniel H

    2012-01-02

    In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. The expression of plasticity-related genes in an acute model of stress is modulated by chronic desipramine in a time-dependent manner within medial prefrontal cortex.

    Science.gov (United States)

    Nava, Nicoletta; Treccani, Giulia; Müller, Heidi Kaastrup; Popoli, Maurizio; Wegener, Gregers; Elfving, Betina

    2017-01-01

    It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI). In the present study we evaluated the effects of acute Foot-shock (FS)-stress and pre-treatment with the traditional antidepressant DMI on the gene expression of key regulators of synaptic plasticity and structure. Expression of Homer, Shank, Spinophilin, Densin-180, and the small RhoGTPase related gene Rac1 and downstream target genes, Limk1, Cofilin1 and Rock1 were investigated 1 day (1d), 7 d and 14d after FS-stress exposure. We found that DMI specifically increases the short-term expression of Spinophilin, as well as Homer and Shank family genes, and that both acute stress and DMI exert significant long-term effects on mRNA levels of genes involved in spine plasticity. These findings support the knowledge that acute FS stress and antidepressant treatment induce both rapid and sustained time-dependent alterations in structural components of synaptic plasticity in rodent medial PFC. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  8. [Glucose-monitoring neurons of the medial ventrolateral prefrontal (orbitofrontal) cortex are involved in the maintenance of homeostasis].

    Science.gov (United States)

    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Karádi, Zoltán

    2017-05-01

    The medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells. The functional significance of these chemosensory neurons was to be elucidated. Electrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed. Fifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group. Glucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis. Orv Hetil. 2017; 158(18): 692-700.

  9. Neural activity in ventral medial prefrontal cortex is modulated more before approach than avoidance during reinforced and extinction trial blocks.

    Science.gov (United States)

    Gentry, Ronny N; Roesch, Matthew R

    2018-04-16

    Ventromedial prefrontal cortex (vmPFC) is thought to provide regulatory control over Pavlovian fear responses and has recently been implicated in appetitive approach behavior, but much less is known about its role in contexts where appetitive and aversive outcomes can be obtained and avoided, respectively. To address this issue, we recorded from single neurons in vmPFC while male rats performed our combined approach and avoidance task under reinforced and non-reinforced (extinction) conditions. Surprisingly, we found that cues predicting reward modulated cell firing in vmPFC more often and more robustly than cues preceding avoidable shock; additionally, firing of vmPFC neurons was both response (press or no-press) and outcome (reinforced or extinction) selective. These results suggest a complex role for vmPFC in regulating behavior and supports its role in appetitive contexts during both reinforced and non-reinforced conditions. SIGNIFICANCE STATEMENT Selecting context-appropriate behaviors to gain reward or avoid punishment is critical for survival. While the role of ventromedial prefrontal cortex (vmPFC) in mediating fear responses is well-established, vmPFC has also been implicated in the regulation of reward-guided approach and extinction. Many studies have used indirect methods and simple behavioral procedures to study vmPFC, which leaves the literature incomplete. We recorded vmFPC neural activity during a complex cue-driven combined approach and avoidance task and during extinction. Surprisingly, we found very little vmPFC modulation to cues predicting avoidable shock, while cues predicting reward approach robustly modulated vmPFC firing in a response- and outcome-selective manner. This suggests a more complex role for vmPFC than current theories suggest, specifically regarding context-specific behavioral optimization. Copyright © 2018 the authors.

  10. NMDA and AMPA/kainate glutamatergic receptors in the prelimbic medial prefrontal cortex modulate the elaborated defensive behavior and innate fear-induced antinociception elicited by GABAA receptor blockade in the medial hypothalamus.

    Science.gov (United States)

    de Freitas, Renato Leonardo; Salgado-Rohner, Carlos José; Biagioni, Audrey Francisco; Medeiros, Priscila; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre S; Coimbra, Norberto Cysne

    2014-06-01

    The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) and amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptors of the prelimbic (PL) division of the medial prefrontal cortex (MPFC) on the panic attack-like reactions evoked by γ-aminobutyric acid-A receptor blockade in the medial hypothalamus (MH). Rats were pretreated with NaCl 0.9%, LY235959 (NMDA receptor antagonist), and NBQX (AMPA/kainate receptor antagonist) in the PL at 3 different concentrations. Ten minutes later, the MH was treated with bicuculline, and the defensive responses were recorded for 10 min. The antagonism of NMDA receptors in the PL decreased the frequency and duration of all defensive behaviors evoked by the stimulation of the MH and reduced the innate fear-induced antinociception. However, the pretreatment of the PL cortex with NBQX was able to decrease only part of defensive responses and innate fear-induced antinociception. The present findings suggest that the NMDA-glutamatergic system of the PL is critically involved in panic-like responses and innate fear-induced antinociception and those AMPA/kainate receptors are also recruited during the elaboration of fear-induced antinociception and in panic attack-related response. The activation of the glutamatergic neurotransmission of PL division of the MPFC during the elaboration of oriented behavioral reactions elicited by the chemical stimulation of the MH recruits mainly NMDA receptors in comparison with AMPA/kainate receptors.

  11. Characterization of excitatory and inhibitory neuron activation in the mouse medial prefrontal cortex following palatable food ingestion and food driven exploratory behavior

    Directory of Open Access Journals (Sweden)

    Ronald P Gaykema

    2014-07-01

    Full Text Available The medial prefrontal cortex (mPFC is implicated in aspects of executive function, that include the modulation of attentional and memory processes involved in goal selection. Food-seeking behavior has been shown to involve activation of the mPFC, both during the execution of strategies designed to obtain food and during the consumption of food itself. As these behaviors likely require differential engagement of the prefrontal cortex, we hypothesized that the pattern of neuronal activation would also be behavior dependent. In this study we describe, for the first time, the expression of Fos in different layers and cell types of the infralimbic/dorsal peduncular (IL/DP and prelimbic/anterior cingulate (PL/AC subdivisions of mouse mPFC following both the consumption of palatable food and following exploratory activity of the animal directed at obtaining food reward. While both manipulations led to increases of Fos expression in principal excitatory neurons relative to control, food-directed exploratory activity produced a significantly greater increase in Fos expression than observed in the food intake condition. Consequently, we hypothesized that mPFC interneuron activation would also be differentially engaged by these manipulations. Interestingly, Fos expression patterns differed substantially between treatments and interneuron subtype, illustrating how the differential engagement of subsets of mPFC interneurons depends on the behavioral state. In our experiments, both vasoactive intestinal peptide- and parvalbumin-expressing neurons showed enhanced Fos expression only during the food-dependent exploratory task and not during food intake. Conversely, elevations in arcuate and paraventricular hypothalamic fos expression were only observed following food intake and not following food driven exploration. Our data suggest that activation of select mPFC interneurons may be required to support high cognitive demand states while being dispensable during

  12. The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

    Science.gov (United States)

    Wu, Jade Q; Peters, Greg J; Rittner, Pedro; Cleland, Thomas A; Smith, David M

    2014-09-01

    Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function. © 2014 Wiley

  13. Bidirectional Control of Anxiety-Related Behaviors in Mice: Role of Inputs Arising from the Ventral Hippocampus to the Lateral Septum and Medial Prefrontal Cortex.

    Science.gov (United States)

    Parfitt, Gustavo Morrone; Nguyen, Robin; Bang, Jee Yoon; Aqrabawi, Afif J; Tran, Matthew M; Seo, D Kanghoon; Richards, Blake A; Kim, Jun Chul

    2017-07-01

    Anxiety is an adaptive response to potentially threatening situations. Exaggerated and uncontrolled anxiety responses become maladaptive and lead to anxiety disorders. Anxiety is shaped by a network of forebrain structures, including the hippocampus, septum, and prefrontal cortex. In particular, neural inputs arising from the ventral hippocampus (vHPC) to the lateral septum (LS) and medial prefrontal cortex (mPFC) are thought to serve as principal components of the anxiety circuit. However, the role of vHPC-to-LS and vHPC-to-mPFC signals in anxiety is unclear, as no study has directly compared their behavioral contribution at circuit level. We targeted LS-projecting vHPC cells and mPFC-projecting vHPC cells by injecting the retrogradely propagating canine adenovirus encoding Cre recombinase into the LS or mPFC, and injecting a Cre-responsive AAV (AAV8-hSyn-FLEX-hM3D or hM4D) into the vHPC. Consequences of manipulating these neurons were examined in well-established tests of anxiety. Chemogenetic manipulation of LS-projecting vHPC cells led to bidirectional changes in anxiety: activation of LS-projecting vHPC cells decreased anxiety whereas inhibition of these cells produced opposite anxiety-promoting effects. The observed anxiety-reducing function of LS-projecting cells was in contrast with the function of mPFC-projecting cells, which promoted anxiety. In addition, double retrograde tracing demonstrated that LS- and mPFC-projecting cells represent two largely anatomically distinct cell groups. Altogether, our findings suggest that the vHPC houses discrete populations of cells that either promote or suppress anxiety through differences in their projection targets. Disruption of the intricate balance in the activity of these two neuron populations may drive inappropriate behavioral responses seen in anxiety disorders.

  14. Inactivation of the Medial-Prefrontal Cortex Impairs Interval Timing Precision, but Not Timing Accuracy or Scalar Timing in a Peak-Interval Procedure in Rats

    Directory of Open Access Journals (Sweden)

    Catalin V. Buhusi

    2018-06-01

    Full Text Available Motor sequence learning, planning and execution of goal-directed behaviors, and decision making rely on accurate time estimation and production of durations in the seconds-to-minutes range. The pathways involved in planning and execution of goal-directed behaviors include cortico-striato-thalamo-cortical circuitry modulated by dopaminergic inputs. A critical feature of interval timing is its scalar property, by which the precision of timing is proportional to the timed duration. We examined the role of medial prefrontal cortex (mPFC in timing by evaluating the effect of its reversible inactivation on timing accuracy, timing precision and scalar timing. Rats were trained to time two durations in a peak-interval (PI procedure. Reversible mPFC inactivation using GABA agonist muscimol resulted in decreased timing precision, with no effect on timing accuracy and scalar timing. These results are partly at odds with studies suggesting that ramping prefrontal activity is crucial to timing but closely match simulations with the Striatal Beat Frequency (SBF model proposing that timing is coded by the coincidental activation of striatal neurons by cortical inputs. Computer simulations indicate that in SBF, gradual inactivation of cortical inputs results in a gradual decrease in timing precision with preservation of timing accuracy and scalar timing. Further studies are needed to differentiate between timing models based on coincidence detection and timing models based on ramping mPFC activity, and clarify whether mPFC is specifically involved in timing, or more generally involved in attention, working memory, or response selection/inhibition.

  15. Regulation of Alcohol Extinction and Cue-Induced Reinstatement by Specific Projections among Medial Prefrontal Cortex, Nucleus Accumbens, and Basolateral Amygdala.

    Science.gov (United States)

    Keistler, Colby R; Hammarlund, Emma; Barker, Jacqueline M; Bond, Colin W; DiLeone, Ralph J; Pittenger, Christopher; Taylor, Jane R

    2017-04-26

    The ability to inhibit drinking is a significant challenge for recovering alcoholics, especially in the presence of alcohol-associated cues. Previous studies have demonstrated that the regulation of cue-guided alcohol seeking is mediated by the basolateral amygdala (BLA), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC). However, given the high interconnectivity between these structures, it is unclear how mPFC projections to each subcortical structure, as well as projections between BLA and NAc, mediate alcohol-seeking behaviors. Here, we evaluate how cortico-striatal, cortico-amygdalar, and amygdalo-striatal projections control extinction and relapse in a rat model of alcohol seeking. Specifically, we used a combinatorial viral technique to express diphtheria toxin receptors in specific neuron populations based on their projection targets. We then used this strategy to create directionally selective ablations of three distinct pathways after acquisition of ethanol self-administration but before extinction and reinstatement. We demonstrate that ablation of mPFC neurons projecting to NAc, but not BLA, blocks cue-induced reinstatement of alcohol seeking and neither pathway is necessary for extinction of responding. Further, we show that ablating BLA neurons that project to NAc disrupts extinction of alcohol approach behaviors and attenuates reinstatement. Together, these data provide evidence that the mPFC→NAc pathway is necessary for cue-induced reinstatement of alcohol seeking, expand our understanding of how the BLA→NAc pathway regulates alcohol behavior, and introduce a new methodology for the manipulation of target-specific neural projections. SIGNIFICANCE STATEMENT The vast majority of recovering alcoholics will relapse at least once and understanding how the brain regulates relapse will be key to developing more effective behavior and pharmacological therapies for alcoholism. Given the high interconnectivity of cortical, striatal, and limbic

  16. Resting-state functional connectivity of antero-medial prefrontal cortex sub-regions in major depression and relationship to emotional intelligence.

    Science.gov (United States)

    Sawaya, Helen; Johnson, Kevin; Schmidt, Matthew; Arana, Ashley; Chahine, George; Atoui, Mia; Pincus, David; George, Mark S; Panksepp, Jaak; Nahas, Ziad

    2015-03-05

    Major depressive disorder has been associated with abnormal resting-state functional connectivity (FC), especially in cognitive processing and emotional regulation networks. Although studies have found abnormal FC in regions of the default mode network (DMN), no study has investigated the FC of specific regions within the anterior DMN based on cytoarchitectonic subdivisions of the antero-medial pre-frontal cortex (PFC). Studies from different areas in the field have shown regions within the anterior DMN to be involved in emotional intelligence. Although abnormalities in this region have been observed in depression, the relationship between the ventromedial PFC (vmPFC) function and emotional intelligence has yet to be investigated in depressed individuals. Twenty-one medication-free, non-treatment resistant, depressed patients and 21 healthy controls underwent a resting state functional magnetic resonance imaging session. The participants also completed an ability-based measure of emotional intelligence: the Mayer-Salovey-Caruso Emotional Intelligence Test. FC maps of Brodmann areas (BA) 25, 10 m, 10r, and 10p were created and compared between the two groups. Mixed-effects analyses showed that the more anterior seeds encompassed larger areas of the DMN. Compared to healthy controls, depressed patients had significantly lower connectivity between BA10p and the right insula and between BA25 and the perigenual anterior cingulate cortex. Exploratory analyses showed an association between vmPFC connectivity and emotional intelligence. These results suggest that individuals with depression have reduced FC between antero-medial PFC regions and regions involved in emotional regulation compared to control subjects. Moreover, vmPFC functional connectivity appears linked to emotional intelligence. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  17. Impulse control disorder and response-inhibition alterations in Parkinson's disease. A rare case of totally absent functionality of the medial-prefrontal cortex and review of literature.

    Science.gov (United States)

    Palermo, Sara; Morese, Rosalba; Zibetti, Maurizio; Dematteis, Francesca; Sirgiovanni, Stefano; Stanziano, Mario; Valentini, Maria Consuelo; Lopiano, Leonardo

    2017-11-01

    This report illustrates a Parkinson's disease (PD) patient with impulse-control disorder (ICD) and selective impairment in response-inhibition abilities as revealed by the performance in a functional magnetic resonance imaging (fMRI) anterior cingulate cortex - sensitive go-nogo task. In line with hypothesis on the role of response-inhibition disabilities in the arising of impulsivity in PD, the patient completely failed the go-nogo task. Moreover, fMRI acquisition revealed absent task-sensitive activity in the anterior cingulate cortex, medial prefrontal, and orbitofrontal cortices for the contrast nogo versus go, which signifying that a hypo-function of this network could be associated with ICD. A fronto-striatal and cingulo-frontal dysfunction may reflect impairment in metacognitive-executive abilities (such as response-inhibition, action monitoring, and error awareness) and promote compulsive repetition of behavior. Response-inhibition tasks may be useful in PD post-diagnostic phase, to better identify individuals at risk of developing ICD with dopaminergic medication.

  18. Chronic Gestational Stress Leads to Depressive-Like Behavior and Compromises Medial Prefrontal Cortex Structure and Function during the Postpartum Period

    Science.gov (United States)

    Leuner, Benedetta; Fredericks, Peter J.; Nealer, Connor; Albin-Brooks, Christopher

    2014-01-01

    Postpartum depression, which affects approximately 15% of new mothers, is associated with impaired mother-infant interactions and deficits in cognitive function. Exposure to stress during pregnancy is a major risk factor for postpartum depression. However, little is known about the neural consequences of gestational stress. The medial prefrontal cortex (mPFC) is a brain region that has been linked to stress, cognition, maternal care, and mood disorders including postpartum depression. Here we examined the effects of chronic gestational stress on mPFC function and whether these effects might be linked to structural modifications in the mPFC. We found that in postpartum rats, chronic gestational stress resulted in maternal care deficits, increased depressive-like behavior, and impaired performance on an attentional set shifting task that relies on the mPFC. Furthermore, exposure to chronic stress during pregnancy reduced dendritic spine density on mPFC pyramidal neurons and altered spine morphology. Taken together, these findings suggest that pregnancy stress may contribute to postpartum mental illness and its associated symptoms by compromising structural plasticity in the mPFC. PMID:24594708

  19. Brain networks of social action-outcome contingency: The role of the ventral striatum in integrating signals from the sensory cortex and medial prefrontal cortex.

    Science.gov (United States)

    Sumiya, Motofumi; Koike, Takahiko; Okazaki, Shuntaro; Kitada, Ryo; Sadato, Norihiro

    2017-10-01

    Social interactions can be facilitated by action-outcome contingency, in which self-actions result in relevant responses from others. Research has indicated that the striatal reward system plays a role in generating action-outcome contingency signals. However, the neural mechanisms wherein signals regarding self-action and others' responses are integrated to generate the contingency signal remain poorly understood. We conducted a functional MRI study to test the hypothesis that brain activity representing the self modulates connectivity between the striatal reward system and sensory regions involved in the processing of others' responses. We employed a contingency task in which participants made the listener laugh by telling jokes. Participants reported more pleasure when greater laughter followed their own jokes than those of another. Self-relevant listener's responses produced stronger activation in the medial prefrontal cortex (mPFC). Laughter was associated with activity in the auditory cortex. The ventral striatum exhibited stronger activation when participants made listeners laugh than when another did. In physio-physiological interaction analyses, the ventral striatum showed interaction effects for signals extracted from the mPFC and auditory cortex. These results support the hypothesis that the mPFC, which is implicated in self-related processing, gates sensory input associated with others' responses during value processing in the ventral striatum. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. The default modes of reading: Modulation of posterior cingulate and medial prefrontal cortex connectivity associated with subjective and objective differences in reading experience

    Directory of Open Access Journals (Sweden)

    Jonathan eSmallwood

    2013-11-01

    Full Text Available Reading is a fundamental human capacity and yet it can easily be derailed by the simple act of mind-wandering. A large-scale brain network, referred to as the default mode network (DMN, has been shown to be involved in both mind-wandering and reading, raising the question as to how the same neural system could be implicated in processes with both costs and benefits to narrative comprehension. Resting-state functional magnetic resonance imaging (rs-fMRI was used to explore whether the intrinsic functional connectivity of the two key midline hubs of the DMN — the posterior cingulate (PCC and medial prefrontal cortex (aMPFC — was predictive of individual differences in reading effectiveness (better comprehension, superior and task focus recorded outside of the scanner. Worse comprehension was associated with greater functional connectivity between the PCC and a region of the ventral striatum. By contrast reports of increasing task focus were associated with functional connectivity from the aMPFC to clusters in the PCC, the left parietal and temporal cortex, and the cerebellum. Our results suggest that the DMN has both costs (such as poor comprehension and benefits to reading (such as an on-task focus because its midline core can couple its activity with other regions to form distinct functional communities that allow seemingly opposing mental states to occur. This flexible coupling allows the DMN to participate in cognitive states that complement the act of reading as well as others that do not.

  1. Chronic gestational stress leads to depressive-like behavior and compromises medial prefrontal cortex structure and function during the postpartum period.

    Directory of Open Access Journals (Sweden)

    Benedetta Leuner

    Full Text Available Postpartum depression, which affects approximately 15% of new mothers, is associated with impaired mother-infant interactions and deficits in cognitive function. Exposure to stress during pregnancy is a major risk factor for postpartum depression. However, little is known about the neural consequences of gestational stress. The medial prefrontal cortex (mPFC is a brain region that has been linked to stress, cognition, maternal care, and mood disorders including postpartum depression. Here we examined the effects of chronic gestational stress on mPFC function and whether these effects might be linked to structural modifications in the mPFC. We found that in postpartum rats, chronic gestational stress resulted in maternal care deficits, increased depressive-like behavior, and impaired performance on an attentional set shifting task that relies on the mPFC. Furthermore, exposure to chronic stress during pregnancy reduced dendritic spine density on mPFC pyramidal neurons and altered spine morphology. Taken together, these findings suggest that pregnancy stress may contribute to postpartum mental illness and its associated symptoms by compromising structural plasticity in the mPFC.

  2. Enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the medial prefrontal cortex is triggered by the expression of Fos protein in guinea pigs.

    Science.gov (United States)

    Zheng, Ya-Juan; Dong, Yu-Chen; Zhu, Chao; Zhao, Mei-Sheng

    2016-03-01

    Eyelid conditioning, including delay eyelid conditioning and trace eyelid conditioning, has been used extensively to study neural structures and mechanisms of learning and memory as a form of associative learning. In the present study, microcurrent electrical stimulation was used to stimulate the medial prefrontal cortex (mPFC) to induce delay eyelid conditioning in guinea pigs. The acquisition rate and relative latency of the conditioned eyelid response (CR) and the startle eyelid response (SR) were analyzed. The mPFC sites in the guinea pigs were examined under a light microscope following Nissl staining. In addition, the expression of Fos protein in neurons was detected using immunohistochemistry and western blot analysis. The results indicated that the acquisition rates of CR and SR were increased significantly (Pmicrocurrent electrical stimulation of the mPFC in guinea pigs was triggered by the expression of Fos protein. The observations of the present study further expand the understanding of conditioned reflexes and may aid future investigations into the formation of eyelid conditioning and the mechanisms underlying the circuit in various conditions.

  3. Transcranial Direct Current Stimulation over the Medial Prefrontal Cortex and Left Primary Motor Cortex (mPFC-lPMC) Affects Subjective Beauty but Not Ugliness

    Science.gov (United States)

    Nakamura, Koyo; Kawabata, Hideaki

    2015-01-01

    Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC) and the left primary motor cortex (lPMC) correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS) to examine whether non-invasive brain stimulation modulates two types of esthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions. PMID:26696865

  4. Sex specific recruitment of a medial prefrontal cortex-hippocampal-thalamic system during context-dependent renewal of responding to food cues in rats.

    Science.gov (United States)

    Anderson, Lauren C; Petrovich, Gorica D

    2017-03-01

    the medial prefrontal cortex-hippocampal-thalamic system is a critical site of sex differences during renewal of appetitive Pavlovian responding to food cues. These findings provide evidence for novel neural mechanisms underlying sex differences in food motivation and contextual processing in associative learning and memory. The results should also inform future molecular and translational work investigating sex differences and maladaptive eating habits. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Adjunctive Treatment with Asenapine Augments the Escitalopram-Induced Effects on Monoaminergic Outflow and Glutamatergic Neurotransmission in the Medial Prefrontal Cortex of the Rat

    Science.gov (United States)

    Björkholm, Carl; Frånberg, Olivia; Malmerfelt, Anna; Marcus, Monica M.; Konradsson-Geuken, Åsa; Schilström, Björn; Jardemark, Kent

    2015-01-01

    Background: Substantial clinical data support the addition of low doses of atypical antipsychotic drugs to selective serotonin reuptake inhibitors (SSRIs) to rapidly enhance the antidepressant effect in treatment-resistant depression. Preclinical studies suggest that this effect is at least partly explained by an increased catecholamine outflow in the medial prefrontal cortex (mPFC). Methods: In the present study we used in vivo microdialysis in freely moving rats and in vitro intracellular recordings of pyramidal cells of the rat mPFC to investigate the effects of adding the novel atypical antipsychotic drug asenapine to the SSRI escitalopram with regards to monoamine outflow in the mPFC and dopamine outflow in nucleus accumbens as well as glutamatergic transmission in the mPFC. Results: The present study shows that addition of low doses (0.05 and 0.1 mg/kg) of asenapine to escitalopram (5 mg/kg) markedly enhances dopamine, noradrenaline, and serotonin release in the rat mPFC as well as dopamine release in the nucleus accumbens. Moreover, this drug combination facilitated both N-methyl-d-Aspartate (NMDA)– and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–induced currents as well as electrically evoked excitatory postsynaptic potentials in pyramidal cells of the rat mPFC. Conclusions: Our results support the notion that the augmentation of SSRIs by atypical antipsychotic drugs in treatment-resistant depression may, at least in part, be related to enhanced catecholamine output in the prefrontal cortex and that asenapine may be clinically used to achieve this end. In particular, the subsequent activation of the D1 receptor may be of importance for the augmented antidepressant effect, as this mechanism facilitated both NMDA and AMPA receptor-mediated transmission in the mPFC. Our novel observation that the drug combination, like ketamine, facilitates glutamatergic transmission in the mPFC may contribute to explain the rapid and potent antidepressant

  6. Dopamine, Noradrenaline and Differences in Sexual Behavior between Roman High and Low Avoidance Male Rats: A Microdialysis Study in the Medial Prefrontal Cortex.

    Science.gov (United States)

    Sanna, Fabrizio; Bratzu, Jessica; Piludu, Maria A; Corda, Maria G; Melis, Maria R; Giorgi, Osvaldo; Argiolas, Antonio

    2017-01-01

    Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the mesolimbic dopaminergic system of RHA rats vs. RLA rats, revealed by the higher increase of dopamine found in the dialysate obtained from the nucleus accumbens of RHA than RLA rats during sexual activity. This work shows that extracellular dopamine and noradrenaline (NA) also, increase in the dialysate from the medial prefrontal cortex (mPFC) of male RHA and RLA rats put in the presence of an inaccessible female rat and more markedly during direct sexual interaction. Such increases in dopamine (and its main metabolite 3,4-dihydroxyphenylacetic acid, DOPAC) and NA were found in both sexually naïve and experienced animals, but they were higher: (i) in RHA than in RLA rats; and (ii) in sexually experienced RHA and RLA rats than in their naïve counterparts. Finally, the differences in dopamine and NA in the mPFC occurred concomitantly to those in sexual activity, as RHA rats displayed higher levels of sexual motivation and copulatory performance than RLA rats in both the sexually naïve and experienced conditions. These results suggest that a higher dopaminergic tone also occurs in the mPFC, together with an increased noradrenergic tone, which may be involved in the different copulatory patterns found in RHA and RLA rats, as suggested for the mesolimbic dopaminergic system.

  7. Activation of pyramidal neurons in mouse medial prefrontal cortex enhances food seeking behavior while reducing impulsivity in the absence of an effect on food intake

    Directory of Open Access Journals (Sweden)

    Daniel McAllister Warthen

    2016-03-01

    Full Text Available The medial prefrontal cortex (mPFC is involved in a wide range of executive cognitive functions, including reward evaluation, decision-making, memory extinction, mood, and task switching. Manipulation of the mPFC has been shown to alter food intake and food reward valuation, but whether exclusive stimulation of mPFC pyramidal neurons, which form the principle output of the mPFC, is sufficient to mediate food rewarded instrumental behavior is unknown. We sought to determine the behavioral consequences of manipulating mPFC output by exciting pyramidal neurons in mouse mPFC during performance of a panel of behavioral assays, focusing on food reward. We found that increasing mPFC pyramidal cell output using Designer Receptors Exclusively Activated by Designer Drugs (DREADD enhanced performance in instrumental food reward assays that assess food seeking behavior, while sparing effects in affect and food intake. Specifically, activation of mPFC pyramidal neurons enhanced operant responding for food reward, reinstatement of palatable food seeking, and suppression of impulsive responding for food reward. Conversely, activation of mPFC pyramidal neurons had no effect on unconditioned food intake, social interaction, or behavior in an open field. Furthermore, we found that behavioral outcome is influenced by the degree of mPFC activation, with a low drive sufficient to enhance operant responding and a higher drive required to alter impulsivity. Additionally, we provide data demonstrating that DREADD stimulation involves a nitric oxide synthase dependent pathway, similar to endogenous muscarinic M3 receptor stimulation, a finding that provides novel mechanistic insight into an increasingly widespread method of remote neuronal control.

  8. External incentives and internal states guide goal-directed behavior via the differential recruitment of the nucleus accumbens and the medial prefrontal cortex.

    Science.gov (United States)

    Moscarello, J M; Ben-Shahar, O; Ettenberg, A

    2010-10-13

    Goal-directed behavior is governed by internal physiological states and external incentives present in the environment (e.g. hunger and food). While the role of the mesocorticolimbic dopamine (DA) system in behavior guided by environmental incentives has been well studied, the effect of relevant physiological states on the function of this system is less understood. The current study examined the role of the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAcc) in the kind of food-reinforced behaviors known to be sensitive to the internal state produced by food deprivation conditions. Operant lever-press reinforced on fixed ratio 1 (FR1) and progressive ratio (PR) schedules was tested after temporary inactivation of, or DA receptor blockade in, the prelimbic mPFC or NAcc core of rats with differing levels of food deprivation (0, 12 and 36-h). Food deprivation increased PR breakpoints, as well as the number of lever-presses emitted on the FR1 schedule. Both temporary inactivation and DA blockade of NAcc reduced breakpoints across deprivation conditions, while temporary inactivation and DA blockade of mPFC reduced breakpoints only in food-deprived rats. Neither manipulation of mPFC and NAcc had any effect on behavior reinforced on the FR1 schedule. Thus, mPFC and NAcc were differentially relevant to the behaviors tested-NAcc was recruited when the behavioral cost per reinforcer was rising or high regardless of food deprivation conditions, while mPFC was recruited when food-deprived animals behaved through periods of sparse reinforcement density in order to maximize available gain. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. 5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats.

    Science.gov (United States)

    Solati, Jalal; Salari, Ali-Akbar; Bakhtiari, Amir

    2011-10-31

    Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 μg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 μg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 μg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 μg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Induction and requirement of gene expression in the anterior cingulate cortex and medial prefrontal cortex for the consolidation of inhibitory avoidance memory

    Directory of Open Access Journals (Sweden)

    Zhang Yue

    2011-01-01

    Full Text Available Abstract Background Memory consolidation is a process to stabilize short-term memory, generating long-term memory. A critical biochemical feature of memory consolidation is a requirement for gene expression. Previous studies have shown that fear memories are consolidated through the activation of gene expression in the amygdala and hippocampus, indicating essential roles of these brain regions in memory formation. However, it is still poorly understood whether gene expression in brain regions other than the amygdala/hippocampus is required for the consolidation of fear memory; however, several brain regions are known to play modulatory roles in fear memory formation. Results To further understand the mechanisms underlying the formation of fear memory, we first identified brain regions where gene expression is activated after learning inhibitory avoidance (IA by analyzing the expression of the immediately early genes c-fos and Arc as markers. Similarly with previous findings, the induction of c-fos and Arc expression was observed in the amygdala and hippocampus. Interestingly, we also observed the induction of c-fos and Arc expression in the medial prefrontal cortex (mPFC: prelimbic (PL and infralimbic (IL regions and Arc expression in the anterior cingulate cortex (ACC. We next examined the roles of these brain regions in the consolidation of IA memory. Consistent with previous findings, inhibiting protein synthesis in the hippocampus blocked the consolidation of IA memory. More importantly, inhibition in the mPFC or ACC also blocked the formation of IA memory. Conclusion Our observations indicated that the formation of IA memory requires gene expression in the ACC and mPFC as well as in the amygdala and hippocampus, suggesting essential roles of the ACC and mPFC in IA memory formation.

  11. Glycogen synthase kinase-3β inhibition in the medial prefrontal cortex mediates paradoxical amphetamine action in a mouse model of ADHD

    Directory of Open Access Journals (Sweden)

    Yi-Chun eYen

    2015-03-01

    Full Text Available Psychostimulants show therapeutic efficacy in the treatment of attention-deficit hyperactivity disorder (ADHD. It is generally assumed that they ameliorate ADHD symptoms via interfering with monoaminergic signaling. We combined behavioral pharmacology, neurochemistry and molecular analyses to identify mechanisms underlying the paradoxical calming effect of amphetamine in low trait anxiety behavior (LAB mice, a novel multigenetic animal model of ADHD. Amphetamine (1 mg/kg and methylphenidate (10 mg/kg elicited similar dopamine and norepinephrine release in the medial prefrontal cortex (mPFC and in the striatum of LAB mice. In contrast, amphetamine decreased, while methylphenidate increased locomotor activity. This argues against changes in dopamine and/or norepinephrine release as mediators of amphetamine paradoxical effects. Instead, the calming activity of amphetamine corresponded to the inhibition of glycogen synthase kinase3β (GSK3β activity, specifically in the mPFC. Accordingly, not only systemic administration of the GSK3β inhibitor TDZD-8 (20 mg/kg, but also local microinjections of TDZD-8 and amphetamine into the mPFC, but not into the striatum, decreased locomotor activity in LAB mice. Amphetamine effects seem to depend on NMDA receptor signaling, since pre- or co-treatment with MK-801 (0.3 mg/kg abolished the effects of amphetamine (1 mg/kg on the locomotion and on the phosphorylation of GSK3β at the level of the mPFC. Taken together, the paradoxical calming effect of amphetamine in hyperactive LAB mice concurs with a decreased GSK3β activity in the mPFC. This effect appears to be independent of dopamine or norepinephrine release, but contingent on NMDA receptor signaling.

