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Medial Prefrontal Cortex (medial + prefrontal_cortex)
Selected AbstractsRegional cerebral brain metabolism correlates of neuroticism and extraversionDEPRESSION AND ANXIETY, Issue 3 2006Thilo Deckersbach Ph.D. Abstract Factor-analytic approaches to human personality have consistently identified several core personality traits, such as Extraversion/Introversion, Neuroticism, Agreeableness, Consciousness, and Openness. There is an increasing recognition that certain personality traits may render individuals vulnerable to psychiatric disorders, including anxiety disorders and depression. Our purpose in this study was to explore correlates between the personality dimensions neuroticism and extraversion as assessed by the NEO Five-Factor Inventory (NEO-FFI) and resting regional cerebral glucose metabolism (rCMRglu) in healthy control subjects. Based on the anxiety and depression literatures, we predicted correlations with a network of brain structures, including ventral and medial prefrontal cortex (encompassing anterior cingulate cortex and orbitofrontal cortex), insular cortex, anterior temporal pole, ventral striatum, and the amygdala. Twenty healthy women completed an 18FFDG (18F-fluorodeoxyglucose) positron emission tomography (PET) scan at rest and the NEO-FFI inventory. We investigated correlations between scores on NEO-FFI Neuroticism and Extraversion and rCMRglu using statistical parametric mapping (SPM99). Within a priori search territories, we found significant negative correlations between Neuroticism and rCMRglu in the insular cortex and positive correlations between Extraversion and rCMRglu in the orbitofrontal cortex. No significant correlations were found involving anterior cingulate, amygdala, or ventral striatum. Neuroticism and Extraversion are associated with activity in insular cortex and orbitofrontal cortex, respectively. Depression and Anxiety 23:133,138, 2006. © 2006 Wiley-Liss, Inc. [source] Circuits and systems in stress.DEPRESSION AND ANXIETY, Issue 1 2002Abstract This paper follows the preclinical work on the effects of stress on neurobiological and neuroendocrine systems and provides a comprehensive working model for understanding the pathophysiology of posttraumatic stress disorder (PTSD). Studies of the neurobiology of PTSD in clinical populations are reviewed. Specific brain areas that play an important role in a variety of types of memory are also preferentially affected by stress, including hippocampus, amygdala, medial prefrontal cortex, and cingulate. This review indicates the involvement of these brain systems in the stress response, and in learning and memory. Affected systems in the neural circuitry of PTSD are reviewed (hypothalamic-pituitary-adrenal axis (HPA-axis), catecholaminergic and serotonergic systems, endogenous benzodiazepines, neuropeptides, hypothalamic-pituitary-thyroid axis (HPT-axis), and neuro-immunological alterations) as well as changes found with structural and functional neuroimaging methods. Converging evidence has emphasized the role of early-life trauma in the development of PTSD and other trauma-related disorders. Current and new targets for systems that play a role in the neural circuitry of PTSD are discussed. This material provides a basis for understanding the psychopathology of stress-related disorders, in particular PTSD. Depression and Anxiety 16:14,38, 2002. © 2002 Wiley-Liss, Inc. [source] Changes in hyporesponsiveness to acute amphetamine and age differences in tyrosine hydroxylase immunoreactivity in the brain over adolescence in male and female ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2009Iva Z. Mathews Abstract We investigated hyposensitivity after amphetamine in early (postnatal Day 30; P30) and late (P45) adolescent rats compared to adults (P70) in experiment 1. Locomotor activity was measured for 1,hr after the first (acute) and second (24,hr later) injection of amphetamine (0.5 or 1.5,mg/kg). P30 and P45 rats were transiently hypoactive compared to adults, as indicated by reduced locomotor activity after acute amphetamine and enhanced activity after the second injection in adolescents only. In experiment 2, ovariectomy did not alter locomotor activity during habituation at any age compared to intact rats, and, as for intact adolescents, ovariectomized adolescents continued to be less active after amphetamine than adults, suggesting gonadal immaturity alone cannot account for age differences in experiment 1. However, ovariectomy attenuated the increase in activity after the second treatment. In experiment 3 involving untreated rats, tyrosine hydroxylase immunoreactivity was reduced in P30, P40, and P50 compared to P90 rats in the nucleus accumbens core and the medial prefrontal cortex. Thus, adolescents may have an increased threshold of behavioral activation that can be overcome with either a higher dose or with repeated amphetamine treatment, and may be related to changes in the dopamine system over development. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 417,428, 2009. [source] An exploration of anger phenomenology in multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2009U. Nocentini Background and purpose:, Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics. Patients and methods:, About 195 cognitively unimpaired MS patients (150 relapsing,remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients' anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance. Results:, Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients. Conclusions:, The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex. [source] Adaptative response of antioxidant enzymes in different areas of rat brain after repeated d -amphetamine administrationADDICTION BIOLOGY, Issue 3 2001Félix Carvalho d-Amphetamine has been shown to be a potential brain neurotoxic agent, particularly to dopaminergic neurones. Reactive oxygen species indirectly generated by this drug have been indicated as an important factor in the appearance of neuronal damage but little is known about the adaptations of brain antioxidant