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Sample records for left medial prefrontal

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

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    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

  2. Optogenetic dissection of medial prefrontal cortex circuitry

    NARCIS (Netherlands)

    Riga, D.; Matos, R.M.; Glas, A.; Smit, A.B.; Spijker, S.; van den Oever, M.C.

    2014-01-01

    The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and

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

    Indian Academy of Sciences (India)

    The medial prefrontal cortex (mPFC) is implicated in anxiety-like behaviour. In rodent models, perturbations of mPFCneuronal activity through pharmacological manipulations, optogenetic activation of mPFC neurons or cell-type specificpharmacogenetic inhibition of somatostatin interneurons indicate conflicting effects on ...

  4. Optogenetic dissection of medial prefrontal cortex circuitry

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    Danai eRiga

    2014-12-01

    Full Text Available The medial prefrontal cortex (mPFC is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g. thalamus, striatum, amygdala and hippocampus, the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders.

  5. The role of the medial prefrontal cortex in achieving goals.

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    Matsumoto, Kenji; Tanaka, Keiji

    2004-04-01

    Achieving goals in changing environments requires the course of action to be selected on the basis of goal expectation and memory of action-outcome contingency. It is often also essential to evaluate action on the basis of immediate outcomes and the discrimination of early action steps from the final step towards the goal. Recently, in single-cell recordings in monkeys, the neuronal activity that appears to underlie these processes has been noted in the medial part of the prefrontal cortex. Medial prefrontal cells were also active when the subjects extracted the rules of a task in a novel environment. The processes described above might play important roles in rule learning.

  6. Dopaminergic Activity in the Medial Prefrontal Cortex Modulates Fear Conditioning

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    Parvin Babaei

    2011-07-01

    Full Text Available "nThe purpose of the present study was to determine the role of medial prefrontal cortex (mPFC dopaminergic system in fear conditioning response considering individual differences. Animals were initially counterbalanced and classified based on open field test, and then were given a single infusion of the dopamine agonist, amphetamine (AMPH and antagonist, clozapine (CLZ into the medial prefrontal cortex. Rats received tone-shock pairing in a classical fear conditioning test and then exposed to the tone alone. Freezing responses were measured as conditioned fear index. The results showed that both AMPH and CLZ infusion in mPFC reduced the expression of conditioned fear. This finding indicates that elevation or reduction in the dopaminergic activity is associated with the decrease of fear responses, despite preexisting individual-typological differences.

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

    DEFF Research Database (Denmark)

    Geday, Jacob; Gjedde, Albert

    2008-01-01

    significantly lowered blood flow (rCBF) in left IMPC, left and right insula, and right amygdala, and significantly raised blood flow in motor cortex and right precuneus. Restricted searches of rCBF changes by emotion, at coordinates of significant effect in previous studies of the medial prefrontal and temporal...... 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...

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

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    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. Behavioral effects of chronically elevated corticosterone in subregions of the medial prefrontal cortex.

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    Croteau, Joshua D; Schulkin, Jay; Shepard, Jack D

    2017-01-01

    The medial prefrontal cortex is a key mediator of behavioral aspects of the defense response. Since chronic exposure to elevated glucocorticoids alters the dendritic structure of neurons in the medial prefrontal cortex, such exposure may alter behavioral responses to danger as well. We examined the effects of chronically elevated corticosterone in discrete regions of the medial prefrontal cortex on exploration of the elevated plus-maze. Chronically elevated corticosterone in the prelimbic or infralimbic cortices reduced open arm exploration. This effect was specific to the ventral regions of the medial prefrontal cortex as corticosterone had no effect on plus-maze exploration when administered into the anterior cingulate cortex. Taken together, these findings demonstrate clear regional differences for the effects of corticosterone in the medial prefrontal cortex. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Role of the medial prefrontal cortex in coping and resilience.

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    Maier, Steven F; Watkins, Linda R

    2010-10-08

    The degree of behavioral control that an organism has over an aversive event is well known to modulate the behavioral and neurochemical consequences of exposure to the event. Here we review recent research that suggests that the experience of control over a potent stressor alters how the organism responds to future aversive events as well as to the stressor being controlled. More specifically, subjects that have experienced control show blunted behavioral and neurochemical responses to subsequent stressors occurring days to months later. Indeed, these subjects respond as if a later uncontrollable stressor is actually controllable. Further, we review research indicating that the stress resistance induced by control depends on control-induced activation of ventral medial prefrontal cortical (vmPFC) inhibitory control over brainstem and limbic structures. Furthermore, there appears to be plasticity in these circuits such that the experience of control alters the vmPFC in such a way that later uncontrollable stressors now activate the vmPFC circuitry, leading to inhibition of stress-responsive limbic and brainstem structures, i.e., stressor resistance. This controllability-induced proactive stressor resistance generalizes across very different stressors and may be involved in determining individual difference in reactions to traumatic events. Copyright © 2010 Elsevier B.V. All rights reserved.

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

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    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. Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex.

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    Glasper, Erica R; LaMarca, Elizabeth A; Bocarsly, Miriam E; Fasolino, Maria; Opendak, Maya; Gould, Elizabeth

    2015-11-01

    The medial prefrontal cortex is important for cognitive flexibility, a capability that is affected by environmental conditions and specific experiences. Aversive experience, such as chronic restraint stress, is known to impair performance on a task of cognitive flexibility, specifically attentional set-shifting, in rats. Concomitant with this performance decrement, chronic stress reduces the number of dendritic spines on pyramidal neurons in the medial prefrontal cortex. No previous studies have examined whether a rewarding experience, namely mating, affects cognitive flexibility and dendritic spines in the medial prefrontal cortex of male rats. To test this possibility, we exposed adult male rats to sexual receptive females once daily for one week, assessed attentional set-shifting performance, and then analyzed their brains for changes in dendritic spines. We found that sexual experience improved performance on extradimensional set-shifting, which is known to require the medial prefrontal cortex. Additionally, we observed increased dendritic spine density on apical and basal dendrites of pyramidal neurons in the medial prefrontal cortex, but not the orbitofrontal cortex, after sexual experience. We also found that sexual experience enhanced dendritic spine density on granule neurons of the dentate gyrus. The ventral hippocampus sends a direct projection to the medial prefrontal cortex, raising the possibility that experience-dependent changes in the hippocampus are necessary for alterations in medial prefrontal cortex structure and function. As a first attempt at investigating this, we inactivated the ventral hippocampus with the GABA agonist muscimol, after each daily bout of sexual experience to observe whether the beneficial effects on cognitive flexibility were abolished. Contrary to our hypothesis, blocking hippocampal activity after sexual experience had no impact on enhanced cognitive flexibility. Taken together, these findings indicate that sexual

  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. Segregation of the human medial prefrontal cortex in social cognition

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    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.

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

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    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

  16. Distinct Regions within Medial Prefrontal Cortex Process Pain and Cognition

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    Jahn, Andrew; Nee, Derek Evan; Alexander, William H.

    2016-01-01

    Neuroimaging studies of the medial prefrontal cortex (mPFC) suggest that the dorsal anterior cingulate cortex (dACC) region is responsive to a wide variety of stimuli and psychological states, such as pain, cognitive control, and prediction error (PE). In contrast, a recent meta-analysis argues that the dACC is selective for pain, whereas the supplementary motor area (SMA) and pre-SMA are specifically associated with higher-level cognitive processes (Lieberman and Eisenberger, 2015). To empirically test this claim, we manipulated effects of pain, conflict, and PE in a single experiment using human subjects. We observed a robust dorsal-ventral dissociation within the mPFC with cognitive effects of PE and conflict overlapping dorsally and pain localized more ventrally. Classification of subjects based on the presence or absence of a paracingulate sulcus showed that PE effects extended across the dorsal area of the dACC and into the pre-SMA. These results begin to resolve recent controversies by showing the following: (1) the mPFC includes dissociable regions for pain and cognitive processing; and (2) meta-analyses are correct in localizing cognitive effects to the dACC, although these effects extend to the pre-SMA as well. These results both provide evidence distinguishing between different theories of mPFC function and highlight the importance of taking individual anatomical variability into account when conducting empirical studies of the mPFC. SIGNIFICANCE STATEMENT Decades of neuroimaging research have shown the mPFC to represent a wide variety of stimulus processing and cognitive states. However, recently it has been argued whether distinct regions of the mPFC separately process pain and cognitive phenomena. To address this controversy, this study directly compared pain and cognitive processes within subjects. We found a double dissociation within the mPFC with pain localized ventral to the cingulate sulcus and cognitive effects localized more dorsally within

  17. A microdialysis study of the medial prefrontal cortex of adolescent and adult rats.

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    Staiti, Amanda M; Morgane, Peter J; Galler, Janina R; Grivetti, Janice Y; Bass, Donna C; Mokler, David J

    2011-09-01

    The medial prefrontal cortex (mPFC) of the rat has become a key focus of studies designed to elucidate the basis of behavior involving attention and decision-making, i.e. executive functions. The adolescent mPFC is of particular interest given the role of the mPFC in impulsivity and attention, and disorders such as attentional deficit disorder. In the present study we have examined the basal extracellular concentrations of the neurotransmitters 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the ventral portion of the mPFC (vmPFC) in both adolescent (post-natal day 45-50) and adult, and male and female rats using in vivo microdialysis. We have also examined both the left and right vmPFCs given reports of laterality in function between the hemispheres. Basal extracellular concentrations of 5-HT differed significantly between male and female rats. Extracellular DA also differed significantly between male and female rats and between the left and the right vmPFC in adult males. No differences were seen in basal extracellular NE. There was a significant age difference between groups in the laterality of extracellular NE levels between right and left vmPFC. Infusion of 100 μM methamphetamine through the dialysis probe increased the extracellular concentration of all the monoamines although there were no differences between groups in methamphetamine stimulated release. The findings from this study demonstrate that there are differences in monoaminergic input to the mPFC of the rat based on age, gender and hemisphere. This work sets the neurochemical baseline for further investigations of the prefrontal cortex during development. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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    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. Medial Prefrontal Cortex Is Selectively Involved in Response Selection Using Visual Context in the Background

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    Lee, Inah; Shin, Ji Yun

    2012-01-01

    The exact roles of the medial prefrontal cortex (mPFC) in conditional choice behavior are unknown and a visual contextual response selection task was used for examining the issue. Inactivation of the mPFC severely disrupted performance in the task. mPFC inactivations, however, did not disrupt the capability of perceptual discrimination for visual…

  20. Attention, Emotion, and Deactivation of Default Activity in Inferior Medial Prefrontal Cortex

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    Geday, Jacob; Gjedde, Albert

    2009-01-01

    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…

  1. Hippocampus and Medial Prefrontal Cortex Contributions to Trace and Contextual Fear Memory Expression over Time

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    Beeman, Christopher L.; Bauer, Philip S.; Pierson, Jamie L.; Quinn, Jennifer J.

    2013-01-01

    Previous work has shown that damage to the dorsal hippocampus (DH) occurring at recent, but not remote, timepoints following acquisition produces a deficit in trace conditioned fear memory expression. The opposite pattern has been observed with lesions to the medial prefrontal cortex (mPFC). The present studies address: (1) whether these lesion…

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

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

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    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…

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

    NARCIS (Netherlands)

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

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

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    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.

  6. Brain Rewarding Stimulation Reduces Extracellular Glutamate Through Glial Modulation in Medial Prefrontal Cortex of Rats.

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    Murakami, Gen; Nakamura, Masato; Takita, Masatoshi; Ishida, Yasushi; Ueki, Takatoshi; Nakahara, Daiichiro

    2015-11-01

    Growing evidence implicates a critical involvement of prefrontal glial modulation of extracellular glutamate (GLU) in aversive behaviors. However, nothing is known about whether prefrontal glial cells modulate GLU levels in rewarding behaviors. To address this question, we measured GLU efflux in the medial prefrontal cortex (PFC) of rats associated with rewarding behaviors. We used intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB) as the rewarding behavior. GLU was indirectly measured using microdialysis combined with on-line fluorometric detection of NADH resulting from the reaction of GLU and NAD(+) catalyzed by GLU dehydrogenase with a time resolution of 1 min. ICSS caused a minute-by-minute change of extracellular GLU in the medial PFC, with a slight decrease during the stimulation, followed by an increase afterward. This bidirectional change was tetrodotoxin insensitive and abolished by the gliotoxin fluorocitrate. To confirm and extend the previous studies of aversion-induced increase of extracellular GLU in the medial PFC, we also measured prefrontal GLU efflux associated with an aversive stimulation, immobilization stress. The temporal change in extracellular GLU caused by this stress was markedly different from that observed during ICSS. A rapid increase in GLU was detected during the aversive stimulation, followed by a large increase afterward. This bimodal change was tetrodotoxin insensitive, similar to that detected for ICSS. These findings indicate a bidirectional regulation of extracellular GLU by prefrontal glial cells associated with rat ICSS behavior, and reveal that glial modulation of GLU neurochemistry in the medial PFC contributes to rewarding as well as aversive behaviors in rats.

  7. Too Little and Too Much: Hypoactivation and Disinhibition of Medial Prefrontal Cortex Cause Attentional Deficits

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    McGarrity, Stephanie; Mason, Rob; Fone, Kevin C.

    2014-01-01

    Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis

  8. Representation of Behavioral Tactics and Tactics-Action Transformation in the Primate Medial Prefrontal Cortex.

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    Matsuzaka, Yoshiya; Tanji, Jun; Mushiake, Hajime

    2016-06-01

    To expedite the selection of action under a structured behavioral context, we develop an expedient to promote its efficiency: tactics for action selection. Setting up a behavioral condition for subhuman primates (Macaca fuscata) that induced the development of a behavioral tactics, we explored neuronal representation of tactics in the medial frontal cortex. Here we show that neurons in the posterior medial prefrontal cortex, but not much in the medial premotor cortex, exhibit activity representing the behavioral tactics, in advance of action-selective activity. Such activity appeared during behavioral epochs of its retrieval from instruction cues, maintenance in short-term memory, and its implementation for the achievement of action selection. At a population level, posterior medial prefrontal cortex neurons take part in transforming the tactics information into the information representing action selection. The tactics representation revealed an aspect of neural mechanisms for an adaptive behavioral control, taking place in the medial prefrontal cortex. We studied behavioral significance of neuronal activity in the posterior medial prefrontal cortex (pmPFC) and found the representation of behavioral tactics defined as specific and efficient ways to achieve objectives of actions. Neuronal activity appeared during behavioral epochs of its retrieval from instruction cues, maintenance in short-term memory, and its use preceding the achievement of action selection. We found further that pmPFC neurons take part in transforming the tactics information into the information representing action selection. A majority of individual neurons was recruited during a limited period in each behavioral epoch, constituting, as a whole, a temporal cascade of activity. Such dynamics found in behavioral-tactics specific activity characterize the participation of pmPFC neurons in executive control of purposeful behavior. Copyright © 2016 the authors 0270-6474/16/365974-14$15.00/0.

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

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    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.

  10. Dorsal Raphe Nucleus Down-Regulates Medial Prefrontal Cortex during Experience of Flow

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    Martin Ulrich

    2016-09-01

    Full Text Available Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus, and relative activation decreases of the medial prefrontal cortex and of the amygdala. In the present study, Dynamic Causal Modeling (DCM was used to explore effective connectivity between those brain regions. To test our hypothesis that the dorsal raphe nucleus causally down-regulates activity of the medial prefrontal cortex and/or of the amygdala, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A flow condition, with task demands automatically balanced with participants’ skill level, was compared with conditions of boredom and overload. DCM models were constructed modeling full reciprocal endogenous connections between the dorsal raphe nucleus, the medial prefrontal cortex, the amygdala, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the dorsal raphe nucleus, the medial prefrontal cortex, and the amygdala, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection was applied to identify a possible winning family (and model. Although Bayesian Model Selection revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the dorsal raphe nucleus on the medial prefrontal cortex when

  11. Insensitive parenting may accelerate the development of the amygdala-medial prefrontal cortex circuit.

    Science.gov (United States)

    Thijssen, Sandra; Muetzel, Ryan L; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Tiemeier, Henning; Verhulst, Frank C; White, Tonya; Van Ijzendoorn, Marinus H

    2017-05-01

    This study examined whether the association between age and amygdala-medial prefrontal cortex (mPFC) connectivity in typically developing 6- to 10-year-old children is correlated with parental care. Resting-state functional magnetic resonance imaging scans were acquired from 124 children of the Generation R Study who at 4 years old had been observed interacting with their parents to assess maternal and paternal sensitivity. Amygdala functional connectivity was assessed using a general linear model with the amygdalae time series as explanatory variables. Higher level analyses assessing Sensitivity × Age as well as exploratory Sensitivity × Age × Gender interaction effects were performed restricted to voxels in the mPFC. We found significant Sensitivity × Age interaction effects on amygdala-mPFC connectivity. Age was related to stronger amygdala-mPFC connectivity in children with a lower combined parental sensitivity score (b = 0.11, p = .004, b = 0.06, p = .06, right and left amygdala, respectively), but not in children with a higher parental sensitivity score, (b = -0.07, p = .12, b = -0.06, p = .12, right and left amygdala, respectively). A similar effect was found for maternal sensitivity, with stronger amygdala-mPFC connectivity in children with less sensitive mothers. Exploratory (parental, maternal, paternal) Sensitivity × Age × Gender interaction analyses suggested that this effect was especially pronounced in girls. Amygdala-mPFC resting-state functional connectivity has been shown to increase from age 10.5 years onward, implying that the positive association between age and amygdala-mPFC connectivity in 6- to 10-year-old children of less sensitive parents represents accelerated development of the amygdala-mPFC circuit.

  12. Neural mechanisms of economic commitment in the human medial prefrontal cortex.

    Science.gov (United States)

    Tsetsos, Konstantinos; Wyart, Valentin; Shorkey, S Paul; Summerfield, Christopher

    2014-10-21

    Neurobiologists have studied decisions by offering successive, independent choices between goods or gambles. However, choices often have lasting consequences, as when investing in a house or choosing a partner. Here, humans decided whether to commit (by acceptance or rejection) to prospects that provided sustained financial return. BOLD signals in the rostral medial prefrontal cortex (rmPFC) encoded stimulus value only when acceptance or rejection was deferred into the future, suggesting a role in integrating value signals over time. By contrast, the dorsal anterior cingulate cortex (dACC) encoded stimulus value only when participants rejected (or deferred accepting) a prospect. dACC BOLD signals reflected two decision biases-to defer commitments to later, and to weight potential losses more heavily than gains-that (paradoxically) maximised reward in this task. These findings offer fresh insights into the pressures that shape economic decisions, and the computation of value in the medial prefrontal cortex.

  13. Hyperconnectivity and slow synapses during early development of medial prefrontal cortex in a mouse model for mental retardation and autism

    NARCIS (Netherlands)

    Testa-Silva, G.; Loebel, A.; Giugliano, M.; de Kock, C.P.J.; Mansvelder, H.D.; Meredith, R.M.

    2012-01-01

    Neuronal theories of neurodevelopmental disorders (NDDs) of autism and mental retardation propose that abnormal connectivity underlies deficits in attentional processing. We tested this theory by studying unitary synaptic connections between layer 5 pyramidal neurons within medial prefrontal cortex

  14. 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

  15. Repeated exposure to morphine alters surface expression of AMPA receptors in the rat medial prefrontal cortex.

    Science.gov (United States)

    Mickiewicz, Amanda L; Napier, T Celeste

    2011-01-01

    Behavioral sensitization describes the intensification of motor activity that results from repeated exposure to drugs of misuse, and the underlying neuronal adaptations are hypothesized to model aspects of the brain changes that occur in humans misusing such drugs. The α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor is an ionotropic glutamate receptor involved in the neuroplasticity that accompanies acute and repeated drug administration. Changing surface expression is one means to regulate AMPA receptor function, and the present study tested the hypothesis that behavioral sensitization to the μ-opioid receptor agonist morphine is accompanied by changes in the subcellular distribution of AMPA receptors in limbic brain regions. To test this hypothesis, we used a protein cross-linking assay to assess cell surface and intracellular levels of GluA1 and GluA2 subunits in the nucleus accumbens, medial prefrontal cortex and ventral pallidum. Repeated morphine treatment decreased surface expression of GluA1 in the medial prefrontal cortex without affecting levels of GluA2. In contrast, surface levels of GluA1 or GluA2 were unchanged in the nucleus accumbens and ventral pallidum, demonstrating that although AMPA receptors in accumbal and pallidal regions are critical mediators of behaviors induced by repeated opiate exposure, these effects are not accompanied by changes in surface expression. The findings reveal that the involvement of AMPA receptor trafficking in opiate-induced behavioral sensitization is relegated to selective regions and that AMPA receptors in the medial prefrontal cortex may be particularly sensitive to these actions. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  16. 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.

  17. A Microdialysis Study of the Medial Prefrontal Cortex of Adolescent and Adult Rats

    OpenAIRE

    Staiti, Amanda M.; Morgane, Peter J.; Galler, Janina R.; Grivetti, Janice Y.; Bass, Donna C.; Mokler, David J.

    2011-01-01

    The medial prefrontal cortex (mPFC) of the rat has become a key focus of studies designed to elucidate the basis of behavior involving attention and decision making, i.e. executive functions. The adolescent mPFC is of particular interest given the role of the mPFC in impulsivity and attention, and disorders such as attentional deficit disorder. In the present study we have examined the basal extracellular concentrations of the neurotransmitters 5-hydroxytryptamine (5-HT), dopamine (DA) and no...

  18. Structured event complexes in the medial prefrontal cortex support counterfactual representations for future planning.

    Science.gov (United States)

    Barbey, Aron K; Krueger, Frank; Grafman, Jordan

    2009-05-12

    We propose that counterfactual representations for reasoning about the past or predicting the future depend on structured event complexes (SECs) in the human prefrontal cortex (PFC; 'What would happen if X were performed in the past or enacted in the future?'). We identify three major categories of counterfactual thought (concerning action versus inaction, the self versus other and upward versus downward thinking) and propose that each form of inference recruits SEC representations in distinct regions of the medial PFC. We develop a process model of the regulatory functions these representations serve and draw conclusions about the importance of SECs for explaining the past and predicting the future.

  19. 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.

  20. 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.

  1. White matter integrity between left basal ganglia and left prefrontal cortex is compromised in gambling disorder.

    Science.gov (United States)

    van Timmeren, Tim; Jansen, Jochem M; Caan, Matthan W A; Goudriaan, Anna E; van Holst, Ruth J

    2017-11-01

    Pathological gambling (PG) is a behavioral addiction characterized by an inability to stop gambling despite the negative consequences, which may be mediated by cognitive flexibility deficits. Indeed, impaired cognitive flexibility has previously been linked to PG and also to reduced integrity of white matter connections between the basal ganglia and the prefrontal cortex. It remains unclear, however, how white matter integrity problems relate to cognitive inflexibility seen in PG. We used a cognitive switch paradigm during functional magnetic resonance imaging in pathological gamblers (PGs; n = 26) and healthy controls (HCs; n = 26). Cognitive flexibility performance was measured behaviorally by accuracy and reaction time on the switch task, while brain activity was measured in terms of blood oxygen level-dependent responses. We also used diffusion tensor imaging on a subset of data (PGs = 21; HCs = 21) in combination with tract-based spatial statistics and probabilistic fiber tracking to assess white matter integrity between the basal ganglia and the dorsolateral prefrontal cortex. Although there were no significant group differences in either task performance, related neural activity or tract-based spatial statistics, PGs did show decreased white matter integrity between the left basal ganglia and prefrontal cortex. Our results complement and expand similar findings from a previous study in alcohol-dependent patients. Although we found no association between white matter integrity and task performance here, decreased white matter connections may contribute to a diminished ability to recruit prefrontal networks needed for regulating behavior in PG. Hence, our findings could resonate an underlying risk factor for PG, and we speculate that these findings may extend to addiction in general. © 2016 Society for the Study of Addiction.

  2. Inhibitory modulation of medial prefrontal cortical activation on lateral orbitofrontal cortex-amygdala information flow.

    Science.gov (United States)

    Chang, Chun-Hui; Ho, Ta-Wen

    2017-09-01

    The basolateral complex of the amygdala (BLA) receives input from the lateral orbitofrontal cortex (lOFC) for cue-outcome contingencies and the medial prefrontal cortex (mPFC) for emotion control. Here we examined how the mPFC modulates lOFC-BLA information flow. We found that the majority of BLA neurons responsive to lOFC stimulation were also responsive to mPFC stimulation. Activation of the mPFC exerted an inhibitory modulation of the lOFC-BLA pathway, which was reversed with intra-amygdala blockade of GABAergic receptors. mPFC tetanus potentiated the lOFC-BLA pathway, but did not alter its inhibitory modulatory gating. These results show that the mPFC potently inhibits lOFC drive of the BLA in a GABA-dependent manner, which is informative in understanding the normal and potential pathophysiological state of emotion and contingency associations in regulating behaviour. Several neocortical projections converge onto the basolateral complex of the amygdala (BLA), including the lateral orbitofrontal cortex (lOFC) and the medial prefrontal cortex (mPFC). Lateral orbitofrontal input to the BLA is important for cue-outcome contingencies, while medial prefrontal input is essential for emotion control. In this study, we examined how the mPFC, specifically the infralimbic division of the mPFC, modulates lOFC-BLA information flow, using combined in vivo extracellular single-unit recordings and pharmacological manipulations in anaesthetized rats. We found that the majority (over 95%) of BLA neurons that responded to lOFC stimulation also responded to mPFC stimulation. Compared to basal condition, pharmacological (N-methyl-d-aspartate) or electrical activation of the mPFC exerted an inhibitory modulation of the lOFC-BLA pathway, which was reversed with intra-amygdala blockade of GABAergic receptors with combined GABA A and GABA B antagonists (bicuculline and saclofen). Moreover, mPFC tetanus potentiated the lOFC-BLA pathway, but mPFC tetanus or low-frequency stimulation did

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

    Directory of Open Access Journals (Sweden)

    María Carolina Gonzalez

    2014-11-01

    Full Text Available 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-tem aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 hour 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.

  4. Medial prefrontal activity during delay period contributes to learning of a working memory task.

    Science.gov (United States)

    Liu, Ding; Gu, Xiaowei; Zhu, Jia; Zhang, Xiaoxing; Han, Zhe; Yan, Wenjun; Cheng, Qi; Hao, Jiang; Fan, Hongmei; Hou, Ruiqing; Chen, Zhaoqin; Chen, Yulei; Li, Chengyu T

    2014-10-24

    Cognitive processes require working memory (WM) that involves a brief period of memory retention known as the delay period. Elevated delay-period activity in the medial prefrontal cortex (mPFC) has been observed, but its functional role in WM tasks remains unclear. We optogenetically suppressed or enhanced activity of pyramidal neurons in mouse mPFC during the delay period. Behavioral performance was impaired during the learning phase but not after the mice were well trained. Delay-period mPFC activity appeared to be more important in memory retention than in inhibitory control, decision-making, or motor selection. Furthermore, endogenous delay-period mPFC activity showed more prominent modulation that correlated with memory retention and behavioral performance. Thus, properly regulated mPFC delay-period activity is critical for information retention during learning of a WM task. Copyright © 2014, American Association for the Advancement of Science.

  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. Mental calculation in a prodigy is sustained by right prefrontal and medial temporal areas.

    Science.gov (United States)

    Pesenti, M; Zago, L; Crivello, F; Mellet, E; Samson, D; Duroux, B; Seron, X; Mazoyer, B; Tzourio-Mazoyer, N

    2001-01-01

    Calculating prodigies are individuals who are exceptional at quickly and accurately solving complex mental calculations. With positron emission tomography (PET), we investigated the neural bases of the cognitive abilities of an expert calculator and a group of non-experts, contrasting complex mental calculation to memory retrieval of arithmetic facts. We demonstrated that calculation expertise was not due to increased activity of processes that exist in non-experts; rather, the expert and the non-experts used different brain areas for calculation. We found that the expert could switch between short-term effort-requiring storage strategies and highly efficient episodic memory encoding and retrieval, a process that was sustained by right prefrontal and medial temporal areas.

  7. 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

  8. Lesions of the medial prefrontal cortex cause maladaptive sexual behavior in male rats.

    Science.gov (United States)

    Davis, Jon F; Loos, Maarten; Di Sebastiano, Andrea R; Brown, Jennifer L; Lehman, Michael N; Coolen, Lique M

    2010-06-15

    An inability to inhibit behaviors once they become maladaptive is a component of several psychiatric illnesses, and the medial prefrontal cortex (mPFC) was identified as a potential mediator of behavioral inhibition. The current study tested if the mPFC is involved in inhibition of sexual behavior when associated with aversive outcomes. Using male rats, effects of lesions of the infralimbic and prelimbic areas of the mPFC on expression of sexual behavior and ability to inhibit mating were tested using a paradigm of copulation-contingent aversion. Medial prefrontal cortex lesions did not alter expression of sexual behavior. In contrast, mPFC lesions completely blocked the acquisition of sex-aversion conditioning and lesioned animals continued to mate, in contrast to the robust behavioral inhibition toward copulation in mPFC intact male animals, resulting in only 22% of intact male animals continuing to mate. However, rats with mPFC lesions were capable of forming a conditioned place preference to sexual reward and conditioned place aversion for lithium chloride, suggesting that these lesions did not alter associative learning or sensitivity for lithium chloride. The current study indicates that animals with mPFC lesions are likely capable of forming the associations with aversive outcomes of their behavior but lack the ability to suppress seeking of sexual reward in the face of aversive consequences. These data may contribute to a better understanding of a common pathology underlying impulse control disorders, as compulsive sexual behavior has a high prevalence of comorbidity with psychiatric disorders and Parkinson's disease.

  9. Dopamine and noradrenaline efflux in the medial prefrontal cortex during serial reversals and extinction of instrumental goal-directed behavior

    NARCIS (Netherlands)

    van der Meulen, Jamilja A. J.; Joosten, Ruud N. J. M. A.; de Bruin, Jan P. C.; Feenstra, Matthijs G. P.

    2007-01-01

    The prefrontal cortex (PFC) of the rat supports cognitive flexibility, the ability to spontaneously adapt goal-directed behavior in response to radically changing situational demands. We have shown previously that transient inactivation of the rat medial PFC (mPFC) impairs initial reversal learning

  10. The noradrenaline-dopamine interaction in the rat medial prefrontal cortex studied by multi-probe microdialysis

    NARCIS (Netherlands)

    Kawahara, H; Kawahara, Y; Westerink, BHC

    2001-01-01

    Multi-probe microdialysis was used to investigate the interaction between the release of noradrenaline and dopamine in the medial prefrontal cortex. Retrograde microdialysis was used to stimulate or inhibit the activity of the locus coeruleus for a restricted period of time, and the response of

  11. Temporal Dynamics of Acute Stress-Induced Dendritic Remodeling in Medial Prefrontal Cortex and the Protective Effect of Desipramine

    DEFF Research Database (Denmark)

    Nava, Nicoletta; Treccani, Giulia; Alabsi, Abdelrahman

    2017-01-01

    Stressful events are associated with increased risk of mood disorders. Volumetric reductions have been reported in brain areas critical for the stress response, such as medial prefrontal cortex (mPFC), and dendritic remodeling has been proposed as an underlying factor. Here, we investigated...

  12. Endocannabinoids produced upon action potential firing evoke a Cl− current via type-2 cannabinoid receptors in the medial prefrontal cortex

    NARCIS (Netherlands)

    den Boon, F.S.; Chameau, P.; Houthuijs, K.; Bolijn, S.; Mastrangelo, N.; Kruse, C.G.; Maccarrone, M.; Wadman, W.J.; Werkman, T.R.

    2014-01-01

    The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide

  13. Role of the Ventral Medial Prefrontal Cortex in Mediating Behavioral Control-Induced Reduction of Later Conditioned Fear

    Science.gov (United States)

    Baratta, Michael V.; Lucero, Thomas R.; Amat, Jose; Watkins, Linda R.; Maier, Steven F.

    2008-01-01

    A prior experience of behavioral control over a stressor interferes with subsequent Pavlovian fear conditioning, and this effect is dependent on the activation of the ventral medial prefrontal cortex (mPFCv) at the time of the initial experience with control. It is unknown whether mPFCv activity is necessary during fear learning and/or testing for…

  14. The role of catecholamine innervation in the medial prefrontal cortex on the regulation of body weight and food intake.

    Science.gov (United States)

    Gálosi, Rita; Hajnal, Andras; Petykó, Zoltán; Hartmann, Géza; Karádi, Zoltán; Lénárd, László

    2015-06-01

    Effects of 6-hydroxydopamine (6-OHDA) lesions in the medial prefrontal cortex with or without protection of norepinephrine (NE) fibers were examined on basic regulatory processes of feeding. Daily body weight, food and water intake were measured. Locomotor activity, ingestion after food or water deprivation, and preference for 5% and 10% glucose solution were examined. Dopamine (DA) and NE content, as well as, tyrosine hydroxylase immunoreactivity were assessed to confirm the neurotoxic effect of treatments. 6-OHDA lesions of the medial prefrontal cortex with or without NE fiber protection resulted in body weight loss. Diminished habituation in open field tests, i.e. a persistently high motor activity, was also observed. Application of 6-OHDA with NE fiber protection led to increased food consumption following food-deprivation and to enhanced glucose preference. Enhanced intake of 10% over 5% glucose solution was also detected. 6-OHDA lesion resulted in a decrease to 20% of NE tissue concentration and only to 75% of DA concentration. In case of lesion with NE protection the NE content decreased to 69% and DA level to 51% with significant loss of tyrosine hydroxylase positive fibers in the deeper layers of the medial prefrontal cortex. DA depletion in the medial prefrontal cortex resulted in increased behavioral responsiveness to hunger and glucose, as well as, to open field environment. Pronounced lesion of NE terminals caused increased reaction to the environment in open field but not to hunger or glucose solution. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Trace and Contextual Fear Conditioning Require Neural Activity and NMDA Receptor-Dependent Transmission in the Medial Prefrontal Cortex

    Science.gov (United States)

    Gilmartin, Marieke R.; Helmstetter, Fred J.

    2010-01-01

    The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a…

  16. Transcription profile of aging and cognition-related genes in the medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Lara eIanov

    2016-05-01

    Full Text Available Cognitive function depends on transcription; however, there is little information linking altered gene expression to impaired prefrontal cortex function during aging. Young and aged F344 rats were characterized on attentional set shift and spatial memory tasks. Transcriptional differences associated with age and cognition were examined using RNA sequencing to construct transcriptomic profiles for the medial prefrontal cortex (mPFC, white matter, and region CA1 of the hippocampus. The results indicate regional differences in vulnerability to aging. Age-related gene expression in the mPFC was similar to, though less robust than, that in the dorsolateral PFC of aging humans suggesting that aging processes may be similar. Importantly, the pattern of transcription associated with aging did not predict cognitive decline. Rather, increased mPFC expression of genes involved in regulation of transcription, including transcription factors that regulate the strength of excitatory and inhibitory inputs, and neural activity-related immediate-early genes was observed in aged animals that exhibit delayed set shift behavior. The specificity of impairment on a mPFC-dependent task, associated with a particular mPFC transcriptional profile indicates that impaired executive function involves altered transcriptional regulation and neural activity/plasticity processes that are distinct from that described for impaired hippocampal function.

  17. Medial prefrontal and anterior insular connectivity in early schizophrenia and major depressive disorder: a resting functional MRI evaluation of large-scale brain network models

    Directory of Open Access Journals (Sweden)

    Jacob ePenner

    2016-03-01

    Full Text Available Anomalies in the medial prefrontal cortex, anterior insulae and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD. In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed-based, 3 Tesla resting state functional MRI analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with schizophrenia compared to controls while patients with MDD had reduced connectivity between the medial prefrontal cortex and ventral prefrontal emotional encoding regions compared to controls. Reduced connectivity was found between the anterior insulae and the medial prefrontal cortex in schizophrenia compared to controls, but contrary to some models emotion processing regions failed to demonstrate increased connectivity with the medial prefrontal cortex in MDD compared to controls. Although not statistically significant after correction for multiple comparisons, patients with schizophrenia tended to demonstrate decreased connectivity between basal ganglia-thalamocortical regions and the medial prefrontal cortex compared to patients with MDD, which might be expected as these regions effect action. Results were interpreted to support anomalies in nodes associated with directed effort in schizophrenia and nodes associated with emotional encoding network in MDD compared to healthy controls.

  18. Refinement of neuronal synchronization with gamma oscillations in the medial prefrontal cortex after adolescence.

    Directory of Open Access Journals (Sweden)

    Julián de Almeida

    Full Text Available The marked anatomical and functional changes taking place in the medial prefrontal cortex (PFC during adolescence set grounds for the high incidence of neuropsychiatric disorders with adolescent onset. Although circuit refinement through synapse pruning may constitute the anatomical basis for the cognitive differences reported between adolescents and adults, a physiological correlate of circuit refinement at the level of neuronal ensembles has not been demonstrated. We have recorded neuronal activity together with local field potentials in the medial PFC of juvenile and adult mice under anesthesia, which allowed studying local functional connectivity without behavioral or sensorial interference. Entrainment of pyramidal neurons and interneurons to gamma oscillations, but not to theta or beta oscillations, was reduced after adolescence. Interneurons were synchronized to gamma oscillations across a wider area of the PFC than pyramidal neurons, and the span of interneuron synchronization was shorter in adults than juvenile mice. Thus, transition from childhood to adulthood is characterized by reduction of the strength and span of neuronal synchronization specific to gamma oscillations in the mPFC. The more restricted and weak ongoing synchronization in adults may allow a more dynamic rearrangement of neuronal ensembles during behavior and promote parallel processing of information.

  19. Sodium fluoride does not affect the working memory and number of pyramidal cells in rat medial prefrontal cortex.

    Science.gov (United States)

    Pulungan, Zulhaini Sartika A; Sofro, Zaenal Muttaqien; Partadiredja, Ginus

    2018-01-01

    Fluoride is a chemical compound known to bring about fluorosis. It is thought to disrupt the central nervous system because of its ability to induce excitotoxicity and oxidative stress. Any damage of pyramidal cells in the prefrontal cortex would result in cognitive function and working memory regulation disorders. The present study aimed at investigating the effects of sodium fluoride (NaF) on the working memory and estimated total number of medial prefrontal cortex pyramidal cells of adult male rats. Thirty-two male Wistar rats were assigned into four groups, namely control and three treated groups receiving 5, 10 and 20 mg/kg BW, respectively, of oral NaF solution for 30 days. The working memory test was carried out using a Y-maze. The number of pyramidal cells in the medial prefrontal cortex was estimated using an unbiased stereological method. There was no significant difference among groups in the working memory and number of pyramidal neurons in the medial prefrontal cortex cells.

  20. 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.

  1. Subcellular Localization and Activity of TRPM4 in Medial Prefrontal Cortex Layer 2/3

    Science.gov (United States)

    Riquelme, Denise; Silva, Ian; Philp, Ashleigh M.; Huidobro-Toro, Juan P.; Cerda, Oscar; Trimmer, James S.; Leiva-Salcedo, Elias

    2018-01-01

    TRPM4 is a Ca2+-activated non-selective cationic channel that conducts monovalent cations. TRPM4 has been proposed to contribute to burst firing and sustained activity in several brain regions, however, the cellular and subcellular pattern of TRPM4 expression in medial prefrontal cortex (mPFC) during postnatal development has not been elucidated. Here, we use multiplex immunofluorescence labeling of brain sections to characterize the postnatal developmental expression of TRPM4 in the mouse mPFC. We also performed electrophysiological recordings to correlate the expression of TRPM4 immunoreactivity with the presence of TRPM4-like currents. We found that TRPM4 is expressed from the first postnatal day, with expression increasing up to postnatal day 35. Additionally, in perforated patch clamp experiments, we found that TRPM4-like currents were active at resting membrane potentials at all postnatal ages studied. Moreover, TRPM4 is expressed in both pyramidal neurons and interneurons. TRPM4 expression is localized in the soma and proximal dendrites, but not in the axon initial segment of pyramidal neurons. This subcellular localization is consistent with a reduction in the basal current only when we locally perfused 9-Phenanthrol in the soma, but not upon perfusion in the medial or distal dendrites. Our results show a specific localization of TRPM4 expression in neurons in the mPFC and that a 9-Phenanthrol sensitive current is active at resting membrane potential, suggesting specific functional roles in mPFC neurons during postnatal development and in adulthood. PMID:29440991

  2. 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.