  12. Effect of Transcranial Direct Current Stimulation of the Medial Prefrontal Cortex on the Gratitude of Individuals with Heterogeneous Ability in an Experimental Labor Market

    Directory of Open Access Journals (Sweden)

    Pengcheng Wang

    2017-11-01

    Full Text Available Gratitude is an important aspect of human sociality, which benefits mental health and interpersonal relationships. Thus, elucidating the neural mechanism of gratitude, which is only now beginning to be investigated, is important. To this end, this study specifies the medial prefrontal cortex (mPFC involved in the gratitude of heterogeneous individuals using the transcranial direct current stimulation (tDCS technique. Previous neural studies have shown the involvement of mPFC in social cognition and value evaluation, which are closely related to gratitude. However, the causal relationship between this neural area and gratitude has not been fully examined and the effect of individual social heterogeneity has been ignored. Meanwhile, behavioral economics studies have proposed that the abilities of employees in the labor market would affect their gratitude and emotional response. Thus, we designed an experiment based on gift exchange game to investigate the relationship between mPFC and gratitude of heterogeneous employees. Before the experiment, participants were asked to perform self-cognition of their abilities through an appropriately difficult task. We then used the effort of participants to imply their gratitude and analyzed the effort levels of employees with different abilities under anodal, cathodal, and sham stimulations. The results showed that employees under anodal stimulation were significantly likely to increase their effort than those under sham stimulation, and employees under cathodal stimulation ranked at the bottom of the list. Moreover, the effort levels of low-ability employees were obviously higher than those of high-ability employees. The cathodal stimulation of mPFC significantly reduced the effort levels of low-ability employees, whereas its anodal tDCS stimulation increased the effort levels of high-ability employees. These outcomes verify the relationship between mPFC and gratitude using tDCS and provided one of the first

  13. Self-generation and positivity effects following transcranial random noise stimulation in medial prefrontal cortex: A reality monitoring task in older adults.

    Science.gov (United States)

    Mammarella, Nicola; Di Domenico, Alberto; Palumbo, Rocco; Fairfield, Beth

    2017-06-01

    Activation of medial Prefrontal Cortex (mPFC) has been typically found during reality monitoring tasks (i.e., distinguishing between internal self-generated vs external information). No study, however, has yet investigated whether transcranial Random Noise Stimulation (tRNS) over the mPFC leads to a reduction in reality-monitoring misattributions in aging. In particular, stimulating mPFC should increase the number of cognitive operations engaged while encoding and this distinctive information may help older adults to discriminate between internal and external sources better. In addition, given that older adults are more sensitive to positively-charged information compared to younger adults and that mPFC is typically recruited during encoding of positive stimuli with reference to themselves, activation of mPFC should further sustain source retrieval in older adults. In this double-blind, sham-controlled study, we examined whether tRNS over the mPFC of healthy younger and older adults during encoding enhances subsequent reality monitoring for seen versus imagined emotionally-charged words. Our findings show that tRNS enhances reality monitoring for positively-charged imagined words in the older adult group alone, highlighting the role that mPFC plays in their memory for positive information. In line with the control-based account of positivity effects, our results add evidence about the neurocognitive processes involved in reality monitoring when older adults face emotionally-charged events. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Early-stage attenuation of phase-amplitude coupling in the hippocampus and medial prefrontal cortex in a transgenic rat model of Alzheimer's disease.

    Science.gov (United States)

    Bazzigaluppi, Paolo; Beckett, Tina L; Koletar, Margaret M; Lai, Aaron Y; Joo, Illsung L; Brown, Mary E; Carlen, Peter L; McLaurin, JoAnne; Stefanovic, Bojana

    2018-03-01

    Alzheimer's disease (AD) is pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ-dependent neuronal dysfunction including modulation of gamma-aminobutyric acid-ergic signaling. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broad repertoire of AD-like pathologies to investigate the neuronal network functioning using simultaneous intracranial recordings from the hippocampus (HPC) and the medial prefrontal cortex (mPFC), followed by pathological analyses of gamma-aminobutyric acid (GABA A ) receptor subunits α1 , α5, and δ, and glutamic acid decarboxylases (GAD65 and GAD67). Concomitant to amyloid deposition and tau hyperphosphorylation, low-gamma band power was strongly attenuated in the HPC and mPFC of TgF344-AD rats in comparison to those in non-transgenic littermates. In addition, the phase-amplitude coupling of the neuronal networks in both areas was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude in TgF344-AD animals. Finally, the gamma coherence between HPC and mPFC was attenuated as well. These results demonstrate significant neuronal network dysfunction at an early stage of AD-like pathology. This network dysfunction precedes the onset of cognitive deficits and is likely driven by Aβ and tau pathologies. This article is part of the Special Issue "Vascular Dementia". © 2017 Her Majesty the Queen in Right of Canada Journal of Neurochemistry © 2017 International Society for Neurochemistry.

  15. 5-Aza-2'-deoxycytidine in the medial prefrontal cortex regulates alcohol-related behavior and Ntf3-TrkC expression in rats.

    Directory of Open Access Journals (Sweden)

    Xiaomeng Qiao

    Full Text Available Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc, an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC. Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test. We found that 5-Aza-dc injection into the mPFC significantly decreased alcohol consumption and alcohol preference in alcohol-exposure rats, corresponding to the reduced blood alcohol levels. Although 5-Aza-dc potentiated the anxiety-like behavior of alcohol-exposure rats, it had no effect on the locomotor activity. Moreover, both of the mRNA and protein levels of DNA Methyltransferase 3A (DNMT3A and DNMT3B in the mPFC were upregulated after 35 days of alcohol exposure and this upregulation could be reversed by 5-Aza-dc treatment. Additionally, 5-Aza-dc reversed the alcohol-induced downregulation of neurotrophin-3 (Ntf3, correspondingly the expression of its receptor-TrkC was reduced. These findings identified a functional role of 5-Aza-dc in alcohol-related behavioral phenotypes and one of the potential target genes, Ntf3. We also provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcohol abuse.

  16. Evidence for a Specific Integrative Mechanism for Episodic Memory Mediated by AMPA/kainate Receptors in a Circuit Involving Medial Prefrontal Cortex and Hippocampal CA3 Region.

    Science.gov (United States)

    de Souza Silva, Maria A; Huston, Joseph P; Wang, An-Li; Petri, David; Chao, Owen Yuan-Hsin

    2016-07-01

    We asked whether episodic-like memory requires neural mechanisms independent of those that mediate its component memories for "what," "when," and "where," and if neuronal connectivity between the medial prefrontal cortex (mPFC) and the hippocampus (HPC) CA3 subregion is essential for episodic-like memory. Unilateral lesion of the mPFC was combined with unilateral lesion of the CA3 in the ipsi- or contralateral hemispheres in rats. Episodic-like memory was tested using a task, which assesses the integration of memories for "what, where, and when" concomitantly. Tests for novel object recognition (what), object place (where), and temporal order memory (when) were also applied. Bilateral disconnection of the mPFC-CA3 circuit by N-methyl-d-aspartate (NMDA) lesions disrupted episodic-like memory, but left the component memories for object, place, and temporal order, per se, intact. Furthermore, unilateral NMDA lesion of the CA3 plus injection of (6-cyano-7-nitroquinoxaline-2,3-dione) (CNQX) (AMPA/kainate receptor antagonist), but not AP-5 (NMDA receptor antagonist), into the contralateral mPFC also disrupted episodic-like memory, indicating the mPFC AMPA/kainate receptors as critical for this circuit. These results argue for a selective neural system that specifically subserves episodic memory, as it is not critically involved in the control of its component memories for object, place, and time. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Differential Effects of Inactivation of Discrete Regions of Medial Prefrontal Cortex on Memory Consolidation of Moderate and Intense Inhibitory Avoidance Training

    Directory of Open Access Journals (Sweden)

    María E. Torres-García

    2017-11-01

    Full Text Available It has been found that the medial prefrontal cortex (mPFC is involved in memory encoding of aversive events, such as inhibitory avoidance (IA training. Dissociable roles have been described for different mPFC subregions regarding various memory processes, wherein the anterior cingulate cortex (ACC, prelimbic cortex (PL, and infralimbic cortex (IL are involved in acquisition, retrieval, and extinction of aversive events, respectively. On the other hand, it has been demonstrated that intense training impedes the effects on memory of treatments that typically interfere with memory consolidation. The aim of this work was to determine if there are differential effects on memory induced by reversible inactivation of neural activity of ACC, PL, or IL produced by tetrodotoxin (TTX in rats trained in IA using moderate (1.0 mA and intense (3.0 mA foot-shocks. We found that inactivation of ACC has no effects on memory consolidation, regardless of intensity of training. PL inactivation impairs memory consolidation in the 1.0 mA group, while no effect on consolidation was produced in the 3.0 mA group. In the case of IL, a remarkable amnestic effect in LTM was observed in both training conditions. However, state-dependency can explain the amnestic effect of TTX found in the 3.0 mA IL group. In order to circumvent this effect, TTX was injected into IL immediately after training (thus avoiding state-dependency. The behavioral results are equivalent to those found after PL inactivation. Therefore, these findings provide evidence that PL and IL, but not ACC, mediate LTM of IA only in moderate training.

  18. Noradrenergic signaling in the medial prefrontal cortex and amygdala differentially regulates vicarious trial-and-error in a spatial decision-making task.

    Science.gov (United States)

    Amemiya, Seiichiro; Kubota, Natsuko; Umeyama, Nao; Nishijima, Takeshi; Kita, Ichiro

    2016-01-15

    In uncertain choice situations, we deliberately search and evaluate possible options before taking an action. Once we form a preference regarding the current situation, we take an action more automatically and with less deliberation. In rats, the deliberation process can be seen in vicarious trial-and-error behavior (VTE), which is a head-orienting behavior toward options at a choice point. Recent neurophysiological findings suggest that VTE reflects the rat's thinking about future options as deliberation, expectation, and planning when rats feel conflict. VTE occurs depending on the demand: an increase occurs during initial learning, and a decrease occurs with progression in learning. However, the brain circuit underlying the regulation of VTE has not been thoroughly examined. In situations in which VTE often appears, the medial prefrontal cortex (mPFC) and the amygdala (AMY) are crucial for learning and decision making. Our previous study reported that noradrenaline regulates VTE. Here, to investigate whether the mPFC and AMY are involved in regulation of VTE, we examined the effects of local injection of clonidine, an alpha2 adrenergic autoreceptor agonist, into either region in rats during VTE and choice behavior during a T-maze choice task. Injection of clonidine into either region impaired selection of the advantageous choice in the task. Furthermore, clonidine injection into the mPFC suppressed occurrence of VTE in the early phase of the task, whereas injection into the AMY inhibited the decrease in VTE in the later phase and thus maintained a high level of VTE throughout the task. These results suggest that the mPFC and AMY play a role in the increase and decrease in VTE, respectively, and that noradrenergic mechanisms mediate the dynamic regulation of VTE over experiences. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Differential dorsal and ventral medial prefrontal representations of the implicit self modulated by individualism and collectivism: An fMRI study.

    Science.gov (United States)

    Harada, Tokiko; Li, Zhang; Chiao, Joan Y

    2010-01-01

    Individualism and collectivism, or self-construal style, refer to cultural values that influence how people think about themselves and their relation to the social and physical environment. Recent neuroimaging evidence suggests that cultural values of individualism and collectivism dynamically modulate neural response within cortical midline structures, such as the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), during explicit self-evaluation. However, it remains unknown whether cultural priming modulates neural response during self-evaluation due to explicit task demands. Here we investigated how cultural priming of self-construal style affects neural activity within cortical midline structures during implicit self-evaluation in bicultural individuals. Results indicate that ventral MPFC showed relatively less deactivation during implicit evaluation of both self- and father-relevant information as compared to control condition (e.g., information of an unfamiliar person), irrespective of cultural priming. By contrast, dorsal MPFC showed relatively less deactivation during implicit evaluation of father-relevant information, but not self-relevant information, as compared to control condition, only when they were primed with individualism. Furthermore, dorsal MPFC showed relatively less deactivation during implicit evaluation of father-relevant information as compared to self-relevant condition only when they were primed with individualism. Hence, our results indicate that cultural priming modulates neural response within dorsal, but not ventral, portions of MPFC in a stimulus-driven rather than task-driven manner. More broadly, these findings suggest that cultural values dynamically shape neural representations during the evaluation, rather than the detection, of self-relevant information.

  20. The Stressed Female Brain: Neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress

    Directory of Open Access Journals (Sweden)

    Lisa Y. Maeng

    2013-12-01

    Full Text Available Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD, indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL and infralimbic (IL subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. 24h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similar to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful

  1. Effect of Transcranial Direct Current Stimulation of the Medial Prefrontal Cortex on the Gratitude of Individuals with Heterogeneous Ability in an Experimental Labor Market.

    Science.gov (United States)

    Wang, Pengcheng; Wang, Guangrong; Niu, Xiaofei; Shang, Huiliang; Li, Jianbiao

    2017-01-01

    Gratitude is an important aspect of human sociality, which benefits mental health and interpersonal relationships. Thus, elucidating the neural mechanism of gratitude, which is only now beginning to be investigated, is important. To this end, this study specifies the medial prefrontal cortex (mPFC) involved in the gratitude of heterogeneous individuals using the transcranial direct current stimulation (tDCS) technique. Previous neural studies have shown the involvement of mPFC in social cognition and value evaluation, which are closely related to gratitude. However, the causal relationship between this neural area and gratitude has not been fully examined and the effect of individual social heterogeneity has been ignored. Meanwhile, behavioral economics studies have proposed that the abilities of employees in the labor market would affect their gratitude and emotional response. Thus, we designed an experiment based on gift exchange game to investigate the relationship between mPFC and gratitude of heterogeneous employees. Before the experiment, participants were asked to perform self-cognition of their abilities through an appropriately difficult task. We then used the effort of participants to imply their gratitude and analyzed the effort levels of employees with different abilities under anodal, cathodal, and sham stimulations. The results showed that employees under anodal stimulation were significantly likely to increase their effort than those under sham stimulation, and employees under cathodal stimulation ranked at the bottom of the list. Moreover, the effort levels of low-ability employees were obviously higher than those of high-ability employees. The cathodal stimulation of mPFC significantly reduced the effort levels of low-ability employees, whereas its anodal tDCS stimulation increased the effort levels of high-ability employees. These outcomes verify the relationship between mPFC and gratitude using tDCS and provided one of the first instances of

  2. Activation of type 4 dopaminergic receptors in the prelimbic area of medial prefrontal cortex is necessary for the expression of innate fear behavior.

    Science.gov (United States)

    Vergara, Macarena D; Keller, Victor N; Fuentealba, José A; Gysling, Katia

    2017-05-01

    The prelimbic area (PL) of the medial Prefrontal cortex (mPFC) is involved in the acquisition and expression of conditioned and innate fear. Both types of fear share several neuronal pathways. It has been documented that dopamine (DA) plays an important role in the regulation of aversive memories in the mPFC. The exposure to an aversive stimulus, such as the smell of a predator odor or the exposure to footshock stress is accompanied by an increase in mPFC DA release. Evidence suggests that the type 4 dopaminergic receptor (D4R) is the molecular target through which DA modulates fear expression. In fact, the mPFC is the brain region with the highest expression of D4R; however, the role of D4R in the expression of innate fear has not been fully elucidated. Therefore, the principal objective of this work was to evaluate the participation of mPFC D4R in the expression of innate fear. Rats were exposed to the elevated plus-maze (EPM) and to the cat odor paradigm after the intra PL injection of L-745,870, selective D4R antagonist, to measure the expression of fear-related behaviors. Intra PL injection of L-745,870 increased the time spent in the EPM open arms and decreased freezing behavior in the cat odor paradigm. Our results also showed that D4R is expressed in GABAergic and pyramidal neurons in the PL region of PFC. Thus, D4R antagonism in the PL decreases the expression of innate fear-behavior indicating that the activation of D4R in the PL is necessary for the expression of innate fear-behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The effect of chronic phenytoin administration on single prolonged stress induced extinction retention deficits and glucocorticoid upregulation in the rat medial prefrontal cortex.

    Science.gov (United States)

    George, Sophie A; Rodriguez-Santiago, Mariana; Riley, John; Rodriguez, Elizabeth; Liberzon, Israel

    2015-01-01

    Post-traumatic stress disorder (PTSD) is a chronic, debilitating disorder. Only two pharmacological agents are approved for PTSD treatment, and they often do not address the full range of symptoms nor are they equally effective in all cases. Animal models of PTSD are critical for understanding the neurobiology involved and for identification of novel therapeutic targets. Using the rodent PTSD model, single prolonged stress (SPS), we have implicated aberrant excitatory neural transmission and glucocorticoid receptor (GR) upregulation in the medial prefrontal cortex (mPFC) and hippocampus (HPC) in fear memory abnormalities associated with PTSD. The objective of this study is to examine the potential protective effect of antiepileptic phenytoin (PHE) administration on SPS-induced extinction retention deficits and GR expression. Forty-eight SPS-treated male Sprague Dawley rats or controls were administered PHE (40, 20 mg/kg, vehicle) for 7 days following SPS stressors; then, fear conditioning, extinction, and extinction retention were tested. Fear conditioning and extinction were unaffected by SPS or PHE, but SPS impaired extinction retention, and both doses of PHE rescued this impairment. Similarly, SPS increased GR expression in the mPFC and dorsal HPC, and PHE prevented SPS-induced GR upregulation in the mPFC. These data demonstrate that PHE administration can prevent the development of extinction retention deficits and upregulation of GR. PHE exerts inhibitory effects on voltage-gated sodium channels and decreases excitatory neural transmission via glutamate antagonism. If glutamate hyperactivity in the days following SPS contributes to SPS-induced deficits, then these data may suggest that the glutamatergic system constitutes a target for secondary prevention.

  4. Too much of a good thing: blocking noradrenergic facilitation in medial prefrontal cortex prevents the detrimental effects of chronic stress on cognition.

    Science.gov (United States)

    Jett, Julianne D; Morilak, David A

    2013-03-01

    Cognitive impairments associated with dysfunction of the medial prefrontal cortex (mPFC) are prominent in stress-related psychiatric disorders. We have shown that enhancing noradrenergic tone acutely in the rat mPFC facilitated extra-dimensional (ED) set-shifting on the attentional set-shifting test (AST), whereas chronic unpredictable stress (CUS) impaired ED. In this study, we tested the hypothesis that the acute facilitatory effect of norepinephrine (NE) in mPFC becomes detrimental when activated repeatedly during CUS. Using microdialysis, we showed that the release of NE evoked in mPFC by acute stress was unchanged at the end of CUS treatment. Thus, to then determine if repeated elicitation of this NE activity in mPFC during CUS may have contributed to the ED deficit, we infused a cocktail of α(1)-, β(1)-, and β(2)-adrenergic receptor antagonists into the mPFC prior to each CUS session, then tested animals drug free on the AST. Antagonist treatment prevented the CUS-induced ED deficit, suggesting that NE signaling during CUS compromised mPFC function. We confirmed that this was not attributable to sensitization of adrenergic receptor function following chronic antagonist treatment, by administering an additional microinjection into the mPFC immediately prior to ED testing. Acute antagonist treatment did not reverse the beneficial effects of chronic drug treatment during CUS, nor have any effect on baseline ED performance in chronic vehicle controls. Thus, we conclude that blockade of noradrenergic receptors in mPFC protected against the detrimental cognitive effects of CUS, and that repeated elicitation of noradrenergic facilitatory activity is one mechanism by which chronic stress may promote mPFC cognitive dysfunction.

  5. Using vitamin E to prevent the impairment in behavioral test, cell loss and dendrite changes in medial prefrontal cortex induced by tartrazine in rats.

    Science.gov (United States)

    Rafati, Ali; Nourzei, Nasrin; Karbalay-Doust, Saied; Noorafshan, Ali

    2017-03-01

    Tartrazine is a food color that may adversely affect the nervous system. Vitamin E is a neuro-protective agent. This study aimed to evaluate the effects of tartrazine and vitamin E on the performance of rats in memory and learning tests as well as the structure of medial Prefrontal Cortex (mPFC). The rats were first divided into seven groups which received the followings for a period of seven weeks: distilled water, corn oil, vitamin E (100mg/kg/day), a low dose (50mg/kg/day) and a high dose (50mg/kg/day) of tartrazine with and without vitamin E. Behavioral tests were conducted and the brain was extracted for stereological methods The high dose of tartrazine decreased the exploration time of novel objects (Ptartrazine led into an increase in working and reference memory errors in acquisition and retention phases (eight-arm radial maze) compared to distilled water group (Ptartrazine induced a reduction in the volume of mPFC (∼13%) and its subdivision. Not only that, but the number of neurons and glial cells (∼14%) as well as the mushroom and thin spines per dendrite length declined. The length of dendrites per neuron also reduced in comparison to the distilled water group (Ptartrazine prevented the above-mentioned changes. An acceptable daily dose of tartrazine could induce impairment in spatial memory and dendrite structure. Moreover, a high dose of tartrazine may defect the visual memory, mPFC structure, the spatial memory and also cause dendrite changes. Vitamin E could prevent the behavioral and structural changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Trace Fear Conditioning Differentially Modulates Intrinsic Excitability of Medial Prefrontal Cortex-Basolateral Complex of Amygdala Projection Neurons in Infralimbic and Prelimbic Cortices.

    Science.gov (United States)

    Song, Chenghui; Ehlers, Vanessa L; Moyer, James R

    2015-09-30

    Neuronal activity in medial prefrontal cortex (mPFC) is critical for the formation of trace fear memory, yet the cellular mechanisms underlying these memories remain unclear. One possibility involves the modulation of intrinsic excitability within mPFC neurons that project to the basolateral complex of amygdala (BLA). The current study used a combination of retrograde labeling and in vitro whole-cell patch-clamp recordings to examine the effect of trace fear conditioning on the intrinsic excitability of layer 5 mPFC-BLA projection neurons in adult rats. Trace fear conditioning significantly enhanced the intrinsic excitability of regular spiking infralimbic (IL) projection neurons, as evidenced by an increase in the number of action potentials after current injection. These changes were also associated with a reduction in spike threshold and an increase in h current. In contrast, trace fear conditioning reduced the excitability of regular spiking prelimbic (PL) projection neurons, through a learning-related decrease of input resistance. Interestingly, the amount of conditioned freezing was (1) positively correlated with excitability of IL-BLA projection neurons after conditioning and (2) negatively correlated with excitability of PL-BLA projection neurons after extinction. Trace fear conditioning also significantly enhanced the excitability of burst spiking PL-BLA projection neurons. In both regions, conditioning-induced plasticity was learning specific (observed in conditioned but not in pseudoconditioned rats), flexible (reversed by extinction), and transient (lasted extinction of trace fear conditioning. Significance statement: Frontal lobe-related function is vital for a variety of important behaviors, some of which decline during aging. This study involves a novel combination of electrophysiological recordings from fluorescently labeled mPFC-to-amygdala projection neurons in rats with acquisition and extinction of trace fear conditioning to determine how

  7. Activation of the mouse primary visual cortex by medial prefrontal subregion stimulation is not mediated by cholinergic basalo-cortical projections

    Directory of Open Access Journals (Sweden)

    Hoang Nam eNguyen

    2015-02-01

    Full Text Available The medial prefrontal cortex (mPFC exerts top-down control of primary visual cortex (V1 activity. As there is no direct neuronal projection from mPFC to V1, this functional connection may use an indirect route, i.e., via basalo-cortical cholinergic projections. The cholinergic projections to V1 originate from neurons in the horizontal limb of the diagonal band of Broca (HDB, which receive neuronal projections from the ventral part of the mPFC, composed of prelimbic (PrL and infralimbic cortices (IL. Therefore, the objective of this study was to determine whether electrical stimulation of mice mPFC subregions activate 1 V1 neurons and 2 HDB cholinergic neurons, suggesting that the HDB serves as a relay point in the mPFC-V1 interaction. Neuronal activation was quantified using c-Fos immunocytochemistry or thallium autometallography for each V1 layer using automated particle analysis tools and optical density measurement. Stimulation of IL and PrL induced significantly higher c-Fos expression or thallium labelling in layers II/III and V of V1 in the stimulated hemisphere only. A HDB cholinergic neuron-specific lesion by saporin administration reduced IL-induced c-Fos expression in layers II/III of V1 but not in layer V. However, there was no c-Fos expression or thallium labelling in the HDB neurons, suggesting that this area was not activated by IL stimulation. Stimulation of another mPFC subarea, the anterior cingulate cortex (AC, which is involved in attention and receives input from V1, activated neither V1 nor HDB. The present results indicate that IL and PrL, but not AC, stimulation activates V1 with the minor involvement of the HDB cholinergic projections. These results suggest a functional link between the ventral mPFC and V1, but this function is only marginally supported by HDB cholinergic neurons and may involve other brain regions.

  8. The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats

    Directory of Open Access Journals (Sweden)

    Di Marzo Vincenzo

    2011-01-01

    Full Text Available Abstract Background Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1 and the catabolic enzyme fatty acid amide hydrolase (FAAH in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL cortex in neuropathic rats. Results The effect of N-arachidonoyl-serotonin (AA-5-HT, a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. Conclusion These data suggest a possible involvement of endovanilloids in the cortical

  9. EXTRAÍBLES DE CORTEZAS CHILENAS: EFECTO SOBRE LA LUMINISCENCIA DE BACTERIAS

    OpenAIRE

    Poblete,Hernán; Roffael,Edmone; Miertzsch,Helmut

    2007-01-01

    Se determinó la disminución de la bioluminiscencia de bacterias como indicador de la actividad biológica de extractos de corteza. Se analizaron cuatro cortezas nativas chilenas. La reducción de la bioluminiscencia fue diferente dependiendo de la especie de corteza. El aumento del tiempo de un tratamiento térmico de la corteza (24, 48, 72 y 144 horas con 103ºC) produjo una reducción de la actividad biológica de los extractos. El estudio indica que los terpenos podrían ser responsables del efec...

  10. Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats.

    Science.gov (United States)

    Abekawa, Tomohiro; Ito, Koki; Nakagawa, Shin; Koyama, Tsukasa

    2007-06-01

    Neurodevelopmental deficits of parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)ergic interneurons in prefrontal cortex have been reported in schizophrenia. Glutamate influences the proliferation of this type of interneuron by an N-methyl-D-aspartate (NMDA)-receptor-mediated mechanism. The present study hypothesized that prenatal blockade of NMDA receptors would disrupt GABAergic neurodevelopment, resulting in differences in effects on behavioral responses to a noncompetitive NMDA antagonist, phencyclidine (PCP), and a dopamine releaser, methamphetamine (METH). GABAergic neurons were immunohistochemically stained with parvalbumin antibody. Psychostimulant-induced hyperlocomotion was measured using an infrared sensor. Prenatal exposure (E15-E18) to the NMDA receptor antagonist MK-801 reduced the density of parvalbumin-immunoreactive neurons in rat medial prefrontal cortex on postnatal day 63 (P63) and enhanced PCP-induced hyperlocomotion but not the acute effects of METH on P63 or the development of behavioral sensitization. Prenatal exposure to MK-801 reduced the number of parvalbumin-immunoreactive neurons even on postnatal day 35 (P35) and did not enhance PCP-induced hyperlocomotion, the acute effects of METH on P35, or the development of behavioral sensitization to METH. These findings suggest that prenatal blockade of NMDA receptors disrupts GABAergic neurodevelopment in medial prefrontal cortex, and that this disruption of GABAergic development may be related to the enhancement of the locomotion-inducing effect of PCP in postpubertal but not juvenile offspring. GABAergic deficit is unrelated to the effects of METH. This GABAergic neurodevelopmental disruption and the enhanced PCP-induced hyperlocomotion in adult offspring prenatally exposed to MK-801 may prove useful as a new model of the neurodevelopmental process of pathogenesis of treatment-resistant schizophrenia via an NMDA-receptor-mediated hypoglutamatergic mechanism.

  11. Activation of beta2-Adrenoceptor Enhances Synaptic Potentiation and Behavioral Memory via cAMP-PKA Signaling in the Medial Prefrontal Cortex of Rats

    Science.gov (United States)

    Zhou, Hou-Cheng; Sun, Yan-Yan; Cai, Wei; He, Xiao-Ting; Yi, Feng; Li, Bao-Ming; Zhang, Xue-Han

    2013-01-01

    The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation, behavioral inhibition, as well as memory storage. The functions of PFC are very sensitive to norepinephrine (NE), and even low levels of endogenously released NE exert a dramatic influence on the functioning of the PFC.…

  12. The transition from childhood to adolescence is marked by a general decrease in amygdala reactivity and an affect-specific ventral-to-dorsal shift in medial prefrontal recruitment

    Directory of Open Access Journals (Sweden)

    Jennifer A. Silvers

    2017-06-01

    Full Text Available Understanding how and why affective responses change with age is central to characterizing typical and atypical emotional development. Prior work has emphasized the role of the amygdala and prefrontal cortex (PFC, which show age-related changes in function and connectivity. However, developmental neuroimaging research has only recently begun to unpack whether age effects in the amygdala and PFC are specific to affective stimuli or may be found for neutral stimuli as well, a possibility that would support a general, rather than affect-specific, account of amygdala-PFC development. To examine this, 112 individuals ranging from 6 to 23 years of age viewed aversive and neutral images while undergoing fMRI scanning. Across age, participants reported more negative affect and showed greater amygdala responses for aversive than neutral stimuli. However, children were generally more sensitive to both neutral and aversive stimuli, as indexed by affective reports and amygdala responses. At the same time, the transition from childhood to adolescence was marked by a ventral-to-dorsal shift in medial prefrontal responses to aversive, but not neutral, stimuli. Given the role that dmPFC plays in executive control and higher-level representations of emotion, these results suggest that adolescence is characterized by a shift towards representing emotional events in increasingly cognitive terms.

  13. The transition from childhood to adolescence is marked by a general decrease in amygdala reactivity and an affect-specific ventral-to-dorsal shift in medial prefrontal recruitment.

    Science.gov (United States)

    Silvers, Jennifer A; Insel, Catherine; Powers, Alisa; Franz, Peter; Helion, Chelsea; Martin, Rebecca; Weber, Jochen; Mischel, Walter; Casey, B J; Ochsner, Kevin N

    2017-06-01

    Understanding how and why affective responses change with age is central to characterizing typical and atypical emotional development. Prior work has emphasized the role of the amygdala and prefrontal cortex (PFC), which show age-related changes in function and connectivity. However, developmental neuroimaging research has only recently begun to unpack whether age effects in the amygdala and PFC are specific to affective stimuli or may be found for neutral stimuli as well, a possibility that would support a general, rather than affect-specific, account of amygdala-PFC development. To examine this, 112 individuals ranging from 6 to 23 years of age viewed aversive and neutral images while undergoing fMRI scanning. Across age, participants reported more negative affect and showed greater amygdala responses for aversive than neutral stimuli. However, children were generally more sensitive to both neutral and aversive stimuli, as indexed by affective reports and amygdala responses. At the same time, the transition from childhood to adolescence was marked by a ventral-to-dorsal shift in medial prefrontal responses to aversive, but not neutral, stimuli. Given the role that dmPFC plays in executive control and higher-level representations of emotion, these results suggest that adolescence is characterized by a shift towards representing emotional events in increasingly cognitive terms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding.

    Science.gov (United States)

    Baldo, Brian A; Spencer, Robert C; Sadeghian, Ken; Mena, Jesus D

    2016-03-01

    A microanalysis of hunger-driven and palatability-driven feeding was carried out after muscimol-mediated inactivation of two frontal regions in rats, the agranular/dysgranular insular cortex (AIC) and the ventromedial prefrontal cortex (vmPFC). Food and water intake, feeding microstructure, and general motor activity were measured under two motivational conditions: food-deprived rats given standard chow or ad libitum-fed rats given a palatable chocolate shake. Muscimol infusions into the AIC diminished intake, total feeding duration, and average feeding bout duration for the palatable-food condition only but failed to alter exploratory-like behavior (ambulation or rearing). In contrast, intra-vmPFC muscimol infusions did not alter the overall intake of chow or chocolate shake. However, these infusions markedly increased mean feeding bout duration for both food types and produced a modest but significant reduction of exploratory-like behavior. The lengthening of feeding-bout duration and reduction in rearing were mimicked by intra-vmPFC blockade of AMPA-type but not NMDA-type glutamate receptors. Neither water consumption nor the microstructure of water drinking was affected by inactivation of either site. These results indicate a regional heterogeneity in frontal control of feeding behavior. Neural processing in AIC supports palatability-driven feeding but is not necessary for intake of a standard food under a food-restriction condition, whereas ventromedial prefrontal cortex, and AMPA signaling therein, modulates the duration of individual feeding bouts regardless of motivational context. Results are discussed in the context of regionally heterogeneous frontal modulation of two distinct components of feeding behavior: reward valuation based upon taste perception (AIC) vs switching between ingestive and non-ingestive (eg, exploratory-like) behavioral repertoires (vmPFC).

  15. Infusions of allopregnanolone into the hippocampus and amygdala, but not into the nucleus accumbens and medial prefrontal cortex, produce antidepressant effects on the learned helplessness rats.

    Science.gov (United States)

    Shirayama, Yukihiko; Muneoka, Katsumasa; Fukumoto, Makoto; Tadokoro, Shigenori; Fukami, Goro; Hashimoto, Kenji; Iyo, Masaomi

    2011-10-01

    Patients with depression showed a decrease in plasma and cerebrospinal fluid allopregnanolone (ALLO). But antidepressants increased the contents of ALLO in the rat brain. We examined the antidepressant-like effects of infusion of ALLO into the cerebral ventricle, hippocampus, amygdala, nucleus accumbens, or prefrontal cortex of learned helplessness (LH) rats (an animal model of depression). Of these regions, infusions of ALLO into the cerebral ventricle, the CA3 region of hippocampus, or the central region of amygdala exerted antidepressant-like effects. Infusion of ALLO into the hippocampal CA3 region or the central amygdala did not produce memory deficits or locomotor activation in the passive avoidance and open field tests. It is well documented that ALLO exerts its effects through GABA receptors. Therefore, we examined the antagonistic effects of flumazenil (a GABA receptor antagonist) on the antidepressant-like effects of ALLO. Coinfusion of flumazenil with ALLO into the hippocampal CA3 region, but not into the central amygdala, blocked the antidepressant-like effects of ALLO. However, coinfusion of (+)MK801 (an NMDA receptor antagonist), but not cycloheximide (a protein synthesis inhibitor), blocked the antidepressant-like effects of ALLO in the central amygdala. These results suggest that ALLO exerts antidepressant-like effects in the CA3 region of hippocampus through the GABA system and in the central region of amygdala, dependently on the activation of the glutamatergic mechanisms. Copyright © 2010 Wiley-Liss, Inc.

  16. Functional inactivation of hypocretin 1 receptors in the medial prefrontal cortex affects the pyramidal neuron activity and gamma oscillations: An in vivo multiple-channel single-unit recording study.