systems to its chronic administration. In this study, the activities of several antioxidant enzymes in different areas of rat brain were measured after repeated administration of d-amphetamine sulphate (sc, 20 mg/kg/day, for 14 days), namely glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GRed), catalase, and superoxide dismutase (SOD). When compared to a pair-fed control group, d-amphetamine treatment enhanced the activity of GST in hypothalamus to 167%, GPx in striatum to 127%, in nucleus accumbens to 192%, and in medial prefrontal cortex to 139%, GRed in hypothalamus to 139%, as well as catalase in medial prefrontal cortex to 153%. However, the same comparison revealed a decrease in the activity of GRed in medial pre-frontal cortex by 35%. Food restriction itself reduced GRed activity by 49% and enhanced catalase activity to 271% in nucleus accumbens. The modifications observed for the measured antioxidant enzymes reveal that oxidative stress probably plays a role in the deleterious effects of this drug in CNS and that, in general, the brain areas studied underwent adaptations which provided protection against the continuous administration of the drug. [source] Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine releaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009A. Zmarowski Abstract We tested the hypothesis that fluctuations in the levels of kynurenic acid (KYNA), an endogenous antagonist of the ,7 nicotinic acetylcholine (ACh) receptor, modulate extracellular ACh levels in the medial prefrontal cortex in rats. Decreases in cortical KYNA levels were achieved by local perfusion of S -ESBA, a selective inhibitor of the astrocytic enzyme kynurenine aminotransferase II (KAT II), which catalyses the formation of KYNA from its precursor l -kynurenine. At 5 mm, S -ESBA caused a 30% reduction in extracellular KYNA levels, which was accompanied by a two-threefold increase in basal cortical ACh levels. Co-perfusion of KYNA in the endogenous range (100 nm), which by itself tended to reduce basal ACh levels, blocked the ability of S -ESBA to raise extracellular ACh levels. KYNA perfusion (100 nm) also prevented the evoked ACh release caused by d -amphetamine (2.0 mg/kg). This effect was duplicated by the systemic administration of kynurenine (50 mg/kg), which resulted in a significant increase in cortical KYNA formation. Jointly, these data indicate that astrocytes, by producing and releasing KYNA, have the ability to modulate cortical cholinergic neurotransmission under both basal and stimulated conditions. As cortical KYNA levels are elevated in individuals with schizophrenia, and in light of the established role of cortical ACh in executive functions, our findings suggest that drugs capable of attenuating the production of KYNA may be of benefit in the treatment of cognitive deficits in schizophrenia. [source] Contrasting effects of selective lesions of nucleus accumbens core or shell on inhibitory control and amphetamine-induced impulsive behaviourEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2008E. R. Murphy Abstract The core and shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. The contributions of these subregions to simple instrumental behaviour, inhibitory control and behavioural flexibility were investigated using a ,forced choice' task, various parameter manipulations and an omission schedule version of the task. Post-training, selective core lesions were achieved with microinjections of quinolinic acid and shell lesions with ibotenic acid. After a series of behavioural task manipulations, rats were re-stabilized on the standard version of the task and challenged with increasing doses of d - amphetamine (vehicle, 0.5 or 1.0 mg/kg i.p. 30 min prior to test). Neither core- nor shell-lesioned rats exhibited persistent deficits in simple instrumental behaviour or challenges to behavioural flexibility or inhibitory control. Significant differences between lesion groups were unmasked by d- amphetamine challenge in the standard version of the forced task. Core lesions potentiated and shell lesions attenuated the dose-dependent effect of d- amphetamine on increasing anticipatory responses seen in sham rats. These data imply that the accumbens core and shell subregions do not play major roles in highly-trained task performance or in challenges to behavioural control, but may have opposed effects following d- amphetamine treatment. Specifically, they suggest the shell subregion to be necessary for dopaminergic activation driving amphetamine-induced impulsive behaviour and the core subregion for the normal control of this behaviour via conditioned influences. [source] Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2008Meng-Yang Zhu Abstract Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with ,-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress. [source] Netrin-1 receptor-deficient mice show enhanced mesocortical dopamine transmission and blunted behavioural responses to amphetamineEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Alanna Grant Abstract The mesocorticolimbic dopamine (DA) system is implicated in neurodevelopmental psychiatric disorders including schizophrenia but it is unknown how disruptions in brain development modify this system and increase predisposition to cognitive and behavioural abnormalities in adulthood. Netrins are guidance cues involved in the proper organization of neuronal connectivity during development. We have hypothesized that variations in the function of DCC (deleted in colorectal cancer), a netrin-1 receptor highly expressed by DA neurones, may result in altered development and organization of mesocorticolimbic DA circuitry, and influence DA function in the adult. To test this hypothesis, we assessed the effects of reduced DCC on several indicators of DA function. Using in-vivo microdialysis, we showed that adult mice that develop with reduced DCC display increased basal DA levels in the medial prefrontal cortex and exaggerated DA release in response to the indirect DA agonist amphetamine. In contrast, these mice exhibit normal levels of DA in the nucleus