  3. Investing in the future: stimulation of the medial prefrontal cortex reduces discounting of delayed rewards.

    Science.gov (United States)

    Cho, Sang Soo; Koshimori, Yuko; Aminian, Kelly; Obeso, Ignacio; Rusjan, Pablo; Lang, Anthony E; Daskalakis, Zafiris J; Houle, Sylvain; Strafella, Antonio P

    2015-02-01

    Generally, rewards that are received sooner are often preferred over future rewards, and the time between the choice and the reception of the reward is an important factor that influences our decisions, a phenomenon called delay discounting (DD). In DD, the medial prefrontal cortex (MePFC) and striatal dopamine neurotransmission both play an important role. We used repetitive transcranial magnetic stimulation (rTMS) to transiently activate the MePFC to evaluate its behavioral effect on the DD paradigm, and subsequently to measure its effect on striatal dopamine. Twenty-four right-handed young healthy subjects (11 females; age: 22.1±2.9 years) underwent DD following 10 Hz-rTMS of the MePFC and vertex stimulation (control condition). Thereafter, 11 subjects (5 females; age: 22.2±2.87 years) completed the PET study at rest using [(11)C]-(+)-PHNO following 10 Hz-rTMS of the MePFC and vertex. Modulation of the MePFC excitability influenced the subjective level of DD for delayed rewards and interfered with synaptic dopamine level in the striatum. The present study yielded findings that might reconcile the role of these areas in inter-temporal decision making and dopamine modulation, suggesting that the subjective sense of time and value of reward are critically controlled by these important regions.

  4. 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.

  5. 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

  6. Transcranial direct current stimulation of the medial prefrontal cortex dampens mind-wandering in men.

    Science.gov (United States)

    Bertossi, Elena; Peccenini, Ludovica; Solmi, Andrea; Avenanti, Alessio; Ciaramelli, Elisa

    2017-12-05

    Mind-wandering, the mind's capacity to stray from external events and generate task-unrelated thought, has been associated with activity in the brain default network. To date, little is understood about the contribution of individual nodes of this network to mind-wandering. Here, we investigated the role of medial prefrontal cortex (mPFC) in mind-wandering, by perturbing this region with transcranial direct current stimulation (tDCS). Young healthy participants performed a choice reaction time task both before and after receiving cathodal tDCS over mPFC, and had their thoughts periodically sampled. We found that tDCS over mPFC - but not occipital or sham tDCS - decreased the propensity to mind-wander. The tDCS-induced reduction in mind-wandering occurred in men, but not in women, and was accompanied by a change in the content of task-unrelated though, which became more related to other people (as opposed to the self) following tDCS. These findings indicate that mPFC is crucial for mind-wandering, possibly by helping construction of self-relevant scenarios capable to divert attention inward, away from perceptual reality. Gender-related differences in tDCS-induced changes suggest that mPFC controls mind-wandering differently in men and women, which may depend on differences in the structural and functional organization of distributed brain networks governing mind-wandering, including mPFC.

  7. 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.

  8. In search of integrative processes: basic psychological need satisfaction predicts medial prefrontal activation during decisional conflict.

    Science.gov (United States)

    Di Domenico, Stefano I; Fournier, Marc A; Ayaz, Hasan; Ruocco, Anthony C

    2013-08-01

    Research has shown that people's abilities to develop and act from a coherent sense of self are facilitated by satisfaction of the basic psychological needs for competence, relatedness, and autonomy. The present study utilized functional near infrared spectroscopy (fNIRS) to examine the effect of need satisfaction on activity in the medial prefrontal cortex (MPFC), a key region in processing information about the self. Participants completed a decision-making task (e.g., Which occupation would you prefer, dancer or chemist?) in which they made a series of forced choices according to their personal preferences. The degree of decisional conflict (i.e., choice difficulty) between the available response options was manipulated on the basis of participants' unique preference ratings for the target stimuli, which were obtained prior to scanning. Need satisfaction predicted elevated MPFC activity during high-conflict relative to low-conflict situations, suggesting that one way need satisfaction may promote self-coherence is by enhancing the utilization of self-knowledge in the resolution of decisional conflicts. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  9. Neuroadaptive technology enables implicit cursor control based on medial prefrontal cortex activity.

    Science.gov (United States)

    Zander, Thorsten O; Krol, Laurens R; Birbaumer, Niels P; Gramann, Klaus

    2016-12-27

    The effectiveness of today's human-machine interaction is limited by a communication bottleneck as operators are required to translate high-level concepts into a machine-mandated sequence of instructions. In contrast, we demonstrate effective, goal-oriented control of a computer system without any form of explicit communication from the human operator. Instead, the system generated the necessary input itself, based on real-time analysis of brain activity. Specific brain responses were evoked by violating the operators' expectations to varying degrees. The evoked brain activity demonstrated detectable differences reflecting congruency with or deviations from the operators' expectations. Real-time analysis of this activity was used to build a user model of those expectations, thus representing the optimal (expected) state as perceived by the operator. Based on this model, which was continuously updated, the computer automatically adapted itself to the expectations of its operator. Further analyses showed this evoked activity to originate from the medial prefrontal cortex and to exhibit a linear correspondence to the degree of expectation violation. These findings extend our understanding of human predictive coding and provide evidence that the information used to generate the user model is task-specific and reflects goal congruency. This paper demonstrates a form of interaction without any explicit input by the operator, enabling computer systems to become neuroadaptive, that is, to automatically adapt to specific aspects of their operator's mindset. Neuroadaptive technology significantly widens the communication bottleneck and has the potential to fundamentally change the way we interact with technology.

  10. 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.

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

    Science.gov (United States)

    Tobler, Philippe N.

    2015-01-01

    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. PMID:25326037

  12. 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

  13. 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

  14. The Role of Nicotinic Acetylcholine Receptors in the Medial Prefrontal Cortex and Hippocampus in Trace Fear Conditioning

    OpenAIRE

    Raybuck, J. D.; Gould, T. J.

    2010-01-01

    Acute nicotine enhances multiple types of learning including trace fear conditioning but the underlying neural substrates of these effects are not well understood. Trace fear conditioning critically involves the medial prefrontal cortex and hippocampus, which both express nicotinic acetylcholine receptors (nAChRs). Therefore, nicotine could act in either or both areas to enhance trace fear conditioning. To identify the underlying neural areas and nAChR subtypes, we examined the effects of inf...

  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. Study the left prefrontal cortex activity of Chinese children with dyslexia in phonological processing by NIRS

    Science.gov (United States)

    Zhang, Zhili; Li, Ting; Zheng, Yi; Luo, Qingming; Song, Ranran; Gong, Hui

    2006-02-01

    Developmental dyslexia, a kind of prevalent psychological disease, represents that dyslexic children have unexpected difficulties in phonological processing and recognition test of Chinese characters. Some functional imaging technologies, such as fMRI and PET, have been used to study the brain activities of the children with dyslexia whose first language is English. In this paper, a portable, 16-channel, continuous-wave (CW) NIRS instrument was used to monitor the concentration changes of each hemoglobin species when Chinese children did the task of phonological processing and recognition test. The NIRS recorded the hemodynamic changes in the left prefrontal cortex of the children. 20 dyslexia-reading children (10~12 years old) and 20 normal-reading children took part in the phonological processing of Chinese characters including the phonological awareness section and the phonological decoding section. During the phonological awareness section, the changed concentration of deoxy-hemoglobin in dyslexia-reading children were significantly higher (pchildren in the left ventrolateral prefrontal cortex (VLPFC). While in the phonological decoding section, both normal and dyslexic reading children had more activity in the left VLPFC, but only normal-reading children had activity in the left middorsal prefrontal cortex. In conclusion, both dyslexic and normal-reading children have activity in the left prefrontal cortex, but the degree and the areas of the prefrontal cortex activity are different between them when they did phonological processing.

  17. Decreased Glucose Metabolism in Medial Prefrontal Areas is Associated with Nutritional Status in Patients with Prodromal and Early Alzheimer's Disease.

    Science.gov (United States)

    Sugimoto, Taiki; Nakamura, Akinori; Kato, Takashi; Iwata, Kaori; Saji, Naoki; Arahata, Yutaka; Hattori, Hideyuki; Bundo, Masahiko; Ito, Kengo; Niida, Shumpei; Sakurai, Takashi

    2017-01-01

    Weight loss is frequently observed in patients with Alzheimer's disease (AD); however, the underlying mechanisms are not well understood. To clarify the associations between nutritional status and AD-related brain changes using Pittsburgh Compound-B (PiB)-PET, fluorodeoxyglucose (FDG)-PET, and structural MRI. The subjects were 34 amyloid-β (Aβ)-positive individuals with mild cognitive impairment or early AD (prodromal/early AD), and 55 Aβ-negative cognitively normal (CN) subjects who attended the Multimodal Neuroimaging for AD Diagnosis (MULNIAD) study. Nutritional status of the subjects was assessed by body mass index and waist to height ratio (waist circumference/height). The associations between nutritional status and brain changes were examined by multiple regression analysis using statistical parametric mapping. In the prodromal/early AD group, nutritional status was significantly positively correlated with regional cerebral glucose metabolism (rCGM) in the medial prefrontal cortices, while different topographical associations were seen in the CN group, suggesting these changes were AD-specific. Aβ deposition and gray matter volume were not significantly associated with nutritional status. Sub-analysis in the prodromal/early AD group demonstrated that fat mass index, but not fat-free mass index, was positively correlated with rCGM in the medial prefrontal areas. This present study provides preliminary results suggesting that hypometabolism in the medial prefrontal areas is specifically associated with AD-related weight loss, and decrease in fat mass may have a key role.

  18. Language and Memory Improvements following tDCS of Left Lateral Prefrontal Cortex.

    Directory of Open Access Journals (Sweden)

    Erika K Hussey

    Full Text Available Recent research demonstrates that performance on executive-control measures can be enhanced through brain stimulation of lateral prefrontal regions. Separate psycholinguistic work emphasizes the importance of left lateral prefrontal cortex executive-control resources during sentence processing, especially when readers must override early, incorrect interpretations when faced with temporary ambiguity. Using transcranial direct current stimulation, we tested whether stimulation of left lateral prefrontal cortex had discriminate effects on language and memory conditions that rely on executive-control (versus cases with minimal executive-control demands, even in the face of task difficulty. Participants were randomly assigned to receive Anodal, Cathodal, or Sham stimulation of left lateral prefrontal cortex while they (1 processed ambiguous and unambiguous sentences in a word-by-word self-paced reading task and (2 performed an n-back memory task that, on some trials, contained interference lure items reputed to require executive-control. Across both tasks, we parametrically manipulated executive-control demands and task difficulty. Our results revealed that the Anodal group outperformed the remaining groups on (1 the sentence processing conditions requiring executive-control, and (2 only the most complex n-back conditions, regardless of executive-control demands. Together, these findings add to the mounting evidence for the selective causal role of left lateral prefrontal cortex for executive-control tasks in the language domain. Moreover, we provide the first evidence suggesting that brain stimulation is a promising method to mitigate processing demands encountered during online sentence processing.

  19. 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.

  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. Lesions of the Medial Prefrontal Cortex Abolish Conditioned Aversion Associated with Sexual Behavior in Male Rats

    Science.gov (United States)

    Davis, Jon F.; Loos, Maarten; Di Sebastiano, Andrea R.; Brown, Jennifer L.; Lehman, Michael N.; Coolen, Lique M.

    2010-01-01

    BACKGROUND An inability to inhibit behaviors once they become maladaptive is a component of several psychiatric illnesses and the medial prefrontal cortex (mPFC) was identified as a potential mediator of behavioral inhibition. The current study tested if the mPFC is involved in inhibition of sexual behavior when associated with aversive outcomes. METHODS Using male rats, effects of lesions of the infralimbic (IL) and prelimbic (PL) areas of the mPFC on expression of sexual behavior and ability to inhibit mating were tested using a paradigm of copulation-contingent aversion. RESULTS mPFC lesions did not alter expression of sexual behavior. In contrast, mPFC lesions completely blocked the acquisition of sex-aversion conditioning and lesioned animals continued to mate, in contrast to the robust behavioral inhibition towards copulation in mPFC intact males, resulting in only 22% of intact males continuing to mate. However, rats with mPFC lesions were capable of forming a conditioned place preference to sexual reward and conditioned place aversion for lithium chloride, suggesting that these lesions did not alter associative learning or sensitivity for lithium chloride. DISCUSSION The current study indicates that animals with mPFC lesions are likely capable of forming the associations with aversive outcomes of their behavior, but lack the ability to suppress seeking of sexual reward in the face of aversive consequences. These data may contribute to a better understanding of a common pathology underlying impulse control disorders as compulsive sexual behavior has a high prevalence of comorbidity with psychiatric disorders and Parkinson’s Disease. PMID:20346444

  2. Increased resting functional connectivity of the medial prefrontal cortex in creativity by means of cognitive stimulation.

    Science.gov (United States)

    Wei, Dongtao; Yang, Junyi; Li, Wenfu; Wang, Kangcheng; Zhang, Qinglin; Qiu, Jiang

    2014-02-01

    Creativity is imperative to the progression of civilization and is central to cultural life. Many neuroimaging studies have investigated the patterns of functional activity in the brain during different creative tasks, and the structural and functional characteristics of the highly creative individuals. However, few studies have investigated resting-state functional connectivity (RSFC) in the brain related to individual differences in creativity, and it is still unclear whether the RSFC underlying creativity can be changed by training. The present study therefore used resting-state functional magnetic resonance imaging (Rs-fMRI) to investigate the relationship between RSFC and creativity (divergent thinking, measured by the Torrance Tests of Creative Thinking) to explore whether RSFC can be influenced by cognitive stimulation. The results of 269 adults showed that creativity was positively correlated with the strength of RSFC between the medial prefrontal cortex (mPFC) and the middle temporal gyrus (mTG). In addition, behavioral data showed that cognitive stimulation was successful in enhancing originality in a subset of the original participants (n = 34). Most interesting, we found that there was also a significantly increased RSFC between the mPFC and the mTG by analyzing the data of Rs-fMRI after creativity training. Taken together, these results suggest that increased RSFC between mPFC and mTG, which belong to the default mode network might be crucial to creativity, and that RSFC between the mPFC and mTG can be improved by means of cognitive stimulation (reflecting creativity training-induced changes in functional connectivity, especially in the lower creativity individuals who had lower scores of Torrance Tests of Creative Thinking). Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Medial prefrontal cortex TRPV1 channels modulate the baroreflex cardiac activity in rats.

    Science.gov (United States)

    Lagatta, D C; Ferreira-Junior, N C; Resstel, L B M

    2015-11-01

    The ventral portion of the medial prefrontal cortex (vMPFC) comprises the infralimbic (IL), prelimbic (PL) and dorsopenducular (DP) cortices. The IL and PL regions facilitate the baroreceptor reflex arc. This facilitatory effect on the baroreflex is thought to be mediated by vMPFC glutamatergic transmission, through NMDA receptors. The glutamatergic transmission can be modulated by other neurotransmitters, such as the endocannabinoids, which are agonists of the TRPV1 receptor. TRPV1 channels facilitate glutamatergic transmission in the brain. Thus, we hypothesized that TRPV1 receptors in the vMPFC enhance the cardiac baroreflex response. Stainless steel guide cannulae were bilaterally implanted into the vMPFC of male Wistar rats. Afterwards, a catheter was inserted into the femoral artery, for recording MAP and HR, and into the femoral vein for assessing baroreflex activation. Microinjections of the TRPV1 receptor antagonists capsazepine and 6-iodo-nordihydrocapsaicin (6-IODO) into the vMPFC reduced the cardiac baroreflex activity in unanaesthetized rats. Capsaicin microinjected into the vMPFC increased the cardiac baroreflex activity in unanaesthetized rats. When an ineffective dose of the TRPV1 receptor antagonist 6-IODO was used, the capsaicin-induced increase in the cardiac baroreflex response was abolished. The higher doses of capsaicin administered into the vMPFC after the ineffective dose of 6-IODO displaced the dose-response curve of the baroreflex parameters to the right, with no alteration in the maximum effect of capsaicin. The results of the present study show that stimulation of the TRPV1 receptors in the vMPFC increases the cardiac baroreceptor reflex response. © 2015 The British Pharmacological Society.

  4. High frequency repetitive transcranial magnetic over the medial cerebellum induces a shift in the prefrontal electroencephalography gamma spectrum: a pilot study in humans

    NARCIS (Netherlands)

    Schutter, D.J.L.G.; Honk, E.J. van; d'Alfonso, A.A.L.; Peper, J.S.; Panksepp, J.

    2003-01-01

    In the present study the anatomical projections from the medial cerebellum to the prefrontal cortex (PFC) were investigated in healthy human subjects, using high frequency repetitive transcranial magnetic (rTMS) stimulation and electro-encephalography (EEG). Medial cerebellar rTMS, compared to

  5. Exposure to the Abused Inhalant Toluene Alters Medial Prefrontal Cortex Physiology.

    Science.gov (United States)

    Wayman, Wesley N; Woodward, John J

    2018-03-01

    Inhalants, including toluene, target the addiction neurocircuitry and are often one of the first drugs of abuse tried by adolescents. The medial prefrontal cortex (mPFC) is involved in regulating goal-directed/reward-motivated behaviors and different mPFC sub-regions have been proposed to promote (prelimbic, PRL) or inhibit (infralimbic, IL) these behaviors. While this dichotomy has been studied in the context of other drugs of abuse, it is not known whether toluene exposure differentially affects neurons within PRL and IL regions. To address this question, we used whole-cell electrophysiology and determined the intrinsic excitability of PRL and IL pyramidal neurons in adolescent rats 24 h following a brief exposure to air or toluene vapor (10 500 p.p.m.). Prior to exposure, fluorescent retrobeads were injected into the NAc core (NAcc) or shell (NAcs) sub-regions to identify projection-specific mPFC neurons. In toluene treated adolescent rats, layer 5/6 NAcc projecting PRL (PRL5/6) neurons fired fewer action potentials and this was associated with increased rheobase, increased spike duration, and reductions in membrane resistance and amplitude of the I h current. No changes in excitability were observed in layer 2/3 NAcc projecting PRL (PRL2/3) neurons. In contrast to PRL neurons, layer 5 IL (IL5) and layer 2/3 (IL2/3) NAcc projecting neurons showed enhanced firing in toluene-exposed animals and in IL5 neurons, this was associated with a reduction in rheobase and AHP. For NAcs projecting neurons, toluene exposure significantly decreased firing of IL5 neurons and this was accompanied by an increased rheobase, increased spike duration, and reduced I h amplitude. The intrinsic excitability of PRL5, PRL2/3, and IL2/3 neurons projecting to the NAcs was not affected by exposure to toluene. The changes in excitability observed 24 h after toluene exposure were not observed when recordings were performed 7 days after the exposure. Finally, there were no changes in

  6. 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

  7. 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

  8. 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

  9. 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

  10. A functional MRI study of language networks in left medial temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Yu Aihong; Wang Xiaoyi; Xu Guoqing; Li Yongjie; Qin Wen; Li Kuncheng; Wang, Yuping

    2011-01-01

    Purpose: The purpose of this study was to investigate the abnormality of language networks in left medial temporal lobe epilepsy (MTLE) using fMRI. Materials and methods: Eight patients with left MTLE and 15 healthy subjects were evaluated. An auditory semantic judgment (AJ) paradigm was used. The fMRI data were collected on a 3T MR system and analyzed by AFNI (analysis of functional neuroimages) to generate the activation map. Results: Behavioral data showed that the reaction time of the left MTLE patients was significantly longer than that of controls on the AJ task (t = -3.396, P < 0.05). The left MTLE patients also exhibited diffusively decreased activation in the AJ task. Right hemisphere dominance of Broca's and Wernicke's areas was demonstrated in left MTLE patients. Conclusions: Long-term activation of spikes in left MTLE patients results in language impairment, which is associated with an abnormality of the brain neural network.

  11. Transcranial direct current stimulation over the left prefrontal cortex increases randomness of choice in instrumental learning.

    Science.gov (United States)

    Turi, Zsolt; Mittner, Matthias; Opitz, Alexander; Popkes, Miriam; Paulus, Walter; Antal, Andrea

    2015-02-01

    There is growing evidence from neuro-computational studies that instrumental learning involves the dynamic interaction of a computationally rigid, low-level striatal and a more flexible, high-level prefrontal component. To evaluate the role of the prefrontal cortex in instrumental learning, we applied anodal transcranial direct current stimulation (tDCS) optimized for the left dorsolateral prefrontal cortex, by using realistic MR-derived finite element model-based electric field simulations. In a study with a double-blind, sham-controlled, repeated-measures design, sixteen male participants performed a probabilistic learning task while receiving anodal and sham tDCS in a counterbalanced order. Compared to sham tDCS, anodal tDCS significantly increased the amount of maladaptive shifting behavior after optimal outcomes during learning when reward probabilities were highly dissociable. Derived parameters of the Q-learning computational model further revealed a significantly increased model parameter that was sensitive to random action selection in the anodal compared to the sham tDCS session, whereas the learning rate parameter was not influenced significantly by tDCS. These results congruently indicate that prefrontal tDCS during instrumental learning increased randomness of choice, possibly reflecting the influence of the cognitive prefrontal component. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Altered neuronal spontaneous activity correlates with glutamate concentration in medial prefrontal cortex of major depressed females: An fMRI-MRS study.

    Science.gov (United States)

    Zhang, Xiaoliu; Tang, Yingying; Maletic-Savatic, Mirjana; Sheng, Jianhua; Zhang, Xuanhong; Zhu, Yajing; Zhang, Tianhong; Wang, Junjie; Tong, Shanbao; Wang, Jijun; Li, Yao

    2016-09-01

    Major depressive disorder (MDD) is twice more prevalent in females than in males. Yet, there have only been a few studies on the functional brain activity in female MDD patients and the detailed mechanisms underlying their neurobiology merit further investigations. In the present work, we used combined fMRI-MRS methods to investigate the altered intrinsic neuronal activity and its association with neurotransmitter concentration in female MDD patients. The whole brain amplitude of low frequency fluctuation (ALFF) analysis using resting state functional magnetic resonance imaging (fMRI) was performed to explore the alteration of intrinsic neuronal signals in MDD females (n=11) compared with female healthy controls (n=11). With a specific interest in the medial prefrontal cortex (mPFC) area, we quantified the concentration of amino acid neurotransmitters including GABA ((r-aminobutyric acid)), Glu (Glutamate), and Glx (Glutamate + Glutamine) using (1)H-MRS technology. Moreover, we conducted Pearson correlation analysis between the ALFF value and neurotransmitter concentration to find out the functional-biochemical relation in mPFC area. The relationship between the metabolites concentration and MDD symptomatology was also examined through Spearman correlation analysis. We found that the female MDD patients showed increased neuronal spontaneous activity in left medial prefrontal cortex (mPFC) and left middle frontal cortex, with decreased ALFF level in right putamen and right middle temporal cortex (pconcentration in female MDD patients (r=0.67, p=0.023). The Glu concentration in mPFC was positively correlated with patients HAMA scores (r=0.641, p=0.033). The relatively small sample size, metabolite information acquired only in mPFC and not all patients were unmedicated are the major limitations of our study. Using combined fMRI-MRS methods, we found increased spontaneous neuronal activity was correlated with Glu concentration in mPFC of female MDD patients. Other

  17. 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...

  18. 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…

  19. 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…

  20. Functioning of medial olivocochlear bundle in right- and left-handed individuals.

    Science.gov (United States)

    Kaipa, Ramesh; Kumar, U Ajith

    2017-07-01

    Functional symmetry of medial olivocochlear bundle (MOCB) as a function of handedness remains to be well investigated. The current study aimed to assess the functional symmetry of MOCB through contralateral inhibition of otoacoustic emissions (OAEs) in right- and left-handed individuals. Thirteen left-handed and 13 right-handed individuals in the age range of 19-25 years participated. Behavioural experiment involved measuring speech perception in noise and vocal reaction time. Physiological experiment involved measuring the contralateral inhibition of OAEs in both the ears of participants. Findings of the current study revealed lack of functional asymmetry in right- as well as left-handed individuals. Results of the current study suggest that right- as well as left-handed individuals do not demonstrate functional asymmetry at the level of descending auditory pathways unlike the higher cortical centres.

  1. Deconstructing the brain’s moral network: dissociable functionality between the temporoparietal junction and ventro-medial prefrontal cortex

    Science.gov (United States)

    Mobbs, Dean; Dalgleish, Tim

    2014-01-01

    Research has illustrated that the brain regions implicated in moral cognition comprise a robust and broadly distributed network. However, understanding how these brain regions interact and give rise to the complex interplay of cognitive processes underpinning human moral cognition is still in its infancy. We used functional magnetic resonance imaging to examine patterns of activation for ‘difficult’ and ‘easy’ moral decisions relative to matched non-moral comparators. This revealed an activation pattern consistent with a relative functional double dissociation between the temporoparietal junction (TPJ) and ventro-medial prefrontal cortex (vmPFC). Difficult moral decisions activated bilateral TPJ and deactivated the vmPFC and OFC. In contrast, easy moral decisions revealed patterns of activation in the vmPFC and deactivation in bilateral TPJ and dorsolateral PFC. Together these results suggest that moral cognition is a dynamic process implemented by a distributed network that involves interacting, yet functionally dissociable networks. PMID:23322890

  2. 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

  3. 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).

  4. NMDA Receptor-Dependent Processes in the Medial Prefrontal Cortex Are Important for Acquisition and the Early Stage of Consolidation during Trace, but Not Delay Eyeblink Conditioning

    Science.gov (United States)

    Takehara-Nishiuchi, Kaori; Kawahara, Shigenori; Kirino, Yutaka

    2005-01-01

    Permanent lesions in the medial prefrontal cortex (mPFC) affect acquisition of conditioned responses (CRs) during trace eyeblink conditioning and retention of remotely acquired CRs. To clarify further roles of the mPFC in this type of learning, we investigated the participation of the mPFC in mnemonic processes both during and after daily…

  5. NR2A- and NR2B-Containing NMDA Receptors in the Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, and Contextual Fear Conditioning

    Science.gov (United States)

    Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.

    2013-01-01

    Activation of "N"-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially…

  6. 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…

  7. 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.

  8. Age-dependent expression of Nav1.9 channels in medial prefrontal cortex pyramidal neurons in rats.

    Science.gov (United States)

    Gawlak, Maciej; Szulczyk, Bartłomiej; Berłowski, Adam; Grzelka, Katarzyna; Stachurska, Anna; Pełka, Justyna; Czarzasta, Katarzyna; Małecki, Maciej; Kurowski, Przemysław; Nurowska, Ewa; Szulczyk, Paweł

    2017-12-01

    Developmental changes that occur in the prefrontal cortex during adolescence alter behavior. These behavioral alterations likely stem from changes in prefrontal cortex neuronal activity, which may depend on the properties and expression of ion channels. Nav1.9 sodium channels conduct a Na + current that is TTX resistant with a low threshold and noninactivating over time. The purpose of this study was to assess the presence of Nav1.9 channels in medial prefrontal cortex (mPFC) layer II and V pyramidal neurons in young (20-day old), late adolescent (60-day old), and adult (6- to 7-month old) rats. First, we demonstrated that layer II and V mPFC pyramidal neurons in slices obtained from young rats exhibited a TTX-resistant, low-threshold, noninactivating, and voltage-dependent Na + current. The mRNA expression of the SCN11a gene (which encodes the Nav1.9 channel) in mPFC tissue was significantly higher in young rats than in late adolescent and adult rats. Nav1.9 protein was immunofluorescently labeled in mPFC cells in slices and analyzed via confocal microscopy. Nav1.9 immunolabeling was present in layer II and V mPFC pyramidal neurons and was more prominent in the neurons of young rats than in the neurons of late adolescent and adult rats. We conclude that Nav1.9 channels are expressed in layer II and V mPFC pyramidal neurons and that Nav1.9 protein expression in the mPFC pyramidal neurons of late adolescent and adult rats is lower than that in the neurons of young rats. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1371-1384, 2017. © 2017 Wiley Periodicals, Inc.

  9. Cellular resolution optical access to brain regions in fissures: imaging medial prefrontal cortex and grid cells in entorhinal cortex.

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    Low, Ryan J; Gu, Yi; Tank, David W

    2014-12-30

    In vivo two-photon microscopy provides the foundation for an array of powerful techniques for optically measuring and perturbing neural circuits. However, challenging tissue properties and geometry have prevented high-resolution optical access to regions situated within deep fissures. These regions include the medial prefrontal and medial entorhinal cortex (mPFC and MEC), which are of broad scientific and clinical interest. Here, we present a method for in vivo, subcellular resolution optical access to the mPFC and MEC using microprisms inserted into the fissures. We chronically imaged the mPFC and MEC in mice running on a spherical treadmill, using two-photon laser-scanning microscopy and genetically encoded calcium indicators to measure network activity. In the MEC, we imaged grid cells, a widely studied cell type essential to memory and spatial information processing. These cells exhibited spatially modulated activity during navigation in a virtual reality environment. This method should be extendable to other brain regions situated within deep fissures, and opens up these regions for study at cellular resolution in behaving animals using a rapidly expanding palette of optical tools for perturbing and measuring network structure and function.

  10. 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.

  11. Cathodal tDCS over the left prefrontal cortex diminishes choice-induced preference change.

    Science.gov (United States)

    Mengarelli, Flavia; Spoglianti, Silvia; Avenanti, Alessio; di Pellegrino, Giuseppe

    2015-05-01

    In everyday life, people often find themselves facing difficult decisions between options that are equally attractive. Cognitive dissonance theory states that after making a difficult choice between 2 equally preferred options, individuals no longer find the alternatives similarly desirable. Rather, they often change their existing preferences to align more closely with the choice they have just made. Despite the relevance of cognitive dissonance in modulating behavior, little is known about the brain processes crucially involved in choice-induced preference change. In the present study, we applied cathodal transcranial Direct Current Stimulation (tDCS) with the aim of downregulating the activity of the left or the right dorsolateral prefrontal cortex (DLPFC) during a revised version of Brehm's (in 1956. Post-decision changes in the desirability of alternatives. J Abnorm Soc Psychol. 52:384-389) free-choice paradigm. We found that cathodal tDCS over the left, but not over the right, DLPFC caused a reduction of the typical behavior-induced preference change relative to sham stimulation. Our findings highlight the role of prefrontal cortex in cognitive dissonance and provide evidence that left DLPFC plays a necessary role in the implementation of choice-induced preference change. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

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    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.

  13. 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.

  14. 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

  15. Increased Hippocampus–Medial Prefrontal Cortex Resting-State Functional Connectivity and Memory Function after Tai Chi Chuan Practice in Elder Adults

    Science.gov (United States)

    Tao, Jing; Liu, Jiao; Egorova, Natalia; Chen, Xiangli; Sun, Sharon; Xue, Xiehua; Huang, Jia; Zheng, Guohua; Wang, Qin; Chen, Lidian; Kong, Jian

    2016-01-01

    Previous studies provide evidence that aging is associated with the decline of memory function and alterations in the hippocampal (HPC) function, including functional connectivity to the medial prefrontal cortex (mPFC). In this study, we investigated if longitudinal (12-week) Tai Chi Chuan and Baduanjin practice can improve memory function and modulate HPC resting-state functional connectivity (rs-FC). Memory function measurements and resting-state functional magnetic resonance imaging (rs-fMRI) were applied at the beginning and the end of the experiment. The results showed that (1) the memory quotient (MQ) measured by the Wechsler Memory Scale-Chinese Revision significantly increased after Tai Chi Chuan and Baduanjin practice as compared with the control group, and no significant difference was observed in MQ between the Tai Chi Chuan and Baduanjin groups; (2) rs-FC between the bilateral hippocampus and mPFC significantly increased in the Tai Chi Chuan group compared to the control group (also in the Baduanjin group compared to the control group, albeit at a lower threshold), and no significant difference between the Tai Chi Chuan and Baduanjin groups was observed; (3) rs-FC increases between the bilateral hippocampus and mPFC were significantly associated with corresponding memory function improvement across all subjects. Similar results were observed using the left or right hippocampus as seeds. Our results suggest that both Tai Chi Chuan and Baduanjin may be effective exercises to prevent memory decline during aging. PMID:26909038

  16. Increased hippocampus–medial prefrontal cortex resting state functional connectivity and memory function after Tai Chi Chuan practice in elder adults

    Directory of Open Access Journals (Sweden)

    Jing eTao

    2016-02-01

    Full Text Available Previous studies provide evidence that aging is associated with the decline of memory function and alterations in the hippocampal function, including functional connectivity to the medial prefrontal cortex (mPFC. In this study, we investigated if longitudinal (12-week Tai Chi Chuan and Baduanjin practice can improve memory function and modulate hippocampal resting-state functional connectivity (rs-FC. Memory function measurements and resting state functional Magnetic Resonance Imaging (rs-fMRI were applied at the beginning and the end of the experiment. The results showed that 1 the memory quotient (MQ measured by the Wechsler Memory Scale (WMS-CR significantly increased after Tai Chi Chuan and Baduanjin practice as compared with the control group, and no significant difference was observed in MQ between the Tai Chi Chuan and Baduanjin groups; 2)rs-FC between the bilateral hippocampus and mPFC significantly increased in the Tai Chi Chuan group compared to the control group (also in the Baduanjin group compared to the control group, albeit at a lower threshold, and no significant difference between the Tai Chi Chuan and Baduanjin groups was observed; 3 rs-FC increases between the bilateral hippocampus and mPFC were significantly associated with corresponding memory function improvement across all subjects. Similar results were observed using the left or right hippocampus as seeds. Our results suggest that both Tai Chi Chuan and Baduanjin may be effective exercises to prevent memory decline during aging.

  17. 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.

  18. 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.

  19. tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli.

    Directory of Open Access Journals (Sweden)

    Marie-Anne Vanderhasselt

    Full Text Available Transcranial Direct Current Stimulation (tDCS is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation, we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

  20. The effects of black garlic on the working memory and pyramidal cell number of medial prefrontal cortex of rats exposed to monosodium glutamate.

    Science.gov (United States)

    Nurmasitoh, Titis; Sari, Dwi Cahyani Ratna; Partadiredja, Ginus

    2017-12-27

    Monosodium glutamate-induced exitotoxicity causes oxidative stress in many brain areas, including the medial prefrontal cortex. The ethanolic garlic (Allium sativum) extract is considered as a neuroprotective substance. The present study aimed at investigating the effects of the ethanolic fermented garlic extract on the working memory and the pyramidal cell number of the medial prefrontal cortex of adolescent male Wistar rats exposed to monosodium glutamate (MSG). Twenty-five rats were randomly divided into five groups. The C- group was given 0.9% NaCl solution. The C + group was given 2 mg/g bw of MSG. The T1, T2, and T3 groups were given MSG and garlic extract (0.0125, 0.025, and 0.05 mg/g bw, respectively). All treatments were conducted for 10 days. The working memory capability of the rats was measured using Y-maze test. The total number of pyramidal cells of the medial prefrontal cortex was estimated using physical fractionator method. The working memory performances of the T1, T2, and T3 groups were significantly better than that of the C + group. There were no significant differences between groups in the estimated total number of pyramidal cell of medial prefrontal cortex. The MSG may not cause the death of neurons, but it may modify neuronal architectures that are sufficient to disrupt memory functions. Black garlic may play a role as an antioxidant agent that prevents the prefrontal cortex from glutamate-induced oxidative stress. It is concluded that the ethanolic fermented garlic extract prevented the working memory impairment following MSG administration.

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

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    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.

  2. 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.

  3. 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.

  4. 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.

  5. Oscillatory activity in the medial prefrontal cortex and nucleus accumbens correlates with impulsivity and reward outcome.

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    Nicholas A Donnelly

    Full Text Available Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC and nucleus accumbens (NAcb and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT, which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50-60 Hz LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7-9 Hz LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour.

  6. Specific configuration of dendritic degeneration in pyramidal neurons of the medial prefrontal cortex induced by differing corticosteroid regimens.

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    Cerqueira, João J; Taipa, Ricardo; Uylings, Harry B M; Almeida, Osborne F X; Sousa, Nuno

    2007-09-01

    We previously demonstrated that hypercorticalism induces pronounced volumetric reductions in the rat medial prefrontal cortex (mPFC) and that these structural changes correlate with deficits in executive function. By applying 3-dimensional analysis of Golgi-Cox-stained material, we now demonstrate that corticosteroids can exert differential effects on dendritic arborizations of pyramidal neurons in lamina II/III of the mPFC. Treatment with the glucocorticoid receptor-selective agonist dexamethasone and with the natural adrenosteroid, corticosterone (CORT), results in significant reductions in the total length of apical dendrites in the pyramidal neurons in lamina II/III of the anterior cingulate/prelimbic and infralimbic cortices. Interestingly, although these treatments do not affect the number of dendritic branches, they are associated with impoverished arborizations in their distal portions and, in CORT-treated animals, with increased branching in the middle portions of the apical dendritic tree. Deprivation of corticosteroids by adrenalectomy leads to decreases in total apical dendritic length and spine number, but in this case, dendritic impoverishment was restricted to the middle/proximal segments of the dendritic trees. None of the treatments influenced the architecture of the basal dendrites. These results add to our knowledge of the morphological substrates through which corticosteroids may disrupt mPFC-dependent behaviors.

  7. Functional and neurochemical interactions within the amygdala-medial prefrontal cortex circuit and their relevance to emotional processing.

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    Delli Pizzi, Stefano; Chiacchiaretta, Piero; Mantini, Dante; Bubbico, Giovanna; Ferretti, Antonio; Edden, Richard A; Di Giulio, Camillo; Onofrj, Marco; Bonanni, Laura

    2017-04-01

    The amygdala-medial prefrontal cortex (mPFC) circuit plays a key role in emotional processing. GABA-ergic inhibition within the mPFC has been suggested to play a role in the shaping of amygdala activity. However, the functional and neurochemical interactions within the amygdala-mPFC circuits and their relevance to emotional processing remain unclear. To investigate this circuit, we obtained resting-state functional magnetic resonance imaging (rs-fMRI) and proton MR spectroscopy in 21 healthy subjects to assess the potential relationship between GABA levels within mPFC and the amygdala-mPFC functional connectivity. Trait anxiety was assessed using the State-Trait Anxiety Inventory (STAI-Y2). Partial correlations were used to measure the relationships among the functional connectivity outcomes, mPFC GABA levels and STAI-Y2 scores. Age, educational level and amount of the gray and white matters within 1 H-MRS volume of interest were included as nuisance variables. The rs-fMRI signals of the amygdala and the vmPFC were significantly anti-correlated. This negative functional coupling between the two regions was inversely correlated with the GABA+/tCr level within the mPFC and the STAI-Y2 scores. We suggest a close relationship between mPFC GABA levels and functional interactions within the amygdala-vmPFC circuit, providing new insights in the physiology of emotion.

  8. 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.

  9. Bidirectional modulation of anxiety-related and social behaviors by amygdala projections to the medial prefrontal cortex.

    Science.gov (United States)

    Felix-Ortiz, A C; Burgos-Robles, A; Bhagat, N D; Leppla, C A; Tye, K M

    2016-05-03

    The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) modulate anxiety and social behaviors. It remains to be elucidated, however, whether direct projections from the BLA to the mPFC play a functional role in these behaviors. We used optogenetic approaches in behaving mice to either activate or inhibit BLA inputs to the mPFC during behavioral assays that assess anxiety-like behavior and social interaction. Channelrhodopsin-2 (ChR2)-mediated activation of BLA inputs to the mPFC produced anxiogenic effects in the elevated plus maze and open field test, whereas halorhodopsin (NpHR)-mediated inhibition produced anxiolytic effects. Furthermore, activation of the BLA-mPFC pathway reduced social interaction in the resident-intruder test, whereas inhibition facilitated social interaction. These results establish a causal relationship between activity in the BLA-mPFC pathway and the bidirectional modulation of anxiety-related and social behaviors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Association of medial prefrontal cortex connectivity with consciousness level and its outcome in patients with acquired brain injury.