    Science.gov (United States)

    He, C; Chen, Q-H; Ye, J-N; Li, C; Yang, L; Zhang, J; Xia, J-X; Hu, Z-A

    2015-06-25

    The hypocretin signaling is thought to play a critical role in maintaining wakefulness via stimulating the subcortical arousal pathways. Although the cortical areas, including the medial prefrontal cortex (mPFC), receive dense hypocretinergic fibers and express its receptors, it remains unclear whether the hypocretins can directly regulate the neural activity of the mPFC in vivo. In the present study, using multiple-channel single-unit recording study, we found that infusion of the SB-334867, a blocker for the Hcrtr1, beside the recording sites within the mPFC substantially exerted an inhibitory effect on the putative pyramidal neuron (PPN) activity in naturally behaving rats. In addition, functional blockade of the Hcrtr1 also selectively reduced the power of the gamma oscillations. The PPN activity and the power of the neural oscillations were not affected after microinjection of the TCS-OX2-29, a blocker for the Hcrtr2, within the mPFC. Together, these data indicate that endogenous hypocretins acting on the Hcrtr1 are required for the normal neural activity in the mPFC in vivo, and thus might directly contribute cortical arousal and mPFC-dependent cognitive processes. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

    Science.gov (United States)

    Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

    2018-01-01

    Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. The role of right prefrontal and medial cortex in response inhibition: interfering with action restraint and action cancellation using transcranial magnetic brain stimulation.

    Science.gov (United States)

    Dambacher, Franziska; Sack, Alexander T; Lobbestael, Jill; Arntz, Arnoud; Brugmann, Suzanne; Schuhmann, Teresa

    2014-08-01

    The ability of inhibiting impulsive urges is paramount for human behavior. Such successful response inhibition has consistently been associated with activity in pFC. The current study aims to unravel the differential involvement of different areas within right pFC for successful action restraint versus action cancellation. These two conceptually different aspects of action inhibition were measured with a go/no-go task (action restraint) and a stop signal task (action cancellation). Localization of relevant prefrontal activation was based on fMRI data. Significant task-related activation during successful action restraint was localized for each participant individually in right anterior insula (rAI), right superior frontal gyrus, and pre-SMA. Activation during successful action cancellation was localized in rAI, right middle frontal gyrus, and pre-SMA. Subsequently, fMRI-guided continuous thetaburst stimulation was applied to these regions. Results showed that the disruption of neural activity in rAI reduced both the ability to restrain (go/no-go) and cancel (stop signal) responses. In contrast, continuous thetaburst stimulation-induced disruption of the right superior frontal gyrus specifically impaired the ability to restrain from responding (go/no-go), while leaving the ability for action cancellation largely intact. Stimulation applied to right middle frontal gyrus and pre-SMA did not affect inhibitory processing in neither of the two tasks. These findings provide a more comprehensive perspective on the role of pFC in inhibition and cognitive control. The results emphasize the role of inferior frontal regions for global inhibition, whereas superior frontal regions seem to be specifically relevant for successful action restraint.

  19. Norepinephrine in the Medial Pre-frontal Cortex Supports Accumbens Shell Responses to a Novel Palatable Food in Food-Restricted Mice Only

    Directory of Open Access Journals (Sweden)

    Emanuele Claudio Latagliata

    2018-01-01

    Full Text Available Previous findings from this laboratory demonstrate: (1 that different classes of addictive drugs require intact norepinephrine (NE transmission in the medial pre Frontal Cortex (mpFC to promote conditioned place preference and to increase dopamine (DA tone in the nucleus accumbens shell (NAc Shell; (2 that only food-restricted mice require intact NE transmission in the mpFC to develop conditioned preference for a context associated with milk chocolate; and (3 that food-restricted mice show a significantly larger increase of mpFC NE outflow then free fed mice when experiencing the palatable food for the first time. In the present study we tested the hypothesis that only the high levels of frontal cortical NE elicited by the natural reward in food restricted mice stimulate mesoaccumbens DA transmission. To this aim we investigated the ability of a first experience with milk chocolate to increase DA outflow in the accumbens Shell and c-fos expression in striatal and limbic areas of food–restricted and ad-libitum fed mice. Moreover, we tested the effects of a selective depletion of frontal cortical NE on both responses in either feeding group. Only in food-restricted mice milk chocolate induced an increase of DA outflow beyond baseline in the accumbens Shell and a c-fos expression larger than that promoted by a novel inedible object in the nucleus accumbens. Moreover, depletion of frontal cortical NE selectively prevented both the increase of DA outflow and the large expression of c-fos promoted by milk chocolate in the NAc Shell of food-restricted mice. These findings support the conclusion that in food-restricted mice a novel palatable food activates the motivational circuit engaged by addictive drugs and support the development of noradrenergic pharmacology of motivational disturbances.

  20. Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex.

    Science.gov (United States)

    Schindler, Emmanuelle A D; Harvey, John A; Aloyo, Vincent J

    2013-01-23

    The phenethylamine and indoleamine classes of hallucinogens demonstrate distinct pharmacological properties, although they share a serotonin(2A) (5-HT(2A)) receptor mechanism of action (MOA). The 5-HT(2A) receptor signals through phosphatidylinositol (PI) hydrolysis, which is initiated upon activation of phospholipase C (PLC). The role of PI hydrolysis in the effects of hallucinogens remains unclear. In order to better understand the role of PI hydrolysis in the MOA of hallucinogens, the PLC inhibitor, 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to study the effects of two hallucinogens, the phenethylamine, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the indoleamine, lysergic acid diethylamide (LSD). PI hydrolysis was quantified through release of [3H]inositol-4-phosphate from living rabbit frontocortical tissue prisms. Head bobs were counted after hallucinogens were infused into the medial prefrontal cortex (mPFC) of rabbits. Both DOI and LSD stimulated PI hydrolysis in frontocortical tissue through activation of PLC. DOI-stimulated PI hydrolysis was blocked by 5-HT(2A/2C) receptor antagonist, ketanserin, whereas the LSD signal was blocked by 5-HT(2B/2C) receptor antagonist, SB206553. When infused into the mPFC, both DOI- and LSD-elicited head bobs. Pretreatment with U73122 blocked DOI-, but not LSD-elicited head bobs. The two hallucinogens investigated were distinct in their activation of the PI hydrolysis signaling pathway. The serotonergic receptors involved with DOI and LSD signals in frontocortical tissue were different. Furthermore, PLC activation in mPFC was necessary for DOI-elicited head bobs, whereas LSD-elicited head bobs were independent of this pathway. These novel findings urge closer investigation into the intracellular mechanism of action of these unique compounds. Published by Elsevier B.V.

  1. Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure

    Science.gov (United States)

    Schechter, Daniel S.; Moser, Dominik A.; Paoloni-Giacobino, Ariane; Stenz, Ludwig; Gex-Fabry, Marianne; Aue, Tatjana; Adouan, Wafae; Cordero, María I.; Suardi, Francesca; Manini, Aurelia; Sancho Rossignol, Ana; Merminod, Gaëlle; Ansermet, Francois; Dayer, Alexandre G.; Rusconi Serpa, Sandra

    2015-01-01

    Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother–child interactions. Following a mental health assessment, 45 mothers and their children (ages 12–42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother–child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother–child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD

  2. Single-Prolonged-Stress-Induced Changes in Autophagy-Related Proteins Beclin-1, LC3, and p62 in the Medial Prefrontal Cortex of Rats with Post-traumatic Stress Disorder.

    Science.gov (United States)

    Zheng, Shilei; Han, Fang; Shi, Yuxiu; Wen, Lili; Han, Dan

    2017-05-01

    Autophagy, or type II programmed cell death, plays a crucial role in many nervous system diseases. However, few studies have examined the role of autophagy in post-traumatic stress disorder (PTSD), and the mechanisms underlying PTSD are poorly understood. The objective of this research was to explore the expression of three important autophagy-related proteins, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and p62/SQSTM1 (p62), in the medial prefrontal cortex (mPFC) of an animal model of PTSD to identify changes in autophagic activity during PTSD pathogenesis. PTSD was induced in rats by exposure to a single-prolonged stress (SPS). The Morris water maze was used to assess cognitive changes in rats from the SPS and control groups. Transmission electron microscopy (TEM) was employed to observe mPFC morphological changes. Immunohistochemistry, immunofluorescence, and Western blotting techniques were used to detect expression of Beclin-1, LC3, and p62 in the mPFC. The Morris water maze test results showed that the escape latency time was increased and that the percent time in the target quadrant was decreased in the SPS group compared with that in the control group. Numerous visible autolysosomes in mPFC neurons were observed using TEM after SPS stimulation. Compared with that in the control group, the expression of Beclin-1 and the LC3-II/I ratio significantly decreased at 1 day, then increased and peaked at 7 days, and slightly decreased at 14 days after SPS stimulation, whereas the converse was found for p62 expression. In conclusion, dysregulation of autophagic activity in the mPFC may play a crucial role in PTSD pathogenesis.

  3. Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure

    Directory of Open Access Journals (Sweden)

    Daniel Scott Schechter

    2015-05-01

    Full Text Available Prior research has shown that mothers with Interpersonal Violence-related Posttraumatic Stress Disorder (IPV-PTSD report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis, characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC activity in response to video-stimuli of stressful versus non-stressful mother-child interactions. Following a mental health assessment, 45 mothers and their children (ages 12-42 months participated in a behavioral protocol involving free-play and laboratory stressors such as mother-child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother-child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress

  4. Micromicetes asociados a la corteza y madera de podocarpus parlatorei (Podocarpaceae en la Argentina. VI. Ascomycota

    Directory of Open Access Journals (Sweden)

    Myriam del V. Catania

    2010-01-01

    Full Text Available Se describen e ilustran diez especies de Ascomycota que crecen sobre madera y corteza de Podocarpus parlatorei. Se proponen Nemania confluens var. microspora var. nov., Togninia minutissima comb. nov., y se citan por primera vez para la Argentina los siguientes taxones: Botryosphaeria sarmentorum, Ceratostomella pyrenaica, Cochliobolus kusanoi, Heptameria obesa, Hypoxylon duranii, Ophioceras dolichostomum, Tengiomyces indicus, Togninia minima, Trichosphaeria pilosa.

  5. Aislamiento de poligodial de la corteza de drymis granadensis, var. grandiflora

    Directory of Open Access Journals (Sweden)

    Jairo Calle

    2009-07-01

    Full Text Available Del extracto de éter de petróleo (P Eb = 40-60 "O de la corteza de Drymis granadensis, var. grandiflora, se aisló con 8% de rendimiento, poligodial ( I , un sesquiterpeno conocido, cuya estructura se confirmó por métodos espectroscópicos.

  6. Acute pharmacogenetic activation of medial prefrontal cortex ...

    Indian Academy of Sciences (India)

    Sthitapranjya Pati

    2018-01-24

    Jan 24, 2018 ... Exclusively Activated by Designer Drugs (DREADDs) have provided novel ... ad libitum access to food and water. ... testing. 2.3 Drug treatment and behavioural tests .... IL cortex (figure 3E, two-way ANOVA: interaction effect,.

  7. Un acercamiento a las cortezas de meteorización no niquelíferas del nordeste de Cuba

    Directory of Open Access Journals (Sweden)

    Arturo L. Rojas-Purón

    2010-03-01

    Full Text Available Este artículo expone el resultado de la revisión de los estudios sobre cortezas de meteorización no niquelíferas realizados en Cuba Oriental a partir de 1943, los cuales estuvieron dirigidos a la búsqueda de bauxitas, motivados por la existencia en la región de grandes depósitos minerales asociados a diferentes tipos de cortezas de meteorización. Los bajos contenidos de alúmina reportados no permitieron delimitar cortezas perspectivas para la explotación de bauxitas, lo que limitó la evaluación de las posibilidades de asimilar estas cortezas en industrias nacionales como la cerámica, materiales de construcción y refractaria, entre otras. Como elemento común de estos estudios vale señalar la ausencia, casi general, de criterios mineralógicos-geoquímicos sólidos para la caracterización y clasificación de las distintas cortezas de meteorización enriquecidas en alúmina. Los contenidos de SiO2-Al2O3-Fe2O3 en la región apuntan a que la mayoría de las cortezas de meteorización son ferrosialíticas. Cortezas sialíticas, silícicas, ferralíticas y alíticas pueden encontrarse en Cayo Guam, Centeno, Quesigua, Puriales de Caujerí, Quemado del Negro y Cantarrana. El grado de estudio de las cortezas de meteorización no niquelíferas sobre gabros, rocas volcánicas, metamórficas y sedimentarias, en Cuba Oriental es relativamente bajo. Se proponen realizar investigaciones detalladas en Téneme, Centeno, Cayo Guam, Quemado del Negro y Cantarrana con perspectivas para alitas.

  8. Influencias nutricionales sobre las capacidades gluconeogénica y glucolítica de corteza renal de rata

    OpenAIRE

    García Salguero, Leticia

    2013-01-01

    Se ha puesto de manifiesto la importancia de la corteza renal en el mantenimiento de los niveles de glucosa sanguínea. El riñón es capaz de adaptar el metabolismo de carbohidratos ante diferentes situaciones nutricionales. Así cuando hay un aporte excesivo de carbohidratos en la dieta el riñón responde disminuyendo la gluconeogénesis e incrementando la glucólisis igual que ocurre en el hígado. En el ayuno los cambios que tienen lugar en la corteza renal siguen una dirección opuesta

  9. Aporfinoides en corteza de guntteriu lehmannii y evaluación de su actividad antimalárica in vitro

    Directory of Open Access Journals (Sweden)

    Alex Saez

    2010-07-01

    Full Text Available Un extracto de alcaloides de la corteza de Guatteria lehmannii presentó actividad antimalárica in vitro, se aislaron tres alcaloides aporfínicos. Nornuciferína 1, Lysicamína 2 y Norneolilsína 3.. Las estructuras se determinaron por métodos espectrales.

  10. ESTUDIO QUÍMICO DE LA CORTEZA DE Remijia peruviana “Cascarilla”

    Directory of Open Access Journals (Sweden)

    Gabriel Vargas Arana

    2011-07-01

    Full Text Available En el presente trabajo se realizó el análisis cualitativo de los metabolitos secundarios  y la cuantificación e identificación de los alcaloides presentes en la corteza de Remijia peruviana, la cual forma parte de la familia Rubiaceae, caracterizada por sintetizar  mayoritariamente alcaloides. Se ha aislado y determinado la estructura química de cinco alcaloides quinolínicos: tres nuevos derivados, Quinina acetato (1, Quinina alcohol (2 y N-Etil Quinina (3; y dos reportados anteriormente en la literatura: Quinina (4 y Cinchonina (5. La estructura de los nuevos alcaloides fueron elucidados por análisis básicos de espectroscopía RMN, incluyendo correlaciones homonuclear y heteronuclear (COSY, NOESY, HMBC y HSQC.

  11. Plasticity in the Prefrontal Cortex of Adult Rats

    Directory of Open Access Journals (Sweden)

    Bryan eKolb

    2015-02-01

    Full Text Available We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions.

  12. Anatomía funcional del cuerpo estriado y la corteza cerebral: su relación con el movimiento

    OpenAIRE

    Buffone, Gabriel Darío; Dalto, Carlos

    2013-01-01

    El objetivo de la siguiente ponencia es revalorizar y reconocer aquellos aspectos anatómicos y funcionales de algunos elementos del sistema nervioso imprescindibles para el correcto funcionamiento del cuerpo humano, tanto en los movimientos deportivos, como en la variedad infinita de los actos motores resumidos en las contracciones musculares. Ante los diferentes rangos articulares posibles y las determinadas acciones musculares específicas, la corteza cerebral y el cuerpo estriado partici...

  13. PODER CALORÍFICO Y MATERIAL INORGÁNICO EN LA CORTEZA DE SEIS ÁRBOLES FRUTALES

    Directory of Open Access Journals (Sweden)

    Ricardo Martínez-Pérez

    2012-01-01

    Full Text Available El poder calorífico y el contenido de sustancias minerales (cenizas se determinaron en la corteza de seis especies arbóreas frutales (Annona cherimola Mill., Citrus aurantifolia Swingle, Malus domestica Borkh., Psidium guajava L., Prunus dulcis [Mill.] D. A. Webb y Tamarindus indica L.. Las cenizas obtenidas fueron analizadas mediante rayos X. Los valores encontrados de poder calorífico variaron de 3,453.49 kcal•kg-1 en T. indica a 4,076.10 kcal•kg-1 en P. guajava. En el caso de las cenizas, los resultados fluctuaron de 5.76 % en P. guajava a 21.93 % en T. indica. Se observó que un contenido mayor de minerales en las cortezas tiende a disminuir su poder calorífico. Los elementos químicos comunes en las muestras analizadas fueron calcio, potasio, magnesio, fósforo y azufre. No se detectaron metales pesados en las muestras de la corteza.

  14. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Science.gov (United States)

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  15. Modelo gravimétrico del espesor de la corteza terrestre en Colombia

    Directory of Open Access Journals (Sweden)

    Leuro Parra Erick

    2000-08-01

    Full Text Available

    The gravimetric model of the crustal thickness of the earth in Colombia was made from Total Bouguer Anomaly and topographic height given by the Instituto Geográfico Agustín Codazzi. They were transformed to bidimensional series of Fourier, that combined with mathematics expressions of the gravitational potential, both, they made possible to find the crustal thickness starting from observable values across the earth's surface (gravity and topography. The results of several points were converted to surface through Minime Curvature algorithm. In order to obtain reliability of the results, seismic control was applied from another works.

    La determinación del espesor de la corteza terrestre en Colombia, a partir de datos gravimétricos, se hizo utilizando datos de Anomalia Total de Bouguer y altura topográfica suministrados por el Instituto Geográfico Agustin Codazzi. Estos fueron representados mediante series bidimensionales de Fourier, que al ser combinadas con expresiones matemáticas del potencial gravitacional terrestre, permitieron plantear el grosor cortical en términos observables (gravedad y altura sobre la superficie terrestre. Los resultados han sido dispuestos en una malla de puntos que se interpolan a una superficie utilizando el algoritmo de mínima curvatura. Para la estimación de la confiabilidad de los resultados se ha realizado una confrontación con las deducciones geológicas obtenidas de algunas interpretaciones sismicas realizadas en el pais.

  16. Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression

    Directory of Open Access Journals (Sweden)

    Saha Subhash

    2003-10-01

    Full Text Available Abstract Background Experiencing emotions engages high-order orbitofrontal and medial prefrontal areas, and expressing emotions involves low-level autonomic structures and peripheral organs. How is information from the cortex transmitted to the periphery? We used two parallel approaches to map simultaneously multiple pathways to determine if hypothalamic autonomic centres are a key link for orbitofrontal areas and medial prefrontal areas, which have been associated with emotional processes, as well as low-level spinal and brainstem autonomic structures. The latter innervate peripheral autonomic organs, whose activity is markedly increased during emotional arousal. Results We first determined if pathways linking the orbitofrontal cortex with the hypothalamus overlapped with projection neurons directed to the intermediolateral column of the spinal cord, with the aid of neural tracers injected in these disparate structures. We found that axons from orbitofrontal and medial prefrontal cortices converged in the hypothalamus with neurons projecting to brainstem and spinal autonomic centers, linking the highest with the lowest levels of the neuraxis. Using a parallel approach, we injected bidirectional tracers in the lateral hypothalamic area, an autonomic center, to label simultaneously cortical pathways leading to the hypothalamus, as well as hypothalamic axons projecting to low-level brainstem and spinal autonomic centers. We found densely distributed projection neurons in medial prefrontal and orbitofrontal cortices leading to the hypothalamus, as well as hypothalamic axonal terminations in several brainstem structures and the intermediolateral column of the spinal cord, which innervate peripheral autonomic organs. We then provided direct evidence that axons from medial prefrontal cortex synapse with hypothalamic neurons, terminating as large boutons, comparable in size to the highly efficient thalamocortical system. The interlinked orbitofrontal

  17. Comparison of (stereotactic) parcellations in mouse prefrontal cortex

    NARCIS (Netherlands)

    van de Werd, H.J.J.M.; Uylings, H.B.M.

    2014-01-01

    This study compares the cytoarchitectonic parcellation of the prefrontal cortex (PFC) in the mouse as presented in publications that are commonly used for identifying brain areas. Agreement was found to be greater for boundaries in the medial PFC than in the lateral PFC and lowest for those in the

  18. Social cognition in patients following surgery to the prefrontal cortex

    NARCIS (Netherlands)

    Jenkins, L.M.; Andrewes, D.G.; Nicholas, C.L.; Drummond, K.J.; Moffat, B.A.; Phal, P.; Desmond, P.; Kessels, R.P.C.

    2014-01-01

    Impaired social cognition, including emotion recognition, may explain dysfunctional emotional and social behaviour in patients with lesions to the ventromedial prefrontal cortex (VMPFC). However, the VMPFC is a large, poorly defined area that can be sub-divided into orbital and medial sectors. We

  19. Cinética de lixiviación de la corteza de mangle rojo en agua

    Directory of Open Access Journals (Sweden)

    Yanet Rodríguez Perdomo

    2012-03-01

    Full Text Available Objetivo: determinar la naturaleza del fenómeno que rige la transferencia de masa durante la lixiviación del mangle rojo en agua mediante el estudio de la cinética del proceso. Métodos: se estudió la cinética de lixiviación de la corteza de mangle rojo en agua a escala de laboratorio, en una relación sólido/líquido 1:4 a diferentes temperaturas (25, 45, 70 y 90 °C. Para cada temperatura en particular se determinó la constante cinética a partir de la ecuación fundamental de la lixiviación mediante un modelo ajustado empleando el programa estadístico CurveExpert 1.4 para Windows. Resultados: los valores de la concentración de sólidos solubles totales correspondientes a 25 y 45 °C presentaron un incremento apreciable durante los primeros 20 min, y los correspondientes a 70 y 90 °C lo alcanzaron a los 30 min. El valor de la energía de activación obtenida en el experimento correspondió a 2,884 kJ. Conclusiones: la naturaleza de la lixiviación de la corteza de mangle rojo se produce por vía física.

  20. Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices.

    Science.gov (United States)

    Barbas, H

    2000-07-15

    Distinct domains of the prefrontal cortex in primates have a set of connections suggesting that they have different roles in cognition, memory, and emotion. Caudal lateral prefrontal areas (areas 8 and 46) receive projections from cortices representing early stages in visual or auditory processing, and from intraparietal and posterior cingulate areas associated with oculomotor guidance and attentional processes. Cortical input to areas 46 and 8 is complemented by projections from the thalamic multiform and parvicellular sectors of the mediodorsal nucleus associated with oculomotor functions and working memory. In contrast, caudal orbitofrontal areas receive diverse input from cortices representing late stages of processing within every unimodal sensory cortical system. In addition, orbitofrontal and caudal medial (limbic) prefrontal cortices receive robust projections from the amygdala, associated with emotional memory, and from medial temporal and thalamic structures associated with long-term memory. Prefrontal cortices are linked with motor control structures related to their specific roles in central executive functions. Caudal lateral prefrontal areas project to brainstem oculomotor structures, and are connected with premotor cortices effecting head, limb and body movements. In contrast, medial prefrontal and orbitofrontal limbic cortices project to hypothalamic visceromotor centers for the expression of emotions. Lateral, orbitofrontal, and medial prefrontal cortices are robustly interconnected, suggesting that they participate in concert in central executive functions. Prefrontal limbic cortices issue widespread projections through their deep layers and terminate in the upper layers of lateral (eulaminate) cortices, suggesting a predominant role in feedback communication. In contrast, when lateral prefrontal cortices communicate with limbic areas they issue projections from their upper layers and their axons terminate in the deep layers, suggesting a role in

  1. Prefrontal cortex modulates desire and dread generated by nucleus accumbens glutamate disruption.

    Science.gov (United States)

    Richard, Jocelyn M; Berridge, Kent C

    2013-02-15

    Corticolimbic circuits, including direct projections from prefrontal cortex to nucleus accumbens (NAc), permit top-down control of intense motivations generated by subcortical circuits. In rats, localized disruptions of glutamate signaling within medial shell of NAc generate desire or dread, anatomically organized along a rostrocaudal gradient analogous to a limbic keyboard. At rostral locations in shell, these disruptions generate appetitive eating, but at caudal locations the disruptions generate progressively fearful behaviors (distress vocalizations, escape attempts, and antipredator reactions). Here, we asked whether medial prefrontal cortex can modulate intense motivations generated by subcortical NAc disruptions. We used simultaneous microinjections in medial prefrontal cortex regions and in NAc shell to examine whether the desire or dread generated by NAc shell disruptions is modulated by activation/inhibition of three specific regions of prefrontal cortex: medial orbitofrontal cortex, infralimbic cortex (homologous to area 25 or subgenual anterior cingulate in the human), or prelimbic cortex (midventral anterior cingulate). We found that activation of medial orbitofrontal cortex biased intense bivalent motivation in an appetitive direction by amplifying generation of eating behavior by middle to caudal NAc disruptions, without altering fear. In contrast, activation of infralimbic prefrontal cortex powerfully and generally suppressed both appetitive eating and fearful behaviors generated by NAc shell disruptions. These results suggest that corticolimbic projections from discrete prefrontal regions can either bias motivational valence or generally suppress subcortically generated intense motivations of desire or fear. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Transient medial prefrontal perturbation reduces false memory formation

    NARCIS (Netherlands)

    Berkers, R.M.W.J.; Linden, M.H. van der; Almeida, R.F. de; Müller, N.C.J.; Bovy, L.; Dresler, M.; Morris, R.G.M.; Fernandez, G.S.E.

    2017-01-01

    Knowledge extracted across previous experiences, or schemas, benefit encoding and retention of congruent information. However, they can also reduce specificity and augment memory for semantically related, but false information. A demonstration of the latter is given by the Deese-Roediger-McDermott

  3. A General Role for Medial Prefrontal Cortex in Event Prediction

    Science.gov (United States)

    2014-07-11

    al., 2001; Nee and Brown, 2013; Mian et al., 2014) and known to project reciprocally to mPFC (Barbas and Pandya, 1989). Another possible substrate of...A. J., and Li , C. R. (2013). Bayesian prediction and evaluation in the anterior cingulate cortex. J. Neurosci. 33, 2039–2047. doi: 10. 1523/JNEUROSCI...prediction in mPFC Mian , M. K., Sheth, S. A., Patel, S. R., Spiliopoulos, K., Eskandar, E. N., and Williams, Z. M. (2014). Encoding of rules by neurons in the

  4. Specialized prefrontal auditory fields: organization of primate prefrontal-temporal pathways

    Directory of Open Access Journals (Sweden)

    Maria eMedalla

    2014-04-01

    Full Text Available No other modality is more frequently represented in the prefrontal cortex than the auditory, but the role of auditory information in prefrontal functions is not well understood. Pathways from auditory association cortices reach distinct sites in the lateral, orbital, and medial surfaces of the prefrontal cortex in rhesus monkeys. Among prefrontal areas, frontopolar area 10 has the densest interconnections with auditory association areas, spanning a large antero-posterior extent of the superior temporal gyrus from the temporal pole to auditory parabelt and belt regions. Moreover, auditory pathways make up the largest component of the extrinsic connections of area 10, suggesting a special relationship with the auditory modality. Here we review anatomic evidence showing that frontopolar area 10 is indeed the main frontal auditory field as the major recipient of auditory input in the frontal lobe and chief source of output to auditory cortices. Area 10 is thought to be the functional node for the most complex cognitive tasks of multitasking and keeping track of information for future decisions. These patterns suggest that the auditory association links of area 10 are critical for complex cognition. The first part of this review focuses on the organization of prefrontal-auditory pathways at the level of the system and the synapse, with a particular emphasis on area 10. Then we explore ideas on how the elusive role of area 10 in complex cognition may be related to the specialized relationship with auditory association cortices.

  5. EFECTOS A CORTO Y LARGO PLAZO DEL ESTRES CRONICO SOBRE LA ANSIEDAD, EL MIEDO, Y L APLASTICIDAD SINAPTICA EN LA CORTEZA PREFRONTAL

    OpenAIRE

    NEGRON OYARZO, SERGIO IGNACIO

    2012-01-01

    El estrés crónico aumenta la ansiedad y disminuye el recuerdo de la extinción del miedo. En la presente tesis doctoral evaluamos en ratas Sprague-Dawley el efecto a corto y a largo plazo del estrés por restricción de movimiento sobre la ansiedad y el recuerdo de la extinción del miedo condicionado. Encontramos. que el estrés crónico produjo un aumento de la ansiedad y una disminución del recuerdo de la extinción. Tres semanas después del término del estrés, la ansiedad de los animales s...

  6. prefrontal como mecanismo putativo del cambio en psicoterapia

    Directory of Open Access Journals (Sweden)

    Jaime Silva C.

    2005-01-01

    Full Text Available La corteza prefrontal (CPF es definida como la región cerebral cortical que se conecta recíprocamente con el núcleo dorsolateral del tálamo. La visión tradicional en las ciencias del comportamiento atribuye a la CPF un papel en la organización temporal de la conducta. Adicionalmente, estudios convergentes en el campo de la neurociencia afectiva han revelado el papel fundamental que juega la CPF en la determinación del estilo afectivo y en especial de la regulación emocional. El estilo afectivo involucra las diferencias individuales en diferentes parámetros de la reactividad afectiva y el estado de ánimo disposicional (por ejemplo, amplitud de la respuesta emocional, tiempo de recuperación, etc.. Dado que prácticamente todas las alteraciones psicopatológicas incluyen un trastorno en alguno de esos parámetros, proponemos que la modulación de la actividad de la CPF es una variable fundamental del cambio en psicoterapia. Presentamos nuestro modelo putativo, el cual se fundamenta en el control cognitivo en cascada de la CPF. Específicamente, proponemos que la regulación emocional ocurre asociada a la activación de la CPF lateral en un sentido rostralcaudal, donde zonas rostrales involucran formas complejas de control afectivo.

  7. Ipsilateral Medial and Lateral Discoid Meniscus with Medial Meniscus Tear

    OpenAIRE

    Shimozaki, Kengo; Nakase, Junsuke; Ohashi, Yoshinori; Numata, Hitoaki; Oshima, Takeshi; Takata, Yasushi; Tsuchiya, Hiroyuki

    2016-01-01

    Introduction: Discoid meniscus is a well-documented knee pathology, and there are many cases of medial or lateral discoid meniscus reported in the literature. However, ipsilateral concurrent medial and lateral discoid meniscus is very rare, and only a few cases have been reported. Herein, we report a case of concurrent medial and lateral discoid meniscus. Case Report: A 27-year-old Japanese man complained of pain on medial joint space in his right knee that was diagnosed as a complete medial ...

  8. Contribución al estudio experimental del cancer III. Alteraciones de la corteza suprarrenal en la Carcinogenesis Química.

    Directory of Open Access Journals (Sweden)

    Oscar Miro-Quesada C

    1948-12-01

    Full Text Available 1.- Se hace un estudio crítico histo-químico funcional de la corteza suprarrenal en ratones homozigotes C3H (Strong sometidos a la cancerización química con 20-Metilcolantreno. 2.- Se describe un nuevo tipo de reacción funcional de dicha glándula bajo las condiciones experimentales empleadas, sugiriéndose la denominación de "atrofia-hiperactiva", en contraste con las alteraciones histo-químico funcionales de la corteza suprarrenal descritas por varios autores en animales portadores de injertos neoplásicos, las que corresponden al tipo de reacción funcional de la glándula caracterizado por "hipertrofia-hiperactiva". 3.- Los resultados obtenidos sugieren la intervención del sistema endocrino, via la corteza suprarrenal, durante el proceso de carcinogenesis química en el ratón homozigote de raza C3H (Strong.

  9. Distraction decreases prefrontal oxygenation: A NIRS study.

    Science.gov (United States)

    Ozawa, Sachiyo; Hiraki, Kazuo

    2017-04-01

    When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Reduced prefrontal connectivity in psychopathy.

    Science.gov (United States)

    Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

    2011-11-30

    Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

  11. Prefrontal Cortical GABA Modulation of Spatial Reference and Working Memory

    OpenAIRE

    Auger, Meagan L.; Floresco, Stan B.

    2014-01-01

    Background: Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. Methods: We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates ...

  12. Ventromedial prefrontal cortex, adding value to autobiographical memories

    OpenAIRE

    Lin, W. J.; Horner, A. J.; Burgess, N.

    2016-01-01

    The medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found tha...

  13. Default network connectivity in medial temporal lobe amnesia.

    Science.gov (United States)

    Hayes, Scott M; Salat, David H; Verfaellie, Mieke

    2012-10-17

    There is substantial overlap between the brain regions supporting episodic memory and the default network. However, in humans, the impact of bilateral medial temporal lobe (MTL) damage on a large-scale neural network such as the default mode network is unknown. To examine this issue, resting fMRI was performed with amnesic patients and control participants. Seed-based functional connectivity analyses revealed robust default network connectivity in amnesia in cortical default network regions such as medial prefrontal cortex, posterior medial cortex, and lateral parietal cortex, as well as evidence of connectivity to residual MTL tissue. Relative to control participants, decreased posterior cingulate cortex connectivity to MTL and increased connectivity to cortical default network regions including lateral parietal and medial prefrontal cortex were observed in amnesic patients. In contrast, somatomotor network connectivity was intact in amnesic patients, indicating that bilateral MTL lesions may selectively impact the default network. Changes in default network connectivity in amnesia were largely restricted to the MTL subsystem, providing preliminary support from MTL amnesic patients that the default network can be fractionated into functionally and structurally distinct components. To our knowledge, this is the first examination of the default network in amnesia.

  14. Arthroscopic partial medial meniscectomy

    Directory of Open Access Journals (Sweden)

    Dašić Žarko

    2011-01-01

    Full Text Available Background/Aim. Meniscal injuries are common in professional or recreational sports as well as in daily activities. If meniscal lesions lead to physical impairment they usually require surgical treatment. Arthroscopic treatment of meniscal injuries is one of the most often performed orthopedic operative procedures. Methods. The study analyzed the results of arthroscopic partial medial meniscectomy in 213 patients in a 24-month period, from 2006, to 2008. Results. In our series of arthroscopically treated medial meniscus tears we noted 78 (36.62% vertical complete bucket handle lesions, 19 (8.92% vertical incomplete lesions, 18 (8.45% longitudinal tears, 35 (16.43% oblique tears, 18 (8.45% complex degenerative lesions, 17 (7.98% radial lesions and 28 (13.14% horisontal lesions. Mean preoperative International Knee Documentation Committee (IKDC score was 49.81%, 1 month after the arthroscopic partial medial meniscectomy the mean IKDC score was 84.08%, and 6 months after mean IKDC score was 90.36%. Six months after the procedure 197 (92.49% of patients had good or excellent subjective postoperative clinical outcomes, while 14 (6.57% patients subjectively did not notice a significant improvement after the intervention, and 2 (0.93% patients had no subjective improvement after the partial medial meniscectomy at all. Conclusion. Arthroscopic partial medial meniscetomy is minimally invasive diagnostic and therapeutic procedure and in well selected cases is a method of choice for treatment of medial meniscus injuries when repair techniques are not a viable option. It has small rate of complications, low morbidity and fast rehabilitation.