accumbens but significantly blunted amphetamine-induced DA release. Concomitantly, using conditioned place preference, locomotor activity and prepulse inhibition paradigms, we found that reduced DCC diminishes the rewarding and behavioural-activating effects of amphetamine and protects against amphetamine-induced deficits in sensorimotor gating. Furthermore, we found that adult DCC-deficient mice exhibit altered dendritic spine density in layer V medial prefrontal cortex pyramidal neurones but not in nucleus accumbens medium spiny neurones. These findings demonstrate that reduced DCC during development results in a behavioural phenotype opposite to that observed in developmental models of schizophrenia and identify DCC as a critical factor in the development of DA function. [source] Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibilityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Judith R. Homberg Abstract Impulsivity and aggression have been suggested to inversely correlate with central serotonin (5-HT) levels in a trait-like manner. However, this relationship is far from straightforward. In the present study we addressed the effect of lifelong reduced or absent serotonin transporter (SERT) function, which is associated with constitutively increased extracellular 5-HT levels, on impulsivity and aggression. We used unique SERT knockout rats in a resident,intruder test, five-choice serial reaction time task and serial reversal learning task to assay aggression, inhibitory control and behavioural flexibility, respectively. Homozygous SERT knockout rats (SERT,,/,) displayed reduced aggression and improved inhibitory control, but unchanged behavioural flexibility. The behavioural phenotype of heterozygous SERT knockout rats (SERT,+/,) was not different from that of wild-type controls in any of the behavioural paradigms. We determined monoamine (metabolite) tissue levels in the medial prefrontal cortex, orbitofrontal cortex, lateral hypothalamus, raphe nuclei and cerebrospinal fluid, and found that the 5-HT levels, but not other monoamine tissue levels, were reduced in SERT,,/, rats. In addition, the 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio in cerebrospinal fluid was increased in these rats. In conclusion, our data show that the absence of the SERT affects aggression and inhibitory control, but not behavioural flexibility, characteristics that may reflect the trait-like consequences of constitutive changes in central 5-HT levels. [source] Distinct kinds of novelty processing differentially increase extracellular dopamine in different brain regionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006Elvira De Leonibus Abstract Behaviourally relevant novel stimuli are known to activate the mesocorticolimbic dopaminergic (DAergic) system. In this study we tested the reactivity of this system in response to distinct kinds of novelty processing. Using the in vivo microdialysis technique, we measured extracellular amounts of dopamine (DA) in different DAergic terminal regions during a social learning task in rats. In the first session (40 min) rats were exposed to two never previously encountered juveniles (i.e. unconditional novelty). Afterwards, the animals were divided into three groups: Control group was not exposed to any other stimulus; Discrimination group was exposed to one familiar and one new juvenile (i.e. novel stimulus discrimination); and Recognition group was re-exposed to the two familiar juveniles (i.e. familiarity recognition). In both the medial prefrontal cortex and the nucleus accumbens shell DA increased in response to the first presentation of the juveniles, showing that both structures are involved in processing unconditional social novelty. During the novel stimulus discrimination, we found no change in the prefrontal cortex, although DA increased in the accumbal shell in comparison with the group exposed to two familiar juveniles, showing that the shell is also involved in processing novel social stimulus discrimination. None of the stimuli presented affected DA in the accumbal core. This study provided the original evidence that DA in the various terminal regions is differentially coupled to distinct aspects of novelty processing. [source] Microsphere embolism-induced cortical cholinergic deafferentation and impairments in attentional performanceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005Tara K. S. Craft Abstract Ischemic events have been hypothesized to play a critical role on the pathogenesis of dementia and the acceleration of cognitive impairments. This experiment was designed to determine the consequences of microvascular ischemia on the cortical cholinergic input system and associated attention capacities. Injections of microspheres (,50 µm diameter; ,5000 microspheres/100 µL) into the right common carotid artery of rats served as a model of microvascular ischemia and resulted in decreases in the density of cholinergic fibers in the ipsilateral medial prefrontal cortex and frontoparietal areas. Furthermore, dense astrogliosis, indicated by glial fibrillary acidic protein (GFAP) immunohistochemistry, was observed in the globus pallidus, including the areas of origin of cholinergic projections to the cortex. Fluoro-Jade B staining indicated that loss of neurons in the cortex was restricted to areas of microsphere-induced infarcts. Attentional performance was assessed using an operant sustained attention task; performance in this task was previously demonstrated to reflect the integrity and activity of the cortical cholinergic input system. Embolized animals' performance was characterized by a decrease in the animals' ability to detect signals. Their performance in non-signal trials remained unaffected. The residual density of cholinergic axons in prefrontal and frontoparietal areas correlated with the animals' performance. The present data support the hypothesis that microvascular ischemia results in loss of cortical cholinergic inputs and impairs associated attentional performance. Microsphere embolism represents a useful animal model for studying the role of interactions between