    Science.gov (United States)

    Liu, Xiaoyan; Li, Jingqi; Gao, Jian; Zhou, Zhen; Meng, Fanxia; Pan, Gang; Luo, Benyan

    2017-08-01

    Medial prefrontal cortex (mPFC) is usually known for participating in virtually all self related processing. However, few have investigated the role of mPFC in modulating conscious awareness. This study aimed to depict the relationship between the mPFC connectivity and the severity and outcome of the disorders of consciousness (DOC) among patients with acquired brain injury. Thirty-four patients with DOC (17 in a minimally conscious state and 17 in an unresponsive wakefulness syndrome/vegetative state) and 11 healthy controls were recruited, underwent clinical assessment and resting-state functional MRI scan, and were further followed up to evaluate recovery outcome using the Glasgow Outcome Scale. The mPFC connectivity was then analyzed, by comparing DOC patients to healthy controls at baseline, and by comparing "recovered consciousness" and "non-recovered consciousness" patients at follow-up, as identified by graph theory. As a result, enhanced mPFC connectivity against weakened posteromedial cortex connectivity was observed in a minimally conscious state, not in an unresponsive wakefulness syndrome/vegetative state. Besides, increased mPFC connectivity was significantly associated with consciousness recovery. In conclusion, the mPFC connectivity could possibly serve as a mark to track the severity and outcome of DOC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 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).

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

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    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.

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

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    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.

  14. Hyperconnectivity and slow synapses during early development of medial prefrontal cortex in a mouse model for mental retardation and autism.

    Science.gov (United States)

    Testa-Silva, Guilherme; Loebel, Alex; Giugliano, Michele; de Kock, Christiaan P J; Mansvelder, Huibert D; Meredith, Rhiannon M

    2012-06-01

    Neuronal theories of neurodevelopmental disorders (NDDs) of autism and mental retardation propose that abnormal connectivity underlies deficits in attentional processing. We tested this theory by studying unitary synaptic connections between layer 5 pyramidal neurons within medial prefrontal cortex (mPFC) networks in the Fmr1-KO mouse model for mental retardation and autism. In line with predictions from neurocognitive theory, we found that neighboring pyramidal neurons were hyperconnected during a critical period in early mPFC development. Surprisingly, excitatory synaptic connections between Fmr1-KO pyramidal neurons were significantly slower and failed to recover from short-term depression as quickly as wild type (WT) synapses. By 4-5 weeks of mPFC development, connectivity rates were identical for both KO and WT pyramidal neurons and synapse dynamics changed from depressing to facilitating responses with similar properties in both groups. We propose that the early alteration in connectivity and synaptic recovery are tightly linked: using a network model, we show that slower synapses are essential to counterbalance hyperconnectivity in order to maintain a dynamic range of excitatory activity. However, the slow synaptic time constants induce decreased responsiveness to low-frequency stimulation, which may explain deficits in integration and early information processing in attentional neuronal networks in NDDs.

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

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    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.

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

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    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.

  17. Dorsal medial prefrontal cortex (MPFC) circuitry in rodent models of cocaine use: implications for drug addiction therapies.

    Science.gov (United States)

    Jasinska, Agnes J; Chen, Billy T; Bonci, Antonello; Stein, Elliot A

    2015-03-01

    Although the importance of the medial prefrontal cortex (MPFC) in cocaine addiction is well established, its precise contribution to cocaine seeking, taking and relapse remains incompletely understood. In particular, across two different models of cocaine self-administration, pharmacological or optogenetic activation of the dorsal MPFC has been reported to sometimes promote and sometimes inhibit cocaine seeking. We highlight important methodological differences between the two experimental paradigms and propose a framework to potentially reconcile the apparent discrepancy. We also draw parallels between these pre-clinical models of cocaine self-administration and human neuro-imaging studies in cocaine users, and argue that both lines of evidence point to dynamic interactions between cue-reactivity processes and control processes within the dorsal MPFC circuitry. From a translational perspective, these findings underscore the importance of interventions and therapeutics targeting not just a brain region, but a specific computational process within that brain region, and may have implications for the design and implementation of more effective treatments for human cocaine addiction. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  18. 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.

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

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    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.

  20. 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.

  1. 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.

  2. 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.

  3. 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 (...

  4. Specifying the role of the left prefrontal cortex in word selection

    Science.gov (United States)

    Ries, S. K; Karzmark, C. R.; Navarrete, E.; Knight, R. T.; Dronkers, N. F.

    2015-01-01

    Word selection allows us to choose words during language production. This is often viewed as a competitive process wherein a lexical representation is retrieved among semantically-related alternatives. The left prefrontal cortex (LPFC) is thought to help overcome competition for word selection through top-down control. However, whether the LPFC is always necessary for word selection remains unclear. We tested 6 LPFC-injured patients and controls in two picture naming paradigms varying in terms of item repetition. Both paradigms elicited the expected semantic interference effects (SIE), reflecting interference caused by semantically-related representations in word selection. However, LPFC patients as a group showed a larger SIE than controls only in the paradigm involving item repetition. We argue that item repetition increases interference caused by semantically-related alternatives, resulting in increased LPFC-dependent cognitive control demands. The remaining network of brain regions associated with word selection appears to be sufficient when items are not repeated. PMID:26291289

  5. Transcranial direct current stimulation of the left dorsolateral prefrontal cortex shifts preference of moral judgments.

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    Maria Kuehne

    Full Text Available Attitude to morality, reflecting cultural norms and values, is considered unique to human social behavior. Resulting moral behavior in a social environment is controlled by a widespread neural network including the dorsolateral prefrontal cortex (DLPFC, which plays an important role in decision making. In the present study we investigate the influence of neurophysiological modulation of DLPFC reactivity by means of transcranial direct current stimulation (tDCS on moral reasoning. For that purpose we administered anodal, cathodal, and sham stimulation of the left DLPFC while subjects judged the appropriateness of hard moral personal dilemmas. In contrast to sham and cathodal stimulation, anodal stimulation induced a shift in judgment of personal moral dilemmas towards more non-utilitarian actions. Our results demonstrate that alterations of left DLPFC activity can change moral judgments and, in consequence, provide a causal link between left DLPFC activity and moral reasoning. Most important, the observed shift towards non-utilitarian actions suggests that moral decision making is not a permanent individual trait but can be manipulated; consequently individuals with boundless, uncontrollable, and maladaptive moral behavior, such as found in psychopathy, might benefit from neuromodulation-based approaches.

  6. Lesions to the left lateral prefrontal cortex impair decision threshold adjustment for lexical selection.

    Science.gov (United States)

    Anders, Royce; Riès, Stéphanie; Van Maanen, Leendert; Alario, F-Xavier

    Patients with lesions in the left prefrontal cortex (PFC) have been shown to be impaired in lexical selection, especially when interference between semantically related alternatives is increased. To more deeply investigate which computational mechanisms may be impaired following left PFC damage due to stroke, a psychometric modelling approach is employed in which we assess the cognitive parameters of the patients from an evidence accumulation (sequential information sampling) modelling of their response data. We also compare the results to healthy speakers. Analysis of the cognitive parameters indicates an impairment of the PFC patients to appropriately adjust their decision threshold, in order to handle the increased item difficulty that is introduced by semantic interference. Also, the modelling contributes to other topics in psycholinguistic theory, in which specific effects are observed on the cognitive parameters according to item familiarization, and the opposing effects of priming (lower threshold) and semantic interference (lower drift) which are found to depend on repetition. These results are developed for the blocked-cyclic picture naming paradigm, in which pictures are presented within semantically homogeneous (HOM) or heterogeneous (HET) blocks, and are repeated several times per block. Overall, the results are in agreement with a role of the left PFC in adjusting the decision threshold for lexical selection in language production.

  7. [Lesion of extrahippocampal cortices of left medial temporal lobe: a case report].

    Science.gov (United States)

    Spada, J A; Galíndez, C; Spada, A

    The cortex of medial temporal lobe is a group of different allocortical fields which included the hippocampal formation (dentate gyrus, hippocampus proper, and subicular complex) and extrahippocampal cortices (entorhinal, perirhinal, and parahippocampal). It is widely accepted that both of them play an important role in memory process. In humans, several reports indicates that damage to the hippocampus alone would lead to a clinically significant amnesia; when the injuries are more extensive others cognitive disorders, as those related to visual sphere, make worse the clinic picture, and some of these cases were reported as associative visual agnosias. Nevertheless, although evidence from animal studies points to the importance of the extrahippocampal medial temporal lobe cortices in order to recognise visual stimuli, such involvement has not been demonstrated in humans. A 44 year-old male who consulted us because they had lost about of '80% of his vision' after a stroke. Ophthalmological examination was entirely within normal limits, but neuropsychological test put in evidence difficulties in the visuo-verbal naming, discrimination of superposed images, recognition of faces and, mainly, in the test of immediate and deferred visual memory. Anterograde memory impairment was also revealed. Magnetic resonance imaging showed a lesion of left entorhinal, perirhinal and parahippocampal cortices. We suggest, in relation to anatomical evidences, that isolation of hippocampus is responsible for symptomatollogy of our patient.

  8. Storage of Verbal Associations Is Sufficient to Activate the Left Medial Temporal Lobe

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    Andrew R. Mayes

    1999-01-01

    Full Text Available Neuroimaging studies have shown that memory encoding activates the medial temporal lobe (MTL. Many believe that these activations are related to novelty but it remains unproven which is critical - novelty detection or the rich associative encoding it triggers. We examined MTL activation during verbal associative encoding using functional magnetic resonance imaging. First, associative encoding activated left posterior MTL more than single word encoding even though novelty detection was matched, indicating not only that associative encoding activates the MTL particularly strongly, but also that activation does not require novelty detection. Moreover, it remains to be convincingly shown that novelty detection alone does produce such activation. Second, repetitive associative encoding produced less MTL activation than initial associative encoding, indicating that priming of associative information reduces MTL activation. Third, re-encoding familiar associations in a well-established way had a minimal effect on both memory and MTL activation, indicating that MTL activation reflects storage of associations, not merely their initial representation.

  9. Muscarinic receptor control of pyramidal neuron membrane potential in the medial prefrontal cortex (mPFC) in rats.

    Science.gov (United States)

    Kurowski, P; Gawlak, M; Szulczyk, P

    2015-09-10

    Damage to the cholinergic input to the prefrontal cortex has been implicated in neuropsychiatric disorders. Cholinergic endings release acetylcholine, which activates nicotinic and/or G-protein-coupled muscarinic receptors. Muscarinic receptors activate transduction systems, which control cellular effectors that regulate the membrane potential in medial prefrontal cortex (mPFC) neurons. The mechanisms responsible for the cholinergic-dependent depolarization of mPFC layer V pyramidal neurons in slices obtained from young rats were elucidated in this study. Glutamatergic and GABAergic transmission as well as tetrodotoxin (TTX)-sensitive Na(+) and voltage-dependent Ca(++) currents were eliminated. Cholinergic receptor stimulation by carbamoylcholine chloride (CCh; 100 μM) evoked depolarization (10.0 ± 1.3 mV), which was blocked by M1/M4 (pirenzepine dihydrochloride, 2 μM) and M1 (VU 0255035, 5 μM) muscarinic receptor antagonists and was not affected by a nicotinic receptor antagonist (mecamylamine hydrochloride, 10 μM). CCh-dependent depolarization was attenuated by extra- (20 μM) or intracellular (50 μM) application of an inhibitor of the βγ-subunit-dependent transduction system (gallein). It was also inhibited by intracellular application of a βγ-subunit-binding peptide (GRK2i, 10μM). mPFC pyramidal neurons express Nav1.9 channels. CCh-dependent depolarization was abolished in the presence of antibodies against Nav1.9 channels in the intracellular solution and augmented by the presence of ProTx-I toxin (100 nM) in the extracellular solution. CCh-induced depolarization was not affected by the following reagents: intracellular transduction system blockers, including U-73122 (10 μM), chelerythrine chloride (5 μM), SQ 22536 (100 μM) and H-89 (2 μM); channel blockers, including Ba(++) ions (200 μM), apamin (100 nM), flufenamic acid (200 μM), 2-APB (200 μM), SKF 96365 (50 μM), and ZD 7288 (50 μM); and a Na(+)/Ca(++) exchanger blocker, benzamil (20

  10. 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.

  11. Fifteen Minutes of Left Prefrontal Repetitive Transcranial Magnetic Stimulation Acutely Increases Thermal Pain Thresholds in Healthy Adults

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    Jeffrey J Borckardt

    2007-01-01

    Full Text Available BACKGROUND: Transcranial magnetic stimulation (TMS of the motor cortex appears to alter pain perception in healthy adults and in patients with chronic neuropathic pain. There is, however, emerging brain imaging evidence that the left prefrontal cortex is involved in pain inhibition in humans.

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

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    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.

  13. Prenatal MAM administration affects histone H3 methylation in postnatal life in the rat medial prefrontal cortex.

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    Maćkowiak, Marzena; Bator, Ewelina; Latusz, Joachim; Mordalska, Patrycja; Wędzony, Krzysztof

    2014-02-01

    Several findings have indicated that schizophrenia may be connected with the impaired epigenetic regulation of gene transcription. The present study investigated the epigenetic modifications connected with histone H3 methylation at lysine (K)4 and K9 in the medial prefrontal cortex (mPFC) in a neurodevelopmental model of schizophrenia based on prenatal administration of methylazoxymethanol (MAM) at embryonic day 17, which impairs the sensorimotor gating process in adult but not adolescent animals. The effect of MAM was determined at different postnatal ages, pre-puberty (P15, P30 and P45) and post-puberty (P60 and P70), using western blot analyses. MAM treatment altered the levels of H3K9me2 before puberty. H3K9me2 was decreased at P15 and P45 but was increased at P30. In contrast, H3K4me3 was noticeably decreased in adult rats. Immunofluorescence experiments revealed that H3K9me2 protein levels were increased in neuronal cells at P30 and that H3K4me3 levels were decreased in astrocytes at P60 after MAM administration. Decreases in the methyltransferase ASH2L protein levels at P45, P60 and P70 were also observed, while the protein levels of the methyltransferase G9a did not change. In addition, levels of the demethylases LSD1 and JARID1c were analysed after MAM administration. LSD1 protein levels were increased at P15 but decreased at P30. JARID1c protein levels were increased in the MAM-treated animals at P60. Decreased Gad1 mRNA levels were found in adult MAM-treated animals, similar to alternation observed in schizophrenia. The present study indicates that prenatal MAM administration evokes changes in the methylation patterns of histone H3 during postnatal life. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

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

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    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.

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

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    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.

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

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    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.

  17. Perceived Chronic 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.

    2015-01-01

    Introduction 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. Methods 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. Results 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 grey matter, but functional findings remained when accounting for structural differences. Limitation Small sample size, which warrants replication. Conclusion 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. PMID:25898329

  18. 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.

  19. Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task

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    Xilu eJiao

    2015-09-01

    Full Text Available Altered medial prefrontal cortex (mPFC and amygdala function is associated with anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in fear conditioning, these structures are also involved in active avoidance. Given that avoidance perseveration represents a core symptom of anxiety disorders, the neural substrate of avoidance, especially its extinction, requires better understanding. The present study was designed to investigate the activity of mPFC and amygdala neurons during acquisition and extinction of lever-press avoidance in rats. In particular, neural activity was examined in the mPFC, intercalated cell clusters (ITCs, lateral (LA, basal (BA and central (CeA amygdala, at various time points during acquisition and extinction, using induction of the immediate early gene product, c-Fos. Neural activity was greater in the mPFC, LA, BA, and ITC during the extinction phase as compared to the acquisition phase. In contrast, the CeA was the only region that was more activated during acquisition than during extinction. Our results indicate that elevated activity in the mPFC, BA, LA and ITCs, and reduced CeA activity is associated with extinction of active avoidance. Moreover, inhibitory neurons are activated differently in the mPFC and BA during early and late phase of acquisition and extinction, suggesting their dynamic involvement in the development of avoidance response. Together, these data start to identify the key brain regions important in active avoidance behavior, areas that could be associated with avoidance perseveration in anxiety disorders.

  20. M3 muscarinic receptor in the ventral medial prefrontal cortex modulating the expression of contextual fear conditioning in rats.

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    Fedoce, A G; Ferreira-Junior, N C; Reis, D G; Corrêa, F M A; Resstel, L B M

    2016-01-01

    Basal forebrain cholinergic neurons modulate the activation of cortical neurons by several stimuli such as fear and anxiety. However, the role of the muscarinic receptor in the medial prefrontal cortex (MPFC) in the modulation of the conditioned emotional response (CER) evoked in the model contextual conditioned fear remains unclear. The objective of this study is to test the hypothesis that inhibition of the muscarinic receptor in ventral MPFC modulates CER observed during animal's re-exposure to the aversive context. Rats implanted with cannulae aimed at the prelimbic (PL) or the infralimbic (IL) were submitted to a high-intensity contextual fear conditioning protocol. Before the test session, they received microinjections of the hemicholinium (choline reuptake blocker), atropine (muscarinic antagonist), J104129 fumarate (M1-M3 muscarinic antagonists), pirenzepine (M1 muscarinic antagonist), neostigmine (inhibitor acetylcholinesterase enzyme), or the systemic administration of the FG7142 (inverse benzodiazepine agonist). Additional independent groups received the neostigmine or FG7142 before the ineffective doses of J104129 fumarate in the low-intensity protocol of contextual fear conditioning. In the high-intensity protocol, the administration of hemicholinium (1 nmol), atropine (0.06-6 nmol), J104129 fumarate (6 nmol), or pirenzepine (6 nmol) attenuated the expression of CER in rats. However, in the low-intensity protocol, only J10129 fumarate (0.06 nmol) reduced the expression of the CER. Finally, neostigmine (0.1-1 nmol) or FG7142 (8 mg/Kg) increased CER expression, an effect inhibited by the low dose of the J10129 fumarate. These results indicated that the blockade of M3 muscarinic receptor in the vMPFC attenuates the CER expression.

  1. Stable immediate early gene expression patterns in medial prefrontal cortex and striatum after long-term cocaine self-administration.

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    Gao, Ping; Limpens, Jules H W; Spijker, Sabine; Vanderschuren, Louk J M J; Voorn, Pieter

    2017-03-01

    The transition from casual to compulsive drug use is thought to occur as a consequence of repeated drug taking leading to neuroadaptive changes in brain circuitry involved in emotion and cognition. At the basis of such neuroadaptations lie changes in the expression of immediate early genes (IEGs) implicated in transcriptional regulation, synaptic plasticity and intracellular signalling. However, little is known about how IEG expression patterns change during long-term drug self-administration. The present study, therefore, compares the effects of 10 and 60-day self-administration of cocaine and sucrose on the expression of 17 IEGs in brain regions implicated in addictive behaviour, i.e. dorsal striatum, ventral striatum and medial prefrontal cortex (mPFC). Increased expression after cocaine self-administration was found for 6 IEGs in dorsal and ventral striatum (c-fos, Mkp1, Fosb/ΔFosb, Egr2, Egr4, and Arc) and 10 IEGs in mPFC (same 6 IEGs as in striatum, plus Bdnf, Homer1, Sgk1 and Rgs2). Five of these 10 IEGs (Egr2, Fosb/ΔFosb, Bdnf, Homer1 and Jun) and Trkb in mPFC were responsive to long-term sucrose self-administration. Importantly, no major differences were found between IEG expression patterns after 10 or 60 days of cocaine self-administration, except Fosb/ΔFosb in dorsal striatum and Egr2 in mPFC, whereas the amount of cocaine obtained per session was comparable for short-term and long-term self-administration. These steady changes in IEG expression are, therefore, associated with stable self-administration behaviour rather than the total amount of cocaine consumed. Thus, sustained impulses to IEG regulation during prolonged cocaine self-administration may evoke neuroplastic changes underlying compulsive drug use. © 2015 Society for the Study of Addiction.

  2. Optogenetic inhibition of dorsal medial prefrontal cortex attenuates stress-induced reinstatement of palatable food seeking in female rats.

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    Calu, Donna J; Kawa, Alex B; Marchant, Nathan J; Navarre, Brittany M; Henderson, Mark J; Chen, Billy; Yau, Hau-Jie; Bossert, Jennifer M; Schoenbaum, Geoffrey; Deisseroth, Karl; Harvey, Brandon K; Hope, Bruce T; Shaham, Yavin

    2013-01-02

    Relapse to maladaptive eating habits during dieting is often provoked by stress. Recently, we identified a role of dorsal medial prefrontal cortex (mPFC) neurons in stress-induced reinstatement of palatable food seeking in male rats. It is unknown whether endogenous neural activity in dorsal mPFC drives stress-induced reinstatement in female rats. Here, we used an optogenetic approach, in which female rats received bilateral dorsal mPFC microinjections of viral constructs coding light-sensitive eNpHR3.0-eYFP or control eYFP protein and intracranial fiber optic implants. Rats were food restricted and trained to lever press for palatable food pellets. Subsequently, pellets were removed, and lever pressing was extinguished; then the effect of bilateral dorsal mPFC light delivery on reinstatement of food seeking was assessed after injections of the pharmacological stressor yohimbine (an α-2 andrenoceptor antagonist) or pellet priming, a manipulation known to provoke food seeking in hungry rats. Dorsal mPFC light delivery attenuated yohimbine-induced reinstatement of food seeking in eNpHR3.0-injected but not eYFP-injected rats. This optical manipulation had no effect on pellet-priming-induced reinstatement or ongoing food-reinforced responding. Dorsal mPFC light delivery attenuated yohimbine-induced Fos immunoreactivity and disrupted neural activity during in vivo electrophysiological recording in awake rats. Optical stimulation caused significant outward currents and blocked electrically evoked action potentials in eNpHR3.0-injected but not eYFP-injected mPFC hemispheres. Light delivery alone caused no significant inflammatory response in mPFC. These findings indicate that intracranial light delivery in eNpHR3.0 rats disrupts endogenous dorsal mPFC neural activity that plays a role in stress-induced relapse to food seeking in female rats.

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

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    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.

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

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    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.

  5. Self-esteem modulates dorsal medial prefrontal cortical response to self-positivity bias in implicit self-relevant processing.

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    Yang, Juan; Dedovic, Katarina; Guan, Lili; Chen, Yu; Qi, Mingming

    2014-11-01

    Processing self-related material recruits similar neural networks regardless of whether the self-relevance is made explicit or not. However, when considering the neural mechanisms that distinctly underlie cognitive and affective components of self-reflection, it is still unclear whether the same mechanisms are involved when self-reflection is explicit or implicit, and how these mechanisms may be modulated by individual personality traits, such as self-esteem. In the present functional MRI study, 25 participants were exposed to positive and negative words that varied with respect to the degree of self-relevance for each participant; however, the participants were asked to make a judgment about the color of the words. Regions-of-interest analysis showed that medial prefrontal cortex (mPFC) and posterior cingulate cortex were associated with gauging the self-relevance of information. However, no main effect of valence or an interaction effect between self-relevance and valence was observed. Further, positive correlations were observed between levels of self-esteem and response within dorsal mPFC (dmPFC) both in the contrast positive-high in self-relevance trials vs positive-low in self-relevance trials and in the contrast negative-low in self-relevance trials vs positive-low in self-relevance trials. These results suggested that the activation of dmPFC may be particularly associated with the processes of self-positivity bias. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

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    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.

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

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    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.

  8. Enhancement Of Motor Recovery Through Left Dorsolateral Prefrontal Cortex Stimulation After Acute Ischemic Stroke

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    Shahram Oveisgharan

    2017-02-01

    Full Text Available Background: Two previous studies, which investigated transcranial direct current stimulation (tDCS use in motor recovery after acute ischemic stroke, did not show tDCS to be effective in this regard. We speculated that additional left dorsolateral prefrontal cortex ‎(DLPFC ‎stimulation may enhance post stroke motor recovery.  ‎ Methods: In the present randomized clinical trial, 20 acute ischemic stroke patients were recruited. Patients received real motor cortex (M1 stimulation in both arms of the trial. The two arms differed in terms of real vs. sham stimulation over the left DLPFC‎. Motor component of the Fugl-Meyer upper extremity assessment (FM and Action Research Arm Test (ARAT scores were used to assess primary outcomes, and non-linear mixed effects models were used for data analyses. Results: Primary outcome measures improved more and faster among the real stimulation group. During the first days of stimulations, sham group’s FM scores increased 1.2 scores per day, while real group’s scores increased 1.7 scores per day (P = 0.003. In the following days, FM improvement decelerated in both groups. Based on the derived models, a hypothetical stroke patient with baseline FM score of 15 improves to 32 in the sham stimulation group and to 41 in the real stimulation group within the first month after stroke. Models with ARAT scores yielded nearly similar results. Conclusion: The current study results showed that left DLPFC‎ stimulation in conjunction with M1 stimulation resulted in better motor recovery than M1 stimulation alone.

  9. Lateralized hippocampal volume increase following high-frequency left prefrontal repetitive transcranial magnetic stimulation in patients with major depression.

    Science.gov (United States)

    Hayasaka, Shunsuke; Nakamura, Motoaki; Noda, Yoshihiro; Izuno, Takuji; Saeki, Takashi; Iwanari, Hideo; Hirayasu, Yoshio

    2017-11-01

    Repetitive transcranial magnetic stimulation (rTMS) has been applied as a treatment for patients with treatment-resistant depression in recent years, and a large body of evidence has demonstrated its therapeutic efficacy through stimulating neuronal plasticity. The aim of this study was to investigate structural alterations in the hippocampus (HIPP) and amygdala (AM) following conventional rTMS in patients with depression. Twenty-eight patients with depression underwent 10 daily 20-Hz left prefrontal rTMS over 2 weeks. The left dorsolateral prefrontal cortex (DLPFC) was identified using magnetic resonance imaging-guided neuronavigation prior to stimulation. Magnetic resonance imaging scans were obtained at baseline and after the completion of rTMS sessions. The therapeutic effects of rTMS were evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D 17 ), and the volumes of the HIPP and AM were measured by a manual tracing method. Statistical analyses revealed a significant volume increase in the left HIPP (+3.4%) after rTMS but no significant volume change in the AM. No correlation was found between the left HIPP volume increase and clinical improvement, as measured by the HAM-D 17 . The present study demonstrated that conventional left prefrontal rTMS increases the HIPP volume in the stimulated side, indicating a remote neuroplastic effect through the cingulum bundle. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  10. Deficit in rewarding mechanisms and prefrontal left/right cortical effect in vulnerability for internet addiction.

    Science.gov (United States)

    Balconi, Michela; Finocchiaro, Roberta

    2016-10-01

    The present research explored the cortical correlates of rewarding mechanisms and cortical 'unbalance' effect in internet addiction (IA) vulnerability. Internet Addiction Inventory (IAT) and personality trait (Behavioural Inhibition System, BIS; Behavioural Activation System, BAS) were applied to 28 subjects. Electroencephalographic (EEG, alpha frequency band) and response times (RTs) were registered during a Go-NoGo task execution in response to different online stimuli: gambling videos, videogames or neutral stimuli. Higher-IAT (more than 50 score, with moderate or severe internet addiction) and lower-IAT (internet addiction). Alpha band and RTs were affected by IAT, with significant bias (reduced RTs) for high-IAT in response to gambling videos and videogames; and by BAS, BAS-Reward subscale (BAS-R), since not only higher-IAT, but also BAS and BAS-R values determined an increasing of left prefrontal cortex (PFC) activity (alpha reduction) in response to videogames and gambling stimuli for both Go and NoGo conditions, in addition to decreased RTs for these stimuli categories. The increased PFC responsiveness and the lateralisation (left PFC hemisphere) effect in NoGo condition was explained on the basis of a 'rewarding bias' towards more rewarding cues and a deficit in inhibitory control in higher-IAT and higher-BAS subjects. In contrast lower-IAT and lower-BAS predicted a decreased PFC response and increased RTs for NoGo (inhibitory mechanism). These results may support the significance of personality (BAS) and IAT measures for explaining future internet addiction behaviour based on this observed 'vulnerability'.

  11. Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus.

    Directory of Open Access Journals (Sweden)

    Katrina E Furth

    Full Text Available Alterations in the function of the medial prefrontal cortex (mPFC and its major thalamic source of innervation, the mediodorsal (MD thalamus, have been hypothesized to contribute to the symptoms of schizophrenia. The NMDAR antagonist ketamine, used to model schizophrenia, elicits a brain state resembling early stage schizophrenia characterized by cognitive deficits and increases in cortical low gamma (40-70 Hz power. Here we sought to determine how ketamine differentially affects spiking and gamma local field potential (LFP activity in the rat mPFC and MD thalamus. Additionally, we investigated the ability of drugs targeting the dopamine D4 receptor (D4R to modify the effects of ketamine on gamma activity as a measure of potential cognitive therapeutic efficacy. Rats were trained to walk on a treadmill to reduce confounds related to hyperactivity after ketamine administration (10 mg/kg s.c. while recordings were obtained from electrodes chronically implanted in the mPFC and MD thalamus. Ketamine increased gamma LFP power in mPFC and MD thalamus in a similar frequency range, yet did not increase thalamocortical synchronization. Ketamine also increased firing rates and spike synchronization to gamma oscillations in the mPFC but decreased both measures in MD thalamus. Conversely, walking alone increased both firing rates and spike-gamma LFP correlations in both mPFC and MD thalamus. The D4R antagonist alone (L-745,870 had no effect on gamma LFP power during treadmill walking, although it reversed increases induced by the D4R agonist (A-412997 in both mPFC and MD thalamus. Neither drug altered ketamine-induced changes in gamma power or firing rates in the mPFC. However, in MD thalamus, the D4R agonist increased ketamine-induced gamma power and prevented ketamine's inhibitory effect on firing rates. Results provide new evidence that ketamine differentially modulates spiking and gamma power in MD thalamus and mPFC, supporting a potential role for both

  12. Effects of the combination of metyrapone and oxazepam on cocaine-induced increases in corticosterone in the medial prefrontal cortex and nucleus accumbens.

    Science.gov (United States)

    Keller, Courtney M; Breaux, Kelly N; Goeders, Nicholas E

    2017-03-01

    We have previously demonstrated that a combination of drugs (i.e., metyrapone and oxazepam) known to attenuate HPA-axis activity effectively decreases cocaine self-administration and cue reactivity in rats. However, we did not find changes in plasma corticosterone that matched the behavioral effects we observed, indicating that a different mechanism of action must be involved. Therefore, we hypothesized that the combination of metyrapone and oxazepam attenuates cocaine taking and seeking by decreasing cocaine-induced increases in corticosterone in the brain. Male rats were implanted with guide cannulae targeting the medial prefrontal cortex or nucleus accumbens. After the rats recovered from surgery, the microdialysis session was conducted. Rats were housed in the experimental chamber and the dialysis probes inserted into the guide cannulae the night before the session. The following day, dialysate samples were collected over a five-hour session. Baseline samples were collected for the first two hours, every 20min. Samples were then collected following administration of cocaine (15mg/kg, ip). Before injections of cocaine, rats were pretreated with either vehicle or the combination of metyrapone (50mg/kg, ip) and oxazepam (10mg/kg, ip). The administration of cocaine resulted in an increase in corticosterone in the medial prefrontal cortex following vehicle pretreatment, which was not observed in the nucleus accumbens. This cocaine-induced increase in corticosterone was attenuated by metyrapone/oxazepam. Reducing cocaine-induced increases in corticosterone in the medial prefrontal cortex might represent a novel mechanism through which the combination of metyrapone/oxazepam produces its behavioral effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Running wheel exercise reduces renewal of extinguished instrumental behavior and alters medial prefrontal cortex neurons in adolescent, but not adult, rats.

    Science.gov (United States)

    Eddy, Meghan C; Green, John T

    2017-12-01

    Physical exercise in rodents has repeatedly been shown to trigger positive effects on brain function, including increased neurotrophic factors and improved learning and memory. However, most of this work has focused on the adult hippocampus and hippocampal-dependent behavior. Here we examined the effect of running wheel exercise in adult and adolescent male rats on ABA renewal of extinguished instrumental conditioning, in which acquisition occurs in Context A, extinction in Context B, and renewal testing occurs back in Context A. In the first experiment, rats were given unlocked (exercise) or locked (no exercise) running wheel access in their home cages beginning at postnatal Day 30 (adolescent) or postnatal Day 56 (adult). Rats underwent lever-press acquisition in Context A and extinction in Context B. ABA renewal testing took place 2 weeks after the start of running wheel exposure. Nonexercising adolescent rats showed greater ABA renewal than nonexercising adult rats and exercise reduced ABA renewal in adolescents but not adults. ABA renewal depends on medial prefrontal cortex function. In a second experiment, we compared adolescent and adult apical dendrite branch length, branch number, and spine density of medial prefrontal cortex pyramidal neurons after 2 weeks of unlocked or locked running wheel access. The results revealed a higher density of dendritic spines and a lower dendritic branch length in adolescent exercisers than adolescent nonexercisers. Adult exercisers and nonexercisers did not differ. Collectively, these experiments suggest that exercise may have particularly strong effects on adolescent medial prefrontal cortex function and structure. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Modulation of the Left Prefrontal Cortex with High Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Gait in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Amer M. Burhan

    2015-01-01

    Full Text Available Multiple Sclerosis (MS is a chronic central nervous system (CNS demyelinating disease. Gait abnormalities are common and disabling in patients with MS with limited treatment options available. Emerging evidence suggests a role of prefrontal attention networks in modulating gait. High-frequency repetitive transcranial magnetic stimulation (rTMS is known to enhance cortical excitability in stimulated cortex and its correlates. We investigated the effect of high-frequency left prefrontal rTMS on gait parameters in a 51-year-old Caucasian male with chronic relapsing/remitting MS with residual disabling attention and gait symptoms. Patient received 6 Hz, rTMS at 90% motor threshold using figure of eight coil centered on F3 location (using 10-20 electroencephalography (EEG lead localization system. GAITRite gait analysis system was used to collect objective gait measures before and after one session and in another occasion three consecutive daily sessions of rTMS. Two-tailed within subject repeated measure t-test showed significant enhancement in ambulation time, gait velocity, and cadence after three consecutive daily sessions of rTMS. Modulating left prefrontal cortex excitability using rTMS resulted in significant change in gait parameters after three sessions. To our knowledge, this is the first report that demonstrates the effect of rTMS applied to the prefrontal cortex on gait in MS patients.

  15. 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

    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...

  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. 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 (p<0.01) and BA32 (p<0.05) regions and MDD patients with a greater number of depressive episodes displayed thinner cortex in BA32 (p<0

  18. 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.

  19. 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.

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

    Science.gov (United States)

    Asensio, Samuel; Romero, Maria J.; Romero, Francisco J.; Wong, Christopher; Alia-Klein, Nelly; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Volkow, Nora D.; Goldstein, Rita Z.

    2009-01-01

    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 non-drug 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 [11C]raclopride and positron emission tomography and response to monetary reward was measured (an average of 3 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 non-drug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine addicted individuals. PMID:20034014

  1. 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.

  2. Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda; Kroes, Roger A; Stanton, Patric K; Moskal, Joseph R

    2015-09-15

    Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant-like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d-aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  3. Left Prefrontal Activity Reflects the Ability of Vicarious Fear Learning: A Functional Near-Infrared Spectroscopy Study

    Directory of Open Access Journals (Sweden)

    Qingguo Ma

    2013-01-01

    Full Text Available Fear could be acquired indirectly via social observation. However, it remains unclear which cortical substrate activities are involved in vicarious fear transmission. The present study was to examine empathy-related processes during fear learning by-proxy and to examine the activation of prefrontal cortex by using functional near-infrared spectroscopy. We simultaneously measured participants’ hemodynamic responses and skin conductance responses when they were exposed to a movie. In this movie, a demonstrator (i.e., another human being was receiving a classical fear conditioning. A neutral colored square paired with shocks (CSshock and another colored square paired with no shocks (CSno-shock were randomly presented in front of the demonstrator. Results showed that increased concentration of oxygenated hemoglobin in left prefrontal cortex was observed when participants watched a demonstrator seeing CSshock compared with that exposed to CSno-shock. In addition, enhanced skin conductance responses showing a demonstrator's aversive experience during learning object-fear association were observed. The present study suggests that left prefrontal cortex, which may reflect speculation of others’ mental state, is associated with social fear transmission.

  4. Left prefrontal activity reflects the ability of vicarious fear learning: a functional near-infrared spectroscopy study.

    Science.gov (United States)

    Ma, Qingguo; Huang, Yujing; Wang, Lei

    2013-01-01

    Fear could be acquired indirectly via social observation. However, it remains unclear which cortical substrate activities are involved in vicarious fear transmission. The present study was to examine empathy-related processes during fear learning by-proxy and to examine the activation of prefrontal cortex by using functional near-infrared spectroscopy. We simultaneously measured participants' hemodynamic responses and skin conductance responses when they were exposed to a movie. In this movie, a demonstrator (i.e., another human being) was receiving a classical fear conditioning. A neutral colored square paired with shocks (CS(shock)) and another colored square paired with no shocks (CS(no-shock)) were randomly presented in front of the demonstrator. Results showed that increased concentration of oxygenated hemoglobin in left prefrontal cortex was observed when participants watched a demonstrator seeing CS(shock) compared with that exposed to CS(no-shock). In addition, enhanced skin conductance responses showing a demonstrator's aversive experience during learning object-fear association were observed. The present study suggests that left prefrontal cortex, which may reflect speculation of others' mental state, is associated with social fear transmission.

  5. Food cravings and the effects of left prefrontal repetitive transcranial magnetic stimulation using an improved sham condition

    Directory of Open Access Journals (Sweden)

    Kelly eBarth

    2011-03-01

    Full Text Available This study examined whether a single session of repetitive transcranial magnetic stimulation (rTMS of the left prefrontal cortex would inhibit food cravings in healthy women who endorsed frequent food cravings. Ten participants viewed images of food and completed ratings for food cravings before and after receiving either real or sham rTMS over the left prefrontal cortex (10Hz, 100% rMT, 10 seconds-on, 20 seconds-off for 15 minutes; 3000 pulses. Sham TMS was matched with real TMS with respect to perceived painfulness of the stimulation. Each participant received both real and sham rTMS in random order and were blind to the condition in a within-subject cross-over design. With an improved sham control condition, prefrontal rTMS inhibited food cravings no better than sham rTMS. The mild pain from the real and sham rTMS may distract or inhibit food craving, and the decreased craving may not be caused by the effect of rTMS itself. Further studies are needed to elucidate whether rTMS has any true effects on food craving and whether painful stimuli inhibit food or other cravings. A sham condition which matches the painfulness is important to understand the true effects of TMS on behaviors and diseases.

  6. rTMS on left prefrontal cortex contributes to memories for positive emotional cues: a comparison between pictures and words.

    Science.gov (United States)

    Balconi, M; Cobelli, C

    2015-02-26

    The present research explored the cortical correlates of emotional memories in response to words and pictures. Subjects' performance (Accuracy Index, AI; response times, RTs; RTs/AI) was considered when a repetitive Transcranial Magnetic Stimulation (rTMS) was applied on the left dorsolateral prefrontal cortex (LDLPFC). Specifically, the role of LDLPFC was tested by performing a memory task, in which old (previously encoded targets) and new (previously not encoded distractors) emotional pictures/words had to be recognized. Valence (positive vs. negative) and arousing power (high vs. low) of stimuli were also modulated. Moreover, subjective evaluation of emotional stimuli in terms of valence/arousal was explored. We found significant performance improving (higher AI, reduced RTs, improved general performance) in response to rTMS. This "better recognition effect" was only related to specific emotional features, that is positive high arousal pictures or words. Moreover no significant differences were found between stimulus categories. A direct relationship was also observed between subjective evaluation of emotional cues and memory performance when rTMS was applied to LDLPFC. Supported by valence and approach model of emotions, we supposed that a left lateralized prefrontal system may induce a better recognition of positive high arousal words, and that evaluation of emotional cue is related to prefrontal activation, affecting the recognition memories of emotions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. 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.