  15. Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex.

    Science.gov (United States)

    Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

    2017-07-01

    Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. © The Author (2017). Published by Oxford University Press.

  16. Caracterización de algunas propiedades en tableros de corteza de Pinus pinaster Ait. y tableros de vermiculita expandida

    Directory of Open Access Journals (Sweden)

    Pereiro López, G.

    2012-06-01

    Full Text Available The search for new applications to use boards requires innovation of their pro-perties. The improvement of insulation properties, the possibility to regulate the environmental conditions, the improvement of fire resistance and the increase of physical and mechanical properties allow a more diverse use of boards. Using new components in the production of boards and/or component materials also called composites (1, enables the improvement of these properties. This publication analyses different physical and mechanical properties of various types of single-layer boards produced either based on expanded vermiculite particles bonded with soluble silicate glasses (2 or based on lignocelluloses particles bark of "Pinus pinaster" Ait., agglutinated with cement derivatives of magnesium (3, the latter included in the classification of the norm (4. Commercial wood wool boards (5 are used as reference material.La búsqueda de nuevas aplicaciones en el uso de los tableros requiere de la innovación en sus propiedades. Las mejoras en el aislamiento, en la regulación de las condiciones ambientales, en su resistencia al fuego y el incremento en sus propiedades físico-mecánicas, aumentan la diversificación de sus usos. El empleo de nuevas materias en los tableros y/o en los materiales compuestos, denominados composites (1, posibilita la mejora en estas propiedades. Esta publicación analiza diversas propiedades físicas y mecánicas de varios tipos de tableros monocapa, elaborados, por un lado, a base de partículas minerales de vermiculita expandida aglutinadas con silicatos de vidrios solubles (2, y por otro lado, a base de partículas lignocelulósicas de corteza de Pinus pinaster Ait., aglutinadas con cementos derivados del magnesio (3, incluidos ya estos últimos en la clasificación de la norma (4. Como material de referencia se emplean tableros comerciales de virutas de madera (5.

  17. Prefrontal Cortex Lesions and Sex Differences in Fear Extinction and Perseveration

    Science.gov (United States)

    Baran, Sarah E.; Armstrong, Charles E.; Niren, Danielle C.; Conrad, Cheryl D.

    2010-01-01

    Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague-Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h…

  18. Dissociating medial frontal and posterior cingulate activity during self-reflection.

    Science.gov (United States)

    Johnson, Marcia K; Raye, Carol L; Mitchell, Karen J; Touryan, Sharon R; Greene, Erich J; Nolen-Hoeksema, Susan

    2006-06-01

    Motivationally significant agendas guide perception, thought and behaviour, helping one to define a 'self' and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus.

  19. Human Thalamic-Prefrontal Peduncle Connectivity Revealed by Diffusion Spectrum Imaging Fiber Tracking

    Directory of Open Access Journals (Sweden)

    Chuanqi Sun

    2018-04-01

    Full Text Available The thalamic-prefrontal peduncle (TPP is a large bundle connecting the thalamus and prefrontal cortex. The definitive structure and function of the TPP are still controversial. To investigate the connectivity and segmentation patterns of the TPP, we employed diffusion spectrum imaging with generalized q-sampling reconstruction to perform both subject-specific and template-based analyses. Our results confirmed the trajectory and spatial relationship of the TPP in the human brain and identified the connection areas in the prefrontal cortex. The TPP-connecting areas identified based on Brodmann areas (BAs were BAs 8–11 and 45–47. Based on the automated anatomical atlas, these areas were the medial superior frontal gyrus, superior frontal gyrus, middle frontal gyrus, pars triangularis, pars orbitalis, anterior orbital gyrus, and lateral orbital gyrus. In addition, we identified the TPP connection areas in the thalamus, including the anterior and medial nuclei, and the lateral dorsal/lateral posterior nuclei. TPP fibers connected the thalamus with the ipsilateral prefrontal BAs 11, 47, 10, 46, 45, 9, and 8 seriatim from medial to lateral, layer by layer. Our results provide further details of the thalamic-prefrontal peduncle structure, and may aid future studies and a better understanding of the functional roles of the TPP in the human brain.

  20. The medial patellofemoral complex.

    Science.gov (United States)

    Loeb, Alexander E; Tanaka, Miho J

    2018-06-01

    The purpose of this review is to describe the current understanding of the medial patellofemoral complex, including recent anatomic advances, evaluation of indications for reconstruction with concomitant pathology, and surgical reconstruction techniques. Recent advances in our understanding of MPFC anatomy have found that there are fibers that insert onto the deep quadriceps tendon as well as the patella, thus earning the name "medial patellofemoral complex" to allow for the variability in its anatomy. In MPFC reconstruction, anatomic origin and insertion points and appropriate graft length are critical to prevent overconstraint of the patellofemoral joint. The MPFC is a crucial soft tissue checkrein to lateral patellar translation, and its repair or reconstruction results in good restoration of patellofemoral stability. As our understanding of MPFC anatomy evolves, further studies are needed to apply its relevance in kinematics and surgical applications to its role in maintaining patellar stability.

  1. Electrophysiological mapping of novel prefrontal - cerebellar pathways

    Directory of Open Access Journals (Sweden)

    Thomas C Watson

    2009-08-01

    Full Text Available Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre; they were not attenuated by local anesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency. Single-unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

  2. Intralaminar and medial thalamic influence on cortical synchrony, information transmission and cognition

    Directory of Open Access Journals (Sweden)

    Yuri B Saalmann

    2014-05-01

    Full Text Available The intralaminar and medial thalamic nuclei are part of the higher-order thalamus, which receives little sensory input, and instead forms extensive cortico-thalamo-cortical pathways. The large mediodorsal thalamic nucleus predominantly connects with the prefrontal cortex, the adjacent intralaminar nuclei connect with fronto-parietal cortex, and the midline thalamic nuclei connect with medial prefrontal cortex and medial temporal lobe. Taking into account this connectivity pattern, it is not surprising that the intralaminar and medial thalamus has been implicated in a variety of cognitive functions, including memory processing, attention and orienting, as well as reward-based behavior. This review addresses how the intralaminar and medial thalamus may regulate information transmission in cortical circuits. A key neural mechanism may involve intralaminar and medial thalamic neurons modulating the degree of synchrony between different groups of cortical neurons according to behavioral demands. Such a thalamic-mediated synchronization mechanism may give rise to large-scale integration of information across multiple cortical circuits, consequently influencing the level of arousal and consciousness. Overall, the growing evidence supports a general role for the higher-order thalamus in the control of cortical information transmission and cognitive processing.

  3. Medial temporal lobe

    International Nuclear Information System (INIS)

    Silver, A.J.; Cross, D.T.; Friedman, D.P.; Bello, J.A.; Hilal, S.K.

    1989-01-01

    To better define the MR appearance of hippocampal sclerosis, the authors have reviewed over 500 MR coronal images of the temporal lobes. Many cysts were noted that analysis showed were of choroid-fissure (arachnoid) origin. Their association with seizures was low. A few nontumorous, static, medial temporal lesions, noted on T2-weighted coronal images, were poorly visualized on T1-weighted images and did not enhance with gadolinium. The margins were irregular, involved the hippocampus, and were often associated with focal atrophy. The lesions usually were associated with seizure disorders and specific electroencephalographic changes, and the authors believe they represented hippocampal sclerosis

  4. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala...... of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings...... of a regulatory effect of the PFC on the emotional control of our actions....

  5. Selective reductions in prefrontal glucose metabolism in murderers.

    Science.gov (United States)

    Raine, A; Buchsbaum, M S; Stanley, J; Lottenberg, S; Abel, L; Stoddard, J

    1994-09-15

    This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.

  6. Prefrontal gray matter volume mediates genetic risks for obesity.

    Science.gov (United States)

    Opel, N; Redlich, R; Kaehler, C; Grotegerd, D; Dohm, K; Heindel, W; Kugel, H; Thalamuthu, A; Koutsouleris, N; Arolt, V; Teuber, A; Wersching, H; Baune, B T; Berger, K; Dannlowski, U

    2017-05-01

    Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.

  7. Atraumatic medial collateral ligament oedema in medial compartment knee osteoarthritis

    International Nuclear Information System (INIS)

    Bergin, D.; Keogh, C.; O'Connell, M.; Zoga, A.; Rowe, D.; Shah, B.; Eustace, S.

    2002-01-01

    Objective: To describe and determine the prevalence of atraumatic medial collateral oedema identified in patients with medial compartment osteoarthritis. Design and patients: Sixty patients, 30 patients with medial compartment knee osteoarthritis (Kellgren and Lawrence grade 2 to 4) and 30 age-matched patients with atraumatic knee pain without osteoarthritis, referred for MR imaging over a 2 year period were included in the study. In each case, severity of osteoarthritis was recorded on radiographs and correlated with the presence or absence of medial collateral ligament oedema at MR imaging. Results: Medial collateral oedema was identified in 27 of the 30 patients with osteoarthritis, of whom 14 had grade 1 oedema and 13 had grade 2 oedema compared with the presence of medial collateral ligament oedema (grade 1) in only two of the 30 control patients without osteoarthritis (P<<0.0001). Conclusion: Medial collateral oedema is common in patients with osteoarthritis in the absence of trauma. When identified, medial collateral ligament oedema should be considered to be a feature of osteoarthritis and should not be incorrectly attributed to an acute traumatic injury. (orig.)

  8. Fragmented medial coronoid process

    International Nuclear Information System (INIS)

    Juhasz, Cs.; Juhasz, T.

    1997-01-01

    Fragmented medial coronoid process: (FCP) is often considered to be part of the osteochondrosis dissecans complex, but trauma and growth discrepancies between the radius and ulna are proposed as causes. There is little to clinically differentiate FCP, from osteochondrosis dissecans (OCD) of the elbow. Pain on, flexion-extension of the elbow and lateral rotation of the paw is a little more consistent in FCP. Radiographic examination of the elbow is important despite the, fact that radiographic signs of the FCP are often nonspecific. Excessive osteoarthrosis and superimposition of the radial head and coronoid process make identification of the FCP difficult. Craniocaudal, flexed mediolateral and 25 degree craniocaudal-lateromedial views are necessary for diagnosis. Osteophyte production is more dramatic with FCP than with OCD and suggests therefore the occurrence of OCP in many cases. Although the detached process may be seen on any view, the oblique projection offers the least obstructed view. Exposure of the joint is identical to that for OCD, that means a medial approach with osteotomy of the epicondyle. In most cases the process is loose enough to be readily apparent, but in some it is necessary to exert force on the process in order to find the cleavage plane. It is necessary to remove the osteophytes as well and to inspect and irrigate the joint carefully to remove cartilage fragments before closure. Confinement is advisable for 4 weeks before returning the dog to normal activity. The outlook for function is good if the FCP is removed before secondary degenerative joint disease is well established

  9. Enhanced Operant Extinction and Prefrontal Excitability in a Mouse Model of Angelman Syndrome.

    Science.gov (United States)

    Sidorov, Michael S; Judson, Matthew C; Kim, Hyojin; Rougie, Marie; Ferrer, Alejandra I; Nikolova, Viktoriya D; Riddick, Natallia V; Moy, Sheryl S; Philpot, Benjamin D

    2018-03-14

    Angelman syndrome (AS), a neurodevelopmental disorder associated with intellectual disability, is caused by loss of maternal allele expression of UBE3A in neurons. Mouse models of AS faithfully recapitulate disease phenotypes across multiple domains, including behavior. Yet in AS, there has been only limited study of behaviors encoded by the prefrontal cortex, a region broadly involved in executive function and cognition. Because cognitive impairment is a core feature of AS, it is critical to develop behavioral readouts of prefrontal circuit function in AS mouse models. One such readout is behavioral extinction, which has been well described mechanistically and relies upon prefrontal circuits in rodents. Here we report exaggerated operant extinction in male AS model mice, concomitant with enhanced excitability in medial prefrontal neurons from male and female AS model mice. Abnormal behavior was specific to operant extinction, as two other prefrontally dependent tasks (cued fear extinction and visuospatial discrimination) were largely normal in AS model mice. Inducible deletion of Ube3a during adulthood was not sufficient to drive abnormal extinction, supporting the hypothesis that there is an early critical period for development of cognitive phenotypes in AS. This work represents the first formal experimental analysis of prefrontal circuit function in AS, and identifies operant extinction as a useful experimental paradigm for modeling cognitive aspects of AS in mice. SIGNIFICANCE STATEMENT Prefrontal cortex encodes "high-level" cognitive processes. Thus, understanding prefrontal function is critical in neurodevelopmental disorders where cognitive impairment is highly penetrant. Angelman syndrome is a neurodevelopmental disorder associated with speech and motor impairments, an outwardly happy demeanor, and intellectual disability. We describe a behavioral phenotype in a mouse model of Angelman syndrome and related abnormalities in prefrontal cortex function. We

  10. Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

    Science.gov (United States)

    Raine, A; Meloy, J R; Bihrle, S; Stoddard, J; LaCasse, L; Buchsbaum, M S

    1998-01-01

    There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

  11. The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

    Science.gov (United States)

    Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

    2014-07-01

    The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  12. Projections of the central medial nucleus of the thalamus in the rat: Node in cortical, striatal and limbic forebrain circuitry

    Czech Academy of Sciences Publication Activity Database

    Vertes, R. P.; Hoover, W. B.; Rodríguez Arellano, Jose Julio

    2012-01-01

    Roč. 219, 6 SEP (2012), s. 120-136 ISSN 0306-4522 R&D Projects: GA ČR GA309/09/1696 Institutional research plan: CEZ:AV0Z50390703 Keywords : medial prefrontal cortex * insular cortex * nucleus acc umbens Subject RIV: FH - Neurology Impact factor: 3.122, year: 2012

  13. Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent Female Mice Is Associated with Suppression of Food Restriction-Evoked Hyperactivity and Resilience to Activity-Based Anorexia.

    Science.gov (United States)

    Chen, Yi-Wen; Wable, Gauri Satish; Chowdhury, Tara Gunkali; Aoki, Chiye

    2016-06-01

    Many, but not all, adolescent female mice that are exposed to a running wheel while food restricted (FR) become excessive wheel runners, choosing to run even during the hours of food availability, to the point of death. This phenomenon is called activity-based anorexia (ABA). We used electron microscopic immunocytochemistry to ask whether individual differences in ABA resilience may correlate with the lengths of axo-somatic contacts made by GABAergic axon terminals onto layer 5 pyramidal neurons (L5P) in the prefrontal cortex. Contact lengths were, on average, 40% greater for the ABA-induced mice, relative to controls. Correspondingly, the proportion of L5P perikaryal plasma membrane contacted by GABAergic terminals was 45% greater for the ABA mice. Contact lengths in the anterior cingulate cortex correlated negatively and strongly with the overall wheel activity after FR (R = -0.87, P resilience through suppression of wheel running, a behavior that is intrinsically rewarding and helpful for foraging but maladaptive within a cage. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Infralimbic Prefrontal Cortex Interacts with Nucleus Accumbens Shell to Unmask Expression of Outcome-Selective Pavlovianto- Instrumental Transfer

    Science.gov (United States)

    Keistler, Colby; Barker, Jacqueline M.; Taylor, Jane R.

    2015-01-01

    Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context…

  15. Vocal fold injection medialization laryngoplasty.

    Science.gov (United States)

    Modi, Vikash K

    2012-01-01

    Unilateral vocal fold paralysis (UVFP) can cause glottic insufficiency that can result in hoarseness, chronic cough, dysphagia, and/or aspiration. In rare circumstances, UVFP can cause airway obstruction necessitating a tracheostomy. The treatment options for UVFP include observation, speech therapy, vocal fold injection medialization laryngoplasty, thyroplasty, and laryngeal reinnervation. In this chapter, the author will discuss the technique of vocal fold injection for medialization of a UVFP. Copyright © 2012 S. Karger AG, Basel.

  16. Major Thought Restructuring: The Roles of Different Prefrontal Cortical Regions.

    Science.gov (United States)

    Seyed-Allaei, Shima; Avanaki, Zahra Nasiri; Bahrami, Bahador; Shallice, Tim

    2017-07-01

    An important question for understanding the neural basis of problem solving is whether the regions of human prefrontal cortices play qualitatively different roles in the major cognitive restructuring required to solve difficult problems. However, investigating this question using neuroimaging faces a major dilemma: either the problems do not require major cognitive restructuring, or if they do, the restructuring typically happens once, rendering repeated measurements of the critical mental process impossible. To circumvent these problems, young adult participants were challenged with a one-dimensional Subtraction (or Nim) problem [Bouton, C. L. Nim, a game with a complete mathematical theory. The Annals of Mathematics, 3, 35-39, 1901] that can be tackled using two possible strategies. One, often used initially, is effortful, slow, and error-prone, whereas the abstract solution, once achieved, is easier, quicker, and more accurate. Behaviorally, success was strongly correlated with sex. Using voxel-based morphometry analysis controlling for sex, we found that participants who found the more abstract strategy (i.e., Solvers) had more gray matter volume in the anterior medial, ventrolateral prefrontal, and parietal cortices compared with those who never switched from the initial effortful strategy (i.e., Explorers). Removing the sex covariate showed higher gray matter volume in Solvers (vs. Explorers) in the right ventrolateral prefrontal and left parietal cortex.

  17. Dopamine in the medial amygdala network mediates human bonding.

    Science.gov (United States)

    Atzil, Shir; Touroutoglou, Alexandra; Rudy, Tali; Salcedo, Stephanie; Feldman, Ruth; Hooker, Jacob M; Dickerson, Bradford C; Catana, Ciprian; Barrett, Lisa Feldman

    2017-02-28

    Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers' dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the "medial amygdala network") that supports social functioning. We also measured the mothers' behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother's infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted.

  18. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

    Science.gov (United States)

    Schubert, D; Martens, G J M; Kolk, S M

    2015-07-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies.

  19. Mindful attention to breath regulates emotions via increased amygdala-prefrontal cortex connectivity.

    Science.gov (United States)

    Doll, Anselm; Hölzel, Britta K; Mulej Bratec, Satja; Boucard, Christine C; Xie, Xiyao; Wohlschläger, Afra M; Sorg, Christian

    2016-07-01

    Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala-prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala-dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Localization of dysfunction in major depressive disorder: prefrontal cortex and amygdala.

    Science.gov (United States)

    Murray, Elisabeth A; Wise, Steven P; Drevets, Wayne C

    2011-06-15

    Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of "self" underlies the core disorder in MDD; the medial frontal cortex represents "self"; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD. Published by Elsevier Inc.

  1. Reduced prefrontal cortical gray matter volume in young adults exposed to harsh corporal punishment.

    Science.gov (United States)

    Tomoda, Akemi; Suzuki, Hanako; Rabi, Keren; Sheu, Yi-Shin; Polcari, Ann; Teicher, Martin H

    2009-08-01

    Harsh corporal punishment (HCP) during childhood is a chronic, developmental stressor associated with depression, aggression and addictive behaviors. Exposure to traumatic stressors, such as sexual abuse, is associated with alteration in brain structure, but nothing is known about the potential neurobiological consequences of HCP. The aim of this study was to investigate whether HCP was associated with discernible alterations in gray matter volume (GMV) using voxel-based morphometry (VBM). 1455 young adults (18-25 years) were screened to identify 23 with exposure to HCP (minimum 3 years duration, 12 episodes per year, frequently involving objects) and 22 healthy controls. High-resolution T1-weighted MRI datasets were obtained using Siemens 3 T trio scanner. GMV was reduced by 19.1% in the right medial frontal gyrus (medial prefrontal cortex; MPFC, BA10) (P=0.037, corrected cluster level), by 14.5% in the left medial frontal gyrus (dorsolateral prefrontal cortex; DLPFC, BA9) (P=0.015, uncorrected cluster level) and by 16.9% in the right anterior cingulate gyrus (BA24) (P<0.001, uncorrected cluster level) of HCP subjects. There were significant correlations between GMV in these identified regions and performance IQ on the WAIS-III. Exposing children to harsh HCP may have detrimental effects on trajectories of brain development. However, it is also conceivable that differences in prefrontal cortical development may increase risk of exposure to HCP.

  2. Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Athilingam, Jegath; Robinson, Sarah E

    2016-01-01

    Both medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety; however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin...... acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist...... into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency mPFC activity (4-12 Hz), and reduced avoidance of anxiogenic regions in the elevated plus maze. These findings...

  3. Differential roles for medial prefrontal and medial temporal cortices in schema-dependent encoding : from congruent to incongruent

    NARCIS (Netherlands)

    van Kesteren, Marlieke T R; Beul, Sarah F; Takashima, Atsuko; Henson, Richard N; Ruiter, Dirk J; Fernández, Guillén

    2013-01-01

    Information that is congruent with prior knowledge is generally remembered better than incongruent information. This effect of congruency on memory has been attributed to a facilitatory influence of activated schemas on memory encoding and consolidation processes, and hypothesised to reflect a shift

  4. Cinética de lixiviación de la corteza de mangle rojo en agua Leaching kinetics of the red mangrove bark in water

    Directory of Open Access Journals (Sweden)

    Yanet Rodríguez Perdomo

    2012-03-01

    Full Text Available Objetivo: determinar la naturaleza del fenómeno que rige la transferencia de masa durante la lixiviación del mangle rojo en agua mediante el estudio de la cinética del proceso. Métodos: se estudió la cinética de lixiviación de la corteza de mangle rojo en agua a escala de laboratorio, en una relación sólido/líquido 1:4 a diferentes temperaturas (25, 45, 70 y 90 °C. Para cada temperatura en particular se determinó la constante cinética a partir de la ecuación fundamental de la lixiviación mediante un modelo ajustado empleando el programa estadístico CurveExpert 1.4 para Windows. Resultados: los valores de la concentración de sólidos solubles totales correspondientes a 25 y 45 °C presentaron un incremento apreciable durante los primeros 20 min, y los correspondientes a 70 y 90 °C lo alcanzaron a los 30 min. El valor de la energía de activación obtenida en el experimento correspondió a 2,884 kJ. Conclusiones: la naturaleza de la lixiviación de la corteza de mangle rojo se produce por vía física.Objective: to determine the type of phenomenon ruling the mass transfer during leaching of red mangrove in water by studying the kinetics of this process. Methods: the kinetics of leaching of red mangrove bark into water at lab was studied in a solid/liquid ratio of 1:4 at different temperatures (25, 45, 70 and 90 ºC. For each temperature, the kinetic constant was estimated from the fundamental leaching equation by a fitted model using the statistical program CurveExpert 1.4 for Windows. Results: the total soluble solid concentration values showed a sizeable increase at 25 and 45 °C in the first 20 minutes and at 70 and 90 °C in 30 minutes. The activation energy in the experiment amounted to 2.884 kJ. Conclusions: the leaching of the red mangrove bark is of physical origin.

  5. Action control is mediated by prefrontal BDNF and glucocorticoid receptor binding.

    Science.gov (United States)

    Gourley, Shannon L; Swanson, Andrew M; Jacobs, Andrea M; Howell, Jessica L; Mo, Michelle; Dileone, Ralph J; Koleske, Anthony J; Taylor, Jane R

    2012-12-11

    Stressor exposure biases decision-making strategies from those based on the relationship between actions and their consequences to others restricted by stimulus-response associations. Chronic stressor exposure also desensitizes glucocorticoid receptors (GR) and diminishes motivation to acquire food reinforcement, although causal relationships are largely not established. We show that a history of chronic exposure to the GR ligand corticosterone or acute posttraining GR blockade with RU38486 makes rodents less able to perform actions based on their consequences. Thus, optimal GR binding is necessary for the consolidation of new response-outcome learning. In contrast, medial prefrontal (but not striatal) BDNF can account for stress-related amotivation, in that selective medial prefrontal cortical Bdnf knockdown decreases break-point ratios in a progressive-ratio task. Knockdown also increases vulnerability to RU38486. Despite the role of BDNF in dendritic spine reorganization, deep-layer spine remodeling does not obviously parallel progressive-ratio response patterns, but treatment with the Na(+)-channel inhibitor riluzole reverses corticosteroid-induced motivational deficits and restores prefrontal BDNF expression after corticosterone. We argue that when prefrontal neurotrophin systems are compromised, and GR-mediated hypothalamic-pituitary-adrenal axis feedback is desensitized (as in the case of chronic stress hormone exposure), amotivation and inflexible maladaptive response strategies that contribute to stress-related mood disorders result.

  6. Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

    Science.gov (United States)

    Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

    2011-03-01

    Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. The relationship between chondromalacia patella, medial meniscal tear and medial periarticular bursitis in patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Resorlu Mustafa

    2017-11-01

    Full Text Available This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa in osteoarthritis, chondromalacia patella and medial meniscal tears.

  8. Injerto libre braquial medial Free medial arm graft

    Directory of Open Access Journals (Sweden)

    P. Martos Díaz

    2007-12-01

    Full Text Available Introducción. Entre las reconstrucciones de defectos titulares de cabeza y cuello, el injerto libre microvascularizado braquial medial no ha adquirido mucha popularidad debido a las variaciones anatómicas que se reflejan en la vascularización de éste. Nuestro objetivo es realizar una descripción de la anatomía y técnica quirúrgica, así como una revisión de la literatura describiendo las ventajas y desventajas de este tipo de injerto. Material y método. Presentamos el caso de una paciente con carcinoma epidermoide de mucosa yugal izquierda con afectación ganglionar ipsilateral. Se procedió a su resección con márgenes más disección cervical funcional. La reconstrucción del defecto se llevó a cabo mediante un injerto libre microvascularizado braquial medial de brazo izquierdo. Discusión. Pensamos que el injerto libre braquial medial de brazo se trata de una opción más segura a la hora de la reconstrucción de defectos cervicofaciales, aportando una serie de ventajas entre las que destacan: no sacrificio de una arteria terminal, cierre primario de la zona donante, mínimo defecto estético, y poseer una piel fina, elástica y sin vello.Introduction. Free medial microvascularized arm grafts have not become very popular for the reconstruction of head and neck defects due to anatomic variations in their vascularization. Our objective was to describe the anatomy and surgical technique and to review the literature on the advantages and disadvantages of free medial arm grafts. Material and methods. We report the case of a patient with squamous cell carcinoma of the left jugal mucosa with same-side lymph node involvement. The tumor was resected with margins and a functional cervical dissection was performed. The defect was reconstructed using a free medial microvascularized graft from the left arm. Discussion. We believe that free medial arm grafts are a safer option for the reconstruction of cervicofacial defects and that they offer

  9. MRI volumetry of prefrontal cortex

    Science.gov (United States)

    Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.

    1995-05-01

    Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was volumetry by stereology can yield accurate and repeatable measurements. Small frontal lobe volume reductions in patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

  10. Prefrontal control of cerebellum-dependent associative motor learning.

    Science.gov (United States)

    Chen, Hao; Yang, Li; Xu, Yan; Wu, Guang-yan; Yao, Juan; Zhang, Jun; Zhu, Zhi-ru; Hu, Zhi-an; Sui, Jian-feng; Hu, Bo

    2014-02-01

    Behavioral studies have demonstrated that both medial prefrontal cortex (mPFC) and cerebellum play critical roles in trace eyeblink conditioning. However, little is known regarding the mechanism by which the two brain regions interact. By use of electrical stimulation of the caudal mPFC as a conditioned stimulus, we show evidence that persistent outputs from the mPFC to cerebellum are necessary and sufficient for the acquisition and expression of a trace conditioned response (CR)-like response. Specifically, the persistent outputs of caudal mPFC are relayed to the cerebellum via the rostral part of lateral pontine nuclei. Moreover, interfering with persistent activity by blockade of the muscarinic Ach receptor in the caudal mPFC impairs the expression of learned trace CRs. These results suggest an important way for the caudal mPFC to interact with the cerebellum during associative motor learning.

  11. Medial Canthoplasty Combined with Conjunctivodacryocystorhinostomy for the Treatment of Delayed Medial Telecanthal Deformity

    Directory of Open Access Journals (Sweden)

    Hua Sun

    2017-01-01

    Conclusions: Medial canthoplasty combined with CDCR is an effective surgical method for treatment of patients with medial telecanthal deformity and lacrimal drainage system obstruction. The study indicates that medial canthoplasty combined with CDCR surgery rebuilds normal appearance of eyelid and contour of the medial canthus and successfully repairs the function of the lacrimal drainage system.

  12. Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: Effects of novelty and handling and comparison to the nucleus accumbens

    NARCIS (Netherlands)

    Feenstra, M. G.; Botterblom, M. H.; Mastenbroek, S.

    2000-01-01

    We used on-line microdialysis measurements of dopamine and noradrenaline extracellular concentrations in the medial prefrontal cortex of awake, freely moving rats during the dark and the light period of the day to study whether (i) basal efflux would be higher in the active, dark period than in the

  13. Medial tibial “spackling” to lessen chronic medial tibial soft tissue irritation

    Directory of Open Access Journals (Sweden)

    J. Ryan Martin, MD

    2016-09-01

    Full Text Available We describe a unique, utilitarian reconstructive treatment option known as tibial “spackling” for chronic, localized medial joint line pain corresponding with progressive radiographic peripheral medial tibial bone loss beneath a well-fixed revision total knee arthroplasty tibial baseplate. It is believed that this localized pain is due to chronic irritation of the medial capsule and collateral ligament from the prominent medial edge of the tibial component. In the setting of failed nonoperative treatment, our experience with utilizing bone cement to reconstruct the medial tibial bone defect and create a smooth medial tibial surface has been successful in eliminating chronic medial soft tissue irritation.

  14. Resection of the medial temporal lobe disconnects the rostral superior temporal gyrus from some of its projection targets in the frontal lobe and thalamus.

    Science.gov (United States)

    Muñoz, Monica; Mishkin, Mortimer; Saunders, Richard C

    2009-09-01

    Auditory memory in the monkey does not appear to extend beyond the limits of working memory. It is therefore surprising that this ability is impaired by medial temporal lobe (MTL) resections, because such lesions spare working memory in other sensory modalities. To determine whether MTL ablations might have caused the auditory deficit through inadvertent transection of superior temporal gyrus (STG) projections to its downstream targets, and, if so, which targets might have been compromised, we injected anterograde tracer (biotinylated dextran amine) in the STG of both the normal and MTL-lesioned hemispheres of split-brain monkeys. Interhemispheric comparison of label failed to show any effect of the MTL ablation on efferents from caudal STG, which projects to the inferior prefrontal convexity. However, the ablation did consistently interrupt the normally dense projections from rostral STG to both the ventral medial prefrontal cortex and medial thalamic nuclei. The findings support the possibility that the auditory working memory deficit after MTL ablation is due to transection of downstream auditory projections, and indicate that the candidate structures for mediating auditory working memory are the ventral medial prefrontal cortical areas, the medial thalamus, or both.

  15. Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients.

    Science.gov (United States)

    Arbula, Sandra; Pacella, Valentina; De Pellegrin, Serena; Rossetto, Marta; Denaro, Luca; D'Avella, Domenico; Della Puppa, Alessandro; Vallesi, Antonino

    2017-06-01

    The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies. Copyright © 2017 The Authors

  16. Directional hippocampal-prefrontal interactions during working memory.

    Science.gov (United States)

    Liu, Tiaotiao; Bai, Wenwen; Xia, Mi; Tian, Xin

    2018-02-15

    Working memory refers to a system that is essential for performing complex cognitive tasks such as reasoning, comprehension and learning. Evidence shows that hippocampus (HPC) and prefrontal cortex (PFC) play important roles in working memory. The HPC-PFC interaction via theta-band oscillatory synchronization is critical for successful execution of working memory. However, whether one brain region is leading or lagging relative to another is still unclear. Therefore, in the present study, we simultaneously recorded local field potentials (LFPs) from rat ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) and while the rats performed a Y-maze working memory task. We then applied instantaneous amplitudes cross-correlation method to calculate the time lag between PFC and vHPC to explore the functional dynamics of the HPC-PFC interaction. Our results showed a strong lead from vHPC to mPFC preceded an animal's correct choice during the working memory task. These findings suggest the vHPC-leading interaction contributes to the successful execution of working memory. Copyright © 2017. Published by Elsevier B.V.

  17. Ventromedial prefrontal cortex, adding value to autobiographical memories.

    Science.gov (United States)

    Lin, Wen-Jing; Horner, Aidan J; Burgess, Neil

    2016-06-24

    The medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found that the blood oxygen level dependent (BOLD) signal in ventromedial prefrontal cortex (vmPFC) was parametrically modulated by the affective values of items in participants' memories when they were recalling and evaluating these items. An unrelated modulation by the participant's familiarity with the items was also observed. During retrieval of the event, the BOLD signal in the same region was modulated by the personal significance and emotional intensity of the memory, which was correlated with the values of the items within them. These results support the idea that vmPFC processes self-relevant information, and suggest that it is involved in representing the personal emotional values of the elements comprising autobiographical memories.

  18. The topology of connections between rat prefrontal and temporal cortices

    Directory of Open Access Journals (Sweden)

    Stacey eBedwell

    2015-05-01

    Full Text Available Understanding the structural organisation of the prefrontal cortex (PFC is an important step towards determining its functional organisation. Here we investigated the organisation of PFC using different neuronal tracers. We injected retrograde (Fluoro-Gold, 100nl and anterograde (Biotinylated dextran amine (BDA or Fluoro-Ruby, 100nl tracers into sites within PFC subdivisions (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital along a coronal axis within PFC. At each injection site one injection was made of the anterograde tracer and one injection was made of the retrograde tracer. The projection locations of retrogradely labelled neurons and anterogradely labelled axon terminals were then analysed in the temporal cortex: area Te, entorhinal and perirhinal cortex. We found evidence for an ordering of both the anterograde (anterior-posterior, dorsal-ventral and medial-lateral axes: p<0.001 and retrograde (anterior-posterior, dorsal-ventral and medial-lateral axes: p<0.001 connections of PFC. We observed that anterograde and retrograde labelling in ipsilateral temporal cortex (i.e. PFC inputs and outputs often occurred reciprocally (i.e. the same brain region, such as area 35d in perirhinal cortex, contained anterograde and retrograde labelling. However, often the same specific columnar temporal cortex regions contained only either labelling of retrograde or anterograde tracer, indicating that PFC inputs and outputs are frequently non-matched.