microvascular disorder and impaired forebrain cholinergic neurotransmission in the manifestation of cognitive impairments. [source] Cocaine increases medial prefrontal cortical glutamate overflow in cocaine-sensitized rats: a time course studyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2004Jason M. Williams Abstract Excitatory amino acid transmission within mesocorticolimbic brain pathways is thought to play an important role in behavioural sensitization to psychomotor stimulants. The current studies evaluated a time course of the effects of cocaine on extracellular glutamate levels within the medial prefrontal cortex (mPFC) following increasing periods of withdrawal from repeated cocaine exposure. Male Sprague,Dawley rats underwent stereotaxic surgeries and were pretreated daily with saline (1 mL/kg/day × 4 days, i.p.) or cocaine (15 mg/kg/day × 4 days, i.p.) and withdrawn for 1, 7 or 30 days. After withdrawal rats were challenged with the same dose of saline or cocaine and in vivo microdialysis of the mPFC was conducted with concurrent analysis of locomotor activity. Animals that were withdrawn from repeated daily cocaine for 1 day and 7 days displayed an augmentation in cocaine-induced mPFC glutamate levels compared to saline and acute control subjects, which were similarly unaffected by cocaine challenge. At the 7 day time point, a subset of animals that received repeated cocaine did not express behavioural sensitization, nor did these animals exhibit the enhancement in mPFC glutamate in response to cocaine challenge. In contrast to these early effects, 30 days of withdrawal resulted in no significant changes in cocaine-induced mPFC glutamate levels regardless of the pretreatment or behavioural response. These data suggest that repeated cocaine administration transiently increases cocaine-induced glutamate levels in the mPFC during the first week of withdrawal, which may play an important role in the development of behavioural sensitization to cocaine. [source] Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residuesGENES, BRAIN AND BEHAVIOR, Issue 8 2008D. B. Fegley Tuberoinfundibular peptide of 39 residues (TIP39) is synthesized by two groups of neurons, one in the subparafascicular area at the caudal end of the thalamus and the other in the medial paralemniscal nucleus within the lateral brainstem. The subparafascicular TIP39 neurons project to a number of brain regions involved in emotional responses, and these regions contain a matching distribution of a receptor for TIP39, the parathyroid hormone 2 receptor (PTH2-R). We have now evaluated the involvement of TIP39 in anxiety-related behaviors using mice with targeted null mutation of the TIP39 gene (Tifp39). Tifp39,/, mice (TIP39-KO) did not significantly differ from wild-type (WT) littermates in the open field, light/dark exploration and elevated plus-maze assays under standard test conditions. However, the TIP39-KO engaged in more active defensive burying in the shock-probe test. In addition, when tested under high illumination or after restraint, TIP39-KO displayed significantly greater anxiety-like behavior in the elevated plus-maze than WT. In a Pavlovian fear-conditioning paradigm, TIP39-KO froze more than WT during training and during tone and context recall but showed normal fear extinction. Disruption of TIP39 projections to the medial prefrontal cortex, lateral septum, bed nucleus of the stria terminalis, hypothalamus and amygdala likely account for the fear- and anxiety-related phenotype of TIP39-KO. Current data support the hypothesis that TIP39 modulates anxiety-related behaviors following environmental provocation. [source] Contributions of the hippocampus and medial prefrontal cortex to energy and body weight regulationHIPPOCAMPUS, Issue 3 2009Terry L. Davidson Abstract 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 with 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 with 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. © 2008 Wiley-Liss, Inc. [source] Emotional imagery: Assessing pleasure and arousal in the brain's reward circuitryHUMAN BRAIN MAPPING, Issue 9 2010Vincent D. Costa Abstract Research on emotional perception and learning indicates appetitive cues engage nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), whereas amygdala activity is modulated by the emotional intensity of appetitive and aversive cues. This study sought to determine patterns of functional activation and connectivity among these regions during narrative emotional imagery. Using event-related fMRI, we investigate activation of these structures when participants vividly imagine pleasant, neutral, and unpleasant scenes. Results indicate that pleasant imagery selectively activates NAc and mPFC, whereas amygdala activation was enhanced during both pleasant and unpleasant imagery. NAc and mPFC activity were each correlated with the rated pleasure of the imagined scenes, while amygdala activity was correlated with rated emotional arousal. Functional connectivity of NAc and mPFC was evident throughout imagery, regardless of hedonic content, while correlated activation of the amygdala with NAc and mPFC was specific to imagining pleasant scenes. These findings provide strong evidence that pleasurable text-driven imagery engages a core appetitive circuit, including NAc, mPFC, and the amygdala. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. [source] Neurocognitive processes of the religious leader in ChristiansHUMAN BRAIN MAPPING, Issue 12 2009Jianqiao Ge Abstract Our recent work suggests that trait judgment of the self in Christians, relative to nonreligious subjects, is characterized by weakened neural coding of stimulus self-relatedness in the ventral medial prefrontal cortex (VMPFC) but enhanced evaluative processes of self-referential stimuli in the dorsal medial prefrontal cortex (DMPFC). The current study tested the hypothesis that Christian belief and practice produce a trait summary about the religious leader (Jesus) in the believers and thus episodic memory retrieval is involved to the minimum degree when making trait judgment of Jesus. Experiment 1 showed that to recall a specific incident to exemplify Jesus' trait facilitated behavioral performances associated with the following trait judgment of Jesus in nonreligious subjects but not in Christians. Experiment 2 showed that, for nonreligious subjects, trait judgments of both government and religious leaders resulted in enhanced functional connectivity between MPFC and posterior parietal cortex (PPC)/precuneus compared with self judgment. For Christian subjects, however, the functional connectivity between MPFC and PPC/precuneus differentiated between trait judgments of the government leader and the self but not between trait judgments of Jesus and the self. Our findings suggest that Christian belief and practice modulate the neurocognitive processes of the religious leader so that trait judgment of Jesus engages increased employment of semantic trait summary but decreased memory retrieval of behavioral episodes. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] A voxel-based morphometry study of frontal gray matter correlates of impulsivity,HUMAN BRAIN MAPPING, Issue 4 2009Koji Matsuo Abstract Impulsivity is a personality trait exhibited by healthy individuals, but excessive impulsivity is associated with some mental disorders. Lesion and functional neuroimaging studies indicate that the ventromedial prefrontal region (VMPFC), including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and medial prefrontal cortex, and the amygdala may modulate impulsivity and aggression. However, no morphometric study has examined the association between VMPFC and impulsivity. We hypothesized that healthy subjects with high impulsivity would have smaller volumes in these brain regions compared with those with low impulsivity. Sixty-two healthy subjects were studied (age 35.4 ± 12.1 years) using a 1.5-T MRI system. The Barratt impulsiveness scale (BIS) was used to assess impulsivity. Images were processed using an optimized voxel-based morphometry (VBM) protocol. We calculated the correlations between BIS scale scores and the gray matter (GM) and white matter (WM) volumes of VMPFC and amygdala. GM volumes of the left and right OFC were inversely correlated with the BIS total score (P = 0.04 and 0.02, respectively). Left ACC GM volumes had a tendency to be inversely correlated with the BIS total score (P = 0.05). Right OFC GM volumes were inversely correlated with BIS nonplanning impulsivity, and left OFC GM volumes were inversely correlated with motor impulsivity. There were no significant WM volume correlations with impulsivity. The results of this morphometry study indicate that small OFC volume relate to high impulsivity and extend the prior finding that the VMPFC is involved in the circuit modulating impulsivity. Hum Brain Mapp 2009. © 2008 Wiley-Liss, Inc. [source] Social cognition and the brain: A meta-analysisHUMAN BRAIN MAPPING, Issue 3 2009Frank Van Overwalle Abstract This meta-analysis explores the location and function of brain areas involved in social cognition, or the capacity to understand people's behavioral intentions, social beliefs, and personality traits. On the basis of over 200 fMRI studies, it tests alternative theoretical proposals that attempt to explain how several brain areas process information relevant for social cognition. The results suggest that inferring temporary states such as goals, intentions, and desires of other people,even when they are false and unjust from our own perspective,strongly engages the temporo-parietal junction (TPJ). Inferring more enduring dispositions of others and the self, or interpersonal norms and scripts, engages the medial prefrontal cortex (mPFC), although temporal states can also activate the mPFC. Other candidate tasks reflecting general-purpose brain processes that may potentially subserve social cognition are briefly reviewed, such as sequence learning, causality detection, emotion processing, and executive functioning (action monitoring, attention, dual task monitoring, episodic memory retrieval), but none of them overlaps uniquely with the regions activated during social cognition. Hence, it appears that social cognition particularly engages the TPJ and mPFC regions. The available evidence is consistent with the role of a TPJ-related mirror system for inferring temporary goals and intentions at a relatively perceptual level of representation, and the mPFC as a module that integrates social information across time and allows reflection and representation of traits and norms, and presumably also of intentionality, at a more abstract cognitive level. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [source] Biphasic hemodynamic responses influence deactivation and may mask activation in block-design fMRI paradigmsHUMAN BRAIN MAPPING, Issue 4 2008Jed A. Meltzer Abstract A previous block-design fMRI study revealed deactivation in the hippocampus in the transverse patterning task, specifically designed, on the basis of lesion literature, to engage hippocampal information processing. In the current study, a mixed block/event-related design was used to determine the temporal nature of the signal change leading to the seemingly paradoxical deactivation. All positive activations in the hippocampal-dependent condition, relative to a closely matched control task, were seen to result from positive BOLD transients in the typical 4,7 s poststimulus time range. However, most deactivations, including in the hippocampus and in other "default mode" regions commonly deactivated in cognitive tasks, were attributable to enhanced negative transient signals in a later time range, 10,12 s. This late hemodynamic transient was most pronounced in medial prefrontal cortex. In some regions, the hippocampal-dependent condition enhanced both the early positive and late negative transients to approximately the same degree, resulting in no significant signal change when block analysis is used, despite very different event-related responses. These results imply that delayed negative transients can play a role in determining the presence and sign of brain activation in block-design studies, in which case