  8. 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…

  9. 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

    Background: Limbic structures where glutamatergic transmission is considered to be prevalent such as amygdala, hippocampus and prefrontal cortex, have shown a deep impairment in stress-related disorders [1]. A number of studies have highlighted the cumulative effects of stress and its major media...

  10. Effects of Unilateral Transcranial Direct Current Stimulation of Left Prefrontal Cortex on Processing and Memory of Emotional Visual Stimuli.

    Science.gov (United States)

    Balzarotti, Stefania; Colombo, Barbara

    2016-01-01

    The dorsolateral prefrontal cortex (DLPFC) is generally thought to be involved in affect and emotional processing; however, the specific contribution of each hemisphere continues to be debated. In the present study, we employed unilateral tDCS to test the unique contribution of left DLPFC in the encoding and retrieval of emotional stimuli in healthy subjects. Forty-two right handed undergraduate students received either anodal, cathodal or sham stimulation of left DLPFC while viewing neutral, pleasant, and unpleasant pictures. After completing a filler task, participants were asked to remember as many pictures as possible. Results showed that participants were able to remember a larger amount of emotional (both pleasant and unpleasant) pictures than of neutral ones, regardless of the type of tDCS condition. Participants who received anodal stimulation recalled a significantly higher number of pleasant images than participants in the sham and cathodal conditions, while no differences emerged in the recall of neutral and unpleasant pictures. We conclude that our results provide some support to the role of left prefrontal cortex in the encoding and retrieval of pleasant stimuli.

  11. Effects of Unilateral Transcranial Direct Current Stimulation of Left Prefrontal Cortex on Processing and Memory of Emotional Visual Stimuli.

    Directory of Open Access Journals (Sweden)

    Stefania Balzarotti

    Full Text Available The dorsolateral prefrontal cortex (DLPFC is generally thought to be involved in affect and emotional processing; however, the specific contribution of each hemisphere continues to be debated. In the present study, we employed unilateral tDCS to test the unique contribution of left DLPFC in the encoding and retrieval of emotional stimuli in healthy subjects. Forty-two right handed undergraduate students received either anodal, cathodal or sham stimulation of left DLPFC while viewing neutral, pleasant, and unpleasant pictures. After completing a filler task, participants were asked to remember as many pictures as possible. Results showed that participants were able to remember a larger amount of emotional (both pleasant and unpleasant pictures than of neutral ones, regardless of the type of tDCS condition. Participants who received anodal stimulation recalled a significantly higher number of pleasant images than participants in the sham and cathodal conditions, while no differences emerged in the recall of neutral and unpleasant pictures. We conclude that our results provide some support to the role of left prefrontal cortex in the encoding and retrieval of pleasant stimuli.

  12. Noradrenergic lesion of the locus coeruleus increases the firing activity of the medial prefrontal cortex pyramidal neurons and the role of alpha2-adrenoceptors in normal and medial forebrain bundle lesioned rats.

    Science.gov (United States)

    Wang, Yong; Zhang, Qiao Jun; Liu, Jian; Ali, Umar; Gui, Zhen Hua; Hui, Yan Ping; Wang, Tao; Chen, Li; Li, Qiang

    2010-04-09

    Degeneration of noradrenergic neurons in the locus coeruleus (LC) and dysfunction of the prefrontal cortex were regarded as playing a specific role in the occurrence of non-motor symptoms in Parkinson's disease. The present study examined the spontaneous firing rate and firing pattern of medial prefrontal cortex (mPFC) pyramidal neurons, and effects of alpha(2)-adrenoceptor agonist UK-14,304 and antagonist yohimbine on the neuronal activity in rats with 6-hydroxydopamine lesions of the LC, medial forebrain bundle (MFB) and with combined MFB and LC lesions. The firing rate of mPFC pyramidal neurons in rats with lesions of the LC and with combine LC and MFB lesions is significantly higher than that of normal and MFB-lesioned rats and the firing pattern of these neurons in rats with lesions of the LC and with combine LC and MFB lesions also changed significantly towards more regular compared with normal and MFB-lesioned rats. The local administration of UK-14,304 in the mPFC inhibited the firing activity of the pyramidal neurons in normal rats and rats with lesions of the LC, MFB and with combined LC and MFB lesions, while yohimbine increased the firing activity of the pyramidal neurons. These results indicate that the lesions of the LC lead to hyperactivity of mPFC pyramidal neurons in normal and MFB-lesioned rats, and the postsynaptic alpha(2)-adrenoceptors may partially mediate the inhibitory effects of LC-noradrenergic system on the firing activity of pyramidal neurons in the mPFC, suggesting that LC-noradrenergic system plays an important role in the functional disorders of mPFC in Parkinson's disease. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  13. Emergence of realism: Enhanced visual artistry and high accuracy of visual numerosity representation after left prefrontal damage.

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    Takahata, Keisuke; Saito, Fumie; Muramatsu, Taro; Yamada, Makiko; Shirahase, Joichiro; Tabuchi, Hajime; Suhara, Tetsuya; Mimura, Masaru; Kato, Motoichiro

    2014-05-01

    Over the last two decades, evidence of enhancement of drawing and painting skills due to focal prefrontal damage has accumulated. It is of special interest that most artworks created by such patients were highly realistic ones, but the mechanism underlying this phenomenon remains to be understood. Our hypothesis is that enhanced tendency of realism was associated with accuracy of visual numerosity representation, which has been shown to be mediated predominantly by right parietal functions. Here, we report a case of left prefrontal stroke, where the patient showed enhancement of artistic skills of realistic painting after the onset of brain damage. We investigated cognitive, functional and esthetic characteristics of the patient׳s visual artistry and visual numerosity representation. Neuropsychological tests revealed impaired executive function after the stroke. Despite that, the patient׳s visual artistry related to realism was rather promoted across the onset of brain damage as demonstrated by blind evaluation of the paintings by professional art reviewers. On visual numerical cognition tasks, the patient showed higher performance in comparison with age-matched healthy controls. These results paralleled increased perfusion in the right parietal cortex including the precuneus and intraparietal sulcus. Our data provide new insight into mechanisms underlying change in artistic style due to focal prefrontal lesion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. The role of the left ventrolateral prefrontal cortex in online sentence processing

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    Nazbanou Nozari

    2014-04-01

    Full Text Available Introduction: Patients with damage to the left ventrolateral prefrontal cortex (VLPFC are often not impaired in understanding simple sentences. It is, however, possible that the damage may cause subclinical effects. If VLPFC has a role in biasing competition towards what is relevant to the task, we would expect patients with VLPFC damage to be slower in using the relevant information and discarding the irrelevant information when they process sentences online. Methods: Nine patients, five with lesions limited to VLPFC, and four with lesions sparing VLPFC participated. The groups were matched in age, education, WAB-AQ and total lesion volume. Two experiments explored processing of online cues during sentence comprehension by tracking eye fixations in a Visual World paradigm with four pictures. Participants only listened to the sentences and looked at the pictures. Experiment 1 investigated how quickly cues can be used for target identification using a simple “She will [verb] the [target].” sentence structure. The verbs in the restrictive condition were compatible with only one of the four pictures (e.g., “eat”; target “apple” + three inedible competitors. The verbs in the control conditions were matched to the restrictive verbs in length and frequency, but did not point to a unique target (e.g., “see”. If VLPFC is critical for quickly biasing competition towards the relevant target, the VLPFC patients should to be slower than the non-VLPFC patients in fixating the noun when the verb is restrictive. Experiment 2 probed how effectively irrelevant cues are suppressed. A similar Visual World paradigm was used, but all verbs were restrictive, and one of the distractors was also compatible with the verb (e.g., “banana”. The sentences contained an adjective that ruled out one of verb-compatible pictures (e.g., “red”. The critical manipulation involved a third picture (the adjective competitor which was compatible with the

  15. Medial prefrontal cortex dissociation between self and others in a referential task: an fMRI study based on word traits.

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    Yaoi, Ken; Osaka, Mariko; Osaka, Naoyuki

    2013-12-01

    A number of recent neuroimaging studies using self referential tasks have investigated whether self referential processing depends on a unique neural basis that operates specifically in the medial prefrontal cortex. However, these studies have provided contradictory results despite the use of similar methodologies. We hypothesized that these discrepancies are partially related to the task-difficulty that presents dissociations reaction times in the self- and other-referential tasks. We therefore measured brain activity during self and other referential tasks to determine if such activity can be dissociated according to the reaction times (fast versus slow) for the trait words. Activation differed across self and other only in the slow word condition. The self referential condition with slow reaction time produced greater activation in the ventromedial prefrontal cortex, whereas the other referential condition with slow reaction time produced activation of the middle temporal gyrus. Results suggested that the task-difficulty might affect whether or not brain activities within MPFC would be dissociated between self- and other-referential processing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Disrupted MEK/ERK signaling in the medial orbital cortex and dorsal endopiriform nuclei of the prefrontal cortex in a chronic restraint stress mouse model of depression.

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    Leem, Yea-Hyun; Yoon, Sang-Sun; Kim, Yu-Han; Jo, Sangmee Ahn

    2014-09-19

    Depression is one of the most prevalent mental illnesses, and causes a constant feeling of sadness and lose of interest, which often leads to suicide. Evidence suggests that depression is associated with aberrant MEK/ERK signaling. However, studies on MEK/ERK signaling in depression have only been done in a few brain regions, such as the hippocampus and mesolimbic reward pathways. Recent studies also implicate the involvement of the prefrontal cortex in depression. Thus, we examined the changes in MEK/ERK signaling in subregions of the prefrontal cortex of C57BL/6 mice by immunohistochemistry using phospho-MEK1/2 (Ser 217/221) and ERK1/2 (Thr202/Tyr204) antibodies. Mice were subjected to 21 consecutive days of restraint stress (for 2h daily), and depression-like behavior was evaluated using a sociability test and tail suspension test. The antidepressant, imipramine (20mg/kg) was injected intraperitoneally 30min before restraint stress exposure. Chronic/repeated restraint stress produced depressive-like behavior, such as increased social avoidance in the social interaction test, and enhanced immobility time in the tail suspension test. This depressive behavior was ameliorated by imipramine. The behavioral changes well corresponded to a decrease in MEK/ERK immunoreactivity in the medial orbital (MO) cortex and dorsal endopiriform nuclei (DEn), which was averted by imipramine, but not in cingulate, prelimbic, infralimbic, and motor cortex. These results suggest that MEK/ERK signaling is disrupted in the DEn and MO subregions of the prefrontal cortex in the depressive phenotype, and that blocking a decrease in activated MEK/ERK is inherent to the antidepressant imipramine response. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Trace and contextual fear conditioning are impaired following unilateral microinjection of muscimol in the ventral hippocampus or amygdala, but not the medial prefrontal cortex

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    Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.

    2012-01-01

    Trace fear conditioning, in which a brief empty “trace interval” occurs between presentation of the CS and UCS, differs from standard delay conditioning in that contributions from both the hippocampus and prelimbic medial prefrontal cortex (PL mPFC) are required to form a normal long term memory. Little is currently known about how the PL interacts with various temporal lobe structures to support learning across this temporal gap between stimuli. We temporarily inactivated PL along with either ventral hippocampus or amygdala in a disconnection design to determine if these structures functionally interact to acquire trace fear conditioning. Disconnection (contralateral injections) of the PL with either the ventral hippocampus or amygdala impaired trace fear conditioning; however, ipsilateral control rats were also impaired. Follow-up experiments examined the effects of unilateral inactivation of the PL, ventral hippocampus, or amygdala during conditioning. The results of this study demonstrate that unilateral inactivation of the ventral hippocampus or amygdala impairs memory, while bilateral inactivation of the PL is required to produce a deficit. Memory deficits after unilateral inactivation of the ventral hippocampus or amygdala prevent us from determining whether the mPFC functionally interacts with the medial temporal lobe using a disconnection approach. Nonetheless, our findings suggest that the trace fear network is more integrated than previously thought. PMID:22469748

  18. Left dorsolateral prefrontal cortex atrophy is associated with frontal lobe function in Alzheimer's disease and contributes to caregiver burden.

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    Matsuoka, Kiwamu; Yasuno, Fumihiko; Hashimoto, Akiko; Miyasaka, Toshiteru; Takahashi, Masato; Kiuchi, Kuniaki; Iida, Junzo; Kichikawa, Kimihiko; Kishimoto, Toshifumi

    2017-12-27

    Caregivers of patients with dementia experience physical and mental deterioration. We have previously reported a correlation between caregiver burden and the Frontal Assessment Battery (FAB) total scores of patients with Alzheimer's disease (AD), especially regarding the dependency factor from the Zarit Burden Interview. The present study aimed to identify an objective biomarker for predicting caregiver burden. The participants were 26 pairs of caregivers and patients with AD and mild-to-moderate dementia. Correlations between regional gray matter volumes in the patients with AD and the FAB total scores were explored by using whole-brain voxel-based morphometric analysis. Path analysis was used to estimate the relationships between regional gray matter volumes, FAB total scores, and caregiver burden based on the Zarit Burden Interview. The voxel-based morphometric revealed a significant positive correlation between the FAB total scores and the volume of the left dorsolateral prefrontal cortex. This positive correlation persisted after controlling for the effect of general cognitive dysfunction, which was assessed by using the Mini-Mental State Examination. Path analysis revealed that decreases in FAB scores, caused by reduced frontal lobe volumes, negatively affected caregiver burden. The present study revealed that frontal lobe function, based on FAB scores, was affected by the volume of the left dorsolateral prefrontal cortex. Decreased scores were associated with greater caregiver burden, especially for the dependency factor. These findings may facilitate the development of an objective biomarker for predicting caregiver burden. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Left prefrontal neuronavigated electrode localization in tDCS: 10-20 EEG system versus MRI-guided neuronavigation.

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    De Witte, Sara; Klooster, Debby; Dedoncker, Josefien; Duprat, Romain; Remue, Jonathan; Baeken, Chris

    2018-04-30

    Transcranial direct current stimulation (tDCS) involves positioning two electrodes at specifically targeted locations on the human scalp. In neuropsychiatric research, the anode is often placed over the left dorsolateral prefrontal cortex (DLPFC), while the cathode is positioned over a contralateral cephalic region above the eye, referred-to as the supraorbital region. Although the 10-20 EEG system is frequently used to locate the DLPFC, due to inter-subject brain variability, this method may lack accuracy. Therefore, we compared in forty participants left DLPFC-localization via the 10-20 EEG system to MRI-guided neuronavigation. In one participant, with individual electrode positions in close proximity to the mean electrode position across subjects, we also investigated whether distinct electrode localizations were associated with different tDCS-induced electrical field distributions. Furthermore, we aimed to examine which neural region is targeted when placing the reference-electrode on the right supraorbital region. Compared to the 10-20 EEG system, MRI-guided neuronavigation localizes the DLPFC-targeting anode more latero-posteriorly, targeting the middle prefrontal gyrus. tDCS-induced electric fields (n = 1) suggest that both localization methods induce significantly different electric fields in distinct brain regions. Considering the frequent application of tDCS as a neuropsychiatric treatment, an evaluation and direct comparison of the clinical efficacy of targeting methods is warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Involvement of neuronal and glial activities in control of the extracellular d-serine concentrations by the AMPA glutamate receptor in the mouse medial prefrontal cortex.

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    Ishiwata, Sayuri; Umino, Asami; Nishikawa, Toru

    2017-09-28

    It has been well accepted that d-serine may be an exclusive endogenous coagonist for the N-methyl-d-aspartate (NMDA)-type glutamate receptor in mammalian forebrain regions. We have recently found by using an in vivo dialysis method that an intra-medial prefrontal cortex infusion of S-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (S-AMPA), a selective AMPA-type glutamate receptor agonist, causes a reduction in the extracellular levels of d-serine in a calcium-permeable AMPA receptor antagonist-sensitive manner. The inhibitory influence by the AMPA receptor on the extracellular d-serine, however, contradicts the data obtained from in vitro experiments that the AMPA receptor stimulation leads to facilitation of the d-serine liberation. This discrepancy appears to be due to the different cell setups between the in vivo and in vitro preparations. From the viewpoints of the previous reports indicating (1) the neuronal presence of d-serine synthesizing enzyme, serine racemase, and d-serine-like immunoreactivity and (2) the same high tissue concentrations of d-serine in the glia-enriched white matter and in the neuron-enriched gray matter of the mammalian neocortex, we have now investigated in the mouse medial prefrontal cortex, the effects of attenuation of neuronal and glial activities, by tetrodotoxin or fluorocitrate, respectively, on the S-AMPA-induced downregulation of the extracellular d-serine contents. In vivo dialysis studies revealed that a local infusion of tetrodotoxin or fluorocitrate eliminated the ability of S-AMPA given intra-cortically to cause a significant decrease in the dialysate concentrations of d-serine without affecting the elevating effects of S-AMPA on those of glycine, another intrinsic coagonist for the NMDA receptor. These findings suggest that the control by the AMPA receptor of the extracellular d-serine levels could be modulated by the neuronal and glial activities in the prefrontal cortex. It cannot be excluded that

  1. Dopamine D2 Receptors Modulate Pyramidal Neurons in Mouse Medial Prefrontal Cortex through a Stimulatory G-Protein Pathway.

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    Robinson, Sarah E; Sohal, Vikaas S

    2017-10-18

    Dopaminergic modulation of prefrontal cortex (PFC) is thought to play key roles in many cognitive functions and to be disrupted in pathological conditions, such as schizophrenia. We have previously described a phenomenon whereby dopamine D2 receptor (D2R) activation elicits afterdepolarizations (ADPs) in subcortically projecting (SC) pyramidal neurons within L5 of the PFC. These D2R-induced ADPs only occur following synaptic input, which activates NMDARs, even when the delay between the synaptic input and ADPs is relatively long (e.g., several hundred milliseconds). Here, we use a combination of electrophysiological, optogenetic, pharmacological, transgenic, and chemogenetic approaches to elucidate cellular mechanisms underlying this phenomenon in male and female mice. We find that knocking out D2Rs eliminates the ADP in a cell-autonomous fashion, confirming that this ADP depends on D2Rs. Hyperpolarizing current injection, but not AMPA receptor blockade, prevents synaptic stimulation from facilitating D2R-induced ADPs, suggesting that this phenomenon depends on the recruitment of voltage-dependent currents (e.g., NMDAR-mediated Ca 2+ influx) by synaptic input. Finally, the D2R-induced ADP is blocked by inhibitors of cAMP/PKA signaling, insensitive to pertussis toxin or β-arrestin knock-out, and mimicked by G s -DREADD stimulation, suggesting that D2R activation elicits the ADP by stimulating cAMP/PKA signaling. These results show that this unusual physiological phenomenon, in which D2Rs enhance cellular excitability in a manner that depends on synaptic input, is mediated at the cellular level through the recruitment of signaling pathways associated with G s , rather than the G i/o -associated mechanisms that have classically been ascribed to D2Rs. SIGNIFICANCE STATEMENT Dopamine D2 receptors (D2Rs) in the prefrontal cortex (PFC) are thought to play important roles in behaviors, including working memory and cognitive flexibility. Variation in D2Rs has also been

  2. Multimodal connectivity mapping of the human left anterior and posterior lateral prefrontal cortex.

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    Reid, Andrew T; Bzdok, Danilo; Langner, Robert; Fox, Peter T; Laird, Angela R; Amunts, Katrin; Eickhoff, Simon B; Eickhoff, Claudia R

    2016-06-01

    Working memory is essential for many of our distinctly human abilities, including reasoning, problem solving, and planning. Research spanning many decades has helped to refine our understanding of this high-level function as comprising several hierarchically organized components, some which maintain information in the conscious mind, and others which manipulate and reorganize this information in useful ways. In the neocortex, these processes are likely implemented by a distributed frontoparietal network, with more posterior regions serving to maintain volatile information, and more anterior regions subserving the manipulation of this information. Recent meta-analytic findings have identified the anterior lateral prefrontal cortex, in particular, as being generally engaged by working memory tasks, while the posterior lateral prefrontal cortex was more strongly associated with the cognitive load required by these tasks. These findings suggest specific roles for these regions in the cognitive control processes underlying working memory. To further characterize these regions, we applied three distinct seed-based methods for determining cortical connectivity. Specifically, we employed meta-analytic connectivity mapping across task-based fMRI experiments, resting-state BOLD correlations, and VBM-based structural covariance. We found a frontoparietal pattern of convergence which strongly resembled the working memory networks identified in previous research. A contrast between anterior and posterior parts of the lateral prefrontal cortex revealed distinct connectivity patterns consistent with the idea of a hierarchical organization of frontoparietal networks. Moreover, we found a distributed network that was anticorrelated with the anterior seed region, which included most of the default mode network and a subcomponent related to social and emotional processing. These findings fit well with the internal attention model of working memory, in which representation of

  3. Direct current induced short-term modulation of the left dorsolateral prefrontal cortex while learning auditory presented nouns

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    Meyer Martin

    2009-07-01

    Full Text Available Abstract Background Little is known about the contribution of transcranial direct current stimulation (tDCS to the exploration of memory functions. The aim of the present study was to examine the behavioural effects of right or left-hemisphere frontal direct current delivery while committing to memory auditory presented nouns on short-term learning and subsequent long-term retrieval. Methods Twenty subjects, divided into two groups, performed an episodic verbal memory task during anodal, cathodal and sham current application on the right or left dorsolateral prefrontal cortex (DLPFC. Results Our results imply that only cathodal tDCS elicits behavioural effects on verbal memory performance. In particular, left-sided application of cathodal tDCS impaired short-term verbal learning when compared to the baseline. We did not observe tDCS effects on long-term retrieval. Conclusion Our results imply that the left DLPFC is a crucial area involved in short-term verbal learning mechanisms. However, we found further support that direct current delivery with an intensity of 1.5 mA to the DLPFC during short-term learning does not disrupt longer lasting consolidation processes that are mainly known to be related to mesial temporal lobe areas. In the present study, we have shown that the tDCS technique has the potential to modulate short-term verbal learning mechanism.

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

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    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.

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

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    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.

  6. Organization of connections between the amygdala, medial prefrontal cortex, and lateral hypothalamus: a single and double retrograde tracing study in rats.

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    Reppucci, Christina J; Petrovich, Gorica D

    2016-07-01

    The amygdala and medial prefrontal cortex (mPFC) are highly interconnected telencephalic areas critical for cognitive processes, including associative learning and decision making. Both structures strongly innervate the lateral hypothalamus (LHA), an important component of the networks underlying the control of feeding and other motivated behaviors. The amygdala-prefrontal-lateral hypothalamic system is therefore well positioned to exert cognitive control over behavior. However, the organization of this system is not well defined, particularly the topography of specific circuitries between distinct cell groups within these complex, heterogeneous regions. This study used two retrograde tracers to map the connections from the amygdala (central and basolateral area nuclei) and mPFC to the LHA in detail, and to determine whether amygdalar pathways to the mPFC and to LHA originate from the same or different neurons. One tracer was placed into a distinct mPFC area (dorsal anterior cingulate, prelimbic, infralimbic, or rostromedial orbital), and the other into dorsal or ventral LHA. We report that the central nucleus and basolateral area of the amygdala send projections to distinct LHA regions, dorsal and ventral, respectively. The basolateral area, but not central nucleus, also sends substantial projections to the mPFC, topographically organized rostrocaudal to dorsoventral. The entire mPFC, in turn, projects to the LHA, providing a separate route for potential amygdalar influence following mPFC processing. Nearly all amygdalar projections to the mPFC and to the LHA originated from different neurons suggesting amygdala and amygdala-mPFC processing influence the LHA independently, and the balance of these parallel pathways ultimately controls motivated behaviors.

  7. Medial prefrontal cortex Transient Receptor Potential Vanilloid Type 1 (TRPV1) in the expression of contextual fear conditioning in Wistar rats.

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    Terzian, Ana Luisa B; dos Reis, Daniel Gustavo; Guimarães, Francisco S; Corrêa, Fernando M A; Resstel, Leonardo B M

    2014-01-01

    Contextual fear is evoked by re-exposing an animal to an environment that has been previously paired with an aversive or unpleasant stimulus. It can be assessed by freezing and cardiovascular changes such as increase in mean arterial pressure and heart rate. A marked increase in neuronal activity is associated with contextual fear conditioning, especially in limbic structures involved with defense reactions, such as the ventral portion of medial prefrontal cortex. Given the fact that transient receptor potential vanilloid type 1 (TRPV1) receptors could be involved in the expression of defensive behavior, the present work tested the hypothesis that TRPV1 manipulation in the ventromedial prefrontal cortex (vMPFC) modulates the expression of contextual conditioned fear. Male Wistar rats received bilateral microinjections into the vMPFC of the TRPV1 receptor antagonists capsazepine (1, 10, and 60 nmol/200 nL) or 6-iodonordihydrocapsaicin (3 nmol/200 nL), and the TRPV1 agonist capsaicin (1 nmol/200 nL) preceded by vehicle or 6-iodonordihydrocapsaicin before re-exposure to the experimental chamber for 10 min, 48 h after conditioning in two different protocols distinct by their aversiveness. Both antagonists reduced the freezing and cardiovascular responses in the high aversive protocol. Capsaicin caused an increase in fear-associated responses that could be blocked by 6-iodonordihydrocapsaicin. Our results indicate that TRPV1 receptors located in the vMPFC have a tonic involvement in the modulation of the expression of contextual fear conditioning.

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

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    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

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

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    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

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

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    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.

  11. Evidence for Tonic Control by the GABAA Receptor of Extracellular D-Serine Concentrations in the Medial Prefrontal Cortex of Rodents

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    Asami Umino

    2017-08-01

    Full Text Available Endogenous D-serine is a putative dominant co-agonist for the N-methyl-D-aspartate glutamate receptor (NMDAR in the mammalian forebrain. Although the NMDAR regulates the higher order brain functions by interacting with various neurotransmitter systems, the possible interactions between D-serine and an extra-glutamatergic system largely remain elusive. For the first time, we show in the rat and mouse using an in vivo microdialysis technique that the extracellular D-serine concentrations are under tonic increasing control by a major inhibitory transmitter, GABA, via the GABAA (GABAAR in the medial prefrontal cortex (mPFC. Thus, an intra-mPFC infusion of a selective GABAAR antagonist, bicuculline (BIC, caused a concentration-dependent and reversible decrease in the extracellular levels of D-serine in the rat mPFC without affecting those of another intrinsic NMDAR coagonist, glycine and an NMDAR agonist, L-glutamate. The decreasing effects of BIC were eliminated by co-infusion of a selective GABAA agonist, muscimol (MUS and were mimicked by a GABAA antagonist, gabazine (GBZ. In contrast, selective blockade of the GABAB or homomeric ρGABAA (formerly GABAC receptor by saclofen or (1,2,5,6-tetrahydropyridin-4-yl-methylphosphinic acid (TPMPA, respectively, failed to downregulate the prefrontal extracellular D-serine levels. Moreover, the local BIC application attenuated the ability of NMDA given to the mPFC to increase the cortical extracellular concentrations of taurine, indicating the hypofunction of the NMDAR. Finally, in the mouse mPFC, the reduction of the extracellular D-serine levels by a local injection of BIC into the prefrontal portion was replicated, and was precluded by inhibition of the neuronal or glial activity by co-local injection with tetrodotoxin (TTX or fluorocitrate (Fluo, respectively. These findings suggest that the GABAAR-mediated regulation of the D-serine signaling may exert fine-tuning of the NMDAR function and require both

  12. History of Suicide Attempt Is Associated with Reduced Medial Prefrontal Cortex Activity during Emotional Decision-Making among Men with Schizophrenia: An Exploratory fMRI Study

    Directory of Open Access Journals (Sweden)

    Stéphane Potvin

    2018-01-01

    Full Text Available Despite the high prevalence of suicidal ideas/attempts in schizophrenia, only a handful of neuroimaging studies have examined the neurobiological differences associated with suicide risk in this population. The main objective of the current exploratory study is to examine the neurofunctional correlates associated with a history of suicide attempt in schizophrenia, using a risky decision-making task, in order to show alterations in brain reward regions in this population. Thirty-two male outpatients with schizophrenia were recruited: 13 patients with (SCZ + S and 19 without a history of suicidal attempt (SCZ − S. Twenty-one healthy men with no history of mental disorders or suicidal attempt/idea were also recruited. Participants were scanned using fMRI while performing the Balloon Analogue Risk Task. A rapid event-related fMRI paradigm was used, separating decision and outcome events, and the explosion probabilities were included as parametric modulators. The most important finding of this study is that SCZ + S patients had reduced activations of the medial prefrontal cortex during the success outcome event (with parametric modulation, relative to both SCZ − S patients and controls, as illustrated by a spatial conjunction analysis. These exploratory results suggest that a history of suicidal attempt in schizophrenia is associated with blunted brain reward activity during emotional decision-making.

  13. 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.

  14. Afferent drive of medial prefrontal cortex by hippocampus and amygdala is altered in MAM-treated rats: evidence for interneuron dysfunction.

    Science.gov (United States)

    Esmaeili, Behnaz; Grace, Anthony A

    2013-09-01

    Evidence indicates that the prefrontal cortex and its regulation by afferent inputs are disrupted in schizophrenia. Using a validated rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM), we examined the convergent projections from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA) in the medial prefrontal cortex (mPFC). In vivo extracellular recordings were done in anesthetized rats to assess how prior stimulation of the BLA or vHipp input to the mPFC affected mPFC responses to subsequent stimulation of these regions. The interstimulus interval (ISI) of the BLA and vHipp pulse stimulation was varied randomly between 0 and 130 ms, and the probability of evoked spike response in the mPFC measured. We found that BLA input increased vHipp-evoked spike probability at ISIs 40-130 ms, but decreased spike probability at ISIs 10-20 ms. This would be consistent with activation of inhibitory interneurons at shorter ISIs by BLA stimulation. In contrast, in MAM-treated rats BLA stimulation increased vHipp-evoked spike probability in mPFC at all ISIs tested. Given that interneurons are driven primarily by N-methyl-D-aspartate (NMDA) channel activation, the effects of the NMDA channel blocker, phencyclidine (PCP), were tested. PCP was found to completely attenuate the inhibitory effect of BLA input on vHipp-evoked responses in mPFC at shorter ISIs, causing the response in control rats treated with PCP to resemble that observed in the MAM rat. In contrast to the effects of BLA stimulation on vHipp-mPFC-evoked responses, there was no inhibitory period when examining the effects of vHipp stimulation on BLA-mPFC-evoked responses in control rats, but in MAM-treated rats there was a significant inhibition at short intervals. Thus, both affective input arising from the BLA and context-dependent input from the vHipp exert a modulatory effect on mPFC neural activity in response to these inputs. Whereas the

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

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    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

  16. Ketamine treatment involves medial prefrontal cortex serotonin to induce a rapid antidepressant-like activity in BALB/cJ mice.

    Science.gov (United States)

    Pham, T H; Mendez-David, I; Defaix, C; Guiard, B P; Tritschler, L; David, D J; Gardier, A M

    2017-01-01

    Unlike classic serotonergic antidepressant drugs, ketamine, an NMDA receptor antagonist, exhibits a rapid and persistent antidepressant (AD) activity, at sub-anaesthetic doses in treatment-resistant depressed patients and in preclinical studies in rodents. The mechanisms mediating this activity are unclear. Here, we assessed the role of the brain serotonergic system in the AD-like activity of an acute sub-anaesthetic ketamine dose. We compared ketamine and fluoxetine responses in several behavioral tests currently used to predict anxiolytic/antidepressant-like potential in rodents. We also measured their effects on extracellular serotonin levels [5-HT] ext in the medial prefrontal cortex (mPFCx) and brainstem dorsal raphe nucleus (DRN), a serotonergic nucleus involved in emotional behavior, and on 5-HT cell firing in the DRN in highly anxious BALB/cJ mice. Ketamine (10 mg/kg i.p.) had no anxiolytic-like effect, but displayed a long lasting AD-like activity, i.e., 24 h post-administration, compared to fluoxetine (18 mg/kg i.p.). Ketamine (144%) and fluoxetine (171%) increased mPFCx [5-HT] ext compared to vehicle. Ketamine-induced AD-like effect was abolished by a tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA) pointing out the role of the 5-HT system in its behavioral activity. Interestingly, increase in cortical [5-HT] ext following intra-mPFCx ketamine bilateral injection (0.25 μg/side) was correlated with its AD-like activity as measured on swimming duration in the FST in the same mice. Furthermore, pre-treatment with a selective AMPA receptor antagonist (intra-DRN NBQX) blunted the effects of intra-mPFCx ketamine on both the swimming duration in the FST and mPFCx [5-HT] ext suggesting that the AD-like activity of ketamine required activation of DRN AMPA receptors and recruited the prefrontal cortex/brainstem DRN neural circuit in BALB/c mice. These results confirm a key role of cortical 5-HT release in ketamine's AD-like activity following

  17. Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in Schizophrenia Patients with Predominant Negative Symptoms : An Exploratory Study

    NARCIS (Netherlands)

    Dlabac-de Lange, Jozarni J.; Liemburg, Edith J.; Bais, Leonie; van de Poel-Mustafayeva, Aida T.; de Lange-de Klerk, Elly S. M.; Knegtering, Henderikus; Aleman, Andre

    2017-01-01

    Background: Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism. Objective: This study aims to investigate changes in the levels of glutamate and glutamine (Glx,

  18. The stressed female brain: neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress.

    Science.gov (United States)

    Maeng, Lisa Y; Shors, Tracey J

    2013-01-01

    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. About 24 h 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 similarly 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 life

  19. 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.

  20. 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.

  1. Impact of early-life stress on the medial prefrontal cortex functions - a search for the pathomechanisms of anxiety and mood disorders.

    Science.gov (United States)

    Chocyk, Agnieszka; Majcher-Maślanka, Iwona; Dudys, Dorota; Przyborowska, Aleksandra; Wędzony, Krzysztof

    2013-01-01

    Although anxiety and mood disorders (MDs) are the most common mental diseases, the etiologies and mechanisms of these psychopathologies are still a matter of debate. The medial prefrontal cortex (mPFC) is a brain structure that is strongly implicated in the pathophysiology of these disorders. A growing number of epidemiological and clinical studies show that early-life stress (ELS) during the critical period of brain development may increase the risk for anxiety and MDs. Neuroimaging analyses in humans and numerous reports from animal models clearly demonstrate that ELS affects behaviors that are dependent on the mPFC, as well as neuronal activity and synaptic plasticity within the mPFC. The mechanisms engaged in ELS-induced changes in mPFC function involve alterations in the developmental trajectory of the mPFC and may be responsible for the emergence of both early-onset (during childhood and adolescence) and adulthood-onset anxiety and MDs. ELS-evoked changes in mPFC synaptic plasticity may constitute an example of metaplasticity. ELS may program brain functions by affecting glucocorticoid levels. On the molecular level, ELS-induced programming is registered by epigenetic mechanisms, such as changes in DNA methylation pattern, histone acetylation and microRNA expression. Vulnerability and resilience to ELS-related anxiety and MDs depend on the interaction between individual genetic predispositions, early-life experiences and later-life environment. In conclusion, ELS may constitute a significant etiological factor for anxiety and MDs, whereas animal models of ELS are helpful tools for understanding the pathomechanisms of these disorders.

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

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    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

  3. Cognitive control links alcohol use, trait disinhibition, and reduced cognitive capacity: Evidence for medial prefrontal cortex dysregulation during reward-seeking behavior.

    Science.gov (United States)

    Bogg, Tim; Fukunaga, Rena; Finn, Peter R; Brown, Joshua W

    2012-04-01

    Guided by the prediction of response-outcome theory of cognitive control (Alexander and Brown, 2010a), the present study examined reward-seeking medial prefrontal cortex (mPFC) activity as a common neuro-functional marker of excessive alcohol consumption, trait disinhibition, and reduced cognitive capacity; all of which have shown consistent patterns of covariation in previous psychometric research (e.g., Bogg and Finn, 2010). A sample of 18-23-year-old university students with a heterogeneous prevalence of alcohol dependence was assessed with functional magnetic resonance imaging (fMRI) while completing a version of the Balloon Analogue Risk Task (Lejuez et al., 2002). A follow-back typical weekly alcohol consumption interview, self-report measures of trait disinhibition and IQ, and a complex span working memory task also were administered. Correlational region-of-interest analyses showed greater typical weekly alcohol consumption, greater trait disinhibition, and lower IQ were associated with greater reductions in mPFC activity during reward-seeking behaviors (successive inflation choices). The results also showed greater typical weekly alcohol consumption, greater trait disinhibition, and lower IQ were associated with greater increases in mPFC activity during reward-seeking outcomes (successive successful inflation outcomes). No significant relations with the measure of working memory were found. The findings suggest mPFC activity during risk/reward appraisal and performance monitoring is a common neuro-functional feature of co-varying expressions of excessive alcohol consumption, trait disinhibition, and lower IQ. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. 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.

  5. 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.

  6. 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

  7. Feeding-modulatory effects of mu-opioids in the medial prefrontal cortex: a review of recent findings and comparison to opioid actions in the nucleus accumbens.

    Science.gov (United States)

    Selleck, Ryan A; Baldo, Brian A

    2017-05-01

    Whereas reward-modulatory opioid actions have been intensively studied in subcortical sites such as the nucleus accumbens (Acb), the role of cortical opioid transmission has received comparatively little attention. The objective of this study is to describe recent findings on the motivational actions of opioids in the prefrontal cortex (PFC), emphasizing studies of food motivation and ingestion. PFC-based opioid effects will be compared/contrasted to those elicited from the Acb, to glean possible common functional principles. Finally, the motivational effects of opioids will be placed within a network context involving the PFC, Acb, and hypothalamus. Mu-opioid receptor (μ-OR) stimulation in both the Acb and PFC induces eating and enhances food-seeking instrumental behaviors; μ-OR signaling also enhances taste reactivity within a highly circumscribed zone of medial Acb shell. In both the Acb and PFC, opioid-sensitive zones are aligned topographically with the sectors that project to feeding-modulatory zones of the hypothalamus and intact glutamate transmission in the lateral/perifornical (LH-PeF) hypothalamic areas is required for both Acb- and PFC-driven feeding. Conversely, opioid-mediated feeding responses elicited from the PFC are negatively modulated by AMPA signaling in the Acb shell. Opioid signaling in the PFC engages functionally opposed PFC➔hypothalamus and PFC➔Acb circuits, which, respectively, drive and limit non-homeostatic feeding, producing a disorganized and "fragmented" pattern of impulsive food-seeking behaviors and hyperactivity. In addition, opioids act directly in the Acb to facilitate food motivation and taste hedonics. Further study of this cortico-striato-hypothalamic circuit, and incorporation of additional opioid-responsive telencephalic structures, could yield insights with translational relevance for eating disorders and obesity.

  8. 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.

  9. Regulation of synaptic MAPK/ERK phosphorylation in the rat striatum and medial prefrontal cortex by dopamine and muscarinic acetylcholine receptors.