  19. Caracterización de los efectos de la administración de la lectina antinutricional nigrina de corteza de Sambucus nigra L. y efecto sinérgico con los polifenoles del té verde

    OpenAIRE

    Cabrero Lobato, Patricia

    2012-01-01

    Las proteínas inactivadoras de ribosomas (RIPs) son enzimas con actividad N-glicosidasa del ARN ribosómico. Algunas poseen dos cadenas una con actividad enzimática y otra con actividad lectina (RIPs de tipo dos). Entre estas RIPs se encuentra la nigrina b presente en la corteza de Sambucus nigra L. La nigrina b presenta toxicidad selectiva en función de la dosis y la vía de administración. El blanco son las células de las criptas del intestino delgado. Nuestra hipótesis es que los efectos tóx...

  20. Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder

    OpenAIRE

    Rogers, Tiffany D.; Dickson, Price E.; McKimm, Eric; Heck, Detlef H.; Goldowitz, Dan; Blaha, Charles D.; Mittleman, Guy

    2013-01-01

    Imaging, clinical and pre-clinical studies have provided ample evidence for a cerebellar involvement in cognitive brain function including cognitive brain disorders, such as autism and schizophrenia. We previously reported that cerebellar activity modulates dopamine release in the mouse medial prefrontal cortex (mPFC) via two distinct pathways: (1) cerebellum to mPFC via dopaminergic projections from the ventral tegmental area [VTA] and (2) cerebellum to mPFC via glutamatergic projections fro...

  1. Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.

    Science.gov (United States)

    Kegeles, Lawrence S; Mao, Xiangling; Stanford, Arielle D; Girgis, Ragy; Ojeil, Najate; Xu, Xiaoyan; Gil, Roberto; Slifstein, Mark; Abi-Dargham, Anissa; Lisanby, Sarah H; Shungu, Dikoma C

    2012-05-01

    Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness. To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls. Case-control study. Inpatient psychiatric research unit and associated outpatient clinic. Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking. Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects. The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy. In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found. To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with

  2. Inactivation of Medial Prefrontal Cortex or Acute Stress Impairs Odor Span in Rats

    Science.gov (United States)

    Davies, Don A.; Molder, Joel J.; Greba, Quentin; Howland, John G.

    2013-01-01

    The capacity of working memory is limited and is altered in brain disorders including schizophrenia. In rodent working memory tasks, capacity is typically not measured (at least not explicitly). One task that does measure working memory capacity is the odor span task (OST) developed by Dudchenko and colleagues. In separate experiments, the effects…

  3. The Role of the Medial Prefrontal Cortex in Trace Fear Extinction

    Science.gov (United States)

    Kwapis, Janine L.; Jarome, Timothy J.; Helmstetter, Fred J.

    2015-01-01

    The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that…

  4. Medial prefrontal cortex activation facilitates re-extinction of fear in rats

    OpenAIRE

    Chang, Chun-hui; Maren, Stephen

    2011-01-01

    It has been suggested that reduced infralimbic (IL) cortical activity contributes to impairments of fear extinction. We therefore explored whether pharmacological activation of the IL would facilitate extinction under conditions it normally fails (i.e., immediate extinction). Rats received auditory fear conditioning 1 h before extinction training. Immediately prior to extinction, rats received microinfusions into the IL of the GABAA receptor antagonist, picrotoxin, or the NMDA receptor partia...

  5. Medial Prefrontal Lesions in Mice Impair Sustained Attention but Spare Maintenance of Information in Working Memory

    Science.gov (United States)

    Kahn, Julia B.; Ward, Ryan D.; Kahn, Lora W.; Rudy, Nicole M.; Kandel, Eric R.; Balsam, Peter D.; Simpson, Eleanor H.

    2012-01-01

    Working memory and attention are complex cognitive functions that are disrupted in several neuropsychiatric disorders. Mouse models of such human diseases are commonly subjected to maze-based tests that can neither distinguish between these cognitive functions nor isolate specific aspects of either function. Here, we have adapted a simple visual…

  6. The emotive nature of conflict monitoring in the medial prefrontal cortex.

    Science.gov (United States)

    Saunders, Blair; Lin, Hause; Milyavskaya, Marina; Inzlicht, Michael

    2017-09-01

    The detection of conflict between incompatible impulses, thoughts, and actions is a ubiquitous source of motivation across theories of goal-directed action. In this overview, we explore the hypothesis that conflict is emotive, integrating perspectives from affective science and cognitive neuroscience. Initially, we review evidence suggesting that the mental and biological processes that monitor for information processing conflict-particularly those generated by the anterior midcingulate cortex-track the affective significance of conflict and use this signal to motivate increased control. In this sense, variation in control resembles a form of affect regulation in which control implementation counteracts the aversive experience of conflict. We also highlight emerging evidence proposing that states and dispositions associated with acceptance facilitate control by tuning individuals to the emotive nature of conflict, before proposing avenues for future research, including investigating the role of affect in reinforcement learning and decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Medial prefrontal-hippocampal connectivity and motor memory consolidation in depression and schizophrenia

    NARCIS (Netherlands)

    Genzel, L.K.E.; Dresler, M.; Cornu, M.; Jager, E.; Konrad, B.; Adamczyk, M.; Friess, E.; Steiger, A.; Czisch, M.; Goya-Maldonado, R.

    2015-01-01

    BACKGROUND: Overnight memory consolidation is disturbed in both depression and schizophrenia, creating an ideal situation to investigate the mechanisms underlying sleep-related consolidation and to distinguish disease-specific processes from common elements in their pathophysiology. METHODS: We

  8. Dynamic Expression of FKBP5 in the Medial Prefrontal Cortex Regulates Resiliency to Conditioned Fear

    Science.gov (United States)

    Criado-Marrero, Marangelie; Morales Silva, Roberto J.; Velazquez, Bethzaly; Hernández, Anixa; Colon, María; Cruz, Emmanuel; Soler-Cedeño, Omar; Porter, James T.

    2017-01-01

    The factors influencing resiliency to the development of post-traumatic stress disorder (PTSD) remain to be elucidated. Clinical studies associate PTSD with polymorphisms of the FK506 binding protein 5 (FKBP5). However, it is unclear whether changes in FKBP5 expression alone could produce resiliency or susceptibility to PTSD-like symptoms. In this…

  9. Reduced Medial Prefrontal Cortex Volume in Adults Reporting Childhood Emotional Maltreatment

    NARCIS (Netherlands)

    van Harmelen, Anne-Laura; van Tol, Marie-Jose; van der Wee, Nic J. A.; Veltman, Dick J.; Aleman, Andre; Spinhoven, Philip; van Buchem, Mark A.; Zitman, Frans G.; Penninx, Brenda W. J. H.; Elzinga, Bernet M.

    2010-01-01

    Background: Childhood emotional maltreatment (CEM) has been associated with a profound and enduring negative impact on behavioral and emotional functioning. Animal models have shown that adverse rearing conditions, such as maternal separation, can induce a cascade of long-term structural alterations

  10. Medial Prefrontal Cortex Activation Facilitates Re-Extinction of Fear in Rats

    Science.gov (United States)

    Chang, Chun-hui; Maren, Stephen

    2011-01-01

    It has been suggested that reduced infralimbic (IL) cortical activity contributes to impairments of fear extinction. We therefore explored whether pharmacological activation of the IL would facilitate extinction under conditions it normally fails (i.e., immediate extinction). Rats received auditory fear conditioning 1 h before extinction training.…

  11. Acute Medial Plantar Fascia Tear.

    Science.gov (United States)

    Pascoe, Stephanie C; Mazzola, Timothy J

    2016-06-01

    A 32-year-old man who participated in competitive soccer came to physical therapy via direct access for a chief complaint of plantar foot pain. The clinical examination findings and mechanism of injury raised a concern for a plantar fascia tear, so the patient was referred to the physician and magnetic resonance imaging was obtained. The magnetic resonance image confirmed a high-grade, partial-thickness, proximal plantar fascia tear with localized edema at the location of the medial band. J Orthop Sports Phys Ther 2016;46(6):495. doi:10.2519/jospt.2016.0409.

  12. Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Daniel W. Sparks

    2018-01-01

    Full Text Available Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh and serotonin (5-HT have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

  13. Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex.

    Science.gov (United States)

    Sparks, Daniel W; Tian, Michael K; Sargin, Derya; Venkatesan, Sridevi; Intson, Katheron; Lambe, Evelyn K

    2017-01-01

    Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

  14. Back to front: cerebellar connections and interactions with the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Thomas C Watson

    2014-02-01

    Full Text Available Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the contralateral cerebellar fastigial nucleus (FN in awake, behaving rats evokes distinct local field potential (LFP responses (onset latency ~13 ms in the prelimbic (PrL subdivision of the medial prefrontal cortex. Trains of FN stimulation evoke heterogeneous patterns of response in putative pyramidal cells in frontal and prefrontal regions in both urethane-anaesthetized and awake, behaving rats. However, the majority of cells showed decreased firing rates during stimulation and subsequent rebound increases; more than 90% of cells showed significant changes in response. Simultaneous recording of on-going LFP activity from FN and PrL while rats were at rest or actively exploring an open field arena revealed significant network coherence restricted to the theta frequency range (5-10 Hz. Granger causality analysis indicated that this coherence was significantly directed from cerebellum to PrL during active locomotion. Our results demonstrate the presence of a cerebello-prefrontal pathway in rat and reveal behaviorally dependent coordinated network activity between the two structures, which could facilitate transfer of sensorimotor information into ongoing neocortical processing during goal directed behaviors.

  15. Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior

    DEFF Research Database (Denmark)

    Brumback, A C; Ellwood, I T; Kjaerby, C

    2017-01-01

    Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior...... in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered...... SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially...

  16. Snapping Knee Caused by Medial Meniscal Cyst

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Ohishi

    2014-01-01

    Full Text Available Snapping phenomenon around the medial aspect of the knee is rare. We present this case of snapping knee caused by the sartorius muscle over a large medial meniscal cyst in a 66-year-old female. Magnetic resonance images demonstrated a large medial meniscal cyst with a horizontal tear of the medial meniscus. Arthroscopic cyst decompression with limited meniscectomy resulted in the disappearance of snapping, and no recurrence of the cyst was observed during a 2-year follow-up period.

  17. Efecto de la infección por el virus de la rabia sobre la expresión de parvoalbúmina, calbindina y calretinina en la corteza cerebral de ratones.

    Directory of Open Access Journals (Sweden)

    Orlando Torres-Fernández

    2004-03-01

    Full Text Available Algunas manifestaciones clínicas de la rabia, así como los resultados de experimentos con cultivos celulares y animales de laboratorio han llevado a sugerir que el virus de la rabia afecta la neurotransmisión gabaérgica. En la corteza cerebral existen diferentes tipos de neuronas que sintetizan el neurotransmisor GABA. Éstas se pueden identificar con marcadores neuronales, entre los que se destacan tres proteínas ligadoras de calcio: la parvoalbúmina (PV, la calbindina (CB y la calretinina (CR. El virus de la rabia se disemina a través de la corteza cerebral pero se desconocen sus posibles efectos citopáticos sobre las neuronas gabaérgicas. Para evaluar el efecto de la rabia sobre estas neuronas, se estudió mediante inmunohistoquímica la expresión de PV, CB y CR en la corteza frontal de ratones normales y ratones infectados con virus 'calle' o virus 'fijo' de la rabia. La PV se expresó en neuronas multipolares dispersas regularmente entre las capas II y VI, y en botones sinápticos que bordeaban el soma de las neuronas piramidales. La inmunorreactividad a CB se manifestó en dos franjas corticales: la primera, en las capas supragranulares II y III en neuronas con somas redondeados e inmersos en un neuropilo intensamente marcado; la segunda, en las capas infragranulares V y VI en neuronas multipolares dispersas y rodeadas por un neuropilo menos reactivo. La CR se expresó en neuronas bipolares con somas fusiformes distribuidas en las seis capas corticales, pero concentradas principalmente en las capas II y III. Hubo una característica común en las muestras infectadas con los dos tipos de virus: la inmunotinción a PV fue más intensa que en las muestras normales. La infección derivada del virus 'calle' no causó alteraciones adicionales en la expresión de las tres proteínas. En contraste, la infección con virus 'fijo' produjo una reducción notable del número de neuronas CB+, así como de la inmunorreactividad a CB en el

  18. Compulsive Sexual Behavior: Prefrontal and Limbic Volume and Interactions

    DEFF Research Database (Denmark)

    Schmidt, Casper; Morris, Laurel S.; Kvamme, Timo L.

    2017-01-01

    prefrontal cortex (whole brain, cluster corrected FWE P motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions...

  19. Medial subtalar dislocation: Case report

    Directory of Open Access Journals (Sweden)

    Manojlović Radovan

    2010-01-01

    Full Text Available Introduction. Subtalar dislocation (SI is a term that refers to an injury in which there is dislocation of the talonavicular and talocalcanear joint, although the tibiotalar joint is intact. Case Outline. A case of medial subtalar dislocation as a result of basketball injury, so-called 'basketball foot', is presented. Closed reposition in i.v. anaesthesia was performed with the patient in supine position and a knee flexed at 90 degrees. Longitudinal manual traction in line of deformity was carried out in plantar flexion. The reposition continued with abduction and eversion simultaneously increasing dorsiflexion. It was made in the first attempt and completed instantly. Rehabilitation was initiated after 5 weeks of immobilization. One year after the injury, the functional outcome was excellent with full range of motion and the patient was symptom-free. For better interpretation of roentgenogram, bone model of subtalar dislocation was made using the cadaver bone. Conclusion. Although the treatment of such injury is usually successful, diagnosis can be difficult because it is a rare injury, and moreover, X-ray of the injury can be confusing due to superposition of bones. Radiograms revealed superposition of the calcaneus, tarsal and metatarsal bones which was radiographically visualized in the anterior-posterior projection as one osseous block inward from the talus, and on the lateral view as in an osteal block below the tibial bone. Prompt recognition of these injuries followed by proper, delicately closed reduction under anaesthesia is crucial for achieving a good functional result in case of medial subtalar dislocation.

  20. Differences in prefrontal, limbic, and white matter lesion volumes according to cognitive status in elderly patients with first-onset subsyndromal depression.

    Directory of Open Access Journals (Sweden)

    Jun-Young Lee

    Full Text Available The purpose of this preliminary study was to test the hypothesis that subsyndromal depression is associated with the volume of medial prefrontal regional gray matter and that of white matter lesions (WMLs in the brains of cognitively normal older people. We also explored the relationships between subsyndromal depression and medial prefrontal regional gray matter volume, limbic regional gray matter volume, and lobar WMLs in the brains of patients with mild cognitive impairment (MCI and Alzheimer's disease (AD. We performed a cross-sectional study comparing patients with subsyndromal depression and nondepressed controls with normal cognition (n = 59, MCI (n = 27, and AD (n = 27, adjusting for sex, age, years of education, and results of the Mini-Mental State Examination. Frontal WML volume was greater, and right medial orbitofrontal cortical volume was smaller in cognitively normal participants with subsyndromal depression than in those without subsyndromal depression. No volume differences were observed in medial prefrontal, limbic, or WML volumes according to the presence of subsyndromal depression in cognitively impaired patients. The absence of these changes in patients with MCI and AD suggests that brain changes associated with AD pathology may override the changes associated with subsyndromal depression.

  1. Outside-In Deep Medial Collateral Ligament Release During Arthroscopic Medial Meniscus Surgery.

    Science.gov (United States)

    Todor, Adrian; Caterev, Sergiu; Nistor, Dan Viorel

    2016-08-01

    Arthroscopic partial medial meniscectomy is a very common orthopaedic procedure performed for symptomatic, irreparable meniscus tears. It is usually associated with a very good outcome and minimal complications. In some patients with tight medial compartment, the posterior horn of the medial meniscus can be difficult to visualize, and access in this area with instruments may be challenging. To increase the opening of the medial compartment, after valgus-extension stress position of the knee, different techniques of deep medial collateral ligament release have been described. The outside-in pie-crusting technique shown in this technical note has documented effectiveness and good outcomes with minimal or no morbidity.

  2. Predicting Treatment Outcomes from Prefrontal Cortex Activation for Self-Harming Patients with Borderline Personality Disorder: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Anthony Charles Ruocco

    2016-05-01

    Full Text Available Self-harm is a potentially lethal symptom of borderline personality disorder (BPD that often improves with dialectical behavior therapy (DBT. While DBT is effective for reducing self-harm in many patients with BPD, a small but significant number of patients either does not improve in treatment or ends treatment prematurely. Accordingly, it is crucial to identify factors that may prospectively predict which patients are most likely to benefit from and remain in treatment. In the present preliminary study, twenty-nine actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex during impulse control prior to beginning DBT and after seven months of treatment. Patients that reduced their frequency of self-harm the most over treatment displayed lower levels of neural activation in the bilateral dorsolateral prefrontal cortex prior to beginning treatment, and they showed the greatest increases in activity within this region after seven months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial prefrontal cortex and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right dorsolateral prefrontal cortex even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the prefrontal cortex underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT.

  3. Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

    Science.gov (United States)

    Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Macià, Dídac; Pera, Vanessa; Hernández-Ribas, Rosa; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

    2015-11-01

    Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy. High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping. Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy. Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with

  4. Prefrontal cortical GABA modulation of spatial reference and working memory.

    Science.gov (United States)

    Auger, Meagan L; Floresco, Stan B

    2014-10-31

    Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates susceptibility to proactive interference. Male rats were well-trained to retrieve food from the same 4 arms of an 8-arm maze, receiving 5 trials/day (1-2 min intervals). Infusions of the GABAA receptor antagonist bicuculline (12.5-50 ng) markedly increased working and reference memory errors and response latencies. Similar treatments also impaired short-term memory on an 8-baited arm task. These effects did not appear to be due to increased susceptibility to proactive interference. In contrast, PFC inactivation via infusion of GABA agonists baclofen/muscimol did not affect reference/working memory. In comparison to the pronounced effects on the 8-arm maze tasks, PFC GABAA antagonism only causes a slight and transient decrease in accuracy on a 2-arm spatial discrimination. These findings demonstrate that prefrontal GABA hypofunction severely disrupts spatial reference and short-term memory and that disinhibition of the PFC can, in some instances, perturb memory processes not normally dependent on the frontal lobes. Moreover, these impairments closely resemble those observed in schizophrenic patients, suggesting that perturbation in PFC GABA signaling may contribute to these types of cognitive deficits associated with the disorder. © The Author 2014. Published by Oxford University Press on behalf of CINP.

  5. Power spectrum scale invariance identifies prefrontal dysregulation in paranoid schizophrenia.

    Science.gov (United States)

    Radulescu, Anca R; Rubin, Denis; Strey, Helmut H; Mujica-Parodi, Lilianne R

    2012-07-01

    Theory and experimental evidence suggest that complex living systems function close to the boundary of chaos, with erroneous organization to an improper dynamical range (too stiff or chaotic) underlying system-wide dysregulation and disease. We hypothesized that erroneous organization might therefore also characterize paranoid schizophrenia, via optimization abnormalities in the prefrontal-limbic circuit regulating emotion. To test this, we acquired fMRI scans from 35 subjects (N = 9 patients with paranoid schizophrenia and N = 26 healthy controls), while they viewed affect-valent stimuli. To quantify dynamic regulation, we analyzed the power spectrum scale invariance (PSSI) of fMRI time-courses and computed the geometry of time-delay (Poincaré) maps, a measure of variability. Patients and controls showed distinct PSSI in two clusters (k(1) : Z = 4.3215, P = 0.00002 and k(2) : Z = 3.9441, P = 0.00008), localized to the orbitofrontal/medial prefrontal cortex (Brodmann Area 10), represented by β close to white noise in patients (β ≈ 0) and in the pink noise range in controls (β ≈ -1). Interpreting the meaning of PSSI differences, the Poincaré maps indicated less variability in patients than controls (Z = -1.9437, P = 0.05 for k(1) ; Z = -2.5099, P = 0.01 for k(2) ). That the dynamics identified Brodmann Area 10 is consistent with previous schizophrenia research, which implicates this area in deficits of working memory, executive functioning, emotional regulation and underlying biological abnormalities in synaptic (glutamatergic) transmission. Our results additionally cohere with a large body of work finding pink noise to be the normal range of central function at the synaptic, cellular, and small network levels, and suggest that patients show less supple responsivity of this region. Copyright © 2011 Wiley-Liss, Inc.

  6. The Modulation of Error Processing in the Medial Frontal Cortex by Transcranial Direct Current Stimulation

    Directory of Open Access Journals (Sweden)

    Lisa Bellaïche

    2013-01-01

    Full Text Available Background. In order to prevent future errors, we constantly control our behavior for discrepancies between the expected (i.e., intended and the real action outcome and continuously adjust our behavior accordingly. Neurophysiological correlates of this action-monitoring process can be studied with event-related potentials (error-related negativity (ERN and error positivity (Pe originating from the medial prefrontal cortex (mPFC. Patients with neuropsychiatric diseases often show performance monitoring dysfunctions potentially caused by pathological changes of cortical excitability; therefore, a modulation of the underlying neuronal activity might be a valuable therapeutic tool. One technique which allows us to explore cortical modulation of neural networks is transcranial direct current stimulation (tDCS. Therefore, we tested the effect of medial-prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly assigned to anodal, cathodal, or sham stimulation. Results. We found that cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham stimulation, but no effect for the ERN. Conclusions. Our results indicate that cathodal tDCS over the mPFC results in an attenuated cortical excitability leading to decreased Pe amplitudes. We therefore conclude that tDCS has a neuromodulatory effect on error-monitoring systems suggesting a future approach to modify the sensitivity of corresponding neural networks in patients with action-monitoring deficits.

  7. Theta oscillations orchestrate medial temporal lobe and neocortex in remembering autobiographical memories.

    Science.gov (United States)

    Fuentemilla, L; Barnes, G R; Düzel, E; Levine, B

    2014-01-15

    Remembering autobiographical events can be associated with detailed visual imagery. The medial temporal lobe (MTL), precuneus and prefrontal cortex are held to jointly enable such vivid retrieval, but how these regions are orchestrated remains unclear. An influential prediction from animal physiology is that neural oscillations in theta frequency may be important. In this experiment, participants prospectively collected audio recordings describing personal autobiographical episodes or semantic knowledge over 2 to 7 months. These were replayed as memory retrieval cues while recording brain activity with magnetoencephalography (MEG). We identified a peak of theta power within a left MTL region of interest during both autobiographical and General Semantic retrieval. This MTL region was selectively phase-synchronized with theta oscillations in precuneus and medial prefrontal cortex, and this synchrony was higher during autobiographical as compared to General Semantic knowledge retrieval. Higher synchrony also predicted more detailed visual imagery during retrieval. Thus, theta phase-synchrony orchestrates in humans the MTL with a distributed neocortical memory network when vividly remembering autobiographical experiences. © 2013.

  8. Endoscopic medial maxillectomy breaking new frontiers.

    Science.gov (United States)

    Mohanty, Sanjeev; Gopinath, M

    2013-07-01

    Endoscopy has changed the perspective of rhinologist towards the nose. It has revolutionised the surgical management of sinonasal disorders. Sinus surgeries were the first to get the benefit of endoscope. Gradually the domain of endoscopic surgery extended to the management of sino nasal tumours. Traditionally medial maxillectomy was performed through lateral rhinotomy or mid facial degloving approach. Endoscopic medial maxillectomy has been advocated by a number of authors in the management of benign sino-nasal tumours. We present our experience of endoscopic medial maxillectomy in the management of sinonasal pathologies.

  9. Complex Medial Meniscus Tears Are Associated With a Biconcave Medial Tibial Plateau.

    Science.gov (United States)

    Barber, F Alan; Getelman, Mark H; Berry, Kathy L

    2017-04-01

    To determine whether an association exists between a biconcave medial tibial plateau and complex medial meniscus tears. A consecutive series of stable knees undergoing arthroscopy were evaluated retrospectively with the use of preoperative magnetic resonance imaging (MRI), radiographs, and arthroscopy documented by intraoperative videos. Investigators independently performed blinded reviews of the MRI or videos. Based on the arthroscopy findings, medial tibial plateaus were classified as either biconcave or not biconcave. A transverse coronal plane ridge, separating the front of the tibial plateau from the back near the inner margin of the posterior body of the medial meniscus, was defined as biconcave. The medial plateau slope was calculated with MRI sagittal views. General demographic information, body mass index, and arthroscopically confirmed knee pathology were recorded. A total of 179 consecutive knees were studied from July 2014 through August 2015; 49 (27.2%) biconcave medial tibial plateaus and 130 (72.8%) controls were identified at arthroscopy. Complex medial meniscus tears were found in 103. Patients with a biconcave medial tibial plateau were found to have more complex medial meniscus tears (69.4%) than those without a biconcavity (53.1%) (P = .049) despite having lower body mass index (P = .020). No difference in medial tibial plateau slope was observed for biconcavities involving both cartilage and bone, bone only, or an indeterminate group (P = .47). Biconcave medial tibial plateaus were present in 27.4% of a consecutive series of patients undergoing knee arthroscopy. A biconcave medial tibial plateau was more frequently associated with a complex medial meniscus tear. Level III, case-control study. Copyright © 2016 Arthroscopy Association of North America. All rights reserved.

  10. Crude extracts of Drimys winteri bark to inhibit growth of Gaeumannomyces graminis var. tritici Inhibición del crecimiento de Gaeumannomyces graminis var. tritici empleando extractos obtenidos de corteza de Drimys winteri

    Directory of Open Access Journals (Sweden)

    Nelson Zapata

    2011-03-01

    Full Text Available The aim of this study was to assess the effect of Drimys winteri J.R. Forst. & G. Forst. bark and its extracts, obtained sequentially with n-hexane, acetone, and methanol, against Gaeumannomyces graminis var. tritici (Ggt. Ground bark of D. winteri was mixed with potato dextrose agar growth media at concentrations of 250, 500, 1000, 2000, and 4000 mg L-1 in Petri plates. Each extract was mixed at concentrations of 100, 200, 400, and 800 mg L-1. Petri plates were inoculated in the center with a 5-mm mycelium disk and were incubated at 24 ± 1 ºC. Daily measurements of mycelium radial growth were taken to determine growth rate and growth inhibition (%. A ground bark concentration of 978 mg L-1 was needed to inhibit Ggt growth by 50%, while extracts obtained with n-hexane and acetone only required 198 and 234 mg L-1, respectively. The methanol extract only inhibited Ggt growth by 33% when tested at the highest concentration. In conclusion, ground bark and crude extracts, obtained sequentially with n-hexane, acetone, and methanol, from D. winteri bark inhibit Ggt growth when applied in vitro. The n-hexane extract showed the highest inhibitory growth activity.El objetivo de esta investigación fue evaluar la actividad de la corteza de Drimys winteri J.R Forst. & G. Forst. y sus extractos obtenidos secuencialmente con n-hexano, acetona y metanol sobre el crecimiento in vitro de Gaeumannomyces graminis var. tritici (Ggt. Con este propósito se mezclaron en placas Petri, corteza molida de D. winteri con medio de crecimiento agar papa dextrosa a concentraciones de 250, 500, 1000, 2000 y 4000 mg L-1. Cada extracto fue mezclado a concentraciones de 100, 200, 400 y 800 mg L-1. Las placas se inocularon en su centro con un disco de 5 mm de micelio de Ggt y se incubaron a 24 ± 1 ºC. Diariamente se midió el crecimiento radial del micelio, se determinó velocidad de crecimiento e índice de inhibición del crecimiento (%. Para inhibir el crecimiento de Ggt

  11. [Tibial periostitis ("medial tibial stress syndrome")].

    Science.gov (United States)

    Fournier, Pierre-Etienne

    2003-06-01

    Medial tibial stress syndrome is characterised by complaints along the posteromedial tibia. Runners and athletes involved in jumping activities may develop this syndrome. Increased stress to stabilize the foot especially when excessive pronation is present explain the occurrence this lesion.

  12. Changes in prefrontal-limbic function in major depression after 15 months of long-term psychotherapy.

    Directory of Open Access Journals (Sweden)

    Anna Buchheim

    Full Text Available Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV unmedicated outpatients (N = 16 and control participants matched for sex, age, and education (N = 17 before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.

  13. Changes in Prefrontal-Limbic Function in Major Depression after 15 Months of Long-Term Psychotherapy

    Science.gov (United States)

    Buchheim, Anna; Viviani, Roberto; Kessler, Henrik; Kächele, Horst; Cierpka, Manfred; Roth, Gerhard; George, Carol; Kernberg, Otto F.; Bruns, Georg; Taubner, Svenja

    2012-01-01

    Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy. PMID:22470470

  14. Endoscopic Medial Maxillectomy Breaking New Frontiers

    OpenAIRE

    Mohanty, Sanjeev; Gopinath, M.

    2011-01-01

    Endoscopy has changed the perspective of rhinologist towards the nose. It has revolutionised the surgical management of sinonasal disorders. Sinus surgeries were the first to get the benefit of endoscope. Gradually the domain of endoscopic surgery extended to the management of sino nasal tumours. Traditionally medial maxillectomy was performed through lateral rhinotomy or mid facial degloving approach. Endoscopic medial maxillectomy has been advocated by a number of authors in the management ...

  15. The relationship between chondromalacia patella, medial meniscal tear and medial periarticular bursitis in patients with osteoarthritis

    OpenAIRE

    Resorlu Mustafa; Doner Davut; Karatag Ozan; Toprak Canan Akgun

    2017-01-01

    Abstract Background This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia patella and medial meniscal tears. Patients and methods Radiological findings of 100 patients undergoing magnetic resonance imaging with a preliminary diagnosis of knee pain were retrospectively evaluated by two radiologists. The first radiologist assessed al...

  16. UMAPRM: Uniformly sampling the medial axis

    KAUST Repository

    Yeh, Hsin-Yi Cindy

    2014-05-01

    © 2014 IEEE. Maintaining clearance, or distance from obstacles, is a vital component of successful motion planning algorithms. Maintaining high clearance often creates safer paths for robots. Contemporary sampling-based planning algorithms That utilize The medial axis, or The set of all points equidistant To Two or more obstacles, produce higher clearance paths. However, They are biased heavily Toward certain portions of The medial axis, sometimes ignoring parts critical To planning, e.g., specific Types of narrow passages. We introduce Uniform Medial Axis Probabilistic RoadMap (UMAPRM), a novel planning variant That generates samples uniformly on The medial axis of The free portion of Cspace. We Theoretically analyze The distribution generated by UMAPRM and show its uniformity. Our results show That UMAPRM\\'s distribution of samples along The medial axis is not only uniform but also preferable To other medial axis samplers in certain planning problems. We demonstrate That UMAPRM has negligible computational overhead over other sampling Techniques and can solve problems The others could not, e.g., a bug Trap. Finally, we demonstrate UMAPRM successfully generates higher clearance paths in The examples.

  17. Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

    Directory of Open Access Journals (Sweden)

    Gregory R Rompala

    Full Text Available Pharmacological and genetic studies support a role for NMDA receptor (NMDAR hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1 deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice, in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior. Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

  18. Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

    Science.gov (United States)

    Rompala, Gregory R; Zsiros, Veronika; Zhang, Shuqin; Kolata, Stefan M; Nakazawa, Kazu

    2013-01-01

    Pharmacological and genetic studies support a role for NMDA receptor (NMDAR) hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1) deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice), in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior). Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

  19. Food seeking in spite of harmful consequences is under prefrontal cortical noradrenergic control

    Directory of Open Access Journals (Sweden)

    Patrono Enrico

    2010-02-01

    Full Text Available Abstract Background Eating disorders are multifactorial psychiatric disorders. Chronic stressful experiences and caloric restriction are the most powerful triggers of eating disorders in human and animals. Although compulsive behavior is considered to characterize pathological excessive food intake, to our knowledge, no evidence has been reported of continued food seeking/intake despite its possible harmful consequences, an index of compulsive behavior. Brain monoamine transmission is considered to have a key role in vulnerability to eating disorders, and norepinephrine in medial prefrontal cortex has been shown to be critical for food-related motivated behavior. Here, using a new paradigm of conditioned suppression, we investigated whether the ability of a foot-shock-paired conditioned stimulus to suppress chocolate-seeking behavior was reversed by previous exposure to a food restriction experience, thus modeling food seeking in spite of harmful consequences in mice. Moreover, we assessed the effects of selective norepinephrine inactivation in medial prefrontal cortex on conditioned suppression test in stressed and caloric restricted mice. Results While Control (non food deprived animals showed a profound conditioned suppression of chocolate seeking during presentation of conditioned stimulus, previously food restricted animals showed food seeking/intake despite its possible harmful consequences. Moreover, food seeking in spite of harmful consequences was prevented by selective norepinephrine inactivation, thus showing that prefrontal cortical norepinephrine is critical also for maladaptive food-related behavior. Conclusions These findings indicate that adaptive food seeking/intake can be transformed into maladaptive behaviors and point to "top-down" influence on eating disturbances and to new targets for therapy of aberrant eating behaviors.

  20. Structural Covariance of the Prefrontal-Amygdala Pathways Associated with Heart Rate Variability.

    Science.gov (United States)

    Wei, Luqing; Chen, Hong; Wu, Guo-Rong

    2018-01-01

    The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV. The results showed that covariance patterns of the amygdala encompassed large portions of cortical (e.g., prefrontal, cingulate, and insula) and subcortical (e.g., striatum, hippocampus, and midbrain) regions, lending evidence from structural covariance analysis to the notion that the amygdala was a pivotal node in neural pathways for HRV modulation. Importantly, participants with higher resting HRV showed increased covariance of amygdala to dorsal medial prefrontal cortex and anterior cingulate cortex (dmPFC/dACC) extending into adjacent medial motor regions [i.e., pre-supplementary motor area (pre-SMA)/SMA], demonstrating structural covariance of the prefrontal-amygdala pathways implicated in HRV, and also implying that resting HRV may reflect the function of neural circuits underlying cognitive regulation of emotion as well as facilitation of adaptive behaviors to emotion. Our results, thus, provide anatomical substrates for the neurovisceral integration model that resting HRV may index an integrative neural network which effectively organizes emotional, cognitive, physiological and behavioral responses in the service of goal-directed behavior and adaptability.