an event-related analysis can be more sensitive than a block analysis, even if the different conditions occur within blocks. In this case, default mode deactivations are timelocked to stimulus presentation as much as positive activations are, but in a later time range, suggesting a specific role of negative transient signals in task performance. Hum Brain Mapp, 2008. © 2007 Wiley-Liss, Inc. [source] Feature uncertainty activates anterior cingulate cortex,HUMAN BRAIN MAPPING, Issue 1 2004Szabolcs Kéri Abstract In visual discrimination tasks, the relevant feature to discriminate is defined before stimulus presentation. In feature uncertainty tasks, a cue about the relevant feature is provided after stimulus offset. We used 15O-butanol positron emission tomography (PET) in order to investigate brain activation during a feature uncertainty task. There was greater activity during the feature uncertainty task, compared with stimulus detection and discrimination of orientation and spatial frequency, in the lateral and medial prefrontal cortex, the cuneus, superior temporal and inferior parietal cortex, cortical motor areas, and the cerebellum. The most robust and consistent activation was observed in the dorsal anterior cingulate cortex (Brodmann area 32; x = 0 y = 16, z = 40). The insula, located near the claustrum (x = ,38, y = 8, z = 4), was activated during the discrimination tasks compared with the feature uncertainty condition. These results suggest that the dorsal anterior cingulate cortex is important in feature uncertainty conditions, which include divided attention, expectancy under uncertainty, and cognitive monitoring. Hum. Brain Mapp. 21:26,33, 2004. © 2003 Wiley-Liss, Inc. [source] Differential interictal activity of the precuneus/posterior cingulate cortex revealed by resting state functional MRI at 3T in generalized vs.JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2008Partial seizure Abstract Purpose To characterize, using functional MRI (fMRI), the pattern of active brain regions in the resting state in patients with epilepsy. Materials and Methods We studied 28 patients with epilepsy, divided into a partial seizure (PS; N = 9) and a generalized seizure group (GS; N = 19), and 34 control subjects. Resting state fMRI was performed using a GE 3T scanner by collecting 200 volumes of echo-planar imaging (EPI) images with subjects relaxed, eyes closed. Data were processed using a modification of the method of Fransson (Hum Brain Mapp 2005;26:15,29), which reveals information on regional low-frequency Blood Oxygenation Level Dependent (BOLD) signal oscillations in the resting state without any a priori hypothesis. The significant active areas in brain were identified with both individual and group analysis. Results Controls showed active regions in the precuneus/posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC)/ventral anterior cingulate cortex (vACC), theregions associated with the brain "default mode." Similar active regions were observed in PS, whereas GS showed no significant activation of precuneus/PCC. Conclusion In GS, the lack of activation in precuneus/PCC may partly account for their more severe interictal deficits, compared to PS, in cognitive functions such as concentration and memory. J. Magn. Reson. Imaging 2008;27:1214,1220. © 2008 Wiley-Liss, Inc. [source] Endogenous serotonin and serotonin2C receptors are involved in the ability of M100907 to suppress cortical glutamate release induced by NMDA receptor blockadeJOURNAL OF NEUROCHEMISTRY, Issue 2 2009Eleonora Calcagno Abstract Blockade of NMDA receptors by intracortical infusion of 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) increases glutamate (GLU) and serotonin (5-HT) release in the medial prefrontal cortex and impairs attentional performance in the 5-choice serial reaction time task. These effects are prevented by the 5-HT2A receptor antagonist, (R)-(+)-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidine methanol (M100907). We explored the roles of endogenous 5-HT and 5-HT1A and 5-HT2C receptors in the mechanisms by which M100907 suppresses CPP-induced release of cortical GLU and 5-HT using in vivo microdialysis. CPP raised extracellular GLU and 5-HT by about 250% and 170% respectively. The 5-HT synthesis inhibitor, p -chlorophenylalanine (300 mg/kg), prevented M100907 suppressing CPP-induced GLU release. The effect of M100907 on these rises of GLU and 5-HT and attentional performance deficit was mimicked by the 5-HT2C receptor agonist, (S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine fumarate, (Ro60-0175, 30 ,g/kg) while intra-mPFC (SB242084, 6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline, 0.1 ,M), a 5-HT2C receptor antagonist, prevented the effect of M100907 on extracellular GLU. The 5-HT1A receptor antagonist, N -[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N -(2-pyridinyl)cyclohexane carboxenide trihydrochloride (100 ,M) abolished the effect of M100907 on the CPP-induced 5-HT release. The data show that blockade of 5-HT2A receptors is not sufficient to suppress the CPP-induced rise of extracellular GLU and 5-HT and suggest that M100907 suppresses GLU release induced by CPP by enhancing the action of endogenous 5-HT on 5-HT2C receptors. [source] Effects of chronic paroxetine treatment on dialysate serotonin in 5-HT1B receptor knockout miceJOURNAL OF NEUROCHEMISTRY, Issue 1 2003A. M. Gardier Abstract The role of serotonin (5-HT)1B receptors in the mechanism of action of selective serotonin re-uptake inhibitors (SSRI) was studied by using intracerebral in vivo microdialysis in conscious, freely moving wild-type and 5-HT1B receptor knockout (KO 5-HT1B) mice in order to compare the effects of chronic administration of paroxetine via osmotic minipumps (1 mg per kg per day for 14 days) on extracellular 5-HT levels ([5-HT]ext) in the medial prefrontal cortex and ventral hippocampus. Basal [5-HT]ext values in the medial prefrontal cortex and ventral hippocampus, ,,20 h after removing the minipump, were not altered by chronic paroxetine treatment in both genotypes. On day 15, in the ventral hippocampus, an