    Science.gov (United States)

    Xue, Bing; Mao, Li-Min; Jin, Dao-Zhong; Wang, John Q

    2015-10-01

    Dopamine and acetylcholine are two principal transmitters in the striatum and are usually balanced to modulate local neural activity and to maintain striatal homeostasis. This study investigates the role of dopamine and muscarinic acetylcholine receptors in the regulation of a central signaling protein, i.e., the mitogen-activated protein kinase (MAPK). We focus on the synaptic pool of MAPKs because of the fact that these kinases reside in peripheral synaptic structures in addition to their somatic locations. We show that a systemic injection of dopamine D1 receptor (D1R) agonist SKF81297 enhances phosphorylation of extracellular signal-regulated kinases (ERKs), a prototypic subclass of MAPKs, in the adult rat striatum. Similar results were observed in another dopamine-responsive region, the medial prefrontal cortex (mPFC). The dopamine D2 receptor agonist quinpirole had no such effects. Pretreatment with a positive allosteric modulator (PAM) of muscarinic acetylcholine M4 receptors (M4Rs), VU0152100, attenuated the D1R agonist-stimulated ERK phosphorylation in the two regions, whereas the PAM itself did not alter basal ERK phosphorylation. All drug treatments had no effect on phosphorylation of c-Jun N-terminal kinases (JNKs), another MAPK subclass, in the striatum and mPFC. These results demonstrate that dopamine and acetylcholine are integrated to control synaptic ERK but not JNK activation in striatal and mPFC neurons in vivo. Activation of M4Rs exerts an inhibitory effect on the D1R-mediated upregulation of synaptic ERK phosphorylation. © 2015 Wiley Periodicals, Inc.

  10. Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-Possible involvement of 5-HT1A and CB1 receptors.

    Science.gov (United States)

    Sartim, A G; Guimarães, F S; Joca, S R L

    2016-04-15

    Systemic administration of cannabidiol (CBD), the main non-psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects. The mechanism of action of CBD is thought to involve the activation of 5-HT1A receptors and the modulation of endocannabinoid levels with subsequent CB1 activation. The brain regions involved in CBD-induced antidepressant-like effects remain unknown. The ventral medial prefrontal cortex (vmPFC), which includes the infralimbic (IL) and prelimbic (PL) subregions, receives dense serotonergic innervation and plays a significant role in stress responses. To test the hypothesis that the administration of CBD into the IL or PL would induce an antidepressant-like effect through 5-HT1A and CB1 activation. Rats received intra-IL or -PL microinjections of CBD (10-60 nmol/side), 8-OH-DPAT (5-HT1A agonist, 5-10 nmol/side), anandamide (AEA, 0.5 pmol/side) or vehicle (0.2 μl/side) and were submitted to the forced swimming (FST) or to the open field (OFT) tests. Independent CBD-treated groups were pre-treated with WAY100635 (10, 30 nmol/side, 5-HT1A antagonist) or AM251 (10 pmol/side, CB1 antagonist) and submitted to the same tests. An additional group was treated with WAY100635 followed by anandamide. CBD (PL: 10-60 nmol; IL:45-60 nmol) and 8-OH-DPAT (10 nmol) administration significantly reduced the immobility time in the FST, without changing locomotor activity in the OFT. WAY100635 (30 nmol) did not induce effect per se but blocked CBD, 8-OH-DPAT and AEA effects. Additionally, AM251 blocked CBD-effects. administration of CBD into the vmPFC induces antidepressant-like effects possibly through indirect activation of CB1 and 5-HT1A receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Medial prefrontal cortex neuronal activation and synaptic alterations after stress-induced reinstatement of palatable food seeking: a study using c-fos-GFP transgenic female rats.

    Science.gov (United States)

    Cifani, Carlo; Koya, Eisuke; Navarre, Brittany M; Calu, Donna J; Baumann, Michael H; Marchant, Nathan J; Liu, Qing-Rong; Khuc, Thi; Pickel, James; Lupica, Carl R; Shaham, Yavin; Hope, Bruce T

    2012-06-20

    Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavior.

  12. 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.

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

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    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

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

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    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.

  15. Impaired personal trait knowledge, but spared other-person trait knowledge, in an individual with bilateral damage to the medial prefrontal cortex

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    Marquine, María J.; Grilli, Matthew D.; Rapcsak, Steven Z.; Kaszniak, Alfred W.; Ryan, Lee; Walther, Katrin; Glisky, Elizabeth L.

    2016-01-01

    Functional neuroimaging has revealed that in healthy adults retrieval of personal trait knowledge is associated with increased activation in the medial prefrontal cortex (mPFC). Separately, neuropsychology has shown that the self-referential nature of memory can be disrupted in individuals with mPFC lesions. However, it remains unclear whether damage to the mPFC impairs retrieval of personal trait knowledge. Therefore, in this neuropsychological case study we investigated the integrity of personal trait knowledge in J.S., an individual who sustained bilateral damage to the mPFC as a result of an anterior communicating artery aneurysm. We measured both accuracy and consistency of J.S.’s personal trait knowledge as well as his trait knowledge of another, frequently seen person, and compared his performance to a group of healthy adults. Findings revealed that J.S. had severely impaired accuracy and consistency of his personal trait knowledge relative to control participants. In contrast, J.S.’s accuracy and consistency of other-person trait knowledge was intact in comparison to control participants. Moreover, J.S. showed a normal positivity bias in his trait ratings. These results, albeit based on a single case, implicate the mPFC as critical for retrieval of personal trait knowledge. Findings also cast doubt on the likelihood that the mPFC, in particular the ventral mPFC, is necessary for storage and retrieval of trait knowledge of other people. Therefore, this case study adds to a growing body of evidence that mPFC damage can disrupt the link between self and memory. PMID:27342256

  16. Medial prefrontal cortex N-methyl-D-aspartate receptor/nitric oxide/cyclic guanosine monophosphate pathway modulates both tachycardic and bradycardic baroreflex responses.

    Science.gov (United States)

    Ferreira-Junior, Nilson C; Fedoce, Alessandra G; Alves, Fernando H F; Resstel, Leonardo B M

    2013-10-01

    Neural reflex mechanisms, such as the baroreflex, are involved in regulating cardiovascular system activity. Previous results showed that the ventral portion of the medial prefrontal cortex (vMPFC) is involved in modulation only of the cardiac baroreflex bradycardic component. Moreover, vMPFC N-methyl-D-aspartate (NMDA) receptors modulate the bradycardia baroreflex, but the baroreflex tachycardic component has not been investigated. Furthermore, glutamatergic neurotransmission into the vMPFC is involved in activation of the cardiac sympathetic and parasympathetic nervous system. Finally, it has been demonstrated that glutamatergic neurotransmission into the vMPFC can be modulated by the endocannabinoid system and that activation of the CB1 cannabinoid receptor by anandamide, an endocannabinoid, can decrease both cardiac baroreflex bradycardic and tachycardic responses. Thus, there is the possibility that glutamatergic neurotransmission into the vMPFC does not modulate only the cardiac bradycardic component of the baroreflex. Therefore, the present study investigated whether glutamatergic neurotransmission into the vMPFC modulates both cardiac baroreflex bradycardic and tachycardic responses. We found that vMPFC bilateral microinjection of the NMDA receptor antagonist AP7 (4 nmol/200 nl), of a selective inhibitor of neuronal nitric oxide (NO) synthase N-propyl (0.08 nmol/200 nl), of the NO scavenger carboxy-PTIO (2 nmol/200 nl), or of the NO-sensitive guanylate cyclase ODQ (2 nmol/200 nl) decreased the baroreflex activity in unanesthetized rats. Therefore, our results demonstrate the participation of NMDA receptors, production of NO, and activation of guanylate cyclase in the vMPFC in the modulation of both cardiac baroreflex bradycardic and tachycardic responses. Copyright © 2013 Wiley Periodicals, Inc.

  17. Functional activity of the right temporo-parietal junction and of the medial prefrontal cortex associated with true and false belief reasoning.

    Science.gov (United States)

    Döhnel, Katrin; Schuwerk, Tobias; Meinhardt, Jörg; Sodian, Beate; Hajak, Göran; Sommer, Monika

    2012-04-15

    Since false belief reasoning requires mental state representation independently of the state of reality, it is seen as a key ability in Theory of Mind (ToM). Although true beliefs do not have to be processed independently of the state of reality, growing behavioural evidence indicates that true belief reasoning is different from just reasoning about the state of reality. So far, neural studies on true and false belief reasoning revealed inconsistent findings in the medial prefrontal cortex (MPFC) and in the right temporo-parietal junction (R-TPJ), brain regions that are hypothesized to play an important role in ToM. To further explore true and false belief reasoning, the present functional magnetic resonance imaging (fMRI) study in eighteen adult subjects used methodological refinements such as ensuring that the true belief trials did not elicit false belief reasoning, as well as including paralleled control conditions requiring reasoning about the state of reality. When compared to its control condition, common R-TPJ activity was observed for true and false belief reasoning, supporting its role in belief reasoning in general, and indicating that, at least in adults, also true belief reasoning appears to be different from reasoning about the state of reality. Differential activity was observed in a broad network of brain regions such as the MPFC, the inferior frontal cortex, and the precuneus. False over true belief reasoning induced activation in the posterior MPFC (pMPFC), supporting its role in the decoupling mechanisms, which is defined as processing a mental state independently of the state of reality. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. 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.

  19. Affective emotion increases heart rate variability and activates left dorsolateral prefrontal cortex in post-traumatic growth.

    Science.gov (United States)

    Wei, Chuguang; Han, Jin; Zhang, Yuqing; Hannak, Walter; Dai, Yanyan; Liu, Zhengkui

    2017-11-30

    The present study evaluated the activities of heart rate variability (HRV) and dorsolateral prefrontal cortex (DLPFC) in response to the presentation of affective pictures correlated with posttraumatic growth (PTG) among adults exposed to the Tianjin explosion incident. The participants who were directly involved in the Tianjin explosions were divided into control, post-traumatic stress disorder (PTSD) and PTG group according to the scores of PTSD Checklist-Civilian Version and PTG Inventory survey. All participants received exposure to affective images. Electrocardiogram recording took place during the process for the purpose of analyzing HRV. Meanwhile, functional near-infrared spectroscopy (fNIRS) was used to measure DLPFC activity through hemodynamic response. Our results indicated that, while performing the negative and positive picture stimulating, PTG increased both in low and high frequency components of HRV compared with the control group, but PTSD was not observed in this phenomenon. Moreover, the fNIRS data revealed that PTG had an increased activation in the left DLPFC compared to the control in the condition of negative pictures stimulating, wheras PTSD showed a higher activation in the right DLPFC while receiving positive pictures stimulating. To our knowledge, this is the first study which provides the differences between PTSD and PTG in emotional regulation.

  20. Varus deformity of the left lower extremity causing degenerative lesion of the posterior horn of the left medial meniscus in a patient with Paget’s disease of bone

    Directory of Open Access Journals (Sweden)

    Al Kaissi, Ali

    2014-09-01

    Full Text Available [english] We report on a 42-year-old woman who presented with persistent pain in her left knee with no history of trauma. Sagittal T1-weighted MRI of the left knee showed discontinuity between the anterior and posterior horns of the left medial meniscus, causing effectively the development of degenerative lesion of the posterior horn. The latter was correlated to varus deformity of the left lower extremity associated with subsequent narrowing of the medial knee joint. The unusual craniofacial contour of the patient, the skeletal survey and the elevated serum alkaline phosphatase were compatible with the diagnosis of Paget’s disease of the bone. To alleviate the adverse effect of the mal-alignment of the left femur onto the left knee, corrective osteotomy of the left femoral diaphysis by means of fixators was performed. To the best of our knowledge this is the first clinical report describing the management and the pathological correlation of a unilateral varus deformity of the femoral shaft and degenerative lesions of the left knee in a patient with Paget’s disease of the bone.

  1. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. ¹H-NMR Spectroscopy Study.

    Science.gov (United States)

    Strzelecki, Dominik; Grzelak, Piotr; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka

    2015-10-15

    Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (¹H-NMR) spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC), the left frontal white matter (WM) and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission--Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology.

  2. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectroscopy Study

    Science.gov (United States)

    Strzelecki, Dominik; Grzelak, Piotr; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka

    2015-01-01

    Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (1H-NMR) spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC), the left frontal white matter (WM) and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology. PMID:26501256

  3. Oxytocin Increases the Perceived Value of Both Self- and Other-Owned Items and Alters Medial Prefrontal Cortex Activity in an Endowment Task.

    Science.gov (United States)

    Zhao, Weihua; Geng, Yayuan; Luo, Lizhu; Zhao, Zhiying; Ma, Xiaole; Xu, Lei; Yao, Shuxia; Kendrick, Keith M

    2017-01-01

    The neuropeptide oxytocin (OXT) can influence self-processing and may help motivate us to value the attributes of others in a more self-like manner by reducing medial prefrontal cortex (mPFC) responses. We do not know however whether this OXT effect extends to possessions. We tend to place a higher monetary value on specific objects that belong to us compared to others, known as the "endowment effect". In two double-blind, between-subject placebo (PLC) controlled experiments in subjects from a collectivist culture, we investigated the influence of intranasal OXT on the endowment effect, with the second study incorporating functional magnetic resonance imaging (fMRI). In the task, subjects decided whether to buy or sell their own or others' (mother/father/classmate/stranger) possessions at various prices. Both experiments demonstrated an endowment effect in the self-owned condition which extended to close others (mother/father) and OXT increased this for self and all other-owned items. This OXT effect was associated with reduced activity in the ventral mPFC (vmPFC) in the self-owned condition but increased in the mother-condition. For the classmate- and stranger-owned conditions OXT increased activity in the dorsal mPFC (dmPFC). Changes in vmPFC activation were associated with the size of the endowment effect for self- and mother-owned items. Functional connectivity between the dmPFC and ventral striatum (VStr) was reduced by OXT in self- and mother-owned conditions and between vmPFC and precuneus in the self-condition. Overall our results show that OXT enhances the endowment effect for both self- and other-owned items in Chinese subjects. This effect is associated with reduced mPFC activation in the self-condition but enhanced activation in all other-conditions and involves differential actions on both dorsal and ventral regions as well as functional connectivity with brain reward and other self-processing regions. Overall our findings suggest that OXT increases

  4. Repeated methamphetamine and modafinil induce differential cognitive effects and specific histone acetylation and DNA methylation profiles in the mouse medial prefrontal cortex.

    Science.gov (United States)

    González, Betina; Jayanthi, Subramaniam; Gomez, Natalia; Torres, Oscar V; Sosa, Máximo H; Bernardi, Alejandra; Urbano, Francisco J; García-Rill, Edgar; Cadet, Jean-Lud; Bisagno, Verónica

    2018-03-02

    Methamphetamine (METH) and modafinil are psychostimulants with different long-term cognitive profiles: METH is addictive and leads to cognitive decline, whereas modafinil has little abuse liability and is a cognitive enhancer. Increasing evidence implicates epigenetic mechanisms of gene regulation behind the lasting changes that drugs of abuse and other psychotropic compounds induce in the brain, like the control of gene expression by histones 3 and 4 tails acetylation (H3ac and H4ac) and DNA cytosine methylation (5-mC). Mice were treated with a seven-day repeated METH, modafinil or vehicle protocol and evaluated in the novel object recognition (NOR) test or sacrificed 4days after last injection for molecular assays. We evaluated total H3ac, H4ac and 5-mC levels in the medial prefrontal cortex (mPFC), H3ac and H4ac promotor enrichment (ChIP) and mRNA expression (RT-PCR) of neurotransmitter systems involved in arousal, wakefulness and cognitive control, like dopaminergic (Drd1 and Drd2), α-adrenergic (Adra1a and Adra1b), orexinergic (Hcrtr1 and Hcrtr2), histaminergic (Hrh1 and Hrh3) and glutamatergic (AMPA Gria1 and NMDA Grin1) receptors. Repeated METH and modafinil treatment elicited different cognitive outcomes in the NOR test, where modafinil-treated mice performed as controls and METH-treated mice showed impaired recognition memory. METH-treated mice also showed i) decreased levels of total H3ac and H4ac, and increased levels of 5-mC, ii) decreased H3ac enrichment at promoters of Drd2, Hcrtr1/2, Hrh1 and Grin1, and increased H4ac enrichment at Drd1, Hrh1 and Grin1, iii) increased mRNA of Drd1a, Grin1 and Gria1. Modafinil-treated mice shared none of these effects and showed increased H3ac enrichment and mRNA expression at Adra1b. Modafinil and METH showed similar effects linked to decreased H3ac in Hrh3, increased H4ac in Hcrtr1, and decreased mRNA expression of Hcrtr2. The specific METH-induced epigenetic and transcriptional changes described here may be

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

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    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.

  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.

    2015-01-01

    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 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 specific neurons change

  7. Effects of 10 Hz Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex in Disorders of Consciousness

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    Xiaoyu Xia

    2017-05-01

    Full Text Available BackgroundWhile repetitive transcranial magnetic stimulation (rTMS has been applied in treatment of patients with disorders of consciousness (DOC, a standardized stimulation protocol has not been proposed, and its therapeutic effects are inconsistently documented.ObjectivesTo assess the efficacy of rTMS in improving consciousness in patients with persistent minimally conscious state (MCS or unresponsive wakefulness syndrome (UWS, previously known as vegetative state (VS.MethodA prospective single-blinded study, with selected subjects, was carried out. In total, 16 patients (5 MCS and 11 VS/UWS with chronic DOC were included. All patients received active 10 Hz rTMS at the left dorsolateral prefrontal cortex (DLPFC, at one session per day, for 20 consecutive days. A single daily session of stimulation consisted of 1,000 pulses (10 s of 10 Hz trains; repeated 10 times with an inter-train interval of 60 s; and 11 min and 40 s for total session. The main outcome measures were changes in the total score on the JFK Coma Recovery Scale-Revised (CRS-R scale. Additional measures were the impressions of caregivers after the conclusion of the interventions, which were assessed using the Clinical Global Impression-Improvement (CGI-I scale.ResultsThe CRS-R scores were increased in all 5 MCS patients and 4 of 11 VS/UWS patients, while a significant enhancement of CRS-R scores was observed compared to the baseline in all participants (p = 0.007. However, the improvement was more notable in MCS patients (p = 0.042 than their VS/UWS counterparts (p = 0.066. Based on the CGI-I scores, two patients improved considerably, two improved, six minimally improved, six experienced no change, and none deteriorated. Good concordance was seen between the CGI-I result and the increases in CRS-R scores.ConclusionTreatment of 10 Hz multisession rTMS applied to the left DLPFC is promising for the rehabilitation of DOC patients, especially those in MCS

  8. Spontaneous Activity Associated with Delusions of Schizophrenia in the Left Medial Superior Frontal Gyrus: A Resting-State fMRI Study.

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    Bin Gao

    Full Text Available Delusions of schizophrenia have been found to be associated with alterations of some brain regions in structure and task-induced activation. However, the relationship between spontaneously occurring symptoms and spontaneous brain activity remains unclear. In the current study, 14 schizophrenic patients with delusions and 14 healthy controls underwent a resting-state functional magnetic resonance imaging (RS-fMRI scan. Patients with delusions of schizophrenia patients were rated with Positive and Negative Syndrome Scale (PANSS and Characteristics of Delusional Rating Scale (CDRS. Regional homogeneity (ReHo was calculated to measure the local synchronization of the spontaneous activity in a voxel-wise way. A two-sample t-test showed that ReHo of the right anterior cingulate gyrus and left medial superior frontal gyrus were higher in patients, and ReHo of the left superior occipital gyrus was lower, compared to healthy controls. Further, among patients, correlation analysis showed a significant difference between delusion scores of CRDS and ReHo of brain regions. ReHo of the left medial superior frontal gyrus was negatively correlated with patients' CDRS scores but not with delusional PANSS scores. These results suggested that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of delusion in schizophrenia.

  9. Increased Low-Frequency Resting-State Brain Activity by High-Frequency Repetitive TMS on the Left Dorsolateral Prefrontal Cortex.

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    Xue, Shao-Wei; Guo, Yonghu; Peng, Wei; Zhang, Jian; Chang, Da; Zang, Yu-Feng; Wang, Ze

    2017-01-01

    Beneficial effects of repetitive transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) have been consistently shown for treating various neuropsychiatrical or neuropsychological disorders, but relatively little is known about its neural mechanisms. Here we conducted a randomized, double-blind, SHAM-controlled study to assess the effects of high-frequency left DLPFC rTMS on resting-state activity. Thirty-eight young healthy subjects received two sessions of either real rTMS ( N = 18, 90% motor-threshold; left DLPFC at 20 Hz) or SHAM TMS ( N = 20) and functional magnetic resonance imaging scan during rest in 2 days separated by 48 h. Resting-state bran activity was measured with the fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC). Increased fALFF was found in rostral anterior cingulate cortex (rACC) after 20 Hz rTMS, while no changes were observed after SHAM stimulation. Using the suprathreshold rACC cluster as the seed, increased FC was found in left temporal cortex (stimulation vs. group interaction). These data suggest that high-frequency rTMS on left DLPFC enhances low-frequency resting-state brain activity in the target site and remote sites as reflected by fALFF and FC.

  10. Effects of Food and Water Deprivation on Self-Stimulation of the Medial and Sulcal Prefrontal Cortex and Caudate Putamen in the Rat

    NARCIS (Netherlands)

    Koolhaas, J.M.; Mora, F.; Phillips, A.G.

    1977-01-01

    Self-stimulation rates from electrodes, implanted in the terminal areas of the mesocortical and nigrostriatal dopaminergic systems, were measured during food or water deprivation. A significant increase of sulcal prefrontal cortex self-stimulation was observed after 24 and 48 hr of food deprivation.

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

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    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.

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    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.

  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

    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.

  14. Left and right High Frequency repetitive Transcranial Magnetic Stimulation of the dorsolateral prefrontal cortex does not affect mood in female volunteers.

    Science.gov (United States)

    Baeken, C; Leyman, L; De Raedt, R; Vanderhasselt, M A; D'haenen, H

    2008-03-01

    High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) has yielded divergent results concerning its effect on mood in normal volunteers. In a former study, we were unable to demonstrate negative mood effects after one session of HF-rTMS on the left dorsolateral prefrontal cortex (DLPFC) in a large group of healthy female volunteers: researchers had focused mainly on negative mood changes, overlooking a possible positive mood induction, while no studies had yet examined mood effects of HF-rTMS delivered on the right prefrontal cortex. In this study, we have tried to replicate our previous HF-rTMS findings on the left DLPFC in a new (large) group of healthy female subjects, and we focused especially on positive mood changes. We also extended our former research by stimulating the right DLPFC in a different but comparable (large) group of healthy female volunteers with the same HF-rTMS parameters. In this sham-controlled, single blind, crossover HF-rTMS study, stimulus parameters were an exact copy of our previous healthy volunteer study. To exclude individual anatomical differences, the left and right DLPFC were targeted under magnetic resonance (MRI) guidance. To examine subjective mood changes we used Visual Analogue Scales (VAS), the Profile of Mood States (POMS), and the Positive Affect and Negative Affect Schedule (PANAS), the latter to assure assessment of positive emotions. To detect any delayed mood changes, assessments were also re-administered 30min post-HF-rTMS. We were unable to demonstrate immediate or delayed mood changes after one single active HF-rTMS session on the left or right DLPFC. Although we took into account several methodological problems which might have confounded previous rTMS mood induction studies, the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence mood in healthy female volunteers was not supported. One HF-rTMS session has no effect on subjective mood in healthy female

  15. At-home tDCS of the left dorsolateral prefrontal cortex improves visual short-term memory in mild vascular dementia.

    Science.gov (United States)

    André, Sebastian; Heinrich, Simon; Kayser, Friederike; Menzler, Katja; Kesselring, Jürg; Khader, Patrick H; Lefaucheur, Jean-Pascal; Mylius, Veit

    2016-10-15

    Previous studies have shown that anodal transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) led to an improvement of various cognitive functions in patients with Alzheimer dementia, early affected by short-term memory deficits. Since this approach has not been evaluated in the context of vascular dementia, which rather affects the velocity of cognitive responses, we aimed at improving these functions by applying repetitive sessions of anodal tDCS. Four 20-minute sessions of 2mA anodal or sham at-home tDCS were applied to the left DLPFC in a single-blinded randomised study of 21 patients with mild vascular dementia, with parallel-group design. The effect of tDCS on cognitive testing was assessed up to two weeks beyond the stimulation time. A similar clinically meaningful improvement of various cognitive and behavioral dysfunction characteristics could be observed following either active or sham tDCS, whereas visual recall, and reaction times in the n-back task as well as in the go/no-go test improved only in the active tDCS group. In patients with mild vascular dementia, anodal tDCS of the left DLPFC is able to produce additional effects to cognitive training on visual short-term memory, verbal working memory, and executive control. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Impact of Anodal and Cathodal Transcranial Direct Current Stimulation over the Left Dorsolateral Prefrontal Cortex during Attention Bias Modification: An Eye-Tracking Study.

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    Alexandre Heeren

    Full Text Available People with anxiety disorders show an attentional bias for threat (AB, and Attention Bias Modification (ABM procedures have been found to reduce this bias. However, the underlying processes accounting for this effect remain poorly understood. One explanation suggests that ABM requires the modification of attention control, driven by the recruitment of the dorsolateral prefrontal cortex (DLPFC. In the present double-blind study, we examined whether modifying left DLPFC activation influences the effect of ABM on AB. We used transcranial direct current stimulation (tDCS to directly modulate cortical excitability of the left DLPFC during an ABM procedure designed to reduce AB to threat. Anodal tDCS increases excitability, whereas cathodal tDCS decreases it. We randomly assigned highly trait-anxious individuals to one of three conditions: 1 ABM combined with cathodal tDCS, 2 ABM combined with anodal tDCS, or 3 ABM combined with sham tDCS. We assessed the effects of these manipulations on both reaction times and eye-movements on a task indexing AB. Results indicate that combining ABM and anodal tDCS over the left DLPFC reduces the total duration that participants' gaze remains fixated on threat, as assessed using eye-tracking measurement. However, in contrast to previous studies, there were no changes in AB from baseline to post-training for participants that received ABM without tDCS. As the tendency to maintain attention to threat is known to play an important role in the maintenance of anxiety, the present findings suggest that anodal tDCS over the left DLPFC may be considered as a promising tool to reduce the maintenance of gaze to threat. Implications for future translational research combining ABM and tDCS are discussed.

  17. Examining Brain-Cognition Effects of Ginkgo Biloba Extract: Brain Activation in the Left Temporal and Left Prefrontal Cortex in an Object Working Memory Task

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    R. B. Silberstein

    2011-01-01

    Full Text Available Ginkgo Biloba extract (GBE is increasingly used to alleviate symptoms of age related cognitive impairment, with preclinical evidence pointing to a pro-cholinergic effect. While a number of behavioral studies have reported improvements to working memory (WM associated with GBE, electrophysiological studies of GBE have typically been limited to recordings during a resting state. The current study investigated the chronic effects of GBE on steady state visually evoked potential (SSVEP topography in nineteen healthy middle-aged (50-61 year old male participants whilst completing an object WM task. A randomized double-blind crossover design was employed in which participants were allocated to receive 14 days GBE and 14 days placebo in random order. For both groups, SSVEP was recorded from 64 scalp electrode sites during the completion of an object WM task both pre- and 14 days post-treatment. GBE was found to improve behavioural performance on the WM task. GBE was also found to increase the SSVEP amplitude at occipital and frontal sites and increase SSVEP latency at left temporal and left frontal sites during the hold component of the WM task. These SSVEP changes associated with GBE may represent more efficient processing during WM task completion.

  18. Organization of cortico-cortical pathways supporting memory retrieval across subregions of the left ventrolateral prefrontal cortex.

    Science.gov (United States)

    Barredo, Jennifer; Verstynen, Timothy D; Badre, David

    2016-09-01

    Functional magnetic resonance imaging (fMRI) evidence indicates that different subregions of ventrolateral prefrontal cortex (VLPFC) participate in distinct cortical networks. These networks have been shown to support separable cognitive functions: anterior VLPFC [inferior frontal gyrus (IFG) pars orbitalis] functionally correlates with a ventral fronto-temporal network associated with top-down influences on memory retrieval, while mid-VLPFC (IFG pars triangularis) functionally correlates with a dorsal fronto-parietal network associated with postretrieval control processes. However, it is not known to what extent subregional differences in network affiliation and function are driven by differences in the organization of underlying white matter pathways. We used high-angular-resolution diffusion spectrum imaging and functional connectivity analysis in unanesthetized humans to address whether the organization of white matter connectivity differs between subregions of VLPFC. Our results demonstrate a ventral-dorsal division within IFG. Ventral IFG as a whole connects broadly to lateral temporal cortex. Although several different individual white matter tracts form connections between ventral IFG and lateral temporal cortex, functional connectivity analysis of fMRI data indicates that these are part of the same ventral functional network. By contrast, across subdivisions, dorsal IFG was connected with the midfrontal gyrus and correlated as a separate dorsal functional network. These qualitative differences in white matter organization within larger macroanatomical subregions of VLPFC support prior functional distinctions among these regions observed in task-based and functional connectivity fMRI studies. These results are consistent with the proposal that anatomical connectivity is a crucial determinant of systems-level functional organization of frontal cortex and the brain in general. Copyright © 2016 the American Physiological Society.

  19. No change in N-acetyl aspartate in first episode of moderate depression after antidepressant treatment: 1H magnetic spectroscopy study of left amygdala and left dorsolateral prefrontal cortex

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    Bajs Janović M

    2014-09-01

    Full Text Available Maja Bajs Janović,1,3 Petra Kalember,2 Špiro Janović,1,3 Pero Hrabač,2 Petra Folnegović Grošić,1 Vladimir Grošić,4 Marko Radoš,5 Neven Henigsberg2,61University Department of Psychiatry, Clinical Hospital Center Zagreb, Zagreb, 2Polyclinic Neuron, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, 3University North, Varaždin, 4Psychiatric Hospital Sveti Ivan, Zagreb, 5University Department of Radiology, Clinical Hospital Center Zagreb, Zagreb, 6Psychiatric Clinic Vrapče, Zagreb, CroatiaBackground: The role of brain metabolites as biological correlates of the intensity, symptoms, and course of major depression has not been determined. It has also been inconclusive whether the change in brain metabolites, measured with proton magnetic spectroscopy, could be correlated with the treatment outcome. Methods: Proton magnetic spectroscopy was performed in 29 participants with a first episode of moderate depression occurring in the left dorsolateral prefrontal cortex and left amygdala at baseline and after 8 weeks of antidepressant treatment with escitalopram. The Montgomery-Asberg Depression Rating Scale, the Hamilton Rating Scale for Depression, and the Beck Depression Inventory were used to assess the intensity of depression at baseline and at the endpoint of the study. At endpoint, the participants were identified as responders (n=17 or nonresponders (n=12 to the antidepressant therapy. Results: There was no significant change in the N-acetyl aspartate/creatine ratio (NAA/Cr after treatment with antidepressant medication. The baseline and endpoint NAA/Cr ratios were not significantly different between the responder and nonresponder groups. The correlation between NAA/Cr and changes in the scores of clinical scales were not significant in either group. Conclusion: This study could not confirm any significant changes in NAA after antidepressant treatment in the first episode of moderate depression, or in

  20. 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.

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

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    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.

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

    Science.gov (United States)

    Latagliata, Emanuele Claudio; Puglisi-Allegra, Stefano; Ventura, Rossella; Cabib, Simona

    2018-01-01

    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.

  3. Low-frequency brain stimulation to the left dorsolateral prefrontal cortex increases the negative impact of social exclusion among those high in personal distress.

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    Fitzgibbon, Bernadette Mary; Kirkovski, Melissa; Bailey, Neil Wayne; Thomson, Richard Hilton; Eisenberger, Naomi; Enticott, Peter Gregory; Fitzgerald, Paul Bernard

    2017-06-01

    The dorsolateral prefrontal cortex (DLPFC) is thought to play a key role in the cognitive control of emotion and has therefore, unsurprisingly, been implicated in the regulation of physical pain perception. This brain region may also influence the experience of social pain, which has been shown to activate similar neural networks as seen in response to physical pain. Here, we applied sham or active low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC, previously shown to exert bilateral effects in pain perception, in healthy participants. Following stimulation, participants played the "Cyberball Task"; an online ball-tossing game in which the subject participant is included or excluded. Compared to sham, rTMS did not modulate behavioural response to social exclusion. However, within the active rTMS group only, greater trait personal distress was related to enhanced negative outcomes to social exclusion. These results add further support to the notion that the effect of brain stimulation is not homogenous across individuals, and indicates the need to consider baseline individual differences when assessing response to brain stimulation. This seems particularly relevant in social neuroscience investigations, where trait factors may have a meaningful effect.

  4. High-definition transcranial direct current stimulation (HD-tDCS) of left dorsolateral prefrontal cortex affects performance in Balloon Analogue Risk Task (BART).

    Science.gov (United States)

    Guo, Heng; Zhang, Zhuoran; Da, Shu; Sheng, Xiaotian; Zhang, Xichao

    2018-02-01

    Studies on risk preferences have long been of great concern and have examined the neural basis underlying risk-based decision making. However, studies using conventional transcranial direct current stimulation (tDCS) revealed that bilateral stimulation could change risk propensity with limited evidence of precisely focalized unilateral high-definition transcranial direct current stimulation (HD-tDCS). The aim of this experiment was to investigate the effect of HD-tDCS focalizing the left dorsal lateral prefrontal cortex (DLPFC) on risk-taking behavior during the Balloon Analogue Risk Task (BART). This study was designed as a between-subject, single-blind, sham-controlled experiment. University students were randomly assigned to three groups: the anodal group (F3 anode, AF3, F1, F5, FC3 returned), the cathodal group (F3 cathodal, AF3, F1, F5, FC3 returned) and the sham group. Subsequently, 1.5-mA 20-min HD-tDCS was applied during the BART, and the Positive Affect and Negative Affect Scale (PANAS), the Sensation Seeking Scale-5 (SSS-5), and the Behavioral Inhibition System and Behavioral Approach System scale (BIS/BAS) were measured as control variables. The cathodal group earned less total money than the sham group, and no significant difference was observed between the anodal group and the sham group. These results showed that, to some extent, focalized unilateral cathodal HD-tDCS on left DLPFC could change performance during risky tasks and diminish risky decision making. Further studies are needed to investigate the dose effect and electrode distribution of HD-tDCS during risky tasks and examine synchronous brain activity to show the neural basis.

  5. The Sport Expert's Attention Superiority on Skill-related Scene Dynamic by The Activation of Left Medial Frontal Gyrus: An ERP and LORETA Study.

    Science.gov (United States)

    He, Mengyang; Qi, Changzhu; Lu, Yang; Song, Amanda; Hayat, Saba Z; Xu, Xia

    2018-03-07

    Extensive studies have shown that a sports expert is superior to a sports novice in visually perceptual-cognitive processes of sports scene information, however the attentional and neural basis of it has not been thoroughly explored. The present study examined whether a sport expert has the attentional superiority on scene information relevant to his/her sport skill, and explored what factor drives this superiority. To address this problem, EEGs were recorded as participants passively viewed sport scenes (tennis vs. non-tennis) and negative emotional faces in the context of a visual attention task, where the pictures of sport scenes or of negative emotional faces randomly followed the pictures with overlapping sport scenes and negative emotional faces. ERP results showed that for experts, the evoked potential of attentional competition elicited by the overlap of tennis scene was significantly larger than that evoked by the overlap of non-tennis scene, while this effect was absent for novices. The LORETA showed that the experts' left medial frontal gyrus (MFG) cortex was significantly more active as compared to the right MFG when processing the overlap of tennis scene, but the lateralization effect was not significant in novices. Those results indicate that experts have attentional superiority on skill-related scene information, despite intruding the scene through negative emotional faces that are prone to cause negativity bias towards their visual field as a strong distractor. This superiority is actuated by the activation of left MFG cortex and probably due to self-reference. Copyright © 2018. Published by Elsevier Ltd.

  6. Differential effects of continuous theta burst stimulation over left premotor cortex and right prefrontal cortex on modulating upper limb somatosensory input.

    Science.gov (United States)

    Brown, Matt J N; Staines, W Richard

    2016-02-15

    Somatosensory evoked potentials (SEPs) represent somatosensory processing in non-primary motor areas (i.e. frontal N30 and N60) and somatosensory cortices (i.e. parietal P50). It is well-known that the premotor cortex (PMC) and prefrontal cortex (PFC) are involved in the preparation and planning of upper limb movements but it is currently unclear how they modulate somatosensory processing for upper limb motor control. In the current study, two experiments examined SEP modulations after continuous theta burst stimulation (cTBS) was used to transiently disrupt the left PMC (Experiment 1) and right PFC (Experiment 2). Both Experiment 1 (n=15) and Experiment 2 (n=16) used pre-post experimental designs. In both experiments participants performed a task requiring detection of varying amplitudes of attended vibrotactile (VibT) stimuli to the left index finger (D2) and execution of a pre-matched finger sequence with the right (contralateral) hand to specific VibT targets. During the task, SEPs were measured to median nerve (MN) stimulations time-locked during pre-stimulus (250 ms before VibT), early response selection (250 ms after VibT), late preparatory (750 ms after VibT) and execution (1250 ms VibT) phases. The key findings of Experiment 1 revealed significant decreases in N30 and N60 peak amplitudes after cTBS to PMC. In contrast, the results of Experiment 2, also found significant decreased N60 peak amplitudes as well as trends for increased N30 and P50 peak amplitudes. A direct comparison of Experiment 1 and Experiment 2 confirmed differential modulation of N30 peak amplitudes after PMC (gated) compared to PFC (enhanced) cTBS. Collectively, these results support that both the left PMC and right PFC have modulatory roles on early somatosensory input into non-primary motor areas, such as PMC and supplementary motor area (SMA), represented by frontal N30 and N60 SEPs. These results confirm that PMC and PFC are both part of a network that regulates somatosensory input

  7. 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

  8. Involvement of prelimbic medial prefrontal cortex in panic-like elaborated defensive behaviour and innate fear-induced antinociception elicited by GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei: role of the endocannabinoid CB1 receptor.

    Science.gov (United States)

    Freitas, Renato Leonardo de; Salgado-Rohner, Carlos José; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre de Souza; Coimbra, Norberto Cysne

    2013-09-01

    It has been shown that GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei (DMH and VMH, respectively) induces elaborated defensive behavioural responses accompanied by antinociception, which has been utilized as an experimental model of panic attack. Furthermore, the prelimbic (PL) division of the medial prefrontal cortex (MPFC) has been related to emotional reactions and the processing of nociceptive information. The aim of the present study was to investigate the possible involvement of the PL cortex and the participation of local cannabinoid CB1 receptors in the elaboration of panic-like reactions and in innate fear-induced antinociception. Elaborated fear-induced responses were analysed during a 10-min period in an open-field test arena. Microinjection of the GABAA receptor antagonist bicuculline into the DMH/VMH evoked panic-like behaviour and fear-induced antinociception, which was decreased by microinjection of the non-selective synaptic contact blocker cobalt chloride in the PL cortex. Moreover, microinjection of AM251 (25, 100 or 400 pmol), an endocannabinoid CB1 receptor antagonist, into the PL cortex also attenuated the defensive behavioural responses and the antinociception that follows innate fear behaviour elaborated by DMH/VMH. These data suggest that the PL cortex plays an important role in the organization of elaborated forward escape behaviour and that this cortical area is also involved in the elaboration of innate fear-induced antinociception. Additionally, CB1 receptors in the PL cortex modulate both panic-like behaviours and fear-induced antinociception elicited by disinhibition of the DMH/VMH through microinjection of bicuculline.

  9. 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

  10. 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.

  11. 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.

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

    Indian Academy of Sciences (India)

    Sthitapranjya Pati

    2018-01-24

    isoxazolepropionic acid (AMPA) or N- methyl-D-aspartate (NMDA) receptor antagonist infusions into the mPFC lead to decreased anxiety-like behavioural responses (Dunn et al. 1989; Corbett and Dunn 1993). In contrast, reports also reveal ...

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

    Indian Academy of Sciences (India)

    Sthitapranjya Pati

    2018-01-24

    Jan 24, 2018 ... like behaviour in a task-specific fashion accompanied by enhanced c-Fos expression in the mPFC and multiple target circuits implicated in the ..... but exhibited a strong trend (figure 2I, two-way ANOVA: Figure 1. Selective ..... keeping with the former interpretation of pharmacogenetic silencing of SST ...