  1. Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

    Science.gov (United States)

    Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole; Sotty, Florence

    2017-08-01

    Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia. NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease. Copyright © 2017 the American Physiological Society.

  2. Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

    Science.gov (United States)

    Miotto, Eliane C; Savage, Cary R; Evans, Jonathan J; Wilson, Barbara A; Martin, Maria G M; Balardin, Joana B; Barros, Fabio G; Garrido, Griselda; Teixeira, Manoel J; Amaro Junior, Edson

    2013-03-01

    Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections.

    Science.gov (United States)

    Barker, Gareth R I; Banks, Paul J; Scott, Hannah; Ralph, G Scott; Mitrophanous, Kyriacos A; Wong, Liang-Fong; Bashir, Zafar I; Uney, James B; Warburton, E Clea

    2017-02-01

    Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

  4. Single-trial regression elucidates the role of prefrontal theta oscillations in response conflict

    Directory of Open Access Journals (Sweden)

    Michael X Cohen

    2011-02-01

    Full Text Available In most cognitive neuroscience experiments there are many behavioral and experimental dynamics, and many indices of brain activity, that vary from trial to trial. For example, in studies of response conflict, conflict is usually treated as a binary variable (i.e., response conflict exists or does not in any given trial, whereas some evidence and intuition suggests that conflict may vary in intensity from trial to trial. Here we demonstrate that single-trial multiple regression of time-frequency electrophysiological activity reveals neural mechanisms of cognitive control that are not apparent in cross-trial averages. We also introduce a novel extension to oscillation phase coherence and synchronization analyses, based on weighted phase modulation, that has advantages over standard coherence measures in terms of linking electrophysiological dynamics to trial-varying behavior and experimental variables. After replicating previous response conflict findings using trial-averaged data, we extend these findings using single trial analytic methods to provide novel evidence for the role of medial frontal-lateral prefrontal theta-band synchronization in conflict-induced response time dynamics, including a role for lateral prefrontal theta-band activity in biasing response times according to perceptual conflict. Given that these methods shed new light on the prefrontal mechanisms of response conflict, they are also likely to be useful for investigating other neurocognitive processes.

  5. Cadherin-8 expression, synaptic localization, and molecular control of neuronal form in prefrontal corticostriatal circuits.

    Science.gov (United States)

    Friedman, Lauren G; Riemslagh, Fréderike W; Sullivan, Josefa M; Mesias, Roxana; Williams, Frances M; Huntley, George W; Benson, Deanna L

    2015-01-01

    Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex-striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin-8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real-time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High-resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self-avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. © 2014 Wiley Periodicals, Inc.

  6. Prefrontal-amygdala fear networks come into focus

    Directory of Open Access Journals (Sweden)

    Maithe eArruda-Carvalho

    2015-10-01

    Full Text Available The ability to form associations between aversive threats and their predictors is fundamental to survival. However, fear and anxiety in excess are detrimental and are a hallmark of psychiatric diseases such as post-traumatic stress disorder (PTSD. PTSD symptomatology includes persistent and intrusive thoughts of an experienced trauma, suggesting an inability to downregulate fear when a corresponding threat has subsided. Convergent evidence from human and rodent studies supports a role for the medial prefrontal cortex (mPFC-amygdala network in both PTSD and the regulation of fear memory expression. In particular, current models stipulate that the prelimbic and infralimbic subdivisions of the rodent mPFC bidirectionally regulate fear expression via differential recruitment of amygdala neuronal subpopulations. However, an array of recent studies that employ new technical approaches has fundamentally challenged this interpretation. Here we explore how a new emphasis on the contribution of inhibitory neuronal populations, subcortical structures and the passage of time is reshaping our understanding of mPFC-amygdala circuits and their control over fear.

  7. Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

    Science.gov (United States)

    Benn, Abigail; Barker, Gareth R I; Stuart, Sarah A; Roloff, Eva V L; Teschemacher, Anja G; Warburton, E Clea; Robinson, Emma S J

    2016-05-04

    Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance. These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement. Copyright © 2016 Benn et al.

  8. Altered amygdala-prefrontal connectivity during emotion perception in schizophrenia.

    Science.gov (United States)

    Bjorkquist, Olivia A; Olsen, Emily K; Nelson, Brady D; Herbener, Ellen S

    2016-08-01

    Individuals with schizophrenia evidence impaired emotional functioning. Abnormal amygdala activity has been identified as an etiological factor underlying affective impairment in this population, but the exact nature remains unclear. The current study utilized psychophysiological interaction analyses to examine functional connectivity between the amygdala and medial prefrontal cortex (mPFC) during an emotion perception task. Participants with schizophrenia (SZ) and healthy controls (HC) viewed and rated positive, negative, and neutral images while undergoing functional neuroimaging. Results revealed a significant group difference in right amygdala-mPFC connectivity during perception of negative versus neutral images. Specifically, HC participants demonstrated positive functional coupling between the amygdala and mPFC, consistent with co-active processing of salient information. In contrast, SZ participants evidenced negative functional coupling, consistent with top-down inhibition of the amygdala by the mPFC. A significant positive correlation between connectivity strength during negative image perception and clinician-rated social functioning was also observed in SZ participants, such that weaker right amygdala-mPFC coupling during negative compared to neutral image perception was associated with poorer social functioning. Overall, results suggest that emotional dysfunction and associated deficits in functional outcome in schizophrenia may relate to abnormal interactions between the amygdala and mPFC during perception of emotional stimuli. This study adds to the growing literature on abnormal functional connections in schizophrenia and supports the functional disconnection hypothesis of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine.

    Science.gov (United States)

    Sullivan, R M

    2004-06-01

    The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.

  10. Auditory Connections and Functions of Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Bethany ePlakke

    2014-07-01

    Full Text Available The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC. In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition.

  11. Working Memory in the Prefrontal Cortex

    Science.gov (United States)

    Funahashi, Shintaro

    2017-01-01

    The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified. PMID:28448453

  12. Auditory connections and functions of prefrontal cortex

    Science.gov (United States)

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

    The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

  13. Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

    Science.gov (United States)

    Nair, Sunila G; Gudelsky, Gary A

    2004-09-15

    The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

  14. The prefrontal cortex in the Göttingen minipig brain defined by neural projection criteria and cytoarchitecture

    DEFF Research Database (Denmark)

    Jelsing, J; Hay-Schmidt, Anders; Dyrby, Tim

    2006-01-01

    In an attempt to delineate the prefrontal cortex (PFC) in the Gottingen minipig brain the distribution of reciprocal thalamocortical projections was investigated using anterograde and retrograde tracing techniques and evaluated in relation to the specific cytoarchitectonic organization. Tracers...... the medial and rostral pole of the frontal lobe as well as the anterior cingulate, anterior insular and dorsomedial frontal cortices. Subsequently, the reciprocity and specificity of these connections were tested from injections into the traced frontal cortices indicating that the PFC has cortical...... connections to different parts of the MD nucleus. Although the granular layer IV, characteristic of primate PFC could not be identified, both cytoarchitectonic and connectional data suggests that the Gottingen minipig has a structurally divided prefrontal cortex. Stereological estimates of PFC volume showed...

  15. I find you more attractive … after (prefrontal cortex) stimulation

    NARCIS (Netherlands)

    Ferrari, C.; Lega, C.; Tamietto, M.; Nadal, M.; Cattaneo, Z.

    2015-01-01

    Facial attractiveness seems to be perceived immediately. Neuroimaging evidence suggests that the appraisal of facial attractiveness is mediated by a network of cortical and subcortical regions, mainly encompassing the reward circuit, but also including prefrontal cortices. The prefrontal cortex is

  16. The Relationship between Chondromalacia Patella, Medial Meniscal Tear and Medial Periarticular Bursitis in Patients with Osteoarthritis.

    Science.gov (United States)

    Resorlu, Mustafa; Doner, Davut; Karatag, Ozan; Toprak, Canan Akgun

    2017-12-01

    This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia patella and medial meniscal tears. Radiological findings of 100 patients undergoing magnetic resonance imaging with a preliminary diagnosis of knee pain were retrospectively evaluated by two radiologists. The first radiologist assessed all patients in terms of osteoarthritis, chondromalacia patella and medial meniscal tear. The second radiologist was blinded to these results and assessed the presence of bursitis in all patients. Mild osteoarthritis (grade I and II) was determined in 55 patients and severe osteoarthritis (grade III and IV) in 45 cases. At retropatellar cartilage evaluation, 25 patients were assessed as normal, while 29 patients were diagnosed with mild chondromalacia patella (grade I and II) and 46 with severe chondromalacia patella (grade III and IV). Medial meniscus tear was determined in 51 patients. Severe osteoarthritis and chondromalacia patella were positively correlated with meniscal tear (p chondromalacia patella (p = 0.023 and p = 0.479, respectively). Evaluation of lateral compartment bursae revealed lateral collateral ligament bursitis in 2 patients and iliotibial bursitis in 5 patients. We observed a greater prevalence of bursitis in the medial compartment of the knee in patients with severe osteoarthritis and medial meniscus tear.

  17. The Relationship between Chondromalacia Patella, Medial Meniscal Tear and Medial Periarticular Bursitis in Patients with Osteoarthritis

    Science.gov (United States)

    Doner, Davut; Karatag, Ozan; Toprak, Canan Akgun

    2017-01-01

    Abstract Background This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia patella and medial meniscal tears. Patients and methods Radiological findings of 100 patients undergoing magnetic resonance imaging with a preliminary diagnosis of knee pain were retrospectively evaluated by two radiologists. The first radiologist assessed all patients in terms of osteoarthritis, chondromalacia patella and medial meniscal tear. The second radiologist was blinded to these results and assessed the presence of bursitis in all patients. Results Mild osteoarthritis (grade I and II) was determined in 55 patients and severe osteoarthritis (grade III and IV) in 45 cases. At retropatellar cartilage evaluation, 25 patients were assessed as normal, while 29 patients were diagnosed with mild chondromalacia patella (grade I and II) and 46 with severe chondromalacia patella (grade III and IV). Medial meniscus tear was determined in 51 patients. Severe osteoarthritis and chondromalacia patella were positively correlated with meniscal tear (p chondromalacia patella (p = 0.023 and p = 0.479, respectively). Evaluation of lateral compartment bursae revealed lateral collateral ligament bursitis in 2 patients and iliotibial bursitis in 5 patients. Conclusions We observed a greater prevalence of bursitis in the medial compartment of the knee in patients with severe osteoarthritis and medial meniscus tear. PMID:29333118

  18. Connections of the medial posterior parietal cortex (area 7m) in the monkey.

    Science.gov (United States)

    Leichnetz, G R

    2001-06-01

    The afferent and efferent cortical and subcortical connections of the medial posterior parietal cortex (area 7m) were studied in cebus (Cebus apella) and macaque (Macaca fascicularis) monkeys using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique. The principal intraparietal corticocortical connections of area 7m in both cebus and macaque cases were with the ipsilateral medial bank of the intraparietal sulcus (MIP) and adjacent superior parietal lobule (area 5), inferior parietal lobule (area 7a), lateral bank of the IPS (area 7ip), caudal parietal operculum (PGop), dorsal bank of the caudal superior temporal sulcus (visual area MST), and medial prestriate cortex (including visual area PO and caudal medial lobule). Its principal frontal corticocortical connections were with the prefrontal cortex in the shoulder above the principal sulcus and the cortex in the shoulder above the superior ramus of the arcuate sulcus (SAS), the area purported to contain the smooth eye movement-related frontal eye field (FEFsem) in the cebus monkey by other investigators. There were moderate connections with the cortex in the rostral bank of the arcuate sulcus (purported to contain the saccade-related frontal eye field; FEFsac), supplementary eye field (SEF), and rostral dorsal premotor area (PMDr). Area 7m also had major connections with the cingulate cortex (area 23), particularly the ventral bank of the cingulate sulcus. The principal subcortical connections of area 7m were with the dorsal portion of the ventrolateral thalamic (VLc) nucleus, lateral posterior thalamic nucleus, lateral pulvinar, caudal mediodorsal thalamic nucleus and medial pulvinar, central lateral, central superior lateral, and central inferior intralaminar thalamic nuclei, dorsolateral caudate nucleus and putamen, middle region of the claustrum, nucleus of the diagonal band, zona incerta, pregeniculate nucleus, anterior and posterior pretectal nuclei, intermediate layer of

  19. Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram

    Directory of Open Access Journals (Sweden)

    Shreaya Chakroborty

    2017-10-01

    Full Text Available Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC, however, the impact of this compound on related prefrontal-subcortical circuits is less clear. Thus, the current study examined the impact of systemic vortioxetine administration (0.8 mg/kg, i.v. on spontaneous spiking and spikes evoked by electrical stimulation of the mPFC in the anterior cingulate cortex (ACC, medial shell of the nucleus accumbens (msNAc, and lateral septal nucleus (LSN in urethane-anesthetized rats. We also examined whether vortioxetine modulated afferent drive in the msNAc from hippocampal fimbria (HF inputs. Similar studies were performed using the selective 5-HT reuptake inhibitor [selective serotonin reuptake inhibitors (SSRI] escitalopram (1.6 mg/kg, i.v. to enable comparisons between the multimodal actions of vortioxetine and SSRI-mediated effects. No significant differences in spontaneous activity were observed in the ACC, msNAc, and LSN across treatment groups. No significant impact of treatment on mPFC-evoked responses was observed in the ACC. In contrast, vortioxetine decreased mPFC-evoked activity recorded in the msNAc as compared to parallel studies in control and escitalopram treated groups. Thus, vortioxetine may reduce mPFC-msNAc afferent drive via a mechanism that, in addition to an SSRI-like effect, requires 5-HT receptor modulation. Recordings in the LSN revealed a significant increase in mPFC-evoked activity following escitalopram administration as compared to control and vortioxetine treated groups

  20. Medial structure generation for registration of anatomical structures

    DEFF Research Database (Denmark)

    Vera, Sergio; Gil, Debora; Kjer, Hans Martin

    2017-01-01

    structures. Methods for generation of medial structures, however, are prone to the generation of medial artifacts (spurious branches) that traditionally need to be pruned before the medial structure can be used for further computations. The act of pruning can affect main sections of the medial surface......Medial structures (skeletons and medial manifolds) have shown capacity to describe shape in a compact way. In the field of medical imaging, they have been employed to enrich the description of organ anatomy, to improve segmentation, or to describe the organ position in relation to surrounding...

  1. Modeling Conflict and Error in the Medial Frontal Cortex

    Science.gov (United States)

    Mayer, Andrew R.; Teshiba, Terri M.; Franco, Alexandre R.; Ling, Josef; Shane, Matthew S.; Stephen, Julia M.; Jung, Rex E.

    2014-01-01

    Despite intensive study, the role of the dorsal medial frontal cortex (dMFC) in error monitoring and conflict processing remains actively debated. The current experiment manipulated conflict type (stimulus conflict only or stimulus and response selection conflict) and utilized a novel modeling approach to isolate error and conflict variance during a multimodal numeric Stroop task. Specifically, hemodynamic response functions resulting from two statistical models that either included or isolated variance arising from relatively few error trials were directly contrasted. Twenty-four participants completed the task while undergoing event-related functional magnetic resonance imaging on a 1.5-Tesla scanner. Response times monotonically increased based on the presence of pure stimulus or stimulus and response selection conflict. Functional results indicated that dMFC activity was present during trials requiring response selection and inhibition of competing motor responses, but absent during trials involving pure stimulus conflict. A comparison of the different statistical models suggested that relatively few error trials contributed to a disproportionate amount of variance (i.e., activity) throughout the dMFC, but particularly within the rostral anterior cingulate gyrus (rACC). Finally, functional connectivity analyses indicated that an empirically derived seed in the dorsal ACC/pre-SMA exhibited strong connectivity (i.e., positive correlation) with prefrontal and inferior parietal cortex but was anticorrelated with the default-mode network. An empirically derived seed from the rACC exhibited the opposite pattern, suggesting that sub-regions of the dMFC exhibit different connectivity patterns with other large scale networks implicated in internal mentations such as daydreaming (default-mode) versus the execution of top-down attentional control (fronto-parietal). PMID:21976411

  2. Modeling conflict and error in the medial frontal cortex.

    Science.gov (United States)

    Mayer, Andrew R; Teshiba, Terri M; Franco, Alexandre R; Ling, Josef; Shane, Matthew S; Stephen, Julia M; Jung, Rex E

    2012-12-01

    Despite intensive study, the role of the dorsal medial frontal cortex (dMFC) in error monitoring and conflict processing remains actively debated. The current experiment manipulated conflict type (stimulus conflict only or stimulus and response selection conflict) and utilized a novel modeling approach to isolate error and conflict variance during a multimodal numeric Stroop task. Specifically, hemodynamic response functions resulting from two statistical models that either included or isolated variance arising from relatively few error trials were directly contrasted. Twenty-four participants completed the task while undergoing event-related functional magnetic resonance imaging on a 1.5-Tesla scanner. Response times monotonically increased based on the presence of pure stimulus or stimulus and response selection conflict. Functional results indicated that dMFC activity was present during trials requiring response selection and inhibition of competing motor responses, but absent during trials involving pure stimulus conflict. A comparison of the different statistical models suggested that relatively few error trials contributed to a disproportionate amount of variance (i.e., activity) throughout the dMFC, but particularly within the rostral anterior cingulate gyrus (rACC). Finally, functional connectivity analyses indicated that an empirically derived seed in the dorsal ACC/pre-SMA exhibited strong connectivity (i.e., positive correlation) with prefrontal and inferior parietal cortex but was anti-correlated with the default-mode network. An empirically derived seed from the rACC exhibited the opposite pattern, suggesting that sub-regions of the dMFC exhibit different connectivity patterns with other large scale networks implicated in internal mentations such as daydreaming (default-mode) versus the execution of top-down attentional control (fronto-parietal). Copyright © 2011 Wiley Periodicals, Inc.

  3. Altered Communicative Decisions following Ventromedial Prefrontal Lesions

    NARCIS (Netherlands)

    Stolk, A.; D'Imperio, D.; Pellegrino, G. di; Toni, I.

    2015-01-01

    Damage to the human ventromedial prefrontal cortex (vmPFC) leads to profound changes in everyday social interactions [1, 2]. Yet, in the lab, vmPFC patients show surprising proficiency in reasoning about other agents [3-8]. These conflicting observations suggest that what vmPFC patients lack in

  4. Monetary reward activates human prefrontal cortex

    International Nuclear Information System (INIS)

    Thut, G.; Roelcke, U.; Nienhusmeier, M.; Missimer, J.; Maguire, R.P.; Leenders, K.L.; Schultz, W.

    1997-01-01

    We present a rCBF PET activation study, in which we demonstrated that reward processing in humans activates a cortical-subcortical network including dorsolateral prefrontal, orbital frontal, thalamic and midbrain regions. It is suggested that, as found for non-human primates, the basal ganglia-thalamo-cortical system is implicated in reward processing. (author) 1 fig., 3 refs

  5. Neural modeling of prefrontal executive function

    Energy Technology Data Exchange (ETDEWEB)

    Levine, D.S. [Univ. of Texas, Arlington, TX (United States)

    1996-12-31

    Brain executive function is based in a distributed system whereby prefrontal cortex is interconnected with other cortical. and subcortical loci. Executive function is divided roughly into three interacting parts: affective guidance of responses; linkage among working memory representations; and forming complex behavioral schemata. Neural network models of each of these parts are reviewed and fit into a preliminary theoretical framework.

  6. Medial branch neurotomy in low back pain

    Energy Technology Data Exchange (ETDEWEB)

    Masala, Salvatore; Mammucari, Matteo; Simonetti, Giovanni [Interventional Radiology and Radiotherapy University ' ' Tor Vergata' ' , Department of Diagnostic and Molecular Imaging, Rome (Italy); Nano, Giovanni [Interventional Radiology and Radiotherapy University ' ' Tor Vergata' ' , Department of Diagnostic and Molecular Imaging, Rome (Italy); University ' ' Tor Vergata' ' , Department of Radiology, Rome (Italy); Marcia, Stefano [S. Giovanni di Dio Hospital, Department of Diagnostic and Molecular Imaging, Cagliari (Italy)

    2012-07-15

    This study aimed to assess the effectiveness of pulsed radiofrequency medial branch dorsal ramus neurotomy in patients with facet joint syndrome. From January 2008 to April 2010, 92 patients with facet joint syndrome diagnosed by strict inclusion criteria and controlled diagnostic blocks undergone medial branch neurotomy. We did not exclude patients with failed back surgery syndrome (FBSS). Electrodes (20G) with 5-mm active tip were placed under fluoroscopy guide parallel to medial branch. Patients were followed up by physical examination and by Visual Analog Scale and Oswestry Disability Index at 1, 6, and 12 months. In all cases, pain improvement was statistically significant and so quality of life. Three non-FBSS patients had to undergo a second neurotomy because of non-satisfactory pain decrease. Complications were reported in no case. Medial branch radiofrequency neurotomy has confirmed its well-established effectiveness in pain and quality of life improvement as long as strict inclusion criteria be fulfilled and nerve ablation be accomplished by parallel electrode positioning. This statement can be extended also to FBSS patients. (orig.)

  7. Medial branch neurotomy in low back pain

    International Nuclear Information System (INIS)

    Masala, Salvatore; Mammucari, Matteo; Simonetti, Giovanni; Nano, Giovanni; Marcia, Stefano

    2012-01-01

    This study aimed to assess the effectiveness of pulsed radiofrequency medial branch dorsal ramus neurotomy in patients with facet joint syndrome. From January 2008 to April 2010, 92 patients with facet joint syndrome diagnosed by strict inclusion criteria and controlled diagnostic blocks undergone medial branch neurotomy. We did not exclude patients with failed back surgery syndrome (FBSS). Electrodes (20G) with 5-mm active tip were placed under fluoroscopy guide parallel to medial branch. Patients were followed up by physical examination and by Visual Analog Scale and Oswestry Disability Index at 1, 6, and 12 months. In all cases, pain improvement was statistically significant and so quality of life. Three non-FBSS patients had to undergo a second neurotomy because of non-satisfactory pain decrease. Complications were reported in no case. Medial branch radiofrequency neurotomy has confirmed its well-established effectiveness in pain and quality of life improvement as long as strict inclusion criteria be fulfilled and nerve ablation be accomplished by parallel electrode positioning. This statement can be extended also to FBSS patients. (orig.)

  8. Medial tibial stress syndrome: a critical review

    NARCIS (Netherlands)

    Moen, Maarten H.; Tol, Johannes L.; Weir, Adam; Steunebrink, Miriam; de Winter, Theodorus C.

    2009-01-01

    Medial tibial stress syndrome (MTSS) is one of the most common leg injuries in athletes and soldiers. The incidence of MTSS is reported as being between 4% and 35% in military personnel and athletes. The name given to this condition refers to pain on the posteromedial tibial border during exercise,

  9. Acute compartment syndrome after medial gastrocnemius tear.

    Science.gov (United States)

    Sit, Yan Kit; Lui, Tun Hing

    2015-02-01

    Acute compartment syndrome after medial gastrocnemius tear is very rare. It can involve the superficial posterior compartment alone or progress to involve all the 4 compartments of the lower legs. Those patients with high pain tolerance and minor trauma can lead to delayed presentation. Immediate fasciotomy is the treatment of choice. Therapeutic Level IV, Case Study. © 2014 The Author(s).

  10. Rheo: Japanese Sound Art Interrogating Digital Mediality

    DEFF Research Database (Denmark)

    Vandsø, Anette

    2014-01-01

    THe article asks in what way the Japanese sound artist Ryoichi Kurokawa's audiovisual installation Rheo 5 Horisonz (2010) is 'digital'. Using Professor Lars Elleströms concept of 'mediality, the main claim in this article is that Rheo no only uses digital tehcnology, but also interrogates digital...

  11. Medial frontal cortex and response conflict: Evidence from human intracranial EEG and medial frontal cortex lesion

    NARCIS (Netherlands)

    Cohen, M.X.; Ridderinkhof, K.R.; Haupt, S.; Elger, C.E.; Fell, J.

    2008-01-01

    The medial frontal cortex (MFC) has been implicated in the monitoring and selection of actions in the face of competing alternatives, but much remains unknown about its functional properties, including electrophysiological oscillations, during response conflict tasks. Here, we recorded intracranial

  12. The Medial Dorsal Thalamic Nucleus and the Medial Prefrontal Cortex of the Rat Function Together to Support Associative Recognition and Recency but Not Item Recognition

    Science.gov (United States)

    Cross, Laura; Brown, Malcolm W.; Aggleton, John P.; Warburton, E. Clea

    2013-01-01

    In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In…

  13. Stimulation of the medial amygdala enhances medial preoptic dopamine release: implications for male rat sexual behavior.

    Science.gov (United States)

    Dominguez, J M; Hull, E M

    2001-11-02

    Increased dopamine (DA) in the medial preoptic area (MPOA) facilitates male sexual behavior. A major source of innervation to the MPOA is the medial amygdala (MeA). We now report that chemical stimulation of the MeA enhanced levels of extracellular MPOA DA in anesthetized male rats. These results suggest that DA activity in the MPOA can be regulated by input from the MeA to the MPOA.

  14. Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Wu, Wan-Chen; Cummings, Kirstie A; Clem, Roger L

    2017-03-15

    A brain network comprising the medial prefrontal cortex (mPFC) and amygdala plays important roles in developmentally regulated cognitive and emotional processes. However, very little is known about the maturation of mPFC-amygdala circuitry. We conducted anatomical tracing of mPFC projections and optogenetic interrogation of their synaptic connections with neurons in the basolateral amygdala (BLA) at neonatal to adult developmental stages in mice. Results indicate that mPFC-BLA projections exhibit delayed emergence relative to other mPFC pathways and establish synaptic transmission with BLA excitatory and inhibitory neurons in late infancy, events that coincide with a massive increase in overall synaptic drive. During subsequent adolescence, mPFC-BLA circuits are further modified by excitatory synaptic strengthening as well as a transient surge in feedforward inhibition. The latter was correlated with increased spontaneous inhibitory currents in excitatory neurons, suggesting that mPFC-BLA circuit maturation culminates in a period of exuberant GABAergic transmission. These findings establish a time course for the onset and refinement of mPFC-BLA transmission and point to potential sensitive periods in the development of this critical network. SIGNIFICANCE STATEMENT Human mPFC-amygdala functional connectivity is developmentally regulated and figures prominently in numerous psychiatric disorders with a high incidence of adolescent onset. However, it remains unclear when synaptic connections between these structures emerge or how their properties change with age. Our work establishes developmental windows and cellular substrates for synapse maturation in this pathway involving both excitatory and inhibitory circuits. The engagement of these substrates by early life experience may support the ontogeny of fundamental behaviors but could also lead to inappropriate circuit refinement and psychopathology in adverse situations. Copyright © 2017 the authors 0270-6474/17/372976-10$15.00/0.

  15. Prefrontal Neuronal Excitability Maintains Cocaine-Associated Memory During Retrieval

    Directory of Open Access Journals (Sweden)

    James M. Otis

    2018-06-01

    Full Text Available Presentation of drug-associated cues provokes craving and drug seeking, and elimination of these associative memories would facilitate recovery from addiction. Emotionally salient memories are maintained during retrieval, as particular pharmacologic or optogenetic perturbations of memory circuits during retrieval, but not after, can induce long-lasting memory impairments. For example, in rats, inhibition of noradrenergic beta-receptors, which control intrinsic neuronal excitability, in the prelimbic medial prefrontal cortex (PL-mPFC can cause long-term memory impairments that prevent subsequent cocaine-induced reinstatement. The physiologic mechanisms that allow noradrenergic signaling to maintain drug-associated memories during retrieval, however, are unclear. Here we combine patch-clamp electrophysiology ex vivo and behavioral neuropharmacology in vivo to evaluate the mechanisms that maintain drug-associated memory during retrieval in rats. Consistent with previous studies, we find that cocaine experience increases the intrinsic excitability of pyramidal neurons in PL-mPFC. In addition, we now find that this intrinsic plasticity positively predicts the retrieval of a cocaine-induced conditioned place preference (CPP memory, suggesting that such plasticity may contribute to drug-associated memory retrieval. In further support of this, we find that pharmacological blockade of a cAMP-dependent signaling cascade, which allows noradrenergic signaling to elevate neuronal excitability, is required for memory maintenance during retrieval. Thus, inhibition of PL-mPFC neuronal excitability during memory retrieval not only leads to long-term deficits in the memory, but this memory deficit provides protection against subsequent cocaine-induced reinstatement. These data reveal that PL-mPFC intrinsic neuronal excitability maintains a cocaine-associated memory during retrieval and suggest a unique mechanism whereby drug-associated memories could be targeted

  16. Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear

    DEFF Research Database (Denmark)

    Marek, Roger; Jin, Jingji; Goode, Travis D.

    2018-01-01

    The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished...... fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons...... in the IL eliminated vHPC-mediated inhibition. In behaving rats, pharmacogenetic activation of vHPC→IL projections impaired extinction recall, whereas silencing IL projectors diminished fear renewal. Intra-IL infusion of GABA receptor agonists or antagonists, respectively, reproduced these effects. Together...

  17. Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons

    Science.gov (United States)

    Nakajima, Miho; Görlich, Andreas; Heintz, Nathaniel

    2014-01-01

    SUMMARY Human imaging studies have revealed that intranasal administration of the “prosocial” hormone oxytocin (OT) activates the frontal cortex, and that this action of OT correlates with enhanced brain function in autism. Here we report the discovery of a population of somatostatin (Sst) positive, regular spiking interneurons that express the oxytocin receptor (OxtrINs). Silencing of OxtrINs in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice specifically during the sexually receptive phase of the estrous cycle. This sociosexual deficit was also present in mice in which the Oxtr gene was conditionally deleted from the mPFC, and in control mice infused with an Oxtr antagonist. Our data demonstrate a gender, cell type and state specific role for OT/Oxtr signaling in the mPFC, and identify a latent cortical circuit element that may modulate other complex social behaviors in response to OT. PMID:25303526

  18. Extinction of fear is facilitated by social presence: Synergism with prefrontal oxytocin.

    Science.gov (United States)

    Brill-Maoz, Naama; Maroun, Mouna

    2016-04-01

    This study addressed the question of whether extinction in pairs would have a beneficial effect on extinction of fear conditioning. To that end, we established an experimental setting for extinction in which we trained animals to extinguish contextual fear memory in pairs. Taking advantage of the role of oxytocin (OT) in the medial prefrontal cortex (mPFC) in the mediation of memory extinction and social interaction, we also sought to study its role in social interaction-induced effects on extinction. Our results clearly show that the social presence of another animal in the extinction context facilitates extinction, and that this facilitation is mediated through mPFC-OT. Our results suggest that social interaction may be a positive regulator of fear inhibition, implying that social interaction may be an easy, accessible therapeutic tool for the treatment of fear-associated disorders. Copyright © 2016. Published by Elsevier Ltd.

  19. Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type: deafferentation and functional compensation?

    International Nuclear Information System (INIS)

    Guedj, Eric; Barbeau, Emmanuel J.; Didic, Mira; Poncet, Michel; Ceccaldi, Mathieu; Felician, Olivier; Laforte, Catherine de; Mundler, Olivier; Ranjeva, Jean-Philippe; Cozzone, Patrick J.

    2009-01-01

    Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer's disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage. We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD. Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL. These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the ''net sum'' of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective. (orig.)

  20. Effects of medial temporal lobe degeneration on brain perfusion in amnestic MCI of AD type: deafferentation and functional compensation?

    Energy Technology Data Exchange (ETDEWEB)

    Guedj, Eric [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Marseille Cedex 5 (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR CNRS 6612, Faculte de Medecine, Marseille (France); Barbeau, Emmanuel J. [CNRS - Universite Paul Sabatier Toulouse 3, Centre de Recherche Cerveau et Cognition, UMR-5549, Toulouse (France); Didic, Mira; Poncet, Michel; Ceccaldi, Mathieu [CHU Timone, Service de Neurologie et de Neuropsychologie, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Felician, Olivier [CHU Timone, Service de Neurologie et de Neuropsychologie, Marseille (France); Universite de la Mediterranee Aix-Marseille II, Laboratoire de Neurophysiologie et Neuropsychologie, Inserm U751, Faculte de Medecine, Marseille (France); Centre Saint-Charles, Laboratoire de Neurobiologie Integrative et Adaptative, UMR CNRS 6149, Marseille (France); Laforte, Catherine de; Mundler, Olivier [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Marseille Cedex 5 (France); Ranjeva, Jean-Philippe; Cozzone, Patrick J. [Universite de la Mediterranee Aix-Marseille II, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), UMR CNRS 6612, Faculte de Medecine, Marseille (France)

    2009-07-15

    Cortical atrophy is correlated with the progression of neuropathological lesions within the medial temporal lobes (MTL) in Alzheimer's disease (AD). Our aim was to determine which local and remote functional changes result from MTL volume loss at the predementia stage. We studied the relationship between entorhinal and hippocampal MR volumes and whole-brain SPECT perfusion via a voxel-based correlative analysis in 19 patients with amnestic mild cognitive impairment with a memory profile suggestive of early AD. Right MTL volumes were positively correlated with remote posterior perfusion of the posterior cingulate cortex, and negatively correlated with remote anterior perfusion of the right medial and dorsolateral prefrontal cortex. There was no local correlation between volumes and perfusion within the MTL. These findings provide further insight into functional changes that result from MTL volume loss during the predementia stage of AD. The positive correlation between MTL volumes and posterior cingulate perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration. The paradoxical negative correlation between MTL volumes and prefrontal perfusion may result from recruitment of an alternative anterior temporofrontal network. It remains to be investigated how the ''net sum'' of this perfusion modulation affects memory and other cognitive domains through a possible compensatory perspective. (orig.)