acute paroxetine challenge (1 mg/kg i.p.) induced a larger increase in [5-HT]ext in saline-pretreated mutant than in wild-type mice. This difference between the two genotypes in the effect of the paroxetine challenge persisted following chronic paroxetine treatment. Conversely, in the medial prefrontal cortex, the paroxetine challenge increased [5-HT]ext similarly in saline-pretreated mice of both genotypes. Such a challenge produced a further increase in cortical [5-HT]ext compared with that in saline-pretreated groups of both genotypes, but no differences were found between genotypes following chronic treatment. To avoid the interaction with raphe 5-HT1A autoreceptors, 1 µm paroxetine was perfused locally through the dialysis probe implanted in the ventral hippocampus; similar increases in hippocampal [5-HT]ext were found in acutely or chronically treated wild-type mice. Systemic administration of the mixed 5-HT1B/1D receptor antagonist GR 127935 (4 mg/kg) in chronically treated wild-type mice potentiated the effect of a paroxetine challenge dose on [5-HT]ext in the ventral hippocampus, whereas systemic administration of the selective 5-HT1A receptor antagonist WAY 100635 did not. By using the zero net flux method of quantitative microdialysis in the medial prefrontal cortex and ventral hippocampus of wild-type and KO 5-HT1B mice, we found that basal [5-HT]ext and the extraction fraction of 5-HT were similar in the medial prefrontal cortex and ventral hippocampus of both genotypes, suggesting that no compensatory response to the constitutive deletion of the 5-HT1B receptor involving changes in 5-HT uptake capacity occurred in vivo. As steady-state brain concentrations of paroxetine at day 14 were similar in both genotypes, it is unlikely that differences in the effects of a paroxetine challenge on hippocampal [5-HT]ext are due to alterations of the drug's pharmacokinetic properties in mutants. These data suggest that there are differences between the ventral hippocampus and medial prefrontal cortex in activation of terminal 5-HT1B autoreceptors and their role in regulating dialysate 5-HT levels. These presynaptic receptors retain their capacity to limit 5-HT release mainly in the ventral hippocampus following chronic paroxetine treatment in mice. [source] Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2005Yi Fan Abstract Aquaporin-4 (AQP4), a predominant water channel of the brain, mediates transmembrane water movement at the blood,brain barrier and brain,cerebrospinal fluid interface. A broad pattern of evidence indicates that AQP4 and regulators of its expression are potential targets for treatment of brain swelling, but whether it participates in the regulation of neurotransmission has not been reported. We examined neurochemical differences between AQP4-knockout and wild-type mice with particular focus on neurotransmission. Basal tissue neurotransmitter and metabolite levels were measured by high-performance liquid chromatography. Significant sex- and region-specific differences of amino acids and monoamines were found in the brain of wild-type and AQP4-knockout mice. In cortex, striatum, and hippocampus of male AQP4-knockout mice, an increase of glutamine and decrease of aspartate were observed. Glutamate was increased only in female AQP4-knockout mice. The lack of AQP4 failed to affect the levels of ,-aminobutyric acid and taurine. In the medial prefrontal cortex of AQP4-knockout mice, the levels of serotonin and norepinephrine were increased, but no significant change in dopamine level was found. In the striatum of male AQP4-knockout mice, the levels of dopamine and serotonin were remarkably increased, which was not found in female mice. In the hypothalamus of AQP4-knockout mice, only the serotonin level was altered. These results provide the first evidence that the lack of AQP4 expression is accompanied by sex- and region-specific alterations in brain amino acid and monoamine metabolism. © 2005 Wiley-Liss, Inc. [source] Region-Specific Induction of FosB/,FosB by Voluntary Alcohol Intake: Effects of NaltrexoneALCOHOLISM, Issue 10 2010Jing Li Background:, ,FosB is the best characterized transcription factor induced by chronic stimulation. Although previous studies have demonstrated that chronic passive ethanol exposure alters ,FosB immunoreactivity (IR), the effect of chronic voluntary ethanol consumption on ,FosB remains unknown. Furthermore, although previous studies have demonstrated that the opioid antagonist naltrexone reduces alcohol consumption in clinical and preclinical settings, the effect of naltrexone on FosB/,FosB has not been explored. Here, we examined the effects of chronic voluntary ethanol intake and naltrexone on FosB/,FosB IR in striatal region and prefrontal cortex, and the effect of naltrexone on voluntary ethanol intake. Methods:, We utilized immunohistochemistry to define the changes in FosB/,FosB IR induced by chronic voluntary ethanol intake under a two-bottle intermittent access of 20% ethanol model and by systematic administration (intraperitoneal injection) of naltrexone in Sprague-Dawley rats. Results:, Chronic (15 drinking sessions in 35 days) voluntary ethanol intake robustly induces FosB/,FosB IR in nucleus accumbens core, dorsolateral striatum, and orbitofrontal cortex, but not in nucleus accumbens shell, dorsomedial striatum, and medial prefrontal cortex. Systemic administration of naltrexone for 6 days significantly reduced voluntary ethanol consumption and FosB/,FosB IR induced by chronic voluntary ethanol intake. Conclusion:, Our results suggest that chronic voluntary ethanol intake induces FosB/,FosB IR in a subregion-specific manner which involves the activation of endogenous opioid system. [source] Effect of Chronic Ethanol on Enkephalin in the Hypothalamus and Extra-Hypothalamic AreasALCOHOLISM, Issue 5 2010Guo-Qing Chang Background:, Ethanol may be consumed for reasons such as reward, anxiety reduction, or caloric content, and the opioid enkephalin (ENK) appears to be involved in many of these functions. Previous studies in Sprague,Dawley rats have demonstrated that ENK in the hypothalamic