  14. Ginkgo biloba leaf extract (EGb 761®) and its specific acylated flavonol constituents increase dopamine and acetylcholine levels in the rat medial prefrontal cortex: possible implications for the cognitive enhancing properties of EGb 761®.

    Science.gov (United States)

    Kehr, J; Yoshitake, S; Ijiri, S; Koch, E; Nöldner, M; Yoshitake, T

    2012-08-01

    Experimental and clinical data suggest that the Ginkgo biloba standardized extract EGb 761® exerts beneficial effects in conditions which are associated with impaired cognitive function. However, the neurochemical correlates of these memory enhancing effects are not yet fully clarified. The aim of this study was to examine the effect of repeated oral administration of EGb 761® and some of its characteristic constituents on extracellular levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT), acetylcholine (ACh) and the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the medial prefrontal cortex (mPFC) of awake rats by use of in vivo microdialysis technique. Subacute (14 days, once daily), but not acute, oral treatment with EGb 761® (100 and 300 mg/kg) or the flavonoid fraction, which represents about 24% of the whole extract caused a significant and dose-dependent increase in extracellular DA levels in the mPFC. Repeated administration of EGb 761® also caused a modest but significant increase in the NA levels, whereas the concentrations of 5-HT and those of the metabolites DOPAC, HVA and 5-HIAA were not affected. The same treatment regimen was used in a subsequent study with the aim of investigating the effects of two Ginkgo-specific acylated flavonols, 3-O-(2''-O-(6'''-O-(p-hydroxy-trans-cinnamoyl)-β-D-glucosyl)-α-L-rhamnosyl)quercetin (Q-ag) and 3-O-(2''-O-(6'''-O-(p-hydroxy-trans-cinnamoyl)-β-D-glucosyl)-α-L-rhamnosyl)kaempferol (K-ag). Both compounds together represent about 4.5% of the whole extract. Repeated oral treatment with Q-ag (10 mg/kg) for 14 days caused a significant increase in extracellular DA levels of 159% and extracellular acetylcholine (ACh) levels of 151% compared to controls. Similarly, administration of K-ag (10 mg/kg) induced a significant rise of DA levels to 142% and ACh levels to 165% of controls, whereas treatment with isorhamnetin, an O

  15. Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

    Science.gov (United States)

    Smith, Ian M; Pang, Kevin C H; Servatius, Richard J; Jiao, Xilu; Beck, Kevin D

    2016-10-01

    The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. This data shows pair

  16. 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.

  17. Decreased neural activity and neural connectivity while performing a set-shifting task after inhibiting repetitive transcranial magnetic stimulation on the left dorsal prefrontal cortex

    NARCIS (Netherlands)

    Gerrits, N.J.H.M.; van den Heuvel, O.A.; van der Werf, Y.D.

    2015-01-01

    Background: Sub-optimal functioning of the dorsal prefrontal cortex (PFC) is associated with executive dysfunction, such as set-shifting deficits, in neurological and psychiatric disorders. We tested this hypothesis by investigating the effect of low-frequency 'inhibiting' off-line repetitive

  18. Decreased neural activity and neural connectivity while performing a set-shifting task after inhibiting repetitive transcranial magnetic stimulation on the left dorsal prefrontal cortex

    NARCIS (Netherlands)

    Gerrits, Niels J H M; van den Heuvel, Odile A; van der Werf, Ysbrand D

    2015-01-01

    BACKGROUND: Sub-optimal functioning of the dorsal prefrontal cortex (PFC) is associated with executive dysfunction, such as set-shifting deficits, in neurological and psychiatric disorders. We tested this hypothesis by investigating the effect of low-frequency 'inhibiting' off-line repetitive

  19. 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.

    2010-01-01

    Objective 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). Methods 1,455 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 3T trio scanner. Results 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, BA 9) (P = 0.015, uncorrected cluster level) and by 16.9% in the right anterior cingulate gyrus (BA 24) (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. Conclusions 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. PMID:19285558

  20. 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.

  1. Is the self special in the dorsomedial prefrontal cortex? An fMRI study.

    Science.gov (United States)

    Yaoi, Ken; Osaka, Naoyuki; Osaka, Mariko

    2009-01-01

    In recent years, several neuroimaging studies have suggested that the neural basis of the self-referential process1 is special, especially in the medial prefrontal cortex (MPFC). However, it remains controversial whether activity of the MPFC (and other related brain regions) appears only during the self-referential process. We investigated the neural correlates during the processing of references to the self, close other (friend), and distant other (prime minister) using fMRI. In comparison with baseline findings, referential processing to the three kinds of persons defined above showed common activation patterns in the dorsomedial prefrontal cortex (DMPFC), left middle temporal gyrus, left angular gyrus, posterior cingulate cortex and right cerebellum. Additionally, percent changes in BOLD signal in five regions of interest demonstrated the same findings. The result indicated that DMPFC was not special for the self-referential process, while there are common neural bases for evaluating the personalities of the self and others.

  2. 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.

  3. 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

  4. A Role for the Left Angular Gyrus in Episodic Simulation and Memory

    OpenAIRE

    Thakral, Preston P.; Madore, Kevin P.; Schacter, Daniel L.

    2017-01-01

    Functional magnetic resonance imaging (fMRI) studies indicate that episodic simulation (i.e., imagining specific future experiences) and episodic memory (i.e., remembering specific past experiences) are associated with enhanced activity in a common set of neural regions referred to as the core network. This network comprises the hippocampus, medial prefrontal cortex, and left angular gyrus, among other regions. Because fMRI data are correlational, it is unknown whether activity increases in c...

  5. Plasticity in the prefrontal cortex of adult rats

    Science.gov (United States)

    Kolb, Bryan; Gibb, Robbin

    2015-01-01

    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. PMID:25691857

  6. 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.

  7. Rostral and caudal prefrontal contribution to creativity: A meta-analysis of functional imaging data

    Directory of Open Access Journals (Sweden)

    Gil eGonen-Yaacovi

    2013-08-01

    Full Text Available Creativity is of central importance for human civilization, yet its neurocognitive bases are poorly understood. The aim of the present study was to integrate existing functional imaging data by using the meta-analysis approach. We reviewed 34 functional imaging studies that reported activation foci during tasks assumed to engage creative thinking in healthy adults. A coordinate-based meta-analysis using Activation Likelihood Estimation (ALE first showed a set of predominantly left-hemispheric regions shared by the various creativity tasks examined. These regions included the caudal lateral prefrontal cortex (PFC, the medial and lateral rostral PFC, and the inferior parietal and posterior temporal cortices. Further analyses showed that tasks involving the combination of remote information (combination tasks activated more anterior areas of the lateral PFC than tasks involving the free generation of unusual responses (unusual generation tasks, although both types of tasks shared caudal prefrontal areas. In addition, verbal and non-verbal tasks involved the same regions in the left caudal prefrontal, temporal, and parietal areas, but also distinct domain-oriented areas. Taken together, these findings suggest that several frontal and parieto-temporal regions may support cognitive processes shared by diverse creativity tasks, and that some regions may be specialized for distinct types of processes. In particular, the lateral PFC appeared to be organized along a rostro-caudal axis, with rostral regions involved in combining ideas creatively and more posterior regions involved in freely generating novel ideas.

  8. 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...

  9. 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.

  10. 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

  11. Theta oscillations orchestrate medial temporal lobe and neocortex in remembering autobiographical memories.

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    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.

  12. Prefrontal cortical GABAergic signaling and impaired behavioral flexibility in aged F344 rats.

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    Beas, B S; McQuail, J A; Ban Uelos, C; Setlow, B; Bizon, J L

    2017-03-14

    The prefrontal cortex (PFC) is critical for the ability to flexibly adapt established patterns of behavior in response to a change in environmental contingencies. Impaired behavioral flexibility results in maladaptive strategies such as perseveration on response options that no longer produce a desired outcome. Pharmacological manipulations of prefrontal cortical GABAergic signaling modulate behavioral flexibility in animal models, and prefrontal cortical interneuron dysfunction is implicated in impaired behavioral flexibility that accompanies neuropsychiatric disease. As deficits in behavioral flexibility also emerge during the normal aging process, the goal of this study was to determine the role of GABAergic signaling, specifically via prefrontal cortical GABA(B) receptors, in such age-related deficits. Young and aged rats were trained in a set shifting task performed in operant chambers. First, rats learned to discriminate between two response levers to obtain a food reward on the basis of a cue light illuminated above the correct lever. Upon acquisition of this initial discrimination, the contingencies were shifted such that rats had to ignore the cue light and respond on the levers according to their left/right positions. Both young and aged rats acquired the initial discrimination similarly; however, aged rats were impaired relative to young following the set shift. Among aged rats, GABA(B) receptor expression in the medial prefrontal cortex (mPFC) was strongly correlated with set shifting, such that lower expression was associated with worse performance. Subsequent experiments showed that intra-mPFC administration of the GABA(B) receptor agonist baclofen enhanced set shifting performance in aged rats. These data directly link GABAergic signaling via GABA(B) receptors to impaired behavioral flexibility associated with normal aging. Copyright © 2016. Published by Elsevier Ltd.

  13. Prefrontal norepinephrine determines attribution of "high" motivational salience.

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    Rossella Ventura

    Full Text Available Intense motivational salience attribution is considered to have a major role in the development of different psychopathologies. Numerous brain areas are involved in "normal" motivational salience attribution processes; however, it is not clear whether common or different neural mechanisms also underlie intense motivational salience attribution. To elucidate this a brain area and a neural system had to be envisaged that were involved only in motivational salience attribution to highly salient stimuli. Using intracerebral microdialysis, we found that natural stimuli induced an increase in norepinephrine release in the medial prefrontal cortex of mice proportional to their salience, and that selective prefrontal norepinephrine depletion abolished the increase of norepinephrine release in the medial prefrontal cortex induced by exposure to appetitive (palatable food or aversive (light stimuli independently of salience. However, selective norepinephrine depletion in the medial prefrontal cortex impaired the place conditioning induced exclusively by highly salient stimuli, thus indicating that prefrontal noradrenergic transmission determines approach or avoidance responses to both reward- and aversion-related natural stimuli only when the salience of the unconditioned natural stimulus is high enough to induce sustained norepinephrine outflow. This affirms that prefrontal noradrenergic transmission determines motivational salience attribution selectively when intense motivational salience is processed, as in conditions that characterize psychopathological outcomes.

  14. Decreased prefrontal cortical dopamine transmission in alcoholism.

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    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. Complementary Patterns of Direct Amygdala and Hippocampal Projections to the Macaque Prefrontal Cortex.

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    Aggleton, John P; Wright, Nicholas F; Rosene, Douglas L; Saunders, Richard C

    2015-11-01

    The projections from the amygdala and hippocampus (including subiculum and presubiculum) to prefrontal cortex were compared using anterograde tracers injected into macaque monkeys (Macaca fascicularis, Macaca mulatta). Almost all prefrontal areas were found to receive some amygdala inputs. These connections, which predominantly arose from the intermediate and magnocellular basal nucleus, were particularly dense in parts of the medial and orbital prefrontal cortex. Contralateral inputs were not, however, observed. The hippocampal projections to prefrontal areas were far more restricted, being confined to the ipsilateral medial and orbital prefrontal cortex (within areas 11, 13, 14, 24a, 32, and 25). These hippocampal projections principally arose from the subiculum, with the fornix providing the sole route. Thus, while the lateral prefrontal cortex essentially receives only amygdala inputs, the orbital prefrontal cortex receives both amygdala and hippocampal inputs, though these typically target different areas. Only in medial prefrontal cortex do direct inputs from both structures terminate in common sites. But, even when convergence occurs within an area, the projections predominantly terminate in different lamina (hippocampal inputs to layer III and amygdala inputs to layers I, II, and VI). The resulting segregation of prefrontal inputs could enable the parallel processing of different information types in prefrontal cortex. © The Author 2015. Published by Oxford University Press.

  16. Resting state amygdala-prefrontal connectivity predicts symptom change after cognitive behavioral therapy in generalized social anxiety disorder.

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    Klumpp, Heide; Keutmann, Michael K; Fitzgerald, Daniel A; Shankman, Stewart A; Phan, K Luan

    2014-01-01

    Aberrant amygdala-prefrontal interactions at rest and during emotion processing are implicated in the pathophysiology of generalized social anxiety disorder (gSAD), a common disorder characterized by fears of potential scrutiny. Cognitive behavioral therapy (CBT) is first-line psychotherapy for gSAD and other anxiety disorders. While CBT is generally effective, there is a great deal of heterogeneity in treatment response. To date, predictors of success in CBT for gSAD include reduced amygdala reactivity and increased activity in prefrontal regulatory regions (e.g., anterior cingulate cortex, "ACC") during emotion processing. However, studies have not examined whether tonic (i.e., at rest) coupling of amygdala and these prefrontal regions also predict response to CBT. Twenty-one patients with gSAD participated in resting-state functional magnetic resonance imaging (fMRI) before 12 weeks of CBT. Overall, symptom severity was significantly reduced after completing CBT; however, the patients varied considerably in degree of symptom change. Whole-brain voxel-wise findings showed symptom improvement after CBT was predicted by greater right amygdala-pregenual ACC ("pgACC") connectivity and greater left amygdala-pgACC coupling encompassing medial prefrontal cortex. In support of their predictive value, area under receiver operating characteristic curve was significant for the left and right amygdala-pgACC in relation to treatment responders. Improvement after CBT was predicted by enhanced resting-state bilateral amygdala-prefrontal coupling in gSAD. Preliminary results suggest baseline individual differences in a fundamental circuitry that may underlie emotion regulation contributed to variation in symptom change after CBT. Findings offer a new approach towards using a biological measure to foretell who will most likely benefit from CBT. In particular, the departure from neural predictors based on illness-relevant stimuli (e.g., socio-emotional stimuli in gSAD) permits

  17. Gene expression profiling of the dorsolateral and medial orbitofrontal cortex in schizophrenia

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    Mladinov Mihovil

    2016-01-01

    Full Text Available Schizophrenia is a complex polygenic disorder of unknown etiology. Over 3,000 candidate genes associated with schizophrenia have been reported, most of which being mentioned only once. Alterations in cognitive processing - working memory, metacognition and mentalization - represent a core feature of schizophrenia, which indicates the involvement of the prefrontal cortex in the pathophysiology of this disorder. Hence we compared the gene expression in postmortem tissue from the left and right dorsolateral prefrontal cortex (DLPFC, Brodmann's area 46, and the medial part of the orbitofrontal cortex (MOFC, Brodmann's area 11/12, in six patients with schizophrenia and six control brains. Although in the past decade several studies performed transcriptome profiling in schizophrenia, this is the first study to investigate both hemispheres, providing new knowledge about possible brain asymmetry at the level of gene expression and its relation to schizophrenia. We found that in the left hemisphere, twelve genes from the DLPFC and eight genes from the MOFC were differentially expressed in patients with schizophrenia compared to controls. In the right hemisphere there was only one gene differentially expressed in the MOFC. We reproduce the involvement of previously reported genes TARDBP and HNRNPC in the pathogenesis of schizophrenia, and report seven novel genes: SART1, KAT7, C1D, NPM1, EVI2A, XGY2, and TTTY15. As the differentially expressed genes only partially overlap with previous studies that analyzed other brain regions, our findings indicate the importance of considering prefrontal cortical regions, especially those in the left hemisphere, for obtaining disease-relevant insights.

  18. Injerto libre braquial medial Free medial arm graft

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    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

  19. Discourse Production Following Injury to the Dorsolateral Prefrontal Cortex

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    Coelho, Carl; Le, Karen; Mozeiko, Jennifer; Krueger, Frank; Grafman, Jordan

    2012-01-01

    Individuals with damage to the prefrontal cortex, and the dorsolateral prefrontal cortex (DLPFC) in particular, often demonstrate difficulties with the formulation of complex language not attributable to aphasia. The present study employed a discourse analysis procedure to characterize the language of individuals with left (L) or right (R) DLPFC…

  20. Finding prefrontal cortex in the rat.

    Science.gov (United States)

    Leonard, Christiana M

    2016-08-15

    The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections The cortical projection field of the mediodorsal nucleus of the thalamus (MD) was identified in the rat using the Fink-Heimer silver technique for tracing degenerating fibers. Small stereotaxic lesions confined to MD were followed by terminal degeneration in the dorsal bank of the rhinal sulcus (sulcal cortex) and the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum (medial cortex). No degenerating fibers were traced to the convexity of the hemisphere. The cortical formation receiving a projection from MD is of a relatively undifferentiated type which had been previously classified as juxtallocortex. A study of the efferent fiber connections of the rat׳s MD-projection cortex demonstrated some similarities to those of monkey prefrontal cortex. A substantial projection to the pretectal area and deep layers of the superior colliculus originates in medial cortex, a connection previously reported for caudal prefrontal (area 8) cortex in the monkey. Sulcal cortex projects to basal olfactory structures and lateral hypothalamus, as does orbital frontal cortex in the monkey. The rat׳s MD-projection cortex differs from that in the monkey in that it lacks a granular layer and appears to have no prominent direct associations with temporal and juxtahippocampal areas. Furthermore, retrograde degeneration does not appear in the rat thalamus after damage to MD-projection areas, suggesting that the striatum or thalamus receives a proportionally larger share of the MD-projection in this animal than it does in the monkey. Comparative behavioral investigations are in progress to investigate functional differences between granular prefrontal cortex in the primate and the relatively primitive MD-projection cortex in the rat. © 1969. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B

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

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    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

  2. 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

  3. 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

  4. Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories.

    Science.gov (United States)

    Warren, Brandon L; Mendoza, Michael P; Cruz, Fabio C; Leao, Rodrigo M; Caprioli, Daniele; Rubio, F Javier; Whitaker, Leslie R; McPherson, Kylie B; Bossert, Jennifer M; Shaham, Yavin; Hope, Bruce T

    2016-06-22

    In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in "neuronal ensembles." Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area. A current popular hypothesis is that neuronal ensembles in different prefrontal cortex areas control reward-associated versus extinction-associated memories: the dorsal medial prefrontal cortex (mPFC) promotes reward seeking, whereas the

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

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    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.

  6. Negative emotion modulates prefrontal cortex activity during a working memory task: A NIRS study

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    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.

  7. Verbal Memory Deficits Are Correlated with Prefrontal Hypometabolism in 18FDG PET of Recreational MDMA Users

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    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

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

    Science.gov (United States)

    2014-07-11

    experiment, two classes of stimuli were used. In each stimulus class, two specific colors could be combined to generate Stroop stimuli. For example...is also engaged in tasks without a significant behavioral com- ponent, or when a specific motor command is neither planned nor executed (Büchel et al...Model activity was averaged over the first 20 model iterations following the onset of the target and flanker cues. SIMULATION 2: ITEM- SPECIFIC VS. GLOBAL

  9. Trait impulsivity and impaired prefrontal impulse inhibition function in adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study.

    Science.gov (United States)

    Ding, Wei-na; Sun, Jin-hua; Sun, Ya-Wen; Chen, Xue; Zhou, Yan; Zhuang, Zhi-guo; Li, Lei; Zhang, Yong; Xu, Jian-rong; Du, Ya-song

    2014-05-30

    Recent studies suggest that Internet gaming addiction (IGA) is an impulse disorder, or is at least related to impulse control disorders. In the present study, we hypothesized that different facets of trait impulsivity may be specifically linked to the brain regions with impaired impulse inhibition function in IGA adolescents. Seventeen adolescents with IGA and seventeen healthy controls were scanned during performance of a response-inhibition Go/No-Go task using a 3.0 T MRI scanner. The Barratt Impulsiveness Scale (BIS)-11 was used to assess impulsivity. There were no differences in the behavioral performance on the Go/No-Go task between the groups. However, the IGA group was significantly hyperactive during No-Go trials in the left superior medial frontal gyrus, right anterior cingulate cortex, right superior/middle frontal gyrus, left inferior parietal lobule, left precentral gyrus, and left precuneus and cuneus. Further, the bilateral middle temporal gyrus, bilateral inferior temporal gyrus, and right superior parietal lobule were significantly hypoactive during No-Go trials. Activation of the left superior medial frontal gyrus was positively associated with BIS-11 and Chen Internet Addiction Scale (CIAS) total score across IGA participants. Our data suggest that the prefrontal cortex may be involved in the circuit modulating impulsivity, while its impaired function may relate to high impulsivity in adolescents with IGA, which may contribute directly to the Internet addiction process.

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

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    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.

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

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    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.

  12. The effects of transcranial magnetic stimulation over the dorsolateral prefrontal cortex on suppression of habitual counting during random number generation.

    Science.gov (United States)

    Jahanshahi, M; Profice, P; Brown, R G; Ridding, M C; Dirnberger, G; Rothwell, J C

    1998-08-01

    Random number generation is an attention-demanding task that engages working memory and executive processes. Random number generation requires holding information 'on line', suppression of habitual counting, internally driven response generation and monitoring of responses. Evidence from PET studies suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in the generation of random responses. We examined the effects of short trains of transcranial magnetic stimulation (TMS) over the left or right DLPFC or medial frontal cortex on random number generation in healthy normal participants. As in previous evidence, in control trials without stimulation participants performed poorly on the random number generation task, showing repetition avoidance and a tendency to count. Brief disruption of processing with TMS over the left DLPFC changed the balance of the individuals' counting bias, increasing the most habitual counting in ones and reducing the lower probability response of counting in twos. This differential effect of TMS over the left DLPFC on the balance of the subject's counting bias was not obtained with TMS over the right DLPFC or the medial frontal cortex. The results suggest that, with disruption of the left DLPFC with TMS, habitual counting in ones that has previously been suppressed is released from inhibition. From these findings a network modulation model of random number generation is proposed, whereby suppression of habitual responses is achieved through the modulatory influence of the left DLPFC over a number-associative network in the superior temporal cortex. To allow emergence of appropriate random responses, the left DLPFC inhibits the superior temporal cortex to prevent spreading activation and habitual counting in ones.

  13. Prefrontal versus motor cortex transcranial direct current stimulation (tDCS) effects on post-surgical opioid use.

    Science.gov (United States)

    Borckardt, Jeffrey J; Reeves, Scott T; Milliken, Cole; Carter, Brittan; Epperson, Thomas I; Gunselman, Ryan J; Madan, Alok; Del Schutte, H; Demos, Harry A; George, Mark S

    Pain is often a complaint that precedes total knee arthroplasty (TKA), however the procedure itself is associated with considerable post-operative pain lasting days to weeks which can predict longer-term surgical outcomes. Previously, we reported significant opioid-sparing effects of motor cortex transcranial direct current stimulation from a single-blind trial. In the present study, we used double-blind methodology to compare motor cortex tDCS and prefrontal cortex tDCS to both sham and active-control (active electrodes over non-pain modulating brain areas) tDCS. 58 patients undergoing unilateral TKA were randomly assigned to receive 4 20-min sessions (a total of 80 min) of tDCS (2 mA) post-surgery with electrodes placed to create 4 groups: 1) MOTOR (n = 14); anode-motor/cathode-right prefrontal, 2) PREFRONTAL (n = 16); anode-left-prefrontal/cathode-right-sensory, 3) ACTIVE-CONTROL (n = 15); anode-left-temporal-occipital junction/cathode-medial-anterior-premotor-area, and 4) SHAM (n = 13); 0 mA-current stimulation using placements 1 or 2. Patient controlled analgesia (PCA; hydromorphone) use was tracked during the ∼72-h post-surgery. Patients in the sham group and the active-control group used 15.4 mg (SD = 14.1) and 16.0 mg (SD = 9.7) of PCA hydromorphone respectively. There was no difference between the slopes of the cumulative PCA usage curves between these two groups (p = 0.25; ns). Patients in the prefrontal tDCS group used an average of 11.7 mg (SD = 5.0) of PCA hydromporhone, and the slope of the cumulative PCA usage curve was significantly lower than sham (p prefrontal cortex may be a reasonable approach to reducing post-TKA opioid requirements. Given the unexpected finding that motor cortex failed to produce an opioid sparing effect in this follow-up trial, further research in the area of post-operative cortical stimulation is still needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 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

  15. Dissociable contributions of the prefrontal cortex to hippocampus- and caudate nucleus-dependent virtual navigation strategies.

    Science.gov (United States)

    Dahmani, Louisa; Bohbot, Véronique D

    2015-01-01

    The hippocampus and the caudate nucleus are critical to spatial- and stimulus-response-based navigation strategies, respectively. The hippocampus and caudate nucleus are also known to be anatomically connected to various areas of the prefrontal cortex. However, little is known about the involvement of the prefrontal cortex in these processes. In the current study, we sought to identify the prefrontal areas involved in spatial and response learning. We used functional magnetic resonance imaging (fMRI) and voxel-based morphometry to compare the neural activity and grey matter density of spatial and response strategy users. Twenty-three healthy young adults were scanned in a 1.5 T MRI scanner while they engaged in the Concurrent Spatial Discrimination Learning Task, a virtual navigation task in which either a spatial or response strategy can be used. In addition to increased BOLD activity in the hippocampus, spatial strategy users showed increased BOLD activity and grey matter density in the ventral area of the medial prefrontal cortex, especially in the orbitofrontal cortex. On the other hand, response strategy users exhibited increased BOLD activity and grey matter density in the dorsal area of the medial prefrontal cortex. Given the prefrontal cortex's role in reward-guided decision-making, we discuss the possibility that the ventromedial prefrontal cortex, including the orbitofrontal cortex, supports spatial learning by encoding stimulus-reward associations, while the dorsomedial prefrontal cortex supports response learning by encoding action-reward associations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices of human alcoholics

    OpenAIRE

    Watanabe, Hiroyuki; Henriksson, Richard; Ohnishi, Yoshinori N.; Ohnishi, Yoko H.; Harper, Clive; Sheedy, Donna; Garrick, Therese; Nyberg, Fred; Nestler, Eric J.; Bakalkin, Georgy; Yakovleva, Tatjana

    2009-01-01

    The transcription factor DeltaFosB is accumulated in the addiction circuitry, including the orbitofrontal and medial prefrontal cortices of rodents chronically exposed to ethanol or other drugs of abuse, and has been suggested to play a direct role in addiction maintenance. To address this hypothesis in the context of substance dependence in humans, we compared the immunoreactivities of FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices (OFC and DLPFC respectively) betwee...

  17. 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 ...

  18. 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.

  19. Financial literacy is associated with medial brain region functional connectivity in old age.

    Science.gov (United States)

    Han, S Duke; Boyle, Patricia A; Yu, Lei; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue; Bennett, David A

    2014-01-01

    Financial literacy refers to the ability to access and utilize financial information in ways that promote better outcomes. In old age, financial literacy has been associated with a wide range of positive characteristics; however, the neural correlates remain unclear. Recent work has suggested greater co-activity between anterior-posterior medial brain regions is associated with better brain functioning. We hypothesized financial literacy would be associated with this pattern. We assessed whole-brain functional connectivity to a posterior cingulate cortex (PCC) seed region of interest (ROI) in 138 participants of the Rush Memory and Aging Project. Results revealed financial literacy was associated with greater functional connectivity between the PCC and three regions: the right ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right precuneus. Results also revealed financial literacy was associated negatively with functional connectivity between the PCC and left caudate. Post hoc analyses showed the PCC-vmPFC relationship accounted for the most variance in a regression model adjusted for all four significant functional connectivity relationships, demographic factors, and global cognition. These findings provide information on the neural mechanisms associated with financial literacy in old age. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Executive Semantic Processing Is Underpinned by a Large-scale Neural Network: Revealing the Contribution of Left Prefrontal, Posterior Temporal, and Parietal Cortex to Controlled Retrieval and Selection Using TMS

    Science.gov (United States)

    Whitney, Carin; Kirk, Marie; O'Sullivan, Jamie; Ralph, Matthew A. Lambon; Jefferies, Elizabeth

    2012-01-01

    To understand the meanings of words and objects, we need to have knowledge about these items themselves plus executive mechanisms that compute and manipulate semantic information in a task-appropriate way. The neural basis for semantic control remains controversial. Neuroimaging studies have focused on the role of the left inferior frontal gyrus…

  1. 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.

  2. Linking trait-based phenotypes to prefrontal cortex activation during inhibitory control.

    Science.gov (United States)

    Rodrigo, Achala H; Di Domenico, Stefano I; Graves, Bryanna; Lam, Jaeger; Ayaz, Hasan; Bagby, R Michael; Ruocco, Anthony C

    2016-01-01

    Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  3. 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.

  4. Medial subtalar dislocation

    African Journals Online (AJOL)

    Pr KODO

    A 27- year old female patient suffered from a closed medial subtalar dislocation treated by ... injury. She presented with pain, swelling of and internal rotation of the foot in relation to the knee joint. The talus was prominent dorsolaterally. Globally the clinical appearance was that ... frequently than the lateral ones and can be.

  5. A Role for the Left Angular Gyrus in Episodic Simulation and Memory.

    Science.gov (United States)

    Thakral, Preston P; Madore, Kevin P; Schacter, Daniel L

    2017-08-23

    Functional magnetic resonance imaging (fMRI) studies indicate that episodic simulation (i.e., imagining specific future experiences) and episodic memory (i.e., remembering specific past experiences) are associated with enhanced activity in a common set of neural regions referred to as the core network. This network comprises the hippocampus, medial prefrontal cortex, and left angular gyrus, among other regions. Because fMRI data are correlational, it is unknown whether activity increases in core network regions are critical for episodic simulation and episodic memory. In the current study, we used MRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of the left angular gyrus would impair both episodic simulation and memory (16 participants, 10 females). Relative to TMS to a control site (vertex), disruption of the left angular gyrus significantly reduced the number of internal (i.e., episodic) details produced during the simulation and memory tasks, with a concomitant increase in external detail production (i.e., semantic, repetitive, or off-topic information), reflected by a significant detail by TMS site interaction. Difficulty in the simulation and memory tasks also increased after TMS to the left angular gyrus relative to the vertex. In contrast, performance in a nonepisodic control task did not differ statistically as a function of TMS site (i.e., number of free associates produced or difficulty in performing the free associate task). Together, these results are the first to demonstrate that the left angular gyrus is critical for both episodic simulation and episodic memory. SIGNIFICANCE STATEMENT Humans have the ability to imagine future episodes (i.e., episodic simulation) and remember episodes from the past (i.e., episodic memory). A wealth of neuroimaging studies have revealed that these abilities are associated with enhanced activity in a core network of neural regions, including the hippocampus, medial prefrontal

  6. Prefrontal Cortex and Neostriatum Self-Stimulation In the Rat : Differential Effects Produced by Apomorphine

    NARCIS (Netherlands)

    Mora, F.; Phillips, A.G.; Koolhaas, J.M.; Rolls, E.T.

    1976-01-01

    In a dose-response experiment, the effects of intraperitoneal injections of the dopamine receptor agonist, apomorphine (0.075, 0.15, 0.3, 0.6 and 1.2 mg/kg) were studied on self-stimulation elicited from electrodes implanted in the medial and sulcal prefrontal cortex and caudate-putamen in the rat.

  7. 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…

  8. Noradrenaline and dopamine efflux in the prefrontal cortex in relation to appetitive classical conditioning

    NARCIS (Netherlands)

    Mingote, Susana; de Bruin, Jan P. C.; Feenstra, Matthijs G. P.

    2004-01-01

    We trained rats to learn that an auditory stimulus predicted delivery of reward pellets in the Skinner box. After 2 d of training, we measured changes in efflux of noradrenaline (NA) and dopamine (DA) in the medial prefrontal cortex using microdialysis on the third day. Animals were subjected to a

  9. 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.

  10. Increased perceived stress is related to decreased prefrontal cortex volumes among older adults.

    Science.gov (United States)

    Moreno, Georgina L; Bruss, Joel; Denburg, Natalie L

    2017-05-01

    Several of the brain regions vulnerable to increased levels of stress (i.e., hippocampus and prefrontal cortex) are also known to undergo disproportionate decline during normal aging. To date, surprisingly little research has examined the effects of stress on the brain among healthy human populations, much less in the elderly. The aim of the current study was to investigate the relationship between chronic stress and brain morphometry in regions known for their involvement in the stress response, namely the prefrontal cortex, hippocampus, and amygdala, in a sample of healthy older adults. The Perceived Stress Scale and structural magnetic resonance imaging (MRI) were collected in 28 older adult individuals aged 65 to 90 years. Gray and white matter volumes in various regions of interest in the prefrontal cortex and medial temporal lobes were calculated using semiautomated segmentation tools. Perceived stress was negatively correlated with overall prefrontal cortex (PFC) volume, specifically in overall white matter volume of the PFC. Additionally, perceived stress was negatively correlated with gray and white matter volumes in lateral regions of the PFC, specifically, in the ventrolateral and dorsolateral PFC. Perceived stress was not significantly related to medial temporal lobe volumes. These findings suggest that among healthy older adults, there is a salient relationship between prefrontal cortex volumes and levels of perceived stress. This research fills a critical gap in the current literature and provides initial groundwork for future studies investigating the relationship between perceived stress and the prefrontal cortex in the context of healthy aging.

  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. Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

    Science.gov (United States)

    Moretti, Rita; Signori, Riccardo

    2016-01-01

    Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday 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 gray 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 decision, major responsible 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

  13. Verbal memory impairment in new onset bipolar disorder: Relationship with frontal and medial temporal morphology.

    Science.gov (United States)

    Chakrabarty, Trisha; Kozicky, Jan-Marie; Torres, Ivan J; Lam, Raymond W; Yatham, Lakshmi N

    2015-06-01

    Verbal memory (VM) impairment is a trait feature of bipolar I disorder (BDI) that is present at illness onset and associated with functional outcome. However, little is known about the morphological abnormalities underlying this deficit early in the disease course. This study examined the neurobiological correlates of VM impairment in euthymic newly diagnosed patients, with attention to frontal and medial temporal (MT) structures known to contribute to VM. Euthymic patients with BDI recently recovered from their first episode of mania (n = 42) were compared with healthy subjects (n = 37) using measures of the California Verbal Learning Test (CVLT-II) associated with frontal and MT functioning. A subset of participants had 3T MRI scan (n = 31 patient group, n = 30 healthy subject group). Hippocampal and prefrontal volumes were analyzed using FreeSurfer 5.1 and correlated with their corresponding CVLT-II subscores. Patients showed decreased performance in total learning as well as short and long delay verbal recall. Consistent with MT dysfunction, they also showed deficits in recognition discriminability and learning slope. In the patient group only, left hippocampal volumes were negatively correlated with these measures. These results suggest that anomalous MT functioning is involved with VM impairment early in the course of BDI.

  14. 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.

  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...... mPFC neurons in VPA-exposed mice, or by inhibiting D2R+ neurons in wild-type mice. These findings suggest that multiple forms of autism may alter the physiology of specific deep-layer prefrontal neurons that project to subcortical targets. Furthermore, a highly overlapping population-prefrontal D2R...

  16. 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.)

  17. 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

  18. Right prefrontal cortex transcranial direct current stimulation enhances multi-day savings in sensorimotor adaptation.

    Science.gov (United States)

    Seidler, Rachael D; Gluskin, Brittany S; Greeley, Brian

    2017-01-01

    We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of visuomotor adaptation. Recent behavioral studies suggest that sensorimotor savings, or faster relearning on second exposure to a task, are due to recall of these early, strategic components of adaptation. In the present study we applied anodal transcranial direct current stimulation to right or left prefrontal cortex or left motor cortex. We found that all groups adapted dart throwing movements while wearing prism lenses at the same rate as subjects receiving sham stimulation on day 1 On test day 2, which was conducted a few days later, the right prefrontal and left motor cortex groups adapted faster than the sham group. Moreover, only the right prefrontal group exhibited greater savings, expressed as a greater difference between day 1 and day 2 errors, compared with sham stimulation. These findings support the hypothesis that the right prefrontal cortex contributes to sensorimotor adaptation and savings. We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of manual visuomotor adaptation. Sensorimotor savings, or faster adaptation to a previously experienced perturbation, has been recently linked to cognitive processes. We show that facilitating the right prefrontal cortex with anodal transcranial direct current stimulation enhances sensorimotor savings compared with sham stimulation. Copyright © 2017 the American Physiological Society.

  19. 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...... and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive...... pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor...

  20. 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

  1. Working memory and left medial temporal cortical thickness

    OpenAIRE

    Pastura, Giuseppe; Kubo, Tadeu Takao Almodovar; Regalla, Maria Angélica; Mesquita, Cíntia Machado; Coutinho, Gabriel; Gasparetto, Emerson Leandro; Figueiredo, Otávio; Mattos, Paulo; Araújo, Alexandra Prüfer de Queiroz Campos

    2016-01-01

    ABSTRACT Objective To perform a pilot study to investigate the association between working memory and cortical thickness in a sample of attention deficit/hyperactivity disorder (ADHD) children. Methods Seventeen children aged 7-10 years diagnosed with ADHD and 16 healthy children underwent a magnetic resonance scan for cortical thickness measurements. Data was correlated with working memory performance using the Backwards Digit Span subtest of the Wechsler Intelligence Scale for Children. ...

  2. 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

  3. Symptomatic Os Subtibiale Associated with Chronic Pain Around the Medial Malleolus in a Young Athlete

    Directory of Open Access Journals (Sweden)

    Iliev Alexandar A.

    2016-03-01

    Full Text Available An os subtibiale is a rare accessory bone located below or behind the medial malleolus. Herein we present a rare case of a painful os subtibiale in a young triathlete who presented with pain, redness and swelling below his left medial malleolus. Plain radiographs and three-dimensional computed tomography revealed a well-defined oval bone distal to the left medial malleolus. After conservative treatment failed, the ossicle was excised in an open surgery with complete resolution of symptoms. This case report emphasizes the need for clinical awareness of different anatomical variations of the bones of the foot.

  4. Timing of emotion representation in right and left occipital region: Evidence from combined TMS-EEG.

    Science.gov (United States)

    Mattavelli, Giulia; Rosanova, Mario; Casali, Adenauer G; Papagno, Costanza; Romero Lauro, Leonor J

    2016-07-01

    Neuroimaging and electrophysiological studies provide evidence of hemispheric differences in processing faces and, in particular, emotional expressions. However, the timing of emotion representation in the right and left hemisphere is still unclear. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) was used to explore cortical responsiveness during behavioural tasks requiring processing of either identity or expression of faces. Single-pulse TMS was delivered 100ms after face onset over the medial prefrontal cortex (mPFC) while continuous EEG was recorded using a 60-channel TMS-compatible amplifier; right premotor cortex (rPMC) was also stimulated as control site. The same face stimuli with neutral, happy and fearful expressions were presented in separate blocks and participants were asked to complete either a facial identity or facial emotion matching task. Analyses performed on posterior face specific EEG components revealed that mPFC-TMS reduced the P1-N1 component. In particular, only when an explicit expression processing was required, mPFC-TMS interacted with emotion type in relation to hemispheric side at different timing; the first P1-N1 component was affected in the right hemisphere whereas the later N1-P2 component was modulated in the left hemisphere. These findings support the hypothesis that the frontal cortex exerts an early influence on the occipital cortex during face processing and suggest a different timing of the right and left hemisphere involvement in emotion discrimination. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum

    NARCIS (Netherlands)

    Westerink, B.H.C.; Kawahara, Y; de Boer, P; Geels, C; de Vries, J.B; Wikström, H.V; van Kalkeren, A; van Vliet, B; Kruse, C.H; Long, S.K

    2001-01-01

    Dose-effect curves were established for the effects of the antipsychotic drugs haloperidol, clozapine, olanzapine, risperidone and ziprasidone on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex, and of dopamine in the striatum. Haloperidol was more effective in

  6. 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…

  7. Dopamine and noradrenaline efflux in the rat prefrontal cortex after classical aversive conditioning to an auditory cue

    NARCIS (Netherlands)

    Feenstra, M. G.; Vogel, M.; Botterblom, M. H.; Joosten, R. N.; de Bruin, J. P.