  1. Natural history of medial clavicle fractures.

    Science.gov (United States)

    Salipas, Andrew; Kimmel, Lara A; Edwards, Elton R; Rakhra, Sandeep; Moaveni, Afshin Kamali

    2016-10-01

    Fractures of the medial third of the clavicle comprise less than 3% of all clavicle fractures. The natural history and optimal management of these rare injuries are unknown. The aim of our study is to describe the demographics, management and outcomes of patients with medial clavicle fractures treated at a Level 1 Trauma Centre. A retrospective review was conducted of patients presenting to our institution between January 2008 and March 2013 with a medial third clavicle fracture. Clinical and radiographic data were recorded including mechanism of injury, fracture pattern and displacement, associated injuries, management and complications. Functional outcomes were assessed using the Glasgow Outcome Scale Extended (GOS-E) scores from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). Shoulder outcomes were assessed using two patient reported outcomes scores, the American Shoulder and Elbow Society Score (ASES) and the Subjective Shoulder Value (SSV). Sixty eight medial clavicle fractures in 68 patients were evaluated. The majority of patients were male (n=53), with a median age of 53.5 years (interquartile range (IQR) 37.5-74.5 years). The most common mechanism of injury was motor vehicle accident (n=28). The in-hospital mortality rate was 4.4%. The fracture pattern was almost equally distributed between extra articular (n=35) and intra-articular (n=33). Fifty-five fractures (80.9%) had minimal or no displacement. Associated injuries were predominantly thoracic (n=31). All fractures were initially managed non-operatively, with a broad arm sling. Delayed operative fixation was performed for painful atrophic delayed union in two patients (2.9%). Both patients were under 65 years of age and had a severely displaced fracture of the medial clavicle. One intra-operative vascular complication was seen, with no adverse long-term outcome. Follow-up was obtained in 85.0% of the surviving cohort at an average of three years post injury (range 1-6 years). The mean ASES

  2. The role of rostral prefrontal cortex in prospective memory: a voxel-based lesion study.

    Science.gov (United States)

    Volle, Emmanuelle; Gonen-Yaacovi, Gil; Costello, Angela de Lacy; Gilbert, Sam J; Burgess, Paul W

    2011-07-01

    Patients with lesions in rostral prefrontal cortex (PFC) often experience problems in everyday-life situations requiring multitasking. A key cognitive component that is critical in multitasking situations is prospective memory, defined as the ability to carry out an intended action after a delay period filled with unrelated activity. The few functional imaging studies investigating prospective memory have shown consistent activation in both medial and lateral rostral PFC but also in more posterior prefrontal regions and non-frontal regions. The aim of this study was to determine regions that are necessary for prospective memory performance, using the human lesion approach. We designed an experimental paradigm allowing us to assess time-based (remembering to do something at a particular time) and event-based (remembering to do something in a particular situation) prospective memory, using two types of material, words and pictures. Time estimation tasks and tasks controlling for basic attention, inhibition and multiple instructions processing were also administered. We examined brain-behaviour relationships with a voxelwise lesion method in 45 patients with focal brain lesions and 107 control subjects using this paradigm. The results showed that lesions in the right polar prefrontal region (in Brodmann area 10) were specifically associated with a deficit in time-based prospective memory tasks for both words and pictures. This deficit could not be explained by impairments in basic attention, detection, inhibition or multiple instruction processing, and there was also no deficit in event-based prospective memory conditions. In addition to their prospective memory difficulties, these polar prefrontal patients were significantly impaired in time estimation ability compared to other patients. The same region was found to be involved using both words and pictures, suggesting that right rostral PFC plays a material nonspecific role in prospective memory. This is the first

  3. Prefrontal contributions to visual selective attention.

    Science.gov (United States)

    Squire, Ryan F; Noudoost, Behrad; Schafer, Robert J; Moore, Tirin

    2013-07-08

    The faculty of attention endows us with the capacity to process important sensory information selectively while disregarding information that is potentially distracting. Much of our understanding of the neural circuitry underlying this fundamental cognitive function comes from neurophysiological studies within the visual modality. Past evidence suggests that a principal function of the prefrontal cortex (PFC) is selective attention and that this function involves the modulation of sensory signals within posterior cortices. In this review, we discuss recent progress in identifying the specific prefrontal circuits controlling visual attention and its neural correlates within the primate visual system. In addition, we examine the persisting challenge of precisely defining how behavior should be affected when attentional function is lost.

  4. Prefrontal system dysfunction and credit card debt.

    Science.gov (United States)

    Spinella, Marcello; Yang, Bijou; Lester, David

    2004-10-01

    Credit card use often involves a disadvantageous allocation of finances because they allow for spending beyond means and buying on impulse. Accordingly they are associated with increased bankruptcy, anxiety, stress, and health problems. Mounting evidence from functional neuroimaging and clinical studies implicates prefrontal-subcortical systems in processing financial information. This study examined the relationship of credit card debt and executive functions using the Frontal System Behavior Scale (FRSBE). After removing the influences of demographic variables (age, sex, education, and income), credit card debt was associated with the Executive Dysfunction scale, but not the Apathy or Disinhibition scales. This suggests that processes of conceptualizing and organizing finances are most relevant to credit card debt, and implicates dorsolateral prefrontal dysfunction.

  5. An integrative theory of prefrontal cortex function.

    Science.gov (United States)

    Miller, E K; Cohen, J D

    2001-01-01

    The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

  6. The role of prefrontal cortex in psychopathy

    Science.gov (United States)

    Koenigs, Michael

    2014-01-01

    Psychopathy is a personality disorder characterized by remorseless and impulsive antisocial behavior. Given the significant societal costs of the recidivistic criminal activity associated with the disorder, there is a pressing need for more effective treatment strategies, and hence, a better understanding of the psychobiological mechanisms underlying the disorder. The prefrontal cortex (PFC) is likely to play an important role in psychopathy. In particular, the ventromedial and anterior cingulate sectors of PFC are theorized to mediate a number of social and affective decision-making functions that appear to be disrupted in psychopathy. This article provides a critical summary of human neuroimaging data implicating prefrontal dysfunction in psychopathy. A growing body of evidence associates psychopathy with structural and functional abnormalities in ventromedial PFC and anterior cingulate cortex. Although this burgeoning field still faces a number of methodological challenges and outstanding questions that will need to be resolved by future studies, the research to date has established a link between psychopathy and PFC. PMID:22752782

  7. Capacity-speed relationships in prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Vivek Prabhakaran

    Full Text Available Working memory (WM capacity and WM processing speed are simple cognitive measures that underlie human performance in complex processes such as reasoning and language comprehension. These cognitive measures have shown to be interrelated in behavioral studies, yet the neural mechanism behind this interdependence has not been elucidated. We have carried out two functional MRI studies to separately identify brain regions involved in capacity and speed. Experiment 1, using a block-design WM verbal task, identified increased WM capacity with increased activity in right prefrontal regions, and Experiment 2, using a single-trial WM verbal task, identified increased WM processing speed with increased activity in similar regions. Our results suggest that right prefrontal areas may be a common region interlinking these two cognitive measures. Moreover, an overlap analysis with regions associated with binding or chunking suggest that this strategic memory consolidation process may be the mechanism interlinking WM capacity and WM speed.

  8. Insulin Resistance Predicts Medial Temporal Hypermetabolism in Mild Cognitive Impairment Conversion to Alzheimer Disease

    Science.gov (United States)

    Willette, Auriel A.; Modanlo, Nina

    2015-01-01

    Alzheimer disease (AD) is characterized by progressive hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans. Peripheral insulin resistance (IR) increases AD risk. No studies have examined associations between FDG metabolism and IR in mild cognitive impairment (MCI) and AD, as well as MCI conversion to AD. We studied 26 cognitively normal (CN), 194 MCI (39 MCI-progressors, 148 MCI-stable, 2 years after baseline), and 60 AD subjects with baseline FDG-PET from the Alzheimer’s Disease Neuroimaging Initiative. Mean FDG metabolism was derived for AD-vulnerable regions of interest (ROIs), including lateral parietal and posteromedial cortices, medial temporal lobe (MTL), hippocampus, and ventral prefrontal cortices (vPFC), as well as postcentral gyrus and global cerebrum control regions. The homeostasis model assessment of IR (HOMA-IR) was used to measure IR. For AD, higher HOMA-IR predicted lower FDG in all ROIs. For MCI-progressors, higher HOMA-IR predicted higher FDG in the MTL and hippocampus. Control regions showed no associations. Higher HOMA-IR predicted hypermetabolism in MCI-progressors and hypometabolism in AD in medial temporal regions. Future longitudinal studies should examine the pathophysiologic significance of the shift from MTL hyper- to hypometabolism associated with IR. PMID:25576061

  9. Pediatric Glial Heterotopia in the Medial Canthus.

    Science.gov (United States)

    Kim, Soung Min; Amponsah, Emmanuel Kofi; Eo, Mi Young; Cho, Yun Ju; Lee, Suk Keun

    2017-11-01

    Glial heterotopias are rare, benign, congenital, midline, and nonteratomatous extracranial glial tissue. They may be confused as encephalocele or dermoid cysts and are mostly present in the nose.An 8-month-old African female child presented with a slow growing paranasal mass. The mass had been present at the left upper medial canthus since birth and had slowly and progressively enlarged. There was no communication between the mass and the cranial cavity during the operational procedure. The mass was immunohistochemically positive for S-100 protein as well as for glial fibrillary acidic protein, but negative for proliferating cell nuclear antigen. This suggested that the mass was composed of benign glial tissues with many astrocytes.The purpose of this report is to demonstrate the first patient with pediatric glial heterotopic tissue in the medial canthus and to report the clinical importance of its immunohistochemical findings.

  10. Neuromuscular Exercise Post Partial Medial Meniscectomy

    DEFF Research Database (Denmark)

    Hall, Michelle; Hinman, Rana S; Wrigley, Tim V

    2015-01-01

    PURPOSE: To evaluate the effects of a 12-week, home-based, physiotherapist-guided neuromuscular exercise program on the knee adduction moment (an indicator of mediolateral knee load distribution) in people with a medial arthroscopic partial meniscectomy within the past 3-12 months. METHODS......: An assessor-blinded, randomised controlled trial including people aged 30-50 years with no to mild pain following medial arthroscopic partial meniscectomy was conducted. Participants were randomly allocated to either a 12-week neuromuscular exercise program that targeted neutral lower limb alignment...... or a control group with no exercise. The exercise program included eight individual sessions with one of seven physiotherapists in private clinics, together with home exercises. Primary outcomes were the peak external knee adduction moment during normal pace walking and during a one-leg sit-to-stand. Secondary...

  11. [SECOT consensus on medial femorotibial osteoarthritis].

    Science.gov (United States)

    Moreno, A; Silvestre, A; Carpintero, P

    2013-01-01

    A consensus, prepared by SECOT, is presented on the management of medial knee compartment osteoarthritis, in order to establish clinical criteria and recommendations directed at unifying the criteria in its management, dealing with the factors involved in the pathogenesis of medial femorotibial knee osteoarthritis, the usefulness of diagnostic imaging techniques, and the usefulness of arthroscopy. Conservative and surgical treatments are also analysed. The experts consulted showed a consensus (agreed or disagreed) in 65.8% of the items considered, leaving 14items where no consensus was found, which included the aetiopathogenesis of the osteoarthritis, the value of NMR in degenerative disease, the usefulness of COX-2 and the chondroprotective drugs, as well as on the ideal valgus tibial osteotomy technique. © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  12. Foot medial longitudinal-arch deformation during quiet standing and gait in subjects with medial tibial stress syndrome

    DEFF Research Database (Denmark)

    Bandholm, Thomas Quaade; Boysen, Lisbeth; Haugaard, Stine

    2008-01-01

    The objective of this study was to investigate (1) if subjects with medial tibial stress syndrome demonstrate increased navicular drop and medial longitudinal-arch deformation during quiet standing and gait compared with healthy subjects, and (2) the relationship between medial longitudinal-arch ...

  13. Medial thalamic 18-FDG uptake following inescapable shock correlates with subsequent learned helpless behavior

    International Nuclear Information System (INIS)

    Mirrione, M.M.; Schulz, D.; Dewey, S.L.; Henn, F.A.

    2009-01-01

    in additional regions analyzed including the nucleus accumbens, caudate putamen, substantia nigra, and amygdala. These data suggest that medial thalamic 18-FDG uptake during inescapable shock may contribute to subsequent escape deficits, and are not confounded by shock effects per se, since all animals received the same treatment prior to scanning. We have previously explored 18-FDG differences following the escape test session which also showed hyperactivity in the medial thalamus of learned helpless animals compared to non-learned helpless, and included additional cortical-limbic changes. Given the neuroanatomical connections between the medial thalamus (and habenula) with the prefrontal cortex and monoaminergic brain stem, one possible speculation is that abnormal neuronal activity in these areas during stress may set in motion circuitry changes that correlate with learned helpless behavior.

  14. Unicameral Bone Cyst of the Medial Cuneiform.

    Science.gov (United States)

    Schick, Faith A; Daniel, Joseph N; Miller, Juliane S

    2016-09-02

    A unicameral bone cyst is a relatively uncommon, benign bone tumor found in the metaphysis of long bones, such as the humerus and the femur, in skeletally immature persons. In the foot, these benign, fluid-filled cavities are most commonly found within the os calcis. We present a case report of a 10-year-old female with a unicameral bone cyst of the medial cuneiform.

  15. Osteoligamentous injuries of the medial ankle joint.

    Science.gov (United States)

    Lötscher, P; Lang, T H; Zwicky, L; Hintermann, B; Knupp, M

    2015-12-01

    Injuries of the ankle joint have a high incidence in daily life and sports, thus, playing an important socioeconomic role. Therefore, proper diagnosis and adequate treatment are mandatory. While most of the ligament injuries around the ankle joint are treated conservatively, great controversy exists on how to treat deltoid ligament injuries in ankle fractures. Missed injuries and inadequate treatment of the medial ankle lead to inferior outcome with instability, progressive deformity, and ankle joint osteoarthritis.

  16. Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats

    Science.gov (United States)

    Achterberg, E.J. Marijke; van Kerkhof, Linda W.M.; Damsteegt, Ruth; Trezza, Viviana

    2015-01-01

    Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD. PMID:25568111

  17. Dampened dopamine-mediated neuromodulation in prefrontal cortex of fragile X mice.

    Science.gov (United States)

    Paul, Kush; Venkitaramani, Deepa V; Cox, Charles L

    2013-02-15

    Fragile X syndrome (FXS) is the most common form of inheritable mental retardation caused by transcriptional silencing of the Fmr1 gene resulting in the absence of fragile X mental retardation protein (FMRP). The role of this protein in neurons is complex and its absence gives rise to diverse alterations in neuronal function leading to neurological disorders including mental retardation, hyperactivity, cognitive impairment, obsessive-compulsive behaviour, seizure activity and autism. FMRP regulates mRNA translation at dendritic spines where synapses are formed, and thus the lack of FMRP can lead to disruptions in synaptic transmission and plasticity. Many of these neurological deficits in FXS probably involve the prefrontal cortex, and in this study, we have focused on modulatory actions of dopamine in the medial prefrontal cortex. Our data indicate that dopamine produces a long-lasting enhancement of evoked inhibitory postsynaptic currents (IPSCs) mediated by D1-type receptors seen in wild-type mice; however, such enhancement is absent in the Fmr1 knock-out (Fmr1 KO) mice. The facilitation of IPSCs produced by direct cAMP stimulation was unaffected in Fmr1 KO, but D1 receptor levels were reduced in these animals. Our results show significant disruption of dopaminergic modulation of synaptic transmission in the Fmr1 KO mice and this alteration in inhibitory activity may provide insight into potential targets for the rescue of deficits associated with FXS.

  18. Enhanced pain expectation in migraine: EEG-based evidence for impaired prefrontal function.

    Science.gov (United States)

    Lev, Rina; Granovsky, Yelena; Yarnitsky, David

    2013-01-01

    Dysexcitability characterizes the interictal migraineous brain. The main central expressions of this dysexcitability are decreased habituation and enhanced anticipation and attention to pain and other external sensory stimuli. This study evaluates the effects of anticipation on pain modulation and their neural correlates in migraine. In 39 migraineurs (20 migraine with aura [MWA] and 19 migraine without aura [MOA]) and 22 healthy controls, cortical responses to 2 successive trains of noxious contact-heat stimuli, presented in either predicted or unpredicted manner, were analyzed using standardized low-resolution electromagnetic tomography key. A lack of habituation to repeated predicted pain was associated with significantly increased pain-evoked potential amplitudes in MWAs (increase of 3.9 μV) and unchanged ones in MOAs (1.1 μV) but not in controls (decrease of 5 μV). Repeated unpredicted pain resulted in enhanced pain-evoked potential amplitudes in both MWA and MOA groups (increase of 5.5 μV and 4.4 μV, respectively) compared with controls (decrease of 0.2 μV). Source localization revealed reduced activations in the anterior-medial prefrontal cortices and subsequent increased somatosensory activity in migraineurs (P < .05). The prefrontal-somatosensory dysfunction positively correlated with lifetime headache duration (P < .05) and concern of upcoming migraine attacks (P < .05) in MWAs, and with frequency of migraine attacks in MOAs (P < .05). Our findings of impaired modulation of anticipated pain in migraine suggest a heightened state of anticipatory readiness combined with ineffective recruitment of prefrontal inhibitory pathways during experience of pain; the latter might account for the former, at least partially. In line, less efficient inhibitory capability is a plausible mechanistic explanation for patients' high concern about their upcoming migraine attacks. © 2012 American Headache Society.

  19. Verbal Memory Deficits Are Correlated with Prefrontal Hypometabolism in 18FDG PET of Recreational MDMA Users

    Science.gov (United States)

    Bosch, Oliver G.; Wagner, Michael; Jessen, Frank; Kühn, Kai-Uwe; Joe, Alexius; Seifritz, Erich; Maier, Wolfgang; Biersack, Hans-Jürgen; Quednow, Boris B.

    2013-01-01

    Introduction 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users. Methods Brain glucose metabolism in rest was assessed using 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18FDG PET) in 19 male recreational users of MDMA and 19 male drug-naïve controls. 18FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test. Results As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei) of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex. Conclusions Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users arise from combined

  20. Negative emotion modulates prefrontal cortex activity during a working memory task: A NIRS study

    Directory of Open Access Journals (Sweden)

    Sachiyo eOzawa

    2014-02-01

    Full Text Available This study investigated the neural processing underlying the cognitive control of emotions induced by the presentation of task-irrelevant emotional pictures before a working memory task. Previous studies have suggested that the cognitive control of emotion involves the prefrontal regions. Therefore, we measured the hemodynamic responses that occurred in the prefrontal region with a 16-channel near-infrared spectroscopy (NIRS system. In our experiment, participants observed two negative or two neutral pictures in succession immediately before a 1-back or 3-back task. Pictures were selected from the International Affective Picture System. We measured the changes in the concentration of oxygenated hemoglobin (oxyHb during picture presentation and during the n-back task. The emotional valence of the picture affected the oxyHb changes in anterior parts of the medial prefrontal cortex (located in the left and right superior frontal gyrus and left inferior frontal gyrus during the n-back task; the oxyHb changes during the task were significantly greater following negative rather than neutral stimulation. As indicated in a number of previous studies, and the time courses of the oxyHb changes in our study, activation in these locations is possibly led by cognitive control of emotion, though we cannot deny it may simply be emotional responses. There were no effects of emotion on oxyHb changes during picture presentation or on n-back task performance. Although further studies are necessary to confirm this interpretation, our findings suggest that NIRS can be used to investigate neural processing during emotional control.

  1. Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions.

    Science.gov (United States)

    Perry, Jennifer L; Joseph, Jane E; Jiang, Yang; Zimmerman, Rick S; Kelly, Thomas H; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P; Bardo, Michael T

    2011-01-01

    Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex.

    Science.gov (United States)

    Neves, Ricardo M; van Keulen, Silvia; Yang, Mingyu; Logothetis, Nikos K; Eschenko, Oxana

    2018-03-01

    The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α 2 -adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information

  3. Posterior and prefrontal contributions to the development posttraumatic stress disorder symptom severity: an fMRI study of symptom provocation in acute stress disorder.

    Science.gov (United States)

    Cwik, Jan C; Sartory, Gudrun; Nuyken, Malte; Schürholt, Benjamin; Seitz, Rüdiger J

    2017-09-01

    Acute stress disorder (ASD) is predictive of the development of posttraumatic stress disorder (PTSD). In response to symptom provocation, the exposure to trauma-related pictures, ASD patients showed increased activation of the medial posterior areas of precuneus and posterior cingulate cortex as well as of superior prefrontal cortex in a previous study. The current study aimed at investigating which activated areas are predictive of the development of PTSD. Nineteen ASD patients took part in an fMRI study in which they were shown personalized trauma-related and neutral pictures within 4 weeks of the traumatic event. They were assessed for severity of PTSD 4 weeks later. Activation contrasts between trauma-related and neutral pictures were correlated with subsequent PTSD symptom severity. Greater activation in, among others, right medial precuneus, left retrosplenial cortex, precentral and right superior temporal gyrus as well as less activation in lateral, superior prefrontal and left fusiform gyrus was related to subsequently increased PTSD severity. The results are broadly in line with neural areas related to etiological models of PTSD, namely multisensory associative learning recruiting posterior regions on the one hand and failure to reappraise maladaptive cognitions, thought to involve prefrontal areas, on the other.

  4. Evidence for a neural correlate of a framing effect: bias-specific activity in the ventromedial prefrontal cortex during credibility judgments.

    Science.gov (United States)

    Deppe, M; Schwindt, W; Krämer, J; Kugel, H; Plassmann, H; Kenning, P; Ringelstein, E B

    2005-11-15

    Neural processes within the medial prefrontal cortex play a crucial role in assessing and integrating emotional and other implicit information during decision-making. Phylogenetically, it was important for the individual to assess the relevance of all kinds of environmental stimuli in order to adapt behavior in a flexible manner. Consequently, we can in principle not exclude that environmental information covertly influences the evaluation of actually decision relevant facts ("framing effect"). To test the hypothesis that the medial prefrontal cortex is involved into a framing effect we employed functional magnetic resonance imaging (fMRI) during a binary credibility judgment task. Twenty-one subjects were asked to judge 30 normalized news magazine headlines by forced answers as "true" or "false". To confound the judgments by formally irrelevant framing information we presented each of the headlines in four different news magazines characterized by varying credibility. For each subject the susceptibility to the judgment confounder (framing information) was assessed by magazine-specific modifications of the answers given. We could show that individual activity changes of the ventromedial prefrontal cortex during the judgments correlate with the degree of an individual's susceptibility to the framing information. We found (i) a neural correlate of a framing effect as postulated by behavioral decision theorists that (ii) reflects interindividual differences in the degree of the susceptibility to framing information.

  5. Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts

    Directory of Open Access Journals (Sweden)

    Marlos Vasconcelos Rocha

    2015-01-01

    Full Text Available Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD, but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H+MRS. The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H+MRS. Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H+MRS. Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects. Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H+MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.

  6. Dopamine Modulates Delta-Gamma Phase-Amplitude Coupling in the Prefrontal Cortex of Behaving Rats

    Science.gov (United States)

    Andino-Pavlovsky, Victoria; Souza, Annie C.; Scheffer-Teixeira, Robson; Tort, Adriano B. L.; Etchenique, Roberto; Ribeiro, Sidarta

    2017-01-01

    Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC. PMID:28536507

  7. Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder.

    Science.gov (United States)

    Buchsbaum, Monte S; Nenadic, Igor; Hazlett, Erin A; Spiegel-Cohen, Jacqueline; Fleischman, Michael B; Akhavan, Arash; Silverman, Jeremy M; Siever, Larry J

    2002-03-01

    In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients.

  8. Radiographic evaluation of the canine elbow joint with special reference to the medial humeral condyle and the medial coronoid process

    International Nuclear Information System (INIS)

    Voorhout, G.; Hazewinkel, H.A.W.

    1987-01-01

    The results of radiographic examination of clinically affected elbow joints in 14 young, large-breed dogs, including standard and oblique projections and linear tomography, were compared with the findings of medial arthrotomy. Radiographs revealed arthrosis (13 dogs), osteochondrosis of the medial humeral condyle (2 dogs), fragmentation of the medial coronoid process (5 dogs), and a combination of osteochondrosis of the medial humeral condyle and fragmentation of the medial coronoid process (2 dogs). In one dog fissures in the medial coronoid process and in another dog a linear radiopacity along the articular surface of the medial coronoid process were found. In three dogs both medial humeral condyle and medial coronoid process appeared normal. The radiographic findings were confirmed during surgery in 11 dogs. Cartilage erosion of the medial humeral condyle in two dogs and of the medial coronoid process in one dog had not resulted in radiographically visible abnormalities. Radiographic examination of the elbow joints in young, large-breed dogs should include standard mediolateral and craniocaudal projections, a mediolateral projection with the joint maximally extended and the leg supinated 15°, and a craniolateral-to-caudomedial projection

  9. Extracción y evaluación de taninos condensados a partir de la corteza de once especies maderables de Costa Rica Extraction and evaluation of condensed tannins from bark of eleven species of trees from Costa Rica

    Directory of Open Access Journals (Sweden)

    Jorge Aguilar López

    2012-12-01

    Full Text Available La naturaleza química de los taninos condensados los convierte en una fuente natural de compuestos orgáni- cos, con una aplicación potencialmente amplia para usos medicinales e industriales. La extracción y análisis de este tipo de metabolitos a partir de la flora de diversas regiones del planeta ha sido el objetivo del estudio de diversos grupos de trabajo, y en este caso se ha querido hacer un aporte al estado del conocimiento actual, realizando un estudio sobre la natu- raleza y la cantidad del tanino condensado que se puede extraer de la corteza de 11 especies arbóreas presentes en Costa Rica: guanacaste (Enterolobium cyclocarpum, alcornoque (Licania arborea, jobo (Spondias mom- bin, pochote (Pachira quinata, níspero (Manilkara chicle, almendro (Andira inermis, roble (Tabebuia rosea, cedro (Cedrela odorata, cenízaro (Samanea saman, pino (Pinus caribaea y ciprés (Cupressus lusitanica. Las muestras de corteza fueron preparadas, secadas y extraídas con etanol. Se analizaron los extractos etanóli- cos para determinar el contenido de taninos condensa- dos a través del número de Stiasny, y se caracterizaron mediante espectroscopía infrarroja (FT-IR. Las especies con mayor proporción de material extraído fueron guanacaste (9.5841% m/m, pochote (15.0066% m/m, pino (19.3400% m/m y ciprés (10.5300% m/m, mientras que los extractos con una mayor proporción de taninos condensados correspondieron a alcornoque (61.9% m/m, jobo (66.1% m/m, pochote (72.8% m/m, níspero (50.5% m/m, cedro (72.7% m/m y pino (70.7% m/m.The chemical nature of condensed tannins offers a natural source of such organic compounds, with potential application to medicinal and industrial uses. The extraction and analysis of this type of metabo- lites from plants of many regions of the world have been the objective of researching groups. In this case, it is desired to contribute to present knowledge, establishing the nature and amounts of condensed tannins extracted

  10. Medial Prefrontal Cortex and HPA Axis Roles in Generation of PTSD-Like Symptoms in SPS Model

    Science.gov (United States)

    2012-09-01

    concentration of glutamine (a major precursor molecule for synthesis of neuronal glutamate) (Nicholls, 1994) was also attenuated in the mPFC. The concentration...glutamate used for neural transmission because glutamate is a precursor molecule for the synthesis of GABA (Cooper et al., 1996). There was no...onsecutive weight gain. The PL and IL were temporarily inactivated by infusion of the odium channel blocker, lidocaine HCL (Sigma–Aldrich, St. Louis, O) in

  11. D-Cycloserine Administered Directly to Infralimbic Medial Prefrontal Cortex Enhances Extinction Memory in Sucrose-Seeking Animals

    NARCIS (Netherlands)

    Peters, J.; de Vries, T.J.

    2013-01-01

    d-Cycloserine (DCS), a co-agonist at the N-methyl-D-aspartate (NMDA) receptor, has proven to be an effective adjunct to cognitive behavioral therapies that utilize extinction. This pharmacological-based enhancement of extinction memory has been primarily demonstrated in neuropsychiatric disorders

  12. Stress-induced impairment of glutamatergic terminals ultrastructure: High vulnerability of medial prefrontal cortex and preventing action of desipramine

    DEFF Research Database (Denmark)

    Nava, N.; Popoli, M.; Musazzi, L.

    2013-01-01

    mediators, glucocorticoids, on brain volume and dendritic remodeling, in both humans and rodents. Nevertheless, few is still known on the structural changes exerted by behavioral stress on the features of glutamatergic synapses as sites of neuronal communication. Indeed, in excitatory synapses synaptic...... communication is driven by neurotransmitter which is stored, within the presynaptic terminal, in morphologically distinct pools of vesicles, namely the readily-releasable pool of vesicles (RRP), docked to the active zone and ready for release, and the reserve pool of vesicles. When neurotransmitter is released...

  13. Protein Kinase A Deregulation in the Medial Prefrontal Cortex Impairs Working Memory in Murine Oligophrenin-1 Deficiency.

    Science.gov (United States)

    Zhang, Chun-Lei; Aime, Mattia; Laheranne, Emilie; Houbaert, Xander; El Oussini, Hajer; Martin, Christelle; Lepleux, Marilyn; Normand, Elisabeth; Chelly, Jamel; Herzog, Etienne; Billuart, Pierre; Humeau, Yann

    2017-11-15

    Classical and systems genetics have identified wide networks of genes associated with cognitive and neurodevelopmental diseases. In parallel to deciphering the role of each of these genes in neuronal or synaptic function, evaluating the response of neuronal and molecular networks to gene loss of function could reveal some pathophysiological mechanisms potentially accessible to nongenetic therapies. Loss of function of the Rho-GAP oligophrenin-1 is associated with cognitive impairments in both human and mouse. Upregulation of both PKA and ROCK has been reported in Ophn1 -/ y mice, but it remains unclear whether kinase hyperactivity contributes to the behavioral phenotypes. In this study, we thoroughly characterized a prominent perseveration phenotype displayed by Ophn1 -deficient mice using a Y-maze spatial working memory (SWM) test. We report that Ophn1 deficiency in the mouse generated severe cognitive impairments, characterized by both a high occurrence of perseverative behaviors and a lack of deliberation during the SWM test. In vivo and in vitro pharmacological experiments suggest that PKA dysregulation in the mPFC underlies cognitive dysfunction in Ophn1 -deficient mice, as assessed using a delayed spatial alternation task results. Functionally, mPFC neuronal networks appeared to be affected in a PKA-dependent manner, whereas hippocampal-PFC projections involved in SWM were not affected in Ophn1 -/y mice. Thus, we propose that discrete gene mutations in intellectual disability might generate "secondary" pathophysiological mechanisms, which are prone to become pharmacological targets for curative strategies in adult patients. SIGNIFICANCE STATEMENT Here we report that Ophn1 deficiency generates severe impairments in performance at spatial working memory tests, characterized by a high occurrence of perseverative behaviors and a lack of decision making. This cognitive deficit is consecutive to PKA deregulation in the mPFC that prevents Ophn1 KO mice to exploit a correctly acquired rule. Functionally, mPFC neuronal networks appear to be affected in a PKA-dependent manner, whereas behaviorally important hippocampal projections were preserved by the mutation. Thus, we propose that discrete gene mutations in intellectual disability can generate "secondary" pathophysiological mechanisms prone to become pharmacological targets for curative strategies in adults. Copyright © 2017 the authors 0270-6474/17/3711114-13$15.00/0.

  14. Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity

    NARCIS (Netherlands)

    Berkers, R.M.W.J.; Klumpers, F.; Fernandez, G.S.E.

    2016-01-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to

  15. Being asked to tell an unpleasant truth about another person activates anterior insula and medial prefrontal cortex

    DEFF Research Database (Denmark)

    Littlefield, Melissa M; Dietz, Martin; Fitzgerald, Des

    2015-01-01

    “Truth” has been used as a baseline condition in several functional magnetic resonance imaging (fMRI) studies of deception. However, like deception, telling the truth is an inherently social construct, which requires consideration of another person’s mental state, a phenomenon known as Theory of ...

  16. Observational Learning in Mice Can Be Prevented by Medial Prefrontal Cortex Stimulation and Enhanced by Nucleus Accumbens Stimulation

    Science.gov (United States)

    Jurado-Parras, M. Teresa; Gruart, Agnes; Delgado-Garcia, Jose M.

    2012-01-01

    The neural structures involved in ongoing appetitive and/or observational learning behaviors remain largely unknown. Operant conditioning and observational learning were evoked and recorded in a modified Skinner box provided with an on-line video recording system. Mice improved their acquisition of a simple operant conditioning task by…

  17. Glucocorticoid Effects on Memory Consolidation Depend on Functional Interactions between the Medial Prefrontal Cortex and Basolateral Amygdala

    NARCIS (Netherlands)

    Roozendaal, Benno; McReynolds, Jayme R.; Van der Zee, Eddy A.; Lee, Sangkwan; McGaugh, James L.; McIntyre, Christa K.

    2009-01-01

    Considerable evidence indicates that the basolateral complex of the amygdala (BLA) interacts with efferent brain regions in mediating glucocorticoid effects on memory consolidation. Here, we investigated whether glucocorticoid influences on the consolidation of memory for emotionally arousing

  18. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

    Science.gov (United States)

    Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

    2017-01-01

    The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Prefrontal Dopamine D1 Receptors and Working Memory in Schizotypal Personality Disorder: A PET Study with [11C]NNC112

    Science.gov (United States)

    Thompson, Judy L.; Rosell, Daniel R.; Slifstein, Mark; Girgis, Ragy R.; Xu, Xiaoyan; Ehrlich, Yosefa; Kegeles, Lawrence S.; Hazlett, Erin A.; Abi-Dargham, Anissa; Siever, Larry J.