paraventricular nucleus (PVN) is stimulated by voluntary consumption of ethanol. This suggests that this opioid peptide may be involved in promoting the drinking of ethanol, consistent with our recent findings that PVN injections of ENK analogs stimulate ethanol intake. To broaden our understanding of how this peptide functions throughout the brain to promote ethanol intake, we measured, in rats trained to drink 9% ethanol, the expression of the ENK gene in additional brain areas outside the hypothalamus, namely, the ventral tegmental area (VTA), nucleus accumbens shell (NAcSh) and core (NAcC), medial prefrontal cortex (mPFC), and central nucleus of the amygdala (CeA). Methods:, In the first experiment, the brains of rats chronically drinking 1 g/kg/d ethanol, 3 g/kg/d ethanol, or water were examined using real-time quantitative polymerase chain reaction (qRT-PCR). In the second experiment, a more detailed, anatomic analysis of changes in gene expression, in rats chronically drinking 3 g/kg/d ethanol compared to water, was performed using radiolabeled in situ hybridization (ISH). The third experiment employed digoxigenin-labeled ISH (DIG) to examine changes in the density of cells expressing ENK and, for comparison, dynorphin (DYN) in rats chronically drinking 3 g/kg/d ethanol versus water. Results:, With qRT-PCR, the rats chronically drinking ethanol plus water compared to water alone showed significantly higher levels of ENK mRNA, not only in the PVN but also in the VTA, NAcSh, NAcC, and mPFC, although not in the CeA. Using radiolabeled ISH, levels of ENK mRNA in rats drinking ethanol were found to be elevated in all areas examined, including the CeA. The experiment using DIG confirmed this effect of ethanol, showing an increase in density of ENK-expressing cells in all areas studied. It additionally revealed a similar change in DYN mRNA in the PVN, mPFC, and CeA, although not in the NAcSh or NAcC. Conclusions:, While distinguishing the NAc as a site where ENK and DYN respond differentially, these findings lead us to propose that these opioids, in response to voluntary ethanol consumption, are generally elevated in extra-hypothalamic as well as hypothalamic areas, possibly to carry out specific area-related functions that, in turn, drive animals to further consume ethanol. These functions include calorie ingestion in the PVN, reward and motivation in the VTA and NAcSh, response-reinforcement learning in the NAcC, stress reduction in the CeA, and behavioral control in the mPFC. [source] Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: A functional MRI case studyMOVEMENT DISORDERS, Issue 12 2003Taresa Stefurak MD Abstract Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta). © 2003 Movement Disorder Society [source] Apical vulnerability to dendritic retraction in prefrontal neurones of ageing SAMP10 mouse: a model of cerebral degenerationNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2006A. Shimada The SAMP10 mouse is a model of accelerated ageing in which senescence is characterized by age-related atrophy of the cerebral cortex and limbic structures, poor learning and memory task performance with depressive behaviour and cholinergic and dopaminergic alterations. Here we studied age-related changes in the dendritic arbors and spine density of pyramidal cells in the medial prefrontal cortex of SAMP10 mice using a quantitative Golgi method. Dendrites of prefrontal neurones gradually retracted with ageing towards the soma with the relative preservation of overall complexity. Apical dendrites were much more severely affected than basal dendrites. The combined length of the apical dendrites and spine density were decreased by 45% and 55%, respectively, in mice at 12 months, compared with mice at 3 months of age. Immunohistochemical and immunoblot analyses indicated that expression of microtubule-associated protein (MAP) 2, a marker of dendrites, decreased in an age-related manner not only in the anterior cortex but also in the posterior cortex and olfactory structures in SAMP10 mice. Decreased expression of MAP2 mRNA caused the decrease in MAP2 protein expression. These results suggest that retraction of apical, but not of basal dendrites, with a loss of spines in prefrontal neurones, appears to be responsible for poor learning and memory performance in aged SAMP10 mice. It is also suggested that age-related dendritic retraction occurs in a wide area including the entire cerebral cortex and olfactory structures. [source] Persistent proteomic alterations in the medial prefrontal cortex with abstinence from cocaine self-administrationPROTEOMICS - CLINICAL APPLICATIONS, Issue 4 2009Melinda E. Lull Abstract Neuroproteomic studies of drug abuse offer the potential for a systems-level understanding of addiction. Understanding cocaine-responsive alterations in brain protein expression that persist even with extended abstinence may provide insight into relapse liability. In the current study, protein changes in the medial prefrontal cortex of cocaine self-administering rats following 1 and 100,days of enforced abstinence were quantified by 2-D DIGE. We have previously reported increased drug-seeking and drug-taking, as well as mRNA and epigenetic changes in this model even after 100,days of enforced abstinence. A number of statistically significant changes in proteins relating to synapse function and neuronal remodeling were evident, including neurofilament medium and Hsp73, which increased at 1,day of abstinence, but returned to normal levels following 100,days of abstinence. Dynamin-1 and synaptosome-associated protein 25,kDa (SNAP-25) were unchanged at 1,day of abstinence, but were significantly decreased after 100,days. These data demonstrate that while some protein changes return to normal levels following enforced cocaine abstinence, a number remain or become altered after long periods, up to 100,days, of cocaine abstinence. Those protein expression changes that do not reset to pre-cocaine exposure levels may contribute to the persistent relapse potential that occurs in response to cocaine abstinence. [source] | ||||||||||||||||