    2001-01-01

    We used bilateral microdialysis in the medial prefrontal cortex (PFC) of awake, freely moving rats to study aversive conditioning to an auditory cue in the controlled environment of the Skinner box. The presentation of the explicit conditioned stimuli (CS), previously associated with foot shocks,

  8. Prelimbic and infralimbic prefrontal cortex interact during fast network oscillations.

    Directory of Open Access Journals (Sweden)

    Karlijn I van Aerde

    Full Text Available BACKGROUND: The medial prefrontal cortex has been implicated in a variety of cognitive and executive processes such as decision making and working memory. The medial prefrontal cortex of rodents consists of several areas including the prelimbic and infralimbic cortex that are thought to be involved in different aspects of cognitive performance. Despite the distinct roles in cognitive behavior that have been attributed to prelimbic and infralimbic cortex, little is known about neuronal network functioning of these areas, and whether these networks show any interaction during fast network oscillations. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that fast network oscillations in rat infralimbic cortex slices occur at higher frequencies and with higher power than oscillations in prelimbic cortex. The difference in oscillation frequency disappeared when prelimbic and infralimbic cortex were disconnected. CONCLUSIONS/SIGNIFICANCE: Our data indicate that neuronal networks of prelimbic and infralimbic cortex can sustain fast network oscillations independent of each other, but suggest that neuronal networks of prelimbic and infralimbic cortex are interacting during these oscillations.

  9. The regional neuronal activity in left posterior middle temporal gyrus is correlated with the severity of chronic aphasia.

    Science.gov (United States)

    Li, Jianlin; Du, Dunren; Gao, Wei; Sun, Xichun; Xie, Haizhu; Zhang, Gang; Li, Jian; Li, Honglun; Li, Kefeng

    2017-01-01

    Aphasia is one of the most disabling cognitive deficits affecting >2 million people in the USA. The neuroimaging characteristics of chronic aphasic patients (>6 months post onset) remain largely unknown. The objective of this study was to investigate the regional signal changes of spontaneous neuronal activity of brain and the inter-regional connectivity in chronic aphasia. Resting-state blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) was used to obtain fMRI data from 17 chronic aphasic patients and 20 healthy control subjects in a Siemens Verio 3.0T MR Scanner. The amplitude of low-frequency fluctuation (ALFF) was determined, which directly reflects the regional neuronal activity. The functional connectivity (FC) of fMRI was assessed using a seed voxel linear correlation approach. The severity of aphasia was evaluated by aphasia quotient (AQ) scores obtained from Western Aphasia Battery test. Compared with normal subjects, aphasic patients showed decreased ALFF values in the regions of left posterior middle temporal gyrus (PMTG), left medial prefrontal gyrus, and right cerebellum. The ALFF values in left PMTG showed strong positive correlation with the AQ score (coefficient r =0.79, P temporal gyrus (BA20), fusiform gyrus (BA37), and inferior frontal gyrus (BA47\\45\\44). Left PMTG might play an important role in language dysfunction of chronic aphasia, and ALFF value might be a promising indicator to evaluate the severity of aphasia.

  10. Fracture of an unossified humeral medial epicondyle: use of magnetic resonance imaging for diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Katsuhisa; Miyamoto, Nao [Nishinomiya Municipal Central Hospital, Department of Orthopaedic Surgery, Nishinomiya (Japan)

    2016-10-15

    Fracture of the humeral medial epicondyle is a relatively common injury in children. Surgery is a good option for treatment, but correct diagnosis is important. Most fractures occur after the ossification of the medial epicondylar apophysis. If a fracture occurs before the ossification of the medial epicondyle, it is undetectable by radiographs. Here we report a case of an unossified medial epicondyle fracture of the humerus. A 9-year-old boy had persistent pain in the medial side of the right elbow after a fall. Despite his pain, he could move his injured elbow with a range from 60 to 90 . Radiographs and computed tomography showed neither fracture nor dislocation in the injured elbow, and soft tissue swelling was the only finding. Neither the trochlea nor the medial epicondyle was ossified. Magnetic resonance imaging showed that the medial epicondyle was separated from the medial metaphysis and displaced. This clear finding led us to surgical fixation. Under general anesthesia, valgus stress showed gross instability of the injured elbow. Two years after the operation, he had no complaints and could play sports with the same range of motion as the left elbow. It is important to keep in mind that medial epicondylar fractures may be hidden in a normal radiograph before the ossification of the medial epicondylar apophysis. (orig.)

  11. Fracture of an unossified humeral medial epicondyle: use of magnetic resonance imaging for diagnosis

    International Nuclear Information System (INIS)

    Tanabe, Katsuhisa; Miyamoto, Nao

    2016-01-01

    Fracture of the humeral medial epicondyle is a relatively common injury in children. Surgery is a good option for treatment, but correct diagnosis is important. Most fractures occur after the ossification of the medial epicondylar apophysis. If a fracture occurs before the ossification of the medial epicondyle, it is undetectable by radiographs. Here we report a case of an unossified medial epicondyle fracture of the humerus. A 9-year-old boy had persistent pain in the medial side of the right elbow after a fall. Despite his pain, he could move his injured elbow with a range from 60 to 90 . Radiographs and computed tomography showed neither fracture nor dislocation in the injured elbow, and soft tissue swelling was the only finding. Neither the trochlea nor the medial epicondyle was ossified. Magnetic resonance imaging showed that the medial epicondyle was separated from the medial metaphysis and displaced. This clear finding led us to surgical fixation. Under general anesthesia, valgus stress showed gross instability of the injured elbow. Two years after the operation, he had no complaints and could play sports with the same range of motion as the left elbow. It is important to keep in mind that medial epicondylar fractures may be hidden in a normal radiograph before the ossification of the medial epicondylar apophysis. (orig.)

  12. Prefrontal and occipital asymmetry and volume in boys with autism spectrum disorder.

    Science.gov (United States)

    Knaus, Tracey A; Tager-Flusberg, Helen; Mock, Jeffrey; Dauterive, Rachel; Foundas, Anne L

    2012-12-01

    To examine prefrontal and occipital asymmetry (brain torque) in boys with autism spectrum disorder (ASD) and controls. A secondary aim was to study age-related changes in gray and white matter volume. Several studies have found atypical early cortical development in ASD. Atypical brain torque, defined as a greater-than-normal left prefrontal and right occipital asymmetry, has been found in some studies of children and adults with ASD. This configuration may be an early neural marker of ASD risk. We studied 24 right-handed boys with ASD and 27 typically developing right-handed boys, 7 to 15 years old, obtaining neuropsychological profiles and measuring prefrontal and occipital volumes on magnetic resonance images. Most participants had the expected rightward prefrontal and leftward occipital asymmetry, with no group differences in direction or degree of asymmetry. We found a trend toward larger prefrontal volume in the ASD group than in the controls. The controls also had a trend toward differences in age associations, correlating with total and left prefrontal white matter volumes. Our findings suggest that atypical brain torque may not be a neural signature of ASD, although our sample was limited to high-functioning, right-handed boys. Our results provide support for aberrant cortical development in ASD, continuing into adolescence, with prefrontal regions being disproportionally affected.

  13. The Anterior Prefrontal Cortex and the Hippocampus Are Negatively Correlated during False Memories.

    Science.gov (United States)

    Jeye, Brittany M; Karanian, Jessica M; Slotnick, Scott D

    2017-01-23

    False memories commonly activate the anterior/dorsolateral prefrontal cortex (A/DLPFC) and the hippocampus. These regions are assumed to work in concert during false memories, which would predict a positive correlation between the magnitudes of activity in these regions across participants. However, the A/DLPFC may also inhibit the hippocampus, which would predict a negative correlation between the magnitudes of activity in these regions. In the present functional magnetic resonance imaging (fMRI) study, during encoding, participants viewed abstract shapes in the left or right visual field. During retrieval, participants classified each old shape as previously in the "left" or "right" visual field followed by an "unsure"-"sure"-"very sure" confidence rating. The contrast of left-hits and left-misses produced two activations in the hippocampus and three activations in the left A/DLPFC. For each participant, activity associated with false memories (right-"left"-"very sure" responses) from the two hippocampal regions was plotted as a function of activity in each A/DLPFC region. Across participants, for one region in the left anterior prefrontal cortex, there was a negative correlation between the magnitudes of activity in this region and the hippocampus. This suggests that the anterior prefrontal cortex might inhibit the hippocampus during false memories and that participants engage either the anterior prefrontal cortex or the hippocampus during false memories.

  14. 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

    2015-01-01

    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. PMID:25450230

  15. Prelimbic prefrontal cortex mediates respiratory responses to mild and potent prolonged, but not brief, stressors.

    Science.gov (United States)

    Bondarenko, E; Hodgson, D M; Nalivaiko, E

    2014-12-01

    The prefrontal cortex is one of the key areas of the central mechanism of cardiovascular and respiratory control. Disinhibition of the prelimbic medial prefrontal cortex elicits tachypnoeic responses in anesthetized rats (Hassan et al., J. Physiol. 591: 6069-6088, 2013). The current study examines the effects of inhibition of the prelimbic prefrontal cortex during presentation of stressors of various lengths and intensities in conscious unrestrained rats. 8 Wistar rats were implanted with bilateral guide cannulas targeting the prelimbic prefrontal cortex and received microinjections of either saline of GABAA agonist muscimol prior to recording sessions. Inhibition of the prelimbic prefrontal cortex significantly attenuated respiratory responses to a novel environment stress, 30s light stimulus and restraint stress. It did not affect respiratory responses to 500 ms acoustic stimuli of varying intensities (40-90 dB). We conclude that the prelimbic prefrontal cortex contributes to generation of tachypnoeic responses to prolonged stressors, but does not contribute to respiratory arousal in response to brief stressors. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Traumatic fragmented medial coronoid process in a Chihuahua.

    Science.gov (United States)

    Hadley, H S; Wheeler, J L; Manley, P A

    2009-01-01

    Fragmented medial coronoid process (FMCP) is a disease process that has not previously been reported in toy-breed dogs. This report describes a presumptive case of FMCP in a 14-month-old Chihuahua that was presented for evaluation approximately four weeks following acute onset of moderate lameness in the left forelimb. Definitive diagnosis of a fragmented medial coronoid process was based upon computed tomography (CT) scan. A CT scan also demonstrated moderate joint incongruity in the affected elbow. Surgical removal of the fragment and subtotal coronoidectomy were performed via a medial arthrotomy. An ulnar ostectomy was also performed to address joint incongruity. Histology of specimens removed at surgery did not demonstrate evidence of microdamage as characteristic of FMCP in large breed dogs, and instead, suggested that the fracture was acute and traumatic in nature. Rapid return to function was observed following surgery.

  17. Improved multitasking following prefrontal tDCS.

    Science.gov (United States)

    Filmer, Hannah L; Mattingley, Jason B; Dux, Paul E

    2013-01-01

    We have a limited capacity for mapping sensory information onto motor responses. This processing bottleneck is thought to be a key factor in determining our ability to make two decisions simultaneously - i.e., to multitask (Pashler, 1984, 1994; Welford, 1952). Previous functional imaging research (Dux, Ivanoff, Asplund, & Marois, 2006; Dux et al., 2009) has localised this bottleneck to the posterior lateral prefrontal cortex (pLPFC) of the left hemisphere. Currently, however, it is unknown whether this region is causally involved in multitasking performance. We investigated the role of the left pLPFC in multitasking using transcranial direct current stimulation (tDCS). The behavioural paradigm included single- and dual-task trials, each requiring a speeded discrimination of visual stimuli alone, auditory stimuli alone, or both visual and auditory stimuli. Reaction times for single- and dual-task trials were compared before, immediately after, and 20 min after anodal stimulation (excitatory), cathodal stimulation (inhibitory), or sham stimulation. The cost of responding to the two tasks (i.e., the reduction in performance for dual- vs single-task trials) was significantly reduced by cathodal stimulation, but not by anodal or sham stimulation. Overall, the results provide direct evidence that the left pLPFC is a key neural locus of the central bottleneck that limits an individual's ability to make two simple decisions simultaneously. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Thinning of the lateral prefrontal cortex during adolescence predicts emotion regulation in females.

    Science.gov (United States)

    Vijayakumar, Nandita; Whittle, Sarah; Yücel, Murat; Dennison, Meg; Simmons, Julian; Allen, Nicholas B

    2014-11-01

    Adolescence is a crucial period for the development of adaptive emotion regulation strategies. Despite the fact that structural maturation of the prefrontal cortex during adolescence is often assumed to underlie the maturation of emotion regulation strategies, no longitudinal studies have directly assessed this relationship. This study examined whether use of cognitive reappraisal strategies during late adolescence was predicted by (i) absolute prefrontal cortical thickness during early adolescence and (ii) structural maturation of the prefrontal cortex between early and mid-adolescence. Ninety-two adolescents underwent baseline and follow-up magnetic resonance imaging scans when they were aged approximately 12 and 16 years, respectively. FreeSurfer software was used to obtain cortical thickness estimates for three prefrontal regions [anterior cingulate cortex; dorsolateral prefrontal cortex (dlPFC); ventrolateral prefrontal cortex (vlPFC)]. The Emotion Regulation Questionnaire was completed when adolescents were aged approximately 19 years. Results showed that greater cortical thinning of the left dlPFC and left vlPFC during adolescence was significantly associated with greater use of cognitive reappraisal in females, though no such relationship was evident in males. Furthermore, baseline left dlPFC thickness predicted cognitive reappraisal at trend level. These findings suggest that cortical maturation may play a role in the development of adaptive emotion regulation strategies during adolescence. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  19. Prefrontal connections of the perirhinal and postrhinal cortices in the rat.

    Science.gov (United States)

    Hwang, Eunkyu; Willis, Bailey S; Burwell, Rebecca D

    2017-07-29

    Knowing how prefrontal regions interact with medial temporal lobe structures is important for understanding memory and cognition. Using anterograde and retrograde tract tracing methods in the rat, we report a detailed study of the perirhinal (PER) and postrhinal (POR) connections with the lateral, ventrolateral, and medial orbitofrontal cortices (ORBl, ORBvl, ORBm), infralimbic and prelimbic cortices (IL, PL), ventral and dorsal anterior cingulate cortices (ACAv, ACAd), and secondary motor cortex (MOs). Our analyses included the topography and laminar patterns of these connections. The PER and POR showed reciprocal connectivity with all prefrontal regions examined, but the patterns of connections differed. In general, PER areas 36 and 35 showed patterns of connectivity that were more similar to each other than to those of the POR. Analysis of anterograde tracers showed that PER areas 36 and 35 provide the strongest projections to prefrontal regions. The heaviest fiber labeling was in IL and PL, closely followed by orbital regions. Fiber labeling arising from injections in POR was weaker overall. The strongest POR efferents targeted MOs, ACAv, and ORBvl. For return projections, analysis of retrograde tracers showed that PER areas 36 and 35 receive strong inputs from orbitofrontal and medial prefrontal regions. Interestingly, PER also received substantial inputs from MOs and ACAd. The POR receives a very strong input from MOs, followed by ACAd, and ORBvl. Based on comparison of our findings with those obtained in monkeys, we argue that the rodent ACAd and MOs may be a functional homolog of the primate dorsolateral prefrontal cortex. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 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...

  1. The role of medial frontal gyrus in action anticipation in professional badminton players

    Directory of Open Access Journals (Sweden)

    Huan Xu

    2016-11-01

    Full Text Available Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent (BOLD activation was assessed by means of functional magnetic resonance imaging (fMRI. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex. Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate

  2. Influence of subjective happiness on the prefrontal brain activity: an fNIRS study.

    Science.gov (United States)

    Oonishi, Sayuri; Hori, Shota; Hoshi, Yoko; Seiyama, Akitoshi

    2014-01-01

    Focusing on the relationship between subjective happiness (SH) and emotional changes, we examined influences of SH on emotion-related prefrontal activity using multichannel NIRS. The International Affective Picture System (IAPS) was used to evoke emotional changes. Subjects were a total of 18 right-handed healthy students. Frequency of picture-induced increases in oxygenated haemoglobin (oxy-Hb) was evaluated. Subjects with a high SH score had a higher frequency of increased oxy-Hb in the left prefrontal cortex (PFC) while viewing pleasant pictures, whereas they showed a lower frequency in the right PFC while viewing unpleasant pictures. It is well known that the left PFC and right PFC are engaged in different ways in the emotional processes. Although further investigations are required, the present results indicate that the SH level influences the right-left differences in emotion-related prefrontal activity.

  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. Dopamine Development in the Mouse Orbital Prefrontal Cortex Is Protracted and Sensitive to Amphetamine in Adolescence.

    Science.gov (United States)

    Hoops, Daniel; Reynolds, Lauren M; Restrepo-Lozano, Jose-Maria; Flores, Cecilia

    2018-01-01

    The prefrontal cortex (PFC) is divided into subregions, including the medial and orbital prefrontal cortices. Dopamine connectivity in the medial PFC (mPFC) continues to be established throughout adolescence as the result of the continuous growth of axons that innervated the nucleus accumbens (NAcc) prior to adolescence. During this period, dopamine axons remain vulnerable to environmental influences, such as drugs used recreationally by humans. The developmental trajectory of the orbital prefrontal dopamine innervation remains almost completely unstudied. Nonetheless, the orbital PFC (oPFC) is critical for some of the most complex functions of the PFC and is disrupted by drugs of abuse, both in adolescent humans and rodents. Here, we use quantitative neuroanatomy, axon-initiated viral-vector recombination, and pharmacology in mice to determine the spatiotemporal development of the dopamine innervation to the oPFC and its vulnerability to amphetamine in adolescence. We find that dopamine innervation to the oPFC also continues to increase during adolescence and that this increase is due to the growth of new dopamine axons to this region. Furthermore, amphetamine in adolescence dramatically reduces the number of presynaptic sites on oPFC dopamine axons. In contrast, dopamine innervation to the piriform cortex is not protracted across adolescence and is not impacted by amphetamine exposure during adolescence, indicating that dopamine development during adolescence is a uniquely prefrontal phenomenon. This renders these fibers, and the PFC in general, particularly vulnerable to environmental risk factors during adolescence, such as recreational drug use.

  5. Medial collateral ligament healing one year after a concurrent medial collateral ligament and anterior cruciate ligament injury: an interdisciplinary study in rabbits.

    Science.gov (United States)

    Yamaji, T; Levine, R E; Woo, S L; Niyibizi, C; Kavalkovich, K W; Weaver-Green, C M

    1996-03-01

    The optimal treatment for concurrent injuries to the medial collateral and anterior cruciate ligaments has not been determined, despite numerous clinical and laboratory studies. The objective of this study was to examine the effect of surgical repair of the medial collateral ligament on its biomechanical and biochemical properties 52 weeks after such injuries. In the left knee of 12 skeletally mature New Zealand White rabbits, the medial collateral ligament was torn and the anterior cruciate ligament was transected and then reconstructed. This is an experimental model previously developed in our laboratory. In six rabbits, the torn ends of the medial collateral ligament were repaired, and in the remaining six rabbits, the ligament was not repaired. Fifty-two weeks after injury, we examined varus-valgus and anterior-posterior knee stability; structural properties of the femur-medial collateral ligament-tibia complex; and mechanical properties, collagen content, and mature collagen crosslinking of the medial collateral ligament. We could not detect significant differences between repair and nonrepair groups for any biomechanical or biochemical property. Our data support clinical findings that when the medial collateral and anterior cruciate ligaments are injured concurrently and the anterior cruciate ligament is reconstructed, conservative treatment of the ruptured medial collateral ligament can result in successful healing.

  6. Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder.

    Science.gov (United States)

    Wetterling, Friedrich; McCarthy, Hazel; Tozzi, Leonardo; Skokauskas, Norbert; O'Doherty, John P; Mulligan, Aisling; Meaney, James; Fagan, Andrew J; Gill, Michael; Frodl, Thomas

    2015-11-01

    Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined 'monetary' reward or punishment. Participants were diagnosed with ADHD during their childhood (N=32) and were paired with age, gender, and education matched healthy controls (N=32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N=17) or remitted ADHDs (remitters, N=15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (Pdifferent areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD. © 2015 Wiley Periodicals, Inc.

  7. Evaluative vs. trait representation in intergroup social judgments: distinct roles of anterior temporal lobe and prefrontal cortex.

    Science.gov (United States)

    Gilbert, Sam J; Swencionis, Jillian K; Amodio, David M

    2012-12-01

    When interacting with someone from another social group, one's responses may be influenced by both stereotypes and evaluations. Given behavioral results suggesting that stereotypes and evaluative associations operate independently, we used fMRI to test whether these biases are mediated by distinct brain systems. White participants viewed pairs of Black or White faces and judged them based on an evaluation (who would you befriend?) or a stereotype-relevant trait (who is more likely to enjoy athletic activities?). Multi-voxel pattern analysis revealed that a predominantly occipital network represented race in a context-invariant manner. However, lateral orbitofrontal cortex preferentially represented race during friendship judgments, whereas anterior medial prefrontal cortex preferentially represented race during trait judgments. Furthermore, representation of race in left temporal pole correlated with a behavioral measure of evaluative bias during friendship judgments and, independently, a measure of stereotyping during trait judgments. Whereas early sensory regions represent race in an apparently invariant manner, representations in higher-level regions are multi-componential and context-dependent. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Prefrontal activity and impaired memory encoding strategies in schizophrenia.

    Science.gov (United States)

    Guimond, Synthia; Hawco, Colin; Lepage, Martin

    2017-08-01

    Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome. Copyright © 2017. Published by Elsevier Ltd.

  9. Exploring the neural substrates of attentional control and human intelligence: Diffusion tensor imaging of prefrontal white matter tractography in healthy cognition.

    Science.gov (United States)

    Ohtani, Toshiyuki; Nestor, Paul G; Bouix, Sylvain; Newell, Dominick; Melonakos, Eric D; McCarley, Robert W; Shenton, Martha E; Kubicki, Marek

    2017-01-26

    We combined diffusion tension imaging (DTI) of prefrontal white matter integrity and neuropsychological measures to examine the functional neuroanatomy of human intelligence. Healthy participants completed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) along with neuropsychological tests of attention and executive control, as measured by Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). Stochastic tractography, considered the most effective DTI method, quantified white matter integrity of the medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) circuitry. Based on prior studies, we hypothesized that posterior mOFC-rACC connections may play a key structural role linking attentional control processes and intelligence. Behavioral results provided strong support for this hypothesis, specifically linking attentional control processes, measured by Trails B and WCST perseverative errors, to intelligent quotient (IQ). Hierarchical regression results indicated left posterior mOFC-rACC fractional anisotropy (FA) and Trails B performance time, but not WCST perseverative errors, each contributed significantly to IQ, accounting for approximately 33.95-51.60% of the variance in IQ scores. These findings suggested that left posterior mOFC-rACC white matter connections may play a key role in supporting the relationship of executive functions of attentional control and general intelligence in healthy cognition. Copyright © 2016. Published by Elsevier Ltd.

  10. The mechanical benefit of medial support screws in locking plating of proximal humerus fractures.

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    Wen Zhang

    Full Text Available BACKGROUND: The purpose of this study was to evaluate the biomechanical advantages of medial support screws (MSSs in the locking proximal humeral plate for treating proximal humerus fractures. METHODS: Thirty synthetic left humeri were randomly divided into 3 subgroups to establish two-part surgical neck fracture models of proximal humerus. All fractures were fixed with a locking proximal humerus plate. Group A was fixed with medial cortical support and no MSSs; Group B was fixed with 3 MSSs but without medial cortical support; Group C was fixed with neither medial cortical support nor MSSs. Axial compression, torsional stiffness, shear stiffness, and failure tests were performed. RESULTS: Constructs with medial support from cortical bone showed statistically higher axial and shear stiffness than other subgroups examined (P<0.0001. When the proximal humerus was not supported by medial cortical bone, locking plating with medial support screws exhibited higher axial and torsional stiffness than locking plating without medial support screws (P ≤ 0.0207. Specimens with medial cortical bone failed primarily by fracture of the humeral shaft or humeral head. Specimens without medial cortical bone support failed primarily by significant plate bending at the fracture site followed by humeral head collapse or humeral head fracture. CONCLUSIONS: Anatomic reduction with medial cortical support was the stiffest construct after a simulated two-part fracture. Significant biomechanical benefits of MSSs in locking plating of proximal humerus fractures were identified. The reconstruction of the medial column support for proximal humerus fractures helps to enhance mechanical stability of the humeral head and prevent implant failure.

  11. Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Posthypoglycemic Period in Young Rats.

    Science.gov (United States)

    Rao, Raghavendra; Ennis, Kathleen; Mitchell, Eugena P; Tran, Phu V; Gewirtz, Jonathan C

    2016-01-01

    Recurrent hypoglycemia is common in infants and children. In developing rat models, recurrent moderate hypoglycemia leads to neuronal injury in the medial prefrontal cortex. To understand the effects beyond neuronal injury, 3-week-old male rats were subjected to 5 episodes of moderate hypoglycemia (blood glucose concentration, approx. 30 mg/dl for 90 min) once daily from postnatal day 24 to 28. Neuronal injury was determined using Fluoro-Jade B histochemistry on postnatal day 29. The effects on brain-derived neurotrophic factor (BDNF) and its cognate receptor, tyrosine kinase receptor B (TrkB) expression, which is critical for prefrontal cortex development, were determined on postnatal day 29 and at adulthood. The effects on prefrontal cortex-mediated function were determined by assessing the prepulse inhibition of the acoustic startle reflex on postnatal day 29 and 2 weeks later, and by testing for fear-potentiated startle at adulthood. Recurrent hypoglycemia led to neuronal injury confined primarily to the medial prefrontal cortex. BDNF/TrkB expression in the prefrontal cortex was suppressed on postnatal day 29 and was accompanied by lower prepulse inhibition, suggesting impaired sensorimotor gating. Following the cessation of recurrent hypoglycemia, the prepulse inhibition had recovered at 2 weeks. BDNF/TrkB expression in the prefrontal cortex had normalized and fear-potentiated startle was intact at adulthood. Recurrent moderate hypoglycemia during development has significant adverse effects on the prefrontal cortex in the posthypoglycemic period. © 2016 S. Karger AG, Basel.

  12. 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.

  13. The Anterior Prefrontal Cortex and the Hippocampus Are Negatively Correlated during False Memories

    Directory of Open Access Journals (Sweden)

    Brittany M. Jeye

    2017-01-01

    Full Text Available False memories commonly activate the anterior/dorsolateral prefrontal cortex (A/DLPFC and the hippocampus. These regions are assumed to work in concert during false memories, which would predict a positive correlation between the magnitudes of activity in these regions across participants. However, the A/DLPFC may also inhibit the hippocampus, which would predict a negative correlation between the magnitudes of activity in these regions. In the present functional magnetic resonance imaging (fMRI study, during encoding, participants viewed abstract shapes in the left or right visual field. During retrieval, participants classified each old shape as previously in the “left” or “right” visual field followed by an “unsure”–“sure”–“very sure” confidence rating. The contrast of left-hits and left-misses produced two activations in the hippocampus and three activations in the left A/DLPFC. For each participant, activity associated with false memories (right–“left”–“very sure” responses from the two hippocampal regions was plotted as a function of activity in each A/DLPFC region. Across participants, for one region in the left anterior prefrontal cortex, there was a negative correlation between the magnitudes of activity in this region and the hippocampus. This suggests that the anterior prefrontal cortex might inhibit the hippocampus during false memories and that participants engage either the anterior prefrontal cortex or the hippocampus during false memories.

  14. Case report 483: Discoid lateral meniscus (DLM), medially displaced, with complex tear

    International Nuclear Information System (INIS)

    Howe, M.A.; Buckwalter, K.A.; Braunstein, E.M.; Wojtys, E.M.

    1988-01-01

    A case of a 9-year-old girl who presented with persistent pain in the left knee was demonstrated to have a discoid lateral meniscus (DLM). The sagittal MR images demonstrated the oval shape of the meniscus, consistent with the typical arthrographic appearance. The coronal images showed that the main substance of the meniscus was displaced medially, with overgrowth of the articular cartilage at the lateral aspect of the joint. The medial aspect of the lateral femoral condyle was concave to accommodate the abnormal meniscus. These findings are consistent with long-standing, medial displacement of the torn meniscus. The literature concerning DLM, an uncommon variant, was reviewed and discussed. (orig.)

  15. Lateralized effect of rapid-rate transcranial magnetic stimulation of the prefrontal cortex on mood.

    Science.gov (United States)

    Pascual-Leone, A; Catalá, M D; Pascual-Leone Pascual, A

    1996-02-01

    We studied the effects of rapid-rate transcranial magnetic stimulation (rTMS) of different scalp positions on mood. Ten normal volunteers rated themselves before and after rTMS on five analog scales labeled "Tristeza" (Sadness), "Ansiedad" (Anxiety), "Alegria" (Happiness), "Cansancio" (Tiredness), and "Dolor/Malestar" (Pain/Discomfort). rTMS was applied to the right lateral prefrontal, left prefrontal, or midline frontal cortex in trains of 5 seconds' duration at 10 Hz and 110% of the subject's motor threshold intensity. Each stimulation position received 10 trains separated by a 25-second pause. No clinically apparent mood changes were evoked by rTMS to any of the scalp positions in any subject. However, left prefrontal rTMS resulted in a significant increase in the Sadness ratings (Tristeza) and a significant decrease in the Happiness ratings ("Alegria") as compared with right prefrontal and midfrontal cortex stimulation. These results show differential effects of rTMS of left and right prefrontal cortex stimulation on mood and illustrate the lateralized control of mood in normal volunteers.

  16. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex reduces resting-state insula activity and modulates functional connectivity of the orbitofrontal cortex in cigarette smokers.

    Science.gov (United States)

    Li, Xingbao; Du, Lian; Sahlem, Gregory L; Badran, Bashar W; Henderson, Scott; George, Mark S

    2017-05-01

    Previous studies reported that repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving and decrease cigarette consumption in smokers. The mechanism of this effect however, remains unclear. We used resting-state functional magnetic resonance imaging (rsfMRI) to test the effect of rTMS in non-treatment seeking smokers. We used a single blinded, sham-controlled, randomized counterbalanced crossover design where participants underwent two visits separated by at least 1 week. Participants received active rTMS over the left dorsolateral prefrontal cortex (DLPFC) during one of their visits, and sham rTMS during their other visit. They had two rsFMRI scans before and after each rTMS session. We used the same rTMS stimulation parameters as in a previous study (10Hz, 5s-on, 10s-off, 100% resting motor threshold, 3000 pulses). Ten non-treatment-seeking, nicotine-dependent, cigarette smokers (6 women, an average age of 39.72 and an average cigarette per day of 17.30) finished the study. rsFMRI results demonstrate that as compared to a single session of sham rTMS, a single session of active rTMS inhibits brain activity in the right insula and thalamus in fractional amplitude of low frequency fluctuation (fALFF). For intrinsic brain connectivity comparisons, active TMS resulted in significantly decreased connectivity from the site of rTMS to the left orbitomedial prefrontal cortex. This data suggests that one session of rTMS can reduce activity in the right insula and right thalamus as measured by fALFF. The data also demonstrates that rTMS can reduce rsFC between the left DLPFC and the medial orbitofrontal cortex. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Anterior prefrontal involvement in implicit contextual change detection

    Directory of Open Access Journals (Sweden)

    Stefan Pollmann

    2009-10-01

    Full Text Available Anterior prefrontal cortex is usually associated with high level executive functions. Here, we show that the frontal pole, specifically left lateral frontopolar cortex, is involved in signaling change in implicitly learned spatial contexts, in the absence of conscious change detection. In a variant of the contextual cueing paradigm, participants first learned implicitly contingencies between distractor contexts and target locations. After learning, repeated distractor contexts were paired with new target locations. Left lateral frontopolar (BA10 and superior frontal (BA9 cortices showed selective signal increase for this target location change in repeated displays in an event-related fMRI experiment, which was most pronounced in participants with high contextual facilitation before the change. The data support the view that left lateral frontopolar cortex is involved in signaling contextual change to posterior brain areas as a precondition for adaptive changes of attentional resource allocation. This signaling occurs in the absence of awareness of learned contingencies or contextual change.

  18. Dopamine and noradrenaline release in the prefrontal cortex of rats during classical aversive and appetitive conditioning to a contextual stimulus: interference by novelty effects

    NARCIS (Netherlands)

    Feenstra, M. G.; Teske, G.; Botterblom, M. H.; de Bruin, J. P.

    1999-01-01

    Extracellular dopamine and noradrenaline concentrations in the medial prefrontal cortex were determined using online microdialysis in freely moving rats during classical appetitive or aversive conditioning to a contextual conditioned stimulus (CS). As CS we used placement in a Skinner box where

  19. Simultaneous avascular necrosis of both medial and lateral femoral condyles

    International Nuclear Information System (INIS)

    Mansberg, R.

    2002-01-01

    Full text: Avascular necrosis (AVN) of a femoral condyle is a common orthopaedic condition. While both medial and lateral femoral condyles may be involved either singly or sequentially the simultaneous occurrence of AVN of both femoral condyles is extremely uncommon. A 57-year-old male is presented who developed the onset of severe left sided knee pain suddenly at rest. Plain and tomographic radiography was unremarkable and a bone scan was performed. Markedly increased vascularity was demonstrated in the left knee with intense osteoblastic activity in the left medial and femoral condyles more marked in the lateral femoral condyle. A diagnosis of AVN of both femoral condyles was made and a MRI exam was performed to confirm this unusual diagnosis. The MRI showed a diffuse increase in intensity bilaterally with subtle bony change in the subarticular bone consistent with AVN more marked in the left lateral femoral condyle. The patients' symptoms resolved with supportive treatment. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  20. 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.

  1. 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.

  2. 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.

  3. Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms.

    Science.gov (United States)

    Eriksson, Olle; Wall, Anders; Olsson, Ulf; Marteinsdottir, Ina; Holstad, Maria; Ågren, Hans; Hartvig, Per; Långström, Bengt; Naessén, Tord

    2016-01-01

    To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls. Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women. Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain". There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation. Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal

  4. Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms.

    Directory of Open Access Journals (Sweden)

    Olle Eriksson

    Full Text Available To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD and asymptomatic controls.Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women.Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP, radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs: the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain".There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001. Menstrual phase changes in this asymmetry (premenstrual-follicular correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006. The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular in plasma levels of estradiol and phase changes in the laterality (dx/sin of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027. The control group showed no such correlation.Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral

  5. Transfrontoethmoidal approach to medial intraconal lesions.

    Science.gov (United States)

    Jittapiromsak, Pakrit; Deshmukh, Pushpa; Nakaji, Peter; Spetzler, Robert F; Preul, Mark C

    2009-12-01

    Object The standard superior craniotomy approach through the orbital roof is obstructed by numerous muscles, nerves, and vessels. Accessing the medial intraconal space also involves considerable brain retraction. The authors present a modified approach through the frontal sinus that overcomes these limitations. Methods Seven fixed silicone-injected cadaveric specimens were dissected bilaterally. In addition to the superior orbital wall, the ethmoidal sinuses and medial orbital wall were removed. The anatomical relationships between the major neurovascular complexes in the medial intraconal space and the optic nerve were observed. Results Intraconally, working space was created both in a "superior window" between the superior oblique and levator palpebrae muscle and in a "medial window" between the superior oblique and medial rectus muscle. The superior window mainly created an ipsilateral trajectory to the deep target. The medial window, which created a contralateral trajectory, provided a more inferior view of the medial intraconal space. Removal of the medial orbital wall further widened the exposure obtained from the superior window. The combination of these working windows makes the medial surface of the optic nerve available for exploration from multiple angles. Most of the major neurovascular complexes of the posterior orbit can be retracted safely without impinging on the optic nerve. Conclusions This novel extradural transfrontoethmoidal approach affords a direct view to the medial posterior orbit without major conflicts with intraconal neurovascular structures and requires minimal brain manipulation. The approach appears to offer advantages for medially located intraconal lesions.

  6. Predicting risk-taking behavior from prefrontal resting-state activity and personality.

    Directory of Open Access Journals (Sweden)

    Bettina Studer

    Full Text Available Risk-taking is subject to considerable individual differences. In the current study, we tested whether resting-state activity in the prefrontal cortex and trait sensitivity to reward and punishment can help predict risk-taking behavior. Prefrontal activity at rest was assessed in seventy healthy volunteers using electroencephalography, and compared to their choice behavior on an economic risk-taking task. The Behavioral Inhibition System/Behavioral Activation System scale was used to measure participants' trait sensitivity to reward and punishment. Our results confirmed both prefrontal resting-state activity and personality traits as sources of individual differences in risk-taking behavior. Right-left asymmetry in prefrontal activity and scores on the Behavioral Inhibition System scale, reflecting trait sensitivity to punishment, were correlated with the level of risk-taking on the task. We further discovered that scores on the Behavioral Inhibition System scale modulated the relationship between asymmetry in prefrontal resting-state activity and risk-taking. The results of this study demonstrate that heterogeneity in risk-taking behavior can be traced back to differences in the basic physiology of decision-makers' brains, and suggest that baseline prefrontal activity and personality traits might interplay in guiding risk-taking behavior.

  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. The Representation of Self and Person Knowledge in the Medial Prefrontal Cortex

    OpenAIRE

    Wagner, Dylan D.; Haxby, James V.; Heatherton, Todd F.

    2012-01-01

    Nearly forty years ago, social psychologists began applying the information processing framework of cognitive psychology to the question of how humans understand and represent knowledge about themselves and others. This approach gave rise to the immensely successful field of social cognition and fundamentally changed the way in which social psychological phenomena are studied. More recently, social scientists of many stripes have turned to the methods of cognitive neuroscience to understand t...

  9. 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…

  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. 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…

  12. 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...

  13. Differential Involvement of the Medial Prefrontal Cortex across Variants of Contextual Fear Conditioning

    Science.gov (United States)

    Heroux, Nicholas A.; Robinson-Drummer, Patrese A.; Sanders, Hollie R.; Rosen, Jeffrey B.; Stanton, Mark E.

    2017-01-01

    The context preexposure facilitation effect (CPFE) is a contextual fear conditioning paradigm in which learning about the context, acquiring the context-shock association, and retrieving/expressing contextual fear are temporally dissociated into three distinct phases. In contrast, learning about the context and the context-shock association…

  14. 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

  15. 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…

  16. 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.

  17. Long-term results after external vocal fold medialization thyroplasty with titanium vocal fold medialization implant (TVFMI).

    Science.gov (United States)

    Schneider-Stickler, Berit; Gaechter, Johannes; Bigenzahn, Wolfgang

    2013-05-01

    Since its introduction in 1999 by Friedrich, the titanium vocal fold medialization implant (TVFMI) is widely used for medialization thyroplasty in glottal closure insufficiency. The purpose of this study was to investigate the long-term functional outcome after medialization thyroplasty using TVFMI. Between 1999 and 2009 123 patients (mean age 55.3 years, 76 male and 47 female) underwent medialization thyroplasty with the TVFMI (96 left, 27 right). For purpose of long-term follow-up, 33 patients could be examined. Prior to surgery, about 8 weeks and at least 1 year after surgery perceptual, acoustic, aerodynamic and videolaryngostroboscopic examinations have been performed. The interval between surgery and long-term follow-up was on average 57 (23-120) months. None of the 123 patients presented early major postoperative complications (e.g. implant dislocation, dyspnoea with need of tracheostomy, wound infection, postoperative bleeding). In three patients the TVFMI had to be removed 2-6 months after surgery due to granulation tissue formation. In one patient a subepithelial localization of the implant could be seen without necessity of removal. Perceptual and acoustic parameters were significantly improved after surgery with long-lasting effect even years after surgery. Airway resistance (R(aw)) showed an increase over time without a relevant negative impact on the peak expiratory flow (PEF). Medialization thyroplasty using TVFMI allows precise and save positioning of the implant with stable perceptual and acoustic improvement. The only postoperative complication was the development of endolaryngeal granulation tissue resulting in removal of the implant.

  18. Prefrontal cortical GABAergic dysfunction contributes to age-related working memory impairment.

    Science.gov (United States)

    Bañuelos, Cristina; Beas, B Sofia; McQuail, Joseph A; Gilbert, Ryan J; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L

    2014-03-05

    Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions.