    2014-01-01

    Rationale Schizotypal personality disorder (SPD) is associated with working memory (WM) impairments that are similar to those observed in schizophrenia. Imaging studies have suggested that schizophrenia is associated with alterations in dopamine D1-receptor availability in the prefrontal cortex (PFC) that may be related to the WM impairments that characterize this disorder. Objectives To characterize prefrontal D1-receptor availability and its relation to WM performance in SPD. Methods We used positron emission tomography (PET) and the radiotracer [11C]NNC112 with 18 unmedicated SPD and 21 healthy-control participants; as an index of D1-receptor availability, binding-potential (BP) measures (BPF, BPND, and BPP) were calculated for prefrontal and striatal subregions. To assess WM, SPD participants completed the 2-back and Paced Auditory Serial Addition Test (PASAT). Results There were no significant group differences in PFC BP. BPF and BPP in the medial PFC were significantly negatively related to PASAT performance (rs=-0.551, p=.022 and rs=-0.488, p=.047, respectively), but BP was not related to 2-back performance. Conclusions In contrast to what has been found in schizophrenia, SPD was not associated with significant prefrontal D1-receptor alterations. Similar to previous schizophrenia findings, however, higher prefrontal D1-receptor availability was associated with poorer WM performance (as measured by the PASAT) in SPD. These findings suggest that schizophrenia and SPD may share a common pathophysiological feature related to prefrontal dopamine functioning that contributes to WM dysfunction, but that in SPD, alterations in D1 may occur only in a subset of individuals and/or to an extent that is minor relative to what occurs in schizophrenia. PMID:24781514

  20. Executive deficits, not processing speed relates to abnormalities in distinct prefrontal tracts in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Pettit, Lewis D; Bastin, Mark E; Smith, Colin; Bak, Thomas H; Gillingwater, Thomas H; Abrahams, Sharon

    2013-11-01

    , uncinate fasciculus and hippocampal portion of the cingulum bundles. Significant differences also emerged in the anterior corona radiata as well as in white matter underlying the superior, medial and inferior frontal gyri and the temporal gyri. Dual-task performance significantly correlated with fractional anisotropy measures in the middle frontal gyrus white matter and anterior corona radiata. Letter fluency indices significantly correlated with fractional anisotropy measures of the inferior frontal gyrus white matter and corpus callosum in addition to the corticospinal tracts and mean diffusivity measures in the white matter of the superior frontal gyrus. The current study demonstrates that cognitive impairment in amyotrophic lateral sclerosis is not due to generic slowing of processing speed. Moreover, different executive deficits are related to distinct prefrontal tract involvement in amyotrophic lateral sclerosis with dual-task impairment associating with dorsolateral prefrontal dysfunction and letter fluency showing greater dependence on inferolateral prefrontal dysfunction.

  1. Alternative Splicing of AMPA subunits in Prefrontal Cortical Fields of Cynomolgus Monkeys following Chronic Ethanol Self-Administration

    Directory of Open Access Journals (Sweden)

    Glen eAcosta

    2012-01-01

    Full Text Available Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in alcohol dependence. To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA subunit variant and kainate (GRIK subunit mRNA expression were studied in the orbitofrontal cortex (OFC, dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC of male cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total kainate receptor subunit expression were significantly decreased in alcohol drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. In OFC, AMPA subunit splice variant expression was reduced in the alcohol treated group. GRIA2 flop mRNA levels in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. Results from these studies provide further evidence of transcriptional regulation of iGluR subunits in the primate brain following chronic alcohol self-administration. Additional studies examining the cellular localization of such effects in the framework of primate prefrontal cortical circuitry are warranted.

  2. Prefrontal-hippocampal-fusiform activity during encoding predicts intraindividual differences in free recall ability: an event-related functional-anatomic MRI study.

    Science.gov (United States)

    Dickerson, B C; Miller, S L; Greve, D N; Dale, A M; Albert, M S; Schacter, D L; Sperling, R A

    2007-01-01

    The ability to spontaneously recall recently learned information is a fundamental mnemonic activity of daily life, but has received little study using functional neuroimaging. We developed a functional MRI (fMRI) paradigm to study regional brain activity during encoding that predicts free recall. In this event-related fMRI study, ten lists of fourteen pictures of common objects were shown to healthy young individuals and regional brain activity during encoding was analyzed based on subsequent free recall performance. Free recall of items was predicted by activity during encoding in hippocampal, fusiform, and inferior prefrontal cortical regions. Within-subject variance in free recall performance for the ten lists was predicted by a linear combination of condition-specific inferior prefrontal, hippocampal, and fusiform activity. Recall performance was better for lists in which prefrontal activity was greater for all items of the list and hippocampal and fusiform activity were greater specifically for items that were recalled from the list. Thus, the activity of medial temporal, fusiform, and prefrontal brain regions during the learning of new information is important for the subsequent free recall of this information. These fronto-temporal brain regions act together as a large-scale memory-related network, the components of which make distinct yet interacting contributions during encoding that predict subsequent successful free recall performance.

  3. Efecto de la 2-fenil-4,4-bis-(hidroximetil)-2-oxazolina en la respuesta del giro dentado a la estimulación de la corteza endorrinal y en la actividad eléctrica espontánea del gerbil de Mongolia

    OpenAIRE

    Díaz Molina, Milena; Pérez Saad, Héctor M.

    2006-01-01

    La epilepsia constituye un desorden neurológico de gran incidencia en la población, con un marcado impacto familiar y social. El gerbil de Mongolia es un modelo de epilepsia de gran utilidad, pues este animal desarrolla crisis espontáneas fenomenológicamente similares a las epilepsias refractarias. En el presente trabajo se estudió el efecto de la 2-fenil-4,4-bis-(hidroximetil)-2-oxazolina (OX) en la respuesta del giro dentado a la estimulación eléctrica de la corteza endorrinal y en la activ...

  4. Rheo: Japanese sound art interrogating digital mediality

    Directory of Open Access Journals (Sweden)

    Vandsø Anette

    2014-12-01

    Full Text Available The article asks in what way the Japanese sound artist, Ryoichi Kurokawa’s audiovisual installation, Rheo: 5 Horisonz (2010, is “digital.” Using professor Lars Elleström’s concept of “mediality,” the main claim in this article is that Rheo not only uses digital technology but also interrogates digital mediality as such. This argument is pursued in an analysis of Rheo that draws in various descriptions of digital media by N. Catherine Hayles, Lev Manovic, Bolter, and Grusin among other. The article will show how the critical potential in Rheo is directed both towards digital media as a language (Meyrowitz (or a place for representation and towards the digital as a milieu (Meyrowitz or as our culture (Gere. The overall goal of the article is not just analyse this singular art work, but also to show how such a sound art work can contribute to our understanding of our own contemporary culture as a digital culture.

  5. Arthroscopic treatment of symptomatic type D medial plica

    OpenAIRE

    Uysal, Mustafa; Asik, Mehmet; Akpinar, Sercan; Ciftci, Feyyaz; Cesur, Necip; Tandogan, Reha N.

    2007-01-01

    We aimed to review the results of subtotal arthroscopic resection of symptomatic type D medial plica. We retrospectively evaluated 23 knees with symptomatic type D medial plica in 22 patients without other intra-articular pathology. All patients complained of chronic knee pain that had not been alleviated by medical treatment or physical therapy. In only three (13%) of the patients studied was the plica diagnosed pre-operatively with magnetic resonance imaging. The type D medial plicae in our...

  6. The medial tibial stress syndrome. A cause of shin splints.

    Science.gov (United States)

    Mubarak, S J; Gould, R N; Lee, Y F; Schmidt, D A; Hargens, A R

    1982-01-01

    The medial tibial stress syndrome is a symptom complex seen in athletes who complain of exercise-induced pain along the distal posterior-medial aspect of the tibia. Intramuscular pressures within the posterior compartments of the leg were measured in 12 patients with this disorder. These pressures were not elevated and therefore this syndrome is a not a compartment syndrome. Available information suggests that the medial tibial stress syndrome most likely represents a periostitis at this location of the leg.

  7. Functional results after external vocal fold medialization thyroplasty with the titanium vocal fold medialization implant.

    Science.gov (United States)

    Schneider, Berit; Denk, Doris-Maria; Bigenzahn, Wolfgang

    2003-04-01

    A persistent insufficiency of glottal closure is mostly a consequence of a unilateral vocal fold movement impairment. It can also be caused by vocal fold atrophy or scarring processes with regular bilateral respiratory vocal fold function. Because of consequential voice, breathing, and swallowing impairments, a functional surgical treatment is required. The goal of the study was to outline the functional results after medialization thyroplasty with the titanium vocal fold medialization implant according to Friedrich. In the period of 1999 to 2001, an external vocal fold medialization using the titanium implant was performed on 28 patients (12 women and 16 men). The patients were in the age range of 19 to 84 years. Twenty-two patients had a paralysis of the left-side vocal fold, and six patients, of the right-side vocal fold. Detailed functional examinations were executed on all patients before and after the surgery: perceptive voice sound analysis according to the "roughness, breathiness, and hoarseness" method, judgment of the s/z ratio and voice dysfunction index, voice range profile measurements, videostroboscopy, and pulmonary function tests. In case of dysphagia/aspiration, videofluoroscopy of swallowing was also performed. The respective data were statistically analyzed (paired t test, Wilcoxon-test). All patients reported on improvement of voice, swallowing, and breathing functions postoperatively. Videostroboscopy revealed an almost complete glottal closure after surgery in all of the patients. All voice-related parameters showed a significant improvement. An increase of the laryngeal resistance by the medialization procedure could be excluded by analysis of the pulmonary function test. The results confirm the external medialization of the vocal folds as an adequate method in the therapy of voice, swallowing, and breathing impairment attributable to an insufficient glottal closure. The titanium implant offers, apart from good tissue tolerability, the

  8. Amodal processing in human prefrontal cortex.

    Science.gov (United States)

    Tamber-Rosenau, Benjamin J; Dux, Paul E; Tombu, Michael N; Asplund, Christopher L; Marois, René

    2013-07-10

    Information enters the cortex via modality-specific sensory regions, whereas actions are produced by modality-specific motor regions. Intervening central stages of information processing map sensation to behavior. Humans perform this central processing in a flexible, abstract manner such that sensory information in any modality can lead to response via any motor system. Cognitive theories account for such flexible behavior by positing amodal central information processing (e.g., "central executive," Baddeley and Hitch, 1974; "supervisory attentional system," Norman and Shallice, 1986; "response selection bottleneck," Pashler, 1994). However, the extent to which brain regions embodying central mechanisms of information processing are amodal remains unclear. Here we apply multivariate pattern analysis to functional magnetic resonance imaging (fMRI) data to compare response selection, a cognitive process widely believed to recruit an amodal central resource across sensory and motor modalities. We show that most frontal and parietal cortical areas known to activate across a wide variety of tasks code modality, casting doubt on the notion that these regions embody a central processor devoid of modality representation. Importantly, regions of anterior insula and dorsolateral prefrontal cortex consistently failed to code modality across four experiments. However, these areas code at least one other task dimension, process (instantiated as response selection vs response execution), ensuring that failure to find coding of modality is not driven by insensitivity of multivariate pattern analysis in these regions. We conclude that abstract encoding of information modality is primarily a property of subregions of the prefrontal cortex.

  9. Dorsolateral Prefrontal Contributions to Human Intelligence

    Science.gov (United States)

    Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

    2012-01-01

    Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in executive control functions for human intelligence, the necessity of the dorsolateral prefrontal cortex (dlPFC) for key competencies of general intelligence and executive function remains to be well established. Here we studied human brain lesion patients with dlPFC lesions to investigate whether this region is computationally necessary for performance on neuropsychological tests of general intelligence and executive function, administering the Wechsler Adult Intelligence Scale (WAIS) and subtests of the Delis Kaplan Executive Function System (D-KEFS) to three groups: dlPFC lesions (n = 19), non-dlPFC lesions (n = 152), and no brain lesions (n = 55). The key results indicate that: (1) patients with focal dlPFC damage exhibit lower scores, at the latent variable level, than controls in general intelligence (g) and executive function; (2) dlPFC patients demonstrate lower scores than controls in several executive measures; and (3) these latter differences are no longer significant when the pervasive influence of the general factor of intelligence (g) is statistically removed. The observed findings support a central role for the dlPFC in general intelligence and make specific recommendations for the interpretation and application of the WAIS and D-KEFS to the study of high-level cognition in health and disease. PMID:22634247

  10. Khat distorts the prefrontal cortex histology and function of adult ...

    African Journals Online (AJOL)

    Khat is a psychoactive herbal drug of pronounced ethno-pharmacological significance often abused due to its unregulated use. It affects many brain centers including the prefrontal cortex which is the anterior most part of the frontal lobe. The prefrontal cortex modulates working memory, planning complex cognitive ...

  11. Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex.

    Science.gov (United States)

    Chafee, Matthew V; Crowe, David A

    2017-10-11

    In this issue, Loonis et al. (2017) provide the first description of unique synchrony patterns differentiating implicit and explicit forms of learning in monkey prefrontal networks. Their results have broad implications for how prefrontal networks integrate the two learning mechanisms to control behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The Development of the Ventral Prefrontal Cortex and Social Flexibility

    Science.gov (United States)

    Nelson, Eric E.; Guyer, Amanda E.

    2011-01-01

    Over the last several years a number of studies in both humans and animals have suggested that the orbitofrontal and ventrolateral prefrontal cortices play an important role in generating flexible behavior. We suggest that input from these brain regions contribute to three functions involved in generating flexible behavior within social contexts: valuation, inhibition, and rule use. Recent studies have also demonstrated that the prefrontal cortex undergoes a prolonged course of maturation that extends well after puberty. Here, we review evidence that the prolonged development of these prefrontal regions parallels a slowly emerging ability for flexible social behavior. We also speculate on the possibility that sensitive periods for organizing social behavior may be embedded within this developmental time-fame. Finally, we discuss the role of prefrontal cortex in adolescent mood and anxiety disorders, particularly as orbitofrontal and ventrolateral prefrontal cortices are engaged in a social context. PMID:21804907

  13. Medialized repair for retracted rotator cuff tears.

    Science.gov (United States)

    Kim, Young-Kyu; Jung, Kyu-Hak; Won, Jun-Sung; Cho, Seung-Hyun

    2017-08-01

    The purpose of this study was to evaluate the functional outcomes of medialized rotator cuff repair and the continuity of repaired tendon in chronic retracted rotator cuff tears. Thirty-five consecutive patients were selected from 153 cases that underwent arthroscopic rotator cuff repair for more than medium-sized posterosuperior rotator cuff tears between July 2009 and July 2012 performed with the medialized repair. All cases were available for at least 2 years of postoperative follow-up. The visual analog scale of pain, muscle strength, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and University of California-Los Angeles score were evaluated. At the final follow-up, all clinical outcomes were significantly improved. The visual analog scale score for pain improved from 6 ± 1 preoperatively to 2 ± 1 postoperatively. The range of motion increased from preoperatively to postoperatively: active forward elevation, from 134° ± 49° to 150° ± 16°; active external rotation at the side, from 47° ± 15° to 55° ± 10°; and active internal rotation, from L3 to L1. The shoulder score also improved: Constant score, from 53.5 ± 16.7 to 79 ± 10; American Shoulder and Elbow Surgeons score, from 51 ± 15 to 82 ± 8; and University of California-Los Angeles score, from 14 ± 4 to 28 ± 4. The retear cases at the final follow-up were 6 (17%). Medialized repair may be useful in cases in which anatomic bone-to-tendon repair would be difficult because of the excessive tension of the repaired tendon and a torn tendon that does not reach the anatomic insertion. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  14. Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms.

    Science.gov (United States)

    Müller-Vahl, Kirsten R; Grosskreutz, Julian; Prell, Tino; Kaufmann, Jörn; Bodammer, Nils; Peschel, Thomas

    2014-01-07

    Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS "only" (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded.

  15. Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms

    Science.gov (United States)

    2014-01-01

    Background Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS “only” (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Results Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Conclusions Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded. PMID:24397347

  16. Quadriceps Tendon Autograft Medial Patellofemoral Ligament Reconstruction.

    Science.gov (United States)

    Fink, Christian; Steensen, Robert; Gföller, Peter; Lawton, Robert

    2018-06-01

    Critically evaluate the published literature related to quadriceps tendon (QT) medial patellofemoral ligament (MPFL) reconstruction. Hamstring tendon (HT) MPFL reconstruction techniques have been shown to successfully restore patella stability, but complications including patella fracture are reported. Quadriceps tendon (QT) reconstruction techniques with an intact graft pedicle on the patella side have the advantage that patella bone tunnel drilling and fixation are no longer needed, reducing risk of patella fracture. Several QT MPFL reconstruction techniques, including minimally invasive surgical (MIS) approaches, have been published with promising clinical results and fewer complications than with HT techniques. Parallel laboratory studies have shown macroscopic anatomy and biomechanical properties of QT are more similar to native MPFL than hamstring (HS) HT, suggesting QT may more accurately restore native joint kinematics. Quadriceps tendon MPFL reconstruction, via both open and MIS techniques, have promising clinical results and offer valuable alternatives to HS grafts for primary and revision MPFL reconstruction in both children and adults.

  17. Stress fracture of the medial clavicle secondary to nervous tic

    International Nuclear Information System (INIS)

    Yamada, K.; Sugiura, H.; Suzuki, Y.

    2004-01-01

    The clinical and radiological characteristics of swelling in the region of the medial clavicle may suggest the presence of a neoplastic or inflammatory lesion. This report describes a 27-year-old man with a painful tumor-like lesion over the medial clavicle, which was found to be a stress fracture caused by a nervous tic resulting from mental stress. (orig.)

  18. Anatomical and magnetic resonance imaging study of the medial ...

    African Journals Online (AJOL)

    Introduction: The medial collateral ligament of the ankle joint also known as the deltoid ligament, is a multifascicular group of ligaments. It can be divided into a superficial and deep group of fibers originating from the medial malleolus to insert in the talus, calcaneus, and navicular bones. Wide variations have been noted in ...

  19. Medial shoe-ground pressure and specific running injuries

    DEFF Research Database (Denmark)

    Brund, René B K; Rasmussen, Sten; Nielsen, Rasmus O

    2017-01-01

    pressure. Foot balance was categorized into those which presented a higher lateral shod pressure (LP) than medial pressure, and those which presented a higher medial shod pressure (MP) than lateral pressure during the stance phase. A time-to-event model was used to compare differences in incidence between...

  20. Trochleoplasty and medial patellofemoral ligament reconstruction for recurrent patellar dislocation

    Directory of Open Access Journals (Sweden)

    K Raghuveer Reddy

    2012-01-01

    Full Text Available We report a case of recurrent patellar dislocation with high-grade trochlear dysplasia which persisted despite two previous operations. We did a Dejour′s sulcus deepening trochleoplasty, medial patellofemoral ligament reconstruction, and lateral retinacular release. Trochleoplasty and medial patellofemoral ligament reconstruction is required in patients with high grade trochlear dysplasia.

  1. Low implant migration of the SIGMA® medial unicompartmental knee arthroplasty

    DEFF Research Database (Denmark)

    Koppens, Daan; Stilling, Maiken; Munk, Stig

    2017-01-01

    The purpose of this study was to evaluate implant migration of the fixed-bearing Sigma® medial unicompartmental knee arthroplasty (UKA). UKA is a regularly used treatment for patients with medial osteoarthritis (OA) of the knee. UKA has a higher revision rate than total knee arthroplasty. Implant...

  2. Intrinsic factors associated with medial tibial stress syndrome in ...

    African Journals Online (AJOL)

    Intrinsic factors associated with medial tibial stress syndrome in athletes: A large case-control study. ... Medial tibial stress syndrome (MTSS) is the most common lower-leg injury in athletes, and is thought to be caused by ... from 32 Countries:.

  3. Medial Amygdala and Aggressive Behavior : Interaction Between Testosterone and Vasopressin

    NARCIS (Netherlands)

    Koolhaas, J.M.; Roozendaal, B.; Boorsma, F.; Van Den Brink, T.H.C.

    1990-01-01

    This paper considers the functional significance of the testosterone-dependent vasopressinergic neurons of the medial amygdala (Ame) in intermale aggressive behavior of rats. Local microinfusion of vasopressin into the medial amygdala causes an increase in offensive behavior both in gonadally intact

  4. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

    Science.gov (United States)

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    + and K + channel function could reliably reproduce the observed increase in action potential firing and altered action potential waveform. These results, in conjunction with our prior findings on L5 neurons, suggest that principal neurons in the circuitry of the medial prefrontal cortex are altered in distinct ways in the fmr1 -/y mouse and may contribute to dysfunctional prefrontal cortex processing in fragile X syndrome. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  5. Traumatic posterior root tear of the medial meniscus in patients with severe medial instability of the knee.

    Science.gov (United States)

    Ra, Ho Jong; Ha, Jeong Ku; Jang, Ho Su; Kim, Jin Goo

    2015-10-01

    To examine the incidence and diagnostic rate of traumatic medial meniscus posterior root tear associated with severe medial instability and to evaluate the effectiveness of pullout repair. From 2007 to 2011, 51 patients who underwent operation due to multiple ligament injuries including medial collateral ligament rupture were reviewed retrospectively. The International Knee Documentation Committee (IKDC) subjective and Lysholm score were evaluated pre- and postoperatively. Postoperative magnetic resonance imaging (MRI) was performed, and if indicated, a second-look arthroscopic examination was conducted. Fourteen out of 51 patients were associated with severe medial instability. Seven patients were diagnosed with traumatic medial meniscus posterior root tear and underwent arthroscopic pullout repair. Five of them were missed at initial diagnosis using MRI. In seven patients, the mean Lysholm and IKDC subjective scores improved from 74.6 ± 10.3 and 47.6 ± 7.3 to 93.0 ± 3.7 and 91.6 ± 2.6, respectively. All showed complete healing of meniscus root on follow-up MRI and second-look arthroscopy. Medial meniscus posterior root tear may occur in severe medial instability from trauma. It is a common mistake that surgeons may not notice on the diagnosis of those injuries using MRI. Therefore, a high index of suspicion is required for the diagnosis of medial meniscus posterior root tear in this type of injuries. The traumatic medial meniscus posterior root tear could be healed successfully using arthroscopic pullout repair technique. The possibility of the medial meniscus posterior root tear should be considered in severe medial instability and arthroscopic pullout repair can be an effective option for treatment. Case series with no comparison group, Level IV.

  6. Associative learning beyond the medial temporal lobe: many actors on the memory stage

    Directory of Open Access Journals (Sweden)

    Giulio ePergola

    2013-11-01

    Full Text Available Decades of research have established a model that includes the medial temporal lobe, and particularly the hippocampus, as a critical node for episodic memory. Neuroimaging and clinical studies have shown the involvement of additional cortical and subcortical regions. Among these areas, the thalamus, the retrosplenial cortex and the prefrontal cortices have been consistently related to episodic memory performance.This article provides evidences that these areas are in different forms and degrees critical for human memory function rather than playing only an ancillary role. First we briefly summarize findings on the involvement of the hippocampus and the medial temporal lobe in recognition memory and recall. We then focus on the clinical and neuroimaging evidence available on thalamo-frontal and thalamo-retrosplenial networks. The role of these networks in episodic memory has been considered secondary, partly because disruption of these areas does not always lead to severe impairments; to account for this evidence, we discuss methodological issues related to the investigation of these regions. We propose that these networks contribute differently to recognition memory and recall, and also that the memory stage of their contribution shows specificity to encoding or retrieval in recall tasks. We note that the same mechanisms may be in force when humans perform non-episodic tasks, e.g., semantic retrieval and mental time travel. Functional disturbance of these networks is related to cognitive impairments not only in neurological disorders, but also in psychiatric medical conditions, such as schizophrenia. Finally we discuss possible mechanisms for the contribution of these areas to memory, including regulation of oscillatory rhythms and long-term potentiation. We conclude that integrity of the thalamo-frontal and the thalamo-retrosplenial networks is necessary for the manifold features of episodic memory.

  7. Deep processing activates the medial temporal lobe in young but not in old adults.

    Science.gov (United States)

    Daselaar, Sander M; Veltman, Dick J; Rombouts, Serge A R B; Raaijmakers, Jeroen G W; Jonker, Cees

    2003-11-01

    Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that elderly adults are not able to perform certain cognitive operations under deep processing conditions. We further hypothesised that this inability does not involve regions commonly associated with lexical/semantic retrieval processes, but rather involves a dysfunction of the medial temporal lobe (MTL) memory system. To this end, we used functional MRI on rather extensive groups of young and elderly adults to compare brain activity patterns obtained during a deep (living/nonliving) and a shallow (uppercase/lowercase) classification task. Common activity in relation to semantic classification was observed in regions that have been previously related to semantic retrieval, including mainly left-lateralised activity in the inferior prefrontal, middle temporal, and middle frontal/anterior cingulate gyrus. Although the young adults showed more activity in some of these areas, the finding of mainly overlapping activation patterns during semantic classification supports the idea that lexical/semantic retrieval processes are still intact in elderly adults. This received further support by the finding that both groups showed similar behavioural performances as well on the deep and shallow classification tasks. Importantly, though, the young revealed significantly more activity than the elderly adults in the left anterior hippocampus during deep relative to shallow classification. This finding is in line with the idea that age-related impairments in episodic encoding are, at least partly, due to an under-recruitment of the medial temporal lobe memory system.

  8. Centralization of extruded medial meniscus delays cartilage degeneration in rats.

    Science.gov (United States)

    Ozeki, Nobutake; Muneta, Takeshi; Kawabata, Kenichi; Koga, Hideyuki; Nakagawa, Yusuke; Saito, Ryusuke; Udo, Mio; Yanagisawa, Katsuaki; Ohara, Toshiyuki; Mochizuki, Tomoyuki; Tsuji, Kunikazu; Saito, Tomoyuki; Sekiya, Ichiro

    2017-05-01

    Meniscus extrusion often observed in knee osteoarthritis has a strong correlation with the progression of cartilage degeneration and symptom in the patients. We recently reported a novel procedure "arthroscopic centralization" in which the capsule was sutured to the edge of the tibial plateau to reduce meniscus extrusion in the human knee. However, there is no animal model to study the efficacy of this procedure. The purposes of this study were [1] to establish a model of centralization for the extruded medial meniscus in a rat model; and [2] to investigate the chondroprotective effect of this procedure. Medial meniscus extrusion was induced by the release of the anterior synovial capsule and the transection of the meniscotibial ligament. Centralization was performed by the pulled-out suture technique. Alternatively, control rats had only the medial meniscus extrusion surgery. Medial meniscus extrusion was evaluated by micro-CT and macroscopic findings. Cartilage degeneration of the medial tibial plateau was evaluated macroscopically and histologically. By micro-CT analysis, the medial meniscus extrusion was significantly improved in the centralization group in comparison to the extrusion group throughout the study. Both macroscopically and histologically, the cartilage lesion of the medial tibial plateau was prevented in the centralization group but was apparent in the control group. We developed medial meniscus extrusion in a rat model, and centralization of the extruded medial meniscus by the pull-out suture technique improved the medial meniscus extrusion and delayed cartilage degeneration, though the effect was limited. Centralization is a promising treatment to prevent the progression of osteoarthritis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. The timing of associative memory formation: frontal lobe and anterior medial temporal lobe activity at associative binding predicts memory

    Science.gov (United States)

    Hales, J. B.

    2011-01-01

    The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance. PMID:21248058

  10. Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

    Science.gov (United States)

    Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

    2017-10-01

    We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

  11. NEURAL CORRELATES FOR APATHY: FRONTAL - PREFRONTAL AND PARIETAL CORTICAL - SUBCORTICAL CIRCUITS

    Directory of Open Access Journals (Sweden)

    Rita Moretti

    2016-12-01

    Full Text Available Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional invovlement; it is an important and heavy-burden clinical condition which strongly impacts in every day life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC and basal ganglia; emotional affective apathy may be related to the orbitomedial PFC and ventral striatum; cognitive apathy may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of autoactivation may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to grey matter atrophy in the anterior cingulate (ACC and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies and a reduced speedness in action decsion, major resposnible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control.We will discuss the importance of these circuits in different pathologies

  12. Hypofunction of prefrontal cortex NMDA receptors does not change stress-induced release of dopamine and noradrenaline in amygdala but disrupts aversive memory.

    Science.gov (United States)

    Del Arco, Alberto; Ronzoni, Giacomo; Mora, Francisco

    2015-07-01

    A dysfunction of prefrontal cortex has been associated with the exacerbated response to stress observed in schizophrenic patients and high-risk individuals to develop psychosis. The hypofunction of NMDA glutamatergic receptors induced by NMDA antagonists produces cortico-limbic hyperactivity, and this is used as an experimental model to resemble behavioural abnormalities observed in schizophrenia. The aim of the present study was to investigate whether injections of NMDA antagonists into the medial prefrontal cortex of the rat change (1) the increases of dopamine, noradrenaline and corticosterone concentrations produced by acute stress in amygdala, and (2) the acquisition of aversive memory related to a stressful event. Male Wistar rats were implanted with guide cannulae to perform microdialysis and bilateral microinjections (0.5 μl/side) of the NMDA antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) (25 and 100 ng). Prefrontal injections were performed 60 min before restraint stress in microdialysis experiments, or training (footshock; 0.6 mA, 2 s) in inhibitory avoidance test. Retention latency was evaluated 24 h after training as an index of aversive memory. Acute stress increased amygdala dialysate concentrations of dopamine (160% of baseline), noradrenaline (145% of baseline) and corticosterone (170% of baseline). Prefrontal injections of CPP did not change the increases of dopamine, noradrenaline or corticosterone produced by stress. In contrast, CPP significantly reduced the retention latency in the inhibitory avoidance test. These results suggest that the hypofunction of prefrontal NMDA receptors does not change the sensitivity to acute stress of dopamine and noradrenaline projections to amygdala but impairs the acquisition of aversive memory.

  13. Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism

    Science.gov (United States)

    Barsegyan, Areg; Mackenzie, Scott M.; Kurose, Brian D.; McGaugh, James L.; Roozendaal, Benno

    2010-01-01

    It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions have generally been considered to be independently regulated processes. Here we report that a glucocorticoid receptor agonist administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and impairs working memory. Both memory effects are mediated by activation of a membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC to increase levels of cAMP-dependent protein kinase. These findings provide direct evidence that glucocorticoid effects on both memory consolidation and working memory share a common neural influence within the mPFC. PMID:20810923

  14. Fragmentation of the medial malleolus of dogs with and without tarsal osteochondrosis

    International Nuclear Information System (INIS)

    Newell, S.M.; Mahaffey, M.B.; Aron, D.N.

    1994-01-01

    Fragmentation of the medial malleolus of the tibia was found radiographically in 5 canine tarsi which did not have evidence of osteochondrosis of the medial trochlear ridge. An additional 5 tarsi were found where both medial malleolar fragmentation and osteochondrosis of the medial trochlear ridge were present. Radiographic evidence of degenerative joint disease was present in 3 of 5 dogs with medial malleolar fragmentation alone, and 5 of 5 dogs with medial malleolar fragmentation and medial trochlear ridge osteochondrosis. Eight of the 9 dogs were Rottweilers. Considering the sites of occurrence of osteochondrosis in other species, the authors propose that medial malleolar fragmentation could be secondary to osteochondrosis of the medial malleolus. Osteochondrosis of the medial malleolus has not been previously reported in dogs. Histological examination of the medial malleolar fragmentation was unavailable because surgery was not performed, therefore the hypothesis that the medial malleolar fragmentation is due to osteochondrosis was not proven

  15. Ventromedial prefrontal volume predicts understanding of others and social network size.

    Science.gov (United States)

    Lewis, Penelope A; Rezaie, Roozbeh; Brown, Rachel; Roberts, Neil; Dunbar, R I M

    2011-08-15

    Cognitive abilities such as Theory of Mind (ToM), and more generally mentalizing competences, are central to human sociality. Neuroimaging has associated these abilities with specific brain regions including temporo-parietal junction, superior temporal sulcus, frontal pole, and ventromedial prefrontal cortex. Previous studies have shown both that mentalizing competence, indexed as the ability to correctly understand others' belief states, is associated with social network size and that social group size is correlated with frontal lobe volume across primate species (the social brain hypothesis). Given this, we predicted that both mentalizing competences and the number of social relationships a person can maintain simultaneously will be a function of gray matter volume in these regions associated with conventional Theory of Mind. We used voxel-based morphometry of Magnetic Resonance Images (MRIs) to test this hypothesis in humans. Specifically, we regressed individuals' mentalizing competences and social network sizes against gray matter volume. This revealed that gray matter volume in bilateral posterior frontal pole and left temporoparietal junction and superior temporal sucus varies parametrically with mentalizing competence. Furthermore, gray matter volume in the medial orbitofrontal cortex and the ventral portion of medial frontal gyrus, varied parametrically with both mentalizing competence and social network size, demonstrating a shared neural basis for these very different facets of sociality. These findings provide the first fine-grained anatomical support for the social brain hypothesis. As such, they have important implications for our understanding of the constraints limiting social cognition and social network size in humans, as well as for our understanding of how such abilities evolved across primates. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Medial cortex activity, self-reflection and depression.

    Science.gov (United States)

    Johnson, Marcia K; Nolen-Hoeksema, Susan; Mitchell, Karen J; Levin, Yael

    2009-12-01

    Using functional magnetic resonance imaging, we investigated neural activity associated with self-reflection in depressed [current major depressive episode (MDE)] and healthy control participants, focusing on medial cortex areas previously shown to be associated with self-reflection. Both the MDE and healthy control groups showed greater activity in anterior medial cortex (medial frontal gyrus, anterior cingulate gyrus) when cued to think about hopes and aspirations compared with duties and obligations, and greater activity in posterior medial cortex (precuneus, posterior cingulate) when cued to think about duties and obligations (Experiment 1). However, the MDE group showed less activity than controls in the same area of medial frontal cortex when self-referential cues were more ambiguous with respect to valence (Experiment 2), and less deactivation in a non-self-referential condition in both experiments. Furthermore, individual differences in rumination were positively correlated with activity in both anterior and posterior medial cortex during non-self-referential conditions. These results provide converging evidence for a dissociation of anterior and posterior medial cortex depending on the focus of self-relevant thought. They also provide neural evidence consistent with behavioral findings that depression is associated with disruption of positively valenced thoughts in response to ambiguous cues, and difficulty disengaging from self-reflection when it is appropriate to do so.

  17. Episodic reinstatement in the medial temporal lobe.

    Science.gov (United States)

    Staresina, Bernhard P; Henson, Richard N A; Kriegeskorte, Nikolaus; Alink, Arjen

    2012-12-12

    The essence of episodic memory is our ability to reexperience past events in great detail, even in the absence of external stimulus cue