  19. Reduced synapse and axon numbers in the prefrontal cortex of rats subjected to a chronic stress model for depression

    DEFF Research Database (Denmark)

    Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

    2018-01-01

    Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss...... have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected...... to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem...

  20. 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.

  1. 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.

  2. Effective amygdala-prefrontal connectivity predicts individual differences in successful emotion regulation.

    Science.gov (United States)

    Morawetz, Carmen; Bode, Stefan; Baudewig, Juergen; Heekeren, Hauke R

    2017-04-01

    The ability to voluntarily regulate our emotional response to threatening and highly arousing stimuli by using cognitive reappraisal strategies is essential for our mental and physical well-being. This might be achieved by prefrontal brain regions (e.g. inferior frontal gyrus, IFG) down-regulating activity in the amygdala. It is unknown, to which degree effective connectivity within the emotion-regulation network is linked to individual differences in reappraisal skills. Using psychophysiological interaction analyses of functional magnetic resonance imaging data, we examined changes in inter-regional connectivity between the amygdala and IFG with other brain regions during reappraisal of emotional responses and used emotion regulation success as an explicit regressor. During down-regulation of emotion, reappraisal success correlated with effective connectivity between IFG with dorsolateral, dorsomedial and ventromedial prefrontal cortex (PFC). During up-regulation of emotion, effective coupling between IFG with anterior cingulate cortex, dorsomedial and ventromedial PFC as well as the amygdala correlated with reappraisal success. Activity in the amygdala covaried with activity in lateral and medial prefrontal regions during the up-regulation of emotion and correlated with reappraisal success. These results suggest that successful reappraisal is linked to changes in effective connectivity between two systems, prefrontal cognitive control regions and regions crucially involved in emotional evaluation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  3. Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats.

    Science.gov (United States)

    Sajja, Venkata Siva Sai Sujith; Perrine, Shane A; Ghoddoussi, Farhad; Hall, Christina S; Galloway, Matthew P; VandeVord, Pamela J

    2014-03-01

    Working memory, which is dependent on higher-order executive function in the prefrontal cortex, is often disrupted in patients exposed to blast overpressure. In this study, we evaluated working memory and medial prefrontal neurochemical status in a rat model of blast neurotrauma. Adult male Sprague-Dawley rats were anesthetized with 3% isoflurane and exposed to calibrated blast overpressure (17 psi, 117 kPa) while sham animals received only anesthesia. Early neurochemical effects in the prefrontal cortex included a significant decrease in betaine (trimethylglycine) and an increase in GABA at 24 h, and significant increases in glycerophosphorylcholine, phosphorylethanolamine, as well as glutamate/creatine and lactate/creatine ratios at 48 h. Seven days after blast, only myo-inositol levels were altered showing a 15% increase. Compared to controls, short-term memory in the novel object recognition task was significantly impaired in animals exposed to blast overpressure. Working memory in control animals was negatively correlated with myo-inositol levels (r=-.759, p<0.05), an association that was absent in blast exposed animals. Increased myo-inositol may represent tardive glial scarring in the prefrontal cortex, a notion supported by GFAP changes in this region after blast overexposure as well as clinical reports of increased myo-inositol in disorders of memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Larger mid-dorsolateral prefrontal gray matter volume in young binge drinkers revealed by voxel-based morphometry.

    Directory of Open Access Journals (Sweden)

    Sonia Doallo

    Full Text Available Binge drinking or heavy episodic drinking is a high prevalent pattern of alcohol consumption among young people in several countries. Despite increasing evidence that binge drinking is associated with impairments in executive aspects of working memory (i.e. self-ordered working memory, processes known to depend on the mid-dorsolateral prefrontal cortex (Brodmann areas 46 and 9, less is known about the impact of binge drinking on prefrontal gray matter integrity. Here, we investigated the effects of binge drinking on gray matter volume of mid- dorsolateral prefrontal cortex in youths. We used voxel-based morphometry on the structural magnetic resonance images of subjects reporting a persistent (at least three years binge drinking pattern of alcohol use (n = 11; age 22.43 ± 1.03 and control subjects (n = 21; age 22.18 ± 1.08 to measure differences in gray matter volume between both groups. In a region of interest analysis of the mid-dorsolateral prefrontal cortex, after co-varying for age and gender, we observed significantly larger gray matter volume in the left mid-dorsolateral prefrontal cortex (Brodmann areas 46 and 9 in binge drinkers in comparison with control subjects. Furthermore, there was a significant positive correlation between left mid-dorsolateral prefrontal cortex volume and Self-Ordered Pointing Test (SOPT total errors score in binge drinkers. The left mid-dorsolateral prefrontal cortex volume also correlated with the quantity and speed of alcohol intake. These findings indicate that a repeated exposure to alcohol -that does not meet criteria for alcohol dependence- throughout post-adolescent years and young adulthood is linked with structural anomalies in mid-dorsolateral prefrontal regions critically involved in executive aspects of working memory.

  5. Mapping Prefrontal Cortex Functions in Human Infancy

    Science.gov (United States)

    Grossmann, Tobias

    2013-01-01

    It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

  6. Medial Patella Subluxation: Diagnosis and Treatment

    OpenAIRE

    McCarthy, Mark A.; Bollier, Mathew J.

    2015-01-01

    Medial patella subluxation is a disabling condition typically associated with previous patellofemoral instability surgery. Patients often describe achy pain with painful popping episodes. They often report that the patella shifts laterally, which occurs as the medial subluxed patella dramatically shifts into the trochlear groove during early knee flexion. Physical examination is diagnostic with a positive medial subluxation test. Nonoperative treatment, such as focused physical therapy and pa...

  7. Rare case of pure medial subtalar dislocation in a basketball player ...

    African Journals Online (AJOL)

    A 22 year old male was admitted to the emergency department with pain and ankle deformity following an inversion injury during a basketball game. In his physical examination, the left foot was displaced medially and talus was prominent dorso laterally (A). However, there was not any neurovascular compromise. The X-ray ...

  8. 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.

  9. Structural alterations in lateral prefrontal, parietal and posterior midline regions of men with chronic posttraumatic stress disorder.

    Science.gov (United States)

    Eckart, Cindy; Stoppel, Christian; Kaufmann, Jörn; Tempelmann, Claus; Hinrichs, Hermann; Elbert, Thomas; Heinze, Hans-Jochen; Kolassa, Iris-Tatjana

    2011-05-01

    So far, the neural network associated with posttraumatic stress disorder (PTSD) has been suggested to mainly involve the amygdala, hippocampus and medial prefrontal cortex. However, increasing evidence indicates that cortical regions extending beyond this network might also be implicated in the pathophysiology of PTSD. We aimed to investigate PTSD-related structural alterations in some of these regions. We enrolled highly traumatized refugees with and without (traumatized controls) PTSD and nontraumatized controls in the study. To increase the validity of our results, we combined an automatic cortical parcellation technique and voxel-based morphometry. In all, 39 refugees (20 with and 19 without PTSD) and 13 controls participated in the study. Participants were middle-aged men who were free of psychoactive substances and consumed little to no alcohol. Patients with PTSD (and to a lesser extent traumatized controls) showed reduced volumes in the right inferior parietal cortex, the left rostral middle frontal cortex, the bilateral lateral orbitofrontal cortex and the bilateral isthmus of the cingulate. An influence of cumulative traumatic stress on the isthmus of the cingulate and the lateral orbitofrontal cortex indicated that, at least in these regions, structural alterations might be associated with repeated stress experiences. Voxel-based morphometry analyses produced largely consistent results, but because of a poorer signal-to-noise ratio, conventional statistics did not reach significance. Although we controlled for several important confounding variables (e.g., sex, alcohol abuse) with our particular sample, this might limit the generalizibility of our data. Moreover, high comorbidity of PTSD and major depression hinders a definite separation of these conditions in our findings. Finally, the results concerning the lateral orbito frontal cortex should be interpreted with caution, as magnetic resonance imaging acquisition in this region is affected by a general

  10. Arthroscopic one-piece reshaping for symptomatic discoid medial meniscus with anomalous amalgamating into anterior cruciate ligament

    Science.gov (United States)

    Choi, Hyung Suk

    2015-01-01

    Discoid shapes of lateral menisci are relatively common finding, whereas discoid medial menisci are less common. Discoid medial meniscus with associated anomalous variants has been reported. However, symptomatic complex tear of complete type discoid medial meniscus with anomalous blending with anterior cruciate ligament is an extremely rare pathology. A 35-year-old male was admitted to our hospital with left knee pain and loss of terminal extension for 2 years. On physical examination, the patient presented with clicking and restriction during the extension motion of the knee joint. Magnetic resonance imaging and arthroscopy indicated complex tear of complete discoid medial meniscus in association with anomalous connection between entire apical portion of discoid medial meniscus and tibial insertion portion of the anterior cruciate ligament. We obtained a successful outcome with arthroscopic resection and shaping in one-piece method using no. 11 scalpel blade. PMID:26015618

  11. Prefrontal cortex volume reductions and tic inhibition are unrelated in uncomplicated GTS adults.

    Science.gov (United States)

    Ganos, Christos; Kühn, Simone; Kahl, Ursula; Schunke, Odette; Brandt, Valerie; Bäumer, Tobias; Thomalla, Götz; Haggard, Patrick; Münchau, Alexander

    2014-01-01

    Tics in Gilles de la Tourette syndrome (GTS) are repetitive patterned movements, resembling spontaneous motor behaviour, but escaping voluntary control. Previous studies hypothesised relations between structural alterations in prefrontal cortex of GTS adults and tic severity using voxel-based morphometry (VBM), but could not demonstrate a significant association. The relation between prefrontal cortex structure and tic inhibition has not been investigated. Here, we used VBM to examine 14 GTS adults without associated comorbidities, and 15 healthy controls. We related structural alterations in GTS to clinical measures of tic severity and tic control. Grey matter volumes in the right inferior frontal gyrus and the left frontal pole were reduced in patients relative to healthy controls. These changes were not related to tic severity and tic inhibition. Prefrontal grey matter volume reductions in GTS adults are not related to state measures of tic phenomenology. © 2013.

  12. 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.

  13. Change in emotional self-concept following socio-cognitive training relates to structural plasticity of the prefrontal cortex.

    Science.gov (United States)

    Lumma, Anna-Lena; Valk, Sofie L; Böckler, Anne; Vrtička, Pascal; Singer, Tania

    2018-04-01

    Self-referential processing is a key component of the emotional self-concept. Previous studies have shown that emotional self-referential processing is related to structure and function of cortical midline areas such as medial prefrontal cortex (mPFC), and that it can be altered on a behavioral level by specific mental training practices. However, it remains unknown how behavioral training-related change in emotional self-concept content relates to structural plasticity. To address this issue, we examined the relationship between training-induced change in participant's emotional self-concept measured through emotional word use in the Twenty Statement Test and change in cortical thickness in the context of a large-scale longitudinal mental training study called the ReSource Project . Based on prior behavioral findings showing increased emotional word use particularly after socio-cognitive training targeting perspective-taking capacities, this study extended these results by revealing that individual differences in the degree to which participants changed their emotional self-concept after training was positively related to cortical thickness change in right mPFC extending to dorsolateral PFC (dlPFC). Furthermore, increased self-related negative emotional word use after training was positively associated with cortical thickness change in left pars orbitalis and bilateral dlPFC. Our findings reveal training-related structural brain change in regions known to be involved in self-referential processing and cognitive control, and could indicate a relationship between restructuring of the emotional self-concept content as well as reappraisal of negative aspects and cortical thickness change. As such, our findings can guide the development of psychological interventions targeted to alter specific facets of the self-concept.

  14. 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.

  15. GORE TEX MEDIALIZATION THYROPLASTY- A CASE SERIES

    OpenAIRE

    Balasubramanian Thiagarajan; Karthikeyan Arjunan

    2012-01-01

    Unilateral vocal fold paralysis classically presents with voice change, aspiration of ingested materials and cough. Medialization thyroplasty has become treatment of choice for un recovering vocal fold palsy. Still the ideal implant has not been defined in the surgical medialization of vocal folds. We present our experience of gore tex as the implant material.

  16. Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

    Science.gov (United States)

    Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

    2017-08-01

    Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (pmemory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (pmemory task, patients had lower response in the prefrontal cortices bilaterally (pmemory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Role of the lateral prefrontal cortex in speech monitoring

    Directory of Open Access Journals (Sweden)

    Stephanie K. Riès

    2013-10-01

    Full Text Available The role of lateral prefrontal cortex in speech monitoring has not been delineated. Recent work suggests that medial frontal cortex (MFC is involved in overt speech monitoring initiated before auditory feedback. This mechanism is reflected in an event-related potential (ERP, the error negativity (Ne, peaking within 100 ms after vocal-onset. Critically, in healthy individuals the Ne is sensitive to the accuracy of the response; it is larger for error than correct trials. By contrast, patients with lateral prefrontal cortex (lPFC damage are impaired in nonverbal monitoring tasks showing no amplitude difference between the Ne measured in correct vs. error trials. Interactions between the lPFC and the MFC are assumed to play a necessary role for normal action monitoring. We investigated whether the lPFC was involved in speech monitoring to the same extent as in non-linguistic actions by comparing performance and EEG activity in patients with lPFC damage and in aged-matched controls performing linguistic (Picture Naming and non-linguistic (Simon tasks. Controls did not produce enough errors to allow the comparison of the Ne or other ERP in error vs. correct trials. PFC patients had worse performance than controls in both tasks, but their Ne was larger for error than correct trials only in Naming. This task-dependent pattern can be explained by lPFC-dependent working-memory requirements present in non-linguistic tasks used to study action monitoring but absent in picture naming. This suggests that lPFC may not be necessary for speech monitoring as assessed by simple picture naming. In addition, bilateral temporal cortex activity starting before and peaking around vocal-onset was observed in lPFC and control groups in both tasks but was larger for error than correct trials only in Naming, suggesting the temporal cortex is associated with on-line monitoring of speech specifically when access to lexical representations is necessary.

  18. Dyspnea-Related Cues Engage the Prefrontal Cortex

    Science.gov (United States)

    Herigstad, Mari; Hayen, Anja; Evans, Eleanor; Hardinge, Frances M.; Davies, Robert J.; Wiech, Katja

    2015-01-01

    BACKGROUND: Dyspnea is the major source of disability in COPD. In COPD, environmental cues (eg, the prospect of having to climb stairs) become associated with dyspnea and may trigger dyspnea even before physical activity commences. We hypothesized that brain activation relating to such cues would be different between patients with COPD and healthy control subjects, reflecting greater engagement of emotional mechanisms in patients. METHODS: Using functional MRI (FMRI), we investigated brain responses to dyspnea-related word cues in 41 patients with COPD and 40 healthy age-matched control subjects. We combined these findings with scores on self-report questionnaires, thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enabled identification of brain networks responsible for pain processing despite absence of a physical challenge. RESULTS: Patients with COPD demonstrated activation in the medial prefrontal cortex and anterior cingulate cortex, which correlated with the visual analog scale (VAS) response to word cues. This activity independently correlated with patient responses on questionnaires of depression, fatigue, and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex, and precuneus correlated with the VAS dyspnea scale but not with the questionnaires. CONCLUSIONS: The findings suggest that engagement of the emotional circuitry of the brain is important for interpretation of dyspnea-related cues in COPD and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and the findings suggest that such mechanisms may be relevant in COPD. PMID:26134891

  19. Higher dynamic medial knee load predicts greater cartilage loss over 12 months in medial knee osteoarthritis.

    Science.gov (United States)

    Bennell, Kim L; Bowles, Kelly-Ann; Wang, Yuanyuan; Cicuttini, Flavia; Davies-Tuck, Miranda; Hinman, Rana S

    2011-10-01

    Mechanical factors, in particular increased medial knee joint load, are believed to be important in the structural progression of knee osteoarthritis. This study evaluated the relationship of medial knee load during walking to indices of structural disease progression, measured on MRI, in people with medial knee osteoarthritis. A longitudinal cohort design utilising a subset of participants (n=144, 72%) enrolled in a randomised controlled trial of lateral wedge insoles was employed. Medial knee load parameters including the peak knee adduction moment (KAM) and the KAM impulse were measured at baseline using three-dimensional gait analysis during walking. MRI at baseline and at 12 months was used to assess structural indices. Multiple regression with adjustment for covariates assessed the relationship between medial knee load parameters and the annual change in medial tibial cartilage volume. Binary logistic regression was used for the dichotomous variables of progression of medial tibiofemoral cartilage defects and bone marrow lesions (BML). A higher KAM impulse, but not peak KAM, at baseline was independently associated with greater loss of medial tibial cartilage volume over 12 months (β=29.9, 95% CI 6.3 to 53.5, p=0.01). No significant relationships were seen between medial knee load parameters and the progression of medial tibiofemoral cartilage defects or BML. This study suggests knee loading, in particular the KAM impulse, may be a risk factor for loss of medial tibial cartilage volume. As knee load is modifiable, load-modifying treatments may potentially slow disease progression.

  20. ARE LEFT HANDED SURGEONS LEFT OUT?

    OpenAIRE

    SriKamkshi Kothandaraman; Balasubramanian Thiagarajan

    2012-01-01

    Being a left-handed surgeon, more specifically a left-handed ENT surgeon, presents a unique pattern of difficulties.This article is an overview of left-handedness and a personal account of the specific difficulties a left-handed ENT surgeon faces.

  1. 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.

  2. Prefrontal Gray Matter and Motivation for Treatment in Cocaine-Dependent Individuals with and without Personality Disorders

    Science.gov (United States)

    Moreno-López, Laura; Albein-Urios, Natalia; Martinez-Gonzalez, José Miguel; Soriano-Mas, Carles; Verdejo-García, Antonio

    2014-01-01

    Addiction treatment is a long-term goal and therefore prefrontal–striatal regions regulating goal-directed behavior are to be associated with individual differences on treatment motivation. We aimed at examining the association between gray matter volumes in prefrontal cortices and striatum and readiness to change at treatment onset in cocaine users with and without personality disorders. Participants included 17 cocaine users without psychiatric comorbidities, 17 cocaine users with Cluster B disorders, and 12 cocaine users with Cluster C disorders. They completed the University of Rhode Island Change Assessment Scale, which measures four stages of treatment change (precontemplation, contemplation, action, and maintenance) and overall readiness to change, and were scanned in a 3 T MRI scanner. We defined three regions of interest (ROIs): the ventromedial prefrontal cortex (including medial orbitofrontal cortex and subgenual and rostral anterior cingulate cortex), the dorsomedial prefrontal cortex (i.e., superior medial frontal cortex), and the neostriatum (caudate and putamen). We found that readiness to change correlated with different aspects of ventromedial prefrontal gray matter as a function of diagnosis. In cocaine users with Cluster C comorbidities, readiness to change positively correlated with gyrus rectus gray matter, whereas in cocaine users without comorbidities it negatively correlated with rostral anterior cingulate cortex gray matter. Moreover, maintenance scores positively correlated with dorsomedial prefrontal gray matter in cocaine users with Cluster C comorbidities, but negatively correlated with this region in cocaine users with Cluster B and cocaine users without comorbidities. Maintenance scores also negatively correlated with dorsal striatum gray matter in cocaine users with Cluster C comorbidities. We conclude that the link between prefrontal–striatal gray matter and treatment motivation is modulated by co-existence of personality

  3. Increased prefrontal and parahippocampal activation with reduced dorsolateral prefrontal and insular cortex activation to food images in obesity: a meta-analysis of fMRI studies.

    Directory of Open Access Journals (Sweden)

    Samantha J Brooks

    Full Text Available BACKGROUND AND OBJECTIVES: Obesity is emerging as the most significant health concern of the twenty-first century. A wealth of neuroimaging data suggest that weight gain might be related to aberrant brain function, particularly in prefrontal cortical regions modulating mesolimbic addictive responses to food. Nevertheless, food addiction is currently a model hotly debated. Here, we conduct a meta-analysis of neuroimaging data, examining the most common functional differences between normal-weight and obese participants in response to food stimuli. DATA SOURCE: We conducted a search using several journal databases and adhered to the 'Preferred Reporting Items for Systematic Reviews and Meta-analyses' (PRISMA method. To this aim, 10 studies were found with a total of 126 obese participants, 129 healthy controls, equaling 184 foci (146 increased, 38 decreased activation using the Activation Likelihood Estimation (ALE technique. Out of the 10 studies, 7 investigated neural responses to food versus non-food images. RESULTS: In response to food images, obese in comparison to healthy weight subjects had increased activation in the left dorsomedial prefrontal cortex, right parahippocampal gyrus, right precentral gyrus and right anterior cingulate cortex, and reduced activation in the left dorsolateral prefrontal cortex and left insular cortex. CONCLUSIONS: Prefrontal cortex areas linked to cognitive evaluation processes, such as evaluation of rewarding stimuli, as well as explicit memory regions, appear most consistently activated in response to images of food in those who are obese. Conversely, a reduced activation in brain regions associated with cognitive control and interoceptive awareness of sensations in the body might indicate a weakened control system, combined with hypo-sensitivity to satiety and discomfort signals after eating in those who are prone to overeat.

  4. Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study

    DEFF Research Database (Denmark)

    Korf, E S C; van Straaten, E C W; de Leeuw, F-E

    2007-01-01

    was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95......HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white...

  5. Microsurgical medial plantar flap banking: a method of choice for digital tip injury?

    Science.gov (United States)

    Nagase, T; Ohmori, K

    1998-11-01

    A tip injury of the left thumb was repaired via microsurgical medial plantar flap banking. The medial plantar flap was transferred temporarily to the lower abdominal wall and was anastomosed microsurgically to the deep inferior epigastric artery and vein as a banked flap. It was later grafted to the thumb in a manner similar to a pedicled flap. The flap was transferred successfully, and the tissue texture and bulk was sufficient, with considerable sensory recovery and minimal donor site deformity. This method may be worthwhile to consider as one of the options of digital tip reconstruction, and the concept of microsurgical flap banking may be promising in the field of reconstructive microsurgery.

  6. 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.

  7. Stimulus control of instrumental reflexes in dogs: a comparison of alimentary and avoidance behaviors after prefrontal damage.

    Science.gov (United States)

    Brennan, J; Kowalska, D; Zieliński, K

    1982-01-01

    Two experiments involving parallel procedures to investigate stimulus generalization in prefrontal dogs under alimentary and defensive reinforcement were compared. Twelve dogs in the alimentary study were trained on a 50 percent partial reinforcement schedule, and 24 dogs were trained to avoid shock with either continuous shock availability and response contingent CS termination or with only 50 percent partial shock availability and response independent CS termination. One third of the subjects received bilateral medial prefrontal lesions, 12 dogs were given bilateral lesions of the lateral prefrontal cortex and the remaining subjects served as nonoperated controls. Generalization along the frequency dimension of the tonal CS was assessed during a sampling procedure within normal acquisition training, during complete extinction and following differentiation training. The results indicate specific effects from both the quality and the contingency of reinforcement. Within the limits of each reinforcement treatment, a dissociation occurred such that medial subjects tended to show heightened sensitivity to reinforcement density, while lateral subjects showed characteristic elevated reactivity during all generalization tests.

  8. 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.

  9. Serotonin enhances excitability and gamma frequency temporal integration in mouse prefrontal fast-spiking interneurons.

    Science.gov (United States)

    Athilingam, Jegath C; Ben-Shalom, Roy; Keeshen, Caroline M; Sohal, Vikaas S; Bender, Kevin J

    2017-12-05

    The medial prefrontal cortex plays a key role in higher order cognitive functions like decision making and social cognition. These complex behaviors emerge from the coordinated firing of prefrontal neurons. Fast-spiking interneurons (FSIs) control the timing of excitatory neuron firing via somatic inhibition and generate gamma (30-100 Hz) oscillations. Therefore, factors that regulate how FSIs respond to gamma-frequency input could affect both prefrontal circuit activity and behavior. Here, we show that serotonin (5HT), which is known to regulate gamma power, acts via 5HT2A receptors to suppress an inward-rectifying potassium conductance in FSIs. This leads to depolarization, increased input resistance, enhanced spiking, and slowed decay of excitatory post-synaptic potentials (EPSPs). Notably, we found that slowed EPSP decay preferentially enhanced temporal summation and firing elicited by gamma frequency inputs. These findings show how changes in passive membrane properties can affect not only neuronal excitability but also the temporal filtering of synaptic inputs.

  10. Food seeking in spite of harmful consequences is under prefrontal cortical noradrenergic control.

    Science.gov (United States)

    Latagliata, Emanuele Claudio; Patrono, Enrico; Puglisi-Allegra, Stefano; Ventura, Rossella

    2010-02-08

    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. 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. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Medial and Lateral Plantar Nerve Entrapment

    Science.gov (United States)

    ... Foot Problems Overview of Foot Problems Achilles Tendon Bursitis Achilles Tendon Enthesopathy Bunion Corns and Calluses Damage ... the Foot Freiberg Disease Hammer Toe Inferior Calcaneal Bursitis Medial and Lateral Plantar Nerve Entrapment Metatarsal Joint ...

  15. Behavioral effects of congenital ventromedial prefrontal cortex malformation

    Directory of Open Access Journals (Sweden)

    Boes Aaron D

    2011-12-01

    Full Text Available Abstract Background A detailed behavioral profile associated with focal congenital malformation of the ventromedial prefrontal cortex (vmPFC has not been reported previously. Here we describe a 14 year-old boy, B.W., with neurological and psychiatric sequelae stemming from focal cortical malformation of the left vmPFC. Case Presentation B.W.'s behavior has been characterized through extensive review Patience of clinical and personal records along with behavioral and neuropsychological testing. A central feature of the behavioral profile is severe antisocial behavior. He is aggressive, manipulative, and callous; features consistent with psychopathy. Other problems include: egocentricity, impulsivity, hyperactivity, lack of empathy, lack of respect for authority, impaired moral judgment, an inability to plan ahead, and poor frustration tolerance. Conclusions The vmPFC has a profound contribution to the development of human prosocial behavior. B.W. demonstrates how a congenital lesion to this cortical region severely disrupts this process.

  16. Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information.

    Directory of Open Access Journals (Sweden)

    Massimiliano Conson

    Full Text Available Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS over dorsolateral prefrontal cortex (DLPFC. To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task, and on one cognitive task assessing the ability to adopt another person's visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants' tendency to adopt another's point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males' responses to threatening faces whereas it interferes with the ability to adopt another's viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

  17. Working Memory in the Prefrontal Cortex.

    Science.gov (United States)

    Funahashi, Shintaro

    2017-04-27

    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.

  18. 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.

  19. Working Memory in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Shintaro Funahashi

    2017-04-01

    Full Text Available 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.

  20. 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

  1. Gore tex medialization thyroplasty- A case series

    OpenAIRE

    Arjunan, Karthikeyan; Thiagarajan, Prof.T.Balasubramanian; Narasimman, Prof.N.Seethalakshmi

    2017-01-01

    Unilateral vocal fold paralysis classically presents with voice change, aspiration of ingested materials and cough. Medialization thyroplasty has become treatment of choice for un recovering vocal fold palsy. Still the ideal implant has not been defined in the surgical medialization of vocal folds. We present our experience of gore tex as the implant material. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down.

  2. 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...

  3. 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.

  4. 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 bursitis in the medial compartment (p = 0.038). Presence of medial periarticular bursitis was positively correlated with severity of osteoarthritis but exhibited no correlation with 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.

  5. How isometric are the medial patellofemoral, superficial medial collateral, and lateral collateral ligaments of the knee?

    Science.gov (United States)

    Victor, Jan; Wong, Pius; Witvrouw, Eric; Sloten, Jos Vander; Bellemans, Johan

    2009-10-01

    Ligament isometry is a cornerstone in the description of normal knee function and thorough knowledge is mandatory for successful repair of torn ligaments. This study was undertaken to validate a novel experimental model for the study of ligament strains and to determine the length changes in the superficial medial collateral, lateral collateral, and medial patellofemoral ligaments. Descriptive laboratory study. Passive motions and loaded squats of 12 cadaveric specimens were performed while controlling ankle load and optically tracking the motion of the bones. Preexperiment and postexperiment computed axial tomography scans allow the transformation of rigid body motion to relative motion of relevant anatomic landmarks on the femur, tibia, and patella. The superficial medial collateral ligament is a near-isometric ligament with a strain of less than 2%. The ligament is a little more slack in midflexion (30 degrees to 50 degrees ) and in deep flexion, but length changes are not significant (P > .05). The lateral collateral ligament behaves near isometric (tension from the collateral ligaments (P superficial medial collateral ligament is a near-isometric ligament with no significant length changes. The medial patellofemoral ligament behaves differently in its cranial and caudal parts. In knees with chronic medial collateral ligament insufficiency, isometric repair of the superficial medial collateral ligament can be attempted. A medial patellofemoral ligament reconstruction with a double fixation on the medial patellar border is supported. The cranial bundle should be tightened at full extension and the caudal bundle at 30 degrees of knee flexion.

  6. 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.

  7. Associations between the CNTNAP2 gene, dorsolateral prefrontal cortex, and cognitive performance on the Stroop task.

    Science.gov (United States)

    Zhu, Bi; Chen, Chuansheng; Xue, Gui; Lei, Xuemei; Wang, Yunxin; Li, Jin; Moyzis, Robert K; Li, Jun; Dong, Qi; Lin, Chongde

    2017-02-20

    The CNTNAP2 (contactin-associated protein-like 2) gene, highly expressed in the human prefrontal cortex, has been linked with autism and language impairment. Potential relationships between CNTNAP2, dorsolateral prefrontal cortex (DLPFC), and cognition have been suggested by previous clinical studies, but have not been directly examined in the same study. The current study collected structural MRI, genetic, and behavioral data in 317 healthy Chinese adults, and examined associations between CNTNAP2 variants, DLPFC, and cognitive performance (measured by the Stroop task). After controlling for intracranial volume, sex, and age, the CNTNAP2 genetic polymorphism at SNP rs7809486 had the strongest association with bilateral DLPFC volume (p=0.00015 and 0.00014 for left and right DLPFC volumes, respectively), with GG homozygotes having greater bilateral DLPFC volumes and surface areas than the other genotypes. Furthermore, TT homozygotes of CNTNAP2 rs4726946 (a nearby SNP that had moderate linkage disequilibrium with rs7809486) had greater left DLPFC volume and surface area, and better cognitive performance than the other genotypes. Subjects with greater left DLPFC surface area had better cognitive performance. Importantly, the left DLPFC surface area mediated the association between the CNTNAP2 rs4726946 genotype and cognitive performance. This study provides the first evidence for associations among the CNTNAP2 gene, left DLPFC structure, and cognitive control. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Native rotational knee kinematics is restored after lateral UKA but not after medial UKA.

    Science.gov (United States)

    Wada, Keizo; Hamada, Daisuke; Takasago, Tomoya; Nitta, Akihiro; Goto, Tomohiro; Tonogai, Ichiro; Tsuruo, Yoshihiro; Sairyo, Koichi

    2018-03-26

    The aim of this study was to compare the intraoperative kinematics of medial and lateral unicompartmental knee arthroplasty (UKA) with those of the native knee using a navigation system. Six fresh-frozen cadaveric knees were included in the study. Medial UKA was performed in all right knees and lateral UKA was performed in all left knees. All UKA procedures were performed with a computerised navigation system. The tibial internal rotation angle and coronal alignment of the mechanical axis during passive knee flexion were assessed as rotational and varus/valgus kinematics before and after surgery using the navigation system. The rotation angles of the tibia in the early flexion phase of medial UKA were significantly larger than those of native knees (p = 0.008 at minimum knee flexion, p = 0.008 at 0° knee flexion). The rotational kinematics of lateral UKA was similar to those of the native knees throughout knee flexion. There were no significant differences in varus/valgus kinematics between native and UKA knees. The rotational kinematics of the native knee was not restored after medial UKA but was preserved after lateral UKA. There were no significant differences in the varus/valgus kinematics after either medial or lateral UKA when compared with those of the native knees. Thus, the geometry of the medial tibial articular surface is a determinant of the ability to restore the rotational kinematics of the native knee. Surgeons and implant designers should be aware that the anatomical medial articular geometry is an important factor in restoration of the native knee kinematics after knee arthroplasty.

  9. The regional neuronal activity in left posterior middle temporal gyrus is correlated with the severity of chronic aphasia

    Directory of Open Access Journals (Sweden)

    Li J

    2017-07-01

    Full Text Available Jianlin Li,1,* Dunren Du,2,* Wei Gao,1 Xichun Sun,3 Haizhu Xie,1 Gang Zhang,1 Jian Li,1 Honglun Li,1 Kefeng Li4 1Department of Radiology, Yantai Yuhuangding Hospital, 2Department of Radiology, Yantai Laishan Branch Hospital of Yuhuangding Hospital, Medical College of Qingdao University, 3Department of Radiology, Yantai Hospital of Traditional Chinese Medicine, Yantai, China; 4School of Medicine, University of California, San Diego, CA, USA *These authors contributed equally to this work Background: Aphasia is one of the most disabling cognitive deficits affecting >2 million people in the USA. The neuroimaging characteristics of chronic aphasic patients (>6 months post onset remain largely unknown.Objective: The objective of this study was to investigate the regional signal changes of spontaneous neuronal activity of brain and the inter-regional connectivity in chronic aphasia. Materials and methods: Resting-state blood oxygenation level-dependent functional magnetic resonance imaging (fMRI was used to obtain fMRI data from 17 chronic aphasic patients and 20 healthy control subjects in a Siemens Verio 3.0T MR Scanner. The amplitude of low-frequency fluctuation (ALFF was determined, which directly reflects the regional neuronal activity. The functional connectivity (FC of fMRI was assessed using a seed voxel linear correlation approach. The severity of aphasia was evaluated by aphasia quotient (AQ scores obtained from Western Aphasia Battery test.Results: Compared with normal subjects, aphasic patients showed decreased ALFF values in the regions of left posterior middle temporal gyrus (PMTG, left medial prefrontal gyrus, and right cerebellum. The ALFF values in left PMTG showed strong positive correlation with the AQ score (coefficient r=0.79, P<0.05. There was a positive FC in chronic aphasia between left PMTG and left inferior temporal gyrus (BA20, fusiform gyrus (BA37, and inferior frontal gyrus (BA47\\45\\44. Conclusion: Left PMTG might play

  10. The impact of rTMS over the dorsolateral prefrontal cortex on cognitive processing.

    Science.gov (United States)

    Sato, A; Torii, T; Nakahara, Y; Iwahashi, M; Itoh, Y; Iramina, K

    2013-01-01

    The purpose of the present study was to use event-related potentials (ERP) to clarify the effect of magnetic stimulation on cognitive processing. A figure eight-shaped flat repetitive transcranial magnetic stimulation (rTMS) coil was used to stimulate either the region over the left or the right dorsolateral prefrontal cortex, which is considered to be the origin of the P300 component. Stimulus frequencies were 1.00, 0.75 and 0.50 Hz rTMS. The strength of the magnetic stimulation was set at 80% of the motor threshold for each participant. The auditory oddball task was used to elicit P300s before and shortly after rTMS, and comprised a sequence of sounds containing standard (1 kHz pure tone, 80% of trials) and deviant (2 kHz pure tone, 20% of trials) stimuli. We found that a 1.00 Hz rTMS pulse train over the left dorsolateral prefrontal cortex increased P300 latencies by 8.50 ms at Fz, 12.85 ms at Cz, and 11.25 ms at Pz. In contrast, neither 0.75 and 0.50 Hz rTMS pulse trains over the left dorsolateral prefrontal cortex nor 1.00, 0.75 and 0.50 Hz rTMS pulse trains over the right dorsolateral prefrontal cortex altered P300 latencies. These results indicate that rTMS frequency affects cognitive processing. Thus, we suggest that the effects of rTMS vary according to the activity of excitatory and inhibitory neurons in the cerebral cortex.

  11. 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...

  12. Shared and distinct contributions of rostrolateral prefrontal cortex to analogical reasoning and episodic memory retrieval.

    Science.gov (United States)

    Westphal, Andrew J; Reggente, Nicco; Ito, Kaori L; Rissman, Jesse

    2016-03-01

    Rostrolateral prefrontal cortex (RLPFC) is widely appreciated to support higher cognitive functions, including analogical reasoning and episodic memory retrieval. However, these tasks have typically been studied in isolation, and thus it is unclear whether they involve common or distinct RLPFC mechanisms. Here, we introduce a novel functional magnetic resonance imaging (fMRI) task paradigm to compare brain activity during reasoning and memory tasks while holding bottom-up perceptual stimulation and response demands constant. Univariate analyses on fMRI data from twenty participants identified a large swath of left lateral prefrontal cortex, including RLPFC, that showed common engagement on reasoning trials with valid analogies and memory trials with accurately retrieved source details. Despite broadly overlapping recruitment, multi-voxel activity patterns within left RLPFC reliably differentiated these two trial types, highlighting the presence of at least partially distinct information processing modes. Functional connectivity analyses demonstrated that while left RLPFC showed consistent coupling with the fronto-parietal control network across tasks, its coupling with other cortical areas varied in a task-dependent manner. During the memory task, this region strengthened its connectivity with the default mode and memory retrieval networks, whereas during the reasoning task it coupled more strongly with a nearby left prefrontal region (BA 45) associated with semantic processing, as well as with a superior parietal region associated with visuospatial processing. Taken together, these data suggest a domain-general role for left RLPFC in monitoring and/or integrating task-relevant knowledge representations and showcase how its function cannot solely be attributed to episodic memory or analogical reasoning computations. © 2015 Wiley Periodicals, Inc.

  13. Asymmetric activation in the prefrontal cortex by sound-induced affect.

    Science.gov (United States)

    Kim, Wuon-Shik; Yoon, Young-Ro; Kim, Kyo-Heon; Jho, Moon-Jae; Lee, Sang-Tae

    2003-12-01

    This study is based on previous information regarding asymmetric activation in the prefrontal cortex by film-induced affects, as well as the inverse proportionality of prefrontal cortex activity to power in the alpha band of EEG. To search for a specific EEG band where the asymmetric activation in the prefrontal cortex by sound-induced affects is mainly reflected, we measured 32 college students' EEGs; 11 bands ranged from 6.5 to 35.0 Hz, at Fp1 and Fp2 sites. The power in the alpha band (8.0 to 13.0 Hz) at Fp2, especially in the alpha-2 band (9.0 to 11.0 Hz) increased while the students listened to music, during which participants reported positive affect. In contrast, the power at Fp1 increased while the students listened to noise, during which participants reported negative affect. These results imply that sound-induced positive affect increases relative left-sided activation in the prefrontal cortex, whereas induced negative affect elicits the opposite pattern of asymmetric activation.

  14. Increased functional connectivity between prefrontal cortex and reward system in pathological gambling.

    Directory of Open Access Journals (Sweden)

    Saskia Koehler

    Full Text Available Pathological gambling (PG shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum. PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder.

  15. The medial temporal lobe: memory and beyond.

    Science.gov (United States)

    Lech, Robert K; Suchan, Boris

    2013-10-01

    The structures of the medial temporal lobe, e.g., the hippocampus, entorhinal cortex, perirhinal cortex, and parahippocampal cortex, are known to be essential for long-term memory processing and hence are labeled the medial temporal lobe memory system. Nevertheless, the exact contributions of each structure and the involvement in different cognitive processes remain controversial. This article discusses recent findings dealing with recognition memory and a long lasting involvement of the hippocampus and perirhinal cortex in episodic memory, based on functional imaging and lesion studies. Furthermore, a new paradigm employing objective manipulations of recollection and familiarity is presented, showing no anatomical distinction for these two processes, as opposed to studies using subjective ratings. Additionally, results regarding an involvement of the medial temporal lobe in visual processing are presented, in general supporting the visual-mnemonic theory. The discussed findings show that many questions regarding the functional organization remain unsolved, and that we are in need of further research to create a comprehensive model of the medial temporal lobe. For this, we might need to give up the distinctions into different cognitive processes and start to investigate the different types of representations that are processed by the medial temporal lobe. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. 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